prof sir brian greenwood @ mrf's meningitis & septicaemia in children & adults 2015
TRANSCRIPT
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THE AFRICAN MENINGOCOCCAL
CARRIAGE CONSORTIUM
Brian Greenwood
London School of Hygiene & Tropical Medicine
Meningitis Research Fund MeetingNovember 4th 2015
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THE AFRICAN MENINGITIS BELT
(Lapeyssonnie, Bull WHO 1963;28 suppl:3-114)
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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?
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‘’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)
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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)
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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 .
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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
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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.
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METHODS
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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.
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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
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Method 1 Method 2
Nasopharynx
aloneNasopharynx & tonsil
OPTIMUM METHOD OF SWABBING
(No significant difference between the two methods)
(Basta et al, PLoS One 2013)
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CAPACITY DEVELOPMENT IN LABORATORY ASSAYS
Serology Lab, Mali Training courses, VEU, PHE, Manchester CVD, Bamako, Mali
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MICROBIOLOGY
Culture onselective medium
Swab
Gram stain Oxidase tests
ONPGPositive
Culture blood agar
Molecular characterisation
Biochemicaltests
Seroagglutination
DNA preparation
(MenAfriCar Consortium TMIH 2013;18:968-78)PCR
On-site
Oxford
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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
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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)
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CROSS-SECTIONAL SURVEYS
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CARRIAGE PREVALENCE – CROSS SECTIONAL SURVEYS
1687 carriers from 48,490 participants; 3.5% overall (all meningococci )
Chad Ethiopia Ghana Mali Niger Nigeria Senegal Overall0%
5%
10%
15%
20%
25%
Survey 1 (rainy) Survey 2 (rainy) Survey 3 (dry)ca
rria
ge p
reva
lenc
e
(MenAfriCar consortium. J Infect Dis 2015;212:1298-307)
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CARRIAGE PREVALENCE BY AGE AND SEX
(MenAfriCar consortium. J Infect Dis. 2015;212:1298-307)
<1 years 1-4 years 5-14 years 15-29 years 30+ years0%
1%
2%
3%
4%
5%
6%
Females Males
Carr
iage
pre
vale
nce
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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)
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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)
WW
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SEROGROUP A MENINGITIS EPIDEMIC IN CHAD
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Districts in epidemic/ alert in 2012Districts vaccinated with “MenAfriVac” in December 2011
N’Djaména
MandeliaDistricts in epidemic/alert in 2012Districts vaccinated with “MenAfriVac” in December 2011
N’Djaména
EPIDEMIC MENINGITIS IN CHAD 2012
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13-15 months 2-4 months 4-6 months0
1
2
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]
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CHAD ETHIOPIA
N=14
N=71
N=49
Pre-vaccination Post vaccination
N=120 N=122 N=147
XS1 XS2 XS30
10
20
30
40
50
60
70
80
90
100 no/partial porAP.12-1,2-59P.12-1,13-2P.7-2,30-3P.7-2,30-2P.7,30-6P.7,30-3P.7,30-2P.7,13-18P.7,13-1P.7,13P.5-14,10-86P.5-1,2-2P.5-1,10-1P.5-2,10-2P.5,2P.22-1,14P.22-14P.22-11,15-30P.22-11,15-25P.22-11,15-1P.22-11,9P.19-1,15-1P.19,15P.17-1,23P.17,16-4P.18-1,34P.18,25 P.18,25-21P.18,25-19P.18-11,42P.5-1,10-62P.18-11,42-1
perc
enta
ge o
f N.m
enin
gitid
is (%
)
NO VACCINATION!
IMPACT OF MENAFRIVAC ON STRAIN DISTRIBUTION
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0
1
2
3
4
5
6
7
8
9
Vaccinated
Non-vaccinated
2009 2010 2011 2012
Wee
kly
inci
denc
e/10
0,00
0
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)
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IMPACT OF PsA-TT ON MENINGITIS CASES IN CHAD, WEEKS 1-26, 2009-13
0
1
2
3
4
5
6
7
8
9
N'Djamena
Rest of Chad
2009 2010 2011 2012
Wee
kly
inci
denc
e/10
0,00
0
2013
Vaccination 2012
Vaccination 2011 2012
(Gamougam et al. Emerg Infect Dis 2015;21:115-8)
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MENINGITIS CASES CHAD - UPDATE
WHO Meningitis Weekly Bulletin September 2015
MenAfriVac completed
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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/
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MENINGITIS IN THE AFRICAN MENINGITIS BELT - 2015
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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.