Dataset Information

Investigation of correlates of protection against pharyngeal carriage of Neisseria meningitidis genogroups W and Y in the African meningitis belt.

ABSTRACT: Background: Serum bactericidal antibody titres that correlate with protection against invasive meningococcal disease have been characterised. However, titres that are associated with protection against acquisition of pharyngeal carriage of Neisseria meningitidis are not known.

Methods: Sera were obtained from the members of a household in seven countries of the African meningitis belt in which a pharyngeal carrier of N. meningitidis had been identified during a cross-sectional survey. Serum bactericidal antibody titres at baseline were compared between individuals in the household of the carrier who became a carrier of a meningococcus of the same genogroup during six months of subsequent follow-up and household members who did not become a carrier of a meningococcus of this genogroup during this period.

Results: Serum bacterial antibody titres were significantly higher in carriers of a serogroup W or Y meningococcus at the time of recruitment than in those who were not a carrier of N. meningitidis of the same genogroup. Serum bactericidal antibody titres to a strain of N. meningitis of the same genogroup as the index cases were no different in individuals who acquired carriage with a meningococcus of the same genogroup as the index case than in those who did not become a carrier during six months of follow-up.

Conclusion: Serum bacterial antibody titres to N. meningitidis of genogroup W or Y in the range of those acquired by natural exposure to meningococci of these genogroups, or with cross-reactive bacteria, are not associated with protection against acquisition of carriage with meningococci of either of these genogroups.

SUBMITTER: Cooper LV

PROVIDER: S-EPMC5552120 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Investigation of correlates of protection against pharyngeal carriage of Neisseria meningitidis genogroups W and Y in the African meningitis belt.

Cooper Laura V LV Boukary Rahamatou Moustapha RM Aseffa Abraham A Mihret Wude W Collard Jean-Marc JM Daugla Doumagoum D Hodgson Abraham A Sokhna Cheikh C Omotara Babatunji B Sow Samba S Quaye Stephen Laryea SL Diallo Kanny K Manigart Olivier O Maiden Martin C J MCJ Findlow Helen H Borrow Ray R Stuart James M JM Greenwood Brian M BM Trotter Caroline L CL

PloS one 20170810 8

<h4>Background</h4>Serum bactericidal antibody titres that correlate with protection against invasive meningococcal disease have been characterised. However, titres that are associated with protection against acquisition of pharyngeal carriage of Neisseria meningitidis are not known.<h4>Methods</h4>Sera were obtained from the members of a household in seven countries of the African meningitis belt in which a pharyngeal carrier of N. meningitidis had been identified during a cross-sectional surve ...[more]

PMID: 28796795

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Project description:ObjectiveThe optimal long-term vaccination strategies to provide population-level protection against serogroup A Neisseria meningitidis (MenA) are unknown. We developed an age-structured mathematical model of MenA transmission, colonization, and disease in the African meningitis belt, and used this model to explore the impact of various vaccination strategies.MethodsThe model stratifies the simulated population into groups based on age, infection status, and MenA antibody levels. We defined the model parameters (such as birth and death rates, age-specific incidence rates, and age-specific duration of protection) using published data and maximum likelihood estimation. We assessed the validity of the model by comparing simulated incidence of invasive MenA and prevalence of MenA carriage to observed incidence and carriage data.ResultsThe model fit well to observed age- and season-specific prevalence of carriage (mean pseudo-R2 0.84) and incidence of invasive disease (mean R2 0.89). The model is able to reproduce the observed dynamics of MenA epidemics in the African meningitis belt, including seasonal increases in incidence, with large epidemics occurring every eight to twelve years. Following a mass vaccination campaign of all persons 1-29 years of age, the most effective modeled vaccination strategy is to conduct mass vaccination campaigns every 5 years for children 1-5 years of age. Less frequent campaigns covering broader age groups would also be effective, although somewhat less so. Introducing conjugate MenA vaccine into the EPI vaccination schedule at 9 months of age results in higher predicted incidence than periodic mass campaigns.DiscussionWe have developed the first mathematical model of MenA in Africa to incorporate age structures and progressively waning protection over time. Our model accurately reproduces key features of MenA epidemiology in the African meningitis belt. This model can help policy makers consider vaccine program effectiveness when determining the feasibility and benefits of MenA vaccination strategies.

Project description:BackgroundInvasive meningococcal disease (IMD), including sepsis and meningitis, can develop when Neisseria meningitidis bacteria breach the barrier and gain access to the circulation. While IMD is a rare outcome of bacterial exposure, colonization of the oropharynx is present in approximately 10% of the human population. This asymptomatic carriage can be long or short term, and it is unknown which determining factors regulate bacterial colonization. Despite descriptions of many bacterial virulence factors and recent advances in detailed genetic identification and characterization of bacteria, the factors mediating invasion and disease vs. asymptomatic carriage following bacterial colonization remain unknown. The pharyngeal epithelia play a role in the innate immune defense against pathogens, and the aim of this study was to investigate the proinflammatory response of pharyngeal epithelial cells following meningococcal exposure to describe the potential inflammatory mediation performed during the initial host‒pathogen interaction. Clinically relevant isolates of serogroups B, C, W and Y, derived from patients with meningococcal disease as well as asymptomatic carriers, were included in the study.ResultsThe most potent cellular response with proinflammatory secretion of TNF, IL-6, CXCL8, CCL2, IL-1β and IL-18 was found in response to invasive serogroup B isolates. This potent response pattern was also mirrored by increased bacterial adhesion to cells as well as induced cell death. It was, however, only with serogroup B isolates where the most potent cellular response was toward the IMD isolates. In contrast, the most potent cellular response using serogroup Y isolates was directed toward the carriage isolates rather than the IMD isolates. In addition, by comparing isolates from outbreaks in Sweden (epidemiologically linked and highly genetically similar), we found the most potent proinflammatory response in cells exposed to carriage isolates rather than the IMD isolates.ConclusionAlthough certain expected correlations between host‒pathogen interactions and cellular proinflammatory responses were found using IMD serogroup B isolates, our data indicate that carriage isolates invoke stronger proinflammatory activation of the epithelial lining than IMD isolates.

Dataset Information

Investigation of correlates of protection against pharyngeal carriage of Neisseria meningitidis genogroups W and Y in the African meningitis belt.

Publications

Investigation of correlates of protection against pharyngeal carriage of Neisseria meningitidis genogroups W and Y in the African meningitis belt.

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