Clonal waves of Neisseria colonisation and disease in the African meningitis belt: eight- year longitudinal study in northern Ghana

Abstract

Background: The Kassena-Nankana District of northern Ghana lies in the African "meningitis belt" where epidemics of meningococcal meningitis have been reoccurring every eight to 12 years for the last 100 years. The dynamics of meningococcal colonisation and disease are incompletely understood, and hence we embarked on a long-term study to determine how levels of colonisation with different bacterial serogroups change over time, and how the patterns of disease relate to such changes.

Methods and findings: Between February 1998 and November 2005, pharyngeal carriage of Neisseria meningitidis in the Kassena-Nankana District was studied by twice-yearly colonisation surveys. Meningococcal disease was monitored throughout the eight-year study period, and patient isolates were compared to the colonisation isolates. The overall meningococcal colonisation rate of the study population was 6.0%. All culture-confirmed patient isolates and the majority of carriage isolates were associated with three sequential waves of colonisation with encapsulated (A ST5, X ST751, and A ST7) meningococci. Compared to industrialised countries, the colonising meningococcal population was less constant in genotype composition over time and was genetically less diverse during the peaks of the colonisation waves, and a smaller proportion of the isolates was nonserogroupable. We observed a broad age range in the healthy carriers, resembling that of meningitis patients during large disease epidemics.

Conclusions: The observed lack of a temporally stable and genetically diverse resident pharyngeal flora of meningococci might contribute to the susceptibility to meningococcal disease epidemics of residents in the African meningitis belt. Because capsular conjugate vaccines are known to impact meningococcal carriage, effects on herd immunity and potential serogroup replacement should be monitored following the introduction of such vaccines.

Figure 1. Waves of Colonisation and Disease in the KND from April 1998 until November 2005

Carriage rates recorded during 16 colonisation surveys (April and November each year) and monthly numbers of confirmed meningitis cases of N. meningitidis. (A) Genoclouds of serogroup A ST5 and ST7 meningococci are shown. (B) Genoclouds of serogoup X ST851 and NG ST192 meningococci are shown. (C) Carriage rates of other serogroups and meningococci unrelated to the A, X, or NG ST192 genoclouds are shown. (D) Carriage rates of N. lactamica are shown.

Figure 2. Age and Sex Patterns of Colonisation and Disease

(A) Carriage of meningococci (all serogroups and NG; cumulation of all surveys) in the different age groups of the male (light grey bars) and female (dark grey bars) population are shown. 95% CIs are indicated. These CIs do not allow for repeated sampling. (B) Carriage of N. lactamica in the different age groups (mean over all surveys) of the male (light grey bars) and the female population (dark grey bars) are shown. 95% CIs are indicated. These CIs do not allow for repeated sampling. (C) Age spectrum of IR of meningococcal meningitis in the male (circles) and female (triangles) population of the KND in the epidemic of 1996–1997 (dark grey) versus the interepidemic period 2001–2005 (light grey). Denominator is the district population 1995–1999. On the primary y-axis the epidemic IRs and on the secondary y-axis the interepidemic IRs are indicated.