Meningococcal Meningitis

Presented by Dr Nazrul Islam AGMC Agartala

Meningococcal Infections

• Neisseria meningitidis (meningococcus)

• Gram negative, diplococcus bean shaped

• Found only in man

13 serogroups by surface capsular polysaccharide

A, B, C, Y and W frequent isolates

from meningococcal disease Other groups isolated from carriers

Meningococcal Infections

• Common in temperate and tropical climates

• Nov. to March

• Carriage rates: healthy children upto 10%

• Transmitted via contact with respiratory secretions

Meningococcal Infections

Neisseria meningitidis

DISESES CAUSED BY MENINGOCOCCUS

• Meningitis – 50%• Bacteremia – 35%-40% • Pneumonia – 9%• Other focal infection like Myocardium Pericardium Joints Eye Peritonium Sinuses Middle ear Urethritis Cervicitis Vulvovaginitis Orchitis

Meningococcal InfectionsDisease may occur following

exposure to carriers or infected patients within the family, day care and military camps

Occurs most frequent:(< 5 yrs old )Peak attack rate : 6-12 months old

2nd peak attack rate: 15-19 yrs of age

1Pollard. In: Harrison's Principles of Internal Medicine. 18th ed. 2012;chapter 143; 2Bilukha. Pediatr Infect Dis J. 2007;26(5); 3MacNeil. In: Manual for the Surveillance of Vaccine-Preventable Diseases. 5th ed. 2012; 4Liphaus. Enferm Infecc Microbiol Clin. 2013;31(2)

Impaired immune system1,2/lack of antibodies1

Exposure through close contact with infected person or the live bacteria

Travelers to endemic areas3

Immunocompromised2

Infants, children1,2 Caregivers3

Personnel working with N. meningitidis2,3

Crowding1,3,4

(students, military, Hajj, oil refineries)

At-Risk Populations

Incidence Rates (cases/100,000 inhabitants) for Latin America

Countries of Region 1, 1980–2011

1Safadi. First Regional Meningococcal Symposium 2012; March 19-20, 2012, Buenos Aires, Argentina.

Argentina

ChileBrazil

Uruguay

80–81

2010–201182–83

84–8586–87

88–8990–91

92–9394–95

96–9798–99

2000–2001

2002–2003

2004–2005

2006–2007

2008–20090

1

2

3

4

5

6

7

8

A. Greenbaum et al. Global Estimates of Meningococcal Meningitis Case Fatality Ratios by Region for Children and Adults. Idweek 1164, San Diego, Oct 2015

Studies conducted between 1980 to 2014 & n≥20 cases

< 5 yrs age

20-64 yrs age

Asia: CFR of Meningococcal Meningitis

• Disease is endemic in India and several major epidemics

reported across India especially from Delhi and surrounding

districts

• Disease occurs in dry season

• Surviellance:– Notifiable disease under Integrated Disease Surveillance Programme (IDSP)– Part of IAP ‘ID Surv’ program under acute bacterial meningitis

• Serogroup A majorly responsible for both endemic disease

and epidemics in India

• Some prevalence of disease due to Serogroup C, B & W also

reported. 1. D. Sinclair et al. Tropical Medicine and International Health 2010;15(12):1421-35 2. Manchanda V et al. Indian J Med Microbiol 2006;24(1): 7-19 3. Aggarwal M. Indian Pediatrics 2013;50: 601-3

Epidemiology in India

Year Location Suspected cases

Deaths

1966-67 Delhi 616 1291985-88 Delhi 6133 7991985-88 Maharashtra 15731985-87 Surat 197 342005-09 Delhi 1725 1082008 Meghalaya ~2000 ~ 2002009 Tripura ~ 200 ~50

D. Sinclair et al. Tropical Medicine and International Health 2010;15(12):1421-35; V Manchanda et al. Indian J Med Microbiol 2006;24(1): 7-19; CD Alert. NCDC.DGHS.November 2009.13(3)

Prevalence & Distribution of Neisseria meningitidis isolates during epidemic periods

National Health Profile , India 2006-2015, Central Bureau of Health Intelligence. Available at http://cbhidghs.nic.in

Meningococcal Meningitis Cases & Deaths in India

Out break of Tripura 22nd Jan 2009 from Dhalai dist 1st report ( Chawmanu block) Confirm on 7th Jan 2009 Last case Aug. 2009(peak May 2009) Confirmed cases was 285 Deaths 62. CF 22%

District Population (L)

No. of cases Attack rate/ 1 L

No. of death Case fatality rate

South 7.7 14 1.8 6 43

West 16.4 13 0.8 3 23

North 5.8 35 6 7 20

Dhalai 3.6 223 6.1 46 21

Tripura 33.7 285 8.4 62 22

Indian journal of Medical microbiology, Jan –March 2011

Pathogenesis/Pathology

Meningococci colonize the nasopharynx penetrate mucosal surface transported by leukocytes to blood stream hematogenous dissemination localizes: heart, CNS, skin, mucous and serous membranes adrenals

ENDOTOXEMIA

Release of IL and TNF

hypotension multi-organ system failure

Diffusevasculitis

*Complement activation

DIC

Haemorrhage and necrosis in any organ bleeding into adrenals in patients with septicemia and shock

Waterhouse- Friderichsen syndrome

IMD is difficult to diagnose and rapidly lethal

• Flu-like nature of early symptoms makes a definitive diagnosis challenging1

• Rapid progression, with death in as little as 24 hours1,2

1Thompson et al. Lancet. 2006;367(9508); 2Branco et al. J Pediatr (Rio J). 2007;83(2 suppl)

12–15 Hours1,2

Characteristic15–~24 Hours1,2

Late4–8 Hours1,2

NonspecificFever, irritability, nausea or vomiting,

drowsiness, poor appetite, sore throat, coryza, general aches

Hemorrhagic rash, neck stiffness,photophobia

Confusion or delirium, seizure, unconsciousness;

possible deathHospital admission at median of ~19

hours1

• Meningococcal meningitis clinically indistinguishable from meningitis

due to other bacteria. Non-blanching petechial rash is present in only

a few cases. 1.

• In a study of 110 cases of IMD from a tertiary care hospital in

Meghalaya from Jan 08 –June 09 during an outbreak 2

• In the same study, meningococcal meningitis was seen in 61.8% of

cases, meningococcemia in 20 %. 18.2% had both.

1. Nelson text book of Pediatrics. 19th Ed. 2. Hazarika RD et al, Indian J Pediatr 2012 doi:10.1007/s12098-012-0855-0

100

56.4 53.6

23.69.1 6.4

0

50

100

Fever Headache Vomiting Rashes Seizures Deaths

Clinical profile of 110 cases of IMD

%

Rash is not so common in the absence of fulminant meningococcaemia

Features Indicating Bad Prognosis

• (+) petechial < 12 hrs prior to admission• (+) hypotension• absence of meningitis• WBC < 10,000/mm3• ESR < 10 mm/hr.

Interpretation: (+) 3 or > features: 90% mortality > 2 features; 9% mortality

Other Poor Prognostic Sign

• Rapid progression of petechia to ecchymoses

or purpura • Wakefulness• Poor skin perfusion• respiratory distress• thrombocytopenia• advanced age

DiagnosisMaintain a high index of suspicion

1. Gm stain of petechial scrapings, blood CSF 2. Buffy coat of blood

3. Culture of blood, CSF, petechial scraping, synovial fluid, sputum and other body fluids

4. Antigen detection tests (CSF, urine, serum) latex agglutination, --lack adequate sensitivity and specificity

TreatmentEmpirical 3rd gen Cephalosporin Vancomycin in region with high rate of beta lactum resi. S. pneumoniae

Penicillin G 300,000 u/k/day IV 6 div doses Alternatives : Cefotaxime 200 mg/k/d Ceftriazone 100 mg/k/day

If allergic to B-lactams : Chloramphenicol 75-100 mg/kg dCiprofloxacin 30-40mg/k/dMeropenem 60-120mg/kg/d

ISOLATION: RESPIRATORY isolation until 24hrs after effective antibioticsChemoprophylaxisAll Close contact & lasting >8hrs 7 days before onset of DISEASE• DOC: Rifampicin 10 mg/kg >1 mon, 5 mg/kg in <1

mon• (max 600 mg) q 12hrlyx 2 days

• other drugs: Ceftriaxone Ciprofloxacin Azithromycinmeningococcal vaccine can be used with chemoprophylaxis since 2° cases may occur several weeks later

ComplicationsAdrenal haemorrhage ,waterhouse friderichsen

syndrome Endophthalmatis ArthritisEndocarditis , myocarditis, pericarditisPneumonia, lung abscessPeritonitisRenal infarcts, AKIReactivation of latent herpes simplex virus infection Focal skin infarction(mainly lower limb)Skeletal deformity Deafness Stroke, subdural effusion Ataxia, seizure, blindness, obstuctive hydrocephalus Behavioral and psychosocial complication

Case Series from 10 Children’s Hospitals

Sequelae distribution

amongsurvivors

n = 146

Mortalityn = 159

Percent ofpatients

1.4

2.1

2.8

6.2

9.6

9.6

4.8

21.2

8.0

0 5 10 15 20 25

Amputation

Hemiplegia

Ataxia

Seizures

Skin Necrosis

Hearing Loss

≤11 Years (n=126)

≥11 Years (n=33)

Overall

Kaplan SL, et al. Pediatrics. 2006;118:e979

Percent of patients

27|

Meningococcal Disease: Death and Disability

Prevention

Types of Meningococcal Vaccines

Capsular

Capsular

Non

• Plain Polysaccharide mono, bi, tri or tetravalent0.5 ml SC/IM

• Conjugate vaccines.5ml deep IM• Monovalent A (MenAfrivac)* & C*• Quadrivalent ACWY

A, C, W

Y B

• OMV, OMP Recombinant vaccines

• Not available in India yetCarrier Protein Vaccine

DT Menactra

TT Nimenrix*

Serogroup B antigen has a great similarity with the polysaccharide epitopes of human nerve tissues, it has an immune tolerance to serogroup B capsule1.

1. Halil Özdemir et al. J Pediatr Inf 2014; 8: 178-86

B C Y W

B C Y W

B C

B C Y W A

A WA B W

B Y W

B C B C

A

Global Distribution of epidemic N. meningitidis serogroups1

1. Kate O'Brien. Meningococcal A Meeting of the Strategic Advisory Group of Experts on Immunization (SAGE) Geneva, 22 October 2014

2. D. Sinclair et al. Tropical Medicine and International Health 2010;15(12):1421-353. David S Stephens et al. Epidemic meningitis, meningococcaemia, and Neisseria Meningitidis. Lancet 2007; 369: 2196–210

A C

2

3

• Countries with intermediate or high (2-10 or >10 cases/ 100000

population/year) endemic rates of IMD or with frequent

epidemics introduce appropriate large scale vaccination

programmes

• Countries where disease occurs less frequently (<2 cases/ 100 000 population/year),

vaccination is recommended for defined risk groups:

o Children and young adults residing in closed communities, e.g. boarding

schools or military camps.

o Laboratory workers at risk of exposure to meningococci

o Travellers to high endemic areas

o All individuals suffering from immunodeficiency including asplenia, terminal

complement deficiencies, or advanced HIV infection

WHO recommendations 2011 : meningococcal vaccination

WHO position paper November 2011-11-28

IAP recommendation of MCV Only for certain high risk condition and situation. In children 2yrs or more (3mon or more in risk of

outbreaks/close household contact). Conjugated vaccines preferred over polysaccharide

vaccine due to herd protection and high immunogenicity.

During outbreaks Children with terminal complement defiencies -2

doses primary series 8-12 wks apart in>2yrs and booster every 5 yrs

Children with functional/anatomic asplenia/hyposplenia.

If Splenectomy required Vacctionation should ideally be started 2 wks prior to splenectomy.

Person with HIV Laboratory personal and health workers Student going for study abroad Hajj pilgrims Travelers to African meningitis beltOut break3 or more cases of meningococcal disease have occured in either an organization or a community base outbreak during less then 3 months

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