Strategic orientation paperon prevention and control

of malaria

For national and international programme officersinvolved in malaria control at country level

FIRST EDITION

ROLL BACK MALARIA DEPARTMENTOPERATIONS SUPPORT AND CAPACITY DEVELOPMENT

Strategic orientation paperon prevention and control

of malaria

For national and international programme officersinvolved in malaria control at country level

ROLL BACK MALARIA DEPARTMENTOPERATIONS SUPPORT AND CAPACITY DEVELOPMENT

WHO/HTM/MAL/2005.1105

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iiiContents

Acronyms and abbreviations ..................................................................................... ivForeword ...................................................................................................................... vProvisional schedule .................................................................................................. viAcknowledgements .................................................................................................. vii

IntroductionIntroductionIntroductionIntroductionIntroduction ............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................ 1

UNIT 1UNIT 1UNIT 1UNIT 1UNIT 1. Preventive intervention strategies .............................................................. 31.1 Approaches for scaling up insecticide-treated nets .......................................... 31.2 Other vector control options ............................................................................... 51.3 Malaria during pregnancy ................................................................................... 8

UNIT 2UNIT 2UNIT 2UNIT 2UNIT 2. Access to prompt and effective treatment ............................................... 152.1 Malaria diagnosis .............................................................................................. 152.2 Drug resistance and process for drug policy changes .................................... 182.3 Scaling up effective treatment (home management of malaria) ................... 19

UNIT 3UNIT 3UNIT 3UNIT 3UNIT 3. Prevention and control of malaria epidemics in complex emergencies ... 233.1 Estimating the population at risk for malaria epidemics ................................ 233.2 Long-range forecasting, early warning and early detection systems ............. 233.3 Case management and the effective use of drugs in epidemics ................... 243.4 Vector control in epidemics .............................................................................. 253.5 Monitoring and improving preparedness plans .............................................. 26

UNIT 4UNIT 4UNIT 4UNIT 4UNIT 4. Monitoring and evaluation ........................................................................ 274.1 Monitoring and evaluation of health programmes .......................................... 274.2 Key malaria targets/goals and regional differences ....................................... 284.3 Measurement topics (mortality, morbidity, coverage) ..................................... 304.4 Measurement tools ........................................................................................... 314.5 Routine health information systems and other systems ................................ 32

Annex 1: Annex 1: Annex 1: Annex 1: Annex 1: The Millennium Development Goals ..................................................... 34

AnneAnneAnneAnneAnnex 2: x 2: x 2: x 2: x 2: 10 things you need to know about DDT use ......................................... 36

Annex 3:Annex 3:Annex 3:Annex 3:Annex 3: WHO position on prevention and control of HIV/malaria co-infection ... 38

Annex 4: Annex 4: Annex 4: Annex 4: Annex 4: A note on stratification ........................................................................... 40

Annex 5: Annex 5: Annex 5: Annex 5: Annex 5: Combinations of antimalarial drugs and their applications ................ 45

Annex 6:Annex 6:Annex 6:Annex 6:Annex 6: Exercises and answers ............................................................................ 51

iv Acronyms and abbreviations

ACT artemisinin-based combination therapyAIDS acquired immunodeficiency syndromeAIS AIDS indicator surveyANC antenatal care or antenatal clinicDDT Dichloro-diphenyl-trichloroethaneDFID Department for International Development (United Kingdom)DHS demographic and health surveysDSS demographic surveillance systemDTP3 third dose of diphtheria–tetanus–pertussis vaccineEDS early detection systemEPI expanded programmes on immunizationGDP gross domestic productHIS health information systemHIV human immunodeficiency virusHMM home management of malariaIPT intermittent preventive treatmentIRS indoor residual sprayingITN insecticide-treated netIVM integrated vector managementLBW low birth weightLLIN long-lasting insecticide-treated netLRF long-range forecastingMCO Malaria Operations Support and Capacity Development teamMDG Millennium Development GoalMERG Monitoring and Evaluation Reference GroupMEWS malaria early warning systemMFT mass fever treatmentMICS multiple indicator cluster surveysMOH ministry of healthNAMMIS national antimalarial management information system (India)NGO nongovernmental organizationNPO national programme officerMICS multiple indicator cluster surveysPOP persistent organic pollutantRBM Roll Back MalariaRDT rapid diagnostic testSP sulfadoxine–pyrimethamineSTPf stable [malaria] transmission Plasmodium falciparumUNICEF United Nations Children’s FundUnSTPv unstable [malaria] transmission Plasmodium vivaxUSAID United States Agency for International DevelopmentWHO World Health OrganizationWHOPES WHO Pesticide Evaluation Scheme

vForeword

This strategic orientation document is aimed at informing key national and internationalprogramme officers (NPOs, IPOs) and other senior health officers working on malariapolicy and implementation issues.

It summarizes current World Health Organization (WHO) strategies and policies onmalaria control categorized under four main areas:

1. Preventive intervention strategies2. Access to prompt and effective treatment3. Prevention and control of malaria epidemics4. Monitoring and evaluation

This document will be updated regularly and is open to constructive comments andsuggestions. It is not all-inclusive, but it aims to provide quick and comprehensiveinformation on current WHO-recommended strategies and directions regarding malaria.It also suggests references or resource documents, institutions and networks. Thedocument also offers an opportunity for NPOs or other health officers operating atcountry level to position themselves with strong technical and strategic issues and tooperate with ministries of health or other partners with consistent and up-to-dateinformation. Depending on the background of the users of this document, and thepurpose of the orientation or training, the duration needed may vary from one day toone week. A provisional schedule for one day is given on the next page.

vi Provisional schedule (1 day)

Time Title Remark

08:30–10:30 Targets of Roll Back Malaria To focus on achieving targets(Millennium Development Goals,global, regional)

10:30–11:00 BREAK

11:00– 12:0 Preventive strategies: scaling upinsecticide-treated nets

12:00–13:00 LUNCH

13:00–13:30 Preventive strategies: Country and programme• other vector control options experiences• intermittent preventive treatment

13:30–14:00 Case management: Processes, challenges and• change of antimalarial treatment experiencespolicies• artemisinin-based combination therapies• scaling up treatments at health facilityand community levels

14:00–14:30 Prevention and control of malaria Setting up and following upepidemics: the systems• early warning systems• early detection systems• preparedness and response

14:30–15:00 Monitoring and evaluation of malaria Setting up and following upcontrol: the systems• measuring indicators for malaria• data management systems

15:30–16:00 BREAK

16:00–17:00 Group exercise Mapping problems andsolutions, and taking all theabove intervention strategiesinto account

17:00–17:30 Panel discussion Role playing

viiAcknowledgements

The development of this document has been coordinated by the Malaria OperationsSupport and Capacity Development (MCO) team, with inputs from other teams of theRoll Back Malaria (RBM) Department. The contents of this module have been compiledby Dr Maru Aregawi, with invaluable contributions from Dr A. Bosman, Dr K. Cham, Dr C.Delacollette, De K. Mendis, Dr A. Shapira, Dr P. Olumese, Dr A. Rietveld, Dr W. Were, DrJ. Williams, and Dr S. Fall from AFRO.

The document has been field-tested in various NPO induction workshops and willcontinue to be updated to incorporate new developments, inputs and usefulsuggestions from the field. We would greatly appreciate feedback from all readersaddressed to: aregawim@who.int.

1INTRODUCTION

OBJECTIVES

To orient participants on the global and regional Roll Back Malaria (RBM)goals, objectives and targets.

To equip and direct participants with up-to-date intervention strategies andtools for malaria control under different epidemiological settings.

Goals and strategies of Roll Back Malaria

The RBM Initiative aims to reduce the global malaria burden through the use ofevidence-based interventions and to strengthen health systems. Current malaria controlstrategies are based on:• early diagnosis and effective treatment of malaria cases;• prevention through vector control measures and, in some particular situations,

chemotherapeutic measures;• prevention and control of epidemics.

In most areas of Africa where malaria transmission is rated from moderate to intense,control strategies are based on a combination of three core interventions:1. Access to prompt and effective treatment.2. Universal use of insecticide-treated nets (ITNs), with priority to young children and

pregnant women.3. Intermittent preventive treatment (IPT) with at least two full doses of an effective,

safe antimalarial drug in the second and third trimesters of pregnancy.

The Abuja Malaria Summit in 2000 aimed to strengthen national health systems,with the following goals and targets by the year 2005:• 60% of malaria patients have access to appropriate treatment within 24 hours of

onset of symptoms;• 60% of children and pregnant women are protected from malaria using ITNs;• 60% of pregnant women have access to appropriate malaria chemoprophylaxis/

intermittent preventive treatment.

The Millennium Development Goals (MDGs) were agreed in 2000 (Annex 1).The goals and targets specific to malaria are:

Goal 6. Combat HIV/AIDS, malaria and other diseasesTarget 7: Have halted by 2015 and begun to reverse the spread of HIV/AIDS.Target 8: Have halted by 2015 and begun to reverse the incidence of malaria andother major diseases.

2In spite if all these well defined goals and targets, most countries could not attain theRBM, Abuja targets and MDGs targets may within the expected time unless themagnitude and rate of antimalarial interventions are significantly enhanced, withcoverage reaching all vulnerable populations. Some countries may benefit fromintensification of interventions using existing systems and outlets to accelerate scale-up and ensure achievements in the intended period of time.

In Africa, south of the Sahara, both Expanded Programme on Immunization (EPI) andAntenatal Care (ANC) services routinely and continuously reach substantial proportionof their target populations (infants, young children and pregnant women; DPT3 61%,20031; 70% of pregnant women2). Both traditionally provide free services, and bothaim for high population coverage. In addition, EPI has long advocated a dual-trackapproach through supplementary immunization activities (SIAs), where applicable, torapidly achieve high population coverage while maintaining and strengthening routineimmunization activities to sustain that coverage.

For example, in Madagascar, using the expanded programme on immunization(46% dtp3 coverage) to distribute free or subsidized ITNs would maximizeITNs coverage within a few years.

Using the antenatal care (ANC) programme, the provision of IntermittentProphylactic Therapies (IPT) country could reach up to 63% of the pregnantwomen at risk of acquiring malaria during pregnancy within one year.

Using the measles campaign to distribute ITNs to children aged under 5years of age would ensure significant coverage among young children (whoconstitute 18% of the population).

1 Global and regional coverage estimates, 2003. www.who.int/vaccines-surveillance2 WHO/UNICEF. The Africa malaria report, 2003. Geneva. WHO/CDS/MAL/2003.1093

3PREVENTIVE INTERVENTION STRATEGIES

1.1 Approaches for scaling up insecticide-treated nets

The use of ITNs has shown substantial impact on malaria: regular use can reduce theoverall risk of death for young children by 20% and the number of clinical malariaepisodes in that age group by 50%. ITNs have therefore become an important tool inthe prevention of malaria in highly endemic areas. Large-scale ITN programmes arecurrently implemented in sub-Saharan Africa, Asia and Latin America using variousoperational approaches. One of the main technical approaches of RBM for the reductionof malaria mortality and morbidity is to promote increased ownership and use ofinsecticide-treated netting materials.

The five randomized controlled trials have provided strong evidence that the widescale use of insecticide treated mosquito nets (ITNs) can reduce all cause childhoodmortality by about a fifth in Africa. For every 1000 children protected, on averageabout 5.5 lives can be saved in children aged 1 to 59 months every year. In Africa, fullITN coverage could prevent 370 000 child deaths per year3. The cost-effectiveness ofITNs (US$ 19–85 per DALY)4 is similar to most childhood vaccines. When communitycoverage is high, ITNs not only protect those who sleep under them, but also those inthe same dwelling (the home effect) and those living nearby (the community effect)5.The impact of ITN use on clinical episodes of malaria is also considerable, halvingclinical attacks in areas of stable malaria transmission in Africa. In Asia and LatinAmerica (areas with low malaria transmission), the use of ITNs also significantly reducedthe number of clinical episodes due to both Plasmodium falciparum and P. vivax. Theconcept of “mass effect” will be stronger with one ITN per child than with one ITN percare taker.

CHALLENGES: Countries face two main challenges in scaling up use of ITNs.

A. Cost

Most malaria-endemic countries in Africa spend only US$ 4 per capita a year on health,about the average cost of an untreated net in countries where nets are widely available.It would require US$ 200 million a year to provide 50 million nets and a furtherUS$ 25 million a year to treat these nets with insecticide. Subsidies (cost-sharing) towell-defined vulnerable groups can take several forms:• both donor and user contribute to each ITN,• donors pay the whole cost of some ITNs and users pay the whole cost of others,• users pay for nets and donors pay for insecticides, or vice versa.

UNIT 1

3 Lengeler, C. Insecticide-treated bed nets and curtains for preventing malaria. Cochrane Database of SystematicReviews, 2004(3): CD000363.

4 Hanson, K et al. The Economics of malaria control interventions. Global Forum for Health Research, March 2004.5 Hawley, W. A et al. Community-wide effects of permethrin-treated bed nets on child mortality and malaria

morbidity in Western Kenya. Am. J. Trop. Med. Hyg., 68(Suppl 4) 2003, pp. 121–127

4A revolving fund has been used with limited success. This is a long-term approachaimed at selling nets and insecticides at prices that cover all the costs of an ITNintervention to replenish and maintain the initial fund.

The choice of approaches will depend on the national context and especially on thestatus of the commercial market and other factors related to institutional policy,epidemiology and population, nets and insecticide, as well as knowledge and behaviour.

B. Low re-treatment rates for nets

On average, each net must be re-treated with insecticide after three washings or at leastevery year. Insecticide for net treatment is still an unfamiliar commodity in Africa, andpeople’s motivation for using nets is aimed at mosquito nuisance, not at malariatransmission. Estimates of net use show a great deal of disparity across SSA, but typicallyreveal that 10 to 30% of the population uses untreated nets6,7; the percentage who useITNs is much lower. Since 2002, several countries started scaling-up free of charge orhighly subsidized provision of ITNs for children under 5 years of age and pregnantwomen8. As a result there has been a substantial increase in ITN coverage in several ofthese countries, according to household surveys conducted over time that measuredeither IT use by children under 5 years of age or household ownership of ITNs.9

The increasing availability of branded formulations in Africa should stimulate demand.The development of Long-lasting insecticidal Nets (LLINs) is another potential solutionto the problem of low re-treatment rates.

OVERCOMING THE CHALLENGES

Countries such as Ghana, Kenya, Mozambique and the United Republic of Tanzaniahave already developed national ITN strategies, of which the key steps are:

1. Achieving a national consensus on ITN strategy. Consensus between governmentaland nongovernmental organizations and private sector so that all activities carriedout by partners are compatible with the national ITN strategy. Roles for each partnershould be defined within the national strategy and the current or planned ITNprogrammes of the public sector.

2. Assessing the capacity of the commercial sector. This is often under-estimated:investigate net availability in the commercial market; facilitate and catalyse sourcingand distribution. Promotion should begin only when nets are available.

3. Creating an enabling environment for ITNs. The national situation will determineissues, among which the following are important:

• reducing taxes and tariffs to facilitate procurement, manufacture and distributionof nets and insecticide, and to support expansion of the commercial market;

6 Simon, J., B. Larson, S. Rosen, A. Zusman. 2001. Reducing Tariffs and Taxes on Insecticide-Treated Bednets:Background Paper for Africa Malaria Day, April 25, 2001. Geneva: Roll Back Malaria.

7 Wardlaw, T. Monitoring Malaria Goals: UNICEF MICS Surveys, 1999–2001. Presentation.8 World Malaria Report 2005. WHO/HTM/MAL/2005.1102. Table 6 p23.9 Ibid. Fig. 4, p 23

5• creating demand for nets and insecticide; the role of social marketing for ITN and

insecticides must be carefully evaluated so as to maximize its contribution to thecreation of demand for ITNs. Nongovernmental organizations (NGOs) have animportant role to play in that area;

• establishing partnerships: : : : : public-private partnerships between national malariacontrol programmes (or other public sector institutions) and the commercial sectorhelp support scale up for ITNs.

LONG-LASTING INSECTICIDAL NETS (LLINS)

WHO has prompted industry to develop LLINs. These are ready-to-use, factory-pretreatednets that require no further treatment during their expected lifespan of 4–5 years.LLINs resist washing; their use reduces both human exposure (most of the insecticideis hidden in the net and not bioavailable) and the risk of environmental contamination.LLINs are a major breakthrough in malaria prevention. Various technologies for LLINshave been under development since the early 1990s.10 They have been developed inresponse to low re-treatment rates of conventional ITNs. The WHO Pesticide EvaluationScheme (WHOPES) has approved two types of LLINs: Olyset® and PermaNet.2®. Ataround US$ 5 each, LLINs are more cost-effective than conventionally treated nets.Efforts are being made to scale up production capacity to meet demand, which isalready high. It is estimated that the global production capacity for LLINs will be in theorder of 50 million by the end of this year (20 million Olyset®, 30 million PermaNet®

2.0). The RBM Partnership is facilitating technology transfer and stimulating localproduction of LLINs in Africa. Integration of immunization, ITN distribution anddeworming has proven effective resulting in high coverage some sub-Saharan Africansettings and the strategy is going to scale in many other countries.

The recent efforts of the Togo National Integrated Child Health Campaign in 2004 (Fig.1.1) is a good example. Overall, percentage of eligible children receiving each interventionwas high both in urban and rural with no difference in economic quintiles: measlesvaccination (97.9%), polio vaccination (98.6%), mebendezole administration (97.1%),ITN (94.9%). Overall ITN coverage in Togo rose from 5–16% (MOH unpublished data,Terlouw report Sept 2004) to 67.2% with an increase in equity ratio from 0.32 to 0.96.

10 Report of the Fifth WHOPES Working Group Meeting. Geneva, World Health Organization, 2001.

0

20

40

60

80

100

Togo total Lomé Maritime Plateaux Centrale Kara Savanes

Figure 1.1 Household ownership of ITN in Togo before and after campaign, 2004

perc

enta

ge

before

after

6Table 1.1 WHO-recommended insecticides for indoor residual spraying against malaria vectors

Compounds and formulations Class Dosage Duration of effective(in g/m2) action (in months)

Alpha-cypermethrin WP and SC P 0.02–0.03 4–6Bendiocarb WP C 0.1–0.4 2–6Bifenthrin WP P 0.025–0.05 3–6Cyfluthrin WP P 0.02–0.05 3–6DDT WP OC 1–2 >6Deltamethrin WP, WG P 0.020–0.025 3–6Etofenprox WP P 0.1–0.3 3–6Fenintropen WP OP 2 3–6Lambda–cyhalothrin WP P 0.02–0.03 3–6Malathion WP OP 2 2–3Pirimiphos–methyl WP and EC OP 1–2 2–3Propoxur WP C 1–2 3–6

EC (emulsifiable concentrate); WG (water-dispersible granules); WP (wettable powder); SC (suspensionconcentrate); OC (organochlorine); OP (organophosphate); C (carbamate); P (pyrethroid)Source: Najera JA, Zaim M. (2002). Malaria vector control – Decision-making criteria and procedures for judicioususe of insecticides. Geneva, World Health Organization (WHO/CDS/WHOPES/2002.5; available at http://www.who.int/ctd/whopes/docs/JudiciousUseRev.pdf).

WHEN AND WHERE TO APPLY INDOOR RESIDUAL SPRAYING?

Vector behaviour and susceptibility: resting and feeding habits of the mosquito vector.Indoor residual application may have little impact if the vector tends to rest and biteoutdoors and does not enter houses. Understanding the behaviour of the vector andhuman population in relation to disease transmission is therefore essential beforedeciding on a programme of IRS in preference to other options.

Local vector resistance or increased tolerance to insecticide may affect overalleffectiveness. Pre-existing resistance to pyrethroids may lessen DDT effectivenessthrough cross-resistance. One method of slowing vector resistance is to widen thechoice of insecticides used for IRS and rotate the use of those currently effective againstmosquitoes (but this probably increases operational costs).

IRS may be carried out whenever disease vectors feed and rest indoors. It is mosteffective in areas of unstable transmission, in areas with marked seasonal transmission

1.2 Other vector control options

INDOOR RESIDUAL SPRAYING

Indoor residual spraying (IRS) may be defined as the application to indoor restingplaces of the vectors of a liquid insecticide with long-lasting remanence that dries toleave a crystalline deposit. Insects absorb a lethal dose when they come into contactwith the surface. IRS also has an agitating and excito-repellent effect on mosquitoes,with the added benefit of reducing the number of mosquitoes entering indoor spaces.WHO recommends 12 insecticides from four chemical classes for IRS (Table 1.1).

7peaks and disease outbreaks, and in highland areas. If carried out just before thetransmission period or seasonal peaks, it may disrupt vector population dynamics andshorten the transmission period or even suppress epidemic outbreaks entirely. IRSmust be based on reliable prediction of seasonal disease foci. A good understandingof the risks and benefits associated locally must support the decision to use IRS.

IRS is most effective when coverage in the community is high, and the level of publicacceptance therefore affects effectiveness. Some people may refuse outright to allowtheir house to be sprayed; others may clean or re-plaster sprayed walls in order to hidethe residues left by some insecticides, thus reducing effectiveness.

Interventions such as IRS should be applied as part of an integrated vector management(IVM) strategy,11 ensuring that options for control of local malaria vectors are based on asolid understanding of local conditions and are locally appropriate. For example, ITNsare as effective as IRS in reducing transmission in many settings as long as high coverageis ensured. Other IVM interventions include biological control (bacteria, fungi, nematodes,copepods, larvicidal fish) and environmental modifications to potential breeding places.Decisions should be made only after careful evaluation of effectiveness andprioritization.

WHO champions the continued use of DDT for disease vector control, under theStockholm Convention on persistent organic pollutants (POPs).12 WHO’s position issummed up by the recommendations of a WHO Malaria Expert Committee meeting in1998:13

… for some time … there will continue to be a role for DDT in combating malaria,particularly in the poorest endemic countries. Restrictions on DDT for public healthuse contained in a future Persistent Organic Pollutants Convention should … beaccompanied by technical and financial mechanisms to ensure that effectivemalaria control is maintained, to at least the same level, through vector controlmethods that depend less on pesticides generally, and on DDT in particular.

A premature shift to alternatives to DDT without preparation of Member State capacitymay negatively affect disease burden in endemic countries. The Stockholm conventionon POPs permits production and use of DDT strictly for disease vector control, underWHO recommendations and guidelines,14 and states, inter alia, that:

The production and use of DDT shall be eliminated except for Parties [to the Confe-rence] that have notified the Secretariat of their intention to produce and/or use it;Each Party that produces and/or uses DDT shall restrict such production and/oruse for disease vector control in accordance with the WHO recommendations andguidelines on the use of DDT and when locally safe, effective and affordablealternatives are not available to the Party in question;

11 IVM is the concurrent use of two or more vector control interventions (chemical and/or non-chemical) inorder to limit disease transmission. Options are selected on the basis of local ecology, epidemiology, populationparameters, available resources and probable efficacy of implementation.

12 The Stockholm Convention came into force in May 2004.13 Twentieth report of the WHO Expert Committee on Malaria. Geneva, World Health Organization, 2000 (WHO

Technical Report Series No. 892; point 12.2.28–3, p. 63).14 Frequently asked questions on DDT use for disease vector control. Geneva, World Health Organization,

2005 (WHO/RBM/2004.54/Rev1)

8Commencing at its first meeting, and at least every three years thereafter, theConference of the Parties shall, in consultation with the WHO, evaluate thecontinued need for DDT for disease vector control on the basis of available scientific,technical, environmental and economic information […].

The Convention recognizes three important points:

i. The need for many malaria-endemic countries to maintain their reliance on the useof DDT for IRS to control insect vectors, particularly malaria, until viable effectiveand affordable alternatives are found;

ii. A need to accelerate research and development of safe, effective and affordablealternatives to DDT and the use of such alternatives as a medium-term goal towardsimprovement of vector control in malaria-endemic countries;

iii. A longer-term goal of reducing over-reliance on pesticides in general, to protectboth the ecosystem and human health from negative impacts of POPs.

A basic principle of the Action Plan developed by WHO is that any deadline set in theStockholm Convention is not linked to the phasing-out of DDT, but to the time at whichmechanisms are available to ensure sustainable transition from DDT to alternatives.Such transition should not increase disease transmission risk, nor should it occur atthe expense of resources earmarked for other priority public health issues.

The Plan envisages a global mechanism for the provision of support in:• Country assessments – including national inventories of current use and regulatory

status;• Safe management of DDT stockpiles;• Disease vector control/management needs assessments;• Monitoring – including global reporting and monitoring system on DDT use and

exposure (facilitating strategies to control use and minimize exposure);• Research on locally viable integrated pest and vector management strategies, as

well as the development, testing and/or implementation of sustainable, sound andeffective alternatives to DDT;

• Strengthening country capacity to enable effective vector control;• Advocacy – information to the health sector for balanced decision-making.Provisions for the use of DDT under the Convention are provided in Annex 2.

1.3 Malaria during pregnancy

Each year, more than 25 million pregnant women in malaria-endemic areas (mainlyAfrica) are at risk of Plasmodium falciparum infection, with serious consequences formother and unborn child. Malaria prevention in pregnancy is a priority for RBM, whichrecommends a three-pronged approach:i. Effective case management of malaria infectionsii. Use of ITNsiii. IPT in areas of stable transmission

9The symptoms and complications of malaria in pregnancy vary according to transmissionintensity and the level of acquired immunity (Fig. 1.2). The reality is usually a continuum,with a range of transmission intensity, acquired immunity and clinical presentations.Most pregnant women in malaria-endemic regions of Africa live in areas of high ormoderate (stable) transmission, where the impact of malaria is particularly apparentin first and second pregnancies. Parasite prevalence and density are higher amongpregnant than non-pregnant women, although infection with P. falciparum is usuallyasymptomatic. Partial clinical immunity acquired before pregnancy does not preventinfection, but reduces the risk of severe disease. Clinical malaria is not, therefore, amarked feature of infection in pregnancy, and the main detrimental effects of infectionare low birth weight (LBW) and maternal anaemia. In areas of stable transmission,malaria during pregnancy may cause up to 10 000 maternal deaths each year, mainlyas a result of anaemia, and accounts for 8%–14% of LBWs, and 3%–8% of infant mortality.

Pregnant women living in areas of low or epidemic (unstable) transmission have littleor no immunity to malaria; they are at a 2- to 3-fold higher risk of developing severe diseaseas a result of malaria infection than are non-pregnant adults in the same area. In theseareas, maternal death may result directly from complications of severe malaria (especiallyhypoglycaemia, cerebral malaria and pulmonary oedema) or, indirectly, from severeanaemia. Malaria in pregnancy can also result in stillbirth, spontaneous abortion, LBWand neonatal death. Whatever the epidemiological situation for malaria, infection withthe human immuno-deficiency virus (HIV) impairs a pregnant woman’s ability to controlP. falciparum infection. Pregnant women with HIV infection are more likely to havesymptomatic malaria infections and have an increased risk of adverse birth outcomescaused by malaria. In the presence of HIV infection, placental malaria appears to beindependent of the number of pregnancies.

PREVENTION AND MANAGEMENT OF MALARIA DURING PREGNANCY

All women in malarious areas (regardless of endemicity) should receive iron/folatesupplementation as part of routine antenatal care (ANC).

In areas of stable transmission, , , , , the key components of the preventive package forpregnant women are ITNs and IPT. IPT involves the administration of a curative treatmentdose of an effective antimalarial drug at predefined intervals during pregnancy,beginning after quickening (the time at which foetal movements are first felt by themother) in the second trimester. It replaces the previous policy of weekly chloroquinechemoprophylaxis in pregnancy for those areas, which was limited by poor complianceand increasing resistance of P. falciparum to chloroquine.

P. falciparum parasites may be present in the placenta and contribute to maternalanaemia. Any pregnant woman with severe anaemia from an area of stable transmissionmust therefore be treated presumptively with antimalarials, whether or not peripheralparasitaemia is present and whether or not she has a history of fever. In a large trial inan area of intense malaria transmission in western Kenya, use of ITNs by pregnantwomen was associated with a 38% reduction in the incidence of malaria parasitaemia,a 47% reduction in malarial anaemia (Hb <8 g/dl plus parasitaemia) and a 28%reduction in the prevalence of LBW (ter Kuile et al., 2003).

10

Malaria during pregnancy in areas of high or moderate (stable) transmission

Altered placental integrity

Less nutrient transport

Placental sequestration

Low birth weight Higher infant mortality

Asymptomatic infection

Anaemia

Acquired immunity – high In absence of HIV infection, 1st and 2nd pregnancies at highest risk

IPT, ITNs, case management of malaria and anaemia

Maternal morbidity

Figure 1.2 Clinical consequences of malaria in pregnancy, areas of low or high transmission

Malaria during pregnancyin areas of low or epidemic transmission

Acquired immunity – low or none

Clinical illness

Severe disease

Risk to mother Risk to fetus

All pregnancies

Recognition and case management

Figure 1.3 IPT dosing schedule

11Sulfadoxine–pyrimethamine (SP) for IPT

All women should receive at least 2 doses of IPT after quickening (feeling the firstmovements of the baby). IPT may also be given at the fourth visit if the mother has notreceived the requisite number of doses. Studies in Kenya and Malawi have shown thatIPT with SP reduces the prevalence of maternal anaemia and placental parasitaemia,and the incidence of LBW. SP has a good safety profile in pregnancy, and single-doseregimens allow the health worker direct observation of the treatment. No evidence of anincrease in cutaneous side-effects or neonatal jaundice was found when SP was deliveredin the second and third trimester of pregnancy. SP remains an excellent option for IPT inareas of Africa where malaria transmission is stable and resistance to SP is low.

All women should receive at least 2 doses of IPT in the second and third trimesters ofpregnancy, ideally under direct observation at the time of routinely scheduled antenatalclinic visits. IPT ensures that the placenta is cleared of parasites at the time of rapidfetal growth (Fig. 1.3). Maximum benefit is derived from 2–3 doses of IPT, althougheven a single dose is beneficial. Pregnant women infected with HIV appear to benefitfrom monthly IPT. In settings with HIV prevalence greater than 12%, it is more cost-effective to treat all women with a 3-dose regimen than to screen for HIV and providethe 3-dose regimen only to HIV-positive women. Annex 3 summarizes WHO’s positionon prevention and control of HIV/AIDS and malaria co-infection.

In areas of low or epidemic (unstable) transmission, IPT is relatively ineffective formalaria control during pregnancy, which will be achieved primarily through promptand effective treatment of acute episodes. Malaria in a non-immune pregnant womancan rapidly progress to severe disease; any pregnant women with symptomatic malariamust receive urgent antimalarial treatment plus appropriate supportive treatment. Useof ITNs will also provide protection from symptomatic infection.

Resistance to SP is spreading rapidly throughout Africa, and there is an urgent need toevaluate the efficacy, effectiveness and safety of alternative antimalarials in pregnancy,both alone and in combination with artemisinin compounds. A WHO meeting to reviewthe pre-clinical (animal) and limited human data on the use of artemisinins inpregnancy15 concluded that these drugs have a good safety profile, particularly in thesecond and third trimesters of pregnancy and during lactation.

Programming partnerships for malaria control during pregnancy

Since ANC attendance is reasonably well established in Africa, RBM suggests relyingon ANC to accelerate programme implementation of malaria control during pregnancyin those areas with stable malaria transmission and high ANC attendance. In areaswith low ANC coverage, emphasis is placed on the development and strengthening ofcommunity-based programmes. Many women in Africa, particularly in remote areas,have limited access to standard medical care and effective malaria control tools. Deliveryof cost-effective malaria prevention to pregnant women will require strengthened ANC,integration of malaria control with other health programmes targeted at pregnant womenand infants, increased community awareness and considerable financial investment.

15 The use of artemisinin and its derivatives as antimalarial drugs. Report of a Joint CTD/DMP/TDR InformalConsultation, Geneva, 10–12 June 1998. Geneva, World Health Organization, 1998 (WHO/MAL/98.1086).

12Table 1.2 Intervention strategies for malaria during pregnancy, by intensity of transmission

Insecticide-treated nets(ITNs)

Begin use early inpregnancy and continuepostpartumEmphasize the use ofITNs also for youngchildren.

Begin use early inpregnancy and continuepostpartum.Emphasize the use ofITNs also for youngchildren.

Intermittent preventivetreatment (IPT)

Provide pregnant womenwith standard IPT3 dose atfirst regularly scheduledantenatal clinic visit afterquickening.On subsequent routinevisits,4 provide IPT dose,with a minimum of 2doses at intervals of noless than one month.6

Based on presentevidence, IPT cannot berecommended in theseareas.

Case management

Risk limited for febrile illness andsevere malaria.Screen and treat for anaemia withrecommended antimalarial drug andiron supplementationPromptly recognize all potential malariaillness and treat with an effective drug.

Risk for febrile illness and anaemiahigh.Risk for severe malaria illness high.In East Africa, consider P. vivaxinfection.5

Screen and treat for anaemia withrecommended antimalarial drug andiron supplementation.Promptly recognize all potential malariaillness and treat with an effective drug.

High/mediumtransmission

perennial(stable)1 orseasonal(stable)1

Lowtransmission(unstable)2

1 Adult women have a high level of acquired antimalarial immunity; first and second pregnancies are athigher risk of adverse consequences of malaria.

2 Adult women have no or very low level of acquired antimalarial immunity; first and second pregnancies areat higher risk of adverse consequences of malaria.

3 Currently, the most effective drug for IPT is sulfadoxine–pyrimethamine (SP).4 WHO recommends an ideal visit schedule of three antenatal clinic visits after quickening.5 Chloroquine chemoprophylaxis to decrease the burden of P. vivax infection in pregnancy may be

considered, but no evidence on efficacy/effectiveness of this strategy is presently available.6 In areas where HIV prevalence among pregnant women is ³ 12%, a third dose should be administered at

the last scheduled visit; if each pregnant woman had received only one dose at the time of the lastscheduled visit, a second dose should be administered at this time.

13RRRRRefefefefeferences and furerences and furerences and furerences and furerences and further readingther readingther readingther readingther reading

Parise EM et al. Efficacy of sulfadoxine-pyrimethamine for prevention of placentalmalaria in an area of Kenya with a high prevalence of malaria and human immuno-deficiency virus infection. American Journal of Tropical Medicine & Hygiene, 1998,59(5):813–822.

Shulman CE et al. Intermittent sulphadoxine-pyrimethamine to prevent severeanaemia secondary to malaria in pregnancy: a randomised placebo-controlled trial.Lancet, 1999, 353(9153):632–636.

ter Kuile F et al. Reduction of malaria during pregnancy by permethrin-treated netsin an area of intense perennial malaria transmission in western Kenya. AmericanJournal of Tropical Medicine & Hygiene, 2003, 68(Supplement 4):50–60.

United Nations Environment Programme (2001). Stockholm Convention on PersistentOrganic Pollutants (POPs). UNEP/Chemicals/2001/3. 50 p. (www.pops.int).

Verhoeff FH et al. An evaluation of the effects of intermittent sulfadoxine-pyrime-thamine treatment in pregnancy on parasite clearance and risk of low birthweight inrural Malawi. Annals of Tropical Medicine and Parasitology, 1998, 92(2):141–150.

For additional information, please contact:

Roll Back Malaria Department, World Health Organization, 20 Avenue Appia, 1211Geneva 27, Switzerland; inforbm@who.int

WHO Regional Office for Africa (AFRO), Parirenyatwa Hospital, P.O. Box BE 773, Harare,Zimbabwe; regafro@afro.who.int

WHO Regional Office for the Americas/Pan American Sanitary Bureau (PAHO), 52523rd Street N.W., Washington, DC, 20037, USA; http://www.paho.org/

WHO Regional Office for South-East Asia (SEARO), World Health House, IndraprasthaEstate Mahatma Gandhi Road, New Delhi 110002, India; PANDEYH@whosea.org

WHO Regional Office for the Eastern Mediterranean (EMRO), WHO Post Office

Abdul Razzak Al Sanhouri Street, Nasr City, Cairo 11371, Egypt; PIO@emro.who.int

WHO Regional Office for the Western Pacific (WPRO), P.O. Box 2932, 1000 Manila,

Philippines; Postmaster@who.org.ph

WHO Regional Office for Europe (EURO), 8, Scherfigsvej, DK–2100 Copenhagen,Denmark; postmaster@euro.who.int

15ACCESS TO PROMPT AND EFFECTIVE TREATMENT

2.1 Malaria diagnosis

The diagnosis of malaria relies on clinical examination and demonstration of parasitesin the blood. Malaria diagnosis should precede treatment with antimalarial medicines.

In highly endemic areas (particularly in Africa), the high prevalence of asymptomaticinfections and the lack of resources (e.g. microscopes and trained microscopists) haveled peripheral health facilities to use “presumptive” treatment. Patients who sufferfrom a fever that does not have an obvious cause are presumed to have malaria andtreated for that disease on clinical suspicion alone without laboratory confirmation.This practice, dictated by practical considerations, allows the treatment of a potentiallyfatal disease, but frequently leads to incorrect diagnoses and to the unnecessary useof antimalarial drugs, with additional expenses and increases in the risk of emergenceof drug-resistant parasites. Confirmation of malaria diagnosis requires evidence of thepresence of either:

• blood stage malaria parasites (microscopic examination of stained blood films);

• products of these parasites: rapid diagnostic tests (RDTs) based on the detection ofparasite antigens or enzymes.

In low malaria transmission areas (annual inoculation rates <1 to about 8), a confirmeddiagnosis of malaria prior to treatment is highly desirable. Since at all ages there islittle antimalarial immunity, malaria parasites in the blood almost always indicatemalarial disease. In such cases (mainly outside sub-Saharan Africa), a confirmatorydiagnosis of malaria must normally be sought prior to treatment with antimalarials.

In intense malaria transmission areas (annual inoculation rates >8), e.g. tropical Africawhere the disease and its fatal consequences are largely confined to the under 5s,there has been less dependence on parasitological confirmation, particularly in children.In this situation, malaria is the most frequent cause of fever in under 5s and aparasitological diagnostic tool may not be available in situations that warrant life-savingtreatment.

A parasitological diagnosis is thus indicated and should be made available for malariain situations of low to moderate endemicity and unstable malaria, and possibly also inthe management of adult malaria in high transmission areas in Africa. There is neithera strong case for, nor the feasibility of, making a preliminary parasitological diagnosismandatory for the treatment of childhood malaria in stable high-transmission regionsof Africa.

The practice of treating malaria on clinical grounds of fever rather than on aparasitological diagnosis was economically acceptable when antimalarial medicines

UNIT 2

16were cheap, and cost considerations were not an important part of the decision totreat. With current artemisinin-based combination therapies (ACTs) costing over 10times more than previous monotherapies, an improved diagnosis for better targetingof malaria treatment is called for. The risks associated with making a parasitologicaldiagnosis mandatory in these situations (such as delays in treatment and a consequenthigher child morbidity and mortality) must be weighed carefully against the benefits(e.g. cost savings on ACTs). Other considerations include the feasibility of introducingdiagnostic tools:

• RDTs cost US$ 0.6–1 per test.

• Community health workers and volunteers play an increasing a role in dispensingantimalarial medicines nearer home, and RDTs must be reliable enough for thesepeople to use them.

• The sensitivity of several RDTs currently available is affected by stability-relatedproblems, especially under field conditions.

The choice of a malaria diagnostic tool will depend on local circumstances. Quality-assured microscopy – an established, relatively simple technique familiar to mostlaboratory technicians in endemic countries – is the standard diagnostic tool for malariawhere microscopic services provide for diagnosis of other diseases beyond malaria. Itremains the “gold standard” for laboratory confirmation of malaria, but reliabilitydepends on the quality of reagents and of microscopes, and on technician experience.Rapid diagnostic tests for malaria provide an alternative to microscopy in remote ruralsettings and outside health institutions. With either method, quality assurance of thediagnostic tool is an essential requisite.

Malaria rapid diagnostic tests, sometimes called “dipsticks” or “malaria rapid diagnosticdevices (MRDDs)”, detect specific antigens (proteins) produced by malaria parasites,which are present in the blood of infected or recently infected individuals, thus providingevidence of the presence of malaria parasites in human blood. Some RDTs can detectonly one species (P. falciparum), some one or more of the other three species of malariaparasites infecting humans. Potential uses for RDTs include:

• diagnosis by health workers distant from good microscopy services;

• remote diagnosis in organized workforces entering malaria-endemic areas (e.g.military or mining companies);

• outbreak investigation and surveys of parasite prevalence;

• self-diagnosis by travellers or isolated groups in endemic areas.

Future developments may improve RDTs to the point where they can ensure confirmationof diagnosis in hospital laboratories or clinics.

Factors affecting the sensitivity of RDTs in detecting malaria include:

• species of parasite,

• number of parasites present,

17• condition of the RDT,

• technique used to perform the test (including correct interpretation by the reader).

Recommended sensitivity is 95% at 100 parasites/ml for P. falciparum. Sensitivitycan vary and some products achieve a sensitivity similar to that of microscopy. Thefollowing are important pre-requisites for incorporation of RDTs into malaria control:

• clear plan of action to deal with outcomes (drug treatment or further investigation);

• clear benefit in health outcomes;

• affordability of RDTs;

• adequate systems in place for correct use of RDTs;

• demonstrating parasitaemia provides a clear benefit;

• accuracy of RDTs regularly monitored (quality control);

• a cold chain for transport and storage;

• good health worker training and monitoring is in place;

• clear policy of action on results.

Management decisions should not be based on RDT results alone. With negative RDTresults, treatment may still be indicated on clinical evidence. A negative test resultdoes not exclude malaria with certainty because:

• there may be insufficient parasites to register a positive result;

• the RDT may have been damaged, with consequent reduction in sensitivity;

• illness may be caused by a species of parasite for which the RDT is not designed.

A positive result does not always signify malaria illness because:

• antigen may be detected after infecting parasites have died (after treatment) orbecause sexual forms of the parasite (which do not cause illness) persist;

• the presence of other factors in the blood may produce a false-positive result;

• the presence of parasites does not always signify malaria illness in individuals withhigh immunity, as there may be other causes for fever.

WHO’s recommendation in endemic areas with stable transmission is to apply RDT inall age groups above 5 years old. Febrile children aged under 5s need to havepresumptive treatment. In epidemic-prone areas (unstable transmission), all age groupscan be tested with RDT. For application of RDTs in different epidemiological settings,see Annex 6.

In summary, an RDT result should be used as a guide in management, but decision-making should be based on informed clinical assessment, including history and clinicalexamination. A plan of management may be developed beforehand with the guidanceof a health professional skilled in the management of malaria. The following consider-ations must be taken into account when choosing and purchasing RDTs:

18• Plasmodium species to be detected (P. falciparum only, or pan-specific);

• stability of RDT in intended conditions of storage and use (temperature);

• ease of use;

• requirements for post-treatment testing of patients;

• cost, sensitivity and accuracy.

2.2. Drug resistance and process for drug policy changes

Malaria control is challenged by parasite resistance of P. falciparum to monotherapiessuch as chloroquine, SP and amodiaquine, especially in Africa. Antimalarial treatmentpolicies in countries experiencing resistance to monotherapies emphasize combinationtherapies, preferably artemisinin-based. WHO currently recommends the followingtherapeutic options:

• artemether–lumenfantrine (Coartemâ);

• artesunate + amodiaquine;

• artesunate + sulfadoxine–pyrimethamine (where the latter remains effective);

• amodiaquine + sulfadoxine–pyrimethamine (where both remain effective).

Artesunate + mefloquine is a combination reserved for low-transmission areas. Manycountries have adopted combination drugs as first- or second-line antimalarial treatment;more than 20 have adopted ACTs. This process normally takes 1–3 years and requiresconcerted action among all stakeholders, with stewardship by the ministry of healthin two critical phases:

1. The decision to change policy in the face of failing efficacy of antimalarial drugs inuse, assessed according to WHO protocols at sentinel sites through country andintercountry networks supported by WHO and other RBM partners. Other factors includeconsumer and provider dissatisfaction and levels of malaria morbidity and mortality.Once evidence is available, the MOH, with WHO support, coordinates consensus-building among stakeholders through negotiations and meetings, a technical reviewmeeting leading to a policy recommendation. Challenges include:

• representativeness of evidence on efficacy of drugs in use, and of alternative treatmentoptions;

• delays in arriving at a consensus given diverging interests of various stakeholders;

• political will of the MOH for the adoption of a new treatment policy;

• financial resources for drug procurement and implementation.

2. Implementing a new treatment policy involves multisectoral resource mobilization,updating national treatment guidelines, training health workers, strengthening drugprocurement plans, supply systems and delivery strategies, communication to the public

19and monitoring and evaluation. All RBM partners participate in implementationaccording to expertise and comparative advantages. Challenges to implementationinclude:

• policies on pricing and affordability;

• health systems capacity (support, pharmacovigilance, access in outreach areas);

• effective procurement of new drugs and supply management.

Three factors facilitate the adoption of ACTs as new malaria treatment options:1. The adoption by WHO regional offices of lower thresholds for policy change.2. Clear WHO guidance on a limited number of combination therapies.3. The increased allocation of resources from the Global Fund to Fight AIDS, Tuberculosis

and Malaria (GFATM) to fund procurement of ACTs compared with chloroquine,amodiaquine and SP.

Policy change is increasingly used as an entry point for expanding access to effectivedrugs at all levels. Summary on practical aspects of antimalarial combination therapies,their pros, cons and the suggested epidemiological settings are indicated in Annex 5.

2.3 Scaling up effective treatment (home management ofmalaria)

Access to prompt and effective appropriate treatment is a key element of RBM basedon the recognition that untreated falciparum malaria can be fatal to non-immuneindividuals. Treatment must start within 24 hours of symptom onset to preventprogression to severe malaria or death. A strong health delivery system provides earlyreliable diagnosis and prompt, appropriate treatment. Programmes for managementof malaria seek to make treatment available as near home as possible, in the communityor in the home itself. This “home management of malaria” (HMM) entails educatingcommunity resource people (health workers, volunteers, mothers, drug vendors andshopkeepers) to recognize the symptoms suggestive of malaria and to deliverappropriate antimalarial treatment. HMM aims to improve the self-medication practicesof doubtful effectiveness that are common in endemic countries. The four strategiccomponents of HMM are:

1. Ensuring access to effective antimalarial drugs (preferably prepackaged) atcommunity level.

2. Ensuring that community providers have the necessary skills and knowledge tomanage malarial illness.

3. Ensuring a communication strategy to enable caregivers to recognize malaria illnessearly and take appropriate action.

4. Ensuring mechanisms for supervision and monitoring of community activities(including supply of antimalarial drugs).

20THE RATIONALE FOR HMM AND ITS IMPLEMENTATION

Because of impediments to access, communities have resorted to self-medication,mainly through unregulated private and informal sectors (pharmacies, shops, informaldrug vendors). Poor-quality antimalarials and inappropriate treatments havecontributed to the increasing development of drug resistance.

Mothers or caregivers are usually the first to recognize fever, the decision to seek careis usually made within the home and communities can be trained to recognize malariaand respond appropriately. Efforts are currently under way to scale up homemanagement of malaria in Africa on a nationwide basis (Benin, Ethiopia, Ghana,Madagascar, Uganda). The principles of HMM are embodied within the primary healthcare approach in west Africa. In the Indian subcontinent, experience with community-based health interventions is also being drawn upon for malaria.

National targets of malaria control aiming to appropriately treat malaria episodes within24 hours of symptom onset can only be achieved by ensuring that effective antimalarialdrugs are placed as near as possible to those who need them at home. Many countriesinclude community-based malaria treatment as part of their RBM plans and of theirproposals to the GFATM.

HMM implementation places demands on resources, planning and management. Itinvolves engaging communities, training cadres of community health workers, pre-packaging drugs and putting in place supervisory and monitoring systems, withintensive support from public health services, particularly peripheral health facilities.

The most valuable component of these programmes are the community health workersor their equivalents (volunteers, shopkeepers, mother coordinators), often on a voluntarybasis. In many Asian countries, the backbone of effective public health programmeshas been cadres of village-level workers on a government payroll. In Africa, experienceswith community health nurses in Ghana show the importance of investing in thecommunity level of health care. Governments may wish to consider how these peoplecan be remunerated to prevent loss of trained personnel in these programmes.

FORMULATIONS, PRESENTATION AND PACKAGING OF DRUGS

Currently, WHO recommends a combinations of drugs containing artemisinin derivativesrather than single drugs as first-line antimalarial treatment. Since most drugcombinations for malaria do not yet exist as co-formulated products, blister co-packagingand special paediatric formulations of antimalarial drugs have become a necessity toensure adherence to drug regimens. Information on product label and inserts shouldfocus on the needs of the consumer and may be presented as two separate inserts –one for the prescriber and one for the consumer.

Compliance with dosage and duration of treatment is essential for outcome and todelay the onset of parasite resistance, thus prolonging the usefulness of antimalarialdrugs. Compliance improves significantly when drugs are provided packaged in “units

21of therapy”. Prepackaging treatment courses stratified by age or weight groupingshave improved rational drug use. The minimum contents for prepackaging antimalarialmedicines as course of treatment include:• blister packs, also called primary packs;• mandatory regulatory information as package insert;• secondary pack, which contains the blister pack(s);• consumer information insert – prepared by personnel qualified in the field of

information, education and communication.

THE ROLE OF THE PRIVATE SECTOR

The private sector plays a significant role in delivering antimalarial treatment, and insome communities it may be the sole provider of medicines. It may offer the bestoption for treatment to communities who would otherwise have to travel long distancesto reach health facilities that may refer care givers back to the drug sellers for purchasingtreatment. It is imperative to train local drug vendors on the basics of diseaserecognition, prescription and referral practices.

The informal private sector usually comprises many unregulated and unregistereddrug sellers; investment in training may be costly and must be continued when newtraders enter the market. It is difficult to enforce control over drug quality and prices.The private sector antimalarial drug market is therefore often chaotic, and public sector’sstewardship role is critically important to ensure the quality of drugs sold and theservice delivered through the informal private sector.

IMPACT AND CHALLENGES OF HMM

Providing early and effective treatment reduces clinical progress to severe malaria bymore than 50% and overall childhood mortality by 40% (Fig. 2.1 and Fig. 2.2).

By removing the infected person from the reservoir of infection, early and effectivetreatment with ACTs also has an impact on malaria transmission – as shown in areasof unstable malaria, where incidence can decline dramatically after a treatment centreis established and people begin to be treated effectively and early. Since anaemiaassociated with malaria weakens the individual, prompt treatment reduces debilitationand the number of days off work or school, leading to increased productivity andreduced impact of malaria on economic growth.

Most countries are undergoing a transition in treatment policy and there has not beenenough time to gain experience. The need for new drugs to be taken in combinationoften entails recourse to multiple separate drugs. The public sector health systemmust take on a stewardship role in ensuring, together with NGOs and the private sector:·Maintenance of up-to-date malaria treatment policies – as such, the new ACTs presenta challenge owing to lack of experience in use at community level and in improvingmalaria diagnosis at community level.

22A strong and functional network of community resource persons, health-care facilitiesand institutions that can deliver treatment efficiently for severe malaria cases referredfrom the community.

The drive against malaria will be successful only if the resources of the global communityas a whole together with those of the endemic countries themselves are adequatelyengaged to achieving this end.

Figure 2.1 Proportion of children progressing to severe malaria, treated and not treated with pre-packs, Burkina Faso (after Sirima SB et al., 2003)

Figure 2.2 All-cause mortality in children under 5 years, by intervention or no intervention,Ethiopia (after Kidane and Morrow, 2000)

References and further reading

Kidane G, Morrow RH. Teaching mothers to provide home treatment of malaria in Tigray, Ethiopia:a randomized trial. Lancet, 2000, 356(9229):550–555.

Sirima SB et al. Early treatment of childhood fevers with pre-packaged antimalarial drugs in thehome reduces severe malaria morbidity in Burkina Faso. Tropical Medicine and InternationalHealth, 2003, 8(2):1–7.

perc

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0intervention no intervention

23PREVENTION AND CONTROL OF MALARIAEPIDEMICS IN COMPLEX EMERGENCIES

3.1 Estimating the population at risk for malaria epidemics

As part of realistic contingency planning, countries should:

• plot recent epidemics on hard-copy administrative boundary maps or throughgeographic information systems (GIS);

• develop indicators to stratify epidemic risk on the basis of local experience, includingenvironmental and epidemiological factors and local determinants of epidemic risk.

To assist countries, WHO and RBM partners should support GIS research on:

• risk maps of malaria epidemic-prone areas;

• methods for calculating populations at risk based on (sub)district population data;

• a standard protocol for estimating populations at risk of epidemics (HealthMapper).

3.2 Long-range forecasting, early warning and early detectionsystems

Using such systems, which provide information before an epidemic with increasingaccuracy and spatial resolution and with decreasing lead-time (as low as 1–2 weeks),countries should:

• validate freely available information, e.g. rainfall and temperature estimates, to mapand monitor changes in epidemic risk;

• obtain information from non-health sectors that bears on local epidemics risk (e.g.demographic and environmental information;

• train and encourage district health workers to monitor population vulnerability andenvironmental indicators of epidemic risk – a particularly important and difficult task.

WHO should facilitate collaboration between health programmes, meteorologicalservices and other early warning initiatives such as drought monitoring systems, famineearly warning systems and livestock disease systems, so as to identify relevant indicatorsand key informants, and ensure availability of routine information for forecasting andearly warning of malaria epidemics.

To detect, verify and notify malaria epidemics within two weeks of onset, countriesshould:

UNIT 3

24• train and encourage peripheral health workers to record and interpret disease data

on a weekly basis, especially during the epidemic season;

• select sentinel sites for gathering prospective data in early warning and detection;

• encourage weekly reporting and analysis as part of integrated surveillance activities;

• maintain input (epidemiological common sense) into data processing/interpretation;

• use parasitological confirmation (microscopy and/or RDTs) to check if malaria is theprimary cause of epidemics of fever;

• monitor/evaluate early detection systems for accuracy and effectiveness;

• strengthen district and national capacity to provide necessary technical support;

• regularly review the system to improve coordination by providing feedback onaccuracy and utility of long-range forecasting (LRF), malaria early warning systems(MEWS) and early detection systems (EDS), by improving definitions of indicatorsand their thresholds, and by making recommendations on response action.

To assist countries, WHO and RBM partners at country level should:

• develop a simple public health tool, translating LRF, MEWS and EDS results intoaction points, and evaluate experiences with such results;

• encourage and review experiences with epidemic thresholds and results.

3.3 Case management and the effective use of drugs inepidemics

Parasite diagnosis by microscopy or with RDTs is essential to diagnose malaria as thecause of an epidemic and to confirm the end thereof. Once malaria has been confirmedas the cause of an epidemic, treatment of symptoms is appropriate where laboratoryfacilities are not functioning. Light microscopy should be available at referral facilitiesto follow the progress of high-risk cases, and supported with quality assurance, suppliesand trained personnel. RDTs should not be relied on as the sole basis of treatmentand must be supported by quality assurance, including temperature stability testing.A list of products meeting the requirements of malaria control must be available.

The drugs used to treat (un)complicated epidemic malaria must be efficacious (~100%),safe and offer good compliance. To date, ACT is the only appropriate treatment foruncomplicated malaria in P. falciparum epidemics and in mixed P. falciparum/P. vivaxepidemics (except for Central America and Haiti and San Domingo where P. falciparumremains sensitive to chloroquine and SP). Chloroquine remains the drug of choice invivax-only epidemics. Anti-relapse therapy with primaquine should only be consideredonce the epidemic has subsided. Intramuscular injectable artemether is the drug ofchoice for severe disease in most epidemic situations because quinine use isimpracticable.

25When injectable artemether is unavailable, artesunate suppositories can be recommendedfor emergency use when severely ill patients cannot swallow. Where referral is notpossible, continued treatment with rectal artesunate is recommended until the intakeof oral drugs becomes possible. There is no evidence to support mass drug administration– the indiscriminate distribution of treatment to all the population at risk. Masstreatment of fever cases (MFT) with ACT is appropriate to reduce mortality once malariahas been established as the cause of the outbreak

Parasite diagnosis by light microscopy or RDTs must be supported by trained staff,quality assurance and the availability of supplies and equipment. All epidemic-pronecountries should register ACTs for the treatment of uncomplicated P. falciparum andintramuscular injectable artemether for severe malaria. At regional and national levels,country and manufacturers should establish stockpiles of drugs and of rapid diagnostictest kits to allow rapid deployment and procurement.

3.4 Vector control in epidemics16

Vector control measures in epidemics must be supported by personnel, supplies andequipment, preparedness planning, and supervision and evaluation. Countries thatdo not have this infrastructure should develop it as part of their preparedness plans ofaction, with:

• entomological input, including sensitivity of local vectors to insecticides;

• an understanding of local geography and community structures and habits;

• central stockpiles of insecticides and spraying equipment.

Communities and local authorities must cooperate to ensure vector control, includinghealth education through information channels such as newspapers, radio andtelevision. Vector control is most cost-effective when used for prevention at the beginningof an epidemic, if high (>85%) coverage can be obtained. It can also be used preventivelyfor long-term suppression of transmission:

• to combat a resurgence of malaria in a previously controlled area;

• to prevent build-up of transmission over years and/or surge in seasonal transmission;

• to protect communities where an epidemic is expected soon.

IRS is well adapted to epidemic prevention and response. DDT, where effective, fulfils thecriteria for use under resource constraints where residual action over 6 months is required,provided WHOPES specifications are met and safety precautions are taken. Syntheticpyrethroids provide an alternative to DDT with a residual action of 2–6 months, and aresafer to apply than most other insecticides; resistance to them is limited at present.

16 See also Unit 1, section 1.2.

26There is limited documented evidence on the impact of ITNs for epidemic preventionand control, since behavioural change is requested for ITNs to be effective. The use ofITNs for prevention and control of epidemics may be quicker than recourse to IRS:

• where ITNs and staff experienced in implementing ITNs are already in place;

• where a high level of coverage of untreated nets has already been achieved and theinfrastructure for timely treatment exists (e.g. refugee camps) and in circumstanceswhere IRS implementation would be costly and logistically difficult.

Larval control is generally unsuitable for epidemics but may serve for prevention wherebreeding sites are few, permanent, identifiable and accessible. There is no evidenceto support the use of space spraying (fogging) as a means of epidemic prevention/control.

In the case of malaria epidemics in concentrated populations at risk, caused by floodingand extensive rainfall, environmental management – particularly drainage and clearingof potential breeding sites – can be complementary to the other vector control options.Rapid assessment of the local situations and benefits should precede implementationof environmental management.

3.5 Monitoring and improving preparedness plans

Post-epidemic assessment is required to identify the success and/or failure of activitiescarried out to detect and control a malaria epidemic and to determine if detectingsystems and control options have had an impact on malaria burden. Countries should:

• assess the functioning of MEWS and EDS;

• assess the impact of the response on the disease burden;

• undertake a cost effectiveness/cost analysis of each component of the response;

• assess the functioning of the overall partnerships;

• assess logistics and budgetary matters.

27MONITORING AND EVALUATION

A system for monitoring and evaluating will be critical for the success of RBM and forreporting on progress related to the Abuja targets and the MDGs. For national malariacontrol programmes, monitoring and evaluation should help identify what works andwhat does not, encourage the former and correct the latter, and provide evidence tosecure additional funding for priority areas. In 2003, the RBM partnership establisheda monitoring and evaluation reference group (RBM-MERG) to promote consensus ona comprehensive monitoring and evaluation system on the core indicators of RBM,Abuja Summit, and the MDGs. This (www.rbm.who.int/merg) brings togetherconcerned United Nations agencies (including WHO, UNICEF and the World Bank), aswell as key bilateral donors, RBM regional networks and representatives of country-level malaria control programmes, as well as academic and research organizations.

4.1 Monitoring and evaluation of health programmes

At the global and regional level, the current focus of monitoring and evaluation activitiesrecommended by RBM lies in monitoring coverage of key interventions and of all-cause, under 5s mortality and malaria-related morbidity/mortality through householdsurveys. WHO, through its regional offices, is engaged in helping national malariacontrol programmes through annual monitoring of inputs, processes and outputs ofactivities.

While progress has occurred in country-level monitoring and evaluation, much of thedisease-related measurement in a country may be lost because there is no coherentsystem to capture information for users at different levels. Many countries rely onsurveys such as demographic and health surveys (DHS) or AIDS indicator surveys (AIS),and multiple indicator cluster surveys (MICS) funded through external donors to gatherinformation on the impact of their own and donor-supported programmes. This producesdata that may not be well integrated with national health information and surveillancesystems. A common, comprehensive and coherent monitoring and evaluation systemwill ensure, for example, that indicators and sampling methods are comparable overtime and reduce duplication of effort. Data generated by such a system must servethe needs of many constituents, including programme or project managers, researchersand donors, without unnecessary repetition.

In this document, monitoring is defined as the routine tracking of key elements ofprogramme/project performance through record-keeping, regular reporting andsurveillance systems as well as health facility observation and client surveys. Monitoringverifies step by step the progress of malaria control programmes at various levels inorder to check that activities have been implemented as planned, ensure accountability,detect problems and constraints related to intervention activities, and promote

UNIT 4

28evidence-based planning through timely feedback. Indicators of inputinputinputinputinput, processprocessprocessprocessprocess andoutputoutputoutputoutputoutput are typically used for monitoring purposes at the programme level:

• Input Input Input Input Input indicators measure the level of resources available for use by the programmeor intervention, e.g. funding obtained to purchase ITNs.

• Process Process Process Process Process indicators help check that a programme or intervention is implemented asplanned, e.g. verifying that ITNs have been purchased and are ready for distribution.

• The resulting output output output output output indicators generally measure benchmarks of programme-levelperformance, such as the number of ITNs distributed to a particular target population.

While monitoring is a continuous process, the extent to which results are attributableto particular malaria interventions or control programme strategies requires formalevaluation through outcome outcome outcome outcome outcome and impact impact impact impact impact indicators.

• Outcome Outcome Outcome Outcome Outcome indicators measure medium-term population-level results, e.g. level ofITN coverage for a target population, attributable to an ITN programme or intervention.

• Indicators of impact impact impact impact impact generally refer to overall long-term goals, e.g. the RBM goal ofhalving malaria-related morbidity and mortality by 2010.

4.2 Key malaria targets/goals and regional differences

The MDGsMDGsMDGsMDGsMDGs (see Annex 1) involve indicators for malaria mortality and a reversal in theincidence of malaria and other major diseases:

1. Malaria prevalence rates (all ages and under five years of age)

2. Malaria death rates (all ages and under five years of age)

3. Coverage of malaria interventions including ITNs

4. Coverage by prompt access to antimalarial treatment

5. Infant and under 5s all-cause mortality

RBM initiative: overall goal of halving malaria-associated mortality by 2010 and halvingthis again by 2015.

Abuja Summit in 2000: specific targets for coverage of interventions in the Africa region.Because of differences in availability of monitoring and measurement systems and inthe epidemiology of disease, measurement needs and types differ. For malaria, twobroad categories exist:

• Stable transmission with P. falciparum predominance (STPf): most sub-SaharanAfrican countries and some others, e.g. Papua New Guinea. Transmission intensitytends to be high, and systems and resources for monitoring are limited.

• Unstable transmission (unSTPv): transmission tends to be low or focal, P. vivax maycontribute to a marked proportion of malaria transmission, systems and resources

29may allow for higher rates of vital registration and systematic disease reporting,with higher rates of diagnosis confirmation.

Priorities for use of specific measures to monitor malaria burden and coverage ofinterventions may thus differ, as suggested below. Emphasis should be placed onmeasuring changes in coverage of RBM interventions at the outcome level (desiredchanges in outcome indicators should yield desired reductions in malaria-relatedmorbidity and mortality).

Table 4.1 Malaria-related goals and targets

Group

MillenniumDevelopmentGoals (MDGs)

RollBackMalaria

AbujaSummitTargets

Scale

Global

Global

Africa

Goals/targets

Goal 6.Goal 6.Goal 6.Goal 6.Goal 6. Combat HIV/AIDS, malariaand other diseasesTarget 8: Havehalted by 2015 and begun to reversethe incidence of malaria and othermajor diseases (for malaria, this is tobe measured by malaria prevalenceand deaths rates and by thepercentage of children under 5sleeping under insecticide-treatedmosquito nets; treatment to bemeasured by percentage of childrenunder 5 who are appropriately treated)

To halve malaria-associated mortalityby 2010 and halve it again by 2015At least 60% of those suffering frommalaria should be able to access anduse correct, affordable andappropriate treatment within 24hours of the onset of symptomsAtleast 60% of those at risk of malaria,particularly pregnant women andchildren under five, should benefitfrom suitable personal andcommunity protective measures suchas insecticide-treated mosquito nets

At least 60% of all pregnant womenwho are at risk of malaria, especiallythose in their first pregnancies,should receive intermittent preventivetreatment

Targetdate

2015

2010

2005

Source

http://unstats.un.org/unsd/mi/mi_goals.asp

Nabarro DN,Tayler EM. GlobalHealth: The‘RBM’ Campaign.Science, 1998,280280280280280:2067–2068

http://mosquito.who.int/docs/abuja_declaration.pdf

30Table 4.2 Specificity of measurement

STPf UnSTPvMeasures of mortality

All-cause under 5s mortality rates X XMalaria-specific mortality count/rates X X

Measures of morbidityMalaria infection rates Xa

Malaria case rates XMalaria-associated morbidity e.g. anaemia Xb

Measures of intervention coveragePrompt, effective case management X XUse of prevention in pregnancy XInsecticide-treated mosquito nets X XIndoor residual spraying X

a May be useful in areas of stable malaria transmission for surveys during peak malaria transmission.b In areas of stable malaria transmission, haemoglobin measurement in children aged 6–24 months is

recommended to track improvements in child health resulting from increasing coverage by malaria preventionand treatment.

4.3 Measurement topics (mortality, morbidity, coverage)

Measuring malaria-specific child mortality is not being done widely or consistently inmost highly endemic stable transmission settings. One method to measure malaria-specific mortalitymortalitymortalitymortalitymortality involves “verbal autopsy”. This has sensitivity and specificitylimitations and is unlikely to be available for repeated or continuous use at nationallevel. Verbal autopsy, HIS-data on malaria mortality and vital registration tend tounderestimate the impact of malaria control, because they pick up only a subset oftrue malaria deaths and miss others (e.g. those caused by malarial anaemia). In stabletransmission settings, only countries where coverage with key interventions, or at leastwith ITNs, has reached 60% should embark on evaluations of impact on malaria-specificor all-cause mortality. Mortality impact from cross-sectional surveys can be detected atthe earliest several years after coverage has increased; it is unrealistic to expectconvincing reductions in malaria-specific (or all-cause) mortality within a year or so ofincreased coverage. Impact on malaria-specific mortality may best be estimated fromtrends in all-cause under 5s mortality, together with coverage by key interventions. Inunstable transmission settings, vital registration and health facility records may providea stable and reliable count of malaria deaths, and reporting from these sources maybe more useful to monitor trends.

The use of routine information systems for the systematic collection of morbiditymorbiditymorbiditymorbiditymorbiditydatadatadatadatadata (malaria case counts, infection rates, associated anaemia rates, etc.) as measuresof impact over time in stable transmission settings (STPf), is very limited. Inexistent orinsufficient reporting, differences in treatment-seeking behaviour and inadequateaccess to diagnosis and treatment in the formal health sector render routinely reportedinformation useful only for broad comparisons of disease burden among those whoseek treatment in the formal health sector. RBM-MERG supports evaluation of early

31childhood anaemia as a possible measure of morbidity impact in sub-Saharan settings.It is also possible to consider sentinel site evaluation of child parasite prevalence, butdata indicate that parasite prevalence rates will not decline dramatically until high-coverage multiple interventions have been applied; thus, this measure may respondslowly despite progress in malaria control. For other malaria settings (unSTPv), healthinformation and disease reporting systems may be more robust and useful for MDGand RBM indicators.

Community-based information on prevention and treatment practices will be critical,particularly in isolated rural settings where most cases are managed at home andmost deaths occur outside formal health care. Special household surveys are the mostappropriate mechanism for monitoring trends in coverage for ITNs and appropriatemalaria treatment, but they are time-consuming, costly and require specialized skills.Such surveys can be conducted at 2–3-year intervals at most, whereas smaller surveysmay be conducted more often. In high-transmission settings (STPf), the RBM-MERGrecommends monitoring coverage by three main interventions:

1. Household-level possession and use of ITNs

2. Coverage by at least 2 doses of IPT during pregnancy

3. Coverage by prompt effective treatment of febrile/malaria illness in young children

In other malaria transmission settings (unSTPv), monitoring of coverage for theseinterventions is appropriate where national policy has adopted them against malaria.Monitoring coverage of ITNs and prompt effective treatment may best be achievedamong all ages in areas where the disease burden is not mainly borne by young children.

4.4 Measurement tools

RBM has coordinated household survey activities among partner organizations andcreated standard methods/questionnaires for assessing malaria indicators. The threemajor RBM tools for community surveys are:

Demographic and health surveys (DHS) Demographic and health surveys (DHS) Demographic and health surveys (DHS) Demographic and health surveys (DHS) Demographic and health surveys (DHS) are nationally representative householdsurveys focusing on reproductive and child health through interviews with between4000 and 12 000 women aged 15–49 years in a multiple-stage cluster of households.Results are comparable between countries and over time. Since 1998, specificquestions on malaria prevention and treatment have been included. In 2001, thesequestions were grouped into a standard malaria module to be added to DHS conductedin malarious countries. DHS provide information on major outcome indicators and area primary source of information on all-cause under 5s mortality rates. Recent DHS alsomeasure prevalence of anaemia in under 5s. DHS are funded primarily by USAID.Questionnaires and results are available on the Internet one year after completion offield work (http://www.measuredhs.com).

32Multiple indicator cluster surveys (MICS), conducted in 67 countries between 1999and 2001 with support from UNICEF, are nationally representative, with an average ofaround 6000 households sampled through a two-stage cluster design. Standard MICSquestionnaires include questions on ITNs and on antimalarial drugs for treatment offever among the under 5s; they also provide data on all-cause mortality among thesechildren. Results and questionnaires are freely available (childinfo.org). The round ofMICS started in 2004–2005 includes questions on malaria prevention and treatment.

Malaria indicator survey (MIS), developed by RBM-MERG for use at national orsubnational level, has smaller sample sizes and is likely to be less expensive. DHS andMICS are conducted during the dry season outside the peak malaria transmissionseason; MIS can be targeted to peak transmission and combined with measurementsof haemoglobin and parasite prevalence. The MIS package is available from WHO andthe RBM-MERG.

4.5 Routine health information systems and other systems

Routine health information systems (HIS) are the traditional source of data on malariacases and deaths seen in health facilities. They are crucial for the monitoring of needsfor antimalarial drugs and other commodities. Although these data are useful for themonitoring of trends in the number of cases and deaths, they have limitations. Inpractice, reporting from health facilities and districts varies in completeness andtimeliness; private and nongovernmental facilities are often not included and thenumbers of cases and deaths reported are less than the actual malaria burden, sincemany patients do not seek treatment or are treated outside the formal health sector.Other limitations in most sub-Saharan African countries include the fact that cases ofmalaria at the peripheral level are generally counted on presumptive and not onconfirmed diagnosis. Most deaths do not occur in hospitals and are not routinelyrecorded in HIS nor in (often incomplete) vital registration systems. HIS data are usefulfor local programme planning, but may not reflect the health problems of those whodo not attend. Major investment in improving the quality of HIS and access to formalhealth services will be needed before their usefulness for monitoring changes in malarialdisease can be assessed. In some countries, enhancement of HIS include randomselection of formal health service providers as sentinels for disease presentation. Theseenhanced HIS services require adequate diagnostics and capacity to track changingdisease burdens.

Current limitations in information collected from routine information systems and thecost of household surveys render sentinel sites an important source for malariamonitoring; they are often used for early warning and detection of malaria epidemics,and to monitor the development of antimalarial drug and insecticide resistance.Currently the most reliable data on trends in malaria deaths in children aged under 5years come from surveillance such as sentinel demographic surveillance systems (DSS).DSS measure deaths and possible causes prospectively in populations of known sizeand composition, using representative sampling methods (at least 30 DSS sites in 13

33sub-Saharan countries). Coupling DHS and DSS is being explored as an additionalmethod to measure impact. The INDEPTH network of DSS sites (www.indepth-network.org) should make it easier to harmonize and strengthen methods, and answerquestions across multiple sites.

Mapping populations at malaria risk and malaria early warning and detection systemshave benefited from integrating meteorological data. Information systems such asWHO’s HealthMapper desktop software, together with traditional data modelling,analysis and visualization techniques, are increasingly available to those workingdirectly with malaria control programmes and facilitate rapid spatial analyses andtargeting of malaria control resources. Online data management and reporting tools,e.g. WHO’s Global Atlas of Infectious Diseases, India’s National AntimalarialManagement Information System (NAMMIS), or Kenya’s Malaria Information System,are increasingly used.

34 Annex 1

The Millennium Development Goals

Goal 1. Eradicate extreme poverty and hunger

Target 1 Halve, between 1990 and 2015, the proportion of people whoseincome is less than one dollar a day

Target 2 Halve, between 1990 and 2015, the proportion of people who sufferfrom hunger

Goal 2. Achieve universal primary education

Target 3 Ensure that, by 2015, children everywhere, boys and girls alike, willbe able to complete a full course of primary schooling

Goal 3.Promote gender equality and empower women

Target 4 Eliminate gender disparity in primary and secondary education,preferably by 2005, and at all levels of education no later than 2015

Goal 4. Reduce child mortality

Target 5 Reduce by two thirds, between 1990 and 2015, the under-five mortalityrate

Goal 5. Improve maternal health

Target 6 Reduce by three-quarters, between 1990 and 2015, maternalmortality ratio

Goal 6. Combat HIV/AIDS, malaria and other diseases

Target 7 Have halted by 2015 and begun to reverse the spread of HIV/AIDS

Target 8 Have halted by 2015 and begun to reverse the incidence of malaria andother major diseases

Goal 7. Ensure environmental sustainability

Target 9 Integrate the principles of sustainable development into countrypolicies and programmes and reverse the loss of environmental resources

Target 10 Halve by 2015 the proportion of people without sustainable accessto safe drinking water and basic sanitation

35Target 11 Have achieved by 2020 a significant improvement in the lives of atleast 100 million slum dwellers

Goal 8. Build global partnership for development

Target 12 Develop further, an open, rule-based, predictable, non-discriminatorytrading and financial system. It includes a commitment to good governance,development, and poverty reduction – both nationally and internationally

Target 13 Address the special needs of the least developed countries. Includes:tariff and quota-free access for least-developed countries’ exports; enhancedprogramme of debt relief for HIPCs and cancellation of official bilateral debt; andmore generous ODA for countries committed to poverty reduction

Target 14 Address the special needs of landlocked countries and small islanddeveloping States (through the Programme of Action for the Sustainable Developmentof Small Island Developing States and the outcome of the twenty-second specialsession of the General Assembly)

Target 15 Deal comprehensively with the debt problems of developing countriesthrough national and international measures in order to make debt sustainable inthe long term

Target 16 In cooperation with developing countries, develop and implementstrategies for decent and productive work for youth

Target 17 In cooperation with pharmaceutical companies, provide access toaffordable essential drugs in developing countries

Target 18 In cooperation with the private sector, make available the benefits ofnew technologies, especially information and communications.

36 Annex 2

10 things you need to know about DDT use

UNDER THE STOCKHOLM CONVENTION

The following will apply to all Parties17 when the Stockholm Convention on PersistentOrganic Pollutants (POPs) comes into force:

1. DDT may be produced and used only for disease vector control; according to therecommendations and guidelines of the World Health Organization. DDT will be usedwhen safe, effective and affordable alternatives are not locally available.

2. WHO recommends only INDOOR RESIDUAL SPRAYING of DDT for disease vectorcontrol (spraying only on the inside walls of buildings).

3. A country that decides to use DDT for disease vector control is required to notifythe Convention Secretariat and WHO of the intention to produce and/or use DDT.

4. A public register of countries will be established for all the countries which applyto use DDT. Any country that determines that it needs DDT for disease vector control,and is not listed in the register will be required to notify the Convention Secretariat assoon as possible, in order to have its name added. The country is also required tonotify WHO at the same time.

5. Every three years, each country that uses DDT will be required to provide to theConvention Secretariat and WHO with information on the amount of DDT used, theconditions under which it is being used, and how such use relate to the country’sdisease management strategy. The reporting will be carried out in a format to bedetermined by the Conference of the Parties18 in consultation with WHO.

6. Countries using DDT will be supported and encouraged to strengthen their vectorcontrol programmes. The intention is to reduce and ultimately eliminate the use ofDDT with time, by making such use unnecessary. In this connection, each country willbe assisted to develop a national action plan that will include:

(i) The development of regulatory and other mechanisms to make sure that DDT isONLY used for disease vector control.(ii) The implementation of alternative products, methods and strategies. This willinclude vector resistance management strategies to make sure that the DDTalternatives remain effective.(iii) Actions to strengthen health care and reduce disease incidence.

17 “Party”: A State (country) or regional economic integration organization that has agreed to be bound by theStockholm Convention, and for which the Convention is in force.

18 “Conference of the Parties”: A formal meeting of Parties to the Convention.

377. Appropriate research will be promoted to develop safe alternative chemical andnon-chemical products, methods and strategies that are relevant to the conditions ofthose countries using DDT, and with the goal of reducing the human and economicburden of disease.

8. In developing such DDT alternatives, adequate consideration will be given toensure that viable alternatives present less risk to human health and the environment,and also that the alternatives are suitable for disease control within the particularcontext of each country.

9. Beginning at its first meeting, and at least every three years following that, theConference of the Parties shall, in consultation with WHO, evaluate whether there isstill the need for a country to continue using DDT for disease vector control. Thisevaluation will be done on the basis of available scientific, technical, environmentaland economic information of the country, including:

(i) The production and conditions under which DDT is being used;(ii)The availability, suitability and implementation of DDT alternatives; and(iii) Progress that has been made in strengthening the capacity of countries to transfersafely to reliance on such alternatives.

10. A country may withdraw its name from the DDT Registry at any time, following awritten notification to the Convention Secretariat. The withdrawal will take effect onthe date that has been specified in the notification.

38 Annex 3

WHO position on prevention and control of HIV/malariaco-infection

GeneGeneGeneGeneGenevvvvva – a – a – a – a – To reduce the lethal consequences of HIV/AIDS and malaria coinfection,prevention and treatment programmes of the two diseases must mutually reinforceeach other, according to the World Health Organization. A meeting of internationalexperts in June 2004 agreed upon a set of concrete recommendations to synergizeHIV/AIDS and malaria programmes in affected countries.

HIV/AIDS and malaria count among the worst diseases in the developing world.Together, they cause more than four million deaths per year. Every single day, HIV/AIDS kills 8000 people, resulting in three millions deaths per year, with Africa carryingabout two-thirds of this burden. Malaria is responsible for the death of over 3000people every day; 90% of these deaths occur in tropical Africa, mainly in young children.Any interaction of the two diseases has enormous public health consequences.

Almost all countries in sub-Saharan Africa have a high burden of both, malaria andHIV/AIDS. Cameroon, the Central African Republic, Malawi, Mozambique and Zambiaare among the countries hardest hit by the two epidemics, with an HIV prevalence inadults of above 10%, and more than 90% of the population being exposed to malaria.The two diseases also overlap in India, South-East Asia, and South America.

The impact of the two diseases has serious consequences for reproductive health:Pregnant women who are co-infected with HIV/AIDS and malaria, are at very high riskof anaemia and malarial infection of the placenta. Many children born to co-infectedwomen have low birth weight and increased mortality risk. In men and non-pregnantwomen, AIDS may increase the risk of severe malaria. In addition to that, antimalarialdrugs are less effective in people living with HIV/AIDS.

Malaria can lead to anaemia and require blood transfusions, posing a risk factor forHIV infection. Further, in people with malaria, the virus that causes AIDS has beenshown to replicate more readily.

Based on a detailed analysis of the latest scientific evidence on the interactions betweenthe two diseases, WHO issued the following key recommendations:

1. People living with HIV/AIDS in malaria endemic areas must have access to insecticide-treated nets to prevent malaria transmission.

2. HIV-positive pregnant women must have access to insecticide-treated bed nets. Inaddition, they must receive either intermittent preventive treatment with sulfadoxine–pyrimethamine or daily cotrimoxazole prophylaxis, according to the stage of HIV-infection.

3. Programmes to control the two diseases should collaborate to ensure integratedservice delivery.

394. Additional research on interactions between antiretroviral and antimalarial drugs is

urgently needed.

“Improving the efficiency and effectiveness of joint HIV and malaria disease preventionand treatment programmes can have a significant impact on reducing the burden ofdisease on individuals and families,” said Dr Fatoumata Nafo-Traoré, Director of WHO’sRBM Department. “These recommendations are the beginning to achieve the necessaryconcerted action in countries.”

People seek care for malaria at health posts, health centres and other outlets. Accordingto WHO, these services can serve as entry points for health education, detection andtreatment of both diseases, provided that skilled staff, supplies and equipment areavailable. It is here that both diseases converge. A range of services is required to ensurean effective response to the challenges posed by the two diseases, including counselling,treatment advice and community based support for taking medicines as prescribed.

There is growing political and unprecedented financial commitment to effectively reducethe burden of HIV/AIDS and malaria. As more resources are made available to fightthese diseases, close coordination is critical to make the most of this opportunity.

“Accelerating prevention and treatment for both HIV and malaria are now among thetop priorities for the global public health community,” said Dr Jim Yong Kim, Director ofWHO’s HIV/AIDS Department. “Everyone working on these problems must make themost of the investments that are being made. We can and must integrate and ensuremutual reinforcement of our HIV and malaria response.”

More information on HIV/AIDS-Malaria Coinfection can be found at the following sites:http://mosquito.who.int/cgi-bin/rbm/rbmportal/custom/home/mal/login.jsphttp://mosquito.who.int/malaria_HIV/http://mosquito.who.int/malaria_HIV/malaria_hiv_flyer.pdf

40 Annex 4

A note on stratification

Malaria is a local disease; its distribution varies considerably from one region to another.Administrative, operational, technical and financial opportunities for malaria controlvary from region to region. Identification of the types of malaria problems constitutesthe “stratification” on which to select appropriate interventions.

The process of stratification defines “strata” that share similar epidemiological,geographical, socioeconomic and ecological characteristics. The different strata maybe hierarchically organized according to the magnitude of the malaria problem. Table1 lists variables relevant to malaria control. The process of analysis and synthesis ofinformation is called operational stratification and leads to the selection of homogeneousstrata for which specific objectives, approaches, targets, intervention methods andimplementation dates must be decided. A yearly assessment of results in particularareas should allow more precise determination of the workload for the following yearand a possible reorientation of interventions.

• Stratification according to epidemiological criteriaBelow is a list of strata grouped by epidemiological characteristics. Two characteristicsare common to all strata: P. falciparum is the dominant parasite, and the dominantvectors are highly dependent on clean water collections for their breeding sites. Thelist is not exhaustive, but an attempt has been made to define each stratum by a fewimportant environmental, epidemiological, social, economic and demographic criteria.Tables 2.4 summarize some characteristics of stratification, including macro and micro-ecological variables.

• Presentation of the strataThe most convenient way to present the strata is to display the information graphicallyon superimposed maps. The simplest method to do this is to take several copies of anarea map and depict one or two variables in each copy. Once all variables have beenmapped, the maps are converted to overhead transparencies that can besuperimposed, forming a single map containing all the variables. Digitized maps, ofwhich the Healthmap unit of WHO maintains a library, are required to fully exploit thepotential application of mapping. For most African countries, information such as riversand roads can be available.

• Selection of control measures for the different strata in primary health carePrevention of malaria mortality by early administration of a suitable treatment mustconstitute the first priority of any antimalarial action. Other control measures must beconsidered when mortality prevention has been developed and only in regions whereepidemiological situation, availability of resources and objectives of malaria controlguarantee the preservation of acquired gains.

41

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Rel

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t var

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trol

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latio

n

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grap

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rs

Freq

uent

ane

mia

amon

g in

fant

s(6

–36

mon

ths)

Cere

bral

mal

aria

isco

mpa

rativ

ely r

are

Adul

ts a

re s

emi-

imm

une;

mild

and

limite

d m

alar

ia c

rises

Rura

l are

as o

f tra

ditio

nal a

gric

ultu

re a

ndst

eady

sea

sona

l tra

nsm

issi

on. T

ypic

alsa

vann

ah re

gion

s. C

lose

to th

e eq

uato

r,di

ffere

nce

betw

een

Stra

tum

I an

d II

less

ens

Inci

denc

e an

d pr

eval

ence

of in

fect

ion

and

illne

ss s

ame

as th

ose

of S

trat

um I

The

peak

of m

orbi

dity

and

mor

talit

y m

oves

tow

ard

slig

htly

old

er c

hild

ren

Anem

ia is

less

com

mon

Cere

bral

mal

aria

is m

ore

freq

uent

Rura

l and

arid

zon

es w

ithtr

aditi

onal

agr

icul

ture

and

unst

able

tra

nsm

issi

on.

Inst

abili

ty is

due

mai

nly

toar

idity

Trad

ition

al o

ases

and

nom

ads-

expo

sed

whi

le tr

avel

ing

toot

her s

trat

a

Prol

onge

d m

orbi

dity

unt

il th

ead

ult a

ge, v

aria

ble

from

one

year

to a

noth

er

Expo

sed

popu

latio

ns o

ften

limite

d an

d ep

idem

ics

may

have

nev

er b

een

ackn

owle

dged

by h

ealth

ser

vice

s, e

xcep

t for

refu

gees

Rura

l are

as o

f hig

h al

titud

ew

ith t

radi

tiona

l agr

icul

ture

and

unst

eady

tra

nsm

issi

on

The

popu

latio

n de

nsity

is o

ften

high

.

43

STRA

TUM

VI

NO

MAD

S

Som

e ar

e fu

lly n

omad

ic a

nd m

ove

thro

ugh

larg

ear

eas

depe

ndin

g on

irre

gula

r pr

ecip

itatio

ns, o

ther

sar

e pa

rtly

set

tled

in z

ones

tha

t m

ay in

clud

e St

rata

II,

III a

nd IV

, whe

re t

hey

enga

ge in

sea

sona

l agr

icul

ture

,tr

avel

ing

at o

ther

tim

es w

ithin

a m

ore

rest

ricte

dar

ea.

Tabl

e 3.

Stra

tific

atio

n ac

cord

ing

to s

ocio

econ

omic

crit

eria

(mac

ro-e

colo

gica

l and

soc

ial v

aria

bles

) STRA

TUM

VII

URBA

N M

ALAR

IA

Tran

smis

sion

var

iabl

e w

ithin

an

area

tha

t sp

read

s fro

m t

he u

rban

cen

tre

toth

e pe

riphe

ry. M

orbi

dity

and

mor

talit

y af

fect

you

ng a

dults

, pre

gnan

t w

omen

are

ofte

n vi

ctim

s of

sev

ere

form

s of

the

dis

ease

. Acc

ess

to t

reat

men

t is

rela

tivel

y go

od a

nd li

mits

ove

rall

mor

talit

y. Pe

ople

are

mor

e lik

ely

to b

esu

bjec

t to

inte

nse

mar

ketin

g of

exp

ensi

ve a

nd o

ften

usel

ess

med

icin

es. D

rug

resi

stan

ce le

vels

can

be

high

.

Tran

smis

sion

is s

tead

y an

dpe

rman

ent

Seas

onal

var

iatio

ns e

xist

, but

tra

nsm

issi

onne

ver s

tops

com

plet

ely

at a

ny p

erio

d of

the

year

Vect

or p

opul

atio

ns a

nd e

ntom

olog

ical

inoc

ulat

ion

rate

s in

crea

se q

uick

ly to

hig

hpe

aks

durin

g an

d rig

ht a

fter t

he ra

iny

seas

on

Poss

ible

rec

urre

nt e

pide

mic

sif

prec

ipita

tion

favo

urab

le to

tran

smis

sion

, so

met

imes

follo

w c

yclic

al m

odel

Low

pop

ulat

ion

dens

ity,

impa

ssab

le ro

ads

in ra

iny

seas

on. P

oor d

evel

opm

ent

of h

ealth

ser

vice

s

Pers

onal

mea

sure

sso

met

imes

use

d, e

spec

ially

amon

g ca

ttle

bree

ders

Poss

ible

rec

urre

ntep

idem

ics

rela

ted

topo

pula

tion

mov

emen

ts,

clim

atic

mod

ifica

tions

and

chan

ges

in a

gric

ultu

ral

prac

tices

The

trad

ition

al u

se o

fpe

rson

al p

rote

ctiv

em

easu

res

is v

aria

ble

44Ta

ble

4. S

trat

ifica

tion

acco

rdin

g to

soc

ioec

onom

ic (

mic

ro-e

colo

gica

l) a

nd e

nvir

onm

enta

lch

arac

teris

tics

STRA

TUM

VIII

PROG

RAM

MES

OF

SOCI

OECO

NOM

IC D

EVEL

OPM

ENT

Mod

ern

irrig

atio

n sy

stem

s in

reg

ular

use

are

exam

ples

of

this

str

atum

; with

cha

ract

eris

tics

that

fav

our

long

er t

rans

mis

sion

per

iods

.In

sect

icid

es/p

estic

ides

ofte

n he

avily

use

d to

guar

ante

e ha

rves

ts a

nd c

an c

ontr

ibut

e to

redu

ce m

alar

ia t

rans

mis

sion

; but

als

oac

cele

rate

sel

ectio

n of

inse

ctic

ide-

resi

stan

tve

ctor

s. T

here

is o

ften

one

mig

ratio

n se

ason

for

wor

kers

at

harv

est

time,

whe

ntr

ansm

issi

on c

an b

e m

ost

inte

nse;

thi

sin

crea

ses

para

site

res

ervo

ir an

d/or

num

ber

of s

usce

ptib

le in

divi

dual

s, d

epen

ding

on

loca

lris

k of

mal

aria

, orig

in o

f th

e w

orke

rs,

loca

lizat

ion

of t

he p

roje

ct, l

odgi

ng c

ondi

tions

of w

orke

rs a

nd d

rain

age

char

acte

ristic

s.

STRA

TUM

IXTE

MPO

RARY

DEV

ELOP

MEN

TPR

OJEC

TS

Incl

ude

tem

pora

ryde

velo

pmen

t pr

ojec

ts w

ithm

assi

ve g

athe

ring

of w

orke

rs. S

peci

al r

isks

such

as

an in

crea

se o

fbr

eedi

ng s

ites

and

oppo

rtun

ities

for

hum

an-

vect

or c

onta

cts,

the

imm

igra

tion

of n

on-im

mun

ew

orke

rs a

nd in

crea

sed

mor

talit

y.

STRA

TUM

XNO

N-IM

MUN

E VI

SITO

RS

Non

-imm

une

visi

tors

or t

empo

rary

res

iden

tsin

end

emic

are

as; w

ithris

ks o

f se

vere

mal

aria

and

high

mor

talit

y.

STRA

TUM

XI

REFU

GEES

AND

DIS

PLAC

EDPO

PULA

TION

S

Appl

ies

part

icul

arly

to

refu

gees

and

disp

lace

d pe

ople

set

tled

in c

amps

.

45Annex 5

Combinations of antimalarial drugs and their applications

5.1 Possible antimalarial combinations, pros/cons andsuggested epidemiological settings for their application

Combination therapy is an evolving situation and based on recent studies anddevelopments, a summary is shown below. This situation may change over time. Youmay refer learners to recent reports on antimalarial drugs.19

19 Report of technical consultation, WHO, Geneva. WHO/CDS/RBM/2001.35.

46

Com

bina

tion

Pros

/adv

anta

ges

Cons

/lim

itatio

nsSu

gges

ted

to b

e us

ed in

epi

dem

iolo

gica

lse

tting

(tran

smis

sion

and

type

of p

lasm

odiu

mpa

rasi

te a

nd re

sist

ance

, tar

get g

roup

)

Clor

oqui

ne (C

Q)+ Su

lfado

xine–

pyrim

etha

min

e (S

P)

•Su

itabl

e fo

r com

bina

tion

as b

oth

have

diffe

rent

bio

chem

ical

targ

ets

in th

e pa

rasi

te•

No

cros

s re

sist

ance

doc

umen

ted

•Th

e an

ti-in

flam

mat

ory e

ffect

of C

Qen

hanc

es th

e ef

fect

of C

Q+SP

with

a m

ore

rapi

d re

solu

tion

of s

ympt

oms

•Co

st-e

ffect

ive

May

not

be

used

In a

reas

whe

re P.

falc

ipar

umre

sist

ance

to C

Q is

hig

h

In a

reas

whe

re:

•th

ere

is m

oder

ate

resi

stan

ce o

fP.

falc

ipar

um to

CQ

•in

are

as w

here

P. f

alci

paru

m a

nd P

. viv

axar

e co

mm

on

Amod

iaqu

ine

(AQ)

+ Sulfa

doxin

e–py

rimet

ham

ine

(SP)

•Te

chni

cally

sui

tabl

e fo

r com

bina

tion

asbo

th h

ave

diffe

rent

bio

chem

ical

targ

ets

inth

e pa

rasi

te•

AQ h

as a

ntip

yret

ic a

nd a

nti-i

nfla

mm

ator

yw

ith fa

ster

reco

very

Seve

re a

dver

se re

actio

nsw

hen

used

as

prop

hyla

ctic

In a

reas

whe

re th

ere

is le

ss re

sist

ance

to A

Qth

an th

ose

to C

Q

Atov

aquo

ne–P

rogu

anil

•G

ood

syne

rgis

tic e

ffect

and

mor

eef

ficac

ious

aga

inst

P. f

alci

paru

m in

clud

ing

stra

ins

resi

stan

t to

CQ a

nd M

Q•

The

recr

udes

cenc

e of

par

asita

emia

(whe

nAt

ovaq

uone

is u

sed

alon

e) is

min

imiz

ed

Hype

rsen

sitiv

ityPr

esen

ce o

f ren

alin

suffi

cien

cyH

igh

cost

and

less

ava

ilabl

e

Curr

ently

not

reco

mm

ende

d in

youn

g ch

ildre

n(<

11 k

g), p

regn

ant a

nd b

reas

t fee

ding

wom

en

Mef

loqu

ine

+ Sulfa

doxin

e–py

rimet

ham

ine

(SP)

•N

o ph

arm

acok

inet

ic in

tera

ctio

n be

twee

nco

mpo

nent

s•

Long

elim

inat

ion

half-

life

of M

eflo

quin

e(2

0 da

ys in

adu

lt) fo

r sin

gle

trea

tmen

t(s

o us

ed a

s ch

nem

opro

phyl

actic

)

Poor

mat

ch o

f hal

f-life

of

Mef

loqu

ine

(long

) and

SP

(sho

rt)Re

sidu

al d

rug

leve

l for

long

dura

tion

caus

es ra

pid

deve

lopm

ent o

f res

ista

nce

to M

eflo

quin

eAd

vers

e re

actio

ns

Not

reco

mm

ende

d fo

r are

as w

ith in

tens

em

alar

ia tr

ansm

issi

on

Quin

ine

+ Tetr

acyc

line

or D

oxax

yclin

e

•Hi

gh c

ure

rate

in a

reas

with

dec

reas

ing

susc

eptib

ility

of P

. fal

cipa

rum

to Q

uini

ne•

Dox

icyc

line

has

long

hal

f-life

and

has

oper

atio

nal a

dvan

tage

as

one

day r

egim

enis

eno

ugh

com

pare

d to

tetra

cycl

ine

(giv

en4x

a d

ay) -

bette

r adh

eren

ce a

nd s

afet

y for

seco

nd-li

ne tr

eatm

ent

Diff

icul

t to

reco

mm

end

asfir

st-li

ne tr

eatm

ent

Not

reco

mm

ende

d fo

r pre

gnan

t & b

reas

tfe

edin

g w

omen

, chi

ldre

n <8

yrs

of a

ge.

Reco

mm

ende

d fo

r 2nd

-lin

e tr

eatm

ent

NON

ARTE

MIS

ININ

-BAS

ED C

OMBI

NATI

ONS

47

Arte

suna

te +

Chlo

roqu

ine

Arte

suna

te+A

mod

iaqu

ine

Arte

suna

te+ Su

lfado

xine–

pyrim

etha

min

e

Arte

suna

te +

Mef

loqu

ine

Arte

met

her–

lum

efan

trine

•W

ell t

oler

ated

effi

cacy

•N

o ad

vers

e re

actio

n

•W

ell t

oler

ated

effi

cacy

•W

ell t

oler

ated

effi

cacy

•G

ood

resu

lts w

ith 3

day

regi

men

of

arte

suna

te

•Co

mbi

natio

n re

sults

in re

duce

dad

vers

e re

actio

ns o

f hig

h M

eflo

quin

edo

se th

an w

hen

used

alo

ne

•Co

mbi

natio

n ef

fect

ive

and

wel

lto

lera

ted

•N

o ad

vers

e re

actio

n•

Incr

ease

d co

mpl

ianc

e as

it e

xist

sin

a fi

xed-

dose

form

ulat

ion

Less

par

asito

logi

cal c

ure

rate

(sub

-opt

imal

effi

cacy

of

com

bina

tion)

Incr

easi

ng le

vel o

f res

ista

nce

to S

P m

ay li

mit

the

use

of th

isco

mbi

natio

n

Mul

tiple

dos

eSe

vere

adv

erse

reac

tion

(e.g

neur

al a

nd c

ardi

ac e

ffect

s)D

iffic

ult t

o m

onito

r adv

erse

reac

tions

in u

nsup

ervi

sed

larg

e-sc

ale

use

Mul

tiple

dos

eN

ot re

com

men

ded

for p

regn

ant

and

brea

st fe

edin

g w

omen

Not

via

ble

com

bina

tion

in a

reas

with

pre

-ex

istin

g m

oder

ate

to h

igh

P. fa

lcip

arum

resi

stan

ce to

CQ

Appe

ars

to b

e a

viab

le o

ptio

n in

are

as w

here

CQ e

ffica

cy is

alre

ady c

ompr

omis

ed

A vi

able

opt

ion

whe

re re

sist

ance

to S

P is

low

er. e

.g s

ome

coun

trie

s in

Wes

t Afri

ca

Not

via

ble

optio

n as

a fi

rst-l

ine

trea

tmen

t in

inte

nse

tran

smis

sion

are

as b

ecau

se o

f the

long

hal

f-life

of M

eflo

quin

e

This

is th

e m

ost v

iabl

e co

mbi

natio

n op

tion

for

area

s w

ith in

tens

e m

alar

ia tr

ansm

issi

on w

ithhi

gh im

mun

ity (4

dos

e) a

nd 6

dos

e re

gim

enin

3 d

ays

for n

on-im

mun

e po

pula

tion

Com

bina

tion

Pros

/adv

anta

ges

Cons

/lim

itatio

nsSu

gges

ted

to b

e us

ed in

epi

dem

iolo

gica

lse

tting

(tran

smis

sion

and

type

of p

lasm

odiu

mpa

rasi

te a

nd re

sist

ance

, tar

get g

roup

)

ARTE

MIS

ININ

-BAS

ED C

OMBI

NATI

ONS

48 5.2 Practical aspects of treatment with recommended ACTs

1. Artemether–lumefantrine combination

This is currently available only as coformulated tablets contain 20 mg of artemetherand 120 mg of lumefantrine. The total recommended treatment is a 6-dose regimenof artemether-lumefantrine 1.5/12 mg/kg twice daily for 3 days

Body weight No. of tablets recommended at approximate timing (hours) of dosinga

0 h 8 h 24 h 36 h 48 h 60 h

5–14 kg (<3 y) 1 1 1 1 1 115–24 kg (3–9 y) 2 2 2 2 2 225–34 kg (9–14 y) 3 3 3 3 3 3>34 kg (>14 y) 4 4 4 4 4 4a The regimen can be expressed more simply for ease of use at the programme level as follows: the second doseon the first day should be given anytime between 8 and 12 h after the first dose. Dosage on the second and thirddays is twice a day (morning and evening).

An advantage of this combination is that lumefantrine is not available as a monotherapyand has, therefore, never been used by itself for the treatment of malaria. The 6-doseregimen of artemether-lumefantrine was previously not recommended for childrenweighing under 10 kg. This was because of insufficient data in young children at thattime. However, recent evidence suggest that the therapeutic response and safety profilein young children is similar to that in older children. Artemether-lumefantrine istherefore now recommended for patients of all ages. Lumefantrine absorption is highlydependent on co-administration with fat. Treatment failure may result from inadequatefat intake, and so it is essential that patients or care-givers are informed of the need totake this ACT with milk or fat-containing food – particularly on the second and thirddays of treatment.

2. Artesunate+amodiaquine combination

This is currently available as separate scored tablets containing 50 mg of artesunateand 153 mg base of amodiaquine, respectively. Coformulated tablets are underdevelopment but are not available at present. The total recommended treatment is4 mg/kg of artesunate and 10 mg base/kg of amodiaquine given once daily for 3 days.

Table 1. Dosing schedule for artemether-lumefantrine

Table 2. Dosing schedule for artesunate-amodiaquineDose in mg (no. of tablets)

Age Artesunate AmodiaquineDay 1 Day 2 Day 3 Day 1 Day 2 Day 3

5–11 months 25 (1/2) 25 25 76 (1/2) 76 761–6 years 50 (1) 50 50 153 (1) 153 1537–13 years 100 (2) 100 100 306 (2) 306 306>13 years 200 (4) 200 200 612 (4) 612 612

49This combination is sufficiently efficacious only where 28-day cure rates with amodia-quine monotherapy exceed 80%. Resistance is likely to worsen with continuedavailability of chloroquine and amodiaquine monotherapies. More information on thesafety of artesunate+amodiaquine is needed from prospective pharmacovigilanceprogrammes.

3. Artesunate +sulfadoxine-pyrimethamine combination

This is currently available as separate scored tablets containing 50 mg of artesunateand tablets containing 500 mg of sulfadoxine and 25 mg of pyrimethamine.20 Thetotal recommended treatment is 4 mg/kg of artesunate given once daily for 3 daysand a single administration of sulfadoxine-pyreimethamine 1.25/25 mg base/kg onday 1.

Table 3. Dosing schedule for artesunate-sulfadoxine-pyrimethamine

1 A similar medicine with tablets containing 500 mg of sulfalene 25 mg of pyrimethamine is considered to beequivalent to sulfadoxine-pyrimethamine

Dose in mg (no. of tablets)Age Artesunate Sulfadoxine-pyrimethamine

Day 1 Day 2 Day 3 Day 1 Day 2 Day 3

5–11 months 25 (1/2) 25 25 250/12.5 (1/2) – –1–6 years 50 (1) 50 50 500/25 (1) – –7–13 years 100 (2) 100 100 1000/50 () – –>13 years 200 (4) 200 200 1500/75 (3) – –

While a single dose of sulfadoxine-pyrimethamine is sufficient, it is necessary forartesunate to be given for 3 days for satisfactory efficacy. This combination is sufficientlyefficacious only where 28-day cure rates with sulfadoxine-pyrimethamine alone exceed80%. Resistance is likely to worsen with continued availability of suldoxine-pyrimethamine and trimethoprim-sulfamethoxazole [and sulfalene-[and sulfalene-[and sulfalene-[and sulfalene-[and sulfalene-pyrimethamine?]pyrimethamine?]pyrimethamine?]pyrimethamine?]pyrimethamine?].

4. Artesunate+mefloquine combination

This is currently available as separate scored tablets containing 50 mg of artesunateand 250 mg base of mefloquine, respectively. Coformulated tablets are underdevelopment but are not available at present. The total recommended treatment is4 mg/kg of artesunate given once daily for 3 days and 25 mg base/kg of mefloquineusually split over 2 or 3 days.

20 A similar medicine with tablets containing 500 mg of sulfalene 25 mg of pyrimethamine is considered to be

50Table 4. Dosing schedule for artesunate-mefloquine

Dose in mg (no. of tablets)Age Artesunate Mefloquine

Day 1 Day 2 Day 3 Day 1 Day 2 Day 3

5–11 months 25 (1/2) 25 25 – 125 (1/2) –1–6 years 50 (1) 50 50 – 250 (1) –7–13 years 100 (2) 100 100 – 500 (2) 250 (1)>13 years 200 (4) 200 200 – 1000 (4) 500 (2)

Two different doses of mefloquine have been evaluated, 15 mg base/kg and 25 mgbase/kg. The lower dose is associated with inferior efficacy and is not recommended.To reduce acute vomiting and optimize absorption, the 25 mg/kg dose is usually splitand given either as 15 mg/kg (usually on the second day) followed by 10 mg/kg oneday later, or as 8.3 mg/kg/day for 3 days (future coformulated products will containthis dose). This approach has the advantage of being better tolerated and producinghigher blood concentrations, but the disadvantage of risking inadequate dosing if thepatient does not adhere to the prescribed regimen. Pending development of acoformulated product, malaria control programmes will have to decide on the optimumoperational strategy of mefloquine dosing for their populations. Mefloquine is associatedwith an increased incidence of nausea, vomiting, dizziness, dysphoria and sleepdisturbance in clinical trials, but these are seldom debilitating and in general wherethis ACT has been deployed it has been well accepted.

5.3 Incorrect approaches to treatment

In the presence of symptomatic malaria in semi-immune patients, partial treatmentwith effective medicines (i.e. regimens that would be unsatisfactory in patients withno immunity) may still be curative. In the past, this has led to differentrecommendations for patients considered to be semi-immune as against thoseconsidered to be non-immune. Another potentially dangerous practice is to recommendpartial treatments for patients with suspected but unconfirmed malaria, with theintention of giving full treatment if the diagnosis is eventually confirmed. Neitherpractice is recommended. If symptomatic malaria is diagnosed, then a full treatmentis required.

With the exception of artemether-lumefantrine, the partner medicines of all other ACTshave been previously used as monotherapies, and still continue to be available assuch in many countries. Their continued use as monotherapies will compromise thevalue of ACTs by selecting for drug resistance. Provided there are sufficient ACTreplacements available, the withdrawal of these monotherapies is, therefore, highlyrecommended.

51Annex 6

Interim notes on selection of type of malaria rapiddiagnostic test in relation to the occurrence ofdifferent parasite species

Guidance for national malaria control programmesPrepared by Roll Back Malaria DepartmentWorld Health Organizationwith the collaboration of the Regional Offices for Africa and the Western Pacific August 2005

1. Background

Use of parasite-based diagnosis

Parasitological confirmation of the diagnosis of malaria is part of good clinical practiceand should always be part of malaria case management, with the following exceptions:

• Children under 5 years old in areas of high prevalence as there is not yet evidencethat the benefits of parasitological confirmation outweigh the risk of not treatingfalse negatives.a

• Cases of fever in established malaria epidemics where resources are limited (WHO2004a)

• Where good quality diagnosis is not available (as an interim measure while capacityfor parasite-based diagnosis is being developed).

Justification for parasite-based diagnosis, including improved disease managementand potential savings in health resources, are detailed elsewhere (WHO 2000).a

The appropriateness of microscopy versus antigen-detecting rapid diagnostic tests dependson a number of factors including parasite prevalence, availability of skilled personnel andresources, the capacity for maintaining quality assurance of microscopy and RDT, and theneed for quantitative assessment of parasite density. These are discussed elsewhere (Makler,Palmer et al. 1998; Hanscheid 1999; Moody 2002; WHO 2003).

From here on, this document concentrates only on areas where diagnosis using antigen-detecting RDTs has been deemed appropriate. RDTs detecting anti-malaria antibodieshave indications other than case management, and are not discussed here.

a Technical Consultation to Review the Role of Laboratory Diagnosis to Support Malaria Disease Management:Focus on the Use of RDTs in Areas of High Transmission Deploying ACT Treatments (25-26 October 2004) Reportin preparation

52 2. Types of Malaria Rapid Diagnostic Tests

The three main groups of antigens detected by commercially available RDTs are:

• Histidine-rich protein 2 (HRP2), specific to P. falciparum,

• Plasmodium lactate dehydrogenase (pLDH), currently used in products that includeP. falciparum-specific, pan-specific, and P. vivax-specific pLDH antibodies,

• Aldolase (pan-specific).

Target antigens of commercially-available malaria rapid diagnostic testsHRP2 pLDH Aldolase

P. falciparum-specific + +Pan-specific (all species) + +P. vivax-specific +

Most commercial products include antibodies to:

• HRP2 alone (P. falciparum),

• HRP2 and aldolase (distinguishing P. falciparum/mixed infection from non-falciparum alone)b,

• Falciparum-specific pLDH and pan-specific pLDH (distinguishing P. falciparum/mixedinfection from non-falciparum alone),

• HRP2 and pan-specific pLDH,

• HRP2, pan-specific pLDH and vivax-specific pLDH, or

• Pan-specific aldolase only.

RDT detecting both falciparum-specific and non-falciparum (or pan-specific) targetantigens are commonly called combination or ‘combo’ tests.

The products come in a number of formats:

• Plastic cassette

• Card

• Dipstick

• Hybrid cassette-dipsticks

Cassettes tend to be simpler to perform than dipsticks, and this is likely to affect testaccuracy.c

b As products are commonly more sensitive to HRP2 than aldolase in P. falciparum-only infections, these willcommonly appear as an HRP2 line only if the parasite density is low.c Unpublished report of WHO, Quality Assurance Project (USA), Research Institute for Tropical Medicine (Philippines)and Centre for Malaria, Parasitology and Entomology (Cambodia) at http://www.wpro.who.int/RDT/docs/Developing_and_testing_an_RDT_Job_Aid.pdf

533. Choosing a Malaria Rapid Diagnostic Test

Important considerations involved in choosing an RDT include:

• Sensitivityd (and specificity)

• Stability

• Ease of use (impacts on sensitivity and stability)

• Cost.

Other general considerations are listed elsewhere (WHO 2003).

3.1 Species zones affecting RDT choice

The appropriateness of P. falciparum-specific, pan-specific and non-falciparum RDTsvaries with the relative prevalence of the different human malaria species in theintended area of use. These areas can be categorized as:

Zone 1. P. falciparum-only, or with non-falciparum species occurring almost always asco-infections with P. falciparum (Most areas of sub-saharan Africa and low-land Papua New Guinea)

Zone 2. Falciparum and non-falciparum infections occurring commonly as single-species infections (Most endemic areas in Asia and the Americas, and isolatedareas in Africa, particularly the Ethiopian highlands)

Zone 3. Areas with non-falciparum malaria only (mainly vivax-only areas of East Asiaand central Asia, and some highland areas elsewhere)

Zone 1: Falciparum-only RDT generally indicated

In areas where only falciparum malaria occurs, or non-falciparum malaria rarely occurswithout co-infection of P. falciparum, RDTs that detect only P. falciparum are generallypreferable on grounds of lower cost. Most (or all) commercially-available RDTs in thiscategory detect HRP2.

As treatment for P. falciparum is effective for treating blood-stages of non-falciparumparasites, and anti-relapse treatment for the liver stage of P. vivax and P. ovale is notnormally given in endemic areas in Africa, there is usually little to be gained for case

d The ‘sensitivity’ of an RDT for detecting malaria parasitaemia (or recent parasitaemia) depends on theconcentration of circulating antigen in the patients’ blood, and the ability of the labeled antibody on the RDT tobind the antigen and accumulate to form a visible line. In turn, this depends on the relationship between antigenconcentration and parasite density, which may vary with the host (e.g. immunity) and with the parasite (WHO,2004). In general, it is recommended that at least 95% of P. falciparum infections should be detected at 100parasites per microlitre, and higher at higher parasite densities (WHO 2000; 2003), which is probably similar togood field microscopy. The appropriateness of this figure depends on the clinical situation, and the availablealternative methods of diagnosis. Lower sensitivity for non-falciparum parasites may be clinically acceptable.

54management by identifying co-infection with non-falciparum species. Most commercialRDT do not distinguish mixed infections from falciparum-only infections, so the onlyadvantage of using a combined RDT in these areas is to detect rare infections involvingnon-falciparum parasites alone.

In certain situations, combined RDTs may be appropriate if they have desired propertiesthat falciparum-only RDTs do not have. This applies particularly to situations where itis required to monitor post-treatment parasitaemia, in which case pLDH-detecting RDTmay be used in preference to HRP2-detecting RDT.e However, in general, microscopy isthe preferred tool for monitoring treatment outcomes.

Zone 2. Combination RDT generally indicated

Where falciparum and non-falciparum infections occur commonly as single speciesinfections, combination tests detecting all species and distinguishing P. falciparumfrom non-falciparum infections are indicated.

The use of RDTs that detect P. falciparum alone would result in dilemmas in themanagement of RDT-negative patients, some of whom will have malaria due to P.vivax, P. ovale or P. malariae. RDT negative patients must then be treated withchloroquine (accepting a high rate of unnecessary treatment of non-malaria cases),and the advantage of distinguishing non-malaria cases for specific diseasemanagement would be lost.

Zone 3. Pan-specific or vivax-specific RDT generally indicated

No falciparum occurs. RDT detecting non-falciparum species alone are appropriate(P. vivax-specific or pan-specific).

Note: As the above zones are part of a continuum of species distribution, difficult decisionsin choice of RDT target species can occur. For instance, where a small proportion of non-falciparum single species infections occur (e.g. 1–4% of malaria patients) and P.falciparum infections greatly predominate, decisions on using combo rather thanfalciparum-only RDT will depend on available resources and the importance of distin-guishing small numbers of non-falciparum malaria infections from non-malaria infections.

3.2 Comparison of RDTs detecting both P. falciparum and non-falciparum

infections

The intended conditions of use must be considered when choosing an RDT. If they areto be used in a remote area without temperature-controlled storage, stability (shelf-

e In practice, this means using a combined RDT as no pLDH products are available that include a single (P.falciparum or pan-specific) test line. Pan-specific aldolase may also be appropriate, but more evidence ofduration of persistence is needed and sensitivity may be lower.

55life) will be of great importance, compared to storage and use in temperature-controlledlaboratories. If RDTs are to be used by isolated volunteer health workers, an easy-to-use format will be of greater importance than in a laboratory setting.

There is unpublished evidence that HRP2-detecting RDT are more stable than pLDH-detecting RDT.f There is some unpublished evidence that the aldolase band on a comboRDT is less stable than the HRP2-detecting band, and similar to pLDH-detecting bands.gThere is a need for more data to compare the stability of pLDH and aldolase.

There is fairly consistent evidence that HRP2-detecting RDT are normally more sensitivethan falciparum-specific pLDH RDT (Jelinek, Grobusch et al. 1999; Lee, Aw et al. 1999;Ricci, Viani et al. 2000; Iqbal, Hira et al. 2001; Labbe, Pillai et al. 2001; Rubio, Buhigaset al. 2001; Tarimo, Minjas et al. 2001; Craig, Bredenkamp et al. 2002; Huong, Davis etal. 2002; Iqbal, Khalid et al. 2002; Mason, Kawamoto et al. 2002).h However, thesensitivity of HRP2 detection varies between P. falciparum isolates due to antigenvariation and in some regions pLDH could potentially be of similar sensitivity (Baker,McCarthy et al. 2005).

Published field data indicates that the pLDH antibodies used in the pLDH-detecting‘Optimal’ test variations are more sensitive than the aldolase antibodies used in thealdolase-detecting ‘ICT’ test variations (Cho, Kim et al. 2001; Huong, Davis et al. 2002;Mason, Kawamoto et al. 2002). Other products now have different pLDH and aldolasemonoclonal antibodies combined with HRP2, and the relative sensitivity of these isnot well tested.

There is a need for more data on pLDH and aldolase antigen variation, and thegeographical extent of HRP2 variation.

Some RDT products include a pan-specific band only. In view of the above, these arelikely to have lower sensitivity for P. falciparum than HRP2-detecting tests. They havesome price advantage as less monoclonal antibodies are required, but are probablyonly well suited to areas with only non-falciparum malaria as the implications ofoverlooking a low-density P. falciparum infection may be serious.

f Unpublished multi-centre study coordinated by WHO involving commercially-available products. Two pLDHdetecting products consistently lost capacity to detect P. falciparum standardized cryo-preserved samplesfaster than two HRP2-detecting products when stored at at 60 oC, 45oC, and 35oC, to an extent which couldlimit shelf-life in uncontrolled storage conditions. All the RDTs utilized different sets of monoclonal antigens. Athird HRP2-detecting RDT failed at all storage intervals including baseline testing, but was later shown to havefaults in cassette design preventing antibody-antigen contact.

g Unpublished data from Research Institute for Tropical Medicine, Alabang, Mintinpupa City, Philippines, ofaccelerated temperature stability testing of a small number of commercially-available RDTs.

h 8 of the 11 studies listed indicate greater sensitivity of HRP2-detecting RDT, in some cases to a large degree,and including all that were performed in the field in endemic countries. It is possible that the greater temperaturestability of HRP2-detecting RDT contributed to these results.

56 3.3 Implications

A combined RDT including detection of HRP2 is likely to retain sensitivity for P.falciparum longer than an RDT detecting falciparum-specific pLDH, at ambient endemiccountry conditions. However, the pan-specific line (aldolase or pLDH) will deterioratefaster than the HRP2 line so an HRP2 combined RDT may have reduced ability todetect non-falciparum infections while retaining good sensitivity for P. falciparum.As P. falciparum infection is potentially more severe, it can therefore be argued that inremote situations in areas where combined tests are indicated, RDT including HRP2detection (HRP2/pLDH or HRP2/aldolase) are preferable to those relying on pLDHdetection alone.

It should be noted that evidence is lacking on many currently available products, soconsiderable variation from the above general statements may occur with some RDTs.

3.4 Cost and quality

RDTs can be purchased directly from most manufacturers, and this usually allowsprocurement of large batches at considerably lower cost than purchase throughdistributors.

Cassette format RDTs are usually 10–20% higher priced than dipstick RDTs, thoughthe latter sometimes require the procurer to provide wells, resulting in a similar totalcost. Cassette RDTs when used by health workers are probably more reliable thandipstick RDTs, and so may provide savings through improved diagnosis.i

Combined cassette RDTs may be obtained from manufacturers at prices per test ofUS$ 0.90–1.30 and upward. Prices vary with time, and with the number of unitspurchased.

WHO experience indicates that quality is not directly correlated with higher price. WHOrecommends that all large purchases of RDT be checked for sensitivity before use andmonitored at least 3 monthly during use. Evidence of good manufacturing practice islikely to indicate more reliable products. Advice on procurement and quality controlare found elsewhere (WHO 2004b; WHO/WPRO 2005).

i Unpublished report of WHO, QAP, RITM and CMPE at http://www.wpro.who.int/RDT/docs/Developing_and_testing_an_RDT_Job_Aid.pdf

574. Conclusions

• HRP2-detecting tests are likely to have greater sensitivity than pLDH- and aldolase-detecting tests for detection of current P. falciparum infection in most environments.

• pLDH and aldolase-detecting RDTs are likely to be less temperature stable thanHRP2, and will therefore lose sensitivity more rapidly in uncontrolled storage.

• RDTs detecting non-falciparum species offer little advantage in terms of casemanagement in areas where P. falciparum predominates and non-falciparum speciesnearly always occur as co-infections. In such situations, particularly where tests willbe stored without temperature control, RDTs detecting HRP2 offer advantages interms of sensitivity, stability, cost and format.

• When stored and used in temperature-controlled environments, pLDH-detecting RDTsare likely to have greater sensitivity than aldolase in detection of non-falciparuminfections (more recently available antibodies may differ).

• pLDH detection has advantages over HRP2 detection for monitoring of effectivenessof treatment. Aldolase may have similar properties (Eisen and Saul, 2000).Microscopy is generally the preferred tool for this purpose.

• Cassettes are preferable to dipsticks in remote areas due to simplicity of preparation

• Cassette tests detecting both P. falciparum and non-falciparum parasites can beobtained for prices ranging from US$ 0.90–1.30 per test, and there is no clearadvantage in higher cost RDTs. Most products can be ordered directly from themanufacturers.

• All large batches of RDT should be tested after procurement and monitoredthroughout shelf-life. Evidence of good manufacturing practice and good fieldexperience should be considered during procurement. Standard specifications forprocurement should be followed (WHO 2004b; WHO/WPRO 2005).

List of HRP2-only cassette tests

Numerous products are on the market. Price varies from about US$ 0.65 upward.

Note: This list does not imply any WHO endorsement of any RDT product, or results oftesting, or rating or certification of any product whether or not included on this list.

Product name Manufacturer

Palutop AlldiagdBest Malaria Rapid Test AmeritekMalaria Pf-only Rapid Test Biotech Trading PartnersRapimal CellabsImmu-Sure Malaria Brittney

58Product name Manufacturer

Malaria Test Bio-Analytics C.A.Core Malaria Pf Core DiagnosticsMalar-Check Pf CumberlandAssure Malaria Pf GenelabsSmart Check Malaria GlobaleMedHexagon Malaria Human GmbhKatQuick KAT MedicalMakroMAL Makro MedicalMalaria Pf test Merlin LabsVisitect malaria Pf Omega DiagnosticsParacheck Orchid Biomedical SystemsICT Malaria Pf R&R MarketingParaHIT Span DiagnosticsUni-Gold Malaria Pf Trinity BiotechFirstSign Malaria Pf UnimedMalaria Pf Vision Biotech

Contact details of some manufacturers can be found at www.wpro.who.int/rdt

List of HRP2-based P. falciparum/pan-species cassette tests

Note: This list does not imply any WHO endorsement of any RDT product, or results oftesting, or rating or certification of any product whether or not included on this list.

Manufacturer Product

CASSETTE TESTSHRP2/aldolase

CortezCortezCortezCortezCortez OneStep onestep@rapidtest.com – 23961 Craftsman Road,RapiCard Suite E/F, Calabasas, CA 91302 USAInstatest Tel. +1 818 591 3030 – Fax: +1 818 591 8383

R&RR&RR&RR&RR&R ICT Malaria russellag@icon.co.za – P.O. Box 912, Noordhoek 7985,Pf/pan Cape Town, South Africa Tel/Fax: +27 21 789 2979

SpanSpanSpanSpanSpan ParaHIT-TOTAL spand@vsnl.com – export@spandiag.comRd No.6-G, Udhyognagar, Udhna, 394210 (Surat) IndiaTel. + 91 261 227 7211/7143Fax: +91 261 227 9319/266 5757

MerlinMerlinMerlinMerlinMerlin Malaria bhudak@merlinlabs.com – Merlin Labs, Inc., 6084 CorteCombo Test Del Cedro, Carlsbad, CA 92009, USA

Tel. 760 804 1782 – Fax: 760 804 3885

59HRP2/pLDH

OmegaOmegaOmegaOmegaOmega VISITECT odl@omegadiagnostics.co.uk – Omega House, HillfootsMalaria Combo Business Village, Alva, Clacks, FK12 5DQ Scotland, UK

Tel. +44 1259 763030 – Fax: +44 1259 761853

ZephyrZephyrZephyrZephyrZephyr ParaScreen zephyr@tulipgroup.com – Plot Nos M46/47, Phase IIIB,PAN/Pf Verna Industrial Estate, Verna Goa 403 722, India

Tel. +91 832 288 7023/7025Fax: +91 832 288 7024/2139

UnimedUnimedUnimedUnimedUnimed unimedinc@aol.com – 1101 Grandview Drive,South San Francisco, CA 94080, USATel. (650) 588 7158 – Fax: (650) 588 7159

CoreCoreCoreCoreCore Core Malaria sales@corediag.com – Aspect Court Rd, 4 Temple RowPan-Pf Birmingham B2 5HG, UK

Tel. +44 121 609 4720 – Fax: +44 121 609 4721

CARD TESTSHRP2/aldolase card

Binax* NOW-Malaria brian.conibere@unipath.com – 217 Read Street, Portland(Card test) ME 04103 USA

Tel. +1 207 772 3988 ext.107 – Fax: +1 207 871 5751

DIPSTICK-CASSETTE HYBRIDS

Diamed Optimal IT p.jacquier@diamed.ch – parasitology@diamed.chDiamed SA, 1785, Cressier-sur-Morat, SwitzerlandTel. +41 26 674 5111 – Fax: +41 26 674 5145

Standard SD Bioline johnhkim@standardia.com – 575-34, Pajang-dong,Diagnostics Jangan-ku, Suwon-si, Kyonggi-do, Korea, 440-290

Tel. +82 31 258 2994 – Fax: +82 31 258 2995

Target Antigen not specified

Sanitoets (Pan) info@anytestkits.comSouth Africa – Fax: + 27 12 362 7736

Alldiag Pan lamy@alldiag.com – 2, rue Ettoré Bugatti – BP 667038 Strasbourg Cedex 2 FranceTel. 33 3 88 78 80 88 – Fax: 33 3 88 78 76 78

Notes• Always specify format (i.e. cassette) when ordering. Many manufacturers produce dipsticks by the

same name.• Supply. Most manufacturers of cheaper tests can rapidly increase capacity.• Tests detecting P. falciparum and P. vivax (species-specific) pLDH are marketed by Zephyr, Unimed,

and Core. They are at higher price than the tests using pan-specific pLDH. Falciparum/vivax/pan testsare also available from these companies.

• All manufacturers above (except Cortez, Diamed, and Standard Diagnostics) produce cheaper cassettetests detecting P. falciparum only. Multiple other companies also produce these (www.wpro.who.int/rdt).Some manufacturers produce aldolase-only tests.

• Other tests are available in dipstick format only (e.g. Premier Medical Corporation First responseMalaria Pf/Pv).

60 References

BakerJ, McCarthy J et al. (2005). Genetic Diversity of Plasmodium falciparum Histidine-Rich Protein 2 and Its Effect on the Performance of PfHRP2-Based Rapid DiagnosticTests. Journal of Infectious Diseases in press.

Cho D, Kim KH et al. (2001). Evaluation of rapid immunocapture assays for diagnosisof Plasmodium vivax in Korea. Parasitol Res 8888877777(6):445–448.

Craig MH, Bredenkamp BL et al. (2002). Field and laboratory comparative evaluationof ten rapid malaria diagnostic tests. Trans R Soc Trop Med Hyg 9696969696(3):258–265.

Eisen DP and Saul A. Disappearance of pan-malarial antigen reactivity using the ICTMalaria P.f/P.v kit parallels decline of patent parasitaemia as shown by microscopy.Trans R Soc Trop Med Hyg, 2000; 9999944444(2):169–170.

Hanschei T. Diagnosis of malaria: a review of alternatives to conventional microscopy.Clin Lab Haematol, 1999; 2222211111(4):235–245.

Huong, NM, Davis TM et al. Comparison of three antigen detection methods fordiagnosis and therapeutic monitoring of malaria: a field study from southern Vietnam.Trop Med Int Health, 2002; 77777(4):304–308.

Iqbal J, Hira PR et al. Diagnosis of imported malaria by Plasmodium lactatedehydrogenase (pLDH) and histidine-rich protein 2 (PfHRP-2)-based immunocaptureassays. Am J Trop Med Hyg, 2001; 6666644444(1-2): 20–23.

Iqbal J, Khalid N et al. “Comparison of two commercial assays with expert microscopyfor confirmation of symptomatically diagnosed malaria.” J Clin Microbiol, 2002; 4040404040(12):4675–4678.

Jelinek T, Grobusch MP et al. Sensitivity and specificity of dipstick tests for rapiddiagnosis of malaria in nonimmune travelers. J Clin Microbiol, 1999; 3333377777(3):721–723.

Labbe AC, Pillai DR et al. “The performance and utility of rapid diagnostic assays forPlasmodium falciparum malaria in a field setting in the Lao People’s DemocraticRepublic.” Ann Trop Med Parasitol, 2001; 9595959595(7):671–617.

Lee M A, Aw LT et al. A comparison of antigen dipstick assays with polymerase chainreaction (PCR) technique and blood film examination in the rapid diagnosis of malaria.Ann Acad Med Singapore, 1999; 2828282828(4):498–501.

Makler MT, Palmer CJ et al. A review of practical techniques for the diagnosis of malaria.Ann Trop Med Parasitol, 1998; 9292929292(4):419–433.

Mason DP, Kawamoto F et al. A comparison of two rapid field immunochromatographictests to expert microscopy in the diagnosis of malaria. Acta Trop, 2002; 8282828282(1):51–59.

Moody A. “Rapid diagnostic tests for malaria parasites.” Clin Microbiol Rev, 2002;1515151515(1):66–78.

Ricci L, Viani I et al. Evaluation of OptiMAL Assay test to detect imported malaria inItaly. New Microbiol, 2000; 2323232323(4):391–398.

61Rubio JM, Buhigas I et al. Limited level of accuracy provided by available rapid diagnosistests for malaria enhances the need for PCR-based reference laboratories. J ClinMicrobiol, 2001; 3939393939(7):2736–2737.

Tarimo DS, Minjas JN et al. Malaria diagnosis and treatment under the strategy of theintegrated management of childhood illness (IMCI): relevance of laboratory supportfrom the rapid immunochromatographic tests of ICT Malaria P.f/P.v and OptiMal. AnnTrop Med Parasitol, 2001; 9595959595(5):437–444.

New Perspectives: Malaria Diagnosis. Report of a joint WHO/USAID informal consultation25–27 October 1999. Geneva, World Health Organization, 2000.

Malaria Rapid Diagnosis: Making it Work. Meeting report 20–23 January 2003. Manila,World Health Organization, 2003.

Malaria epidemics: forecasting, prevention, early detection and control. From policy topractice. Report of an informal consultation, Leysin, Switzerland, 8–10 December, 2003.Geneva, World Health Organization, 2004a.

The Use of Malaria Rapid Diagnostic Tests. Manila, World Health Organization-WPRO,2004b.

Malaria Rapid Diagnostic Tests: Making Rapid Diagnosis Work. World Health Organization/Regional Office for the Western Pacific, 2005. www.wpro.who.int/rdt/

62 Annex 7

Exercises and answers

You can find elements to check your answers at the end of the exercises, but first try toanswer on your own.

Question 1As an NPO assigned to assist the MOH in the country, how would you advise thegovernment to approach a comprehensive malaria control strategy? (Think of planningfor malaria control as a first step: setting objectives for malaria control, targeting differentpopulations and epidemiological factors.)

Question 2List three factors in each category (epidemiological, operational and socio-economic)that you would take into account while planning national malaria control, and discussyour choice.

Question 3Participants divide into two groups and facilitators assist in brainstorming. Eachquestion should not take more than 5 minutes. Each group appoints a reporter topresent its views to the plenary.

3.1. Scenario – Country A

Plasmodium species:Malaria endemicity:Current first-line drug:Second-line treatment:

Drug resistance:

85% P. falciparum, 15% P. ovale and P. malariaeMainly stable transmissionChloroquineSulfadoxine–pyrimethamine (SP)

••••• 111119999978 and 178 and 178 and 178 and 178 and 1980,980,980,980,980, WHO missions found no evidence ofchloroquine resistance

••••• 19831983198319831983 increasing slide-confirmed chloroquine-resistance witha rise in admissions for malaria

••••• 19841984198419841984 six sentinel sites established across the country; 7-dayWHO in vivo test used to evaluate choloroquine efficacy

••••• 11111985–1985–1985–1985–1985–1999999999911111,,,,, % overall hospital deaths occurring in under5s increased from 10% to 20%

••••• 1990,1990,1990,1990,1990, parasitological resistance to chloroquine increased toabout 83% in under 5s; RIII resistance increased from 8% in1984 to 26% in 1990

63• 1• 1• 1• 1• 1999999999911111, , , , , SP to replace chloroquine as first-line drug.Severe malaria: quinineIntermittent preventive treatment (IPT) in pregnancy: SP

• 1993, • 1993, • 1993, • 1993, • 1993, new policy launched; ministry of health reportsreduction in malaria-linked deaths and hospital admissions;Regular SP efficacy monitoring continues

• R• R• R• R• Recentlyecentlyecentlyecentlyecently, , , , , with same drugs, SP parasitological failure rateabout 25%; treatment failure rate (early or late) increasedfrom <5% (1991) to national coverage of 13% (11–17%).

Decisions

16%54%60%7.6% of GDPGovernment 60%; donors 40%DecentralizedIrrigation, seasonal migration from highlands 60 000 fromneighbouring malaria-free countrycurrently at war

HIV/AIDS prevalence:Pop. below poverty line:Health coverage:Health expenditure:Financing health care:Health system:Developmentalactivities:Refugees:

Tasks

3.1.1 State objectives for malaria control in this country.

3.1.2. Recommend preventive, diagnosis and treatment measures for population and forminorities.

3.1.3. State possible reasons for delay between decision for change (1991) and launch of newpolicy (1993).

3.1.4. Treatment failure rate increased to 13% and parasitological failure rate to 25%; do yourecommend changes or continue using the first-line drug? If in favour of change, would do youconsider treatment failure or parasitological failure as a basis for your change to a new drug?Why?

3.1.5. Discuss the impact of shifting from chloroquine monotherapy to SP monotherapy onfuture utility of some artemisinin-based combinations therapies, in particular SP plusartesunate?

3.1.6. Suggest viable alternative drugs bearing in mind cost and epidemiological situation.

3.1.7. Would there be any form of epidemics in this country? If yes, which strata?

3.1.8. List indicators for the country to measure progress and outcome.

3.1.9. What special group would be your major concern with the SP treatment regimen?

64 3.2. Scenario – Country B

P. vivax 30–40% and P. falciparum 60–70%Mainly low with more of seasonal malaria transmission,2 provinces have stable transmissionCholoroquineSPQuinineChloroquine resistance first detected in 1986In vivo studies 1991–1996 show increasing resistancemethodological variations make comparisons difficultStandardized in vivo studies at representative sites1997–1998 (overall treatment failure rate with chloroquinefor P. f. 65%, SP nearly 32.8%.Low efficacy of SP against P. v.Resistance to amodiaquine 35%.

Plasmodium species:Malaria pattern:

Current first-line drug:Second-line treatment:Severe malaria:Drug resistance:

7.3%45%50%10%4.6% of GDP (per capita: US$ 4)Government 55%; donors 42.5%Decentralized1%

HIV/AIDS prevalence:Pop. below poverty line:Health coverage:Nomadic population:Health expenditure:Financing health care:Health system:ITN coverage:

The country faces heavy loads of malaria cases Sept.–Dec. with high mortality.

Tasks

3.2.1. State the primary objectives of the malaria programme in this country.

3.2.2. State which of the following antimalarial regimes you would propose as viable andfeasible first-line drug (you may choose one or more)? Assume cost is not a major issue buttry to minimize costs. Justify your suggestion.i. Continue with chloroquine for P. vivax.ii. Replace chloroquine by SP as first-line instead of using SP as a second-line treatment.iii. Alternate use of SP and chloroquine in different seasons.iv. Use ACT as first-line treatment for P. falciparum.v. Use amodiaquine as first-line treatment.

3.2.3. What age group would you target in your prevention and treatment strategy? Why?

3.2.4. Is malaria life-threatening to pregnant women here? What would be your strategy?

653.2.5. In August, the local government received conflicting opinions on whether to use ITNs orIRS or other measures. State your advice and how would you support the MOH and partners inpreventing epidemics. Discuss the primary objective of the interventions.

3.2.6. Is confirmatory diagnosis needed here? If yes, design implementation?

3.2.7. Would there by any form of epidemics in the country? If yes, in which population?

3.2.8. Outline indicators for the country to measure progress and outcome. With regard to IRSdo you think data are obtainable from population or programme level?

3.2.9. What special group would be your major concern with the SP treatment regimen?

ELEMENTS OF ANSWERS FOR THE EXERCISESELEMENTS OF ANSWERS FOR THE EXERCISESELEMENTS OF ANSWERS FOR THE EXERCISESELEMENTS OF ANSWERS FOR THE EXERCISESELEMENTS OF ANSWERS FOR THE EXERCISES(Have you tried answering on your own?)

Question 1As an NPO assigned to assist the MOH in the country, how would you advise thegovernment to approach a comprehensive malaria control strategy? (Think ofplanning for malaria control as a first step: setting objectives of malaria control,targeting different populations and epidemiological factors.)

Answer to question 1The NPO should propose that the MOH develops a strategic plan based on recentassessments. Approaches should include epidemiological stratification to take differentpopulations at risk into account. Planning should start by stratification of the malariaproblem into areas of stable or unstable transmission, developmental areas, refugeeareas, urban, rural, remote/inaccessible areas, etc. This would help strategize preventiveand treatment measures, logistics and supplies for the different strata. Planning mustinclude budgeting, defining indicators, how to measure them, and coordination of partners.

Question 2List three factors in each category (epidemiological, operational and socio-economic) that you would take into account while planning national malariacontrol and discuss your choice.

Answer to question 2

Epidemiological criteria• Initial levels of endemicity• ·Present situation, including levels of endemicity, incidence, morbidity and mortality,

seasonal distribution• ·Parasite species accountable for most infections

66·• Distribution and density of the most important vector species·• Potential instability, or likelihood of change in endemicity regardless of control

measures·• Rate of resurgence in situations where malaria had earlier been reduced)·• Degree and importance of parasite resistance to the available malaria drugs·• Distribution of insecticide resistance for each vector species·• Basic data (hydrological, climatological, topographical and ecological zones)·• Ecological interventions likely to affect the malarial potential of the area (urbanization,

irrigation, deforestation)

Operational criteria• ·Case detection and treatment rate• ·Coverage and impact of vector control measures·• Impact of antiparasitic measures·• Accessibility to the area of operation·• Per capita cost of each type of intervention·• Coverage of health services, primary health care and malaria-related care·• Structure of logistic and administrative services support·• Plans for the improvement and expansion of malaria control operations

Socioeconomic criteria·• Impact on the various socioeconomic groups·• Seasonal migrations in relation to local transmission·• Availability and quality of health services·• Major economic activities, national development plans, geographical areas targeted

for priority intervention·• Potential resources e.g. personnel, facilities, infrastructures, communications, and

their geographical distribution• Political or civil unrest with population displacement, breakdown of health facilities

Question 3Participants divide into two groups and facilitators assist in brainstorming. Eachquestion should not take more than 5 minutes. Each group appoints a reporterto present its views to the plenary.

3.1. Scenario – Country A

Answers to question 3.13.1.1 State objectives for malaria control in this country

Primary objectives for country A (stable transmission).Objective 1: Reduce disease burden and mortality among children under 5sObjective 2: Prevent and reduce severe malaria and mortality in migrant workers/refugees and their dependants

673.1.1 State objectives for malaria control in this country

Primary objectives for country A (stable transmission).Objective 1: Reduce disease burden and mortality among children under 5sObjective 2: Prevent and reduce severe malaria and mortality in migrant workers/refugees and their dependants

3.1.2. Recommend preventive, diagnostic and treatment measures for populationand minorities

(Majority of the population with high immunity)Prevention: ITNs for under 5s and pregnant women, IPT for pregnant womenDiagnosis: Clinical symptoms-fever where lab confirmation is not possibleTreatment: New effective treatment targeting under 5s and pregnant women.

(Developmental area-migrant workers from highlands)Prevention: ITNs targeting all age groupsDiagnosis: Clinical symptoms: feverTreatment: New effective treatment targeting all migrants (all at risk)

(Refugee population)Prevention: ITNs, other insecticide-treated materials, environmental controlDiagnosis: Clinical symptoms: feverTreatment: New effective treatment targeting all refugees (all at risk)

3.1.3. State possible reasons for delay between decision for change (1991) and launchof new policy (1993)

Decisions for change 1991, new policy officially launched 1993. Reasons for delaycould be time taken for consensus-building and information dissemination amongkey groups, production of treatment guidelines, education and communicationmaterials, procurement of adequate stocks of the new drugs.

3.1.4. Treatment failure rate increased to 13% and parasitological failure rate to25%; do you recommend changes or continue using the first-line drug? If in favour ofchange, would do you consider treatment failure or parasitological failure as a basisfor your change to a new drug? Why?

With increased treatment and parasitological failure in areas of high malariatransmission, treatment failures to be considered for decision-making, in this caseat the AlerAlerAlerAlerAlert periodt periodt periodt periodt period (analysis of SP resistance and selection of alternative drugs).

3.1.5. Discuss the impact of shifting from chloroquine monotherapy to SP monotherapyon future utility of some ACTs, in particular SP plus Artesunate?

With a shift from choloroquine to SP monotherapy, resistance level to SP wouldrapidly increase and affect the future possible use of ACT (e.g. artemisinin + SP)

683.1.6. Suggest viable alternative drugs bearing in mind cost and epidemiologicalsituation

If country can afford and sustain combination therapies: artemether–lumefantrine;area has high malaria transmission, shows resistance to chloroquine and moderateresistance to SP (likely to increase). Drugs locally available.

3.1.7. Would there be any form of epidemics in this country? If yes, which strata?

Possible epidemics among refugees and also among migrants, not among locallong-term residents.

3.1.8. Outline indicators for the country to measure progress and outcome.

Possible indicatorsInsecticide-treated nets• % of households with at least one ITN• % of children under five who slept under an ITN the previous night.

Prompt access to effective treatment (children under 5s)• % of under fives with fever in past two weeks who received antimalarial treatmentaccording to national policy within 24 hours of fever onset.

Prevention and control among pregnant women• % of women who receive IPT to prevent malaria during their latest pregnancy• % of pregnant women who slept under ITN the previous night.

3.1.9. What special group would be your major concern with the SP treatment regimen?

HIV prevalence in country A is high, treatment of concomitant malaria infectionwith SP could result in increased frequency of sulfa-drug associated toxicity. Closeobservation of clinical outcomes and care needed for such patients.

3.2. Scenario – Country BAnswers to question 3.2

3.2.1. State the primary objectives of the malaria programme in these circumstances:

Primary objectives for country B would be to aim for what a country with lowtransmission needs to do.

Objective 1: Reduce severe morbidity and mortality for malaria in all age groupsand reduce occurrence of epidemicsObjective 2: Reduce disease burden and mortality in under 5s and preventmorbidity in pregnant women.

693.2.2. Which of the following antimalarial regimes would you propose as viable andfeasible first-line drug (you may choose one or more)? Assume cost is not an issue buttry to minimize costs. Justify your suggestion.

i. Continue with chloroquine for P. vivaxii. Replace chloroquine by sulfadoxine-pyrimethamine as first-line instead of usingSP as a second-line treatmentiii. Alternate use of SP and chloroquine in different seasonsiv. Use ACT as first-line treatment for P. falciparumv. Use amodiaquine as first-line treatment

The most viable solution would be joint recourse to alternative (i and iv) accordingto species diagnosis..... Alternative (i) alone, i.e. continuing with chloroquine is notacceptable given the resistance level (65%).

Alternative (ii) (replacing chloroquine with SP) not acceptable – low SP efficacy onPave.

Alternative (iii) (use of SP and chloroquine in different seasons) not operationallypossible and despite seasonal variations there remains a substantial percentage ofcase mixing from either parasite

Alternative (v) (change first-line from chloroquine to amodiaquine) also not plausiblebecause of high resistance to amodiaquine (35%).

3.2.3. What age group would you target in your prevention and treatment strategy?Why?

Annual inoculation rate usually low (<1–8 per person per year) and so is parasitaemia;population does not develop adequate immunity – all age-groups must be equallycovered in the prevention and treatment strategy.

3.2.4. Is malaria life-threatening to pregnant women here? What would be yourstrategy?

Malaria is life-threatening to pregnant women in this situation. The strategy includesIPT with SP, use of ITNs and case management.

3.2.5. In August, the local government received conflicting opinions on whether touse ITNs or IRS or other measures. State your advice and how would you support theMOH and partners in preventing epidemics. Discuss the primary objective of theinterventions

Epidemic expected to start in September; immediate application of IRS in high-riskareas or districts is useful. ITNs not useful here as coverage low and behaviour ofusing nets not well established. The newly adopted drugs should be immediately

70deployed to peripheral health facilities and communities should be mobilized toincrease awareness, with involvement of the media, local authorities and partners.

3.2.6. Is confirmatory diagnosis needed here? If yes, design implementation?

Country is a low transmission or epidemic area: confirmatory diagnosis will be costeffective by avoiding unnecessary treatments of negatives. Planning for diagnosisshould include the use of microscopy in health facilities with trained personnel andresources. In remote communities or peripheral health facilities use of RDTs withtraining will allow rational drug use.

3.2.7. Would there by any form of epidemics in the country? If yes, in which population?

Yes, all age groups; less likely in the two provinces with stable transmission.

3.2.8. Outline indicators for the country to measure progress and outcome. With regardto IRS do you think data are obtainable from population or programme level?Indicators include:

Prompt access to effective treatmentPercentage of all cases with fever in last 2 weeks who received antimalarial treatmentaccording to national policy within 24 hours of fever onset.

Prevention and control among pregnant womenIPT may not be a good indicator in low transmission areas; focus should be tominimize severe cases.

Percentage of pregnant women who slept under ITN the previous night.

Among indicators, the monitoring of IRS should come from the programme dataand must include all factors related to IRS (e.g. coverage and number of householdsappropriately sprayed).

3.2.9. What special group would be your major concern with the SP treatment regimen?

HIV prevalence in country A is high, treatment of concomitant malaria infectionwith SP could result in increased frequency of sulfa-drug associated toxicity. Closeobservation of clinical outcomes and care needed for such patients.

71