global literature review of haemophilus influenzae type b and

Global literature review of Haemophilus influenzae type b

and Streptococcus pneumoniae invasive disease among children

less than five years of age1980–2005

WHO/IVB/09.02 ORIGINAL: ENGLISH

Immunization, Vaccines and Biologicals

Global literature review of Haemophilus influenzae type b and Streptococcus pneumoniae invasive disease among children less than five years of age 1980–2005

WHO/IVB/09.02ORIGINAL: ENGLIsH

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The Department of Immunization, Vaccines and Biologicals thanks the donors whose unspecified financial support

has made the production of this document possible.

This publication was produced for the Immunization, Vaccines and Biologicals, WHO, by:

Maria Deloria Knoll1, Katherine L. O’Brien1, Emily Henkle1, Ellen Lee1, James P. Watt2, Natalie McCall1, Punam Mangtani2

1 GAVI Alliance’s PneumoADIP, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

2 GAVI Alliance’s Hib Initiative, London School of Hygiene and Tropical Medicine, London, United Kingdom

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Contents

Abbreviations and acronyms ............................................................................................v

Authorship and acknowledgements...............................................................................vii

Executive summary ...........................................................................................................xi

1. Introduction ............................................................................................................1

2. Methods ...................................................................................................................22.1 Literature search strategy ................................................................................22.2 Screening and article retrieval ..........................................................................42.3 Exclusion criteria ..............................................................................................62.4 Abstractor training ...........................................................................................72.5 Article abstraction process ...............................................................................72.6 Information abstracted ....................................................................................82.7 Data entry ........................................................................................................122.8 Data cleaning .................................................................................................122.9 Qualitative assessment of meningitis incidence ..........................................14

3. Other inputs for analysis ....................................................................................183.1 Country classifications ...................................................................................183.2 Geographic and mortality strata used ...........................................................18

4. Results ....................................................................................................................204.1 Hib studies .....................................................................................................214.2 Spn studies ......................................................................................................244.3 Hib meningitis ................................................................................................264.4 Spn meningitis .................................................................................................374.5 Comparison of Hib and Spn meningitis incidence data ..............................494.6 Hib non-pneumonia, non-meningitis invasive disease ...............................574.7 Spn non-pneumonia, non-meningitis invasive disease ................................59

5. Discussion ..............................................................................................................625.1 Clinical standards for case definitions and classification ............................625.2 Limitations of Hib and Spn incidence studies ............................................645.3 Data sparsity and reporting inconsistencies in the published literature ....665.4 Adjusted incidence data ................................................................................665.5 Foreign language papers ................................................................................67

6. References ..............................................................................................................68

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7. Annexes ..................................................................................................................69

Annex 1: Search strategies ...................................................................................70

Annex 2: Article screening instructions ..............................................................81

Annex 3: Data Abstraction Form (DAF) ..........................................................85

Annex 4: Member States by WHO Region .....................................................108

Annex 5: Countries and territories by United Nations region .....................109

Annex 6: Study characteristics and key data from Hib studies entering the meningitis and NPNM analytic database ..................110

Annex 7: Study characteristics and key data from Spn studies entering the meningitis and NPNM analytic database ..................128

Annex 8: References for studies with evaluable outcome data ......................145

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Abbreviations and acronyms

AFR WHO African RegionAMR WHO Region of the AmericasCFR Case-fatality ratioCSF Cerebrospinal fluidDAF Data Abstraction FormEMR WHO Eastern Mediterranean RegionEUR WHO European RegionIndependent Expert Panel Ad Hoc Expert Review Committee for the Global

Burden of Hib and Pneumococcal DiseaseHELLIS Health Literature, Library and Information ServicesHi Haemophilus influenzaeHib Haemophilus influenzae type bHibRAT Hib Rapid Assessment ToolIBIS Invasive Bacterial Infections SurveillanceIMCI integrated management of childhood infectionsIMEMR Index Medicus for the WHO Eastern Mediterranean

RegionIMSEAR Index Medicus for the WHO South-East Asia RegionInvasive disease Organism identified from a normally sterile site, such

as blood, cerebral spinal fluid, or pleural fluidJHBSPH Johns Hopkins Bloomberg School of Public HealthLILACS Latin American and Caribbean Health Sciences

InformationLP lumbar punctureLSHTM London School of Hygiene and Tropical MedicineNPNM Non-pneumonia, non-meningitisPCR polymerase chain reactionSEAR WHO South-East Asia RegionSpn Streptococcus pneumoniaeUNICEF United Nations Children’s FundWHO World Health OrganizationWorking Group Global Burden of Hib and Pneumococcal Disease

Working GroupWPR WHO Western Pacific Region

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Authorship and acknowledgements

This work was performed collaboratively by WHO, the PneumoADIP and the Hib Initiative. The PneumoADIP and the Hib Initiative are funded in full by the GAVI Alliance, and The Vaccine Fund.

Hib and Spn Global Disease Burden Working Group

Core Working Group Members: World Health Organization: Thomas Cherian, Lara J. WolfsonJohns Hopkins Bloomberg School of Public Health: Maria Deloria Knoll, Orin S. Levine,

Katherine L. O’Brien, James P. WattLondon School of Hygiene and Tropical Medicine: Kim Mulholland

Extended Working Group Members:World Health Organization: Maureen BirminghamJohns Hopkins Bloomberg School of Public Health: Emily Henkle, Ellen Lee, Natalie

McCall, Jennifer Moïsi, Suyan TianLondon School of Hygiene and Tropical Medicine: Punam Mangtani

Acknowledgments

Literature Review: Johns Hopkins Bloomberg School of Public Health: Neelam Ahmed, Bethany Baer, Bianca Bell, Will Checkley, Cynthia Fisher,

Yatin Gadgil, Shivam Gupta, Erin Kish, Rachel Lestz, Natalie McCall, Shaun Morris, Riyadh Muhammad, Roopal Patel, Sarah Polk, Stephanie S. Renegold, Hasan Shahib, Melissa Seaman, Jesse Sturm, Andrea Sutherland, Andre Wattiaux, Chizoba Wonodi

Center for Disease Control: Brendan Flannery, Vishnu Sneller, Michael WiederholdLondon School of Hygiene and Tropical Medicine: Venetia Clarke, Andreia Costa Santos, Isaac C. Fung, Hiwot Haile-Selassie,

Kenneth Lee, Hong Huay Lin, Jennifer Palmer, Emily Robinson, Susanna Scott, Beth Temple, Maria VanKerkhove

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Translation: Olga Alexinskaya (Freelance Russian interpreter/translator, Russia; Russian

translation), Ezra Barzilay (Centers for Disease Control and Prevention, USA; Greek translation), Tomoya Saito (Johns Hopkins Bloomberg School of Public Health, USA; Japanese translation), Mark Schapiro (US Department of State, Italy; Italian translation), Jana Shaw (The Children’s Clinic, USA; Czech translation), Masja Straetemans (Centers for Disease Control and Prevention, USA; Dutch translation)

Country Consultation:London School of Hygiene and Tropical Medicine: Ulla GriffithsWorld Health Organization: Marta Gacic DoboJohns Hopkins Bloomberg School of Public Health: Lois Privor-Dumm

Additional Support:Johns Hopkins Bloomberg School of Public Health: Chantelle Boudreaux , LaTia Brinkley, Kimberly Carlton, Ed Chan, Zunera

Gilani, Lindsay Grant, Rana Hajjeh, Avanti Johnson, Kimberly Johnson, Walt Jones, Rula Khoury, Benedicta Kim, Lawrence Moulton, Sharmila Shetty, Katherine Williams

London School of Hygiene and Tropical Medicine: Karen Edmond, Claudia Da Silva, Keith BransonWorld Health Organization: Thomas Allen, Anthony Burton, Ximena Laurie, Kenji Shibuya, Martin

Weber

Sharing unpublished data: Jay Berkley Steve Black Abdullah Brooks Felicity Cutts Rosanna Lagos Shabir Madhi Hanna Nohynek Anthony Scott Samir Saha Mark Steinhoff

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The authors wish to thank the Independent Expert Review Panel of the Global Burden of Hib and Spn Disease Project for reviewing proposed approaches and methodology for estimating Hib and Spn disease burden, and whose recommendations directly impacted the literature search strategy. Dr Zulfiqar Ahmed BHUTTA, Professor, Pediatrics and Child Health, The Aga

Khan University, Pakistan Dr Claire BROOME, Consultant, USA Dr Harry CAMPBELL, Department of Public Health Sciences, Edinburgh

University Dr Daniel CHANDRAMOHAN, Disease Control and Vector Biology Unit,

London School of Hygiene and Tropical Medicine, United Kingdom Dr Paul FINE, Professor of Communicable Disease, Epidemiology, London

School of Hygiene and Tropical Medicine, United Kingdom Dr Bradford GESSNER, Agence de Médecine Préventive (AMP) a l’Institut

Pasteur, Paris, France Dr Bryan GRENFELL, Biology Department, The Pennsylvania State University,

USA Dr Alan R. HINMAN, All Kids Count, Task Force for Child Survival and

Development, Decatur, GA, USA Dr Keith KLUGMAN, Department of International Health, Emory University,

Atlanta, GA, USA Dr Julie LEGLER, Department of Mathematics, Statistics and Computer Science,

St. Olaf College, USA Dr Walt ORENSTEIN, Emory Vaccine Center, Emory University, USA Dr Hanna NOHYNEK, Department of Vaccines, National Public Health

Institute, Finland Dr Anne SCHUCHAT, Centers for Disease Control and Prevention, USA Professor Peter SMITH, London School of Hygiene and Tropical Medicine,

United Kingdom Dr Cynthia WHITNEY, Centers for Disease Control and Prevention, USA

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Introduction:

Estimates of Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (pneumococcus, Spn) global disease burden among children less than five years of age are needed for major policy decisions regarding prevention and treatment priorities. In particular, vaccine policy decisions are a major priority of global health organizations. To this end, a comprehensive literature review of published and unpublished reports of Hib and pneumococcal disease among children less than five years of age was undertaken to provide input parameters for a World Health Organization (WHO) modelling study directed at estimating global, regional, sub-regional and country level Hib and pneumococcal disease burden. This document describes the literature search method and the data abstraction tools, and provides a descriptive analysis of the reports identified by the literature search. The data from this literature search was then used to populate models to estimate the global disease burden of Hib and Spn. The literature review and modelling work was carried out between 2005 and 2007. The methods and results of the models themselves are published elsewhere (Wolfson, 2009; O’Brien, 2009; Watt, 2009).

Literature search methodology:

Using a comprehensive set of search terms formulated with the assistance of a professional librarian at the WHO, nine databases were searched for articles on Hib or Spn disease published between 1 January 1980 and 31 December 2005. A total of 15 099 citations were identified. The titles and abstracts of these citations (where available) were reviewed to exclude those which were unlikely to contain relevant disease burden information. The full text of the remaining 1900 citations was reviewed for inclusion and exclusion criteria. Articles were sought which had information on any of the following: meningitis or any invasive disease incidence; meningitis, non-pneumonia/non-meningitis or any invasive disease case-fatality ratio; age distribution of invasive disease cases, or invasive disease syndrome distribution. In addition to these disease-specific parameters, information was also abstracted from the papers on the study methodology, so that a quality assessment could be done of the data reported in the paper.

Literature review results:

Of the 1900 articles reviewed, 336 studies had evaluable key extracted outcomes (205 reported Hib data, 211 reported Spn data, and 80 of the 336 studies reported on both Hib and Spn disease). Of these 336 studies, 266 provided data for at least one variable in the meningitis or non-pneumonia, non-meningitis (NPNM) model; 176 provided data on Hib disease, 164 provided data on Spn disease, and 74 of the 266 studies provided data on both Hib and Spn disease.

Executive summary

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Hib studies:

General: A total of 205 studies provided evaluable Hib data. Most studies were from the WHO European Region (EUR, N = 65) and the WHO Region of the Americas (AMR, N = 49); fewer studies were from the WHO African Region (AFR, N = 33) and the WHO Western Pacific Region (WPR, N = 35), and fewest were from the WHO Eastern Mediterranean Region (EMR, N = 12) and the WHO South-East Asia Region (SEAR, N = 11).

Meningitis incidence: Of the 205 Hib studies, 110 (54%) provided meningitis incidence data. Of these, few (N = 20, 18%) reported meningitis incidence adjusted for recognized under-detection biases. Although most of the world’s under-5 population lives in countries within AFR and SEAR, these regions had only 12 and 4 Hib meningitis incidence studies respectively, compared with 41 in EUR, and 22 in AMR. Only 59 (54%) studies were assessed to be of sufficient quality to include in the model.

Meningitis CFR: Sixty-two studies (30%) provided case-fatality ratio (CFR) data for any syndrome, 55 (89%) of which reported Hib meningitis CFRs with representation from all regions. Both the greatest absolute CFR and the greatest range of CFRs measured were from AFR and SEAR.

NPNM: There were 27 studies which provided data on the relative distribution of invasive Hib meningitis cases to NPNM cases (invasive Hib disease that was classified as other than meningitis or pneumonia). Studies were available from every region, but no region had more than nine studies. There were fewer NPNM cases relative to the number of meningitis cases, the difference of which increased with increasing mortality. There were only five studies which provided data on both NPNM CFR and meningitis CFR.

Spn studies:

General: A total of 211 studies provided evaluable Spn data. Most studies with Spn data were from EUR (N = 65) and AMR (N = 68); fewer studies were from AFR (N = 32) and WPR (N = 33), and the least were from EMR (N = 8) and SEAR (N = 5).

Meningitis incidence: Out of 211 studies, 90 (43%) provided meningitis incidence data. Of these, none reported meningitis incidence adjusted for recognized under-detection biases, but five reported information that could be used by the reviewers to adjust the estimates. Similarly to Hib meningitis incidence studies, most Spn meningitis incidence studies were from EUR (N = 41) and AMR (N = 24); only 10 and 13 studies were from AFR and EMR, respectively, only two studies were from EMR, and there were none from SEAR. Of the 90 Spn meningitis incidence studies, 51 (57%) were assessed to be of sufficient quality to be included in the model.

Meningitis CFR: Of the 60 (28%) Spn studies reporting CFRs for any Spn syndrome, 34 reported CFRs for meningitis. All regions were represented, with the highest CFR observed in AFR and SEAR.

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NPNM: There were 38 Spn studies providing information on the relative distribution of Spn NPNM cases to meningitis cases. Studies were available from every region except EMR. Non-severe NPNM was documented only in the very low mortality strata. There were more NPNM cases relative to meningitis cases reported in very low mortality countries and more meningitis cases relative to NPNM cases for all other mortality strata. There were only two studies with NPNM CFR and meningitis CFR, from AFR and AMR.

Summary:

There is a large body of literature on serious, invasive, Hib and Spn disease among children less than five years of age, representing all regions of the world. These data provide measures of meningitis incidence, case and syndrome distributions, and CFRs for various severe syndromes of interest. With rigorous literature review criteria and a systematic approach to identifying reports, a comprehensive literature database has been established from which models were constructed of Hib and Spn disease burden among children less than five years. However, Hib and Spn disease burden estimates remain limited by the number and representativeness of studies from some regions of the world, as well as the lack of consistency of information provided in the reports and the quality of surveillance (i.e. case ascertainment and laboratory diagnosis) on which the studies report. Efforts to improve the quality of disease surveillance and the consistency and quality of surveillance reporting will improve the input parameters for such models in the future.

1WHO/IVB/09.02

This document describes the literature review, data abstraction, and descriptive analysis of the data which was used in models to estimate the global disease burden of Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (Spn) among children less than five years of age in the year 2000. This work was carried out between 2005 and 2007.

In a 2002 World Health Organization (WHO) report, Bennett and colleagues presented a summary and analysis of published and unpublished literature on Hib disease in the pre-immunization era, with particular focus on Hib meningitis incidence, age distribution and case-fatality ratios (Bennett, 2002). This analysis included literature published between 1970 and October 2001. From 2004 to 2005, the WHO collaborated with PneumoADIP, the Hib Initiative, and Johns Hopkins Bloomberg School of Public Health (JHBSPH) to update this literature search on Hib disease, and to conduct a new literature search on Spn disease. The objective of this review was to estimate the global burden of Hib and Spn disease using models based on data from the existing literature. In June 2005, the results of the literature searches were presented to an Ad Hoc Expert Review Committee for the Global Burden of Hib and Pneumococcal Disease (Independent Expert Panel) convened by WHO to review the proposed approach and methodology for estimating Hib and Spn disease burden. The Independent Expert Panel made a number of recommendations to the Global Burden of Hib and Pneumococcal Disease Working Group (Working Group) about the modelling methodology. To implement those recommendations, it was necessary to conduct a revised literature search for Hib and Spn. The Working Group aimed to consolidate information extracted from past literature search efforts in a standardized format and to incorporate new information, which may have been missed by the previous reviews or made available after the database for the June 2005 meeting had closed. This effort included implementing the Independent Expert Panel’s recommendation to incorporate data quality-assessments of the studies identified through the literature review.

This report provides the documentation and summary of that systematic, revised literature review conducted between 2005 and 2006.

Introduction1.

Global literature review of Hib and Spn invasive disease among children less than five years of age, 1980–20052

2.1 Literature search strategy

The literature search included articles published between January 1980 and November 2005, inclusive.

2.1.1 Strategy for Hib and Spn literature search

A professional librarian at WHO identified potentially relevant references by systematically searching the published literature using a defined search strategy. This search strategy was modified according to the features of each database. Specific search strategies are described in detail in Section 5.1.2 for Hib, Section 5.1.3 for Spn and Annex 10.1. The results of the literature search were compiled into a password-protected online database of identified references maintained at JHBSPH. Figure 1 depicts the flow of activities and number of references identified at each step. At the last step, articles that presented data from more than one country were treated as a separate study for each country represented.

Figure 1: Summary of references identified and studies abstracted

Methods 2.

* HibRAT = Hib Rapid Assessment Tool (Feikin, 2004; WHO, 2001)

54 unable to obtain full text

1000 screened out for lack of applicable data

352 excluded for meeting at least one exclusion

criteria

216 fail to meet primary outcome

criteria, partial data abstracted

1331 duplicate citations

332 articles (336 stumeet criteria for at least one extracted outcome and

contain evaluable datadies)

899 enter data abstraction process

1899 undergo full text review

3285 met criteria for full text review

15 099 Hib & Spn references identified from database search and title/abstract screened+ 32 HibRATs*

+ 12 references identified from grey literature search and country consultation process

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2.1.2 Databases searched

All databases listed below were searched for both Hib and Spn literature, with the exception of the Pascal database, which was used for the Hib search only. The WHO subscription for the Pascal database expired between the time of the Hib search and Spn search. Furthermore, due to the limited number of unique Hib articles identified through the use of this database, the Working Group decided to omit Pascal for the Spn literature search. All languages were considered in the literature search. A detailed description of the database search criteria can be found in Annex 10.1.

1) Medline (US Library of Medicine) and Embase (Elsevier Science).

2) CAB Health (CAB International).

3) Cochrane (Cochrane Collaboration).

4) Pascal (Institut de l’Information Scientifique et Technique) – Hib search only.

5) Biosis (Thomson Scientific).

6) Regional databases:

a) African Index Medicus;

b) Index Medicus for the WHO Eastern Mediterranean Region (IMEMR);

c) Latin American and Caribbean Health Sciences Information (LILACS) database produced by BIREME, the Latin American and Caribbean Center on Health Sciences Information;

d) Health Literature, Library and Information Services (HELLIS), which also contains Index Medicus for the South-East Asia Region (IMSEAR).

2.1.3 Hib literature search strategy for each database

1) Medline and Embase (Annex 1.1).

2) HELLIS: search terms used were “Haemophilus”, “Hemophilus”, “Hib” or “Hib disease”.

3) Biosis (Annex 1.2).

4) CAB (Annex 1.3).

5) Africa Index Medicus: search terms used were “meningitis”, “meningite”, “Haemophilus”, “Hemophilus”, “Hib”, “bacteraemia”, “bacteremia” or “sepsis”.

6) Cochrane (Annex 1.4).

7) LILACS: search terms used were “Haemophi lus inf luenzae” , “Hemophilus influenzae” or “Hib”.

8) Pascal (Annex 1.5).

9) IMEMR: search terms used were “Haemophilus”, “Hemophilus” or “Hib”.


2.1.4 Spn literature search strategy for each database

1) Medline and Embase (Annex 1.6). 2) HELLIS: search terms used were “Pneumococcal” or “pneumococcus” or

“Streptococcus pneumoniae” or “pneumococci” or “S. pneumoniae” or “(pneumococcal invasive disease)”.

3) Biosis (Annex 1.7). 4) CAB (Annex 1.8).5) Africa Index Medicus: search terms used were “Pneumococcal” or “pneumococcus”

or “Streptococcus pneumoniae”.6) Cochrane (Annex 1.9).7) LILACS: search terms used were “Pneumococcal”, “pneumococcus” or

“pneumococci” or “Streptococcus pneumoniae”.8) IMEMR: search terms used were “Pneumococcal”, “pneumococcus” or

“Streptococcus pneumoniae”.

2.1.5 Unpublished (“grey”) literature

Through personal correspondence, the Working Group sought data from investigators of unpublished but potentially relevant studies. Reports of WHO consultations using the Hib Rapid Assessment Tool (HibRAT) were included in this category. The HibRAT provides an estimate of Hib disease burden in settings where rigorous, long-term studies have not been performed. The HibRAT uses as much local data as possible to generate country or population-specific Hib disease burden estimates (Feikin, 2004; WHO, 2001).

2.2 Screening and article retrieval

To determine whether studies identified through the literature search were eligible for data abstraction, individuals were trained to review all titles and abstracts (when available) of the references identified for potential relevance. Studies deemed not relevant were screened out at this step, leaving studies considered potentially relevant, and studies whose relevance was unknown based on the title and abstract. References in languages other than English were “screened in” if a translation for the title and abstract was not available. The objective of this step was to reduce the workload of retrieving complete references which were obviously not relevant to the project, without losing articles that might have relevant data. Notations were made in the online database to identify the citations retained or excluded at this step. The criteria used for screening are specified in Sections 5.2 and 5.3 and the specific instructions for screening references are available in Annex 2.

Because a summary of 1970–2001 published and unpublished literature on Hib disease was available for comparison (Bennett, 2002), the results of the Hib literature search were screened by one individual only. The Spn references were screened twice to ensure only potentially relevant articles were selected. Approximately 80% of the Spn citations identified by the literature search were screened by two individuals. Of the dually screened articles, there was agreement between the two screeners on whether to include or exclude the article in 87% of cases. Among the 13% of references with discrepant screening status, only 21% were ultimately screened in through an adjudication process (2.6% of the total). This demonstrates that the screening process effectively eliminated irrelevant references and was unlikely to miss potentially useful articles.

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Screeners and data abstractors reviewed full text articles to complete the screening process using the same screening criteria described above. The availability of the full text allowed screeners and data extractors to eliminate articles which clearly did not provide the information of primary interest, but that did not provide sufficient information in the title/abstract to confidently screen them out. If an article had been screened in based on title/abstract review but subsequently excluded based on the screening of the full text of the article, the article was sent to a second reviewer. If the second reviewer decided to include the article for data extraction, an adjudicator evaluated the discrepancy, and their decision was considered final.

Examples of articles screened in

During the screening process, references deemed potentially relevant and screened in were those which included any of the following data.

1) Incidence in children under 15 years of age for:

a) Hib meningitis, pneumonia, or non-pneumonia/non-meningitis (e.g. sepsis, bacteraemia, septic arthritis, epiglottitis, etc.) invasive disease (organism identified from a normally sterile site, such as blood, cerebral spinal fluid, or pleural fluid);

b) Spn meningitis, pneumonia, or non-meningitis/non-pneumonia invasive disease.

2) Age distribution of cases of invasive Hib or invasive Spn disease.3) Case-fatality ratios of invasive Hib or invasive Spn disease.4) Distribution of Hib and Spn disease syndromes (i.e. proportion of cases due to

meningitis, pneumonia, sepsis, or other invasive disease). 5) Etiology by syndrome (i.e. proportion of all meningitis or other invasive disease

by bacterial etiology, if organisms isolated include Hib and/or Spn).

Although the objective of the project was to estimate Hib and Spn disease burden in children less than five years of age, all articles were screened in that included relevant data from children less than 15 years of age.

Examples of articles screened out

Articles containing only the types of data listed below were screened out during the screening process.

1) A case report (single case).2) Antimicrobial resistance studies.3) Vaccine immunogenicity and safety studies.4) Nasopharyngeal carriage studies.5) Molecular characterization of bacterial strains.6) Policy papers. 7) Studies of disease only among adults.8) Studies of species other than Haemophilus influenzae (Hi) or Spn. 9) Studies including only children less than one year of age.10) Studies with isolates only from non-sterile sites.11) Review articles with no original data.


The online reference database specifies the screening status for each identified reference. Screeners distinguished review articles in the online database to facilitate their rapid identification and retrieval for other purposes, for example to check for additional references.

2.3 Exclusion criteria

Following the screening process, data abstractors reviewed the remaining studies and applied exclusion criteria that eliminated studies with the following characteristics from complete data extraction.

1) There was “substantial use” (defined as coverage > 25%) of Hib or Spn conjugate vaccines in the study population either before or during the study period, and there were no data in that reference from the period prior to vaccine introduction or widespread use of vaccine, since the objective of this analysis was to estimate disease burden prior to vaccine introduction.

2) The study report included cases occurring prior to 1980; such studies were deemed too old to include epidemiologically relevant data given the possibility for major changes in disease patterns, and improvements in diagnostic tools over time.

3) The study involved less than 12 months of case ascertainment, and therefore does not account for possible seasonality of disease.

4) The data reported were from a specific sub-population of children (e.g. distinct racial/ethnic background, shared medical condition believed to change the risk of disease such as HIV infection) only, with no information about the general population. As the focus of the Working Group was data which could be generalized to the whole country, studies reporting data only for sub-populations such as Native American or Australian Aboriginal children were excluded. If a study reported data both for the general population and a select sub-population, the study was included; if the data for the populations were reported separately, the reviewer would extract data regarding the general population only.

5) The data reported were not grouped into any of the three following age categories: 1 (±1 month) to 11 month olds (±1 month); 1 (±1 month) to 23 month olds (±1 month); or 1 (±1 month) to 59 month olds (±1 year) (some variability in age categorization was accepted if it was not expected to significantly affect parameter estimates): since the objective was to obtain under-5 parameters, these had to be directly available in the article or calculable from under-1 or under-2 parameters.

There were 352 articles excluded for at least one of the reasons above (Figure 1).

2.3.1 Exclusion criteria for specific variables

Additional exclusion criteria were applied to determine if data on disease incidence, age distribution of cases, distribution of syndromes, or case-fatality ratios could be abstracted (refer to Annex 3 to view the Data Abstraction Form). The criteria below were applied as exclusion criteria.

7WHO/IVB/09.02

Incidence:

• <20 000 child-years of observation on average for each one-year age stratum, unless the area under study was an entire country, in which case the size of the entire population for that age group could be included.

Age distribution, syndrome distribution:

• <30 cases of either Hib or Spn invasive disease in children less than five years of age.

2.4 Abstractor training

All individuals trained to screen references or abstract data had graduate training in medicine and/or epidemiology. All individuals were trained in the objectives and process of screening and data abstraction prior to working on the project. A total of 44 individuals were trained to work on the project. This large number of abstractors was needed because of the extensive screening process instituted, and the time required to complete the data abstraction (approximately one to two hours per full text article).

Multiple training sessions were conducted at JHBSPH and LSHTM from October 2005 to May 2006. With the exception of three individuals who attended data abstraction training via teleconference, all training was conducted in person over one- to three- day sessions. Training sessions included presentations, sample studies for screening and select studies for “practice” data abstraction. To practice the data abstraction process, all data abstractors were assigned the same three studies as a means of comparing the accuracy of the different abstractors and assessing the heterogeneity between them.

2.5 Article abstraction process

A standardized Data Abstraction Form (DAF) was developed through collaboration between the WHO, PneumoADIP, and the Hib Initiative (refer to Annex 3 to view DAF). The abstraction form first prompted the reviewer to apply specific exclusion criteria to studies that had been “screened-in”. These initial exclusion criteria, listed in Section 5.3, determined if abstraction of the complete article was appropriate. If the article met any of the exclusion criteria, it was excluded and data abstraction stopped.

For all studies screened-in after application of the exclusion criteria, data abstractors completed structured abstraction of the full article. Data on the study design, population, and case definitions were abstracted from all articles. If a study met the additional inclusion criteria for abstraction of at least one category of data (e.g. disease incidence, age distribution of cases, distribution of syndromes, or case-fatality ratios), information about the study’s data quality was collected. For all studies, data abstractors were asked to indicate if the references cited contained other potentially relevant articles.


2.6 Information abstracted

(Refer to Annex 3 to view the Data Abstraction Form).

2.6.1 Location of study

The number and names of countries included in the study were recorded. If a paper described a multi-country study, and if possible, data from each of the countries were abstracted separately. However, some papers describing a multi-country study reported only aggregated data making the distinction between each country’s data impossible. In these cases, the names of all countries included and the aggregate data were recorded. The abstractors indicated if case-ascertainment occurred throughout the country or on a sub-national level (e.g. a district or county), and recorded the names of the areas involved (e.g. name of city or county of the study). Information about the study setting (e.g. rural, urban, etc.) as described by the authors was also collected.

2.6.2 Study design

Data abstractors characterized study design by indicating if data collection was prospective or retrospective, active or passive surveillance, and hospital-based or community-based case ascertainment. If the study was hospital-based, the number and type of hospitals involved were recorded.

2.6.3 Study population

The lower age limit for children included in the study, whether HIV prevalence was reported, and the under-5 mortality rate of the study population, were recorded when available. Other information collected included the availability and use of Hib or pneumococcal vaccine, and the proportion of subjects who received antibiotics prior to presentation or specimen collection.

2.6.4 Case definitions

Data abstractors indicated the syndrome of Hi or Spn invasive disease measured and the specific laboratory methods used to characterize children as cases of invasive disease (e.g. culture, latex agglutination, polymerase chain reaction). For studies of invasive Hib disease, abstractors indicated if the authors specified that all Hi isolates were typed, if only some isolates were typed and the others were assumed to be type b, or if no typing was done and all isolates were assumed to be type b.

Hib and Spn invasive syndromes were extracted as reported in the article, with invasive disease defined as an organism identified from a normally sterile site, such as blood, cerebral spinal fluid, or pleural fluid. Syndromes of interest were all invasive disease, all non-meningitis invasive disease, meningitis, pneumonia, or non-pneumonia/non-meningitis (e.g. sepsis, bacteraemia, septic arthritis, epiglottitis, etc.) invasive disease.

2.6.5 Years of surveillance

If a study provided incidence data, the month and year of the start and end dates of surveillance period were recorded.

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2.6.6 Incidence

The data abstractors were prompted to determine if incidence data could be abstracted from each study. If a study did not report Hib or Spn invasive disease incidence, the data abstractor skipped to questions about the age and syndrome distribution reported in the study.

If incidence data were reported, the abstractor then had to determine if the study met the minimum number of child-years of observation for incidence data abstraction. This minimum was established to ensure that incidence estimates would have sufficient precision to be justifiably included in the model. Child-years of observation were calculated by multiplying the average population of children less than five years of age in the area of the study and the number of years of the study. To be included for data abstraction, the study had to include, on average, a minimum 20 000 child-years of observation for each one-year age stratum. For example, if the study included children less than five years, a minimum of 100 000 child-years of observation were required for the study to be included for incidence data abstraction. If the study included only children less than two years, a minimum of 40 000 child-years of observation were required. The criterion of 20 000 child-years per one-year age stratum was an average. Therefore, if a study of children under five years included a total of 100 000 child-years of observation, but had only 15 000 child-years for children under one year, the study would be included. Alternatively, if the area under study was an entire country, the size of the entire population for that age group could be included (e.g. the entire population of children less than five years, or the entire population of children less than two years), even if the minimum number of child-years was not met. In this way, studies from smaller countries could be included for abstraction. If the study did not meet the minimum criterion for child-years of observation, the data abstractor did not abstract data about disease incidence.

Incidence for all age strata and all disease syndromes reported in a study were recorded. Three age strata (< 5 years, < 2 years, < 1 year) were particularly important, as they were the age strata used for data analysis. If incidence within these age strata were not reported but could be calculated using the available data, the calculated values were recorded.

If a study reported incidence data for a special sub-population (e.g. children with HIV infection) as well as the general population, data for the general population only were recorded. This literature search was not used to determine differences in disease risk or mortality in HIV positive children compared to HIV negative children. Wolfson and colleagues describe the separate literature seaches and the products of these searches in another publication (Wolfson, 2009).

Incidence rates adjusted to account for study limitations were also recorded if reported by the authors, as well as the reason for the adjustment (i.e. cases missed because they did not come to a study facility or were not evaluated, diagnostic tests were not done, or results were culture-negative but probably bacterial disease).


2.6.7 Age distribution/syndrome distribution

If a study provided incidence data, age and syndrome distribution, data were usually abstracted with the incidence data. For the remaining studies, to abstract age distribution or syndrome distribution, a minimum of 30 cases of either Hib or Spn invasive disease in children under age five was required. This minimum number of cases was chosen to maintain statistical validity for the distribution of cases across age groups. If a study did not meet this criterion, and did not report incidence data, no further information was abstracted.

To abstract age distribution data, the study must report the proportion of Hib and/or Spn invasive disease occurring in any age group of children less than five years. If data for children under five years were provided without further description of age sub-categories (e.g. under two years, under one year), these data were not abstracted.

To abstract syndrome distribution data, the study must report the distribution of Hib and/or Spn invasive disease by syndrome for any age group among children less than five years. If a study provided incidence data for all Hib invasive disease, without further characterization of the distinct syndromes, it could not be used in the model. At minimum, the manuscript had to provide data for two different categories of invasive disease (e.g. meningitis and all other invasive disease) to have syndrome distribution data abstracted. If age or syndrome distribution data could not be abstracted, the abstractor then evaluated the study for abstraction of case-fatality ratio data.

2.6.8 Case-fatality ratio

Data abstractors evaluated all studies including cases of Hib or Spn invasive disease to determine if case-fatality ratio (CFR) data could be abstracted. To calculate the CFR, the study needed to provide the number of cases due to the disease of interest (denominator), and the number of deaths among those cases (numerator). If CFRs were not reported by the authors but the relevant data for children under five years were available, abstractors calculated and recorded the CFRs. The abstractors were instructed to record for the denominator only the cases for which mortality outcome (i.e. alive or dead) was known. If the manuscript did not provide this information, CFR could not be calculated, and this variable was left blank for this study. Initially a minimum of 30 cases with evaluable death outcome was anticipated as criteria for inclusion in the analytic database, but this was later expanded to a minimum of 25.

2.6.9 Data quality measurements

Objective questions about the quality of the study design and methods were included in the Data Abstraction Form (Sections 5.9.2 to 5.9.3, and Annex 3). The series of objective questions served as a guide for the trained reviewer to make the subjective assessment of data quality as consistent across reviewers as possible. For case ascertainment, reviewers were asked to characterize the participating paediatric hospitals, to describe care-seeking patterns within the study area, and to assess the potential impact of these care-seeking practices on case ascertainment. For laboratory methods, reviewers were encouraged to consider possible limitations in specimen handling and transport, and in diagnostic techniques. The subjective assessment involved one question each about case ascertainment, diagnostic methods, and the population denominator used for incidence-rate calculations as expressed in the questions shown in Figure 2.

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Figure 2: Subjective data collected for determination of quality scores

2.6.10 Spn non-pneumonia, non-meningitis: additional data collected

Spn non-pneumonia, non-meningitis (NPNM) cases were differentiated into “severe” and “non-severe” (occult bacteraemia that was detected in countries where it is standard clinical practice to obtain blood culture in every febrile young child). All studies that reported cases and deaths from Spn NPNM syndromes were re-reviewed by a single Extended Working Group member and cases were separated out into “severe” and “non-severe”. The proportion of severe cases was calculated and abstracted for each article. When it was not possible to decide on the basis of the published paper which proportion of cases were “severe” and “non-severe”, authors were contacted for further details. “Severe” cases of NPNM were defined as:

CASE ASCERTAINMENTSelect the response that best describes your judgment of whether the case ascertainment methods were likely to miss a significant proportion of cases, for any of the disease syndromes studied. Unlikely to have missed a significant proportion of cases May have missed a significant proportion of cases but results

adjusted accordingly May have missed a significant proportion of cases, results not

adjusted Unable to determine

DIAGNOSTIC METHODSIn your opinion, the diagnostic methods described for the study were: Likely to be reliable Unlikely to be reliable Unable to determine reliability

POPULATION SOURCEDoes the study specify the source for the population data provided? Yes (answer question 53a) No, source of population data not specified (skip to question 54) No population data provided (skip to question 56)If yes, did the population denominator come from a reliable source (e.g. current census)? Yes No Unable to determine


• patientswhowerehospitalized;

• patients who had a localized invasive infection (myocarditis, septic arthritis,peritonitis, cellulitis, etc.);

• allNPNMcasesfromhighandveryhighmortalitycountrieswhereit isnotroutine to collect blood cultures in every young patient with a high fever.

• All papers from Africa that reported sufficient NPNM cases were categorized as “severe”.

2.7 Data entry

Abstractors entered data in a Microsoft InfoPath database, which was available online through the JHBSPH password-protected web portal. Paper copies of the DAF were available because abstractors occasionally could not enter data online themselves, and would need to send paper copies to study staff in Baltimore, Maryland, for data entry.

2.8 Data cleaning

2.8.1 Review of discrepancies and adjudication

If a data abstractor determined an article met criteria for abstraction of either disease incidence, age distribution of cases, distribution of syndromes, or CFR, the article was assigned to a second reviewer for repeat data abstraction. If the second reviewer determined the study did not meet criteria for abstraction of these data, or if the numeric data abstracted by the two reviewers differed, an adjudicator evaluated the discrepancy to determine the final result.

For studies published in English, French, German, Italian, Portuguese and Spanish, duplicate review was done as described above. For studies published in other languages, only one review was possible due to the limited number of appropriately trained individuals available to read the articles. The reports from the WHO HibRAT were reviewed by a trained individual familiar with the assessment tool’s methodology, and any useable data was adjudicated by a second trained individual.

Due to time and budgetary constraints, data cleaning efforts focused on the variables of most importance — those influencing the results of the meta-analyses. Data on incidence, CFR, age distribution, or syndrome distribution, were adjudicated by (at least) one of the members of the Extended Working Group. The following steps were taken, looking at the hard copies of the data tables side-by–side.

1) If both abstractors recorded the same numbers, the data was marked as acceptable.

2) If the numbers recorded by both abstractors were the same, but additional age or syndrome strata were recorded by one abstractor, the data abstraction with more information was accepted, as long as the data from that abstractor were internally consistent.

3) If the abstractors did not agree, the full article was retrieved and the correct results were determined by the adjudicator.

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The data quality score was a composite of the subjective responses from both abstractors and therefore did not require adjudication (Section 5.9.2), as were all open response variables. All other variables were drawn from the form of the abstractor deemed more complete or correct in steps two and three above, or chosen randomly if both abstractors were acceptable. It was felt that the abstractor who was more correct and detailed for the key variables would also be more correct in abstracting the remaining data. Other key variables used in the analysis (country, midpoint year of study) were occasionally missing and were obtained from the original article.

2.8.2 Elimination of articles for studies with multiple publications

The country and dates of surveillance were reviewed for articles contributing to the analysis. Possible overlapping surveillance time-periods or reporting of surveillance data in more than one article were identified. Seven articles were eliminated due to overlaps. Several articles were published in Spanish and English; if identical data were presented, the English language article was used.

2.8.3 Identification of missing papers

1) Papers identified by comparison with the previous work by Bennett and colleagues.

The citations that were identified in the literature search were first compared with those cited in the previous work by Bennett and colleagues. Of the citations in the the previous work by Bennett and colleagues, 23 Hib and four Spn articles were found that had not been identified by the 2005–2006 literature search. These were reviewed, and it was found that 18 Hib articles and two Spn articles did not meet the literature search criteria (unpublished articles, review articles etc.). There were five Hib and two Spn articles that had been missed by the literature search despite meeting all the requisite criteria. These articles were then retrieved, screened and abstracted, and were applicable.

2) Papers identified by expert review of articles.

At two dates, October 2006 and February 2007, a list of studies providing meningitis CFR and incidence data for analysis were circulated to a group of five experts in the fields of Hib and Spn research, and to the Working Group, in order to identify important studies which were absent from the list. Twenty-five articles missing from Hib or Spn meningitis CFR or incidence analysis identified by the experts and the Working Group were again reviewed to confirm the reason for exclusion. As a result of this process, one article was added that had been published after the literature search process was concluded, and two unpublished data sources were added. For three vaccine trial articles, the authors were contacted to obtain data that allowed their data to be included in the model.


3) Papers identified through country consultation.

A further source of data was obtained through the country consultation process. Letters were sent to each country in August 2007 with provisional Hib and Spn disease burden estimates and data sources of these estimates. Countries were offered the opportunity to bring to our attention additional sources of local data for review and possible addition to the database. Four data sources were identified during this process. One foreign language article was identified that had been indexed after the original search was completed; one country provided acceptable Ministry of Health data in time for addition to the database; one article identified in the literature review had been erroneously excluded, and a HibRAT with acceptable data was included despite the fact that the resulting peer-reviewed publication was excluded.

2.8.4 Non-pneumonia, non-meningitis (NPNM)

1) Review of all NPNM CFR articles.

All of the articles for which information on NPNM CFR had been abstracted were reviewed. For Spn, a CFR of zero to “non-severe” NPNM patients was assigned, and only the CFR from patients with severe NPNM illness was used in the analysis. All Hib NPNM cases were categorized as “severe” so no additional severity data was collected. NPNM CFRs were excluded from studies where there were fewer than 25 cases reported.

2) Missing NPNM data.

The papers reporting NPNM cases were assessed for the presence of additional variables required for the model. If any NPNM information was missing from an article deemed to have NPNM data, authors of papers included in the analysis were contacted to obtain:

• the proportion of Spn NPNM cases that was “severe” and “non-severe”. An approximate proportion with “severe” and “non-severe” disease from an author was acceptable. All authors were able to stratify cases using this nomenclature.

• Theoutcomeofpatientswith“severe”SpnNPNM.Thisallowedthecalculationof CFR for patients with “severe” NPNM SP infection only.

• The age distribution (under-1, under-2, under-5) of cases and deaths due toNPNM.

• Thenumberofdeathsineachagecategoryforarticlesthatreportedlargecaseseries of NPNM, but did not provide CFRs.

2.9 Qualitative assessment of meningitis incidence

Estimates of childhood meningitis incidence incorporate the number of observed meningitis cases (numerator) and the population of children from which the cases originated (denominator). Inaccuracies with either of these elements can make estimates of meningitis incidence difficult to interpret or compare with other studies. Identification of cases involves two separate activities. Firstly, cases of suspected meningitis must be identified (i.e. case ascertainment). Secondly, appropriate tests must be done to determine the presence of meningitis and to identify its etiology (i.e. diagnostic tests).

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2.9.1 Selection of articles

Criteria were established a priori to exclude studies likely to have results of limited comparability due to small size, limited diagnostic methods, and seasonal variation. These exclusion criteria are detailed in Section 5.3.

2.9.2 Data quality categories

The original approach for evaluating study quality included assessment of the methods used to determine the numerator and denominator for meningitis incidence calculations. However, because only half the studies provided enough information to evaluate the denominator used, no studies were excluded based on the assessment of the denominator. It was felt that this would unacceptably curtail an already sparse dataset.

To evaluate the numerator, abstractors were asked to subjectively assess case ascertainment and diagnostic methods (see section 5.6.9 for more detail). The following were considered important indicators of the likelihood of missing cases: not all hospitals in the study area that admitted children under five for treatment of bacteraemia, pneumonia, or meningitis were included in surveillance; some patients from the study area may have sought care outside the study area; laboratory specimens were not collected for all potential cases; laboratory testing was not performed for all specimens collected; some laboratory/medical records were not available or review of records was incomplete; there was inconsistent recruitment of cases in hospital (recruitment was not 24 hours/day, 7 days/week); study was not conducted in all areas of the facility where potential cases received care; some subjects refused to participate, and there were limitations in diagnostic methods (i.e. poor handling and transport of specimens, poor laboratory techniques). The likely quality of the diagnostic testing was also considered in the light of the type of study conducted; whether it was a prospective study with good quality control, was conducted in an area with generally high-quality health services, was conducted at a research institution or other facility with resources appropriate for study, or was conducted in an area with generally limited health services and facilities. When evaluating the care-seeking patterns, abstractors took the authors’ assessment of whether impact on case ascertainment was likely to be substantial or have little impact.

Based on the information available, the abstractors made a subjective decision on whether the laboratory and case-ascertainment methods were likely to be reliable or not.

Meningitis incidence studies were categorized into the following three groups, in order of decreasing quality.

Category “A”:• Both reviewers judged the case ascertainment and laboratory methods to be reliable.

Category “B”:• One reviewer judged case ascertainment and/or laboratory methods to be unreliable or un-evaluable.

Category “C”:• Both reviewers judged either case ascertainment or laboratory methods to be unreliable or un-evaluable.


Figure 3: Categorization of study quality by assessment of case ascertainment and diagnostic methods by two reviewers

Laboratory methods*

Case ascertainment*

Reviewer A Reliable/ adjusted

Reliable/ adjusted

Not reliable/ unable to determine

Reviewer A Reviewer B Reviewer B Reliable/ adjusted



Reliable Reliable A B C

ReliableNot reliable/

unable to determine

B B C



C C C

* Refer to Figure 2 for exact wording of questions used to determine quality scores.

Category “C” studies were excluded from the meta-analysis of meningitis incidence. For all CFR estimates and the estimate of the ratio of NPNM cases to meningitis cases, no exclusion was made based on the meningitis incidence quality category.

2.9.3 Data quality review

It was recognized that in this initial scoring process, studies where access to care was a limitation of the setting itself (and not of the study design) were categorized as “C”. Those “C” studies were re-reviewed where the study setting was a potential limitation on the access to care (refer to bullet list below) for two reasons — some under-ascertainment was judged to be acceptable as this was the only way to include in the analysis additional geographically representative high mortality data, and mortality estimates are adjusted for access to care, therefore, even if the incidence is underestimated through inclusion of these studies, the mortality estimate will be less affected. “C” quality studies re-reviewed included the following.

• Studiesthathadreceiveda“C”scoreforcaseascertainmentandan“A”ora“B”score for diagnostic methods.

• Studiesfrom(UnitedNationsregions)AfricaandAsiawithan“A”or“B”scorefor diagnostic methods, regardless of their original case ascertainment score.

• Studies with an “A” or “B” diagnostic methods score that reported data onculture-negative purulent meningitis regardless of their original case ascertainment score.

17WHO/IVB/09.02

Studies were assigned a final case ascertainment score based on refined criteria and, if possible, incidence was adjusted as described below.

• Studies that did not miss cases or that may have missed cases but provided an adjustment for this source of under-ascertainment were re-classified as “A”. In some cases, adjusted incidence was recalculated based on adjustment factors available in the paper (e.g. “only 85% of eligible children had a lumbar puncture done”, solution: adjust for the missed 15%).

• Studiesthatusedoptimalcaseascertainmentmethodsbutnecessarilymissedcasesdue to limitations in access to care in the setting where they were conducted. These studies were re-classified as “B” to avoid excluding all papers from high mortality regions from the analysis. The mortality estimates for these and all other papers are adjusted for access to care.

• Studies that missed cases because of flawed methodology and for which noadjustment was possible were classified as “C”.

The Working Group re-reviewed 108 papers for case ascertainment and assigned a score which was considered final. Ten papers with an initial case ascertainment score of “C” were re-categorized as “A”. Six of the ten were found to have good case ascertainment, one presented data adjusted for case ascertainment issues, and three reported adjustment factors that were used to compute adjusted incidence. Of these ten, three were from the African region and four from Asia. In addition, two papers from Africa (the Republic of the Gambia) that were initially scored “C” were re-categorized as “B”.

Final study quality scores by region and incidence are shown in Figure 5 (for Hib studies) and in Figure 9 (for Spn studies). In summary, a total of 59 (54%) Hib studies and 51 (57%) Spn studies with meningitis incidence were evaluated to be of “A” or “B” quality.


3.1 Country classifications

Countries were characterized by region and mortality status using two methods: one for analytic purposes and one for the reporting of results. For the purpose of reporting results, all summary statistics for articles and all disease burden estimates were grouped by region using WHO-defined geo-political strata (Annex 4) and under-5 mortality strata. However, because these strata do not adequately reflect the epidemiology of Spn and Hib disease in some countries, different groupings were used in the modelling of disease burden (Section 6.2).

3.2 Geographic and mortality strata used

Strata were defined by geographic and under-5 mortality criteria in order to group together countries that would have similar patterns of Hib and Spn disease epidemiology. When imputing values for countries where no Hib or Spn data was available, values from “neighbouring” countries within the same stratum were used, and this seemed most applicable to the disease epidemiology of that country.

Geographic strata

For the purpose of the Hib and Spn disease burden model, geographic groupings were required that: (a) reflected geographic proximity; (b) had a fine level of detail to allow step-wise aggregation; (c) defined groups geographically proximate to countries with potential differences in disease epidemiology. Several available definitions of geographic groupings were considered which were available through the World Bank, United Nations Children’s Fund (UNICEF), WHO, and the United Nations (UN), and it was determined that the UN definition of six regions and 21 geographic sub-regions best met the needs (Annex 5). At the sub-regional level, the African countries were further separated into those that were and were not in the so-called “Meningitis Belt” in response to the Independent Expert Panel’s suggestion, since meningitis surveillance in those countries may differ from that in other non-meningitis belt countries. Countries in the “Meningitis Belt” include the Republic of Benin, Burkina Faso, the Republic of Cameroon, the Central African Republic, the Republics respectively of Chad and of the Côte d’Ivoire, Eritrea, the Federal Democratic Republic of Ethiopia, the Republics respectively of Gambia, Ghana, Guinea-Bissau, Kenya and Mali, the Islamic Republic of Mauritania, the Republic of the Niger, the Federal Republic of Nigeria, the Republics respectively of Senegal and Sudan, the Togolese Republic, and the Republic of Uganda.

Other inputs for analysis3.

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Mortality strata

Studies were assigned the mortality strata of the country where the study occurred during the midpoint year of the study. The rationale of grouping the countries not only by geographic proximity but also on mortality strata was that the risk of Hib and Spn disease among children was likely to be associated with general health status and access to care, both of which would be reflected in under-5 mortality figures. Numeric under-5 mortality estimates were obtained from the 2005 United Nations Children’s Fund (UNICEF) State of the World’s Children Report rather than using the combination of child and adult mortality data used to generate WHO mortality regions (UNICEF 2004). Under-5 mortality rates were reported for 1980, 1990, 1995, 2000 and 2003. A time series of estimates for each country was generated by extrapolating the mortality rates for years between the intervals. The “low”, “medium”, “high” and “very high” under-5 mortality strata were defined based on consensus of the working group members as less than 30, 30–75, 75–150 and more than 150 deaths per 1000 live births, respectively.


Results4.

Of the 15 099 articles identified in the literature search (including at least 1331 duplicates), the inclusion/exclusion criteria, article abstraction, and cleaning process yielded 336 unique studies with evaluable extracted outcomes for consideration in the analysis; 205 studies contained Hib data and 211 studies contained Spn data (i.e. there were 80 studies that contained data for both Hib and Spn, 125 with Hib data only, and 131 with Spn data only). Of these, 266 studies contained key extracted outcomes and (176 Hib and 164 Spn) entered the meningitis and NPNM analytic database (with 74 containing data for Hib and Spn, 102 with Hib data only, and 90 with Spn data only). All but 13 Hib, six Spn articles, and two with both, contributed to at least one of the final meningitis and NPNM models (described in detail in the methods paper [Wolfson, 2009]). Note that more than one article may provide information on a single study, and one article may report more than one study (for example, if an article reports on more than one country, each country is considered a separate study).

Figure 4: Summary of references identified and studies abstracted (continued from Figure 1)

332 articles (336 studies) meet criteria for at least one extracted outcome and contain

evaluable data

241 articles (245 studies) used for final meningitis and NPNM

modelling

21 articles (21 studies) with C quality incidence data that have no other

data for the models

70 articles (70 studies) that have no data for the

meningitis and NPNM models

262 articles (266 studies) enter meningitis and NPNM analytic database (all A, B and C

quality incidence studies are included)

21WHO/IVB/09.02

4.1 Hib studies

[Refer to Annex 8 for a list of Hib studies with evaluable extracted outcomes and Annex 6 for key Hib outcome data in the analytic database.]

Of 205 studies that reported evaluable Hib key extracted outcomes, the majority came from EUR (N = 65) and AMR (N = 49) and the least from SEAR (N = 11) and EMR (N = 12) (Table 1 and Map 1). Approximately 65% of the studies in the database provided data on incidence of invasive Hib disease (N = 134 with adjusted and/or unadjusted estimates). A similar percentage described the age distribution of cases (N = 139, 68%). Thirty percent of Hib studies reported data on CFRs due to invasive Hib disease (N = 62), but few studies described how cases (N = 27) or CFRs (N = 5) were distributed by syndrome. In general, these findings were consistent across regions, with the exception of studies reporting incidence data; these were less common in EMR and SEAR (only four and three studies, respectively), most common in EUR, AMR and WPR (65%–75% of studies in those regions, 24–50 studies in each region), and AFR was in the middle with 14 studies (42% of all AFR studies).

Map 1: Number of studies with evaluable key extracted Hib outcomes in each country

Number of studies:

012-56-19


Few (24/134) studies that reported incidence adjusted those estimates (or provided the necessary information to calculate adjusted estimates), to account for under-detection of cases due to limitations of the study. Those studies that did adjust accounted for cases missed because they did not come to a study facility, cases not included because diagnostic tests were not done, or negative culture results that were probable bacterial disease.

Most of the Hib studies reported Hib meningitis incidence and fewer reported on other variables considered for the disease burden model. There were at least three times as many studies with Hib meningitis incidence data than for any other Hib syndrome in every region — of all studies with any incidence data, 82% contained meningitis incidence data compared to 9% for invasive pneumonia (N = 19) and 8% for NPNM data (N = 18). Studies providing data on the age distribution of pneumonia cases were also particularly rare, only 6.3% overall compared with 57% for meningitis.

23WHO/IVB/09.02

Table 1: Number of studies with evaluable Hib data for each of the key extracted outcomes considered for the global disease burden

model, by WHO region

Key extracted outcomes Total

WHO Regions (%)AFR AMR EMR EUR SEAR WPR

Incidence, unadjusted 127 14 (11) 32 (25) 4 (3) 50 (39) 3 (2) 24 (19)

All invasive 56 5 (9) 15 (27) 1 (2) 26 (46) 0 (0) 9 (16)Meningitis 103 12 (12) 22 (21) 4 (4) 40 (39) 2 (2) 23 (22)Pneumonia 18 4 (22) 4 (22) 1 (6) 7 (39) 0 (0) 2 (11)NPNM 18 3 (17) 4 (22) 1 (6) 7 (39) 0 (0) 3 (17)

Incidence, adjusted* 24 2 (8) 4 (17) 4 (17) 6 (25) 2 (8) 6 (25)

All invasive 5 0 (0) 2 (40) 0 (0) 1 (20) 0 (0) 2 (40)Meningitis† 21 1 (5) 2 (10) 4 (20) 6 (29) 3 (14) 5 (24)Pneumonia 1 1 (100) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)NPNM 0 - - - - - -

Age distribution 139 26 (19) 32 (23) 8 (6) 45 (32) 8 (6) 20 (14)


Syndrome distribution of cases (NPNM and meningitis)‡

27 4 (15) 7 (26) 1 (4) 9 (33) 2 (7) 4 (15)

Syndrome distribution of CFRs (NPNM and meningitis)§

5 0 (0) 1 (20) 0 (0) 2 (40) 0 (0) 2 (40)

Case-fatality ratio 62 12 (19) 16 (26) 3 (5) 14 (23) 3 (5) 14 (23)


Total (any data) 205 33 49 12 65 11 35

* Adjusted to account for under-detection of cases due to limitations of the study.† Eight studies provided adjusted estimates only; all other studies with adjusted data also

provided unadjusted data. Refer to Table 10 for a line listing of the Hib meningitis incidence studies.

‡ From the distribution of syndromes from each study, 27 studies had a syndrome distribution of cases that included cases of NPNM and meningitis.

§ From the distribution of syndromes from each study, five studies had a syndrome distribution of CFRs that included CFRs for NPNM and meningitis.


4.2 Spn studies

[Refer to Annex 8 for a list of Spn studies with evaluable extracted outcomes and Annex 7 for key Spn outcome data in the analytic database.]

There were 211 studies that had evaluable Spn extracted outcomes, with the majority from AMR (N = 68) and EUR (N = 65) and very few studies from SEAR (N = 5) and EMR (N = 8) (Table 2 and Map 2), as was observed for Hib. The characterization of Spn studies was remarkably similar to Hib studies with respect to the distribution of the type of primary outcome data of interest available. Most studies provided data on incidence of invasive Spn disease (55%, N = 117) and age distribution (77%, N = 162). Data on the CFR of invasive Spn disease were reported in 28% (N = 60) of papers, and few papers described the syndrome distribution of cases (18%, N = 38) or the syndrome distribution of CFRs (1%, N = 2). While in general these findings were similar across regions, the number of studies reporting incidence data in EMR and SEAR was grossly inadequate (two and one study, respectively), and EUR and AMR dominated (N = 65 and 68 studies, respectively).

Map 2: Number of studies with evaluable key extracted Spn outcomes in each country

Only five of the studies reporting Spn incidence provided the necessary information to adjust estimates to account for under-detection of isolates.

Number of studies:

012-56-19

25WHO/IVB/09.02

As seen for Hib studies, the majority of all Spn data on the extracted outcomes of interest pertained to meningitis. There were about three times as many studies with Spn meningitis data as for any other Spn syndrome for every outcome. This trend was similar across all regions. Very few studies had data on invasive Spn pneumonia incidence; EMR had no invasive Spn pneumonia data for any primary outcome of interest, SEAR only had data on the age distribution of invasive Spn pneumonia cases (two studies) and the CFR of invasive Spn pneumonia (one study), and EUR, with the most data on invasive Spn pneumonia incidence, had only 12 studies.

Table 2: Number of studies with evaluable Spn data for each of the extracted outcomes considered for the global disease burden model, by WHO region

Key extracted outcomes Total

WHO Regions (%)AFR AMR EMR EUR SEAR WPR

Incidence, unadjusted 117 13 (11) 33 (28) 2 (2) 52 (44) 0 (0) 17 (15)


Incidence, adjusted*

Meningitis† 5 1 (20) 3 (60) 0 (0) 0 (0) 0 (0) 1 (20)Age distribution 162 26 (16) 48 (30) 8 (5) 52 (32) 5 (3) 23 (14)


Syndrome distribution of cases (NPNM and meningitis)‡

38 4 (11) 15 (39) 0 12 (32) 3 (8) 4 (1)

Syndrome distribution of CFRs (NPNM and meningitis)§

2 1 (50) 0 (0) 0 0 (0) 0 (0) 1 (50)

Case-fatality ratio 60 8 (13) 27 (45) 1 12 (20) 1 (2) 11 (18)

All invasive 25 1 (4) 10 (40) 0 8 (32) 0 (0) 6 (24)Meningitis 34 6 (18) 16 (47) 1 5 (15) 1 (3) 5 (15)Pneumonia 13 3 (23) 9 (69) 0 0 (0) 0 (0) 1 (8)NPNM 7 2 (29) 3 (43) 0 1 (14) 0 (0) 1 (14)

Total (any data) 211 32 68 8 65 5 33

* Adjusted to account for under-detection of cases due to limitations of the study.† Refer to Table 18 for a line listing of the Spn meningitis incidence studies.‡ From the distribution of syndromes from each study, 38 studies had a syndrome distribution of

cases that included cases of NPNM and meningitis.§ From the distribution of syndromes from each study, two studies had a syndrome distribution

of CFRs that included CFRs for NPNM and meningitis.


4.3 Hib meningitis

4.3.1 Hib meningitis incidence data and study quality

Of the 205 studies that provided evaluable extracted outcomes considered for one or more variables in the Hib models, 126 (61%) had incidence data on any syndrome (Table 1), almost all on meningitis incidence (N = 103, 82%). Only 20 (16%) of the studies reporting meningitis incidence were adjusted for limitations of the study (e.g. cases missed because they did not come to a study facility, cases not included because diagnostic tests were not done, or culture results that were negative but were probable bacterial disease). Most of the Hib studies with meningitis incidence data were from EUR (N = 41), AMR (N = 22), and WPR (N = 24) (Table 3, Map 3 and Map 4). Only 12 studies from AFR contributed meningitis incidence data, and even fewer were available from EMR (N = 7) and SEAR (N = 4). Thus, the regions with the largest number of children under five years of age and with the highest mortality in that age group (SEAR and AFR), were under-represented.

Table 3: Number and percentage of studies with Hib meningitis incidence data, by WHO region

Study statisticsWHO Region

AFR AMR EMR EUR SEAR WPR TotalNumber of studies with Hib meningitis incidence data 12 22 7 41 4 24 110

Number of studies with Hib meningitis incidence data included in analysis

10 12 5 16 3 13 59

Percentage of studies within the region included in analysis

83.3 54.5 71.4 39.0 75 54.2 53.6

Map 3: Number of studies with Hib meningitis incidence data in each country

Number of studies:

012-56-9

27WHO/IVB/09.02

Map 4: Number of studies with included Hib meningitis incidence data in each country

The quality of the studies was considered, and “C” quality studies were excluded from the model analysis (Section 5.9.3). The number of studies rated “A” or “B” quality that were included in analysis is shown in Table 3. Figure 5 shows the distribution of Hib meningitis incidence studies stratified by WHO region and study quality. All regions had “A”, “B” and “C” quality studies. Although the AFR, EMR and SEAR had the fewest number of studies, most of these were of “A” or “B” quality and thus included in the analysis. Conversely, regions that had the most studies (AMR, EUR and WPR), also had the greatest proportion excluded from analyses — roughly 40%–60% of studies were of “C” quality. EUR had the most studies of any region (N = 41), but only 39% were documented to be of sufficient quality for inclusion and so the actual number of studies included in analysis from this region is on a par with those from AMR and WPR.

Number of studies:

0

1

2-5


Figure 5: Number of Hib meningitis incidence studies by data quality and WHO Region

Most of the studies with Hib meningitis incidence data came from countries with very low mortality (Refer to Annex 4 for a list of countries by mortality strata) (Figure 6). There was only one “A” quality study from high or very high mortality countries, but every mortality strata had multiple “B” and “C” quality studies.

Figure 6: Number of Hib meningitis incidence studies by data quality and mortality strata

Num

ber o

f stu

dies

A

A AB

B

B

C

C

AAAB

B

BCC

C

C

0

5

10

15

20

25

30

AFR AMR EMR EUR SEAR WPR

WHO Region

Num

ber o

f stu

dies

A

A

A

B

B BB

C

C

CC

0

5

10

15

20

25

30

35

40

very low medium high very high

Mortality strata

29WHO/IVB/09.02

4.3.2 Hib meningitis incidence data by study method

Vaccine probe studies provide the best estimation of Hib disease burden. In these trials, a vaccine with a known efficacy against microbiologically-confirmed disease is administered to part of the study population and not to the other. If the vaccine efficacy against microbiologically-confirmed disease is 100%, the burden of disease due to that organism is the difference in disease incidence between the vaccinated and unvaccinated groups (i.e. the rate difference, also called the attributable risk or rate).

Vaccine probe studies, the gold standard for estimating Hib meningitis incidence, were conducted in two of the six regions. Approximately half of the studies with Hib meningitis incidence data were retrospective in design (N = 55, 51%), the majority of which were excluded from analyses based on insufficient quality (N = 35, 64%). The next most frequent study types were prospective that employed active surveillance (N = 38, 35%). Prospective studies were less likely to be excluded because of poor quality (“C” score) than were retrospective studies.

Table 4: Type of study method used in studies with evaluable Hib meningitis incidence data, by WHO region

Study method TotalWHO Region


All studies 110 12 22 7 41 4 23

Vaccine probe 2 0 0 0 0 1 1Prospective, active surveillance 39 7 10 3 13 1 5

Prospective, passive surveillance 11 1 2 0 5 1 2

Prospective, other 2 0 0 1 0 0 1

Retrospective 55 4 10 3 23 1 14

Unknown 1 0 0 0 0 0 1

Included in analysis* 59 10 12 5* 16 3 13

Vaccine probe 2 0 0 0 0 1 1Prospective, active surveillance 30 6 6 3 10 1 4




Excluded from analysis* 50 2 10 2 25 1 10Prospective, active surveillance 9 1 4 0 3 0 1




Unknown 1 0 0 0 0 0 1

* Quality “A” and “B” studies were included in analysis and quality “C” studies were excluded (Section 5.6.9).


While all regions had several countries contributing data to estimate Hib meningitis incidence, the absolute number of countries with data included in analyses in each region was very small, ranging from three to eight countries (Table 5 and Map 5). At best, this represented only 30% of all countries in a region, which was in SEAR and WPR where there is felt to be the most diversity in populations. The lowest proportion of countries in a region represented in analyses was AFR (11%), where most of the meningitis deaths occur.

Table 5: The number and percent of countries with Hib meningitis incidence data, by WHO region

Country statisticsWHO Region


Total number of countries in the region 47 35 22 52 11 27

Number of countries with Hib meningitis incidence data 6 7 7 21 4 13

Number of countries with Hib meningitis incidence data included in analysis

5 6 5 8 3 8

Percentage of countries within the region represented in analysis 10.6 17.1 22.7 15.4 27.3 29.6

Map 5: Countries with and without Hib meningitis data

The types of surveillance conducted for the 110 studies with evaluable Hib meningitis incidence data were primarily hospital-based (overall, 57%) as opposed to either community-based, which described the fewest studies (2%), or outpatient (30%) (Table 6). This was true in every region. The type of surveillance was not related to whether the study was excluded or included in analyses, as all types were equally included and excluded.

Data included (35 countries)



31WHO/IVB/09.02

Table 6: Study population assessed in studies with evaluable Hib meningitis incidence data, by region

Study population TotalWHO Region


All studies 110 12 22 7 41 4 24

Community (any) 2 1 1 0 0 0 0

Outpatient (any) 33 4 7 0 14 2 6

Hospital only 63 7 12 6 20 2 16

Unknown 12 0 2 1 7 0 2

Included in analysis 59 10 12 5 16 3 13



Hospital only 33 5 8 4 7 1 8

Unknown 7 0 2 1 3 0 1

Excluded from analysis 51 2 10 2 25 1 11




Unknown 5 0 0 0 4 0 1

4.3.3 Extrapolation of Hib meningitis incidence for studies without data in the age group < 5 years of age

The majority of studies reporting Hib meningitis incidence for any age group <5 years of age had data for that entire age group (94%) (Table 7). Studies that only presented under-1 or under-2 incidence rates required having their under-5 incidence estimated based on ratios of cases under-1:under-5 or under-2:under-5 observed in other studies. Approximately 50% of studies with incidence data were excluded because of poor quality, resulting in 59 studies included in analysis, three of which required extrapolation because they only presented under-1 or under-2 incidence rates (two from AFR and one from SEAR). There were also four “C” quality studies (one AMR, one EMR, and two EUR) for which this extrapolation was made.


Table 7: Number of studies with Hib meningitis incidence data, by age group where incidence is available and by WHO region

Age TotalWHO Region


All studies

<1 50 8 9 2 20 1 10

<2 34 1 7 2 15 0 9

<5 103 10 21 6 39 3 24

<1 or <2 only (extrapolated <5)* 7 2 1 1 2 1 0

Total 110 12 22 7 41 4 24

Included in analysis

<1 26 6 3 2 10 1 4

<2 19 1 5 2 7 0 4

<5 56 8 12 5 16 2 13


Total 59 10 12 5 16 3 13

Excluded from analysis

<1 24 2 6 0 10 0 6

<2 15 0 2 0 8 0 5

<5 47 2 9 1 23 1 11


Total 51 2 10 2 25 1 11

* Only under-1 or under-2 incidence is available, no under-5 incidence; data were extrapolated to estimate under-5 incidence.

Distribution of meningitis cases across age groups may be more similar between countries with similar mortality than from countries within the same region but of differing mortality strata. When a study presented only under-1 or under-2 incidence data, an under-5 incidence was extrapolated using the age distribution of meningitis cases. This process is described in more detail in the methods paper [Wolfson, 2008]. Extrapolation of included studies was needed for studies from medium and high mortality countries only. Table 8 below shows the three included studies requiring extrapolation by mortality strata of the country.

33WHO/IVB/09.02

Table 8: The number of studies with Hib meningitis incidence data available for age groups less than one year or less than two years only (no data for age less

than five years) by mortality strata of the country

Age Number of studies

Mortality strata*

Very Low Medium High

Included<1 only 2 0 1 (AFR) 1 (AFR)

<2 only 1 0 1 (SEAR) 0

Excluded

<1 only 1 0 1 (AMR) 0

<2 only 2 2 (EMR, EUR) 0 0

<1 and <2 only 1 1 (EUR) 0 0

* Refer to section 6.2 for a description of mortality strata.

The number of studies that described the age distribution of meningitis cases used for this extrapolation is presented in Table 9 by region and mortality stratum of the countries within the region. The included studies needing extrapolation were from AFR and SEAR, and from medium and high mortality strata. Included studies needing extrapolation needed both under-1:under-5 and under-2:under-5 case ratios from other studies in the corresponding mortality strata, which was populated by data from both SEAR and AFR.

Table 9: Studies that described the age distribution for cases of Hib meningitis, by mortality strata and WHO region

Mortality strata* TotalWHO Region

AFR AMR EMR EUR SEAR WPRVery high

<1:<5 15 15 0 0 0 0 0

<2:<5 3 3 0 0 0 0 0

High

<1:<5 6 3 1 0 0 1 1

<2:<5 1 0 0 0 0 1 0

Medium

<1:<5 17 1 7 2 2 3 2

<2:<5 15 0 8 3 0 3 1

Very low

<1:<5 53 0 7 4 28 1 13

<2:<5 45 0 6 5 22 0 12

* Refer to section 6.2 for a description of country mortality strata.


4.3.4 Effect of quality score on Hib meningitis incidence

The median incidence of Hib meningitis reported in “C” studies was lower than the median incidence reported in “A/B” studies in AFR, SEAR and WPR; it was similar to the median incidence in “A/B” studies in AMR, EUR and EMR (Figure 7).

Figure 7: Incidence of Hib meningitis in children under five years of age (adjusted where possible) in studies included (“A/B”) versus excluded (“C”)

from analysis, by region*†‡

4.3.5 Effect of adjustment on Hib meningitis incidence

Adjusted Hib meningitis incidence data was available for 20 studies. Eight of these were estimated using a modelling process (HibRAT) that inherently incorporates the adjustments made to data resulting from surveillance studies (N = 7) or was from a vaccine probe trial (N = 1) where cases prevented by Hib vaccine far exceeds the number of invasive cases that can be detected through culture-based surveillance methods. Unadjusted meningitis incidence was not abstracted from the HibRATs. Therefore, only 12 studies had both unadjusted and adjusted incidence data available to evaluate the effect of adjustment.

In all studies with unadjusted and adjusted data, the adjustment resulted in an increase in the Hib meningitis incidence estimate, demonstrating that the use of unadjusted data leads to underestimation of the true burden of disease. The increase in incidence from unadjusted to adjusted estimates ranged from 1.3/100 000 to 64.7/100 000 for children less than five years of age. This equates to fold-rises in incidence of 1.1 to 4.3 (Table 10). The broad variability of the adjustment factor precludes applying a uniform adjustment to studies that do not themselves provide study-specific information to adjust the reported meningitis incidence rate.

0

20

40

60

80

100

8

A/B

2

C

12

A/B

9

C

5

A/B

1

C

16

A/B

23

C

2

A/B

1

C

13

A/B

11

C


Number of studies, quality score & WHO region

Inci

denc

e (p

er 1

00 0

00)

* Hib meningitis incidence estimates are not official WHO estimates, but are summaries of available data from the literature review.

† Excludes seven studies that did not present under-5 data (Table 8).‡ Boxplot key: grey box = interquartile range (IQR), Red dot = median, Range bars = minimum

and maximum values.

35WHO/IVB/09.02

Table 10: Studies reporting adjusted Hib meningitis incidence rates or reporting data sufficient to adjust the reported unadjusted meningitis incidence rates

WHO Region Country Reference** Age

groupUnadjusted incidence

Adjusted incidence

Fold increase

(adjusted/ unadjusted)

AFR South Africa Madhi (2002) <1† 106 117.66* 1.1

AMR

Dominican Republic Gomez (2000) <5 13.4 17.4* 1.3

Guatemala Asturias (2003) <5 13.8 15.9* 1.2

EMR

Egypt‡ Watt (1999) <5 - 23.1 -

Iran‡ Nelson <5 - 9 -

Pakistan‡ Al Awaidy (2003) <5 - 16.3 -

EUR

Bosnia and Herzegovina‡ Al Awaidy (2004) <5 - 14.7 -

Bulgaria Kojouharova (2002) <5 6.1 8.4 1.4

France Livartowski (1989) <5 14.7 17 1.2

France Reinert (1993) <5 13.4 14.77 1.1

Luxembourg De Jonghe (1995) <5 11 12.7 1.2

Ukraine‡ Platanov (2003) <5 - 8 -

SEAR

Indonesia Gessner (2005) <2 - 67 -

Nepal‡ Russell (2003) <5 - 5.4 -

Thailand Rerks-Ngarm (2004) <5 3.8 9.8 2.6

WPR

Australia McIntyre (1991) <5 19.7 22.9* 1.2

Fiji‡ Wilson (2003) <5 19.7 84.4 4.3

Mongolia Watt (2004) <5 28 38 1.4

Republic of Korea Kim (2004) <5 5.98 10.8* 1.8

Samoa‡ Carapetis (2002) <5 - 83.8 -

* Adjusted incidence was not provided directly by the authors but was based on data sufficient to adjust the reported unadjusted incidence rates.

** See Annex 8 for full reference. † <1 = under age one year, <2 = under age two years, <5 = under age five years.‡ HibRat = Hib Rapid Assessment Tool (Feikin, 2004; WHO, 2001).


4.3.6 Hib meningitis case-fatality ratio

Fifty-five studies reported case-fatality ratios (CFR) for Hib meningitis. The CFR data from all studies was included regardless of whether they had incidence data, and regardless of the quality scoring of the incidence data. [Note: CFR from “C” quality studies were similar to those from “A” and “B” quality studies (data not shown).] While all regions had CFR data (Table 1 and Map 6), there were very few studies from the EMR and SEAR with CFR for Hib meningitis. In none of the regions were data available from more than 14 studies.

Map 6: Number of studies with Hib meningitis CFR data in each country

Hib meningitis CFRs were highest in AFR, followed by SEAR and AMR (Figure 8). CFRs reported in the different studies varied widely in AFR and were more consistent across studies in other regions.

Number of studies:

0

1

2-5

37WHO/IVB/09.02

Figure 8: Hib meningitis CFRs by WHO region*†‡

4.4 Spn meningitis

4.4.1 Spn meningitis incidence data by study quality

Of the 211 studies that provided data for one or more variables in the Spn models, 117 (53%) had incidence data on any syndrome (Table 2), of which almost all were meningitis (N = 90, 77%). None of the Spn studies reported an adjusted meningitis incidence estimate. However, five studies provided sufficient information to adjust the published incidence estimate (see Table 18 for list of studies). Examples of such information include the proportion of cases that presented to the hospital but did not have a lumbar puncture, and the proportion of cases that were likely to be treated at non-study hospitals, etc. Most of the studies with Spn meningitis incidence data were from EUR (N = 41), AMR (N = 24), and WPR (N = 13). Only ten studies from AFR contributed meningitis incidence data, and fewer were available from EMR (N = 2). No studies were available from SEAR (N = 0) (Table 11, Map 7 and 8). The regions with the largest number of children under five years of age and the highest mortality (SEAR and AFR) were under-represented, as were children from EMR.

0

10

20

30

40

50

10 14 2 10 2 12


Number of studies & WHO Region

Cas

e-fa

tali

ty r

atio

0

10

20

30

40

50

10

AFR

14

AMR

2

EMR

10

EUR

2

SEAR

Number of studies & WHO region

Cas

e fa

talit

y ra

tio

12

WPR

* CFRs for the age category of <5 years of age.† CFR estimates summarize data from the literature review and are not official WHO estimates.‡ Boxplot key: grey box = interquartile range; dot = median; range bars = minimum and maximum

values.


Table 11: Number and percent of studies with Spn meningitis incidence data, by WHO region

Study statisticsWHO Region

AFR AMR EMR EUR SEAR WPR Total

Number of studies with Spn meningitis incidence data 10 24 2 41 0 13 90

Number of studies with Spn meningitis incidence data included in analysis

7 13 1 20 0 10 51

Percentage of studies within the region included in analysis 70.0 54.2 50.0 48.8 - 76.9 56.7

Map 7: Number of studies with Spn meningitis incidence data in each country

Number of studies:

0

1

2-5

6-12

39WHO/IVB/09.02

Map 8: Number of studies with included Spn meningitis incidence data by country

Studies were evaluated for quality. Those studies of “C” quality were excluded from the Spn global disease burden model analysis (Section 5.6.9). Figure 9 shows the distribution of Spn meningitis incidence studies stratified by WHO region and study quality. All regions with data had “A”, “B” and “C” quality studies. Although AFR had the fewest number of studies, most of these were of “A” or “B” quality and included in the model. The majority of studies from WPR were also included in the model. Conversely, in regions that had the greatest number of published studies (AMR and EUR), a greater proportion of those studies were of “C” quality (approximately 50% compared to approximately 30% in AFR and WPR).

Number of studies:0

1

2-5


Figure 9: Number of Spn meningitis incidence studies by data quality and WHO region

Similarly to Hib, most of the studies with Spn meningitis incidence data came from countries with very low mortality (Refer to Annex 4 for list of countries by mortality strata, Figure 10). There were no “A” quality studies from high or very high mortality countries, but every mortality strata had multiple “B” quality studies and at least one “C” quality study.

Figure 10: Number of Spn meningitis incidence studies by data quality and mortality strata

WHO region

Num

ber o

f stu

dies

A

A

AB

B

BC

C

AA

BC CC

0

5

10

15

20

25


Mortality strata

Num

ber o

f stu

dies

A

A

BBB

B

CC

C

C

0

5

10

15

20

25

30

35


41WHO/IVB/09.02

4.4.2 Spn meningitis incidence data by study method

Vaccine probe studies, also the gold standard for estimating Spn meningitis incidence, were conducted in one of the six WHO regions (AFR). Slightly less than half the studies with Spn meningitis incidence data were retrospective in design (N = 41, 46%), and the majority of these were excluded from analyses based on insufficient quality (N = 25, 66%). The next most frequent study types were prospective that employed active surveillance (N = 35, 39%). The prospective studies were less likely to be excluded because of poor quality (“C” score) than the retrospective studies.

Table 12: Type of study method used in studies with evaluable Spn meningitis incidence data, by WHO region

Study method TotalWHO Region

AFR AMR EMR EUR SEAR WPRAll studies 90 10 24 2 41 0 12

Vaccine probe 2 2 0 0 0 0 0

Prospective, active surveillance 35 4 12 1 14 0 4




Missing 1 0 0 0 0 0 1

Included in analysis* 51 7 13 1 20 0 10

Vaccine probe 2 2 0 0 0 0 0





Excluded from analysis* 38 3 11 1 21 0 2





Missing 1 0 0 0 0 0 1

* Quality “A” and “B” studies were included in analysis and quality “C” studies were excluded (Section 5.6.9).

As previously mentioned, no country in SEAR had data on Spn meningitis incidence and only one country in EMR had data (Table 13 and Map 9). The proportion of countries contributing Spn meningitis incidence data for the other regions ranged from 11% (AFR) to 23% (EUR) (5–12 countries per region). Results were similar to the number of countries providing Hib meningitis data for all regions except EMR and SEAR, for which more countries had Hib meningitis incidence data than Spn meningitis incidence data.


Table 13: Number and percentage of countries in the region with Spn meningitis incidence data, by WHO region

Country statisticsWHO Region


Total number of countries in the region 47 35 22 52 11 27

Number of countries with Spn meningitis incidence data 6 9 1 16 0 8

Number of countries with Spn meningitis incidence data included in analysis 5 6 1 12 0 6

Percentage of countries within the region represented in analysis 10.6 17.1 4.5 23.1 0.0 22.2

Map 9: Countries with and without Spn meningitis incidence data

The type of surveillance conducted for studies with evaluable Spn meningitis incidence data was primarily hospital-based (overall, 58%) as opposed to either community-based (2%) or outpatient studies (29%) (Table 14). This was true in every region with incidence data. The type of surveillance conducted was not strongly related to whether the study was excluded or included in analyses; however, slightly more hospital-based studies were included (63%).




43WHO/IVB/09.02

Table 14: Study population assessed in studies with evaluable Spn meningitis incidence data, by WHO region

Study population TotalWHO Region


All studies 90* 10 24 2 41 0 13




Unknown 10 0 0 1 6 0 3

Included in analysis 51 7 13 1 20 0 10




Unknown 4 0 0 1 1 0 2

Excluded from analysis 39 3 11 1 21 0 3




Unknown 6 0 0 0 5 0 1

Total 360 40 96 8 164 0 52

* Number of studies.

4.4.3 Extrapolation of Spn meningitis incidence for studies without data in the age group <5 years of age

The majority of studies reporting Spn meningitis incidence for any age group <5 years of age had data for that entire age group (88%) (Table 15). Studies that only reported under-1 or under-2 meningitis incidence rates required having their under-5 meningitis incidence rate estimated based on the ratio of under-1:under-5 or under-2:under-5 rates observed in other studies. Forty-three percent of studies were excluded because of poor quality, resulting in 51 studies included in the analysis, eight of which required extrapolation because they only presented under-1 or under-2 incidence rates (four from AFR, three from AMR and one from EUR). There were also three “C” quality studies in EUR for which this extrapolation was made.


Table 15: Number of studies with Spn meningitis incidence data, by age group where incidence is available and WHO region

Age TotalWHO Region

AFR AMR EMR EUR SEAR WPRAll studies

<1 41 4 10 2 22 0 3

<2 41 1 7 2 25 0 6

<5 79 6 21 2 37 0 13


Total 90 10 24 2 41 0 13

Included in analysis

<1 23 2 4 1 14 0 2

<2 25 1 3 1 16 0 4

<5 43 3 10 1 19 0 10


Total 51 7 13 1 20 0 10

Excluded from analysis

<1 18 2 6 1 8 0 1

<2 16 0 4 1 9 0 2

<5 36 3 11 1 18 0 3


Total 39 3 11 1 21 0 3

* Only under-1 or under-2 incidence is available, no under-5 incidence; data were extrapolated to estimate under-5 incidence.

The distribution of meningitis cases across age groups may be more similar between countries with similar mortality than between countries within the same region but of differing mortality strata. Table 16 below shows the eight included studies requiring imputation of the under-5 Spn meningitis incidence rate, by the mortality strata of the country of the study. Extrapolation was needed for studies from all but the “Very High” mortality countries.

45WHO/IVB/09.02

Table 16: The number of studies with Spn meningitis incidence available for age groups less than one year or less than two years only

(no data for age less than five years) by mortality strata of the country

Age Number of studies

Mortality strata*

Very Low Medium High

Included<2 only 7 4 (AMR,EUR) 2 (AFR) 1 (AFR)

<1 and <2 only 1 0 0 1 (AFR)

Excluded<1 only 1 1 (EUR) 0 0

<2 only 2 2 (EUR) 0 0


The number of studies that described the age distribution of meningitis cases available for extrapolation is presented in Table 17. The studies needing extrapolation were from AFR, AMR and EUR. Studies needing extrapolation used primarily under-2: under-5 case ratios from studies in corresponding mortality strata, which were available for these regions in at least one of those mortality strata.

Table 17: Studies that provided data on the age distribution for cases of Spn meningitis data, by mortality strata and WHO region

Mortality strata* TotalWHO Region

AFR AMR EMR EUR SEAR WPRVery high <1:<5 21 14 0 0 0 0 7 <2:<5 6 6 0 0 0 0 0High <1:<5 5 3 1 0 0 0 1 <2:<5 4 1 0 0 0 2 1Medium <1:<5 16 1 6 3 2 2 2 <2:<5 13 0 6 4 0 2 1Very low <1:<5 40 0 14 1 25 0 0 <2:<5 53 0 12 1 28 0 12



4.4.4 Effect of quality score on Spn meningitis incidence

Although for Hib meningitis incidence studies a similar trend was observed across regions in the relationship of “A/B” quality studies and “C” quality studies, the relationship of “A/B” quality studies and “C” quality studies varied across regions for Spn meningitis incidence (Figure 11). In general, the median incidence of Spn meningitis in “C” studies was lower than the median incidence in “A/B” studies in AFR, AMR and WPR, similar to the median incidence in “A/B” studies in EUR, and higher than the median incidence in “A/B” studies in EMR.

Figure 11: Incidence of Spn meningitis in children under five years of age (adjusted where possible) in studies included

(“A/B”) versus excluded (“C”) by WHO region*

4.4.5 Effect of adjustment on Spn meningitis incidence

Only five studies provided sufficient information to adjust the published Spn meningitis incidence estimates — three of these were from AMR, one from AFR and one from WPR.

0

10

20

30

40

50

60

3 3 10 11 1 1 19 18 0 0 10 3

A/B C A/B C A/B C A/B C A/B C A/B C


Number of studies, quali ty score & WHO Region

Inci

denc

e (p

er 1

00 0

00)

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10

20

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11

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A/B

3

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Number of studies, quality score & WHO region

Inci

denc

e (p

er 1

00 0

00)

60

* Spn meningitis incidence estimates are not official WHO estimates, but are summaries of available data from the literature review. Excludes 11 studies that did not have under-5 data (Table 16). Boxplot key: grey box = interquartile range (IQR); red dot = median; range bars = minimum and maximum values.

47WHO/IVB/09.02

In all studies with unadjusted and adjusted data, the adjustment leads to an increase in the Spn meningitis incidence estimate, demonstrating that the use of unadjusted data only leads to underestimates of the true burden of disease. The increase in incidence from unadjusted to adjusted estimates ranged from 1.3/100 000 to 2.4/100 000 children under five years of age. This represents a 1.0 to 1.8 fold-rise in incidence of Spn meningitis rates (Table 18). Although the adjustment factor had lower variability than it did for Hib meningitis incidence, it was judged unwise to apply a uniform adjustment to studies that do not provide study-specific data to adjust the Spn meningitis incidence data reported.

Table 18: Studies reporting data sufficient to adjust the reported unadjusted meningitis incidence rates

WHO Region Country Reference*Under-5

unadjusted incidence

Under-5 adjusted incidence

Fold increase

(adjusted/ unadjusted)

AMRBrazil Reis (2002) 24.7 25.9 1.0

Dominican Republic Gomez (2000) 5.2 7.3 1.4

Guatemala Asturias (2003) 16.3 18.7 1.1

AFR Mali Campbell (2004) 13.4 15.6 1.2

WPR Republic of Korea Kim (2004) 2.13 3.8 1.8

* See Annex 8 for full reference.

4.4.6 Spn meningitis case-fatality ratio

Thirty-four studies reported CFRs for Spn meningitis. All regions except EMR had CFR data, and SEAR had only one study with CFR data, as was observed for studies providing Spn meningitis incidence data (Table 2 and Map 10). AMR had the most data (16 studies), but no other region had more than six published studies.


Map 10: Number of studies with Spn meningitis CFR data in each country

Spn meningitis CFRs were highest in AFR, followed by SEAR and AMR (Figure 12). Observed CFRs varied widely in AMR and were more consistent across studies in other regions.

Figure 12: Spn meningitis CFRs by WHO region*

* CFRs for the age category of <5 years of age. Spn meningitis CFR estimates are not official WHO estimates, but are summaries of available key extracted outcomes from the literature review. Boxplot key: grey box = interquartile range (IQR); red dot = median; range bars = minimum and maximum values.

Number of studies:0

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4 11 0 4 1 3


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Number of studies & WHO region

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49WHO/IVB/09.02

4.5 Comparison of Hib and Spn meningitis incidence data

The number of studies that had data on any evaluable endpoint of interest was remarkably similar between Hib and Spn in each region (Figure 13. and Tables 7.1.1 and 7.2.1). AMR and EUR had the largest number of studies, and EMR and SEAR had the least number for both pathogens.

Figure 13: Number of studies with any evaluable extracted outcomes on Hib and Spn by WHO region

The number of studies that had data on meningitis incidence was also similar between Hib and Spn in AFR, AMR and EUR, but there were more Hib studies in EMR, SEAR, (which had no Spn meningitis incidence studies) and WPR (Figure 14). The number of studies with meningitis incidence data that were included in analysis was similar for Hib and Spn in each region, again with the exception of SEAR, with no Spn studies and only one Spn study in EMR. No region had more than 20 studies for either pathogen, and regions with the most studies were those with the fewest number of under-5 deaths (EUR and AMR).

0

10

20

WHO region

AFR

Num

ber o

f stu

dies

30

40

50

60

70

80

AMR EMR EUR SEAR WPR

Hib Spn


Figure 14: Number of Hib and Spn meningitis incidence studies included and excluded in the analysis by WHO region

At most, 12 countries in any region provided meningitis incidence data that were included in analysis (Figure 15). All regions had at least three countries with Hib data, but two regions were significantly lacking in Spn meningitis incidence data; zero countries from SEAR and only one country from EMR had Spn meningitis data. Spn data was available and included in the analysis for more countries in EUR compared to Hib data; the number of countries with data included in the analysis was the same for Spn and Hib in AFR and AMR.

0

10

15

WHO region

AFR

Num

ber o

f stu

dies

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25

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40

45

AMR EMR EUR SEAR WPR

Excluded Included

5

Hib Spn Hib Spn Hib Spn Hib Spn Hib Spn Hib Spn

51WHO/IVB/09.02

Figure 15: Number of countries with Hib and Spn meningitis incidence data included in analysis by WHO region

There were more studies that provided data on CFRs for Hib meningitis than for Spn, except AMR which had a similar number of studies for Spn and Hib. AMR was also the region with the greatest number of studies providing meningitis CFR data.

Num

ber o

f stu

dies

WHO region

Excluded Included

0

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Figure 16: Number of studies with Hib and Spn meningitis CFR data by WHO region

Num

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f stu

dies

WHO region

Hib Spn

0

2

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8

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4.5.1 Number of Hib and Spn studies by publication year

Studies reporting data on Hib meningitis incidence tended to be published in earlier years than studies reporting Spn meninigitis incidence. Publication of studies in the database increased for both Hib and Spn after 1981 to a maximum of 17 studies in any one year for Hib, and 26 for Spn. The low numbers of studies at or near 1981 is likely to reflect in part the exclusion of studies with cases prior to 1980. Since 1999, the number of studies with meningitis incidence data has been similar for Hib and Spn, and declined steadily to zero-to-one studies in 2004 and 2005 for both. Unlike for Hib in which the number of studies providing meningitis incidence data was relatively stable year-to-year, there was a clear peak for Spn between 1995 and 1998.

4.5.2 Number of Hib and Spn studies by midpoint year of study

Studies with evaluable extracted outcomes on any of the endpoints of interest tended to be from surveillance conducted in earlier years for Hib relative to Spn (Figure 17). The number of studies with Hib data was greatest from 1985 to 1995, and then declined slowly but steadily thereafter. Studies with Spn data by contrast rose steadily in number to a clear peak in 1997 and then declined to numbers similar to the Hib studies after 1999. There was a surge in Spn studies from 1995 to 1998, just prior to introduction of pneumococcal conjugate vaccine in the United States of America in 2000.

53WHO/IVB/09.02

Figure 17: Number of Hib and Spn studies by midpoint year of study

Num

ber o

f stu

dies

Year

Excluded Included

0

5

10

15

20

25

Studies that reported data on meningitis incidence tended to be from more recent surveillance for Spn compared to Hib (Figure 18). Studies in the database increased for both Hib and Spn to approximately three to seven studies per year after 1985, with peaks up to nine studies in any one year for Hib, and 11 studies for Spn. The low number of studies at or near 1981 probably reflects the exclusion of studies with cases prior to 1980. Since 1997 for Spn, and 2000 for Hib, the number of studies with meningitis incidence data has declined steadily to zero and one study, respectively, in 2004. Unlike Hib, in which the number of studies providing meningitis incidence data was relatively stable year-to-year, there was clear peak for Spn between 1997 and 1998.


Figure 18: Number of Hib and Spn meningitis incidence studies by midpoint year of study

Figure 19 below shows the number of studies with Hib and Spn meningitis incidence data by their midpoint year of the surveillance conducted separately for each WHO region. All regions had Hib and Spn data from studies throughout the entire calendar period of data collection, except SEAR which had only recent data for Hib, and no data for Spn, and EMR which had only recent Spn data. Prior to 1995, the number of studies with Hib meningitis incidence data was generally greater than Spn studies in every region. The large peak in Spn studies observed in Figure 18 was primarily the result of a large number of studies conducted in AMR. Similarly, there were a large number of studies with Hib data published in AMR at that time. By contrast, in EUR, the number of studies with Hib meningitis data fell to the lowest numbers for that region during this time period, probably the result of Hib vaccine introduction in many EUR countries, while the number of Spn studies remained at a steady rate. After the year 2000, studies in AMR fell to zero because Spn and Hib vaccine were both in routine use and therefore met exclusion criteria, while all other regions continued to have studies included in the dataset since pneumococcal conjugate vaccine was not introduced until later.

Num

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f stu

dies

Excluded Included

0

2

4

6

8

10

12

19821984

19861988

19901992

19941996

19982000

20022004

Year

55WHO/IVB/09.02

Figures 19: Number of studies with Hib and Spn meningitis incidence data by midpoint year of surveillance and WHO region

0

1

2

3

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6

1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004

AFR

Year

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Num

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1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004

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1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004

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1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004

EUR

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1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004

SEAR

Year

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Num

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1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004

WPR

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Num

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Trends in the number of meningitis incidence studies that were included in analysis were more similar between Hib and Spn than for all studies with meningitis data, with peaks in the number of studies being conducted in the late 1980s and in the late 1990s/early 2000s (Figure 20). The number of Spn studies increased to an average of 3.0 per year after 1992 compared to 1.3 per year prior to 1992. By contrast, Hib studies were more stable, with 2.9 studies conducted per year prior to 1993, compared with 2.4 per year after 1993.


Figure 20: Number of Hib and Spn meningitis incidence studies included in analysis by midpoint year of study

Num

ber o

f stu

dies

Spn Hib

0

2

4

6

8

19821984

19861988

19901992

19941996

19982000

20022004

Year

Spn studies were notably fewer in AFR and EMR compared to Hib studies, particularly in the earlier years (Figure 21). SEAR, which had no Spn studies, also did not have Hib studies until recently. In AMR, EUR and WPR, distribution of Hib and Spn studies over the literature review period were generally similar.

57WHO/IVB/09.02

Figure 21: Number of Hib and Spn meningitis studies included in analysis by midpoint year of study

0

1

2

3

4

1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004

AFR

Year

Spn Hib

Num

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f stu

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1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004

AMR

Year

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Num

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1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004

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Num

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EUR

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Num

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1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004

SEAR

Year

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1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004

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YearYear

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Num

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dies

4.6 Hib non-pneumonia, non-meningitis invasive disease

There were 27 studies that reported the syndrome distribution of Hib NPNM cases to meningitis cases (Table 19). The NPNM analysis also derived cases of NPNM if all invasive disease, meningitis and pneumonia data were available. There were eight studies that presented the distribution of cases ranging from Hib NPNM to meningitis among children less than one year of age, eight among children less than two years, and 25 among children less than five years of age.


Table 19: Number of studies reporting the syndrome distribution of Hib NPNM cases to meningitis cases by WHO region

StudiesWHO Region

TotalAFR AMR EMR EUR SEAR WPR

Number of studies 4 7 1 9 2 4 27

Percentage of total studies 14.8 25.9 3.7 33.3 7.41 14.8 100

Figure 22 shows the range and median of Hib NPNM/meningitis ratio by mortality strata and the number of studies that contributed to the analysis within each mortality strata. Most of the data available on Hib NPNM/meningitis ratio comes from countries in the very low mortality strata. The Hib NPNM/meningitis ratios are all below 1.0 indicating that cases of Hib meningitis always exceeded the number of Hib NPNM cases in these papers. This is consistent with prior knowledge that Hib disease is known to cause mainly meningitis and pneumonia. There is little variation across mortality strata, although a subtle trend can be observed towards a lower Hib NPNM/meningitis ratio in higher mortality countries.

Figure 22: Hib NPNM:meningitis case ratio median and range for studies according to NPNM case severity and mortality strata*

* Key: red dot = median; range bars = minimum and maximum values.

There were only five studies that provided CFRs for both Hib NPNM and meningitis for children less than five years of age, with a denominator consisting of at least 25 cases to allow direct comparison of the CFRs for these two syndromes (Table 20).

Number of studies (countries) and mortality strata

0.01

0.1

1

10

17 (13) 7 (7) 1 (1) 2 (1)


Med

ian

and

rang

e

59WHO/IVB/09.02

Table 20: Number of studies that reported both Hib NPNM and meningitis CFR from at least 25 cases by WHO region

StudiesWHO Region



Percentage of total studies 0 20 0 40 0 40 100

There were no data meeting these criteria from AFR, EMR and SEAR, and the data from the other regions were all from low mortality countries (Table 21). NPNM CFRs ranged between 0 and 3.9 (Table 21), and were in the same range but always lower than the meningitis CFR.

Table 21: Line list of CFRs and denominators for studies with both Hib NPNM and meningitis CFR (and at least 25 cases each)

Country Hib NPNM CFR Hib meningitis CFR

Hib NPNM number of cases

(denominator)

Hib meningitis number of cases

(denominator)

Australia 0.00 3.7 117 135

Australia 0.80 2.5 128 79

United Kingdom 3.90 4.1 51 195

United Kingdom 3.54 4.9 113 284

United States 0.00 4.0 228 457

4.7 Spn non-pneumonia, non-meningitis invasive disease

There were 38 studies that reported the syndrome distribution of Spn NPNM cases to meningitis cases directly or from which the syndrome distribution was inferred when cases of all invasive disease, meningitis, and pneumonia were available (Table 23). There were nine studies that presented the syndrome distribution of Spn NPNM and meningitis cases in children less than one year, 24 among children less than two years and 31 among children less than five years of age.

Table 22: Number of studies that reported the syndrome distribution of Spn NPNM cases to meningitis cases by WHO region

StudiesWHO Region



Percentage of total studies 10.5 39.5 0 31.6 7.9 10.5 100


Figure 23 shows the range and median of the ratio of Spn NPNM cases to meningitis cases according to mortality strata and disease severity of NPNM cases, with the number of studies and countries contributing to each. As expected, non-severe NPNM was documented only in the very low mortality strata. The distribution of cases differed by mortality strata, with more NPNM cases relative to meningitis cases in the very low mortality countries, regardless of NPNM severity, and fewer NPNM cases relative to meningitis cases in medium, high and very high mortality countries. Overall, there is a wider variation in the range of NPNM:meningitis ratio for Spn than for Hib.

Figure 23: Spn NPNM meningitis case ratio median and range for studies according to NPNM case severity and mortality strata

Number of studies (countries) and mortality strata

Med

ian

and

rang

e

0.01

0.1

1

10

100

very low 11(6)

very low27(14)

medium 4(3)

high 3(2)

very high 3(3)

Non-severe Severe

There were two studies that provided CFRs for both Spn NPNM and meningitis in children less than five years, with a denominator of at least 25 cases for each syndrome to allow for comparison of CFRs (Table 24). Since there were only two studies that provided CFRs from both Spn NPNM and meningitis (one in Kenya and one in the United States), it is difficult to draw general conclusions from this data. However, the CFR for Spn NPNM differed considerably between the two studies (Table 25). One explanation may be the heterogeneity of syndromes, and severity of these syndromes which are included in the NPNM category.

Table 23: Number of studies that reported Spn NPNM CFR and meningitis CFR by WHO region

StudiesWHO Region


Number of studies 1 1 0 0 0 0 2Percentage of total studies 50 50 0 0 0 0 100

61WHO/IVB/09.02

Table 24: Line list of CFRs and denominators for studies with both Spn NPNM and meningitis CFR (with at least 25 cases each)

Country Spn NPNM CFR

Spn meningitis CFR

Spn NPNM number of cases

(denominator)

Spn meningitis number of cases

(denominator)

Kenya 29.00 38.4 36 39

United States 0.59 11.0 169 27


The search identified 336 unique studies with evaluable extracted outcomes for consideration in the analysis to estimate Hib and Spn disease burden. The number of studies found with evaluable extracted outcomes for Hib was similar to that of Spn — 205 and 211 studies, respectively. However, while the syndromes caused by these two diseases are very similar, only 24% of the studies contained evaluable extracted outcomes for both Hib and Spn.

Efforts to identify these studies were extensive, with over 15 000 published articles investigated, from nine databases, and the full text reviewed from almost 2000 articles. The process to identify and abstract these articles and to evaluate and clean the database required a large team of people (over 70 people participated in the process), and took over two years to complete.

This literature review provided data to populate the meningitis and NPNM disease burden models. However, the literature search was not used to generate the pneumonia model inputs or to determine differences in disease risk or mortality in HIV-positive children compared to HIV-negative children. Wolfson and colleagues describe the separate literature seaches and the products of those searches in another publication (Wolfson, 2009).

5.1 Clinical standards for case definitions and classification

Studies identified through the literature review used a wide variety of case definitions for meningitis and pneumonia, and these were sometimes very different from the standards recommended by WHO. Keeping track of such heterogeneity across studies was one of the reasons a quality review was instituted. For the purpose of clinical case management, case definitions may differ from one setting to another; however, when definitions used for surveillance vary widely, it makes comparison across studies problematic. To promote uniform standards in clinical case ascertainment used for surveillance, the WHO has recommended the following definitions for meningitis and for pneumonia in children (WHO, 2003; WHO, 1999).

Discussion5.

63WHO/IVB/09.02

Meningitis

Suspected: Any person with sudden onset of fever (>38.5 °C rectal or >38.0 °C axillary) and one of the following signs: neck stiffness, altered consciousness or other meningeal sign.

Probable: A suspected case with cerebrospinal fluid (CSF) examination showing at least one of the following:

• turbid appearance;

• leukocytosis (>100 cells/mm3);

• leukocytosis (10–100 cells/ mm3) AND either an elevated protein (>100 mg/dl) or decreased glucose (<40 mg/dl).

Confirmed: A case that is laboratory-confirmed by growing (i.e. culturing) or identifying (i.e. by Gram stain or antigen detection methods) a bacterial pathogen (Hib, pneumococcus or meningococcus) in the CSF or from the blood, in a child with a clinical syndrome consistent with bacterial meningitis (WHO, 2003).

Pneumonia case definitions and classification

Pneumonia:

• Symptoms:coughordifficultbreathing,and

• signs:breathing>50breathsperminuteforinfantagedtwomonthstolessthanone year, breathing >40 per minute for child aged one to five years, and no chest indrawing, stridor or danger signs.

Severe pneumonia:

• Symptoms:coughordifficultbreathingplusanygeneraldangersignorchestindrawing or stridor in a calm child.

• General danger signs for children aged two months to five years: unable to drink or breastfeed; vomits everything; convulsions; lethargy or unconscious (WHO, 1999).

Clinical diagnosis of meningitis is more straightforward than that of pneumonia. The definition of pneumonia is based on the integrated management of childhood infections (IMCI) approach, which includes other acute lower respiratory tract infections and lacks specificity. In addition, etiological diagnosis of bacterial pathogens is easier in CSF than in blood. While pneumonia constitutes a larger fraction of the Hib and pneumococcal disease spectrum, surveillance of meningitis yields more accurate disease burden estimates compared to surveillance of pneumonia.


There is a need to update the current WHO recommended case definitions for probable and confirmed meningitis to include etiologic detection by use of PCR and possibly BinaxNOW® — an immunochromatographic antigen test to detect Streptococcus pneumoniae. The most recent WHO recommendations mention only blood culture and antigen detection of bacterial pathogens (WHO, 2003). However, since the publication of these guidelines in 2003, diagnostic technology has advanced. Polymerase chain reaction (PCR) has been validated for use in CSF and shown to be more sensitive than culture. Given its increasing use for CSF testing, even in resource- poor settings, there is a need to incorporate PCR diagnostics into the WHO standard case definitions for meningitis syndrome.

In this meta-analysis, invasive Hib and Spn cases were classified that were neither meningitis nor pneumonia, as non-pneumonia, non-meningitis (NPNM) syndrome. Cases in this category are largely confirmed cases of invasive Hib or Spn disease with no locus of infection (i.e. bacteraemia), or in the case of Hib, other clinical presentations such as cellulitis, septic arthritis and epiglottitis. Variability in blood- culturing practices across sites may lead to differences in observed incidence and CFRs of Spn NPNM syndromes. For example, a setting with limited capacity for blood culture will probably obtain cultures only among the sickest children, leading to higher CFRs compared to a setting with a high capacity. To account for this potential confounding the Spn analysis was stratified by “severe” and “non-severe” NPNM cases of Streptococcus pneumoniae. This NPNM classification is used for the first time in this review. A standardized approach to reporting cases by syndrome would provide significant benefit for future surveillance reports and disease burden estimation projects.

5.2 Limitations of Hib and Spn incidence studies

The disease burden due to Hib and Spn is difficult to estimate. Estimates of Hib and Spn incidence are directly related to the microbiologic capacity to perform blood and CSF cultures, including training, experience, and access to optimal materials. In many countries this capacity is wholly lacking. Even in studies where active surveillance is undertaken, there may be limitations in case ascertainment and laboratory diagnosis. Estimating incidence of pneumonia is particularly problematic because such a small proportion of disease is bacteraemic, and lung aspirates, which are more sensitive, are rarely done. For meningitis, several procedures and appropriate tests must be performed for diagnosis, and to identify the pathogen-specific etiology. Meningitis has multiple causes, and laboratory confirmation of disease etiology is needed to confirm a case of Spn or Hib. Complete case ascertainment is very difficult to achieve so the majority of meningitis cases have unknown or unconfirmed etiology. Challenges with both case ascertainment and microbiology may lead meningitis incidence figures in some studies to be a gross underdetection of the real disease burden.

65WHO/IVB/09.02

Some common difficulties with case ascertainment are:

some cases are not treated in hospital;•

some hospitals serving the study population may not be included in surveillance;•

cases may be given an alternative diagnosis; for example, some children with possible •meningitis are diagnosed as having febrile convulsions associated with another infectious disease;

cases with a clinical diagnosis of meningitis may not have diagnostic testing •done;

cases may present at times when study staff are not available;•

children in the study population may seek care outside the area (e.g. some cases •may travel to large cities for care).

Common limitations of lab detection include the following.

Lumbar puncture must be done to collect cerebrospinal fluid (CSF).•

Analysis of CSF must be done to diagnose meningitis. A variety of findings in CSF •are suggestive of bacterial meningitis. Different studies use different case definitions for meningitis cases that are likely to have a bacterial etiology.

For culture results to be accurate, specimens must be collected before antibiotics •are administered and done asceptically to avoid contamination. Culture results may be falsely negative if a specimen is collected after antibiotic administration.

Concentration of pathogen in CSF may be insufficient for detection at the time •of lumbar puncture (LP). Supplemental blood cultures and follow-up LPs may increase detection.

CSF and blood specimens must be handled appropriately (e.g. specimen transport, •storage).

CSF and blood specimens must be cultured using appropriate methods.•

CSF and blood specimens must be cultured using the appropriate reagents.•

Non-culture tests, such as bacterial antigen detection, or PCR, can be done on CSF •to increase sensitivity.

Common problems with the denominator data include:

the source of population data is unreliable or out of date;•

the study is carried out in a setting where the population is very difficult to estimate •(for example, a highly mobile population);

cases that are not from the population at risk are included in the numerator.•


5.3 Data sparsity and reporting inconsistencies in the published literature

The majority of studies that contributed data to primary endpoints of interest for both Hib and Spn were from AMR and EUR, while very few studies were available from SEAR and EMR. Unfortunately, many of the studies in all regions (25% to 50%) were deemed to be of insufficient quality for inclusion in analysis, which reduced even further the available data in all regions.

For both Hib and Spn, most of the data published for any outcome measure pertained to meningitis. Even though both Hib and Spn cause more cases and deaths due to pneumonia than meningitis, there were at least three times as many studies with evaluable meningitis data than for any other syndrome, in every region. It is well known that a significant proportion of pneumonia cases will have no etiology detected even when sample collection and laboratory methods are optimized. The inherent challenge is in obtaining a body fluid specimen from the site of infection (i.e. the lung). It is not surprising therefore that most of the surveillance literature focuses on those syndromes, such as meningitis, where a body fluid specimen can be collected from the site of infection.

Along with data sparsity, one of the limitations of this project was the heterogeneity of studies included for data abstraction and analysis. Apart from the differences in study design and methodology, studies were highly variable with regard to how data were reported. Among studies with incidence data, for example, abstractors often had to closely review the available data, and calculate one of the necessary inputs (e.g. the denominator). With the number of calculations required, it was not possible to verify with study authors the accuracy of the values obtained by the abstractors. However, for studies reviewed by two abstractors, discrepancies between the abstractors justified a review by a third individual who adjudicated the results.

5.4 Adjusted incidence data

Few studies (18% for Hib and less than 5% for Spn) reporting meningitis incidence were adjusted for limitations of the study, such as cases missed because they did not come to a study facility, cases not included because diagnostic tests were not done, or having negative culture results that were probable bacterial disease. In all studies with unadjusted and adjusted data, the adjustment resulted in an increase in the meningitis incidence estimate, demonstrating that the use of unadjusted data only leads to an underestimation of the true burden of disease. Because the amount of adjustment varied from study to study and is relative to the extent of the cases missed (not specified in the publications that were not adjusted), adjustment could not be applied to the majority of the studies. This means that any model using estimates of invasive meningitis incidence as a parameter, will result in an underestimation of the model outputs, potentially quite substantially.

67WHO/IVB/09.02

Those studies providing adjusted results attempt to address limitations in case ascertainment and/or diagnostic testing that could result in underestimates of disease burden. For example, the WHO HibRAT for the estimation of Hib meningitis incidence includes two adjustments that have been adopted in some recent studies (WHO, 2001; Rerks-Ngarm, 2004). Firstly, there is an adjustment for children who do not have lumbar puncture, which accounts for children who do not reach a study hospital or who do reach a hospital but who do not undergo lumbar puncture. Secondly, there is an adjustment for probable bacterial meningitis cases that do not have a pathogen identified to account for difficulties in specimen handling and testing in the laboratory. This adjustment also accounts for cases that might have false negative culture results because antibiotics are administered before lumbar puncture is done.

5.5 Foreign language papers

Most studies published in languages other than English were reviewed by two data abstractors. However, for a limited number of languages there was no individual, or only one trained individual who could screen and abstract data. In these cases, studies were excluded (if no translation could be obtained), or in the case of a limited number of trained reviewers, studies were reviewed only once instead of the standard double-abstraction.


Bennett JV et al. Haemophilus influenzae type b (Hib) meningitis in the pre-vaccine era: a global review of incidence, age distributions, and case-fatality rates. Geneva, World Health Organization, 2002. WHO/V&B/02.18. Available at: http://whqlibdoc.who.int/hq/2002/WHO_V&B_02.18.pdf

Feikin DR et al. Rapid assessment tool for Haemophilus influenzae type b disease in developing countries. Emerging Infectious Diseases, 2004, 10(7):1270–1276.

O’Brien KL et al. The global burden of disease due to Streptococcus pneumoniae in children less than 5 years of age. [submitted], 2009.

Rerks-Ngarm S et al. Prospective population-based incidence of Haemophilus influenzae type b meningitis in Thailand. Vaccine, 2004, 22(8):975–983.

State of the World’s Children 2005 — Childhood under threat. New York, United Nations Children’s Fund, 2004. Available at: http://www.unicef.org/publications/files/SOWC_2005_(English).pdf.

Watt JP e t a l . The g lobal burden of d isease due to Haemophi lus influenzae, type b in children less than 5 years of age, [submitted], 2009.

WHO-recommended surveillance standards. Geneva, World Health Organization, 1999. WHO/CDS/CSR/ISR/99.2. Available at: http://www.who.int/csr/resources/publications/surveillance/whocdscsrisr992.pdf.

Estimating the local burden of Haemophilus influenzae type b (Hib) disease preventable by vaccination: a rapid assessment tool. Geneva, World Health Organization, 2001. WHO/V&B/01.27. Available at: http://www.who.int/vaccines-documents/DocsPDF01/www625.pdf.

WHO-recommended surveillance standards for surveillance of selected vaccine-preventable diseases. Geneva, World Health Organization, 2003. WHO/V&B/03.01. Available at: http://www.who.int/vaccines-documents/DocsPDF06/843.pdf.

Wolfson LJ et al. Methods to estimate the global burden of disease due to Haemophilus influenzae type b and Streptococcus pneumoniae in children less than five years of age, [submitted], 2009.

References6.

http://whqlibdoc.who.int/hq/2002/WHO_V&B_02.18.pdf

http://www.unicef.org/publications/files/SOWC_2005_(English).pdf.

http://www.unicef.org/publications/files/SOWC_2005_(English).pdf.

http://www.who.int/csr/resources/publications/surveillance/whocdscsrisr992.pdf.

http://www.who.int/csr/resources/publications/surveillance/whocdscsrisr992.pdf.

http://www.who.int/vaccines-documents/DocsPDF01/www625.pdf.

http://www.who.int/vaccines-documents/DocsPDF01/www625.pdf.

http://www.who.int/vaccines-documents/DocsPDF06/843.pdf.

69WHO/IVB/09.02

Annex 1. Search strategies ..............................................................................70

1. Search strategy for Hib articles in Embase/Medline ............70

2. Search strategy for Hib articles in Biosis .................................72

3. Search strategy for Hib articles in CAB Abstracts ................73

4. Search strategy for Hib articles in Cochrane Library conducted in October 2005 ........................................................74

5. Search strategy for Hib articles in Pascal BioMed conducted in October 2005 ........................................................74

6. Search strategy for Spn articles in Embase/Medline ............76

7. Search strategy for Spn articles in Biosis .................................78

8. Search strategy for Spn articles in CAB ..................................79

9. Search strategy for Spn articles in COCHRANE ................80

Annex 2. Article screening instructions ........................................................81

Annex 3. Data Abstraction Form (DAF) ......................................................85

Annex 4. Member States by WHO Region .................................................108

Annex 5. Countries and territories by United Nations region ...............109

Annex 6. Study characteristics and key data from Hib studies entering the meningitis and NPNM analytic database ...........110

Annex 7. Study characteristics and key data from Spn studies entering the meningitis and NPNM analytic database ...........128

Annex 8. References for studies with evaluable outcome data ................145

Annexes7.


1. Search strategy for Hib articles in Embase/Medline

Step 1

(‘haemophilus influenzae type b’/exp OR ‘haemophilus influenzae type b’) OR (‘diphtheria pertussis poliomyelitis tetanus haemophilus influenzae type b hepatitis b vaccine’/exp OR ‘diphtheria pertussis poliomyelitis tetanus Haemophilus influenzae type b hepatitis b vaccine’) OR (‘diphtheria pertussis tetanus haemophilus influenzae type b vaccine’/exp OR ‘diphtheria pertussis tetanus haemophilus influenzae type b vaccine’) OR (‘dtp haemophilus influenzae type b vaccine’/exp OR ‘dtp haemophilus influenzae type b vaccine’) OR (‘diphtheria pertussis tetanus haemophilus influenzae type b vaccine’/exp OR ‘diphtheria pertussis tetanus haemophilus influenzae type b vaccine’) OR (‘haemophilus influenzae type b’/exp OR ‘haemophilus influenzae type b’) OR (‘haemophilus influenzae type b dtp vaccine’/exp OR ‘haemophilus influenzae type b dtp vaccine’) OR (‘haemophilus influenzae type b hepatitis b vaccine’/exp OR ‘haemophilus influenzae type b hepatitis b vaccine’) OR (‘haemophilus influenzae type b vaccine’/exp OR ‘Haemophilus influenzae type b vaccine’) OR (‘hepatitis b Haemophilus influenzae type b vaccine’/exp OR ‘hepatitis b Haemophilus influenzae type b vaccine’) OR (‘hib ompc’/exp OR ‘hib ompc’) OR (‘hib vax’/exp OR ‘hib vax’) OR ‘h influenzae’ OR ‘hib disease’ OR ‘hib infection’ OR ‘hib immuni’ OR ‘hemophilius influ’ OR (‘Haemophilus influenzae’/exp OR ‘Haemophilus influenzae’) OR (‘hemophilus influenzae’/exp OR ‘hemophilus influenzae’) OR (‘hemophilus influenzae’/exp OR ‘hemophilus influenzae’) OR (‘Haemophilus influenzae’/exp OR ‘Haemophilus influenzae’) AND [1980–2005]/py

Step 2

(‘purulent meningitis’/exp OR ‘purulent meningitis’) OR (‘bacterial meningitis’/exp OR ‘bacterial meningitis’) OR (‘meningitis, bacterial’/exp OR ‘meningitis, bacterial’) OR ‘meningitis and bacterial’ OR ‘bacterial meningitides’ OR ‘bacterial meningitides’ OR ((‘bacterial infection’/exp OR ‘bacterial infection’) AND (‘meningitis’/exp OR ‘meningitis’)) OR (‘bacterial pneumonia’/exp OR ‘bacterial pneumonia’) OR ((‘bacterial infection’/exp OR ‘bacterial infection’) AND (‘respiratory tract disease’/exp OR ‘respiratory tract disease’)) OR (‘bacteremia’/exp OR ‘bacteremia’) OR (‘septicemia’/exp OR ‘septicemia’) AND (‘bacteraemia’/exp OR ‘bacteraemia’) OR (‘septicemia’/exp OR ‘septicemia’) OR (‘septicaemia’/exp OR ‘septicaemia’) OR (‘sepsis’/exp OR ‘sepsis’) OR ‘lower respiratory tract infection ‘/exp OR ‘lower respiratory tract infection ‘) OR (‘lung infection’/exp OR ‘lung infection’) OR (‘infectious pneumonia’/exp OR ‘infectious pneumonia’) OR (‘community acquired pneumonia’/exp OR ‘community acquired pneumonia’) OR (‘lobar pneumonia’/exp OR ‘lobar pneumonia’) OR (‘bacterial pneumonia’/exp OR ‘bacterial pneumonia’) OR (‘pneumonia’/exp

Annex 1: Search strategies

71WHO/IVB/09.02

OR ‘pneumonia’) OR ‘bacteraemic pneumonia’ OR arli AND [1980–2005]/py # 2 (‘purulent meningitis’/exp OR ‘purulent meningitis’) OR (‘bacterial meningitis’/exp OR ‘bacterial meningitis’) OR (‘meningitis, bacterial’/exp OR ‘meningitis, bacterial’) OR ‘meningitis and bacterial’ OR ‘bacterial meningitides’ OR ‘bacterial meningitides’ OR ((‘bacterial infection’/exp OR ‘bacterial infection’) AND (‘meningitis’/exp OR ‘meningitis’)) OR (‘bacterial pneumonia’/exp OR ‘bacterial pneumonia’) OR ((‘bacterial infection’/exp OR ‘bacterial infection’) AND (‘respiratory tract disease’/exp OR ‘respiratory tract disease’)) OR (‘bacteremia’/exp OR ‘bacteremia’) OR (‘septicemia’/exp OR ‘septicemia’) AND (‘bacteraemia’/exp OR ‘bacteraemia’) OR (‘septicemia’/exp OR ‘septicemia’) OR (‘septicaemia’/exp OR ‘septicaemia’) OR (‘sepsis’/exp OR ‘sepsis’) OR (‘lower respiratory tract infection ‘/exp OR ‘lower respiratory tract infection ‘) OR (‘lung infection’/exp OR ‘lung infection’) OR (‘infectious pneumonia’/exp OR ‘infectious pneumonia’) OR (‘community acquired pneumonia’/exp OR ‘community acquired pneumonia’) OR (‘lobar pneumonia’/exp OR ‘lobar pneumonia’) OR (‘bacterial pneumonia’/exp OR ‘bacterial pneumonia’) OR (‘pneumonia’/exp OR ‘pneumonia’) OR ‘bacteraemic pneumonia’ OR dol AND [1980–2005]/py

Step 3 (1 AND 2)

Step 4

‘meningitis, hemophilius’ OR ‘hemophilius meningitis’ OR ‘meningitis, haemophilius’ AND ‘haemophilius meningitis’ OR ‘hib pneumonia’ OR ‘hib meningitis’ OR ‘invasive hib’ AND [1980–2005]/py # 4 ‘meningitis, hemophilius’ OR ‘hemophilius meningitis’ OR ‘meningitis, haemophilius’ AND ‘haemophilius meningitis’ OR ‘hib pneumonia’ OR ‘hib meningitis’ OR ‘invasive hib’ AND [1980–2005]/py

Step 5 (4 OR 3)

Step 6

(‘child’/exp OR ‘child’) OR (‘children’/exp OR ‘children’) OR (‘youth’/exp OR ‘youth’) OR youth* OR newborn* OR (‘newborn’/exp OR ‘newborn’) OR ‘new born’ OR ‘young people’ OR (‘childhood disease’/exp OR ‘childhood disease’) OR ‘childhood disease’ OR (‘baby’/exp OR ‘baby’) OR babies OR (‘infant’/exp OR ‘infant’) OR infant* OR juvenile* OR (‘juvenile’/exp OR ‘juvenile’) AND dolesce* OR childhood* OR toddler* OR kid OR kids OR ‘young patient’ OR dolescent* OR (‘adolescence’/exp OR ‘adolescence’) OR boy* OR girl* OR teenager* OR ‘young age’ OR pediatr* OR paediatr* OR (‘child death’/exp OR ‘child death’) OR (‘child health’/exp OR ‘child health’) OR (‘child care’/exp OR ‘child care’) OR (‘childhood mortality’/exp OR ‘childhood mortality’) OR (‘child hospitalization’/exp OR ‘child hospitalization’) OR (‘pediatric hospital’/exp OR ‘pediatric hospital’) AND [1980–2005]/py # 6 (‘child’/exp OR ‘child’) OR (‘children’/exp OR ‘children’) OR (‘youth’/exp OR ‘youth’) OR youth* OR newborn* OR (‘newborn’/exp OR ‘newborn’) OR ‘new born’ OR ‘young people’ OR (‘childhood disease’/exp OR ‘childhood disease’) OR ‘childhood disease’ OR (‘baby’/exp OR ‘baby’) OR babies OR (‘infant’/exp OR ‘infant’) OR infant* OR juvenile* OR (‘juvenile’/exp OR ‘juvenile’) AND dolesce* OR childhood* OR toddler* OR kid OR kids OR ‘young patient’ OR dolescent* OR (‘adolescence’/exp OR ‘adolescence’) OR boy* OR girl* OR teenager* OR ‘young age’ OR pediatr* OR paediatr* OR (‘child death’/exp OR ‘child death’) OR (‘child health’/exp OR ‘child health’) OR (‘child care’/exp OR ‘child care’) OR (‘childhood mortality’/exp OR ‘childhood mortality’) OR (‘child hospitalization’/exp OR ‘child hospitalization’) OR (‘pediatric hospital’/exp OR ‘pediatric hospital’) AND [1980–2005]/py


Step 7 (5 AND 6)

Step 8

Limit 5 to ([newborn]/lim OR [infant]/lim OR [preschool]/lim OR [school]/lim OR [child]/lim OR [adolescent]/lim) #8 #3 OR #4 AND ([newborn]/lim OR [infant]/lim OR [preschool]/lim OR [school]/lim OR [child]/lim OR [adolescent]/lim)

Step 9 (8 OR 7)

Step 10

‘case report’/exp

Step 11 (9 NOT 10)

Total number of citations 2213 conducted on the http://www.embase.com interface on Thursday 6 October 2005 at 09:00

2. Search strategy for Hib articles in Biosis

BIOSIS Previews <1997 to 2003> BIOSIS Previews <2005 Week 01 to 2005 Week 44> BIOSIS Previews <2004> Searched October 2005 (OVID Interface)

Step 1

(‘Haemophilus influenzae type b’ OR ‘diphtheria pertussis poliomyelitis tetanus Haemophilus influenzae type b hepatitis b vaccine’ OR ‘diphtheria pertussis tetanus Haemophilus influenzae type b vaccine’ OR ‘dtp Haemophilus influenzae type b vaccine’ OR ‘Haemophilus influenzae type b’ OR ‘Haemophilus influenzae type b dtp vaccine’ OR ‘Haemophilus influenzae type b hepatitis b vaccine’ OR ‘Haemophilus influenzae type b vaccine’

‘hepatitis b Haemophilus influenzae type b vaccine’) OR ‘hib ompc’ OR ‘hib vax’ OR ‘h influenzae’ OR ‘hib disease*’ OR ‘hib infection*’ OR ‘hib immuni*’ OR ‘hemophilius influ*’ OR ‘Haemophilus influenzae’ OR ‘hemophilus influenzae’ OR ‘hemophilus influenzae’ OR ‘Haemophilus influenzae’) AND [1980–2005]/py

Step 2

(‘purulent meningitis’ OR ‘bacterial meningitis’ OR ‘meningitis, bacterial’ OR ( ‘meningitis and bacterial’) OR ‘bacterial meningitides’ OR ((‘bacterial infection’ OR ‘bacterial infection*’) AND (‘meningitis’ OR ‘meningitis’)) OR (‘bacterial pneumonia’ OR ‘bacterial pneumonia’) OR ((‘bacterial infection’ OR ‘bacterial infection’) AND (‘respiratory tract disease’ OR ‘respiratory tract disease’)) OR ‘bacteremia’ OR ‘septicemia’ OR ‘septicaemia’ OR ‘sepsis’ OR ‘lower respiratory tract infection’ OR ‘lung infection’ OR ‘infectious pneumonia’ OR ‘community acquired pneumonia’ OR ‘lobar pneumonia’ OR ‘bacterial pneumonia’ OR ‘pneumonia’ OR ‘bacteraemic pneumonia’ OR arli )AND [1980–2005]/py

http://www.embase.com

73WHO/IVB/09.02

Step 3 (1 AND 2)

Step 4

(‘meningitis, hemophilius’ OR ‘meningitis, haemophilius’ AND ‘haemophilius meningitis’ OR ‘hib pneumonia’ OR ‘hib meningitis’ OR ‘invasive hib’) AND [1980–2005]/py

Step 5 (4 OR 3)

3. Search strategy for Hib articles in CAB Abstracts

1973 to September 2005 (Ovid Interface); search performed October 2005

Step 1

(‘haemophilus influenzae type b’ OR ‘diphtheria pertussis poliomyelitis tetanus haemophilus influenzae type b hepatitis b vaccine’ OR ‘diphtheria pertussis tetanus haemophilus influenzae type b vaccine’ OR ‘dtp haemophilus influenzae type b vaccine’ OR ‘haemophilus influenzae type b’ OR ‘haemophilus influenzae type b dtp vaccine’ OR ‘haemophilus influenzae type b hepatitis b vaccine’ OR ‘haemophilus influenzae type b vaccine’ ‘hepatitis b haemophilus influenzae type b vaccine’) OR ‘hib ompc’ OR ‘hib vax’ OR ‘h influenzae’ OR ‘hib disease*’ OR ‘hib infection*’ OR ‘hib immuni*’ OR ‘hemophilius influ*’ OR ‘haemophilus influenzae’ OR ‘hemophilus influenzae’ OR ‘hemophilus influenzae’ OR ‘haemophilus influenzae’)

AND [1980–2005]/py

Step 2

(‘purulent meningitis’ OR ‘bacterial meningitis’ OR ‘meningitis, bacterial’ OR (‘meningitis and bacterial’) OR ‘bacterial meningitides’ OR ((‘bacterial infection’ OR ‘bacterial infection*’) AND (‘meningitis’ OR ‘meningitis’)) OR (‘bacterial pneumonia’ OR ‘bacterial pneumonia’) OR ((‘bacterial infection’ OR ‘bacterial infection’) AND (‘respiratory tract disease’ OR ‘respiratory tract disease’)) OR ‘bacteremia’ OR ‘septicemia’ OR ‘septicaemia’ OR ‘sepsis’ OR ‘lower respiratory tract infection ‘OR ‘lung infection’ OR ‘infectious pneumonia’ OR ‘community acquired pneumonia’ OR

‘lobar pneumonia’ OR ‘bacterial pneumonia’ OR ‘pneumonia’ OR ‘bacteraemic pneumonia’ OR ril )AND [1980–2005]/py

Step 3 (1 AND 2)

Step 4


Step 5 (4 OR 3)


4. Search strategy for Hib articles in Cochrane Library conducted in October 2005

Step 1 - Search results 1 (1069 citations)

“Haemophilus influenzae type b” OR “diphtheria pertussis poliomyelitis tetanus Haemophilus influenzae type b hepatitis b vaccine” OR “diphtheria pertussis tetanus Haemophilus influenzae type b vaccine” OR “dtp Haemophilus influenzae type b vaccine” OR “Haemophilus influenzae type b” OR “Haemophilus influenzae type b dtp vaccine” OR “Haemophilus influenzae type b hepatitis b vaccine” OR “Haemophilus influenzae type b vaccine” OR “hepatitis b Haemophilus influenzae type b vaccine” OR “hib ompc” OR “hib vax” OR “h influenzae” OR “hib disease*” OR “hib infection*” OR “hib immuni*” OR “hemophilius influ*” OR “Haemophilus influenzae” OR “hemophilus influenzae” OR “hemophilus influenzae” OR “Haemophilus influenzae”

Step 2 - Search Results 2 (7627 citations)

“purulent meningitis” OR “bacterial meningitis” OR “meningitis, bacterial” OR (“meningitis and bacterial”) OR “bacterial meningitides” OR ((“bacterial infection” OR “bacterial infection*”) AND (“meningitis” OR “meningitis”)) OR (“bacterial pneumonia” OR “bacterial pneumonia”) OR ((“bacterial infection” OR “bacterial infection”) AND (“respiratory tract disease” OR “respiratory tract disease*”)) OR “bacteremia” OR “septicemia” OR “septicaemia” OR “sepsis” OR “lower respiratory tract infection” OR “lung infection” OR “infectious pneumonia” OR “community acquired pneumonia” OR “lobar pneumonia” OR “bacterial pneumonia” OR “pneumonia” OR “bacteraemic pneumonia” OR arli

Step 3 - Combine Steps 1 and 2 (260 citations)

Step 4 - Search results (31 citations)

“meningitis, hemophilius” OR “meningitis, haemophilius” OR “haemophilius meningitis” OR “hib pneumonia” OR “hib meningitis” OR “invasive hib”

Combine (Step 4 OR Step 3) (279 citations)

5. Search strategy for Hib articles in Pascal BioMed conducted in October 2005

Pascal BioMed (2005/01-2005/09,2003–2004,2001–2002,1999–2000,1997–1998, 1994–1996,1991–1993, 1987–1990. Searched October 2005 (WebSpirs Interface)

Step 1

(‘Haemophilus influenzae type b’ OR ‘diphtheria pertussis poliomyelitis tetanus Haemophilus influenzae type b hepatitis b vaccine’ OR ‘diphtheria pertussis tetanus Haemophilus influenzae type b vaccine’ OR ‘dtp Haemophilus influenzae type b vaccine’ OR ‘Haemophilus influenzae type b’ OR ‘Haemophilus influenzae type b dtp vaccine’ OR ‘Haemophilus influenzae type b hepatitis b vaccine’ OR ‘Haemophilus influenzae type b vaccine’

75WHO/IVB/09.02

‘hepatitis b Haemophilus influenzae type b vaccine’) OR ‘hib ompc’ OR ‘hib vax’ OR ‘h influenzae’ OR ‘hib disease*’ OR ‘hib infection*’ OR ‘hib immuni*’ OR ‘hemophilius influ*’ OR ‘Haemophilus influenzae’ OR ‘hemophilus influenzae’ OR ‘hemophilus influenzae’ OR ‘Haemophilus influenzae’) AND [1980–2005]/py

Step 2

(‘purulent meningitis’ OR ‘bacterial meningitis’ OR ‘meningitis, bacterial’ OR (meningitis and bacterial’) OR ‘bacterial meningitides’ OR ((‘bacterial infection’ OR ‘bacterial infection*’) AND (‘meningitis’ OR ‘meningitis’)) OR (‘bacterial pneumonia’ OR ‘bacterial pneumonia’) OR ((‘bacterial infection’ OR ‘bacterial infection’) AND (‘respiratory tract disease’ OR ‘respiratory tract disease’)) OR ‘bacteremia’ OR ‘septicemia’ OR ‘septicaemia’ OR ‘sepsis’ OR ‘lower respiratory tract infection’ OR ‘lung infection’ OR ‘infectious pneumonia’ OR ‘community acquired pneumonia’ OR ‘lobar pneumonia’ OR ‘bacterial pneumonia’ OR ‘pneumonia’ OR ‘bacteraemic pneumonia’ OR arli )AND [1980–2005]/py

Step 3 (1 AND 2)

Step 4


Step 5 (4 OR 3)


6. Search strategy for Spn articles in Embase/Medline

Search queries

No. Query Results Date

#1

(‘lower respiratory tract infection’/exp OR ‘lower respiratory tract infection’) OR ‘lower respiratory tract infection’ OR (‘lung infection’/exp OR ‘lung infection’) OR ‘lung infection’ OR (‘infectious pneumonia’/exp OR ‘infectious pneumonia’) OR ‘infectious pneumonia’ OR (‘bacterial pneumonia’/exp OR ‘bacterial pneumonia’) OR ‘bacterial pneumonia’ OR (‘community acquired pneumonia’/exp OR ‘community acquired pneumonia’) OR ‘community acquired pneumonia’ OR (‘lobar pneumonia’/exp OR ‘lobar pneumonia’) OR ‘lobar pneumonia’ OR (‘pneumonia’/exp OR ‘pneumonia’) OR ‘pneumonia’ OR ‘bacteraemic pneumonia’ OR ‘bacteraemic pneumonia’ OR arli OR ‘infectious pneumopath’ OR (‘streptococcus infection’/exp OR ‘streptococcus infection’) OR ‘streptococcus infection’ OR (‘bacterial meningitis’/exp OR ‘bacterial meningitis’) OR ‘bacterial meningit’ AND [1980–2005]/py

153 15317 November 2005

#2

(‘Streptococcus pneumoniae’/exp OR ‘Streptococcus pneumoniae’) OR (‘diplococcus pneumoniae’/exp OR ‘diplococcus pneumoniae’) OR (‘pneumococcus’/exp OR ‘pneumococcus’) OR ‘s pneumoniae’ OR pneumococci OR (‘pneumococcus vaccine’/exp OR ‘pneumococcus vaccine’) OR ‘pneumococcus vaccine’ OR (‘pneumococcus polysaccharide’/exp OR ‘pneumococcus polysaccharide’) OR ‘pneumococcal conjugate’ OR (‘pneumovax 23’/exp OR ‘pneumovax 23’) OR (‘prevnar’/exp OR ‘prevnar’) OR ‘pneumococcal heptavalent conjugate’ OR ‘pneumococcal heptavalent conjugate’ OR (‘pnu-imune 23’/exp OR ‘pnu-imune 23’) OR ‘ 7-valent pncompc vaccine’ OR ‘seven-valent pneumococcal ps-meningococcal ompc conjugate vaccine’ OR ‘pncrm7’ OR ‘mnc-crm197’ OR ‘mncc’ OR ‘pneumococcal polysaccharide vaccine’ OR (‘pneumovax’/exp OR ‘pneumovax’) OR ‘pnu-imune vaccine’ AND [1980–2005]/py

25 79017 November 2005

#3 #1 AND #2 11 392 17 November 2005

#4

‘Strep tococcus pneumoniae men ing i t i s ’ OR (‘pneumococcal meningitis’/exp OR ‘pneumococcal meningitis’) OR (‘meningitis, pneumococcal’/exp OR ‘meningitis, pneumococcal’) OR (‘pneumococcal meningitis’/exp OR ‘pneumococcal meningitis’) OR (‘pneumococcal pneumonia’/exp OR ‘pneumococcal pneumonia’) OR ‘pneumococcal bacteraemia’ OR ‘invasive pneumococcal disease’ OR ‘pneumococcal mortalit’ OR ‘pneumococcal invasive disease’ OR ‘pneumococcal *5 pneumonia’ OR ‘pneumococcal *5 meningitis’ OR ‘pneumococcal *5 bacteraemia’ OR ‘pneumococcal *5 invasive’ AND [1980–2005]/py

10 921 17 November 2005

#5#6 #3 OR #4 18 683 17 November 2005

77WHO/IVB/09.02

No. Query Results Date

#7

((‘child’/exp OR ‘child’) OR (‘child’/exp OR ‘child’)) OR ((‘children’/exp OR ‘children’) OR (‘children’/exp OR ‘children’)) OR child* OR ((‘youth’/exp OR ‘youth’) OR (‘youth’/exp OR ‘youth’)) OR youth* OR newborn* OR ((‘newborn’/exp OR ‘newborn’) OR (‘newborn’/exp OR ‘newborn’)) OR ‘new born’ OR ‘young people’ OR ((‘childhood disease’/exp OR ‘childhood disease’) OR (‘childhood disease’/exp OR ‘childhood disease’)) OR (‘childhood disease’/exp OR ‘childhood disease’) OR ((‘baby’/exp OR ‘baby’) OR (‘baby’/exp OR ‘baby’)) OR babies OR ((‘infant’/exp OR ‘infant’) OR (‘infant’/exp OR ‘infant’)) OR infant* OR juvenile* OR ((‘juvenile’/exp OR ‘juvenile’) OR (‘juvenile’/exp OR ‘juvenile’)) OR juvenille* OR childhood* OR toddler* OR kid OR kids OR ‘young patient’ OR adolescen* OR ((‘adolescence’/exp OR ‘adolescence’) OR (‘adolescence’/exp OR ‘adolescence’)) OR boy* OR girl* OR teenager* OR ‘young age’ OR pediatr* OR paediatr* OR ((‘child death’/exp OR ‘child death’) OR (‘child death’/exp OR ‘child death’)) OR ((‘child health’/exp OR ‘child health’) OR (‘child health’/exp OR ‘child health’)) OR ((‘child care’/exp OR ‘child care’) OR (‘child care’/exp OR ‘child care’)) OR ((‘childhood mortality’/exp OR ‘childhood mortality’) OR (‘childhood mortality’/exp OR ‘childhood mortality’)) OR ((‘child hospitalization’/exp OR ‘child hospitalization’) OR (‘child hospitalization’/exp OR ‘child hospitalization’)) OR ((‘pediatric hospital’/exp OR ‘pediatric hospital’) OR (‘pediatric hospital’/exp OR ‘pediatric hospital’)) AND [1980–2005]/py

1 795 09717 November 2005

#8 #6 AND #7 8423 17 November 2005

#9#3 OR #4 AND ([newborn]/lim OR [infant]/lim OR [preschool]/lim OR [school]/lim OR [child]/lim OR [adolescent]/lim)

648117 November 2005

#10 #8 OR #9 8423 17 November 2005

#11 case report /exp AND [1980–2005]/py1 221 465

17 November 2005

#12 #10 NOT #11 6994 17 November 2005


7. Search strategy for Spn articles in Biosis

Set 1

“lower respiratory tract infection” or “lower respiratory tract infection$” or “lung infection” or “lung infection$” or “infectious pneumonia” or “infectious pneumonia$” or “bacterial pneumonia” or “bacterial pneumonia$” or “community acquired pneumonia” or “community acquired pneumonia$” or “lobar pneumonia” or “lobar pneumonia$” or “pneumonia” or “pneumonia$” or “bacteraemic pneumonia” or “bacteraemic pneumonia$” or ARLI or “infectious pneumopath$” or “Streptococcus infection” or “Streptococcus infection$” or “bacterial meningitis” or “bacterial meningit$”

Set 2

“Streptococcus pneumoniae” or “Diplococcus pneumoniae” or “Pneumococcus” or “s pneumoniae” or Pneumococci or “Pneumococcus vaccine” or “Pneumococcus vaccine$” or “pneumococcus polysaccharide” or “pneumococcal conjugate$” or “Pneumovax 23” or Prevnar or “pneumococcal heptavalent conjugate” or “pneumococcal heptavalent conjugate$” or “Pnu-Imune 23” or “7-valent PncOMPC vaccine” or “seven-valent pneumococcal PS-meningococcal OMPC conjugate vaccine$” or “PNCRM7” or “Mnc-CRM197” or “MnCC” or “Pneumococcal Polysaccharide Vaccine$” or “Pneumovax” or “Pnu-Imune Vaccine$”

Set 3

“Streptococcus pneumoniae Meningitis” or “ P n e u m o c o c c a l M e n i n g i t i s ” or “Meningitis, Pneumococcal” or “Pneumococcal Meningitis” or “Pneumococcal pneumonia” or “Pneumococcal bacteraemia” or “Invasive pneumococcal disease$” or “Pneumococcal mortalit$” or “Pneumococcal invasive disease$” or “pneumococcal adj5 pneumonia” or “pneumococcal adj5 meningitis” or “pneumococcal adj5 bacteraemia” or “Pneumococcal adj5 invasive”

Set 4

(‘child’/exp OR ‘child’) OR (‘children’/exp OR ‘children’) OR child$ OR (‘youth’/exp OR ‘youth’) OR youth$ OR newborn$ OR (‘newborn’/exp OR ‘newborn’) OR ‘new born’ OR ‘young people’ OR (‘childhood disease’/exp OR ‘childhood disease’) OR ‘childhood disease’ OR (‘baby’/exp OR ‘baby’) OR babies OR (‘infant’/exp OR ‘infant’) OR infant$ OR juvenile$ OR (‘juvenile’/exp OR ‘juvenile’) OR juvenille$ OR childhood$ OR toddler$ OR kid OR kids OR ‘young patient’ OR adolescen$ OR (‘adolescence’/exp OR ‘adolescence’) OR boy$ OR girl$ OR teenager$ OR ‘young age’ OR pediatr$ OR paediatr$ OR (‘child death’/exp OR ‘child death’) OR (‘child health’/exp OR ‘child health’) OR (‘child care’/exp OR ‘child care’) OR (‘childhood mortality’/exp OR ‘childhood mortality’) OR (‘child hospitalization’/exp OR ‘child hospitalization’) OR (‘pediatric hospital’/exp OR ‘pediatric hospital’)

79WHO/IVB/09.02

8. Search strategy for Spn articles in CAB

Set 1

“lower respiratory tract infection” or “lower respiratory tract infection$” or “lung infection” or “lung infection$” or “infectious pneumonia” or “infectious pneumonia$” or “bacterial pneumonia” or “bacterial pneumonia$” or “community acquired pneumonia” or “community acquired pneumonia$” or “lobar pneumonia” or “lobar pneumonia$” or “pneumonia” or “pneumonia$” or “bacteraemic pneumonia” or “bacteraemic pneumonia$” or ARLI or “infectious pneumopath$” or “Streptococcus infection” or “Streptococcus infection$” or “bacterial meningitis” or “bacterial meningit$”

Set 2

“Streptococcus pneumoniae” or “Diplococcus pneumoniae” or “Pneumococcus” or “s pneumoniae” or Pneumococci or “Pneumococcus vaccine” or “Pneumococcus vaccine$” or “pneumococcus polysaccharide” or “pneumococcal conjugate$” or “Pneumovax 23” or Prevnar or “pneumococcal heptavalent conjugate” or “pneumococcal heptavalent conjugate$” or “Pnu-Imune 23” or “7-valent PncOMPC vaccine” or “seven-valent pneumococcal PS-meningococcal OMPC conjugate vaccine$” or “PNCRM7” or “Mnc-CRM197” or “MnCC” or “Pneumococcal Polysaccharide Vaccine$” or “Pneumovax” or “Pnu-Imune Vaccine$ “

Set 3

“Streptococcus pneumoniae Meningitis” or “ P n e u m o c o c c a l M e n i n g i t i s ” or “Meningitis, Pneumococcal” or “Pneumococcal Meningitis” or “Pneumococcal pneumonia” or “Pneumococcal bacteraemia” or “Invasive pneumococcal disease$” or “Pneumococcal mortalit$” or “Pneumococcal invasive disease$” or “pneumococcal adj5 pneumonia” or “pneumococcal adj5 meningitis” or “pneumococcal adj5 bacteraemia” or “Pneumococcal adj5 invasive”

Set 4

(‘child’/exp OR ‘child’) OR (‘children’/exp OR ‘children’) OR child$ OR (‘youth’/exp OR ‘youth’) OR youth$ OR newborn$ OR (‘newborn’/exp OR ‘newborn’) OR ‘new born’ OR ‘young people’ OR (‘childhood disease’/exp OR ‘childhood disease’) OR ‘childhood disease’ OR (‘baby’/exp OR ‘baby’) OR babies OR (‘infant’/exp OR ‘infant’) OR infant$ OR juvenile$ OR (‘juvenile’/exp OR ‘juvenile’) OR juvenille$ OR childhood$ OR toddler$ OR kid OR kids OR ‘young patient’ OR adolescen$ OR (‘adolescence’/exp OR ‘adolescence’) OR boy$ OR girl$ OR teenager$ OR ‘young age’ OR pediatr$ OR paediatr$ OR (‘child death’/exp OR ‘child death’) OR (‘child health’/exp OR ‘child health’) OR (‘child care’/exp OR ‘child care’) OR (‘childhood mortality’/exp OR ‘childhood mortality’) OR (‘child hospitalization’/exp OR ‘child hospitalization’) OR (‘pediatric hospital’/exp OR ‘pediatric hospital’)


9. Search strategy for Spn articles in COCHRANE

“lower respiratory tract infection” or “lower respiratory tract infection*” or “lung infection” or “lung infection*” or “infectious pneumonia” or “infectious pneumonia*” or “bacterial pneumonia” or “bacterial pneumonia*” or “community acquired pneumonia” or “community acquired pneumonia*” or “lobar pneumonia” or “lobar pneumonia*” or “pneumonia” or “pneumonia*” or “bacteraemic pneumonia” or “bacteraemic pneumonia*” or ARLI or “infectious pneumopath*” or “Streptococcus infection” or “Streptococcus infection*” or “bacterial meningitis” or “bacterial meningit*” or “Streptococcus pneumoniae” or “Diplococcus pneumoniae” or “Pneumococcus” or “s pneumoniae” or Pneumococci or “Pneumococcus vaccine” or “Pneumococcus vaccine*” or “pneumococcus polysaccharide” or “pneumococcal conjugate*” or “Pneumovax 23” or Prevnar or “pneumococcal heptavalent conjugate” or “pneumococcal heptavalent conjugate*” or “Pnu-Imune 23” or “Pnu Imune 23”or “ 7-valent PncOMPC vaccine” or “7 valent PncOMPC vaccine” or “seven valent pneumococcal PS meningococcal OMPC conjugate vaccine*” or “seven-valent pneumococcal PS-meningococcal OMPC conjugate vaccine*” or “PNCRM7” or “Mnc-CRM197” or “MnCC” or “Pneumococcal Polysaccharide Vaccine*” or “Pneumovax” or “Pnu-Imune Vaccine*” or “Streptococcus pneumoniae Meningitis” or “Pneumococcal Meningitis” or “Meningitis, Pneumococcal” or “Pneumococcal Meningitis” or “Pneumococcal pneumonia” or “Pneumococcal bacteraemia” or “Invasive pneumococcal disease*” or “Pneumococcal mortalit*” or “Pneumococcal invasive disease*” or “pneumococcalNEAR/5 pneumonia” or “pneumococcal NEAR/5 meningitis” or “pneumococcal NEAR/5 bacteraemia” or “Pneumococcal NEAR/5 invasive”

81WHO/IVB/09.02

The procedure for collecting all the published data follows a series of steps as follows:

1) Literature search: Systematically search the published literature to identify articles based on a defined search strategy.

2) Identify potentially relevant articles (Screening): Review the titles and abstracts (when available) of the articles identified in the previous step to remove articles which obviously are not relevant, leaving those which are classified as “potentially relevant” (or whose relevance is unknown based on the title and abstract). The objective of this step is to reduce the workload of retrieving articles that are obviously not relevant based on titles and abstracts, without losing sensitivity.

3) Retrieve the full text of all the potentially relevant articles (=screened articles).

4) Identify relevant articles: Screen again all potentially relevant articles to identify those for structured abstraction, using the same criteria as in Step 2. This fourth step is to eliminate, with the benefit of having the full article text available, those articles which clearly do not provide the information of primary interest (i.e., incidence rates, case-fatality rates). This step likely will eliminate only a small number of articles, as the bulk of the screening occurred in Step 2.

5) Assess eligibility of screened articles: Complete the first 2 pages of abstraction form for articles screened in; these 2 pages describe inclusion/exclusion criteria for the studies (e.g., year of case detection, vaccine use in the population, number of months of case ascertainment, cases from sub-group populations) and will determine if further data abstraction is appropriate.

6) Complete abstraction of eligible articles: For articles meeting inclusion criteria in Step 5, do structured abstraction of methods, results, and data quality, as well as bibliography check for other potentially relevant articles not yet identified.

This document describes the procedure for step 2.

Annex 2: Article screening instructions


Persons screening articles will be provided with a spreadsheet listing the ID # for all references which require screening, and another file with titles/abstracts for these references. This spreadsheet includes columns in which to indicate whether articles should be abstracted or excluded. The articles should be reviewed and placed into one of 5 categories:

1) Include: Reference has relevant data (as described below), should be retrieved for review/abstraction;

2) Review: Reference is a review article and has no primary data. It will not be pulled for abstraction but should be tracked as it may be reviewed later;

3) Exclude: Reference does not have relevant data and is not a review article;

4) Exclude pneumonia etiology: Reference does not have relevant data and is not a review article, but may have data on pneumonia etiology in childhood.

5) Foreign language: Reference is in another language (specify language). If screener is able to make a decision about the article based on the abstract, indicate which of the first 4 categories is appropriate, and also include the language of the article in column 5.

Screening: Categories of Articles (A-E)

A. INCLUDE

Articles should be ABSTRACTED if they have any data that are relevant for the study. Relevant data include:

1) Incidence of invasive disease in children for:

a) Hib meningitis

b) Hib pneumonia

c) Hib non-meningitis, non-pneumonia invasive disease (i.e., sepsis, bacteremia, septic arthritis, epiglottitis, etc.)

d) pneumococcal meningitis

e) pneumococcal pneumonia

f) pneumococcal non-meningitis, non-pneumonia invasive disease (i.e., sepsis, bacteremia, septic arthritis, epiglottitis, etc.)

2) Age distribution of cases of invasive Hib or pneumococcal disease

3) Case fatality rates of invasive Hib or pneumococcal disease

4) Distribution of Hib and pneumococcal disease syndromes (i.e., what proportion of cases are meningitis, pneumonia, sepsis, other invasive disease)

83WHO/IVB/09.02

5) Etiology data by syndrome - Some studies are by syndrome (e.g. meningitis or other invasive disease) and what was found proportionally by etiology. These studies may be useful for plausibility checks, they may provide CFR by syndrome/pathogen, and some of these may have a denominator that we could infer or get.

a) proportion of all meningitis that is Hib and/or pneumococcus

b) proportion of all invasive disease that is Hib and/or pneumococcus

Note: Pneumonia etiology studies should placed in category D below

B. REVIEW

These are review articles and will not be pulled for abstraction. However, these references should be distinguished as a separate category because review articles might provide empirical data not published in journals captured by the search strategy. This category provides us with an option to retrieve review articles and check if their references have been included or missed by the search strategy. (An example of such an article is the review by Heikki Peltola on Hib in Africa, which has a massive number of useful references.)

EXCLUDE

This category is for references without relevant data or references that are not review articles. Examples of types of articles which will be excluded (unless they have relevant data):

1) A case report (i.e. a single case)

2) Antimicrobial resistance studies

3) Vaccine immunogenicity and safety studies

4) Nasopharyngeal carriage studies

5) Molecular characterization of bacterial strains

6) Policy papers (except if the article might also provide primary disease burden data from specified countries)

7) Disease only among adults

8) Articles that don’t specifically cover H. influenzae or pneumococcus- e.g. other types of Haemophilus or syndromic studies. Do include studies of H. influenzae, even if no information about typing is provided, as long as the other criteria are met.

9) Studies including only children less than one year of age (e.g., studies of neonates)

10) Studies with isolates only from non-sterile sites.


There may be several variations of studies encountered:

a) Papers with isolates from sterile sites only Include;

b) Papers with isolates from both sterile and non-sterile sites, and the data can be separated into these 2 groups Abstract data for the sterile sites only;

c) Papers with isolates from both sterile and non-sterile sites, and data from each cannot be separated Exclude;

d) Papers with isolates only from non-sterile isolates Exclude.

Urine antigen should be treated as a non-sterile site isolate. The only exception would be a study with an overwhelming majority of sterile site isolates, and a very small number of non-sterile site isolates that were included for some compelling reason. For these types of studies, the paper should be screened in so the article can be reviewed and discussed with the rest of the group.

C. EXCLUDED (PNEUMONIA ETIOLOGY)

These references include studies that attempt to identify the etiology of pneumonia in children using lung tap, serology, or other methods. These articles should be excluded but marked as pneumonia etiology studies; they may be retrieved for review later. Select this category only if the article has data on children under age 5 years and if they include Hib and/or S. pneumo (otherwise select category C).

D. FOREIGN LANGUAGE

If the article is not in English, write in the space provided the language of the article (if language is not known, indicate “Unknown”).

***Note on screening of and abstracting data from case series with < 30 cases***

As noted in Category C, a case report of a single case should be excluded during screening. A study with more than one case can be included, provided the article’s content is appropriate for abstraction. However, once screened in, if a study does not meet criteria for abstraction of incidence data AND there are fewer than 30 cases included in the study, other data such as age/syndrome distribution and case fatality data will not be abstracted. In this situation, the data abstraction form should be started, but only limited information will be abstracted (see below).

If there are NO incidence data and there are 2-29 cases reported in a case series:

a) Complete Section A (Inclusion Criteria) Questions 1-7.

b) Skip Sections B (Study Design), C (Study Population), D (Case Definition)

c) Skip to Section E (Incidence Data) and answer Question 25 (“Does the manuscript report incidence data…”). The answer to either Q25 or Q26 will be “No.”

d) Skip to Section F (Age and Disease Syndrome Distribution Data) and answer Question 34 (“Does the manuscript report a total of 30 or more cases…”). The response should be “No.”

e) Skip to the last question of the form (Question 61) and end/submit the form.

85WHO/IVB/09.02

1. Study ID number __________________________________________________

Section A. Inclusion criteria

2. Is this a randomized controlled trial to test the effectiveness of Hib or pneumococcal vaccine?

Yes (skip to question 5)

No (continue to question 3)

If study presents Hib data, answer question 3; if study presents S. pneumo data, answer question 4.

3. Was there any use of Hib vaccine before or at any time during the study period?

Yes (answer question 3a)

No (skip to question 4)

Unknown (skip to question 4)

3a. Was Hib vaccine coverage 25% or higher for children under 5 years of age, and/or was there substantial use of Hib vaccine in the study population?

Yes (continue to question 3b) No (skip to question 4) Unknown (skip to question 4)

3b. Does the paper include any data on Hib disease reduction following widespread use of the vaccine?

Yes

No 3c. Are any data available from the period before vaccine coverage reached 25%,

or before vaccine use became substantial?

Yes (continue to question 4) No (STUDY EXCLUDED for Hib data abstraction, continue to

question 4)

Annex 3: Data Abstraction Form (DAF)


4. Was there any use of pneumococcal conjugate vaccine before or at any time during the study period?




4a. Was pneumococcal conjugate vaccine coverage 25% or higher for children under 5 years of age, and/or was there substantial use of pneumococcal conjugate vaccine in the study population?

Yes (continue to question 4b) No (skip to question 5) Unknown (skip to question 5)

4b. Does the paper include any data on S. pneumo disease reduction following widespread use of the vaccine?

Yes

No 4c. Are any data available from the period before vaccine coverage reached 25%,

or before vaccine use became substantial?

Yes (continue to question 5) No (STUDY EXCLUDED for S. pneumo data abstraction)

NOTE 1:

If study is excluded for both Hib and S. pneumo data abstraction, skip to end of form and answer question 61.

5. Did all reported cases occur after 1979?

Yes

No (STOP – EXCLUDE, skip to question 61)

6. Are there at least 12 months of case ascertainment?

Yes

No (STOP – EXCLUDE, skip to question 61)

Unknown (STOP – EXCLUDE, skip to question 61)

87WHO/IVB/09.02

7. Does the manuscript provide data for any subpopulation of children (e.g., HIV infection, sickle cell disease, racial/demographic groups, etc.)?


No (skip to Section B)

7a. What distinguished the sub-population from the general study population?

HIV infection

Shared medical condition other than HIV (e.g., sickle cell disease)

Different ethnic/racial background (e.g., Native Americans)

Displaced population

Degree of antibiotic use

Other (specify in 7b) 7b. If “Other,” describe the sub-population(s) [text]

7c. Are data about the general study population available also?

Yes (continue to section B) No (STOP – EXCLUDE, skip to question 61)

NOTE 2:

If the study is included: Complete sections B, C, and D. If study is excluded: Skip to end of form to question 61.

Section B. Study Design

8. Are data from more than one country presented?



8a. How many countries are included in the study? [numeric]

8b. Can data be distinguished by individual country?

Yes (skip to question 9; a separate abstraction form should be completed for each country whose data meet inclusion criteria )

No (complete question 8c)8c. If data cannot be distinguished by individual country, indicate all the

countries included in the study [text]

9. Describe the geographic area under study:

Whole country

Portion of country

Unknown


10. In which country did the study take place? [picklist of countries, include multi-country as option]

11. If the study was located in a portion of a country, indicate the name of the area where it was located. [text]

12. How is the study area described? (select one)

Rural setting

Urban and/or peri-urban setting

Mixed rural/urban setting

Unknown

13. Were cases identified in hospitals?

Yes (Answer question 13a, 13b, and 13c)

No (Skip to question 14)

Unknown (Skip to question 14)

13a. Is the number of hospitals included in the study known?

Yes

No (Skip to question 13c)

13b. If the number of hospitals is known, specify the number here __ __

13c. Type of hospitals included in study (check all that apply):

Tertiary care or referral hospital, or specialized research hospital

Regional, district, or local hospital (or primary and secondary care hospitals)

Other type of hospital (specify in question 13d) Unknown

13d. Describe the other type(s) of hospital included in the study [text]

14. Were cases identified among children who presented to outpatient facilities (and who may not have been admitted to the hospital)?

Yes

No

Unknown

15. Were cases identified from children in the home setting?

Yes

No

Unknown

89WHO/IVB/09.02

16. Describe data collection (check all that apply):

Retrospective

Prospective (answer question 16a)

16a. If prospective, indicate type of data collection (check all that apply)

Active surveillance

Passive surveillance

Other (specify in question 16b) Unknown

16b. If “Other,” specify data collection method [text]

Section C. Study Population

17. Are neonates (infants less than 1 month old) included?

Yes (skip to question 18)

No (answer question 17a)


17a. If neonates are not included, is the lower age limit for surveillance known?

Yes (specify in question 17b) No (skip to question 18)

17b. Specify the lower age limit in months (include ½ month as “0.5”) __ __ . __

18. Is HIV prevalence described in the manuscript?

Yes

No

19. Does the manuscript describe the under-5 mortality rate for the area under study?

Yes, in numeric terms (answer questions 19a and 19b)

Yes, in general terms (answer questions 19a and 19c)


19a. What is the source for the under-5 mortality rate? [text]

19b. What is the under-5 mortality rate?

More than 150 deaths per 1000 live births

75 to 150 deaths per 1000 live births

30-74 deaths per 1000 live births

Less than 30 deaths per 1000 live births

19c. How is the under-5 mortality rate (U5MR) characterized? [text]


20. Was Hib vaccine available to the population under study during the period of data collection (i.e., available via private market but not through national immunization program)?

Yes (Answer question 20a)


Not applicable - Randomized trial of Hib vaccine (Skip to question 21)


20a. Was information about the proportion of the population who received Hib vaccine provided?

Yes, in numeric terms (Complete question 20b) Yes, in general terms (descriptive, not numeric (Complete Q20c) No (Skip to Question 21)

20b. Enter the numeric estimate of the proportion of the population vaccinated with Hib, if provided __ __ %

20c. If no numeric estimate is provided but the proportion vaccinated with Hib is described, indicate description here (i.e., “few,” “most”) [text]

21. Was S. pneumo vaccine available to the population under study during the period of data collection? (i.e., available via private market but not through national immunization program)?

Yes (Answer question 21a)


Not applicable - Randomized trial of pneumococcal conjugate vaccine (Skip to question 22)


21a. Was information about the proportion of the population who received S. pneumo vaccine provided?

Yes, in numeric terms (Complete question 21b) Yes, in general terms (descriptive, not numeric (Complete Q21c) No (Skip to Question 22)

21b. Enter the numeric estimate of the proportion of population vaccinated with S. pneumo, if provided __ __ %

21c. If no numeric estimate is provided but the proportion vaccinated with S. pneumo is described, indicate description here (i.e., “few,” “most”) [text]

91WHO/IVB/09.02

22. Does the manuscript indicate the proportion of subjects who received antibiotics prior to presentation or specimen collection?

Yes, in numeric terms (Complete question 22a)

Yes, in general terms (Complete Question 22b)

No (Skip to Question 23)

22a. If a numeric estimate for the proportion was provided, enter it here __%

22b. If no numeric estimate is provided but the proportion of subjects who received antibiotics is described, enter the description here (e.g., “few”)

Section D. Case Definitions

23. Which Hib and/or S. pneumo invasive disease(s) was measured? (check all that apply)

Meningitis

Pneumonia

Non-pneumonia, non-meningitis invasive disease

All invasive disease other than meningitis (check here if pneumonia cases were not distinguished from other syndromes)

All invasive disease (check only if cases were not stratified by syndrome)

24. Case definition includes patients with positive result for (check all that apply):

Blood specimens, by culture

CSF specimens, by culture

CSF specimens, by non-culture method (e.g., PCR, latex agglutination)

Other (non-blood, non-CSF) normally sterile fluid specimens (e.g., pleural fluid, joint fluid, peritoneal fluid) by culture

Other normally sterile fluid specimens, by non-culture method

Other laboratory tests (specify in question 24a)

24a. Specify other laboratory test(s) [text]

24b. Indicate which of the following describe the data abstracted from this study:

No data presented on H. influenzae or Hib invasive disease

Presents data on H. influenzae invasive disease, no serotyping was done (for these papers, assume all H. influenzae invasive disease = Hib

Presents data on H. influenzae type b invasive disease, states all isolates were serotyped

Presents data on H. influenzae type b invasive disease, states some isolates were serotyped and others were assumed to be type b

Presents data on H. influenzae, type b invasive disease, but does not state whether serotyping was done


Section E: Incidence Data

Answer the following questions to determine if Section E (Incidence Data) should be completed for the manuscript.

25. Does the manuscript report incidence, or data that can be used to calculate incidence, for Hib and/or S. pneumo invasive disease for any age group among children under age 5 years?

Yes (answer question 26)

No (skip to Section F)

26. Does the study involve at least 20,000 child-years per one-year age group of overall observations, or does it include the size of the entire population of the age group in the country under study? (This criterion does not apply to clinical trials.) For example:

If incidence is for 0-11 months at least 20,000 child-years of observation, or all children <1 year in the country are included;

If incidence is for 0-23 months at least 40,000 child years of observation, or all children <2 years in the country are included;

If incidence is for 0-59 months at least 100,000 child years of observation, or all children <5 years in the country are included

YES, for either Hib or S. pneumo (Continue to Question 27, complete Section E)

NO, for both Hib and S. pneumo (Skip to Section F, starting with Q#34)

Not applicable – study is a clinical trial (Continue to Q#27, complete Section E)

Unknown (Skip to section F, Q#34)

NOTE 3:

If the response for Hib and S. pneumo is “No,” skip to Section F. If the response for either Hib or S. pneumo is “Yes,” continue with Section E.

27. Start date of data collection in study; if no month is provided, use “07” for month [format mm/yyyy]

28. End date of data collection in study; if no month is provided, use “07” for month [format mm/yyyy]

29. Is the number of child-years of observation reported, or can it be calculated from data provided?

Yes (answer questions 29a)


29a. Enter the total number of child-years of observation in children under 5. If the study is a randomized trial, report this for the control group only. [numeric]

93WHO/IVB/09.02

Section E1. Incidence data for surveillance studies

If incidence data will be abstracted, complete Section E1 (starts with question 30).

30. Complete the following table for all incidence data reported in the manuscript, or for data which may be used to calculate incidence. If these data are provided by multiple age categories (e.g, children under 5 years and children under 2 years), include all information as separate entries in the table. Specify age in months. If neonates are included, or if it is not known if neonates are included, indicate lowest age as “00 months.” When available (either reported or derived from data provided), data should be recorded for the following age strata:

lowest age to 59 months (<5 years)•


lowest age to 11 months (<1 year)•

If there are data for the general population, as well as data stratified for sub-groups (e.g. children infected/not infected with HIV), enter data for the overall population only. If the study is a vaccine trial, report data for the control group only, and for the group with the lowest minimum age (i.e., intent-to-treat analysis or children not fully vaccinated with 3 doses). This group will have the broadest age range.

If the authors report adjusted incidence rates only, skip to question 31.

30a. Hib disease(select one) [picklist]

Age range reported Calculation of incidence rate

Lowest age

(mths)

Highest age

(mths)

No. of cases

Denominator (child-years)

Incidence rate per 100,000

child years

Meningitis

Pneumonia


All invasive disease other than meningitis

All invasive disease

[add rows if needed]


30b. S. pneumo disease (select one) [picklist]

Age range reported Calculation of incidence rate

Lowest age

(mths)

Highest age

(mths)

No. of cases

Denominator (child-years)

Incidence rate per

100,000 child years

Meningitis

Pneumonia





31. Does the manuscript report disease incidence for children under age 5 years adjusted for any limitations?

Yes (complete question 31a and/or 31b, then read Note 4)

No (skip to Note 4)

Complete the following table for all adjusted incidence data reported in the manuscript. If there are data for the general population, as well as data stratified for sub-groups (e.g. children infected and not infected with HIV), enter data for the overall population only. If the study is a vaccine trial, report data for the control group only, and for the group with the lowest minimum age (i.e., intent-to-treat analysis or children not fully vaccinated with 3 doses).

For the column titled, “Type of adjustment for this rate,” the picklist will be:

1. Case ascertainment (cases missed because they did not come to a study facility or were missed)

2. Diagnostic techniques (cases not included because diagnostic tests not done or adjustments made for culture-negative, probable bacterial disease)

3. Both (1) and (2).

4. Other type of adjustment (Specify in Question 31b or 31d)

95WHO/IVB/09.02

31a. Hib disease (select all that apply) [picklist]

Age range reported Adjustments to incidence rate

Lowest age

(mths)

Highest age

(mths)

Type of adjustment for

this rate [indicate # from list above]

Adjusted Incidence rate

per 100,000 child –years

Meningitis

Pneumonia





31b. If “Other type of adjustment,” specify adjustment here


31c. S. pneumo disease (select all that apply) [picklist]

Age range reported Adjustments to incidence rate

Lowest age

(mths)

Highest age

(mths)

Type of adjustment for

this rate [indicate # from list above]

Adjusted Incidence rate

per 100,000 child –years

Meningitis

Pneumonia





31d. If “Other type of adjustment,” specify adjustment here

NOTE 4:

If the manuscript reports findings from a vaccine-probe study, in which the incidence of vaccine-preventable clinical disease with unconfirmed etiology is reported, complete Section E2. Otherwise, skip to Section G.

Section E2: Incidence data from vaccine probe studies

32. Intervention administered (check all that apply)

Hib vaccine

S. pneumo vaccine

97WHO/IVB/09.02

33. Complete following table for all categories of clinical disease. These will represent either Hib clinical disease or S. pneumo clinical disease depending on which vaccine was evaluated in the study. If these data are reported in multiple age strata (e.g, children under 5 years, children under 2 years), include all information as separate entries in the table. Specify age in months. If neonates are included, or if it is not known if neonates are included, indicate lowest age as “00 months.” When available (either reported or derived from data provided), data should be recorded for the following age strata:

lowest age to 59 months (<5 years)


lowest age to 11 months (<1 year)

If there are data for the general population, as well as data stratified for sub-groups (e.g. children infected and not infected with HIV), enter data for the overall population only.

33a. Clinical outcome (select all that apply)

Age range Incidence per 100,000 child-years

Lowest age

(mths)

Highest age

(mths)

Intervention Group

Control group

Hospitalization for pneumonia

WHO-defined severe pneumonia

Radiographic findings consistent with WHO criteria for diagnosis of pneumonia

Radiologically-confirmed pneumonia

Any infiltrate on chest x-ray

Clinical signs/symptoms of pneumonia


Age range Incidence per 100,000 child-years

Lowest age

(mths)

Highest age

(mths)

Intervention Group

Control group

Total pneumonia deaths

Hospitalization for meningitis

CSF findings suggestive of bacterial meningitis

Lumbar puncture done

Clinical signs/symptoms of meningitis

Total meningitis deaths

Other (specify in 33b)

33b.

[additional rows added as needed]

33b. If the clinical disease outcome measured is not among the options provided, specify the outcome in the space provided above [text]

NOTE 5:

If Section E1 (± Section E2) has been completed, skip to Section G.

99WHO/IVB/09.02

Section F. Age and Disease Syndrome Distribution Data

Answer the following questions to determine if Section F (Age and Disease Syndrome Distribution Data) should be completed for the manuscript.

34. Does the manuscript report a total of 30 or more cases of either Hib or S. pneumoniae invasive disease among children less than 5 years of age?

Yes (answer question 35)

No (age/syndrome distribution and/or case fatality data cannot be abstracted, skip to section H)

35. Does the manuscript provide data that can be used to determine the proportion of Hib and/or S. pneumo invasive disease occurring in any age group of children under 5 years (e.g., proportion of Hib disease in children under age 2 years)?

Yes

No

36. Does the study provide information about the distribution of disease syndromes caused by Hib and/or S. pneumoniae for any age group of children under 5 years? (e.g., what proportion of invasive Hib disease is meningitis, what proportion is pneumonia, etc.?)

Yes

No

NOTE 6:

If the response to either question 35 or 36 is “Yes,” complete Section F. If the response to both questions 35 and 36 is “No,” skip to section G.

37. Complete the following table to indicate the number of cases reported in each age stratum, for each invasive disease syndrome. If these data are reported in multiple age strata (e.g, children under 5 years, children under 2 years), include all information as separate entries in the table. Specify age in months. If neonates are included, or if it is not known if neonates are included, indicate lowest age as “00 months.” Take note of how the highest age is described [e.g, children 5 years and under (0-71 months), vs. children under 5 years (0-59 months)]. Record all age categories given, including those over 59 months of age. When available (either reported or derived from data provided), data should be recorded for the following age strata:



lowest age to 11 months (<1 year) •

If data are not provided by syndrome, mark the option for “All invasive disease.”



Age range reported (months) Number of cases Lowest age Highest age

Meningitis

Pneumonia





37b. S. pneumo disease (select all that apply) [picklist]

Age range reported (months) Number of cases Lowest age Highest age

Meningitis

Pneumonia





101WHO/IVB/09.02

Section G. Case Fatality Data

Answer the following question to determine if Section G (Case Fatality Data) should be completed for the manuscript.

38. Does the manuscript provide case fatality ratios, or data that can be used to calculate case fatality ratios, for disease due to Hib and/or S. pneumo in children under age 5 years?

Yes (complete section G)

No (skip to section H)

39. Is the proportion of cases with known mortality outcome provided?



39a. What is the proportion of cases with known outcome? For vaccine probe studies or randomized trials, include this proportion for control group only. [numeric]

39b. If the proportion of cases with known outcome is < 100%, for what reason is the outcome unknown for the remainder of cases?

A random sample was selected for follow-up

Reasons other than follow-up of random sample, does not seem to lead to bias

Reasons other than follow-up of random sample, likely to lead to bias

Unknown

40. Complete the following table of case-fatality ratios (CFR) for each invasive disease syndrome, for each age strata reported for children 59 months and younger. If these data are reported in multiple age strata (e.g, children under 5 years, children under 2 years), include all information as separate entries in the table. Specify age in months. If neonates are included, or if it is not known if neonates are included, indicate lowest age as “00 months.” Take note of how the highest age is described [e.g, children 5 years and under (0-71 months), vs. children under 5 years (0-59 months)].

When available (either reported or calculated), data should be recorded for the following age strata:



lowest age to 11 months (<1 year)



Age range reported Case fatality data

Lowest age

(mths)

Highest age

(mths)

Number of cases with

known mortality outcome

(denominator)

Case fatality

ratio (%)

Meningitis

Pneumonia





40b. S. pneumo disease (select all that apply) [picklist]

Age range reported Case fatality data

Lowest age

(mths)

Highest age

(mths)

Number of cases with

known mortality outcome

(denominator)

Case fatality

ratio (%)

Meningitis

Pneumonia





103WHO/IVB/09.02

If Sections E, F, and G could not be completed (no data were abstracted), skip Section H and go to Question 61 at the end.

Section H. Quality Assessment

Complete for all studies abstracted. Note that any methodological issues that could have resulted in 20% or more of cases being missed should be considered “significant.”

i. Numerator/Case ascertainment

41. Characterize the participating pediatric hospitals (defined as any hospital where children under 5 are admitted for treatment of bacteraemia, pneumonia, meningitis), as described in the manuscript. (select one)

All [pediatric hospitals] in study area included

Some [pediatric hospitals] in study area not included, results adjusted accordingly

Some not included, authors state the effect was not significant

Some not included, authors state the effect may have been significant

Some not included, no discussion of the effect

No hospital-based case-ascertainment used

Unable to determine/no information provided by authors

42. Select the response that best describes care-seeking of patients with any of the syndromes studied, as described in the manuscript. (check all that apply)

Unlikely to seek care outside study area

May have sought care outside study area (answer question 42a)

May not have sought any care (answer question 42a)

Unable to determine/no information provided by authors (skip to question 43)

42a. Did the authors characterize the potential impact of these care-seeking patterns?

Authors state the effect was not significant

Authors state the effect may have been significant, results adjusted accordingly

Authors state the effect may have been significant, no adjustment

Authors do not discuss potential impact


43. Indicate which, if any, of the following potential problems with case ascertainment may apply to this study. (check all that apply)

Laboratory specimens not collected for all potential cases, or laboratory testing not performed for all specimens collected

Some laboratory/medical records not available, or review of records was incomplete

Inconsistent recruitment of cases in hospital (recruitment not 24-hours/day, 7 days/week)

Study was not conducted in all areas of facility where potential cases received care

Some subjects refused to participate

None of the above

Other (specify in question 43a)

Unable to determine

43a. Specify other potential problems with case ascertainment [text]

44. Select the response that best describes your judgment of whether the case ascertainment methods were likely to miss a significant proportion of cases, for any of the disease syndromes studied.

Unlikely to have missed a significant proportion of cases

May have missed a significant proportion of cases but results adjusted accordingly

May have missed a significant proportion of cases, results not adjusted

Unable to determine

45. Describe limitations of case ascertainment methods, including any numeric estimate of the limitations (e.g., % of children presenting who did not have lumbar puncture).

ii. Numerator/Diagnostic methods

46. Do the authors acknowledge any limitations in diagnostic methods (i.e., handling and transport of specimens, laboratory techniques)?

Yes (describe in question 47)

No

47. Describe limitations of diagnostic methods used [text]

48. In your opinion, the diagnostic methods described for the study were:

Likely to be reliable

Unlikely to be reliable

Unable to determine reliability

105WHO/IVB/09.02

49. Select reasons for your judgment about the quality of diagnostic testing (check all that apply)

Prospective study with good quality control

Study conducted in area with generally high-quality health services

Study conducted at research institution or other facility with resources appropriate for study

Study conducted in area with generally limited health services and facilities

Other (specify in question 49a)

49a. Specify reason for your judgment about the quality of diagnostic testing

NOTE 7:

If the study does not report any data about Hib and/or S. pneumo meningitis, skip to question 53. If meningitis data were reported, continue to question 50.

50. Are you able to determine the proportion of probable (as defined by the authors, see guide) bacterial meningitis cases with confirmed etiology?

Yes

No

50a. Enter proportion of probable bacterial meningitis with confirmed etiology

51. Are you able to determine the proportion of meningitis cases with confirmed etiology that were due to Hib and pneumococcus combined? __ __ __%

Yes

No

51a. Enter proportion of meningitis cases with confirmed etiology that were due to Hib and S. pneumo combined.

52. Were any adjustments made to account for limitations in diagnostic methods, or for culture-negative, probable bacterial meningitis?

Yes

No


iii. Population/Denominator data

53. Does the study specify the source for the population data provided?


No, source of population data not specified (skip to question 54)

No population data provided (skip to question 56)

53a. If yes, did the population denominator come from a reliable source (e.g., current census)?

Yes

No

Unable to determine

54. For incidence calculations, does the denominator represent a population to which all the cases (numerator) belong?

Yes

No

Unknown

55. Include comments on the population data provided in the manuscript [text]

iv. Time Period

56. Is the study longitudinal and are study data presented in a way that permits estimation of results from different time periods?

Yes (complete questions 56a and 56b)


56a. If yes, indicate time period with most accurate results for Hib and S. pneumo, if appropriate [text]

56b. Indicate the reason why you think this time period is most accurate [text]

v. Other

57. Indicate any other factors that may have affected the accuracy of study results (i.e., study done in 2 populations, one of which was clearly biased)? [text]

58. Can estimates be calculated for a portion of the study results (from a portion of the study period or from a subpopulation) that are more accurate than the overall results?


No

58a. Specify the most accurate portion [text]

107WHO/IVB/09.02

59. Does the manuscript indicate that the results from this study are also reported in another reference?

Yes (specify in question 59a)

No

59a. Specify which reference(s) report the same results as those reported in this manuscript (use the reference numbers from the manuscript itself)

60. Does the manuscript mention other references with potentially relevant data for abstraction?

Yes (specify in question 60a)

No

60a. Specify which reference(s) may include potentially relevant data (use the reference numbers from the manuscript itself)

[For database: field set so anyone can use it, even if the study is excluded and you stopped answering questions before this page.]

61. Are there additional comments for this study? If the study was excluded, but the paper warrants additional review (e.g., a good quality 5-year study that started in 1979, doesn’t meet inclusion criteria but may provide useful data), indicate this here.


These regional groupings of countries were used in the results section of this publication.

Region WHO Member States

AFR

Algeria, Angola, Benin, Botswana, Burkina Faso, Burundi, Cameroon, Cape Verde, Central African Republic, Comoros, Congo, Côte d’Ivoire, Democratic Republic of the Congo, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mauritius, Mozambique, Namibia, Niger, Nigeria, Rwanda, Sao Tome and Principe, Senegal, Seychelles, Sierra Leone, South Africa, Swaziland, Togo, Uganda, United Republic of Tanzania, Zambia, Zimbabwe

AMR

Antigua and Barbuda, Argentina, Bahamas, Barbados, Belize, Bolivia, Brazil, Canada, Chile, Colombia, Costa Rica, Cuba, Dominica, Dominican Republic, Ecuador, El Salvador, Grenada, Guatemala, Guyana, Haiti, Honduras, Jamaica, Mexico, Nicaragua, Panama, Paraguay, Peru, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Suriname, Trinidad and Tobago, United States of America, Uruguay, Venezuela (Bolivarian Republic of)

EMR Afghanistan, Bahrain, Cyprus, Djibouti, Egypt, Iraq, Iran (Islamic Republic of), Jordan, Kuwait, Lebanon, Libyan Arab Jamahiriya, Morocco, Oman, Pakistan, Qatar, Saudi Arabia, Somalia, Sudan, Syrian Arab Republic, Tunisia, United Arab Emirates, Yemen

EUR

Albania, Andorra, Armenia, Austria, Azerbaijan, Belarus, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Georgia, Germany, Greece, Hungary, Iceland, Ireland, Israel, Italy, Kazakhstan, Kyrgyzstan, Latvia, Lithuania, Luxembourg, Malta, Monaco, Montenegro, Netherlands, Norway, Poland, Portugal, Republic of Moldova, Romania, Russian Federation, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Tajikistan, The former Yugoslav Republic of Macedonia, Turkey, Turkmenistan, Ukraine, United Kingdom of Great Britain and Northern Ireland, Uzbekistan

SEAR Bangladesh, Bhutan, Democratic People’s Republic of Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, Timor-Leste

WPRAustralia, Brunei Darussalam, Cambodia, China, Cook Islands, Fiji, Japan, Kiribati, Lao People’s Democratic Republic, Malaysia, Marshall Islands, Micronesia (Federated States of), Mongolia, Nauru, New Zealand, Niue, Palau, Papua New Guinea, Philippines, Republic of Korea, Samoa, Singapore, Solomon Islands, Tonga, Tuvalu, Vanuatu, Viet Nam

Source: WHO (2001) http://www.who.int/quantifying_ehimpacts/global/ebdcountgroup/en/index.html

Sub-regions: AFR=African; AMR=Americas; EMR=Eastern Mediterranean; EUR=European; SEAR=South-East Asia; WPR=Western Pacific.

Annex 4: Member States by WHO Region

http://www.who.int/quantifying_ehimpacts/global/ebdcountgroup/en/index.html

109WHO/IVB/09.02

These regional groupings of countries were used in analysis.

United Nations region Countries in region

Africa

Algeria, Angola, Benin, Botswana, Burkina Faso, Burundi, Cameroon, Cape Verde, Central African Republic,

Chad, Comoros, Congo, Côte d´Ivoire, Democratic Republic of the Congo, Djibouti, Egypt, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Lesotho, Liberia, Libyan Arab Jamahiriya, Madagascar, Malawi, Mali, Mauritania, Mauritius, Morocco, Mozambique, Namibia, Nigeria, Niger, Rwanda, Sao Tome and Principe, Senegal, Seychelles, Sierra Leone, Somalia, South Africa, Sudan, Swaziland, Togo, Tunisia, Uganda, United Republic of Tanzania, Zambia, Zimbabwe

Asia

Afghanistan, Armenia, Azerbaijan, Bahrain, Bangladesh, Bhutan, Brunei Darussalam, Democratic People’s Republic of Korea, Cambodia, China, Cyprus, Georgia, India, Indonesia, Iran (Islamic Republic of), Iraq, Israel, Japan, Jordan, Kazakhstan, Kyrgyzstan, Kuwait, Lao People’s Democratic Republic, Lebanon, Malaysia, Maldives, Myanmar, Mongolia, Nepal, Oman, Pakistan, Philippines, Qatar, Republic of Korea, Saudi Arabia, Singapore, Sri Lanka, Syrian Arab Republic, Tajikistan, Thailand, Timor-Leste, Turkey, Turkmenistan, United Arab Emirates, Uzbekistan, Viet Nam, Yemen

Europe

Albania, Andorra, Austria, Belarus, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Monaco, Montenegro, Netherlands, Norway, Poland, Portugal, Republic of Moldova, Romania, Russian Federation, San Marino, Slovakia, Slovenia, Spain, Sweden, Switzerland, The former Yugoslav Republic of Macedonia, Ukraine, United Kingdom, Serbia and Montenegro

Latin America and the Caribbean

Antigua and Barbuda, Argentina, Bahamas, Barbados, Belize, Bolivia, Brazil, Chile, Colombia, Costa Rica, Cuba, Dominica, Dominican Republic, Ecuador, El Salvador, Grenada, Guatemala, Guyana, Haiti, Honduras, Jamaica, Mexico, Nicaragua, Panama, Paraguay, Peru, Saint Lucia, Saint Kitts and Nevis, Saint Vincent and The Grenadines, Suriname, Trinidad and Tobago, Uruguay, Venezuela

North America Canada, United States of America

OceaniaAustralia, Cook Islands, Fiji, Kiribati, Marshall Islands, Micronesia (Federated States of), New Zealand, Nauru, Niue, Palau, Papua New Guinea, Samoa, Solomon Islands, Tonga, Tuvalu, Vanuatu

Source: The United Nations Country Classification. http://www.un.org/esa/population/publications/WPP2004/WPP2004_Vol3_Final/Preface_TOC_ExpNotes.pdf. Accessed 30 March 2009.

Annex 5: Countries and territories by United Nations region


Annex 6 lists studies containing data that entered the Hib (N = 176) meningitis and NPNM analytic databases. The list includes articles that were eventually excluded from meningitis incidence analysis due to poor quality scores. An electronic dataset containing most of the data presented here in Annex 6 is available on the WHO website at: http://www.who.int/immunization_monitoring/burden/en/. The figure below describes the Annex 6 subset of all studies presented in this document (Annex 8 contains the complete list of studies).

Figure: Summary of references included in Hib meningitis and NPNM analytic database (continued from Figure 1)

Annex 6: Study characteristics and key data

from Hib studies entering the meningitis and NPNM analytic database

From the 332 articles (336 studies) with evaluable outcome data, there were 205 studies identified with any Hib outcome data. The highlighted outcomes in the table below indicate the key outcomes that were included in the meningitis and NPNM analytic database. Annex 6 lists the studies that had evaluable data for these key outcomes, by country, and grouped by WHO region.

332 articles (336 studies) meet criteria for at least one extracted outcome and

contain evaluable data(Annex 8)

Annex 6 contains the 176 Hib studies that entered the meningitis

and NPNM analytic database

Studies with only key Spn

outcomes

Studies without evaluable key Hib outcomes

http://www.who.int/immunization_monitoring/burden/en/

111WHO/IVB/09.02

Table 1: All extracted outcomes and among these the key outcomes (highlighted) entering the analytic database

Extracted outcomes (N = 205)Incidence All invasive Meningitis Pneumonia NPNMAge distribution All invasive Meningitis Pneumonia NPNMSyndrome distribution of cases (NPNM and meningitis)Syndrome distribution of CFRs (NPNM and meningitis)Case-fatality ratio All invasive Meningitis Pneumonia NPNM


Tabl

e 2:

Stu

dy c

hara

cter

isti

cs a

nd k

ey d

ata

from

Hib

stu

dies

ent

erin

g th

e m

enin

giti

s an

d N

PNM

ana

lyti

c da

taba

se

Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

WHO

Afric

an R

egion

(AFR

)

AF

R stu

dies w

ith in

ciden

ce da

ta

Burki

na

Faso

Bobo

-Diou

lasso

Tall (

1992

)19

864.9

1988

Very

High

47 92

427

11

1

22

239

47

Burki

na

Faso

Bobo

-Diou

lasso

Yaro

(200

6)20

023

2003

Very

High

93 13

719

95

97

34

Burki

na

Faso

2 citie

sPa

rent

du C

hatel

et (2

005)

2002

120

02Ve

ry Hi

gh19

1 220

42

78

26

105

41

Gamb

iaBa

njul

Adeg

bola

(199

6)19

902.9

1991

Very

High

84 23

112

0

141

1622

2

57

10

Gamb

iaW

ester

nAd

egbo

la (1

999)

1985

13.7

1992

High

64

21

8

Gamb

iaW

ester

nMu

lholla

nd (1

997)

1993

2.619

94Hi

gh11

011

21

74

4

Gamb

ia4 d

istric

ts, B

anjul

Bijlm

er (1

990)

1985

1.919

86Ve

ry Hi

gh67

163

64

77

37

297

60

Keny

aKi

lifi D

istric

tCo

wgill

(200

6)20

001.9

2000

High

37 34

4

20

28

Mali

Bama

koSo

w (2

005)

2002

220

03Ve

ry Hi

gh22

5 787

104

12

2

104

27

113WHO/IVB/09.02

Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

Nige

rNi

amey

Camp

agne

(199

9)19

8114

.819

89Ve

ry Hi

gh84

801

530

586

611

44

4421

111

649

south

Afric

aCa

pe To

wnHu

ssey

(199

4)19

910.9

1992

Mediu

m24

8 418

51

78

6

112

34

south

Afric

a so

weto

Madh

i (200

2)19

970.9

1997

Mediu

m

26

118

3

AF

R stu

dies w

ithou

t incid

ence

data

Came

roon

Yaou

ndé

Bern

ard-

Bonn

in (1

985)

1982

19

83Ve

ry Hi

gh

2942

51

2424

Came

roon

Yaou

ndé

Fonk

oua (

2001

)19

96

1997

Very

High

22

32

Côte

dÍvo

ireAb

idjan

Faye

-Kett

e (20

03)

1995

19

97Ve

ry Hi

gh

95

117

Côte

dÍvo

ireAb

idjan

Oreg

a (19

97)

1985

19

87Ve

ry Hi

gh

125

14

0

Côte

dÍvo

ireLa

gune

s Reg

ionde

Bar

y (19

90)

1985

19

86Ve

ry Hi

gh

54

65

Ethio

piaAd

dis A

baba

Muhe

(199

9)19

93

1994

Very

High

74

38

Ethio

piaGo

ndar

Gedlu

(199

5)19

90

1992

Very

High

27

31

Gabo

nLib

revil

leKo

ko (2

000)

1989

19

91Hi

gh

16

22

35


Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

Gamb

iaBa

njul

Palm

er (1

999)

1995

19

95Hi

gh

91

109

Gamb

iaUp

per R

iver

Divis

ionO'

Demp

sey (

1994

)19

89

1990

Very

High

10

4

Gamb

iaW

ester

nGo

etghe

buer

(200

0)19

90

1992

High

10

2

121

Keny

aNa

irobi

Nesb

itt (1

988)

1985

19

85Hi

gh

1821

Mada

gasc

arAn

tanan

arivo

Migli

ani (2

002)

1998

19

99Hi

gh

4149

Mada

gasc

arAn

tanan

arivo

Raza

findr

alamb

o (2

004)

1998

19

99Hi

gh

4449

Malaw

iBl

antyr

eMo

lyneu

x (19

98)

1996

19

96Ve

ry Hi

gh

43

Nige

riaBe

nin C

ityAk

pede

(199

4)19

85

1987

Very

High

28

3538

Nige

riaEn

ugu a

nd

Nsuk

kaOn

yeme

lukwe

(1

994)

1989

19

90Ve

ry Hi

gh

1935

sene

gal

Daka

rCi

sse (

1989

)19

83

1985

Very

High

79

94

Togo

Lomé

-Toko

inAt

akou

ma (1

995)

1987

19

88Hi

gh

3746

115WHO/IVB/09.02

Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

WHO

Reg

ion of

the A

meric

as (A

MR)

AM

R stu

dies w

ith in

ciden

ce da

ta

Arge

ntina

Tucu

man

Torre

s (19

95)

1985

7.919

88Me

dium

164 7

6117

0

218

22

2063

17

24

Braz

ilBa

hiaLu

cena

(199

6)19

902.9

1991

Mediu

m10

2 537

12

015

2

93

51

Braz

ilCa

mpina

sW

eiss (

2001

)19

971.9

1997

Mediu

m77

819

1824

26

15

6339

17

Braz

ilGo

ias s

tate

simo

es (2

004)

1995

5.919

98Me

dium

302 2

80

19

4

13

11

Braz

ilPa

rana

stat

eTa

kemu

ra (2

001)

1992

719

95Me

dium

20

Braz

ilRi

o Gra

nde

do s

olKm

etzsc

h (20

03)

1998

0.919

98Me

dium

2

37

Braz

ilsa

lvado

rRi

beiro

(200

3)19

964.5

1998

Mediu

m66

565

65

83

16

54

28

Braz

ilsa

o Pau

loRe

zend

e (19

89)

1983

0.919

83Hi

gh3 7

03 54

878

15

2

10

5

Chile

santi

ago

Ferre

ccio

(199

0)19

852.9

1986

Very

Low

555 6

4615

421

524

216

1616

4733

15

Chile

santi

ago

Lago

s (19

96)

1992

2.419

94Ve

ry Lo

w34

849

22

27

26

8


Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

Cuba

Who

le co

untry

Dick

inson

(200

1)19

981.9

1998

Very

Low

383 8

6851

9312

7

3431

17

Cuba

Who

le co

untry

Dick

inson

(200

2)19

982.9

1999

Very

Low

277 6

1855

13

912

8

34

17

Cuba

Who

le co

untry

Dick

inson

Me

nese

s (20

01)

1993

5.919

95Ve

ry Lo

w85

9 695

334

68

6

34

13

Cuba

Who

le co

untry

Legu

en (1

991)

1989

0.919

89Ve

ry Lo

w95

2 865

115

19

919

63

23

Domi

nican

Re

publi

cNa

tiona

l Dist

rict

regio

nGo

mez (

2000

)19

980.9

1998

Mediu

m35

9 536

3541

44

5231

1317

Guate

mala

Guate

mala

City

Astur

ias (2

003)

1996

2.319

97Me

dium

53 73

0

17

14

14

164

412

Unite

d st

ates

Atlan

ta, G

eorg

iaCo

chi (1

986)

1983

0.919

83Ve

ry Lo

w15

1 023

79

57

Unite

d st

ates

Kans

asW

alling

(199

1)19

835

1985

Very

Low

36 71

4

41

22

Unite

d st

ates

Mass

achu

setts

Loug

hlin (

1995

)19

861

1986

Very

Low

410 0

00

51

13

Unite

d st

ates

Who

le co

untry

scho

endo

rf (1

994)

1980

719

83Ve

ry Lo

w20

116 5

51

55

721

3

40

Unite

d st

ates

2 stat

esMu

rphy

(199

2)19

831.9

1983

Very

Low

512 6

83

45

7

4

46

228

0

Unite

d st

ates

20 st

ates

Adam

s (19

93)

1989

0.919

89Ve

ry Lo

w7 5

14 50

7

13

34

19

117WHO/IVB/09.02

Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

AM

R stu

dies w

ithou

t incid

ence

data

Braz

ilFe

dera

l Dist

rict

Ferra

z (19

96)

1989

19

92Me

dium

13

316

819

2

Braz

ilMi

nas G

erais

Mira

nzi s

de (2

003)

1993

19

95Me

dium

30

2

628

Braz

ilsa

lvado

rNa

scim

ento-

Carva

lho (1

998)

1988

19

92Me

dium

19

3236

Braz

ilW

hole

coun

tryFla

nner

y (20

07)

2000

20

00Me

dium

15

Chile

Medin

aCh

ávez

(199

6)19

89

1992

Very

Low

81

31

Chile

santi

ago

Chav

ez P

(199

4)19

83

1988

Very

Low

154

171

19

Chile

santi

ago

Diaz

(200

1)19

89

1993

Very

Low

16

020

421

9

Chile

Temu

co re

gion

Boeh

me (1

993)

1988

19

89Ve

ry Lo

w

2129

33

1718

Chile

Valdi

viaBu

rgos

(198

8)19

84

1985

Very

Low

19

21

Colom

biaMe

dellin

Oter

o (19

88)

1984

19

85Me

dium

3137

Jama

ica2 c

ities

Barto

n-Fo

rbes

(2

000)

1990

19

91Ve

ry Lo

w

65

11

9


Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

Mexic

oMe

xico C

ityCa

stane

da

Narva

ez (1

990)

1980

19

84Me

dium

52

68

Mexic

oPu

ebla

sosa

-Igles

ias

(199

5)19

85

1987

Mediu

m

23

23

4

7

Para

guay

Asun

ción

Basu

aldo (

2004

)19

91

1993

Mediu

m

22

1616

Unite

d st

ates

New

York

Coan

t (19

92)

1984

19

86Ve

ry Lo

w

96

109

WHO

Eas

tern M

edite

rrane

an R

egion

(EMR

)

EM

R stu

dies w

ith in

ciden

ce da

ta

Egyp

t1 g

over

nora

teW

att (1

999)

1999

0.919

99Me

dium

23

Iran

((Isla

mic

Repu

blic o

f)2 p

rovin

ces

Nelso

n19

991.6

2000

Mediu

m

9

Kuwa

itFa

rwan

iaZa

ki (1

990)

1981

6.919

84Ve

ry Lo

w

40

49

2

31

Pakis

tanPu

njab P

rovin

ceAl

Awa

idy (2

003)

2002

120

02Hi

gh

16

Qatar

Who

le co

untry

Nove

lli (1

989)

1987

2.019

88Ve

ry Lo

w40

944

812

13

16

4

4

saud

i Ar

abia

4 pro

vince

sAl

-Maz

rou (

2004

)19

991.9

2000

Very

Low

179 1

8243

5458

57

3717

Tunis

ia6 c

ities

Solta

ni (2

005)

2000

1.220

01Ve

ry Lo

w99

300

1316

17

5434

1423

119WHO/IVB/09.02

Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

EM

R stu

dies w

ithou

t incid

ence

data

Kuwa

itFa

rwan

ia Ho

spita

lDa

oud (

1989

)19

80

1984

Very

Low

40

5459

saud

i Ar

abia

Easte

rnAb

omelh

a (19

88)

1982

19

83Me

dium

34

4242

saud

i Ar

abia

Riya

dhAb

anam

y (19

91)

1985

19

87Me

dium

43

5760

02

saud

i Ar

abia

Riya

dhAl

mune

ef (1

998)

1984

19

90Ve

ry Lo

w

44

22

saud

i Ar

abia

Tabu

kAz

ubuik

e (19

90)

1982

19

84Me

dium

2427

WHO

Eur

opea

n Reg

ion (E

UR)

EU

R stu

dies w

ith in

ciden

ce da

ta

Austr

iaSt

yria s

tate

Raute

r (19

94)

1983

9.919

87Ve

ry Lo

w17

635

824

36

6

2335

21

Austr

iaW

hole

coun

tryVu

tuc (1

995)

1990

319

91Ve

ry Lo

w45

2 550

146

11

Belgi

umAn

twer

pva

n Hoe

ck (1

997)

1988

619

90Ve

ry Lo

w

1224

202

Bosn

ia an

d He

rzego

vina

Who

le co

untry

Al A

waidy

(200

4)20

021.5

2002

Very

Low

15


Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

Bulga

ria6 r

egion

sKo

jouha

rova

(2

002)

1997

2.419

98Ve

ry Lo

w14

2 305

810

21

128

68

3

Czec

h Re

publi

cW

hole

coun

tryLe

bedo

va (2

003)

2001

0.920

01Ve

ry Lo

w49

3 748

11

42

12

9

220

33

Denm

ark

Who

le co

untry

Krist

ense

n (19

90)

1985

119

85Ve

ry Lo

w52

5 000

142

3

27

Finlan

dHe

lsink

iPe

ltola

(199

2)19

814.9

1983

Very

Low

52 01

8

11

0

43

Fran

ce2 d

epar

tmen

tsLiv

artow

ski (1

989)

1980

6.919

83Ve

ry Lo

w12

0 872

5696

123

43

3

15

17

Fran

ce2 d

epar

tmen

tsRe

inert

(199

3)19

809.9

1985

Very

Low

132 8

0575

135

177

428

2613

15

71

Gree

ceAt

hens

Tsoli

a (19

98)

1992

219

93Ve

ry Lo

w17

5 395

1025

28

1417

8

Israe

lTh

e Neg

evHa

lfon-

Yaniv

(1

990)

1984

4.919

86Ve

ry Lo

w41

841

3441

42

7

6640

22

Israe

lW

hole

coun

tryDa

gan (

1992

)19

8810

.919

94Ve

ry Lo

w86

162

122

158

169

65

4218

8710

9

Israe

lW

hole

coun

tryDa

gan (

1994

)19

882.9

1990

Very

Low

519 2

2520

426

628

0

2

6744

19

Israe

lW

hole

coun

tryDa

gan (

1999

)19

897.9

1992

Very

Low

244 9

3324

7

349

65

18

Italy

Naple

sPi

zzuti

(199

8)19

942

1994

Very

Low

949 5

7728

5055

7

73

121WHO/IVB/09.02

Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

Italy

Pugli

aCh

ironn

a (19

98)

1994

1.919

94Ve

ry Lo

w25

2 987

1217

20

129

4

Italy

Natio

nal a

nd

regio

nal d

ataD'

Ales

sand

ro

(199

5)19

941

1994

Very

Low

2 911

176

3358

73

65

3

Italy

3 pro

vince

ssq

uarci

one (

1999

)19

931.9

1993

Very

Low

189 2

16

3739

1811

Luxe

mbou

rgGr

and D

uchy

of

Luxe

mbou

rgDe

Jong

he (1

995)

1980

14.5

1987

Very

Low

23 18

6

37

3

11

13

Polan

dKi

elce,

Bydg

oszc

zZie

linsk

i (200

1)19

982.1

1999

Very

Low

124 9

60

17

7

Roma

nia2 d

istric

tsLu

ca (2

004)

2000

220

01Ve

ry Lo

w85

438

7

13

4

8

Russ

ian

Fede

ratio

nst

. Pete

rsbur

gKo

stiuk

ova (

1992

)19

855

1987

Very

Low

87 16

7

18

4

slov

akia

8 dist

ricts

Nova

kova

(199

9)19

961.9

1996

Very

Low

105 4

912

35

36

17

spain

Madr

idVi

llo s

irero

l (200

4)19

917

1994

Very

Low

11

8

spain

sevil

leso

ult R

ubio

(199

4)19

884

1990

Very

Low

55 76

9

29

13

swed

enOr

ebro

Cou

ntyHu

goss

on (1

995)

1987

5.919

89Ve

ry Lo

w

31

31

swed

enW

hole

coun

tryBe

rg (1

996)

1987

219

88Ve

ry Lo

w76

1 602

31

842

3

54

28


Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

switz

erlan

dW

hole

coun

tryMu

hlema

nn (1

996)

1980

13.9

1986

Very

Low

299 0

08

10

41

25

1038

swed

enW

hole

coun

tryTr

ollfor

s (19

87)

1981

2.919

82Ve

ry Lo

w49

1 372

440

31

swed

en2 r

egion

sGa

rpen

holt (

1996

)19

874

1989

Very

Low

646 3

5920

637

750

8

4037

20

Ukra

ineKi

ev, D

onets

kPl

atano

v (20

03)

2001

220

01Ve

ry Lo

w

8

Unite

d Ki

ngdo

mGl

asgo

wCo

ggins

(199

3)19

819.9

1985

Very

Low

61 48

9

109

145

4524

Unite

d Ki

ngdo

mGw

yned

d an

d W

ales

Howa

rd (1

991)

1980

1019

85Ve

ry Lo

w53

713

48

118

43

22

Unite

d Ki

ngdo

mNo

ttingh

am

distric

tFo

rtnum

(199

3)19

809.9

1984

Very

Low

45 76

450

99

8

632

22

Unite

d Ki

ngdo

mOx

ford

Booy

(199

3)19

856.9

1988

Very

Low

173 8

4113

922

128

4

5

5846

24

4071

114

4

Unite

d Ki

ngdo

mOx

ford

Tudo

r-Willi

ams

(198

9)19

853.4

1986

Very

Low

170 8

8060

105

138

4

24

19

2951

4

Unite

d Ki

ngdo

msc

otlan

dKy

aw (2

002)

1983

1619

91Ve

ry Lo

w18

1 592

184

47

7

31

16

Unite

d Ki

ngdo

mTh

ames

area

Urwi

n (19

96)

1991

2.919

92Ve

ry Lo

w88

423

31

57

55

22

Unite

d Ki

ngdo

mW

est M

idlan

dsOl

owok

ure (

2000

)19

903.9

1992

Very

Low

178 8

29

13

0

19

Unite

d Ki

ngdo

m5 r

egion

s, En

gland

Slac

k (19

98)

1991

0.919

92Ve

ry Lo

w2 7

83 32

6

35

7

14

205

123WHO/IVB/09.02

Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

EU

R stu

dies w

ithou

t incid

ence

data

Denm

ark

Easte

rnCh

risten

sen (

1988

)19

83

1984

Very

Low

20

3340

Israe

lTh

e Neg

evRo

senth

al (1

988)

1981

19

83Ve

ry Lo

w

3138

Italy

Rome

Ticca

(199

7)19

85

1989

Very

Low

8211

0

Italy

6 pro

vince

sCe

llesi

(199

5)19

87

1989

Very

Low

51

89

Polan

dW

hole

coun

trySk

oczy

nska

(200

0)19

97

1997

Very

Low

17

3746

Roma

niaIas

iCo

rcaci

(200

2)19

84

1992

Very

Low

27

38

11

Russ

ian

Fede

ratio

nMo

scow

Demi

na (1

983)

1980

19

82Me

dium

26

56

Russ

ian

Fede

ratio

nMo

scow

Demi

na (1

986)

1980

19

82Me

dium

34

78

Russ

ian

Fede

ratio

nMo

scow

Devia

tkina

(199

0)19

88

1988

Very

Low

51

98

spain

Madr

idVi

lla-A

lcaza

r (1

994)

1987

19

90Ve

ry Lo

w

19

36

spain

Malag

aMa

rtinez

Leon

(1

998)

1988

19

91Ve

ry Lo

w

1334

40


Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

spain

Not d

escri

bed

Juan

Mar

tin (1

993)

1981

19

85Ve

ry Lo

w

29

11

Unite

d Ki

ngdo

mEn

gland

and

Wale

sde

Louv

ois (1

991)

1985

19

86Ve

ry Lo

w

4

WHO

sou

th-Ea

st As

ia Re

gion (

sEAR

)

sE

AR st

udies

with

incid

ence

data

Indon

esia

Lomb

ok Is

land

Gess

ner (

2005

)19

984

2000

Mediu

m

7

67

Nepa

lTe

rai

Russ

ell (2

003)

2000

120

01Hi

gh

5

sri L

anka

Colom

bo D

istric

tW

HO(2

002)

2004

120

04Ve

ry Lo

w17

9 103

36

20

Thail

and

Lamp

ang a

nd

Phits

anulo

kRe

rks-N

garm

(2

004)

2000

0.920

00Ve

ry Lo

w11

4 696

3

4

18

410

sE

AR st

udies

with

out in

ciden

ce da

ta

Bang

lades

hDh

aka

saha

(199

7)19

87

1990

Mediu

m

191

257

277

22

Bang

lades

hDh

aka,

Chitta

gong

, Mi

rzapu

r

Saha

, per

sona

l co

mmun

icatio

n20

03

2005

Mediu

m

pc*

pcpc

pc

pc

pcpc

India

Vello

resi

ngh (

1992

)19

87

1989

High

3839

India

6 citie

s(2

002)

1993

19

95Hi

gh

30

4820

16

125WHO/IVB/09.02

Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

Thail

and

Bang

kok

Chotp

itaya

suno

ndh

(199

4)19

80

1985

Mediu

m

186

216

Thail

and

Bang

kok

Likitn

ukul

(199

4)19

80

1986

Mediu

m

3538

44

4

WHO

Wes

tern P

acific

Reg

ion (W

PR)

W

PR st

udies

with

incid

ence

data

Austr

alia

Canb

erra

, Qu

eanb

eyan

McGr

egor

(199

2)19

846.9

1987

Very

Low

22 63

918

3748

59

6031

Austr

alia

south

ern

el sa

adi (1

993)

1987

619

89Ve

ry Lo

w95

956

144

25

Austr

alia

Sydn

eyMc

Intyre

(199

1)19

852.9

1986

Very

Low

235 5

1654

9813

50

24

3936

2023

2051

117

0

Austr

alia

Sydn

eyMc

Intyre

(199

3)19

855

1987

Very

Low

243 0

02

22

9

3

19

Austr

alia

Victo

riaGi

lbert

(199

0)19

852.9

1986

Very

Low

303 6

4777

167

225

44

4725

Austr

alia

Wes

tern

Bowe

r (19

94)

1984

619

87Ve

ry Lo

w13

2 924

257

6

32

Austr

alia

Wes

tern

Hann

a (19

91)

1984

4.919

86Ve

ry Lo

w11

5 859

186

5

33

China

Hefei

City

Yang

(199

6)19

902.9

1991

Mediu

m80

365

18

25

38

11


Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

China

, Ho

ng K

ong

sAR

Hong

Kon

g sAR

Lau (

1995

)19

864.9

1988

Very

Low

396 0

23

34

2

China

Taiw

ansh

ao (2

004)

1997

419

99Ve

ry Lo

w39

9 774

5989

89

1814

6

China

Taiw

anCh

en (1

999)

1996

1.219

96Ve

ry Lo

w1 6

50 90

513

1925

810

21

Fiji

Who

le co

untry

Wils

on (2

003)

1992

119

92Ve

ry Lo

w18

7 986

37

2084

Japa

nAi

chi P

refec

ture

Ishika

wa (1

996)

1984

919

88Ve

ry Lo

w42

6 168

3566

893

33

54

2

Japa

nMi

e Pre

fectur

eNa

kano

(200

1)19

971.9

1997

Very

Low

94 89

8

11

6

Japa

n6 p

refec

tures

Kami

ya (1

998)

1994

119

94Ve

ry Lo

w1 4

14 87

6

66

3

5

Mong

olia

Ulaa

nbaa

tarW

att (2

004)

2002

2.920

03Me

dium

61 73

8

50

13

28

38

New

Caled

onia

Who

le co

untry

Angla

ret (

1993

)19

892.9

1990

Mediu

m20

105

22

38

7

New

Zeala

ndAu

cklan

dVo

ss (1

989)

1981

6.919

84Ve

ry Lo

w65

050

121

27

New

Zeala

ndW

hole

coun

tryW

ilson

(200

2)19

885.9

1990

Very

Low

291 8

65

46

5

27

189

2

Philip

pines

Centr

al Ma

nila

Limca

ngco

(200

0)19

942.9

1995

Mediu

m42

694

9510

811

8

11

337

204

95

Repu

blic o

f Ko

rea

Jeon

buk

Prov

ince

Kim

(200

4)19

992.3

2000

Very

Low

103 8

112

614

4

76

11

127WHO/IVB/09.02

Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5 M

orta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age s

tudy

po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Hib

Meni

ngiti

sHi

b NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io

(%)

Incid

ence

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y ra

tio (%

)

<1<2

<5<1

<2<5

<1<2

<5<5

(adj

)<1

<2<5

<1<2

<5

samo

aW

hole

coun

tryCa

rape

tis (2

002)

2000

120

00Ve

ry Lo

w

14

84

Viet

Nam

Hano

iAn

h (20

06)

2000

620

03Ve

ry Lo

w31

915

1116

23

4

3327

12

Viet

Nam

Ho-C

hi Mi

nh C

ityTr

an (2

004)

1995

1.919

96Me

dium

280 2

68

43

8

W

PR st

udies

with

out in

ciden

ce da

ta

Austr

alia

Melbo

urne

Gilbe

rt (1

995)

1988

19

89Ve

ry Lo

w

2655

79

23

1955

116

1

Japa

nAi

chi P

refec

ture

Kurik

i (199

5)19

84

1988

Very

Low

35

66

Japa

nHa

kkaid

osa

kata

(200

0)19

94

1996

Very

Low

19

2646

Japa

n11

hosp

itals

Ishiw

ada (

2004

)20

00

2001

Very

Low

39

8

Malay

siaKe

lantan

, Ma

laysia

Nik K

hairu

lddin

(199

9)19

85

1990

Very

Low

41

4648

Papu

a New

Gu

inea

Easte

rn

High

lands

Lehm

ann (

1999

)19

89

1991

High

22

24

Repu

blic o

f Ko

rea

seou

lKi

m (1

998)

1986

19

90Ve

ry Lo

w

1932

46

Repu

blic o

f Ko

rea

seou

lLe

e (19

98)

1986

19

91Ve

ry Lo

w

11

23

* pc

= p

erso

nal c

omm

unic

atio

n


Annex 7 lists studies containing data that entered the Spn (N = 164) meningitis and NPNM analytic databases. The list includes articles that were eventually excluded from meningitis incidence analysis due to poor quality scores. An electronic dataset containing most of the data presented here in Annex 7 is available on the WHO websiteat: http://www.who.int/immunization_monitoring/burden/en/. The figure below describes the Annex 7 subset of all studies presented in this document (Annex 8 contains the complete list of studies).

Figure: Summary of references included in Spn meningitis and NPNM analytic database (continued from Figure 1)

Annex 7: Study characteristics and key data

from Spn studies entering the meningitis and NPNM analytic database

From the 332 articles (336 studies) with evaluable outcome data, there were 211 studies identified with any Spn outcome data. The table below indicates all outcomes extracted and the key outcomes (highlighted) that were included in the meningitis and NPNM analytic database. Annex 7 lists the studies with evaluable data for these key Spn outcomes, by country, and grouped by WHO region.


contain evaluable data(Annex 8)

Annex 7 contains the 164 Spn studies that entered the meningitis and

NPNM analytic database

Studies with only key Hiboutcomes

Studies without evaluable key Spn outcomes

http://www.who.int/immunization_monitoring/burden/en/

129WHO/IVB/09.02

Table 1: All extracted outcomes and among those the key outcomes (highlighted) entering the analytic database



Tabl

e 2:

Stu

dy c

hara

cter

isti

cs a

nd k

ey d

ata

from

Spn

stu

dies

ent

erin

g th

e m

enin

giti

s an

d N

PNM

ana

lyti

c da

taba

se

Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5

Morta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age

stud

y po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Spn

Men

ingi

tisSp

n NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io (%

)In

ciden

ce

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y rat

io

(%)

<1<2

<5<1

<2<5

<1<2

<5<5

(a

dj)

<1<2

<5<1

<2<5

WHO

Afri

can

Regi

on (A

FR)

AFR

stud

ies w

ith in

ciden

ce d

ata

Burki

na

Faso

Bobo

-Di

oulas

soTa

ll (19

92)

1986

4.919

88Ve

ry Hi

gh47

924

133

55

56

.4

Burki

na

Faso

2 citie

sPa

rent

du C

hatel

et (2

005)

2002

120

02Ve

ry Hi

gh19

1 220

38

100

5295

52

.3

Gamb

iaW

ester

nUs

en (1

998)

1993

2.619

94Hi

gh

22

22

40

55

5

Gamb

ia2 d

ivisio

nsCu

tts (2

005)

2000

3.720

02Hi

gh

pc*

pc

pc

pc

Keny

aKi

lifi D

istric

tBe

rkley

(200

5)19

983.9

2000

High

34 82

7

39

38

26

.4

pc

Mali

Bama

koCa

mpbe

ll (20

04)

2002

120

02Ve

ry Hi

gh21

6 585

19

29

43

13.4

15.6

4

9

Nige

rNi

amey

Camp

agne

(199

9)19

8114

.819

89Ve

ry Hi

gh84

016

373

450

477

58

15

090

38.2

South

Afric

aCa

pe To

wnHu

ssey

(199

7)19

910.9

1992

Mediu

m24

8 418

19

21

42

9

South

Afric

aSo

weto

Klug

man (

2003

)19

983.7

1999

Mediu

m

73

South

Afric

aSo

weto

Madh

i (200

0)19

972

1998

Mediu

m

11

5

131WHO/IVB/09.02

Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5

Morta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age

stud

y po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Spn

Men

ingi

tisSp

n NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io (%

)In

ciden

ce

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y rat

io

(%)

<1<2

<5<1

<2<5

<1<2

<5<5

(a

dj)

<1<2

<5<1

<2<5

AFR

stud

ies w

ithou

t inc

iden

ce d

ata

Came

roon

Yaou

ndé

Bern

ard-

Bonn

in (1

985)

1982

19

83Ve

ry Hi

gh

4149

5941

4139

Came

roon

Yaou

ndé

Fonk

oua (

2001

)19

96

1997

Very

High

45

67

Côte

dÍvo

ireLa

gune

s Re

gion

de B

ary (

1990

)19

85

1986

Very

High

27

33

Côte

dÍvo

ireAb

idjan

Faye

-Kett

e (20

03)

1995

19

97Ve

ry Hi

gh

57

89

Côte

dÍvo

ireAb

idjan

Oreg

a (19

97)

1985

19

87Ve

ry Hi

gh

56

71

Gabo

nLib

revil

leKo

ko (2

000)

1989

19

91Hi

gh

18

33

Gamb

iaBa

njul

Palm

er (1

999)

1995

19

95Hi

gh

75

103

Gamb

iaUp

per R

iver

Divis

ionO'

Demp

sey (

1994

)19

89

1990

Very

High

11

11

Gamb

iaUp

per R

iver

Divis

ionO'

Demp

sey (

1996

)19

89

1990

Very

High

8

911

113

Gamb

iaW

ester

nGo

etghe

buer

(2

000)

1990

19

92Hi

gh

101

12

0

Keny

aNa

irobi

Nesb

itt (1

988)

1985

19

85Hi

gh

2428

29


Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5

Morta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age

stud

y po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Spn

Men

ingi

tisSp

n NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io (%

)In

ciden

ce

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y rat

io

(%)

<1<2

<5<1

<2<5

<1<2

<5<5

(a

dj)

<1<2

<5<1

<2<5

Mada

gasc

arAn

tanan

arivo

Migli

ani (2

002)

1998

19

99Hi

gh

4651

Moza

mbiqu

eMa

nhica

Di

strict

Roca

(200

6)20

01

2002

Very

High

69

3957

7

Nige

riaBe

nin C

ityAk

pede

(199

4)19

85

1987

Very

High

11

2436

Nige

riaEn

ugu

Onye

meluk

we

(199

4)19

89

1990

Very

High

13

1830

Nige

riaEn

ugu S

tate

Ozum

ba (1

995)

1989

19

91Ve

ry Hi

gh

13

18

Nige

riaSo

koto

Emele

(200

0)19

87

1990

Very

High

16

33

Sene

gal

Daka

rCi

sse (

1989

)19

83

1985

Very

High

63

68

Togo

Lomé

-Toko

inAt

akou

ma (1

995)

1987

19

88Hi

gh

2833

WHO

Reg

ion

of th

e Am

erica

s (AM

R)

AMR

stud

ies w

ith in

ciden

ce d

ata

Braz

ilBa

hiaLu

cena

(199

6)19

902.9

1991

Mediu

m10

2 537

44

45

34

15

Braz

ilCa

mpina

sW

eiss (

2001

)19

971.9

1997

Mediu

m77

819

911

13

2818

8.7

133WHO/IVB/09.02

Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5

Morta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age

stud

y po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Spn

Men

ingi

tisSp

n NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io (%

)In

ciden

ce

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y rat

io

(%)

<1<2

<5<1

<2<5

<1<2

<5<5

(a

dj)

<1<2

<5<1

<2<5

Braz

ilGo

ias S

tate

Simo

es (2

004)

1995

5.919

98Me

dium

302 2

80

20

1.1

Braz

ilPa

rana

Stat

eTa

kemu

ra (2

001)

1992

719

95Me

dium

12

Braz

ilSa

lvado

rKo

(200

0)19

952.8

1997

Mediu

m

3.2

4

32

8

Braz

ilSa

lvado

rRe

is (2

002)

1995

3.919

97Me

dium

157 9

97

15

3

60

24.7

25.9

Braz

ilSa

o Pau

loRe

zend

e (19

89)

1983

0.919

83Hi

gh3 7

04 64

110

1

148

13

4.4

Cana

da9 c

ities

Bjor

nson

(200

2)19

944.9

1996

Very

Low

66

9

Chile

Santi

ago

Ferre

ccio

(199

0)19

852.9

1986

Very

Low

546 1

6415

421

524

2

4733

15.2

Chile

Metro

polita

n re

gion

Lago

s Z (2

001)

1994

6.919

97Ve

ry Lo

w58

6 112

155

198

216

1519

125.3

11

216

222

6

Costa

Rica

Who

le co

untry

Ulloa

-Guti

erre

z (2

003)

1995

6.919

98Ve

ry Lo

w48

9 067

34

44

2

1.3

21

27

Cuba

Who

le co

untry

Dick

inson

(200

2)19

982.9

1999

Very

Low

277 6

1819

31

2312

4

Cuba

Who

le co

untry

Dick

inson

Me

nese

s (20

01)

1993

5.919

95Ve

ry Lo

w91

3 430

98

157

10

2.9

Cuba

Who

le co

untry

Legu

en (1

991)

1989

0.919

89Ve

ry Lo

w94

4 625

26

4354

14

5


Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5

Morta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age

stud

y po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Spn

Men

ingi

tisSp

n NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io (%

)In

ciden

ce

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y rat

io

(%)

<1<2

<5<1

<2<5

<1<2

<5<5

(a

dj)

<1<2

<5<1

<2<5

Domi

nican

Re

publi

cNa

tiona

l Di

strict

Reg

ionGo

mez (

2000

)19

980.9

1998

Mediu

m35

9 536

1216

17

1812

5.27.3

Guate

mala

Guate

mala

City

Astur

ias (2

003)

1996

2.319

97Me

dium

125 3

70

46

37

16

.318

.7

1

Unite

d St

ates

Alas

kaDa

vidso

n (19

94)

1986

4.919

88Ve

ry Lo

w52

785

2125

27

1211

3722

10.4

135

169

0.7

0.59

Unite

d St

ates

Kans

asW

alling

(199

1)19

835

1985

Very

Low

36 71

4

19

10

.4

Unite

d St

ates

Mass

achu

setts

Loug

hlin (

1995

)19

861

1986

Very

Low

410 0

00

16

4

Unite

d St

ates

New

York

Liptak

(199

7)19

8211

1987

Very

Low

34

Unite

d St

ates

Texa

sPa

stor (

1998

)19

950.9

1995

Very

Low

12

19

53

Unite

d St

ates

5 citie

sRo

binso

n (20

01)

1995

3.919

96Ve

ry Lo

w

113

157

182

43.9

4.5

8

91

220

8626

22

Unite

d St

ates

20 st

ates

Adam

s (19

93)

1989

0.919

89Ve

ry Lo

w7 5

14 50

7

19

0

2.8

Urug

uay

Who

le co

untry

Camo

u (20

03)

1994

719

97Ve

ry Lo

w32

1 583

105

33

33

4.7

54

135WHO/IVB/09.02

Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5

Morta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age

stud

y po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Spn

Men

ingi

tisSp

n NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io (%

)In

ciden

ce

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y rat

io

(%)

<1<2

<5<1

<2<5

<1<2

<5<5

(a

dj)

<1<2

<5<1

<2<5

AMR

stud

ies w

ithou

t inc

iden

ce d

ata

Arge

ntina

8 citie

sRu

vinsk

y (20

02)

1993

19

97Ve

ry Lo

w

294

14

2

Arge

ntina

Who

le co

untry

Kerte

sz (1

998)

1993

19

94Me

dium

52

8

276

Braz

ilSa

lvado

rNa

scim

ento-

Carva

lho (1

998)

1988

19

92Me

dium

25

2526

Braz

ilSa

nta

Catar

inaSi

lva (1

990)

1980

19

84Hi

gh

44

34

Braz

ilSa

o Pau

loBe

rezin

(199

6)19

89

1991

Mediu

m

2931

36

38.7

2

Braz

ilSa

o Pau

loBe

rezin

(200

2)19

94

1996

Mediu

m

40

28

Braz

ilW

hole

coun

tryFla

nner

y (20

07)

2000

Mediu

m

29

Chile

Santi

ago

Chav

ez P

(199

4)19

83

1988

Very

Low

5858

17

Chile

Santi

ago

Diaz

(200

1)19

89

1993

Very

Low

11

113

015

4

Chile

Santi

ago

Lago

s (pe

rsona

l co

mmun

icatio

n)19

99

2002

Very

Low

pc

pc

pcpc

pcpc

pc

Chile

Temu

co re

gion

Boeh

me (1

993)

1988

19

89Ve

ry Lo

w

1114

17

Chile

Valdi

viaBu

rgos

(198

8)19

84

1985

Very

Low

5

7


Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5

Morta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age

stud

y po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Spn

Men

ingi

tisSp

n NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io (%

)In

ciden

ce

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y rat

io

(%)

<1<2

<5<1

<2<5

<1<2

<5<5

(a

dj)

<1<2

<5<1

<2<5

Colom

biaBo

gotá

Ríos

(199

9)19

94

1995

Very

Low

10

4

19

14

Colom

biaMe

dellin

Oter

o (19

88)

1984

19

85Me

dium

2022

Colom

bia3 c

ities

Agud

elo (1

999)

1994

19

97Ve

ry Lo

w

242

277

361

45

6185

Colom

bia7 d

epar

tmen

tsAg

udelo

(200

0)19

94

1996

Very

Low

11

3

149

Colom

bia7 d

epar

tmen

tsAg

udelo

(200

1)19

94

1997

Very

Low

13

8

191

Mexic

oMe

xico C

ityCa

stane

da

Narva

ez (1

990)

1980

19

84Me

dium

15

18

Unite

d St

ates

North

ern

Califo

rnia

Blac

k (pe

rsona

l co

mmun

icatio

n)19

95

1998

Very

Low

pc

pc

pc

Unite

d St

ates

Memp

his,

Tenn

esse

eBu

cking

ham

(200

1)19

91

1995

Very

Low

46

71

8.5

Unite

d St

ates

8 citie

sKa

plan (

1998

)19

93

1995

Very

Low

10

213

215

3

311

607

768

Unite

d St

ates

8 stat

esKa

plan (

2002

)19

93

1996

Very

Low

264

11

78

Unite

d St

ates

8 stat

esKi

ng (2

003)

1994

19

96Ve

ry Lo

w

199

pc*

pc

Urug

uay

3 dep

artm

ents

Horta

l (199

7)19

94

1995

Very

Low

3442

24

26

Urug

uay

Who

le co

untry

Horta

l Palm

a (2

002)

1994

19

97Ve

ry Lo

w

6475

89

3344

52

137WHO/IVB/09.02

Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5

Morta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age

stud

y po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Spn

Men

ingi

tisSp

n NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io (%

)In

ciden

ce

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y rat

io

(%)

<1<2

<5<1

<2<5

<1<2

<5<5

(a

dj)

<1<2

<5<1

<2<5

WHO

Eas

tern

Med

iterra

nean

Reg

ion

(EMR

)

EMR

stud

ies w

ith in

ciden

ce d

ata

Saud

i Ara

biaRi

yadh

Almu

neef

(200

1)19

955.6

1998

Mediu

m21

639

1517

21

5028

17.4

Saud

i Ara

bia4 p

rovin

ces

Al-M

azro

u (20

04)

1999

1.920

00Ve

ry Lo

w17

9 182

1819

23

2413

6.7

EMR

stud

ies w

ithou

t inc

iden

ce d

ata

Moro

cco

Casa

blanc

aAb

id (1

999)

1980

19

88Me

dium

88

105

133

6

Saud

i Ara

biaEa

stern

Abom

elha (

1988

)19

82

1983

Mediu

m

1316

21

Saud

i Ara

biaTa

buk

Azub

uike (

1990

)19

82

1984

Mediu

m

5

9

WHO

Eur

opea

n Re

gion

(EU

R)

EUR

stud

ies w

ith in

ciden

ce d

ata

Austr

iaSt

yria s

tate

Raute

r (19

94)

1983

9.919

87Ve

ry Lo

w17

635

34

6

96

3.4

Austr

iaW

hole

coun

tryRe

ndi-W

agne

r (2

004)

2001

1.920

02Ve

ry Lo

w50

0 082

24

34

12

8

6

Belgi

umAn

twer

pva

n Hoe

ck (1

997)

1988

619

90Ve

ry Lo

w58

532

1418

20

2415

5.7


Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5

Morta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age

stud

y po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Spn

Men

ingi

tisSp

n NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io (%

)In

ciden

ce

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y rat

io

(%)

<1<2

<5<1

<2<5

<1<2

<5<5

(a

dj)

<1<2

<5<1

<2<5

Bulga

ria6 r

egion

sKo

jouha

rova

(2

002)

1997

2.419

98Ve

ry Lo

w14

1 901

1417

23

21

6.7

Denm

ark

Who

le co

untry

Kalto

ft (20

00)

1981

18.9

1990

Very

Low

366 1

6220

228

632

4

1712

4.6

Denm

ark

Who

le co

untry

Konr

adse

n (20

02)

1995

4.919

97Ve

ry Lo

w34

3 875

93

93

14

5.5

21

828

8

Finlan

dW

hole

coun

tryEs

kola

(199

2)19

854

1987

Very

Low

404 4

8521

3034

7

52.1

88

220

308

2.1

Fran

ce7 d

epar

tmen

tsGa

illat (

1998

)19

914

1993

Very

Low

3.4

Germ

any

Who

le co

untry

von K

ries (

2000

)19

971.9

1997

Very

Low

4 125

179

157

230

307

10

73.9

Germ

any

Who

le co

untry

von K

ries (

2002

)19

974

1999

Very

Low

4 392

640

8750

565

0

8

117

3.7

Israe

lW

hole

coun

tryDa

gan (

1994

)19

882.9

1990

Very

Low

562 5

8359

7787

18

125.3

Italy

Naple

sPi

zzuti

(199

8)19

942

1994

Very

Low

949 5

7712

1625

3

21.3

Italy

Pied

mont,

Pu

glia

D'An

cona

(200

5)20

010.9

2001

Very

Low

424 9

825

710

6

52.3

4

Italy

Pugli

aCh

ironn

a (19

98)

1994

1.919

94Ve

ry Lo

w25

2 987

5

1

Nethe

rland

sW

hole

coun

trySp

anjaa

rd (2

000)

1990

9.919

94Ve

ry Lo

w79

903

65

8.2

139WHO/IVB/09.02

Coun

trySt

udy s

iteRe

fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5

Morta

lity

stra

ta

(stu

dy

mid

poin

t ye

ar)

Estim

ated

an

nual

aver

age

stud

y po

pulat

ion

of

<5 ch

ildre

n fo

r inc

iden

ce

stud

ies

Spn

Men

ingi

tisSp

n NP

NM

Num

ber o

f cas

esCa

se-fa

talit

y rat

io (%

)In

ciden

ce

(per

100 0

00)

Num

ber o

f

case

sCa

se-fa

talit

y rat

io

(%)

<1<2

<5<1

<2<5

<1<2

<5<5

(a

dj)

<1<2

<5<1

<2<5

Roma

nia2 d

istric

tsLu

ca (2

004)

2000

220

01Ve

ry Lo

w85

438

3

6

2

3.5

Russ

ian

Fede

ratio

nSt

. Pete

rsbur

gKo

stiuk

ova (

1992

)19

855

1987

Very

Low

4.9

Spain

Barce

lona

Pine

da (2

002)

1990

10.9

1995

Very

Low

67

8

40

Spain

Canta

bria

Gonz

alez (

2003

)19

956.9

1998

Very

Low

19 29

0

37

65.2

25

Spain

Catal

onia

Domi

ngue

z (20

02)

1997

2.919

98Ve

ry Lo

w

23

7

83

Spain

Gijon

Pere

z (20

02)

1992

8.419

96Ve

ry Lo

w

4

15

36

Spain

Guipu

zcoa

Igles

ias S

anch

ez

(200

2)19

8120

.919

91Ve

ry Lo

w15

249

11

14

9

4.4

Spain

Madr

idVi

llo S

irero

l (200

4)19

917

1994

Very

Low

34 25

9

56

42.5

Spain

Murci

aEs

pin (2

002)

1996

419

98Ve

ry Lo

w

0.60.7

0.39

11

61.3

Spain

Pais

Vasc

o, Na

varra

Bern

aola

Iturb

e (2

002)

1998

319

99Ve

ry Lo

w10

1 329

1417

25

2214

8

Spain

Sevil

leSo

ult R

ubio

(200

5)20

012.1

2002

Very

Low

62 83

4

812

159.2

Spain

Valen

ciaDi

ez-D

oming

o (2

002)

1996

0.919

96Ve

ry Lo

w77

1 766

1013

17

44

2.4


Coun

trySt

udy s

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fere

nce

Year

st

arte

dDu

ratio

n (y

ears

)

Stud

y m

idpo

int

year

<5

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lity

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ta

(stu

dy

mid

poin

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ar)

Estim

ated

an

nual

aver

age

stud

y po

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of

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n fo

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ce

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ies

Spn

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n NP

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Num

ber o

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io (%

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ce

(per

100 0

00)

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ber o

f

case

sCa

se-fa

talit

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(%)

<1<2

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<1<2

<5<5

(a

dj)

<1<2

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Spain

5 reg

ions

Casa

do (2

002)

1998

2.919

99Ve

ry Lo

w90

3 925

4872

93

118

3.5

Spain

5 reg

ions

Casa

do F

lores

(1

997)

2000

120

00Ve

ry Lo

w69

7 592

2638

44

1813

6.3

Swed

enSo

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stern

re

gion

Dahl

(200

1)19

8114

1988

Very

Low

38 61

5

1620

73.7

32

Swed

enW

hole

coun

tryBe

rg (1

996)

1987

219

88Ve

ry Lo

w76

1 602

57

62

10

4.1

Switz

erlan

dW

hole

coun

try

exce

pt Ge

neva

Vene

tz (1

998)

1985

9.919

89Ve

ry Lo

w38

0 016

92

118

63.1

6486

Unite

d Ki

ngdo

m

Tham

es

regio

n, En

gland

Jone

s (19

97)

1991

2.919

92Ve

ry Lo

w20

4 993

23

3.8

Unite

d Ki

ngdo

m

Tham

es

regio

n, En

gland

Urwi

n (19

96)

1991

2.919

92Ve

ry Lo

w88

423

10

19

18

7.4

Unite

d Ki

ngdo

mEn

gland

and

Wale

sde

Louv

ois (1

991)

1985

1.819

86Ve

ry Lo

w

177

9

13

Unite

d Ki

ngdo

mEn

gland

and

Wale

sLa

urich

esse

(1

998)

1993

2.919

94Ve

ry Lo

w3 5

57 50

518

8

280

9

2.7

Unite

d Ki

ngdo

mEn

gland

and

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sMi

ller (

2000

)19

962.9

1997

Very

Low

3 325

275

307

385

449

1213

1416

104.6

Unite

d Ki

ngdo

mEn

gland

and

Wale

sSl

eema

n (20

01)

1995

4.419

97Ve

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w

0.8

1.65

13

5.5

Unite

d Ki

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mNo

ttingh

am

distric

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(199

3)19

809.9

1984

Very

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45 76

421

30

2013

6.6

141WHO/IVB/09.02

Coun

trySt

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Year

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n (y

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dj)

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Unite

d Ki

ngdo

mOx

ford

Shac

kley (

2000

)19

915.6

1993

Very

Low

195 5

68

39

4.1

22

Unite

d Ki

ngdo

mSc

otlan

dKy

aw (2

002)

1983

1619

91Ve

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w33

3 714

129

21

9

10

4

EUR

stud

ies w

ithou

t inc

iden

ce d

ata

Gree

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Syrio

poulo

u (2

000)

1995

19

97Ve

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w

1220

2042

Norw

ay3 c

ounti

esJe

nsse

n (20

00)

1980

19

88Ve

ry Lo

w

712

15

1325

36

Polan

dW

hole

coun

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(2

000)

1997

19

97Ve

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w

3

7

Russ

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Fede

ratio

nMo

scow

Demi

na (1

983)

1980

19

82Me

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17

29

Russ

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Fede

ratio

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Demi

na (1

986)

1980

19

82Me

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19

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Russ

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Fede

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nMo

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Devia

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(199

0)19

88

1988

Very

Low

33

44

Spain

Malag

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(1

998)

1988

19

91Ve

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w

1215

22

Unite

d Ki

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mEn

gland

McInt

osh (

2003

)19

99

1999

Very

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24

5

134

Unite

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003)

1999

20

00Ve

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w

56

49


Coun

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Num

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ber o

f

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sCa

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(%)

<1<2

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(a

dj)

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WHO

Sou

th-E

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SEAR

stud

ies w

ithou

t inc

iden

ce d

ata

Bang

lades

hDh

aka

Saha

(199

7)19

87

1990

Mediu

m

141

164

189

Bang

lades

hDh

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sona

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n)20

03

2005

Mediu

m

pcpc

pcpc

pcpc

pcpc

pc

India

6 citie

sIN

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(199

9)19

93

1995

High

3142

India

6 citie

sSt

einho

ff (pe

rsona

l co

mmun

icatio

n)19

93

1995

High

pcpc

pcpc

Thail

and

Bang

kok

Chotp

itaya

suno

ndh

(199

4)19

80

1985

Mediu

m

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6

WHO

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tern

Pac

ific R

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PR)

WPR

stud

ies w

ith in

ciden

ce d

ata

Austr

alia

Far N

orth

Quee

nslan

dFa

gan (

2001

)19

928

1996

Very

Low

19 40

9

1517

2510

.9

21

31

Austr

alia

Tasm

ania

Chris

tie (2

002)

1994

6.919

97Ve

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w33

493

11

13

12

5.6

26

38

Austr

alia

Victo

riaLiu

(200

3)20

010.9

2001

Very

Low

339 5

46

13

4.1

84

Austr

alia

Wes

tern

Hann

a (19

91)

1984

4.919

86Ve

ry Lo

w11

5 737

36

8.3

6.3

143WHO/IVB/09.02

Coun

trySt

udy s

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fere

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Year

st

arte

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ratio

n (y

ears

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aver

age

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Austr

alia

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3)19

974.5

1999

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330 5

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136.4

66

7

Austr

alia

Who

le co

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Roch

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03)

2002

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02Ve

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51 36

5

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3.5

43

6

China

Hefei

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6)19

902.9

1991

Mediu

m80

365

5

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, Hon

g Ko

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tories

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997)

1984

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89Ve

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w71

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5

0.8

Fiji

Who

le co

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Wils

on (2

003)

1992

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92Ve

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7 986

47

25

Japa

nAi

chi

Prefe

cture

Ishika

wa (1

996)

1984

919

88Ve

ry Lo

w42

6 168

2331

38

1916

32

1

Mong

olia

Ulaa

nbaa

tarW

att (2

004)

2002

2.920

03Me

dium

61 73

8

19

10

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New

Zeala

ndAu

cklan

dVo

ss (1

994)

1984

8.919

88Ve

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w70

842

4157

62

5.34.3

2923

9.8

Repu

blic o

f Ko

rea

Jeon

buk

Prov

ince

Kim

(200

4)19

992.3

2000

Very

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103 8

112

35

4

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WPR

stud

ies w

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t inc

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ce d

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Austr

alia

New

South

W

ales

McInt

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000)

1997

19

98Ve

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w

31

36

20

23

Austr

alia

North

ern

Terri

tory

Krau

se (2

000)

1994

19

96Ve

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w

20

42


Coun

trySt

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st

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dDu

ratio

n (y

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lity

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ta

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ar)

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ated

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age

stud

y po

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ion

of

<5 ch

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n fo

r inc

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ce

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n NP

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Num

ber o

f cas

esCa

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io (%

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ce

(per

100 0

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Num

ber o

f

case

sCa

se-fa

talit

y rat

io

(%)

<1<2

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<1<2

<5<5

(a

dj)

<1<2

<5<1

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Austr

alia

1 ter

ritory,

Qu

eanb

eyan

Andr

esen

(200

4)19

88

1994

Very

Low

47

3137

Austr

alia

Sydn

eyDa

vis (1

995)

1981

19

87Ve

ry Lo

w

87

118

8

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5

7.12.4

Austr

alia

Centr

alTr

otman

(199

5)19

92

1992

Very

Low

45

Austr

alia

Who

le co

untry

Roch

e (20

04)

2003

20

03Ve

ry Lo

w

62

373

China

4 citie

s, 18

pr

ovinc

esSh

en (1

989)

1982

19

83Me

dium

11

6

20

87

Japa

nKa

naga

wa

Prefe

cture

Sato

(200

1)19

85

1987

Very

Low

6

715

5

1720

Papu

a New

Gu

inea

Easte

rn

High

lands

Lehm

ann (

1999

)19

89

1991

High

43

52

Papu

a New

Gu

inea

The h

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d ar

eas

Gratt

en (1

985)

1980

19

82Hi

gh

5354

63

Repu

blic o

f Ko

rea

Seou

lKi

m (1

998)

1986

19

90Ve

ry Lo

w

2126

32

Repu

blic o

f Ko

rea

Seou

lLe

e (19

98)

1986

19

91Ve

ry Lo

w

7

13

Viet

Nam

Ho C

hi Mi

nh

City

Tran

(199

8)19

95

1996

Mediu

m

1819

24

* pc

= pe

rson

al c

omm

unic

atio

n

145WHO/IVB/09.02

Annex 8 lists all studies (332 articles containing 336 studies) that were considered evaluable for any outcome. The articles in Annexes 6 and 7 are found in Annex 8, as well as additional articles that do not contain key outcomes (Tables 7.1.1 (Hib) and 7.1.2 (Spn)). The figure below describes the set of data included in Annex 8.

Figure: Summary of references and studies abstracted (continued from Figure 1)

Annex 8: References for studies with

evaluable outcome data

Of the articles identified with evaluable data, 332 articles (336 studies) contained key outcome data. Annex 8 lists any article that had an evaluable Hib and/or Spn outcome by country and grouped by WHO region.


contain evaluable data


Table 1: All studies with evaluable outcome data


Table 2: Studies from the WHO African Region (AFR) with evaluable outcome data

Countries and other areas Citation Type of data

in article

Burkina Faso

Parent du Chatelet I et al. Bacterial meningitis in Burkina Faso: surveillance using field-based polymerase chain reaction testing. Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America, 2005, 40(1):17–25.

Hib Spn

Burkina FasoTall FR et al. Haemophilus influenzae meningitis in a hospital in Burkina-Faso. Médecine et Maladies Infectieuses, 1992, 22(12):1173–1177.

Hib Spn

Burkina FasoYaro S et al. The epidemiology of Haemophilus influenzae type b meningitis in Burkina Faso. The Pediatric Infectious Disease Journal, 2006, 25(5):415–419.

Hib

Cameroon

Bernard-Bonnin AC, Ekoe T. [Purulent meningitis in children in Yaoundé: epidemiological and prognostic aspects]. Annales de la Société belge de médecine tropicale, 1985, 65(1):59–68.

Hib Spn

CameroonFonkoua MC et al. [Bacterial meningitis in Yaoundé (Cameroon) in 1999–2000]. Bulletin de la Société de pathologie exotique (1990), 2001, 94(4):300–303.

Hib Spn

Côte d´Ivoirede Bary JB et al. [Purulent meningitis at a semi-rural hospital in the forest area of the Ivory Coast]. Bulletin de la Société de pathologie exotique (1990), 1990;83(4):460–467.

Hib Spn

147WHO/IVB/09.02


in article

Côte d´Ivoire

Faye-Kette H et al. [Agents of community acquired purulent meningitis in the child: epidemiologic trends in Abidjan, Côte d’Ivoire, from the year 1995 to 2000]. Bulletin de la Société de pathologie exotique (1990), 2003, 96(4):313–316.

Hib Spn

Côte d´Ivoire

Orega M et al. Les meningites purulentes de l’enfant à Abidjan (À propos de 521 cas). [Purulent meningitis in children in Abidjan (a case-series including 521 cases).]

Médecine d’Afrique Noire, 1997, 44(4).

Hib Spn

EthiopiaGedlu E, Rahlenbeck SI. Pyogenic meningitis in children in north-western Ethiopia. Annals of Tropical Paediatrics, 1995, 15(3):243–247.

Hib

Ethiopia

Muhe L, Klugman KP. Pneumococcal and Haemophilus influenzae meningitis in a children’s hospital in Ethiopia: serotypes and susceptibility patterns. Tropical Medicine and International Health: TM & IH, 1999, 4(6):421–427.

Hib

GabonKoko J et al. Bacterial meningitis in children in Libreville, Gabon. Epidemiologic, therapeutic and prognostic features. Médecine et Maladies Infectieuses, 2000, 30(1):50–56.

Hib Spn

Gambia

Adegbola RA et al. Haemophilus influenzae type b disease in the western region of The Gambia: background surveillance for a vaccine efficacy trial. Annals of Tropical Paediatrics, 1996, 16(2):103–111.

Hib

GambiaAdegbola RA et al. Haemophilus influenzae type b meningitis in The Gambia after introduction of a conjugate vaccine. Lancet, 1999, 354(9184):1091–1092.

Hib

Gambia

Bijlmer HA et al. The epidemiology of Haemophilus influenzae meningitis in children under five years of age in The Gambia, West Africa. The Journal of Infectious Diseases, 1990, 161(6):1210–1215.

Hib

Gambia

Cutts FT et al. Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomized, double-blind, placebo-controlled trial. Lancet, 2005, 365(9465):1139–1146.

Spn

Gambia

Goetghebuer T et al. Outcome of meningitis caused by Streptococcus pneumoniae and Haemophilus influenzae type b in children in The Gambia. Tropical Medicine and International Health: TM & IH, 2000, 5(3):207–213.

Hib Spn



in article

Gambia

Mulholland K et al. Randomized trial of Haemophilus influenzae type-b tetanus protein conjugate vaccine [corrected] for prevention of pneumonia and meningitis in Gambian infants. Lancet, 1997, 349(9060):1191–1197.

Hib

Gambia

O’Dempsey TJ et al. Importance of enteric bacteria as a cause of pneumonia, meningitis and septicemia among children in a rural community in The Gambia, West Africa. The Pediatric Infectious Disease Journal, 1994, 13(2):122–128.

Hib Spn

GambiaO’Dempsey TJ et al. Pneumococcal disease among children in a rural area of west Africa. The Pediatric Infectious Disease Journal, 1996, 15(5):431–437.

Spn

GambiaPalmer A et al. Acute bacterial meningitis in The Gambia: a four-year review of paediatric hospital admissions. Journal of Tropical Pediatrics, 1999, 45(1):51–53.

Hib Spn

GambiaUsen S et al. Epidemiology of invasive pneumococcal disease in the Western Region, The Gambia. The Pediatric Infectious Disease Journal, 1998, 17(1):23–28.

Hib Spn

KenyaBerkley JA et al. Bacteremia among children admitted to a rural hospital in Kenya. The New England Journal of Medicine, 2005, 352(1):39–47.

Spn

Kenya

Cowgill KD et al. Effectiveness of Haemophilus influenzae type b conjugate vaccine introduction into routine childhood immunization in Kenya. JAMA: the journal of the American Medical Association, 2006, 296(6):671–678.

Hib

Kenya Nesbitt A et al. Pyogenic meningitis in Nairobi children. East African Medical Journal, 1988, 65(3):189–196. Hib Spn

Madagascar

Migliani R et al. [Non-tubercular bacterial meningitis in children in Antananarivo, Madagascar]. Archives de pédiatrie : organe officiel de la Sociéte Française de Pédiatrie, 2002, 9(9):892–897.

Hib Spn

Madagascar

Razafindralambo M et al. [Haemophilus influenzae, the second cause of bacterial meningitis in children in Madagascar]. Bulletin de la Société de pathologie exotique (1990), 2004, 97(2):100–103.

Hib

Malawi

Molyneux E et al. Acute bacterial meningitis in children admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi in 1996–97. Tropical Medicine and International Health: TM & IH, 1998, 3(8):610–618.

Hib

149WHO/IVB/09.02


in article

MaliCampbell JD et al. Invasive pneumococcal infections among hospitalized children in Bamako, Mali. The Pediatric Infectious Disease Journal, 2004, 23(7):642–649.

Spn

Mali

Sow SO et al. Burden of invasive disease caused by Haemophilus influenzae type b in Bamako, Mali: impetus for routine infant immunization with conjugate vaccine. The Pediatric Infectious Disease Journal, 2005, 24(6):533–537.

Hib

MozambiqueRoca A et al. Invasive pneumococcal disease in children <5 years of age in rural Mozambique. Tropical Medicine and International Health: TM & IH, 2006, 11(9):1422–1431.

Spn

NigerCampagne G et al. Epidemiology of bacterial meningitis in Niamey, Niger, 1981–96. Bulletin of the World Health Organization, 1999, 77(6):499–508.

Hib Spn

Nigeria

Akpede O et al. Childhood bacterial meningitis beyond the neonatal period in southern Nigeria: changes in organisms/antibiotic susceptibility. East African Medical Journal, 1994, 71(1):14–20.

Hib Spn

NigeriaEmele FE. Etiologic spectrum and pattern of antimicrobial drug susceptibility in bacterial meningitis in Sokoto, Nigeria. Acta Paediatrica, 2000, 89(8):942–946.

Spn

NigeriaOnyemelukwe NF. Haemophilus influenzae meningitis in parts of eastern Nigeria. East African Medical Journal, 1994, 71(2):129–131.

Hib Spn

NigeriaOzumba UC. Acute bacterial meningitis in Enugu, Nigeria. 1 April 1989 to 31 March 1993. The Central African Journal of Medicine, 1995, 41(2):54–59.

Spn

SenegalCisse MF et al. [Bacterial meningitis in a pediatric hospital in a tropical zone]. Médecine tropicale : revue du corps de santé colonial, 1989, 49(3):265–269.

Hib Spn

South AfricaHussey G et al. Epidemiology of invasive Haemophilus influenzae infections in Cape Town, South Africa. Annals of Tropical Paediatrics, 1994, 14(2):97–103.

Hib

South AfricaHussey G et al. Epidemiology of post-neonatal bacterial meningitis in Cape Town children. South African Medical Journal, 1997, 87(1):51–56.

Spn

South Africa

Karstaedt AS, Khoosal M, Crewe-Brown HH. Pneumococcal bacteremia during a decade in children in Soweto, South Africa. The Pediatric Infectious Disease Journal, 2000, 19(5):454–457.

Spn



in article

South Africa

Klugman KP et al. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. The New England Journal of Medicine, 2003, 349(14):1341–1348.

Spn

South Africa

Madhi SA et al. Increased disease burden and antibiotic resistance of bacteria causing severe community-acquired lower respiratory tract infections in human immunodeficiency virus type 1-infected children. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, (2000a), 31(1):170–176.

Hib Spn

South Africa

Madhi SA et al. Impact of human immunodeficiency virus type 1 on the disease spectrum of Streptococcus pneumoniae in South African children. The Pediatric Infectious Disease Journal, (2000b), 19(12):1141–1147.

Spn

South Africa

Madhi SA et al. Reduced effectiveness of Haemophilus influenzae type b conjugate vaccine in children with a high prevalence of human immunodeficiency virus type 1 infection. The Pediatric Infectious Disease Journal, 2002, 21(4):315–321.

Hib

South Africa

Madhi SA et al. The impact of a 9-valent pneumococcal conjugate vaccine on the public health burden of pneumonia in HIV-infected and -uninfected children. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 2005, 40(10):1511–1518.

Spn

Togo

Atakouma DY et al. Aspects cliniques, bacteriologiques, thérapeutiques et évolutifs des meningites aigues purulentes du nourisson dans le service de pédiatrie du CHU de Lomé-Tokoin (Togo). [Clinical, bacteriological, treatment and outcome characteristics of acute purulent meningitis in infants in the University Hospital pediatric ward in Lome-Tokoin (Togo)] Médecine d’Afrique Noire, 1995, 42(5):270–275.

Hib Spn

151WHO/IVB/09.02

Table 3: Studies from the WHO Region of the Americas (AMR) with evaluable outcome data


in article

Argentina

Abate H, Falaschi A, García B. Enfermedad invasiva por Haemophilus influenzae b: disminución de la incidencia en la era postvaccinal. [Invasive disease caused by Haemophilus influenzae b: decreasing incidence in the post vaccination era.] Archivos Argentinos de Pediatría, 2003, 101(1):26–30.

Hib

Argentina

Hortal M et al. [Impact of Streptococcus pneumoniae on pneumonia in Latin American children. SIREVA-Vigia Group]. Revista Panamericana de Salud Pública = Pan American journal of Public Health, 2000, 8(3):185–195.

Spn

Argentina

Kertesz DA et al. Invasive Streptococcus pneumoniae infection in Latin American children: results of the Pan American Health Organization Surveillance Study. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 1998, 26(6):1355–1361.

Spn

ArgentinaRuvinsky R et al. [Streptococcus pneumoniae pneumococcal infections - epidemiology]. Archivos Argentinos de Pediatría, 2002, 100(1):31–43.

Spn

Argentina

Torres A et al. Infecciones invasivas por Haemophilus influenzae tipo b (Hib) en Tucumbn-Argentina. [Haemophilus influenzae type b (Hib) invasive infection in Tucumbn-Argentina.] Archivos Argentinos de Pediatría, 1995, 93(4):238–244.

Hib

Brazil

Berezin EN et al. Streptococcus pneumoniae penicillin-nonsusceptible strains in invasive infections in Sao Paulo, Brazil. The Pediatric Infectious Disease Journal, 1996, 15(11):1051–1053.

Spn

BrazilBerezin EN et al. [Pneumococcal meningitis in children: clinical findings, most frequent serotypes and outcome]. Jornal de Pediatria, 2002, 78(1):19–23.

Spn

Brazil

Ferraz LR et al. Ocorrencia de meningites por Neisseria meningitidis, Haemophilus influenzae e Streptococcus pneumoniae no Distrito Federal, no periodo de 1989 a 1995 [Incidence of meningitis resulting from Neisseria meningitis, Haemophilus influenzae and Streptococcus pneumoniae in Distrito Federal between 1989 and 1995]. Revista de Saúde do Distrito Federal, 1996, 7(1):19–24.

Hib

Brazil Flannery B (personal communication). In: Brazil Ministry of Health Country Letter Response, 2007. Hib Spn

Brazil


Spn



in article

BrazilKmetzsch C et al. Occurrence of Haemophylus influenzae B meningitis after the implementation of a mass vaccination program. Jornal de Pediatria, 2003, 79(6):530–536.

Hib

Brazil

Ko AI et al. Clonally related penicillin-nonsusceptible Streptococcus pneumoniae serotype 14 from cases of meningitis in Salvador, Brazil. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 2000, 30(1):78–86.

Spn

BrazilLucena R et al. [Clinical and laboratorial characteristics of bacterial meningitis in children]. Arquivos de Neuro-Psiquiatria, 1996, 54(4):571–576.

Hib Spn

BrazilMantese OC et al. [Prevalence of serotypes and antimicrobial resistance of invasive strains of Streptococcus pneumoniae]. Jornal de Pediatria, 2003, 79(6):537–542.

Spn

Brazil

Miranzi Sde S, Camacho LA, Valente JG. [Haemophilus influenzae type b: epidemiological situation in the State of Minas Gerais, Brazil, 1993–1997]. Cadernos de saúde pública / Ministério da Saúde, Fundação Oswaldo Cruz, Escola Nacional de Saúde Pública, 2003, 19(5):1267–1275.

Hib

BrazilNascimento-Carvalho CM, Moreno-Carvalho OA. [Etiology of bacterial meningitis in a cohort from Salvador, Bahia]. Arquivos de Neuro-Psiquiatria, 1998, 56(1):83–87.

Hib Spn

Brazil

Reis JN et al. Population-based survey of antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae from meningitis patients in Salvador, Brazil. Journal of Clinical Microbiology, 2002, 40(1):275–277.

Spn

Brazil

Rezende MA, Succi RCdM. Meningites no Estado de Säo Paulo nos anos de 1980 a 1983. [Meningitis in the State of Säo Paulo between 1980 and 1983.] Pediatria Moderna 1989, 24(3):113–120.

Hib Spn

Brazil

Ribeiro GS et al. Prevention of Haemophilus influenzae type b (Hib) meningitis and emergence of serotype replacement with type a strains after introduction of Hib immunization in Brazil. The Journal of Infectious Diseases, 2003, 187(1):109–116.

Hib

Brazil

Silva RJ et al. Fatores prognosticos na meningite pneumococcica. [Prognostic factors for pneumococcal meningitis.] ACM: Arquivos Catarinenses de Medicina, 1990, 19(3):185–188.

Spn

BrazilSimoes LL et al. [Impact of Haemophilus influenzae b (Hib) vaccination on meningitis in Central Brazil]. Revista de Saúde Pública, 2004, 38(5):664–670.

Hib Spn

153WHO/IVB/09.02


in article

BrazilTakemura NS, Andrade SM. [Haemophilus influenzae type b meningitis in the state of Parana, Brazil]. Jornal de Pediatria, 2001, 77(5):387–392.

Hib Spn

BrazilWeiss DP, Coplan P, Guess H. Epidemiology of bacterial meningitis among children in Brazil, 1997–1998. Revista de Saúde Pública, 2001, 35(3):249–255.

Hib Spn

Canada

Bigham M et al. Epidemiology, antibiotic susceptibility, and serotype distribution of Streptococcus pneumoniae associated with invasive pneumococcal disease in British Columbia — A call to strengthen public health pneumococcal immunization programs. The Canadian Journal of Infectious Diseases, 2003, 14(5):261–266.

Spn

Canada

Bjornson G et al. Population-based incidence rate of invasive pneumococcal infection in children: Vancouver, 1994–1998. Canada Communicable Disease Report, 2000, 26(18): 149–151; discussion 151–152.

Spn

Canada

Bjornson GL, Scheifele DW, Halperin SA. Population-based epidemiology of invasive pneumococcal infection in children in nine urban centers in Canada, 1994 through 1998. The Pediatric Infectious Disease Journal, 2002, 21(10): 947–950.

Spn

Canada

Jette LP et al. Surveillance of invasive Streptococcus pneumoniae infection in the province of Quebec, Canada, from 1996 to 1998: serotype distribution, antimicrobial susceptibility, and clinical characteristics. Journal of Clinical Microbiology, 2001, 39(2):733–737.

Spn

CanadaVaudry W, Talling D. Invasive pneumococcal infection in first nations children in northern Alberta. Canada Communicable Disease Report , 2002, 28(20):165–172.

Spn

Chile

Banfi PA, Valenzuela B, Lagos ZR. Vacuna anti Haemophilus influenzae b: impacto epidemiológico en Chile. [Vaccination against Haemophilus influenzae b: epidemiologic impact in Chile.] Revista Chilena de Infectología, 1999, 16(Suppl. 1):S56–S63.

Hib

ChileBoehme C et al. [Three years of acute bacterial meningitis in the pediatric service at the Temuco Regional Hospital]. Revista Médica de Chile, 1993, 121(6):633–638.

Hib Spn

ChileBurgos R et al. [Bacterial meningitis: identification of the etiologic agent by latex agglutination]. Revista Chilena de Pediatría, 1988, 59(2):88–93.

Hib Spn

ChileChavez PA et al. [Acute Bacterial Meningitis: A 10 Years Experience]. Revista Chilena de Infectología: órgano oficial de la Sociedad Chilena de Infectología, 1994, 11(2):92–98.

Hib Spn

Chile

Chávez P et al. Infecciones invasoras por Haemophilus influenzae b. [Invasive infections with Haemophilus influenzae b.] Revista Chilena de Infectología: órgano oficial de la Sociedad Chilena de Infectología, 1996, 13(1):27–33.

Hib



in article

Chile

Diaz JM et al. [Trends of etiology of acute bacterial meningitis in Chilean children from 1989 to 1998. Impact of the anti-H influenzae type b vaccine]. Revista Médica de Chile, 2001, 129(7):719–726.

Hib Spn

Chile

Ferreccio C et al. A population-based retrospective assessment of the disease burden resulting from invasive Haemophilus influenzae in infants and young children in Santiago, Chile. The Pediatric Infectious Disease Journal, 1990, 9(7):488–494.

Hib Spn

Chile

Lagos R et al. Large scale, postlicensure, selective vaccination of Chilean infants with PRP-T conjugate vaccine: practicality and effectiveness in preventing invasive Haemophilus influenzae type b infections. The Pediatric Infectious Disease Journal, 1996, 15(3):216–222.

Hib

Chile

Lagos R et al. Population-based surveillance for hospitalized and ambulatory pediatric invasive pneumococcal disease in Santiago, Chile. The Pediatric Infectious Disease Journal, 2002, 21(12):1115–1123.

Spn

Chile Lagos R (personal communication). 2006. Spn

Chile

Lagos Z R et al. [Epidemiology of Streptococcus pneumoniae invasive diseases in Chilean children: Clinical and Public Health Perspectives.] Revista Chilena de Infectología: órgano oficial de la Sociedad Chilena de Infectología, 2001, 18(s1):15–21.

Spn

Colombia

Agudelo CI et al. Vigilancia por el laboratorio de Streptococcus pneumoniae, aislado de procesos invasores en niños menores de 5 años: actualización de los datos 1994–2000. [Laboratory surveillance of Streptococcus pneumoniae, isolated from invasive sites in children less than 5 years: report from 1994–2000.] Biomédica , 2001, 21:192–199.

Spn

Colombia

Agudelo CI, Muñoz N, De la Hoz F. Evaluacion rapida del impacto de la vacuna contra Haemophilus influenzae serotipo b en Colombia. [Impact assessment of vaccination against Haemophilus influenzae type b in Colombia.] Revista Panamericana de Salud Pública = Pan American journal of Public Health, 2000, 8(3):181–184.

Spn

Colombia

Agudelo CI, Muñoz N, De la Hoz F. Evaluación rápida del impacto de la Vacuna contra Haemophilus influenzae serotipo b en Colombia. [Impact assessment of vaccination against Haemophilus influenzae type b in Colombia.] Revista de la Sociedad Boliviana de Pediatría, 2001, 40(1):9–11.

Spn

155WHO/IVB/09.02


in article

Colombia


Spn

Colombia

Otero R et al. Meningitis bacteriana aguda en ninos: estudio clinico y bacteriologico en el hospital infantil de Medellin. [Bacterial meningitis in children: clinical and bacteriologic study in the children’s hospital of Medellin.] Iatreia, 1988, 1(2):69–76.

Hib Spn

Colombia

Ríos AM et al., pneumoniae yGCdTeS. Impacto de la resistencia a antimicrobianos y de serotipos de Streptococcus pneumoniae en la mortalidad de niños menores de 5 años con enfermedad invasora. [Impact of antimicrobial resistance and serotypes of Streptococcus pneumoniae on mortality of children under 5 years of age with invasive disease.] Revista Panamericana de Salud Pública = Pan American journal of Public Health, 1999, 5(2):69–76.

Spn

Costa RicaUlloa-Gutierrez R et al. Invasive pneumococcal disease in Costa Rican children: a seven year survey. The Pediatric Infectious Disease Journal, 2003, 22(12):1069–1074.

Spn

Cuba

Dickinson FO et al. [Impact of vaccination against Haemophilus influenzae type b in Cuba.] Revista Panamericana de Salud Pública = Pan American journal of Public Health, 2001, 10(3):169–73.

Hib

Cuba

Dickinson M, Félix O, Perez R. Las meningoencefalitis bacterianas en la población infantil cubana. [Bacterial meningoencephalitis in a Cuban population of children.] Revista Cubana de Pediatría, 2002, 74(2):106–114.

Hib Spn

Cuba

Dickinson Meneses FO, Pérez Rodríguez AE. Meningoencefalitis bacterianas en Cuba. [Bacterial meningoencephalitis in Cuba.] Revista Cubana de Higiene y Epidemiología, 2001, 39(2):86–94.

Hib Spn

CubaLeguen CE et al. Non-meningococcal bacterial meningitis in the Republic of Cuba 1989. Revista de Sanidad e Higiene Pública, 1991, 65(6):521–527.

Hib Spn

Dominican Republic

Gomez E et al. Population-based surveillance for bacterial meningitis in the Dominican Republic: implications for control by vaccination. Epidemiology and Infection, 2000, 125(3): 549–554.

Hib Spn

Guatemala

Asturias EJ et al. Meningitis and pneumonia in Guatemalan children: the importance of Haemophilus influenzae type b and Streptococcus pneumoniae. Revista Panamericana de Salud Pública = Pan American journal of Public Health, 2003, 14(6):377–384.

Hib Spn



in article

Jamaica

Barton-Forbes MA, Samms-Vaughan M, Irons B. Epidemiology of Haemophilus influenzae invasive disease in Jamaica, 1990–1993. The West Indian Medical Journal, 2000, 49(3):200–204.

Hib

Mexico Castaneda Narvaez JL et al. Current aspects of bacterial meningitis. Revista Mexicana de Pediatria, 1990, 57(3). Hib Spn

Mexico


Spn

MexicoSosa-Iglesias EG et al. [Haemophilus influenzae infections in 2 hospitals in the city of Puebla, Mexico]. Revista Latinoamericana de Microbiología, 1995, 37(3):189–199.

Hib

ParaguayBasualdo W, Arbo A. Invasive Haemophilus influenzae type b infections in children in Paraguay. Archives of Medical Research, 2004, 35(2):126–133.

Hib

Peru

Instituto Nacional de Salud (Perú). Vigilancia epidemiológica centinela de Haemophilus influenzae y Streptococcus pneumoniae en menores de 5 años en el Perú. [Sentinel surveillance of Haemophilus influenzae and Streptococcus pneumoniae in children less than 5 years old in Peru.] Revista Peruana de Medicina Experimental y Salud Publica, 2003, 20(3):150–155.

Spn

United States

Adams WG et al. Decline of childhood Haemophilus influenzae type b (Hib) disease in the Hib vaccine era. JAMA: the journal of the American Medical Association, 1993, 269(2):221–226.

Hib Spn

United States Black R (personal communication), 2006. Spn

United States

Buckingham SC et al. Pneumococcal meningitis in children: relationship of antibiotic resistance to clinical characteristics and outcomes. The Pediatric Infectious Disease Journal, 2001, 20(9):837–843.

Spn

United States

Byington CL et al. Temporal trends of invasive disease due to Streptococcus pneumoniae among children in the intermountain west: emergence of nonvaccine serogroups. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 2005, 41(1):21–29.

Spn

United StatesCampbell JF et al. Pneumococcal bacteremia in Hawaii: initial findings of a pneumococcal disease prevention project. Hawaii Medical Journal, 1989, 48(12):513–514; 517–518.

Spn

157WHO/IVB/09.02


in article

United StatesCoant PN et al. Blood culture results as determinants in the organism identification of bacterial meningitis. Pediatric Emergency Care, 1992, 8(4):200–205.

Hib

United StatesCochi SL et al. Primary invasive Haemophilus influenzae type b disease: a population-based assessment of risk factors. The Journal of Pediatrics, 1986, 108(6):887–896.

Hib

United StatesCooper TA, Bandy U. Invasive disease attributed to Streptococcus pneumoniae, 1998–1999. Medicine and Health, Rhode Island, 2001, 84(1):24–25.

Spn

United States

Davidson M et al. The epidemiology of invasive pneumococcal disease in Alaska, 1986–1990 — ethnic differences and opportunities for prevention. The Journal of Infectious Diseases, 1994, 170(2):368–376.

Spn

United States

From the Centers for Disease Control and Prevention. Progress toward elimination of Haemophilus influenzae type b disease among infants and children — United States, 1987–1993. JAMA: the journal of the American Medical Association, 1994, 271(16):1231–1232.

Hib

United States

Greenberg DP et al. Protective efficacy of Haemophilus influenzae type b polysaccharide and conjugate vaccines in children 18 months of age and older. JAMA: the journal of the American Medical Association, 1991, 265(8):987–992.

Hib

United States

Gustafson TL et al. Statewide survey of the antimicrobial susceptibilities of Haemophilus influenzae producing invasive disease in Tennessee. Pediatric Infectious Disease, 1983, 2(2):119–122.

Hib

United StatesHarrison LH et al. A day care-based study of the efficacy of Haemophilus b polysaccharide vaccine. JAMA: the journal of the American Medical Association, 1988, 260(10):1413–1418.

Hib

United States

Istre GR et al. Invasive disease due to Streptococcus pneumoniae in an area with a high rate of relative penicillin resistance. The Journal of Infectious Diseases, 1987, 156(5):732–735.

Spn

United StatesKaplan SL et al. Three-year multicenter surveillance of systemic pneumococcal infections in children. Pediatrics, 1998, 102(3 Pt. 1):538–545.

Spn

United StatesKaplan SL et al. Six year multicenter surveillance of invasive pneumococcal infections in children. The Pediatric Infectious Disease Journal, 2002, 21(2):141–147.

Spn



in article

United States

King MD et al. Recurrent invasive pneumococcal disease: a population-based assessment. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 2003, 37(8):1029–1036.

Spn

United States

Liptak GS et al. Decline of pediatric admissions with Haemophilus influenzae type b in New York State, 1982 through 1993: relation to immunizations. The Journal of Pediatrics, 1997, 130(6):923–930.

Spn

United States

Loughlin AM, Marchant CD, Lett SM. The changing epidemiology of invasive bacterial infections in Massachusetts children, 1984 through 1991. American Journal of Public Health, 1995, 85(3):392–394.

Hib Spn

United StatesMakintubee S, Istre GR, Ward JI. Transmission of invasive Haemophilus influenzae type b disease in day care settings. The Journal of Pediatrics, 1987, 111(2):180–186.

Hib

United States

Murphy TV et al. Invasive Haemophilus influenzae type b disease in children less than 5 years of age in Minnesota and in Dallas County, Texas, 1983–1984. The Journal of Infectious Diseases, 1992, 165(Suppl. 1):S7–S10.

Hib

United States

Murphy TV et al. Declining incidence of Haemophilus influenzae type b disease since introduction of vaccination. JAMA: the journal of the American Medical Association, 1993, 269(2):246–248.

Hib

United States

Pastor P, Medley F, Murphy TV. Invasive pneumococcal disease in Dallas County, Texas: results from population-based surveillance in 1995. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 1998, 26(3):590–595.

Spn

United States

Rathore MH et al. Haemophilus influenzae type B invasive disease in urban and rural children: immunization patterns and prevalence of disease. The Southern Medical Journal, 1994, 87(11):1083–1087.

Hib

United States

Robinson KA et al. Epidemiology of invasive Streptococcus pneumoniae infections in the United States, 1995–1998: opportunities for prevention in the conjugate vaccine era. JAMA: the journal of the American Medical Association, 2001, 285(13):1729–1735.

Spn

United StatesSchoendorf KC et al. National trends in Haemophilus influenzae meningitis mortality and hospitalization among children, 1980 through 1991. Pediatrics, 1994, 3(4):663–668.

Hib

United StatesSchutze GE, Tucker NC, Mason EO, Jr. Impact of the conjugate pneumococcal vaccine in Arkansas. The Pediatric Infectious Disease Journal, 2004, 23(12):1125–1129.

Spn

159WHO/IVB/09.02


in article

United States

Singleton R et al. Experience with the prevention of invasive Haemophilus influenzae type b disease by vaccination in Alaska: the impact of persistent oropharyngeal carriage. The Journal of Pediatrics, 2000, 137(3):313–320.

Hib

United StatesTotapally BR, Walsh WT. Pneumococcal bacteremia in childhood: a 6-year experience in a community hospital. Chest, 1998, 113(5):1207–1214.

Spn

United StatesWalling AD et al. The epidemiology of bacterial meningitis. The Journal of the American Board of Family Practice / American Board of Family Practice, 1991, 4(5):307–311.

Hib Spn

United States

Whitney CG et al. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. The New England Journal of Medicine, 2003, 348(18):1737–1746.

Spn

Uruguay

Camou T et al. Invasive pneumococcal diseases in Uruguayan children: comparison between serotype distribution and conjugate vaccine formulations. Vaccine, 2003, 21(17–18):2093–2096.

Spn

Uruguay

Hortal M et al. Capsular type distribution and susceptibility to antibiotics of Streptococcus pneumoniae clinical strains isolated from Uruguayan children with systemic infectionS. pneumococcus Study Group. Microbial drug resistance (Larchmont, N.Y.), 1997, 3(2):159–163.

Spn

Uruguay


Spn

Uruguay

Hortal Palma M et al. Vigilancia de las neumococcias del nino hospitalizado: so prevencion especifica (1994–2000). [Pneumococcal surveillance in hospitalized children: specific prevention (1994–2000).] Revista Médica del Uruguay, 2002, 18(1):66–75.

Spn

Uruguay

Nascimento-Carvalho CM, Moreno-Carvalho OA. Etiology of bacterial meningitis among children aged 2–59 months in Salvador, Northeast Brazil, before and after routine use of Haemophilus influenzae type B vaccine. Arquivos de Neuro-Psiquiatria, 2004, 62(2A):250–252.

Hib

VenezuelaAmnesty de Valbuena A, Sansone D, Torres G. Neumonía por Haemophilus influenzae tipo B en niños: estudio de 5 años. Investigación Clínica, 1988, 29(2):79–92.

Hib


Table 4: Studies from the WHO Eastern Mediterranean Region (EMR) with evaluable outcome data


in article

Egypt

Watt J, Gayed AS. Introduction of routine vaccination against Haemophilus influenzea Type b: a cost-benefit analysis. Unpublished report, World Health Organization Rapid Assessment Tool, 1999.

Hib

Iran (Islamic Republic of)

Nelson CB, Mohsni E. Iran - estimation of disease burden due to Hib. Unpublished report, World Health Organization Rapid Assessment Tool, 2000.

Hib

KuwaitDaoud AS, Zaki M, al-Saleh QA. Prolonged and secondary fever in childhood bacterial meningitis. European Journal of Pediatrics, 1989, 149(2):114–116.

Hib

Kuwait Zaki M et al. Childhood bacterial meningitis in Kuwait. The Journal of Tropical Medicine and Hygiene, 1990, 93(1):7–11. Hib

MoroccoAbid A et al. Pneumococcal meningitis in children. La Semaine des hôpitaux de Paris, 1999, 75(35–36):1308–1315.

Spn

Morocco

Moustaoui N et al. Serotypes, biotypes and antimicrobial susceptibilities of Haemophilus influenzae isolated from invasive disease in children in Casablanca. Clinical Microbiology and Infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2000, 6(1):48–49.

Spn

PakistanAl Awaidy S. Estimation of Hib Disease Burden in Pakistan. Unpublished report, World Health Organization Rapid Assessment Tool, 2003.

Hib

QatarNovelli VM et al. Haemophilus influenzae type b disease in an Arab Gulf state. The Pediatric Infectious Disease Journal, 1989, 8(12):886–887.

Hib

Saudi Arabia Abanamy A et al. Childhood bacterial meningitis in Riyadh. Annals of Saudi Medicine, 1991, 11(6):628–632. Hib

Saudi Arabia Abomelha A et al. Childhood bacterial meningitis. Annals of Saudi Medicine, 1988, 8(4):274–278. Hib Spn

Saudi Arabia

Al-Aqeeli AA, Guy ML, Al-Jumaah SA. Streptococcus pneumoniae resistance to penicillin and ceftriaxone in a tertiary care center in Saudi Arabia. Saudi Medical Journal, 2002, 23(4):400–404.

Spn

Saudi ArabiaAl-Mazrou YY et al. Haemophilus type B meningitis in Saudi children under 5 years old. Journal of Tropical Pediatrics, 2004, 50(3):131–136.

Hib Spn

Saudi Arabia Almuneef M et al. Childhood bacterial meningitis in Saudi Arabia. The Journal of Infection, 1998, 36(2):157–160. Hib

161WHO/IVB/09.02


in article

Saudi Arabia

Almuneef M et al. Bacterial meningitis in Saudi Arabia: the impact of Haemophilus influenzae type b vaccination. Journal of Chemotherapy (Florence, Italy), 2001, 13(Suppl. 1):S34–S39.

Spn

Saudi Arabia Azubuike JC. Childhood bacterial meningitis in Tabuk, Saudi Arabia. Annals of Saudi Medicine, 1990, 10(2):145–148. Hib Spn

Saudi ArabiaKambal AM, Abdullah AM. Childhood pneumococcal bacteraemia in Riyadh, Saudi Arabia. Annals of Tropical Paediatrics, 1997, 17(3):245–251.

Spn

TunisiaSoltani MS et al. [Epidemiology of Haemophilus influenzae meningitis in Tunisia]. Eastern Mediterranean Health Journal, 2005, 11(1–2):14–27.

Hib

Table 5: Studies from the WHO European Region (EUR) with evaluable outcome data


in article

AustriaRauter L, Mutz I. [Haemophilus influenzae meningitis 1983 to 1992 — epidemiology and sequelae of the disease]. Wiener Klinische Wochenschrift, 1994, 106(7):187–192.

Hib Spn

Austria

Rendi-Wagner P et al. Prospective surveillance of incidence, serotypes and antimicrobial susceptibility of invasive Streptococcus pneumoniae among hospitalized children in Austria. The Journal of Antimicrobial Chemotherapy, 2004, 53(5):826–831.

Spn

AustriaVutuc C, Kunze M. [Haemophilus influenzae meningitis in Austria: 1990–1992 incidence]. Wiener Klinische Wochenschrift, 1995, 107(8):256–257.

Hib

BelgiumDucoffre G et al. [Trends in pneumococcal infections in Belgium from 1986 to 1991]. Acta Clinica Belgica, 1993, 48(3):148–155.

Spn

Belgiumvan Hoeck KJ et al. A retrospective epidemiological study of bacterial meningitis in an urban area in Belgium. European Journal of Pediatrics, 1997, 156(4):288–291.

Hib Spn

Bosnia and Herzegovina

Al Awaidy S, Afsar O, Tulisov A. Estimation of Hib disease burden in Bosnia and Herzegovina. 2004. Hib

Bulgaria

Kojouharova M et al. Epidemiology of meningitis due to Haemophilus influenzae type b in children in Bulgaria: a prospective, population-based surveillance study. Bulletin of the World Health Organization, 2002, 80(9):690–695.

Hib Spn



in article

Czech Republic

Kriz P, Lebedova V, Benes C. Large decrease in incidence of invasive Haemophilus influenzae b disease following introduction of routine vaccination in the Czech Republic. Euro Surveillance: European communicable disease bulletin, 2005, 10(7):E050728 4.

Hib

Czech Republic

Lebedova V, Krizova P. The 2001 serological survey in the Czech Republic — Hib invasive disease Haemophilus influenzae b. Central European Journal of Public Health, 2003, (Suppl. 11):S25–S30.

Hib

Denmark Christensen AC, Frederiksen W. [Etiology of bacterial meningitis]. Ugeskrift for Laeger, 1988, 150(11):655–657. Hib

Denmark

Kaltoft MS, Zeuthen N, Konradsen HB. Epidemiology of invasive pneumococcal infections in children aged 0–6 years in Denmark: a 19-year nationwide surveillance study. Acta Paediatrica. Supplementum, 2000, 89(435):3–10.

Spn

Denmark

Konradsen HB, Kaltoft MS. Invasive pneumococcal infections in Denmark from 1995 to 1999: epidemiology, serotypes, and resistance. Clinical and Diagnostic Laboratory Immunology, 2002, 9(2):358–365.

Spn

Denmark

Kristensen K et al. Epidemiology of Haemophilus influenzae type b infections among children in Denmark in 1985 and 1986. Acta Paediatrica Scandinavica, 1990, 79(6–7):587–592.

Hib

Denmark

Nielsen SV, Henrichsen J. Incidence of invasive pneumococcal disease and distribution of capsular types of pneumococci in Denmark, 1989–94. Epidemiology and Infection, 1996, 117(3):411–416.

Spn

FinlandBaer M, Vuento R, Vesikari T. Increase in bacteraemic pneumococcal infections in children. Lancet, 1995, 345(8950):661.

Spn

FinlandEskola J et al. Epidemiology of invasive pneumococcal infections in children in Finland. JAMA: the journal of the American Medical Association, 1992, 268(23):3323–27.

Spn

Finland

Peltola H, Kilpi T, Anttila M. Rapid disappearance of Haemophilus influenzae type b meningitis after routine childhood immunization with conjugate vaccines. Lancet, 1992, 340(8819):592–594.

Hib

Finland

Saarinen M et al. Spectrum of 2836 cases of invasive bacterial or fungal infections in children: results of prospective nationwide five-year surveillance in Finland. Finnish Pediatric Invasive Infection Study Group. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 1995, 21(5):1134–1144.

Hib Spn

FinlandTakala AK et al. Risk factors of invasive Haemophilus influenzae type b disease among children in Finland. The Journal of Pediatrics, 1989, 115(5 Pt. 1):694–701.

Hib

163WHO/IVB/09.02


in article

FranceGaillat J. [Epidemiology of systemic Streptococcus pneumoniae infections]. La Presse Médicale, 1998, 27(Suppl. 1):S9–S16.

Spn

France

Laurichesse H et al. Clinical characteristics and outcome of patients with invasive pneumococcal disease, Puy-de-Dome, France, 1994–1998. European Journal of Clinical Microbiology & Infectious Diseases: official publication of the European Society of Clinical Microbiology, 2001, 20(5):299–308.

Spn

FranceLivartowski A et al. [Epidemiology of Haemophilus influenzae type b meningitis in two French departments]. Archives Françaises de Pédiatrie, 1989, 46(3):175–179.

Hib

France Reinert P et al. Epidemiology of Haemophilus influenzae type b disease in France. Vaccine, 1993, 11 (Suppl. 1):S38–S42. Hib

Germany

von Kries R et al. Proportion of invasive pneumococcal infections in German children preventable by pneumococcal conjugate vaccines. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 2000, 31(2):482–487.

Spn

Germany

von Kries R et al. Prediction of the potential benefit of different pneumococcal conjugate vaccines on invasive pneumococcal disease in German children. The Pediatric Infectious Disease Journal, 2002, 21(11):1017–1023.

Spn

GreeceSyriopoulou V et al. Epidemiology of invasive childhood pneumococcal infections in Greece. Acta Paediatrica. Supplementum, 2000, 89(435):30–34.

Spn

Greece

Tsolia MN et al. Epidemiology of invasive Haemophilus influenzae type b infections among children in Greece before the introduction of immunization. Scandinavian Journal of Infectious Diseases, 1998, 30(2):165–168.

Hib

Israel

Dagan R. A two-year prospective, nationwide study to determine the epidemiology and impact of invasive childhood Haemophilus influenzae type b infection in Israel. The Israeli Pediatric Bacteremia and Meningitis Group. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 1992, 15(4):720–725.

Hib

Israel

Dagan R et al. Epidemiology of pediatric meningitis caused by Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis in Israel: a 3-year nationwide prospective study. Israeli Pediatric Bacteremia and Meningitis Group. The Journal of Infectious Diseases, 1994, 169(4):912–916.

Hib Spn



in article

Israel

Dagan R et al. Effectiveness of a nationwide infant immunization program against Haemophilus influenzae b. The Israeli Pediatric Bacteremia and Meningitis Group. Vaccine, 1999, 17(2):134–141.

Hib Spn

Israel

Fraser D et al. A decade (1989–1998) of pediatric invasive pneumococcal disease in two populations residing in one geographic location: implications for vaccine choice. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 2001, 33(4):421–427.

Spn

Israel

Halfon-Yaniv I, Dagan R. Epidemiology of invasive Haemophilus influenzae type b infections in Bedouins and Jews in southern Israel. The Pediatric Infectious Disease Journal, 1990, 9(5):321–326.

Hib

Israel

Rosenthal J et al. Differences in the epidemiology of childhood community-acquired bacterial meningitis between two ethnic populations cohabiting in one geographic area. The Pediatric Infectious Disease Journal, 1988, 7(9):630–633.

Hib

Italy

Cellesi C et al. Retrospective survey on the epidemiology of H. influenzae type B meningitis in Italy (1987–91). The New Microbiologica: official journal of the Italian Society for Medical, Odontoiatric, and Clinical Microbiology (SIMMOC), 1995, 18(2):183–186.

Hib

Italy

Chironna M et al. [Haemophilus influenzae type b meningitis in Apulia. Retrospective study from the years 1994–1995]. Annali di Igiene: Medicina Preventiva e di Comunità, 1998, 10(3):131–136.

Hib Spn

Italy

Ciofi degli Atti ML et al. Haemophilus influenzae invasive disease in Italy, 1997–1998. European Journal of Clinical Microbiology & Infectious Diseases: official publication of the European Society of Clinical Microbiology, 2001, 20(6):436–437.

Hib

Italy

D’Alessandro D, Biasio LR, Fara GM. [Incidence of Haemophilus influenzae type b meningitis in Italy. Preliminary results]. Annali di Igiene: Medicina Preventiva e di Comunità, 1995, 7(5):319–327.

Hib

ItalyD’Ancona F et al. Incidence of vaccine preventable pneumococcal invasive infections and blood culture practices in Italy. Vaccine, 2005, 23(19):2494–2500.

Spn

Italy

Pizzuti R et al. [Haemophilus influenzae type b meningitis in the city and district of Naples: a retrospective study on hospitalizations in the period 1987–1995]. Annali di Igiene: Medicina Preventiva e di Comunità, 1998, 10(3):137–146.

Hib Spn

ItalySquarcione S, Pompa MG, D’Alessandro D. National Surveillance System and Hib meningitis incidence in Italy. European Journal of Epidemiology, 1999, 15(7):685–686.

Hib

165WHO/IVB/09.02


in article

Italy

Ticca F et al. [Haemophilus influenzae type b in meningitis: antibiotic resistance in pediatric patients]. Le Infezioni in Medicina: rivista periodica di Eziologia, Epidemiologia, Diagnostica, Clinica e Terapia delle Patologie Infettive, 1997, 5(2):96–99.

Hib

Luxembourg

De Jonghe M, Glaesener G. [Type B Haemophilus influenzae infections. Experience at the Pediatric Hospital of Luxembourg]. Bulletin de la Société des Sciences Médicales du Grand-Duché de Luxembourg, 1995, 132(2):17–20.

Hib

Netherlands

Spanjaard L et al. Epidemiology of meningitis and bacteraemia due to Streptococcus pneumoniae in The Netherlands. Acta Paediatrica. Supplementum, 2000, 89(435):22–26.

Spn

Norway

Jenssen KT et al. [Invasive pneumococcal infections in children from Troms, Nordland and Sor-Trondelag 1980–95]. Tidsskrift for den Norske Laegeforening, 2000, 120(3):308–311.

Spn

Poland

Skoczynska A et al. Characteristics of the major etiologic agents of bacterial meningitis isolated in Poland in 1997–1998. Microbial drug resistance (Larchmont, N.Y.), 2000, 6(2):147–153.

Hib Spn

Poland

Zielinski A, Tomaszunas-Blaszczyk J, Kuklinska D. Epidemiology of childhood bacterial meningitis in Poland. Incidence of bacterial meningitis with special reference to Haemophilus influenzae type b among children 0–59 months old in the former Kielce and Bydgoszcz districts in Poland in 1998–1999. European Journal of Epidemiology, 2001, 17(8):779–782.

Hib

Romania

Corcaci C et al. Hemophilus influenzae meningitis— the experience of infectious diseases department between 1984–2001. Revista Medico-Chiruricala A Societatii de Medici si Naturalisti Din Iasi (Iasi), 2002, 107(2):348–351.

Hib

Romania

Luca V et al. Incidence and etiological agents of bacterial meningitis among children <5 years of age in two districts of Romania. European Journal of Clinical Microbiology & Infectious Diseases: official publication of the European Society of Clinical Microbiology, 2004, 23(7):523–528.

Hib Spn

Russian Federation

Demina AA et al. Etiology of purulent bacterial meningitis. Zhurnal Mikrobiologii, Epidemiologii, i Immunobiologii, 1983:3–6.

Hib Spn

Russian Federation

Demina AA et al. Surveillance of meningococcal infections and other forms of purulent meningitis: a 4-year study in the USSR. Bulletin of the World Health Organization, 1986, 64(2):263–269.

Hib Spn



in article

Russian Federation

Deviatkina NP et al. [The characteristics of suppurative meningitis morbidity caused by Streptococcus pneumoniae and Haemophilus influenza type B]. Zhurnal Mikrobiologii, Eepidemiologii, i Immunobiologii, 1990(1):45–49.

Hib Spn

Russian Federation

Kostiukova NN et al. [The etiological structure of acute bacterial meningitis in different regions]. Zhurnal Mikrobiologii, Epidemiologii, i Immunobiologii, 1992(7–8):14–17.

Hib Spn

Slovakia

Novakova E, Gessner BD, Olear V. Incidence of Haemophilus influenzae type b meningitis among children less than 5 years of age in Slovakia. European Journal of Clinical Microbiology & Infectious Diseases: official publication of the European Society of Clinical Microbiology, 1999, 18(6):409–413.

Hib

SloveniaParagi M et al. Possibility of application of new pneumococcal conjugate vaccines in children in Slovenia. Vaccine, 2003, 21(32):4708–4714.

Hib Spn

Spain

Bernaola Iturbe E et al. [Study of the incidence of invasive pneumococcal disease in neonates and children aged less than 5 years in the Basque country and Navarre (Spain)]. Anales Españoles de Pediatría, 2002, 57(4):301–309.

Spn

SpainCasado Flores J et al. [Multicenter prospective study on severe bacterial meningitis in children]. Anales Españoles de Pediatría, 1997, 47(5):466–472.

Spn

SpainCasado Flores J et al. Prevalence of pneumococcal meningitis in Spain. Anales Españoles de Pediatría, 2002, 56(1):5–9.

Spn

SpainDiez-Domingo J et al. Epidemiology of invasive Streptococcus pneumoniae infections in children in Spain, 1996–1998. The Journal of Infection, 2002, 45(3):139–143.

Spn

SpainDominguez A et al. The epidemiology of invasive Streptococcus pneumoniae disease in Catalonia (Spain). A hospital-based study. Vaccine, 2002, 20(23–24):2989–2994.

Spn

SpainEspin MI et al. [Invasive pneumococcal disease in children in the region of Murcia (Spain)]. Gaceta Sanitaria / S.E.S.P.A.S., 2002, 16(5):385–391.

Spn

167WHO/IVB/09.02


in article

SpainGoicoechea-Saez M et al. [Invasive pneumococcal disease in children in the Community of Valencia, Spain]. Gaceta Sanitaria / S.E.S.P.A.S., 2003, 17(6):458–465.

Spn

Spain

Gonzalez A et al. [Incidence of invasive pneumococcal disease in Cantabria, Spain, [1995–2001] and implications for the childhood inmunization schedule]. Gaceta Sanitaria / S.E.S.P.A.S., 2003, 17(6):453–457.

Spn

Spain

Iglesias Sanchez L et al. [Epidemiology of invasive pneumococcal disease in children in Gipuzkoa (Spain) from 1981 to 2001]. Anales Españoles de Pediatría, 2002, 57(5):401–407.

Spn

SpainJuan Martin F, Campos Calleja C. Invasive Haemophilus influenzae type B infections in children (1981–1990). Anales Españoles de Pediatría, 1993, 39(2):111–115.

Hib

Spain

Latorre C, Sierra M, Lite J. [Prospective study of the invasive strains of Streptococcus pneumoniae isolated in 16 hospitals in Cataluna, Spain]. Enfermedades Infecciosas y Microbiología Clínica, 1999, 17(6):286–291.

Spn

SpainMartinez Leon M et al. [Bacterial meningitis. Clinical-epidemiological study. Review of 8 years (1988–1995)]. Anales Españoles de Pediatría, 1998, 48(3):277–282.

Hib Spn

SpainPerez MC et al. Predictive factors for invasive pneumococcal disease: A case-control study. Anales Españoles de Pediatría, 2002, 57(4):310–316.

Spn

SpainPineda Solas V et al. [Bacteremic pneumococcal pneumonia]. Anales Españoles de Pediatría, 2002, 57(5):408–413.

Spn

SpainPineda V et al. Epidemiology of invasive Streptococcus pneumoniae infections in children in an area of Barcelona, Spain. Acta Paediatrica, 2002, 91(11):1251–1256.

Spn

SpainPocheville Gurutzeta I et al. [Invasive disease caused by Streptococcus pneumoniae: a 7-year study]. Anales Españoles de Pediatría, 1997, 47(2):151–155.

Spn

SpainSoult Rubio JA et al. Haemophilus influenzae type B meningitis. A retrospective study. Anales Españoles de Pediatría, 1994, 40(6):443–448.

Hib



in article

SpainSoult Rubio JA et al. Pneumococcal sepsis and meningitis, 2001–2003: Incidence, clinical features and identification of serotypes. Acta Pediátrica Española, 2005, 63(1):8–13.

Spn

SpainVilla-Alcazar M et al. Haemophilus influenzae meningitis: a disease on the increase that may be prevented. Revista Española de Pediatría, 1994, 50(300):529–535.

Hib

Spain

Villo Sirerol N et al. [Streptococcus pneumoniae and Haemophilus influenzae serotype B invasive disease. A 12-year retrospective study]. Anales de Pediatría (Barcelona, Spain: 2003), 2004, 61(2):150–155.

Hib Spn

Sweden

Berg S et al. Incidence and prognosis of meningitis due to Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis in Sweden. Scandinavian Journal of Infectious Diseases, 1996, 28(3):247–252.

Hib Spn

Sweden

Dahl MS et al. Invasive pneumococcal infections in Southwestern Sweden: a second follow-up period of 15 years. Scandinavian Journal of Infectious Diseases, 2001, 33(9):667–672.

Spn

Sweden

Ekdahl K, Martensson A, Kamme C. Bacteraemic pneumococcal infections in Southern Sweden 1981–96: trends in incidence, mortality, age-distribution, serogroups and penicillin-resistance. Scandinavian Journal of Infectious Diseases, 1998, 30(3):257–262.

Spn

SwedenGarpenholt O et al. The impact of Haemophilus influenzae type b vaccination in Sweden. Scandinavian Journal of Infectious Diseases, 1996, 28(2):165–169.

Hib

Sweden

Hugosson S et al. Invasive Haemophilus influenzae disease: epidemiology and clinical spectrum before large-scale H. influenzae type b vaccination. Scandinavian Journal of Infectious Diseases, 1995, 27(1):63–67.

Hib

SwedenTrollfors B et al. Haemophilus influenzae meningitis in Sweden 1981–1983. Archives of Disease in Childhood, 1987, 62(12):1220–1223.

Hib

Switzerland

Muhlemann K et al. Invasive Haemophilus influenzae disease and epiglottitis among Swiss children from 1980 to 1993: evidence for herd immunity among older age groups. The Swiss Haemophilus influenzae Study Group. Scandinavian Journal of Infectious Diseases, 1996, 8(3):265–268.

Hib

169WHO/IVB/09.02


in article

Switzerland

Venetz I, Schopfer K, Muhlemann K. Paediatric, invasive pneumococcal disease in Switzerland, 1985–1994. Swiss Pneumococcal Study Group. International Journal of Epidemiology, 1998, 27(6):1101–1104.

Spn

UkrainePlatanov A, Cowgill K, Linehan M. Haemophilus influenzae type b (Hib) disease burden in Ukraine: WHO Hib Rapid Assessment Tool, Unpublished report, 2003.

Hib

United Kingdom

A survey of invasive Haemophilus influenzae infections — England and Wales. Canada Communicable Disease Report, 1992, 18(6):42–47.

Hib

United Kingdom

Anderson EC et al. Epidemiology of invasive Haemophilus influenzae infections in England and Wales in the pre-vaccination era (1990–2). Epidemiology and Infection, 1995, 115(1):89–100.

Hib

United Kingdom

Booy R et al. Invasive Haemophilus influenzae type b disease in the Oxford region (1985–91). Archives of Disease in Childhood, 1993, 69(2):225–228.

Hib

United Kingdom

Coggins A, Shepherd CW, Cockburn F. Epidemiology of Haemophilus type b invasive disease in childhood in Glasgow. Scottish Medical Journal, 1993, 38(1):18–20.

Hib

United Kingdom

de Louvois J et al. Infantile meningitis in England and Wales: a two year study. Archives of Disease in Childhood, 1991, 66(5):603–607.

Hib Spn

United Kingdom

Fallon RJ, Reid D. Haemophilus influenzae type b invasive disease. BMJ (Clinical research ed.), 1991, 303(6811):1203–1204.

Hib

United Kingdom

Fortnum HM, Davis AC. Epidemiology of bacterial meningitis. Archives of Disease in Childhood, 1993, 68(6):763–767. Hib Spn

United Kingdom

Grant CC et al. Invasive pneumococcal disease in Oxford, 1985–2001: a retrospective case series. Archives of Disease in Childhood, 2003, 88(8):712–714.

Spn

United Kingdom

Howard AJ et al. Epidemiology of Haemophilus influenzae type b invasive disease in Wales. BMJ (Clinical research ed.), 1991, 303(6800):441–445.

Hib

United Kingdom

Jones IR et al. Social deprivation and bacterial meningitis in north east Thames region: three year study using small area statistics. BMJ (Clinical research ed.), 1997, 314(7083):794–795.

Spn

United Kingdom

Kyaw MH et al. The changing epidemiology of bacterial meningitis and invasive non-meningitic bacterial disease in Scotland during the period 1983–99. Scandinavian Journal of Infectious Diseases, (2002a), 34(4):289–298.

Hib Spn

United Kingdom

Kyaw MH et al. Incidence of invasive pneumococcal disease in Scotland, 1988–99. Epidemiology and Infection, (2002b), 128(2):139–147.

Spn



in article

United Kingdom

Kyaw MH et al. Invasive pneumococcal disease in Scotland, 1999–2001: use of record linkage to explore associations between patients and disease in relation to future vaccination policy. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 2003, 37(10):1283–1291.

Spn

United Kingdom

Laurichesse H et al. Pneumococcal bacteraemia and meningitis in England and Wales, 1993 to 1995. Communicable Disease and Public Health / PHLS, 1998, 1(1):22–27.

Spn

United Kingdom

McIntosh ED. How many episodes of hospital care might be prevented by widespread uptake of pneumococcal conjugate vaccine? Archives of Disease in Childhood, 2003, 88(10):859–861.

Spn

United Kingdom

Miller E et al. Epidemiology of invasive and other pneumococcal disease in children in England and Wales 1996–1998. Acta Paediatrica. Supplementum, 2000, 89(435):11–16.

Spn

United Kingdom

Olowokure B et al. Decrease in effectiveness of routine surveillance of Haemophilus influenzae disease after introduction of conjugate vaccine: comparison of routine reporting with active surveillance system. BMJ (Clinical research ed.), 2000, 321(7263):731–732.

Hib

United Kingdom

Quigley C et al. Haemophilus influenzae type b disease in North-West England. The Journal of Infection, 1993, 26(2):215–220.

Hib

United Kingdom

Ramsay ME et al. Estimating Haemophilus influenzae type b vaccine effectiveness in England and Wales by use of the screening method. The Journal of Infectious Diseases, 2003, 188(4):481–485.

Hib

United Kingdom

Shackley F et al. Outcome of invasive pneumococcal disease: a UK based study. Oxford Pneumococcal Surveillance Group. Archives of Disease in Childhood, 2000, 83(3):231–233.

Spn

United Kingdom

Slack MP et al. Enhanced surveillance of invasive Haemophilus influenzae disease in England, 1990 to 1996: impact of conjugate vaccines. The Pediatric Infectious Disease Journal, 1998, 17(Suppl. 9):S204–S207.

Hib

United Kingdom

Sleeman K et al. Invasive pneumococcal disease in England and Wales: vaccination implications. The Journal of Infectious Diseases, 2001, 183(2):239–246.

Spn

United Kingdom

Tudor-Williams G et al. Haemophilus influenzae type b disease in the Oxford region. Archives of Disease in Childhood, 1989, 64(4):517–519.

Hib

United Kingdom

Urwin G et al. Pneumococcal meningitis in the North East Thames Region UK: epidemiology and molecular analysis of isolates. Epidemiology and Infection, 1996, 117(1):95–102.

Hib Spn

171WHO/IVB/09.02

Table 6: Studies from the WHO South-East Asia Region (SEAR) with evaluable outcome data


in article

Bangladesh Saha S, personal communication. PneumoADIP sponsored ICDDRB surveillance sites in Bangladesh, 2007. Hib Spn

BangladeshSaha SK et al. The increasing burden of disease in Bangladeshi children due to Haemophilus influenzae type b meningitis. Annals of Tropical Paediatrics, 1997, 17(1):5–8.

Hib Spn

BangladeshSaha SK et al. Invasive Haemophilus influenzae type B diseases in Bangladesh, with increased resistance to antibiotics. The Journal of Pediatrics, 2005, 146(2):227–233.

Hib

India

Are Haemophilus influenzae infections a significant problem in India? A prospective study and review. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 2002, 34(7):949–957.

Hib

India

Prospective multicentre hospital surveillance of Streptococcus pneumoniae disease in India. Invasive Bacterial Infection Surveillance (IBIS) Group, International Clinical Epidemiology Network (INCLEN). Lancet, 1999, 353(9160):1216–1221.

Spn

IndiaSingh R et al. Occurrence of multiple antimicrobial resistance among Haemophilus influenzae type b causing meningitis. The Indian Journal of Medical Research, 1992, 95:230–233.

Hib

India Steinhoff M, (personal communication), 2007. Spn

Indonesia

Gessner BD et al. Incidences of vaccine-preventable Haemophilus influenzae type b pneumonia and meningitis in Indonesian children: hamlet-randomized vaccine-probe trial. Lancet , 2005, 365(9453):43–52.

Hib

NepalRussell F et al. The Burden of Haemophilus influenzae Type B (Hib), in Nepal. Unpublished report, World Health Organization Rapid Assesment Tool, 2003.

Hib

Sri LankaBurden of Haemophilus influenzae b (Hib) disease study — Sri Lanka. Geneva, WHO report SE / ICP / IVD / 506 / XF / 02 / U, 2002.

Hib

Thailand

Chotpitayasunondh T. Bacterial meningitis in children: etiology and clinical features, an 11-year review of 618 cases. The Southeast Asian Journal of Tropical Medicine and Public Health, 1994, 25(1):107–115.

Hib Spn

ThailandLikitnukul S. Systemic Haemophilus influenzae disease in Thai children. The Southeast Asian Journal of Tropical Medicine and Public Health, 1994, 25(4):672–627.

Hib

ThailandRerks-Ngarm S et al. Prospective population-based incidence of Haemophilus influenzae type b meningitis in Thailand. Vaccine, 2004, 22(8):975–983.

Hib


Table 7: Studies from the WHO Western Pacific Region (WPR) with evaluable outcome data


in article

Australia

Andresen DN, Collignon PJ. Invasive pneumococcal disease in the Australian Capital Territory and Queanbeyan region: do high infant rates reflect more disease or better detection? Journal of Paediatrics and Child Health, 2004, 40(4):184–188.

Spn

Australia

Bower C et al. Sequelae of Haemophilus influenzae type b meningitis in aboriginal and non-aboriginal children under 5 years of age. Journal of Paediatrics and Child Health, 2004, 1994, 30(5):393–397.

Hib

Australia

Bower C et al. Measuring the impact of conjugate vaccines on invasive Haemophilus influenzae type b infection in Western Australia. Australian and New Zealand Journal of Public Health, 1998, 22(1):67–72.

Hib

AustraliaChristie DJ et al. Childhood invasive pneumococcal disease in Tasmania, 1994–2000. Journal of Paediatrics and Child Health, 2002, 38(5):445–449.

Spn

AustraliaDavis CW, McIntyre PB. Invasive pneumococcal infection in children, 1981–92: a hospital-based study. Journal of Paediatrics and Child Health, 1995, 31(4):317–322.

Spn

AustraliaFagan RL et al. The epidemiology of invasive pneumococcal disease in children in Far North Queensland. Journal of Paediatrics and Child Health, 2001, 37(6):571–575.

Spn

Australia

Gilbert GL, Clements DA, Broughton SJ. Haemophilus influenzae type b infections in Victoria, Australia, 1985 to 1987. The Pediatric Infectious Disease Journal, 1990, 9(4):252–257.

Hib

Australia

Gilbert GL, Johnson PD, Clements DA. Clinical manifestations and outcome of Haemophilus influenzae type b disease. Journal of Paediatrics and Child Health, 1995, 31(2):99–104.

Hib

AustraliaGilmour R. EpiReview: invasive pneumococcal disease, NSW, 2002. New South Wales Public Health Bulletin, 2005, 16(1–2):26–30.

Spn

AustraliaGratten M et al. Seroepidemiology of invasive pneumococcal disease in Queensland, 1990 to 1997. Communicable Diseases Intelligence, 1998, 22(12):265–269.

Spn

AustraliaHanna JN, Wild BE. Bacterial meningitis in children under five years of age in Western Australia. The Medical Journal of Australia, 1991, 155(3):160–164.

Hib Spn

AustraliaHogg GG, Strachan JE, Lester RA. Invasive pneumococcal disease in the population of Victoria. The Medical Journal of Australia, 2000, 173(Suppl.):S32–S35.

Spn

173WHO/IVB/09.02


in article

AustraliaKrause VL, Reid SJ, Merianos A. Invasive pneumococcal disease in the Northern Territory of Australia, 1994–1998. The Medical Journal of Australia, 2000, 173(Suppl.):S27–S31.

Spn

AustraliaLiu M et al. Invasive pneumococcal disease among children in Victoria. Communicable Diseases Intelligence, 2003, 27(3):362–366.

Spn

AustraliaMcGregor AR et al. Invasive Haemophilus influenzae infection in the Australian Capital Territory region. The Medical Journal of Australia, 1992, 156(8):569–572.

Hib

Australia

McIntyre P, Gilmour R, Watson M. Differences in the epidemiology of invasive pneumococcal disease, metropolitan NSW, 1997–2001. New South Wales Public Health Bulletin, 2003, 14(4–5):85–89.

Spn

AustraliaMcIntyre P et al. The outcome of childhood Haemophilus influenzae meningitis. A population based study. The Medical Journal of Australia, 1993, 159(11–12):766–772.

Hib

Australia

McIntyre PB, Leeder SR, Irwig LM. Invasive Haemophilus influenzae type b disease in Sydney children 1985–1987: a population-based study. The Medical Journal of Australia, 1991, 154(12):832–837.

Hib

Australia McIntyre PB et al. Blood cultures in hospitalized children. The Medical Journal of Australia, 1987, 147(10):485–489. Hib Spn

AustraliaMcIntyre PB et al. Epidemiology of invasive pneumococcal disease in urban New South Wales, 1997–1999. The Medical Journal of Australia, 2000, 173(Suppl.):S22–S26.

Spn

AustraliaRoche P et al. Invasive pneumococcal disease in Australia, 2002. Communicable Diseases Intelligence, 2003, 27(4):466–477.

Spn

AustraliaRoche P et al. Invasive pneumococcal disease in Australia, 2003. Communicable Diseases Intelligence, 2004, 28(4):441–454.

Spn

Australiael Saadi O, Cameron AS. Epidemiology of Haemophilus influenzae type b (Hib) meningitis in South Australia. The Medical Journal of Australia, 1993, 159(7):494–495.

Hib

Australia

The Vaccine Impact Surveillance Network — Invasive Pneumococcal Study Group. Are current recommendations for pneumococcal vaccination appropriate for Western Australia? The Medical Journal of Australia, 2000, 173 (Suppl.):S36–S40.

Spn



in article

Australia

Trotman J, Hughes B, Mollison L. Invasive pneumococcal disease in central Australia. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 1995, 20(6):1553–1556.

Spn

ChinaShen SJ. [Serotypes and epidemiological study of pneumococcal infection in 18 provinces (cities) in China]. Zhonghua Liu Xing Bing Xue Za Zhi, 1989, 10(3):133–137.

Spn

ChinaYang Y et al. Acute bacterial meningitis in children in Hefei, China 1990–1992. Chinese Medical Journal, 1996, 109(5):385–388.

Hib Spn

ChinaYu CH, Chiu NC, Huang FY. Invasive pneumococcal infection in children. The Southeast Asian Journal of Tropical Medicine and Public Health, 2001, 32(1):126–131.

Spn

China, Hong Kong SAR

Lau YL et al. Invasive Haemophilus influenzae type b infections in children hospitalized in Hong Kong, 1986–1990. Hong Kong Hib Study Group. Acta Paediatrica, 1995, 84(2):173–176.

Hib

China, Hong Kong SAR

Sung RY et al. Meningitis in Hong Kong children, with special reference to the infrequency of haemophilus and meningococcal infection. Journal of Paediatrics and Child Health, 1997, 33(4):296–299.

Spn

Taiwan*, China

Chen MK et al. Prospective surveillance of children with invasive Haemophilus influenzae disease in Taiwan. Journal of Microbiology, Immunology, and Infection, 1999, 32(4):257–260.

Hib

Taiwan*, China

Siu LK et al. Epidemiology of invasive pneumococcal infection in Taiwan: antibiotic resistance, serogroup distribution, and ribotypes analyses. Microbial drug resistance (Larchmont, N.Y.), 2002, 8(3):201–208.

Spn

FijiWilson N et al. Estimating the Haemophilus influenzae type b (Hib) disease burden and the impact of Hib vaccine in Fiji. Vaccine, 2003, 21(17–18):1907–1912.

Hib Spn

JapanIshikawa T et al. Epidemiology of bacterial meningitis in children: Aichi Prefecture, Japan, 1984–1993. Pediatric Neurology, 1996, 14(3):244–250.

Hib Spn

Japan

Ishiwada N, Cao LD, Kohno Y. PCR-based capsular serotype determination of Haemophilus influenzae strains recovered from Japanese paediatric patients with invasive infection. Clinical Microbiology and Infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2004, 10(10):895–898.

Hib

JapanKamiya H et al. Childhood bacterial meningitis in Japan. The Pediatric Infectious Disease Journal, 1998, 17(Suppl. 9):S183–S185.

Hib

175WHO/IVB/09.02


in article

Japan

Kuriki M et al. [Acute encephalitis and bacterial meningitis in children in Aichi Prefecture (1984–1993)]. Nippon Koshu Eisei Zasshi = Japanese Journal of Public Health, 1995, 42(5):338–345.

Hib

Japan

Nakano T et al. Incidence of Haemophilus influenzae type b meningitis in Mie Prefecture, Japan. Pediatrics International: official journal of the Japan Pediatric Society, 2001, 43(3):323–324.

Hib

Japan

Sakata H, Maruyama S. [A study of bacterial meningitis in Hokkaido between 1994 and 1998]. Kansenshogaku Zasshi. The Journal of the Japanese Association for Infectious Diseases, 2000, 74(4):339–44.

Hib

Japan

Sato A et al. [Clinical study of 33 children with systemic pneumococcal infections]. Kansenshogaku Zasshi. The Journal of the Japanese Association for Infectious Diseases, 2001, 75(12):1007–1013.

Spn

Malaysia

Nik Khairulddin NY, Choo KE, Johari MR. Epidemiology of Haemophilus influenzae invasive disease in hospitalised Kelantanese children, 1985–1994. Singapore Medical Journal, 1999, 40(2):96–100.

Hib

MongoliaWatt J. Burden of Haemophilus influenzae b (Hib) disease study — Mongolia. Geneva, WHO report WP / ICP / EPI / 5.2 / 001 / XZ / 04, 2004.

Hib Spn

New CaledoniaAnglaret X et al. Invasive Haemophilus influenzae disease of Melanesian and Caucasian children in New Caledonia. The Pediatric Infectious Disease Journal, 1993, 12(10):888–889.

Hib

New ZealandVoss L, Lennon D, Gillies M. Haemophilus influenzae type b disease in Auckland children 1981–87. The New Zealand Medical Journal, 1989, 102(865):149–151.

Hib

New ZealandVoss L et al. Invasive pneumococcal disease in a pediatric population, Auckland, New Zealand. The Pediatric Infectious Disease Journal, 1994, 13(10):873–878.

Spn

New ZealandWilson N et al. The beneficial impact of Hib vaccine on disease rates in New Zealand children. The New Zealand Medical Journal, 2002, 115(1159):U122.

Hib

Papua New Guinea

Gratten M et al. The aetiology of purulent meningitis in highland children: a bacteriological study. Papua and New Guinea Medical Journal, 1985, 28(4):233–240.

Spn

Papua New Guinea

Lehmann D et al. Aetiology and clinical signs of bacterial meningitis in children admitted to Goroka Base Hospital, Papua New Guinea, 1989–1992. Annals of Tropical Paediatrics, 1999, 19(1):21–32.

Hib Spn



in article

Philippines

Limcangco MR, Salole EG, Armour CL. Epidemiology of Haemophilus influenzae type b meningitis in Manila, Philippines, 1994 to 1996. The Pediatric Infectious Disease Journal, 2000, 19(1):7–11.

Hib

Republic of Korea

Kim JS et al. Incidence of Haemophilus influenzae type b and other invasive diseases in South Korean children. Vaccine, 2004, 22(29–30):3952–3962.

Hib Spn

Republic of Korea

Kim KH et al. The causative organisms of bacterial meningitis in Korean children, 1986–1995. Journal of Korean Medical Science, 1998, 13(1):60–64.

Hib Spn

Republic of Korea

Lee HJ. Epidemiology of systemic Haemophilus influenzae disease in Korean children. The Pediatric Infectious Disease Journal, 1998, 17(Suppl. 9):S185–S189.

Hib Spn

Samoa

Carapetis J. Estimating the burden of Haemophilus influenzae type b, congenital rubella syndrome and mumps in Samoa. Unpublished report, World Health Organization Rapid Assessment Tool, 2002.

Hib

SingaporeLee YS et al. Invasive Haemophilus influenzae type b infections in Singapore children: a hospital-based study. Journal of Paediatrics and Child Health, 2000, 36(2):125–127.

Hib

Viet Nam

Anh DD et al. Haemophilus influenzae type B meningitis among children in Hanoi, Viet Nam: epidemiologic patterns and estimates of H. Influenzae type B disease burden. The American Journal of Tropical Medicine and Hygiene, 2006, 74(3):509–515.

Hib

Viet NamTran TT et al. The etiology of bacterial pneumonia and meningitis in Vietnam. The Pediatric Infectious Disease Journal, 1998, 17(Suppl. 9):S192–S194.

Spn

Viet Nam

Tran TT et al. [Role of Haemophilus influenzae b and pneumococcus in bacterial meningitis in Viet Nam (1995–1997)]. Archives de pédiatrie : organe officiel de la Sociéte Française de Pédiatrie, 2004, 11(4):373–374.

Hib

* Publication of this contribution is not intended to signify any attribution to “Taiwan” other than as a Province of China and to “Hong Kong” other than as a Special Administrative Region of China. Therefore, references to “Taiwan” and to “Hong Kong” in this publication, including in the bibliography, should be interpreted respectively as “China (Province of Taiwan)” and “Hong Kong, Special Administrative Region”.

177WHO/IVB/09.02

The World Health Organization has provided technical support to its Member States in the field of vaccine-preventable diseases since 1975. The office carrying out this function at WHO headquarters is the Department of Immunization, Vaccines and Biologicals (IVB).

IVB’s mission is the achievement of a world in which all people at risk are protected against vaccine-preventable diseases. The Department covers a range of activities including research and development, standard-setting, vaccine regulation and quality, vaccine supply and immunization financing, and immunization system strengthening.

These activities are carried out by three technical units: the Initiative for Vaccine Research; the Quality, Safety and Standards team; and the Expanded Programme on Immunization.

The Initiative for Vaccine Research guides, facilitates and provides a vision for worldwide vaccine and immunization technology research and development efforts. It focuses on current and emerging diseases of global public health importance, including pandemic influenza. Its main activities cover: i ) research and development of key candidate vaccines; ii ) implementation research to promote evidence-based decision-making on the early introduction of new vaccines; and iii ) promotion of the development, evaluation and future availability of HIV, tuberculosis and malaria vaccines.

The Quality, Safety and Standards team focuses on supporting the use of vaccines, other biological products and immunization-related equipment that meet current inter-national norms and standards of quality and safety. Activities cover: i ) setting norms and standards and establishing reference preparation materials; ii ) ensuring the use of quality vaccines and immunization equipment through prequalification activities and strengthening national regulatory authorities; and iii ) monitoring, assessing and responding to immunization safety issues of global concern.

The Expanded Programme on Immunization focuses on maximizing access to high quality immunization services, accelerating disease control and linking to other health interventions that can be delivered during immunization contacts. Activities cover: i ) immunization systems strengthening, including expansion of immunization services beyond the infant age group; ii ) accelerated control of measles and maternal and neonatal tetanus; iii ) introduction of new and underutilized vaccines; iv ) vaccine supply and immunization financing; and v ) disease surveillance and immunization coverage monitoring for tracking global progress.

The Director’s Office directs the work of these units through oversight of immunization programme policy, planning, coordination and management. It also mobilizes resources and carries out communication, advocacy and media-related work.

Family and Community Health

World Health Organization

20, Avenue Appia

CH-1211 Geneva 27

Switzerland

E-mail: [email protected]

Web site: http://www.who.int/immunization/en/

Department of Immunization, Vaccines and Biologicals

global literature review of haemophilus influenzae type b and

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