IMPACT OF SEROGROUP A MENINGOCOCCAL CONJUGATE VACCINE (MENAFRIVAC) ON

MENINGOCOCCAL MENINGITIS AND CARRIAGE IN CHAD

Caroline Trotter

University of Cambridge

GREETINGS FROM CHAD

Dr Daugla,Director

Dr Gamougam, Microbiologist

Centre de Support en Santé Internationale (CSSI)

Cases of meningitis

Year

Whole cell vaccines

Sulphonamides

Polysaccharide vaccines

Conjugate vaccine

MENINGITIS IN CHAD 1930-2011

THE AIMS OF MENAFRICAR

• To define the pattern of meningococcal carriage across the African meningitis belt and rates of acquisition and loss of carriage.

• To measure the impact of a new group A meningococcal conjugate vaccine (MenAfriVac) on carriage and disease.

MENAFRICAR CENTRES

Armauer Hansen Research Institute (AHRI), Ethiopia

Centre de Recherche Médicale et Sanitaire (CERMES), Niger

Centre de Support en Santé Internationale (CSSI), Chad

Centre pour le Développement des Vaccins (CVD-Mali), Mali

University of Maiduguri, Nigeria

The Navrongo Health Research Centre, Ghana

Institut de Recherche pour le Développement, Senegal

MENAFRICAR SURVEYS IN 2010

• First cross sectional studies performed July-December 2010

in seven countries.

• Group A meningococci identified only in carriers in Chad.

• Vaccine evaluation activities originally planned for Mali and

Niger moved to Chad.

CARRIAGE STUDIES IN CHAD

• MenAfriCar standard protocols• Rural area of Mandelia• First survey

• September-November 2010, N= 998

• Pre-vaccination survey• August- October 2011, N=4278

• Post-vaccination survey• April-June 2012, N=5001

Mandelia district - address by the Chef

Mandelia carriage survey - collecting a swab

Microbiology laboratory National hospital, N’Djamena

THE MENINGITIS VACCINE PROJECT

Aim

Production of an affordable,

serogroup A

meningococcal conjugate

vaccine for use in Africa

Established in 2001 with support fromthe Bill and Melinda Gates Foundation

WHO + PATH

MVP – ACHIEVEMENTS

• Efficient conjugation method developed and transferred

successfully to an Indian manufacturer.

• Phase 2 trials showed the vaccine to be safe and highly

immunogenic in children (Gambia and Mali) and young adults

(Mali, Senegal, Gambia).

• Vaccine safe and immunogenic in infants (Ghana).

• Vaccine licensed in India in 2009 and prequalified by WHO in 2010.

• Mass campaigns commenced in Burkina Faso, Mali and Niger

in those aged 1 – 29 years at the end of 2010.

< 10 YEARS FROM VACCINE DEVELOPMENT TO DEPLOYMENT

VACCINE MANUFACTURE

Serum Institute, Pune, India

MenAfriVac

MENAFRIVAC IMMUNISATION IN CHAD

• 1.8 million 1-29 year olds immunised in a planned vaccination campaign in 3 regions in and around N’Djamena over 10 days in December 2011.

• Reactive vaccination campaigns February - May 2012 - 9 districts exceeding the epidemic threshold- 3 other adjacent districts.

Districts in epidemic/ alert in 2012Districts vaccinated with “MenAfriVac” in December 2011

N’Djaména

VACCINATED DISTRICTS IN CHAD 2012

Mandelia

Moissala

MENINGITIS SURVEILLANCE

• Clinically diagnosed meningitis cases and deaths reported to district medical officer Ministry of Health WHO.

• CSF samples N’Djamena.

• Enhanced surveillance in 2012 in 3 vaccinated regions (MenAfriCar).

• Surveillance also enhanced in Moissala district, where reactive vaccination was undertaken in 2012 (MSF).

IMPACT OF MENAFRIVAC ON THE EPIDEMIc

[Adjusted incidence rate ratio =0.096 (95% CI 0.046, 0.198)]

94% difference in vaccinated compared to the unvaccinated areas

0

10

20

30

40

50

60

50 51 52 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

2011 2012

Semaine épidémiologique

No

mb

re d

e ca

s

Cas confirmés

Cas probables

campagne de vaccination

Confirmed cases

Probable cases

Vaccination campaign

Cases of meningitis by week of admission Moissala district, Chad, 2012 (n = 334)

(a)all probable and confirmed cases

(b)cases by serogroup (N=78). *

Vaccination campaign

0

5

10

15

50 51 52 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

2011 2012

Semaine epidémiologique

No

mb

re d

e ca

s

Non isolé

W135

A

campagne de vaccination

No serogroup identified

W

A

Vaccination campaign

a

b

REACTIVE VACCINATION IN MOISSALA DISTRICT

All meningococci

Epidemic strain

VACCINATION

Pre-vaccination Post-vaccination

Percentage carriage

(Daugla et al. Lancet 2013; electronic publication)

CARRIAGE RESULTS (1)

CARRIAGE RESULTS (2)

• 32/4278 group A carriers* in 2011 pre-vaccine survey.

• Only 1/5001 group A carrier post-vaccination.

• 98% difference in group A carriage prevalence.

• Adjusted Odds Ratio 0.019, 95% CI 0.002, 0.14.* serogroup A capsule region, rplF allele 1 (rplF-1), and a porA gene encoding the subtype P1.20,9

CARRIAGE RESULTS (3)

CONCLUSIONS

• MenAfriVac was highly effective at preventing serogroup A invasive meningococcal disease and carriage in Chad

during an epidemic.

• Together with previous studies from Burkina Faso, this study provides strong evidence of vaccine impact.

• Further work is required to evaluate the duration of protection and the influence of vaccination on other serogroups.

ACKNOWLEDGEMENTS Centre de Support en Santé International (CSSI), N’Djamena, Chad: DM Daugla, JP Gami, K Gamougam, N Naibei, L Mbainadji, M Narbé, J Toralta, B Kodbesse

Ministere de la Santé Publique, N’Djamena, Chad: C Ngadoua

Epicentre, Médecins sans Frontières, Paris, France: ME Coldiron, F Fermon U, A-L Page

WHO Intercountry Support Team, Ougadougou, Burkina Faso: MH Djingarey

Department of Pandemic and Epidemic Diseases, WHO, Geneva, Switzerland: S Hugonnet

Department of Zoology, University of Oxford, Oxford, UK: OB Harrison, LS Rebbetts, Y Tekletsion, ER Watkins, D Hill, MCJ Maiden

Norwegian Institute for Public Health, Oslo, Norway: D Caugant

Department of Veterinary Medicine, University of Cambridge, Cambridge, UK: C Trotter

Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK: D Chandramohan, M Hassan-King, O Manigart, M Nascimento, A Woukeu, JM Stuart, BM Greenwood

MenAfriCar is funded by The Bill & Melinda Gates Foundation & The Wellcome Trust