Meningococcal carriage in the African meningitis belt and the impact of MenAfriVac: an overview of the MenAfriCar project http://www.meningitis.org/conference2015

1. THE AFRICAN
MENINGOCOCCAL
CARRIAGE CONSORTIUM
Brian Greenwood
London School of Hygiene & Tropical
Medicine
Meningitis Research Fund Meeting
November 4th 2015

2. THE AFRICAN MENINGITIS BELT
(Lapeyssonnie, Bull WHO 1963;28 suppl:3-114)

3. CHARACTERISTICS OF MENINGOCOCCAL DISEASE
IN THE AFRICAN MENINGITIS BELT
 High rate of endemic infection
 Regular epidemics
- geographical limitation
- periodicity
- marked seasonality
- large size
- mainly serogroup A
(prior to vaccination)
What lies behind this unique epidemiology?

4. ‘’Cases of meningitis can be considered uncertain and irregular
indicators of the spread of meningococcal infections in a
population. The real flow is submerged and can be revealed
solely by uncovering subclinical infections.’’
(Phair and Schoenbach Amer J Hyg 1944; 40:525-41)

5. MENINGOCOCCAL CARRIAGE IN AFRICA
Literature Review to 2007
 Overall carriage rate
varied from 1- 30%
Age pattern very variable
Is the heterogeneity due to
methodological problems?
(Trotter and Greenwood, LID 2007;12:797-803)

6. THE GENESIS OF MENAFRICAR CONSORTIUM
2006 Workshop on meningococcal carriage in Africa, sponsored by the
Wellcome Trust.
2007 Project development grant from the Wellcome Trust,
Workshop in London.
2008 Award of a grant to the consortium by the Gates Foundation.
2009 Award of a strategic award to the consortium from the Wellcome Trust,
First formal meeting of the consortium, Bamako, Mali .

7. THE MENAFRICAR CONSORTIUM
Armauer Hansen Research
Institute, Ethiopia
Centre de Recherche
Médicale et Sanitaire, Niger
Centre de Support en
Santé Internationale, Chad
Centre pour le Développement des
Vaccins, Mali
University of
Maiduguri, Nigeria
The Navrongo Health Research
Centre, Ghana
Institut de Recherche pour
le Développement, Senegal
LSHTM + 13 NORTHERN PARTNERS

8. OBJECTIVES
 Measurement of the prevalence of meningococcal carriage across
the African meningitis belt prior to the introduction of MenAfriVac.
 Investigation of the pattern of spread of meningococci within
households in the African meningitis belt.
 Investigation of the background level of immunity to the serogroup
A meningococcus across the African meningitis belt.
 Determination of the impact of MenAfriVac on serogroup A
meningococcal carriage.

9. METHODS

10. CROSS-SECTIONAL SURVEYS
 Random selection of households (DSS or census).
 Age stratification (<1, 1-4, 5-14, 15-29, 30 or > years).
 Urban and rural sites.
 Target of 2,000 or 5,000 subjects per survey.
 Blood samples obtained from a subset of participants.

11. HOUSEHOLD STUDIES
Cross-sectional
study
First household visit
visit 2
visit 3
visit 4
Identification of a
carrier
Household follow up
6 months of
follow up
Carrier
Missing
Not a carrier

12. Method 1 Method 2
Nasopharynx
alone
Nasopharynx
& tonsil
OPTIMUM METHOD OF SWABBING
(No significant difference between
the two methods)
(Basta et al, PLoS One 2013)

13. CAPACITY DEVELOPMENT IN LABORATORY ASSAYS
Serology Lab, Mali Training courses, VEU, PHE, Manchester
CVD, Bamako, Mali

14. MICROBIOLOGY
Culture on
selective medium
Swab
Gram stain
Oxidase tests
ONPG
Positive
Culture blood agar
Molecular
characterisation
Biochemical
tests
Seroagglutination
DNA preparation
(MenAfriCar Consortium
TMIH 2013;18:968-78)
PCR
On-site
Oxford

15. MOLECULAR BIOLOGY
 Speciation – rplF sequencing assay.
 Genogrouping – RT PCR assay (A, W ,X ,B ,C ,Y)
and capsule null (cnl) assay.
 Genetic diversity – porA and fetA sequencing
 Whole genome sequencing – MenA isolates

16. SEROLOGY
 Meningococcal polysaccharide IgG ELISA
(all centres)
 Bactericidal assay
(Mali and Niger)
Validation at the Vaccine Evaluation Unit,
PHE, Manchester
(MenAfriCar Consortium TMIH 2013;18:968-78)

17. CROSS-SECTIONAL
SURVEYS

18. CARRIAGE PREVALENCE – CROSS SECTIONAL SURVEYS
1687 carriers from 48,490 participants; 3.5% overall (all meningococci )
0%
5%
10%
15%
20%
25%
carriageprevalence
Survey 1 (rainy) Survey 2 (rainy) Survey 3 (dry)
(MenAfriCar consortium. J Infect Dis 2015;212:1298-307)

19. CARRIAGE PREVALENCE BY AGE AND SEX
(MenAfriCar consortium. J Infect Dis. 2015;212:1298-307)
0%
1%
2%
3%
4%
5%
6%
7%
<1 years 1-4 years 5-14 years 15-29 years 30+ years
Carriageprevalence
Females Males

20. RISK FACTORS FOR CARRIAGE
 Country
 Age
 Crowding: >2 people per room) 
 Smoking in household 
 Indoor kitchen 
 Season: dry season
 Recent vaccination with a meningitis vaccine 
No associations with respiratory symptoms
or social gatherings
(MenAfriCar consortium. J Infect Dis. 2015 ;212:1298-307)

21. GENOTYPE OF CARRIERS
A
A/X
B
C
W
X
X/C
Y
cnl
Survey 1; 2010
(rainy)
584/17042
Survey 2; 2011
(rainy)
455/15936
Survey 3; 2012
(dry)
648/15512
Capsule
null
W
A
Capsule
null
Capsule
null
(MenAfriCar Consortium. J Infect Dis. 2015 ;212:1298-307)
W
W

22. SEROGROUP A MENINGITIS EPIDEMIC IN CHAD

23. Districts in epidemic/ alert in 2012
Districts vaccinated with
“MenAfriVac” in December 2011
N’Djaména
Mandelia
Districts in epidemic/alert in 2012
Districts vaccinated with
“MenAfriVac” in December 2011
N’Djaména
EPIDEMIC MENINGITIS IN CHAD 2012

24. 0
1
2
13-15 months 2-4 months 4-6 months
1
All meningococci
Epidemic strain
VACCINATION
Pre-vaccination Post-vaccination
Percentage
carriage
IMPACT OF PsA-TT ON MENINGOCOCCAL CARRIAGE
– CHAD 2012
(Daugla et al. Lancet 2014; 383:40-47)
32
[Adjusted OR = 0.019, 95% CI 0.002, 0.14]

25. CHAD ETHIOPIA
N=1
4
N=7
1
N=4
9
Pre-vaccination Post vaccination
N=120 N=122
N=147
0
10
20
30
40
50
60
70
80
90
100
XS1 XS2 XS3
percentageofN.meningitidis(%)
no/partial porA
P.12-1,2-59
P.12-1,13-2
P.7-2,30-3
P.7-2,30-2
P.7,30-6
P.7,30-3
P.7,30-2
P.7,13-18
P.7,13-1
P.7,13
P.5-14,10-86
P.5-1,2-2
P.5-1,10-1
P.5-2,10-2
P.5,2
P.22-1,14
P.22-14
P.22-11,15-30
P.22-11,15-25
P.22-11,15-1
P.22-11,9
P.19-1,15-1
P.19,15
P.17-1,23
P.17,16-4
P.18-1,34
P.18,25
P.18,25-21
P.18,25-19
P.18-11,42
P.5-1,10-62
P.18-11,42-1
NO VACCINATION!
IMPACT OF MENAFRIVAC ON STRAIN DISTRIBUTION

26. 0
1
2
3
4
5
6
7
8
9
Weeklyincidence/100,000
2009 2010 2011 2012
Vaccinated
Non-vaccinated
Vaccination
PsA-TT
INITIAL IMPACT OF PsA-TT ON CASES OF MENINGITIS
IN CHAD - 2012
Incidence odds ratio 0.096 (0.05,0.19)(Daugla et al. Lancet 2014; 383:40-47)

27. IMPACT OF PsA-TT ON MENINGITIS CASES IN CHAD,
WEEKS 1-26, 2009-13
0
1
2
3
4
5
6
7
8
9
Weeklyincidence/100,000
2009 2010 2011 2012
N'Djamena
Rest of Chad
2013
VaccinationVaccination
2011 2012
(Gamougam et al. Emerg Infect Dis 2015;21:115-8)

28. MENINGITIS CASES CHAD - UPDATE
WHO Meningitis Weekly Bulletin September 2015
MenAfriVac
completed

29. WHAT NEXT?
Disease outbreak news
23 July 2015
Between 1 January and 28 June 2015, the Ministry
of Public Health of Niger notified WHO of 8,500 suspected
cases of meningococcal meningitis, including 573 deaths.
This was the largest meningitis outbreak caused by
Neisseria meningitidis serogroup C in the African meningitis belt.
http://www.who.int/csr/don/23-july-2015-niger/en/

30. MENINGITIS IN THE AFRICAN MENINGITIS BELT - 2015

31. CONCLUSIONS
 Carriage of Neisseria meningitidis and of non-meningococcal Neisseria
species varies markedly by place and time in the African meningitis belt.
 Carriage of Neisseria meningitidis is generally at a lower prevalence
and of shorter duration in the meningitis belt than in industrialised countries.
 In households with a carrier younger children are infected by their older siblings.
 There is a high background prevalence of serogroup A anti-meningococcal
antibodies across the meningitis belt which are probably not protective.
 MenAfriVac protects against serogroup A meningococcal carriage and meningitis.
 There is still much that is unknown about the epidemiology of epidemic meningitis
in the meningitis belt which could be investigated by further carriage studies.

32. ACKNOWLEDMENTS