1. December 14-15, 2009
Washington DC
Meningitis in the African Belt: impact of climate? perhaps but not only!
Hélène Broutin
Division of International Epidemiology and Population Studies, Fogarty International Center, US National Institutes of Health

2. OUTLINE Meningitis overview - Meningitis African Belt
- Key research question in a public health point of view
Climate and MM (Isabelle Jeanne)
Spatio-temporal dynamics of the disease:
- Identify ‘hotspots’/high risk areas
- Complexity of factors
Conclusion/next step …

3. 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
Major Bacterial Meningitis
Streptococcus pneumoniae
Haemophilus influenza
Neisseria meningitidis (Nm)

4. The disease: Meningococcal meningitis
SYMPTOMS
Stiff neck ( babies opposite:"the rag doll")
High fever
Headaches
Vomiting
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.
3-33% of asymptomatic carriers

5. Global Epidemiology Worldwide distribution - seasonality
Sporadic, cluster or large epidemic
12 serogroups (4 of them induce epidemics):
Europe, Americas: B, C
Asia: A
Africa: A, C, W135
Africa: 80 % of the global burden

6. The Meningitis Belt CHARACTERISTICS
21 countries in sub-Saharan Africa million people at risk
cases in the past 10 years
10-50 % case fatality rates
10-20 % of survivors suffer permanent brain damage
DISEASE DYNAMICS
Seasonal epidemic activity (dry season)
Larger epidemics every 8-12 years

7. CHALLENGE: timely vaccination to optimize the control of the epidemics
Control: REACTIVE VACCINATION
Targeted on the high risk population: usually < 30yrs; and on the responsible Nm serogroup: A, C, W
Based on incidence thresholds at district level (enhanced weekly surveillance)
Does not prevent all cases
400
800
1200
1600 w1 w2 w3 w4 w5
wk1
wk8
wk15
wk20 5
Alert threshold
CHALLENGE: timely vaccination to optimize the control of the epidemics
Epidemic threshold 10
Number of Cases
Number of Cases
cases / /wk

8. Vaccination availability
Timely vaccination: a recurrent challenge
District level
Burkina Faso
From E. Bertherat, WHO w1 w1 w2 w2 w3 w3
Why such delays?
Vaccination availability
Logistic in the field w4 w4 w5 w5

9. Conditions of epidemics emergence?
From a public health point of view
Need to improve the current vaccination strategy
= better anticipation of epidemics emergence
Key Research question
What are the determinants of epidemics emergence in the population?

10. MM and Climate
Epidemics occur during dry season and stop with the first rainfalls.
Biological hypothesis
Correlation between cases time series and climate/environmental parameters (Dust, intensity of Harmattan Winds, Humidity)
But the key question is :
WHAT IS THE EXACT ROLE OF CLIMATE?
Unique/major driver?
Initiator and/or Amplifier?
Or climate ‘just’ ends epidemics?

11. Suspected MM cases (clinical diagnostic)
MM in Niger ( )
Local scale (within countries)
Suspected MM cases (clinical diagnostic)
Weekly data
38 districts
Niamey I
Diffa
Agadez
200
400
600
800
1000
100
300
500
Time (weeks)
Number of cases
Data source: National enhanced surveillance system (through WHO)

12. MM in Niger – seasonality
Dogon Doutchi
Birnin K’onni ?
In progress : coherency and phase analyses (SYNCHRONY)

13. MM in Niger – Cluster analyses
Mean
Standard deviation
Maximum
Week of maximum of incidence,
Skewness index
Kurtosis index
6 variables
Agier, Broutin et al, in preparation

14. MM in Niger - Epidemic Definition
WHO : ≥ 100 cases/ pop. a year
Here, district-specific definition:
- Cumulative annual incidence
- Anomalies (Annual incidence – Mean)
EPI
year
year
year

15. MM in Niger - Groups comparison
Epidemic years
Non Epidemic years

16. MM in Niger - Groups comparison
6 new variables related to surveillance system
6 initial variables (cluster analyses)
Gr N1
Gr N2
Gr N3
First week over the alert threshold E
4.1 (3.3)
8.9 (5.8)
13.9 (6.4) NE
11.8 (9.9)
14.2 (8.3)
31.2 (14.0)
Number of weeks over the alert threshold
16.0 (5.0)
8.8 (4.5)
4.1 (2.9)
4.3 (2.9)
2.4 (1.7)
1.0 (0)
Delay between reaching alert threshold and peak
8.2 (3.2)
5.6 (4.0)
5.5 (8.4)
3.4 (6.0)
1.5 (2.6)
0 (0)
Mean weekly incidence
Maximum of weekly incidence
+ 3 with epidemic threshold
Highest incidence
Longer epidemics (in number of weeks over the epidemic/alert threshold defined by WHO)
Early epidemics (first week over the epidemic/alert threshold)
Group N1

17. Comparative Study in 3 countries
Mali ( ), 51 districts
BF ( ), 52 districts
Niger ( ), 38 districts
Cluster analyses
Population distribution
Agier, Broutin et al, in preparation

18. MM in Niger – absence/reappearance
Main roads
Barthi, Broutin et al, in preparation

19. How to explain this high risk areas ?
MM and the complexity of factors at work
How to explain this high risk areas ?
Environmental/climate factors
Serogroup/sub-group dynamics
Asymptomatic carriers
Population Immunity/Vaccination
Population density / movements (roads)
Other respiratory infections
Need for comparative studies at different spatial and temporal scales

20. In progress ….
1/ Understand the spatial and temporal dynamics of the disease
2/ Identify ‘hotspots’ or ‘high risk’ areas
In progress…
3/ Explore relation between MM dynamics and
population density?
population movements (roads)?
birth rate?
vaccination?
Environment?
To quantify the role of each parameter

21. Next step … 4/ transmission dynamics modeling asymptomatic carrier
vaccination
serogroup ?
environment …
5/ operational tool for early epidemics detection at local scale

22. A COLLABORATIVE WORK Lydiane AGIER Lancaster University, UK
Nita BHARTI
Bryan T. GRENFELL
Princeton University, NJ, USA
Eric Bertherat
William Perea
Epidemic Response and Intervention, World Health Organization, Switzerland
Multi-Disease Surveillance Center, World Health Organization, Burkina Faso
Mamoudou A. Djingarey
Ali Djibo
Ministry of Health, Niger
Rebecca Grais
Epicentre, France

23. THANK YOU Hélène Broutin December 14-15, 2009 Washington DC
Division of International Epidemiology and Population Studies, Fogarty International Center, US National Institutes of Health