Investigation of correlates of protection against pharyngeal carriage of <i>Neisseria meningitidis</i> genogroups W and Y in the African meningitis belt

<div><p>Background</p><p>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 <i>Neisseria meningitidis</i> are not known.</p><p>Methods</p><p>Sera were obtained from the members of a household in seven countries of the African meningitis belt in which a pharyngeal carrier of <i>N</i>. <i>meningitidis</i> 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.</p><p>Results</p><p>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 <i>N</i>. <i>meningitidis</i> of the same genogroup. Serum bactericidal antibody titres to a strain of <i>N</i>. <i>meningitis</i> 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.</p><p>Conclusion</p><p>Serum bacterial antibody titres to <i>N</i>. <i>meningitidis</i> 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.</p></div

Index and subsequent carriers by genogroup.

<p>Index and subsequent carriers by genogroup.</p

Geometric mean by exposure and outcome.

<p>Geometric mean SBA titres and 95% CI found in current carriers of <i>N</i>. <i>meningitidis</i> genogroup W or Y and in household members exposed to a carrier who became a carrier of <i>N</i>. <i>meningitidis</i> of the same genogroup as the index case and among those who did not.</p

Factors influencing odds of carriage acquisition.

<p>Factors influencing odds of carriage acquisition.</p

Antibody titres by exposure and outcome.

<p>Antibody titres by exposure and outcome.</p

Reciprocal titre by exposure and outcome.

<p>Reciprocal plots of SBA titre found in individuals exposed to a carrier of <i>N</i>. <i>meningitidis</i> who became a carrier of a meningococcus belonging to the same genogroup as the index carrier during six months of follow-up and those who did not. Sera tested against a genogroup W reference strain, genogroup W local strain, genogroup Y reference strain.</p

Summary of reasons for screen-outs and exclusion from analysis by site.

<p>Percentages shown as a proportion of either total screened (above), or total enrolled (below)</p><p>* Volunteers may be excluded for multiple reasons therefore columns may sum to >100%</p><p>** Systolic blood pressure >140 mm Hg and/or diastolic blood pressure >90 mm Hg</p><p>*** Including headaches, cough, fever, suspected and confirmed malaria</p><p>**** Active STI, including candidiasis, one possible HSV-1 infection, lower abdominal pain in women, and Bartholin's abscess</p>‡<p>Including suspected and confirmed TB, pneumonia</p>†<p>Includes 125/184 (67.9%) medical exclusions not linked to infectious disease (e.g., trauma, diabetes, cancer)</p>§<p>Includes 4/17 (23.5%) medical exclusions not linked to infectious disease (3 peripheral neuropathy and 1 inebriation at time of visit)</p

Map of study sites showing source populations, elevation (meters above sea level) and target enrolment.

<p>Map of study sites showing source populations, elevation (meters above sea level) and target enrolment.</p

Screened, enrolled and analyzed volunteers by site and gender.

<p>Screened, enrolled and analyzed volunteers by site and gender.</p

Equivalent numbers of men and women aged 18-60 were screened for this study.

<p>Among the 2,990 volunteers screened, 2,387 were enrolled, and a further 263 were excluded from analysis leaving a final study cohort of 2,124 volunteers.</p