AUGMENTATION DE L’INCIDENCE DE LA COQUELUCHE DANS LE MONDE ?

1. AUGMENTATION DE L’INCIDENCE DE LA COQUELUCHE DANS LE MONDE ? • Diagnostic biologique plus performant • Couverture vaccinale insuffisante • Adoption des acellulaires dans de nombreux pays • Moins efficace ? • Durée de protection moins longue ? • Modification des souches…vaccins moins efficaces

2. Pourquoi vacciner contre la coqueluche ? • Eradiquer la maladie : Non • Protéger d’une maladie grave chez le petit nourrisson +++ • Protéger d’une maladie gênante chez le grand enfant et l’adulte + • Assurer une immunité de groupe protégeant contre les grandes épidémies +

3. Pourquoi vacciner les adultes contre la coqueluche ? • Eradiquer la maladie • Les protéger d’une maladie gênante, exceptionnellement grave • Les empêcher de contaminer les petits enfants • Assurer une immunité de groupe protégeant contre les grandes épidémies

4. Review of Randomized Trials • Conclusions • aP vaccines effective in preventing confirmed pertussis • Marginally less effective than the best wP vaccines • 1,2,3, and 5 component vaccines all effective • Notably, no resurgence in Denmark despite monocomoponent vaccine • No simple relationship between immunogenicity and efficacy

5. Baboon Study Animal Model Attribution: Tod J. Merkel et al Laboratory of Respiratory and Special Pathogens CBER/FDA

6. wP and aP both protective against disease Animal Model (Baboon Study) Attribution: Tod J. Merkel et al Laboratory of Respiratory and Special Pathogens CBER/FDA

7. aP did not prevent infection Animal Model (Baboon Study) Attribution: Tod J. Merkel et al Laboratory of Respiratory and Special Pathogens CBER/FDA

8. Animal Model (Baboon Study) • aP did not prevent transmission Attribution: Tod J. Merkel et al Laboratory of Respiratory and Special Pathogens CBER/FDA

9. Animal Model (Baboon Study) • Conclusions • Infection, wP, aP all protected against symptomatic disease • wP provided some sterilizing immunity • Less than natural infection • Induces Th1 and Th17 memory • aP did not prevent infection and transmission • Higher Th2 but lower Th1 and Th17 responses • Lack of mucosal immunity induction likely has role in pertussis resurgence References Warfel JM, Beren J, Kelly VK, Lee G, Merkel TJ. Nonhuman primate model of pertussis. Infect Immun 2012;80(4):1530-1536. Warfel JM, Zimmerman LI, Merkel TJ. Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model. Proc Natl Acad Sci 2014;111(2):787-792. Warfel JM, Papin JF, Wolf RF, Zimmerman LI, Merkel TJ. Maternal and neonatal vaccination protects newborn baboons from pertussis infection. J Infect Dis 2014.

10. Summary • Pertussis vaccination very effective in reducing disease • wP and aP both effective in reducing infant mortality • No evidence of broad resurgence at global level • Cyclic recurrent patterns of pertussis still observed • aP disease prevention • Lower initial efficacy and faster waning of immunity • Reduced impact on infection and transmission • Modelling and baboon data support hypothesis that wP to aP transition is associated with localized disease resurgence

11. Si on veut protéger les petits enfants • Vaccination précoce +++ 6 semaines (moins) • Vaccination des femmes enceintes +++ • Cocooning +