Meningococcal Meningitis in Africa:Overview

Response strategiesand Current challenges

Eric Bertherat

The disease

What is Meningitis ?What is Meningitis ?

Meningitis is an inflammation of the meninges, the thin lining that surrounds the brain and the spinal cord.

Different origins:– Mechanical: eg. tumours– Infectious: Cerebrospinal fluid (CSF) found infected

• Viruses• Fungi• Parasites• BACTERIA

Bacterial causes of MeningitisBacterial causes of Meningitis

Many bacteria but some are of specific importance in public health:

Streptococcus pneumoniaeHaemophilus influenza

Neisseria meningitidis (Nm)

The meningococcusThe meningococcus

ADNSequence Type ST

Polysaccharideserogroups A, B, C, W135, Y..

Source: IMTSSA, Marseilles

Source WHO CC Oslo

1996-1997: 250 000 cases in the Belt

Spread of Nm A of the ST-5 clonal complex

Meningococcal meningitisMeningococcal meningitis

• Worldwide distribution

• Sporadic, cluster or large epidemic

• 12 serogroups:

•Europe, Americas: B, C

•Asia: A

•Africa: A, C, W135, X

• Africa: 80 % of the burden

Transmission:Transmission:

Strictly a human disease

Direct transmission, person to person

Close and prolonged contact.

Average incubation period 4 days, ranging between 2 and 10 days.

Carried in the pharynx – can overwhelm the body’s defenses allowing infection to spread through the bloodstream and to the meninges.

1-10% of asymptomatic carriers. Up to 10- 25% during epidemics.

SYMPTOMSSYMPTOMS

Stiff neck

( babies opposite: "the rag doll")

High fever

Headaches

Vomiting

The Meningitis BeltThe Meningitis Belt

21 countries and 300 million people at risk

700 000 cases in the past 10 years

10-50 % case fatality rates

10-20 % of survivors suffer permanent brain damage

Impact of meningitis epidemics the example of Burkina Faso, 2006

Impact of meningitis epidemics the example of Burkina Faso, 2006

Duration of the oubreak : 5 months

N° of cases/deaths: 19,000 / 1,500

N° of districts affected: 35

N° of vaccinated: 4 million (3 months)

N° health workers mobilized: 9,000

Direct cost : 4 million USD (5% of total health expenditure)

Current WHO Strategy

How to reduce the burden of meningitis ?The WHO strategy in the Belt

How to reduce the burden of meningitis ?The WHO strategy in the Belt

Based on:

Characteristics of meningitis in the Belt

Technical and financial capacities of the concerned countries

Performance and Availability of vaccines

The Meningitis Belt: a region presenting distinct epidemiological features

The Meningitis Belt: a region presenting distinct epidemiological features

Hyper incidence– 10-150 per 100,000 in non-epidemic yrs

– 250-1000 per 100,000 in epidemic yrs

(Europe-USA: 1-3 per 100,000)

Seasonal increase

Large epidemics during the dry season

N0 1000 2000 Kilometers

Average annual rates per 100,000

0 - 2.93 - 9.910 - 24.925 - 120

Meningitis belt 4.5

WHO strategy:Capacities of the concerned countries

WHO strategy:Capacities of the concerned countries

Multiple endemic and epidemic diseases

Limited resources

Lack of laboratory capacities

WHO strategy:Performance and Availability of vaccines

WHO strategy:Performance and Availability of vaccines PS vaccines

Poorly immunogenic in children < 2y

Immunity short lived: requires multiple doses

Does not protect from carriage

Routine immunization not feasible in the Belt countries

Limited supply, affordability

bivalent AC

trivalent ACW

tetravalent ACWY

Outbreak control: 2 Core ComponentsOutbreak control: 2 Core Components

To prevent the lethality = case management• Presumptive treatment• Cheap and efficient on the most probable

causative agent

Ceftriaxone / Oily chloramphenicol: single dose IM

To prevent the cases = reactive vaccination

Reactive VaccinationReactive Vaccination

District level

Targeted on the high risk population: usually < 30yrs

Targeted on the responsible Nm serogroup: A, C, W

Timely

60% of cases averted when vaccination is implemented

within 2-4 weeks (Leake et al)

Reactive vaccination: the good timing Reactive vaccination: the good timing

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expected incidence rise or beginning of an outbreak?

the principle of the thresholds the principle of the thresholds

Alert threshold5/100 000/week

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Immediately conduct district mass vaccinationStrengthen case management

Clinical samples + lab confirmation

To immunize with the right vaccine: a rational choice

To immunize with the right vaccine: a rational choice

Mainly Nm identified 3

yes no

laboratory test results available

epidemic threshold reached 2

Conduct active fieldinvestigation andobtain specimens

Specimensobtained

at least one W135identified

> 30% of W135 out of 10-19Nm positive samples,

OR> 20% of W135 out of 20 ormore Nm positive samples

ACW PS AC PSVaccine

W135 epidemic in aneighboring district

in less than 10 samplesin 10 or more samples

W135 not identified

W135 not identified

yes no

AC PSVaccine

Meningitis Surveillance in the BeltMeningitis Surveillance in the Belt

•Early detection = weekly AR

•Identification of the target population = AR/age group

•Identification of responsible germs = confirmation + serogrouping

Enhanced surveillance

(epid./lab).

Countries implementing enhanced meningitis surveillance, 2003-2007.

Countries implementing enhanced meningitis surveillance, 2003-2007.

Niger

Chad

Nigeria

Mali

Burkina Faso

Ghana Togo Bénin

Ivory Coast

Ethiopia

From the reaction to the prevention..

Ziniare 2006

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Vaccination

Ziniare 2006

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Vaccination

The reactive vaccination: a frustrant strategy

Toward a true prevention: a conjugate vaccine for Africa…

Bogande 2007

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Bogande 2007

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The natural history of the disease: still many

question marks…

Figure 1. Trends of epidemic meningitis diisease in the African Belt, 1970-2006

020,00040,00060,00080,000

100,000120,000140,000160,000180,000200,000

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Country-Level Attack Rate - NIGER

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Meningitis weekly ARs Meningitis weekly ARs /100,000 Niger/100,000 Niger

Meningitis weekly ARs Meningitis weekly ARs /100,000 Burkina Faso/100,000 Burkina Faso

Country-level Attack Rates - Burkina Faso, 1997-2006

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Periodicity of Epidemics

Number of meningitis cases per year. Sudan 1977-2007

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Meningitis weekly cases Meningitis weekly cases SudanSudan

1999

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Epidemic districts, Burkina Faso 1999-2004

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District Epidemic Curves, Burkina Faso, 2001

Weekly attack rates , Banfora District, Burkina Faso 1997

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1 3 5 7 9 11 13 15 17 19 21 23 25 27 29

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6-8 weeks

Classical Epidemic Curve at District level

Meningitis outbreaks dynamicsMeningitis outbreaks dynamics

Magnitud of the outbreak determined by simultaneous occurrence of multi-focal outbreaks geographically not related

– A given community/district can be affected while contiguous communities/districts are not

Meningitis outbreaks in the African belt do not "spread "

Transmission is likely to occur through out the year (rainy and dry seasons)  (Blakebrough,1979 – Greenwood 1985)

The Belt, a conjunction of risk factors:

climatic,

socio-demographic,

immunologic…

Relation of seasonal climatic factors to meningococcal meningitis cases

Relation of seasonal climatic factors to meningococcal meningitis cases

* Grenwood et al, Trans Roy Trop Med 1987

Cases start increasing at beginning of the dry season (January)

Sharp decrease with the beginning of rains, May-June

Causes of meningitis epidemics still poorly understood

Causes of meningitis epidemics still poorly understood

Introduction of new epidemic strains– 1996-1997 epidemic associated to spread of Nm A of the ST-5

complex

Accumulation of susceptible cohorts

Environmental factors – Low absolute humidity– Land cover – Atmospheric dust…

….and millions of doses of vaccine injected

From a public health view…From a public health view…

Knowledge of the natural history of the disease:

What can we expect from the research community (environment, socio-demography, mathematical analysis..) ?

From a public health view…From a public health view…

How much this added knowledge can improve the control strategy (reactive response / preventive vaccination) ?

From a public health view…From a public health view…

Long term strategy: What will be the Belt in the coming decades ?

XA

"Everything in the spread of the diseases, like in any

natural biological phenomenon, is a matter of

circumstances"

Charles Nicolle