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.
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.
An analysis of pharyngeal carriage of meningococci in one district of Ghana examined the features of the isolates that might contribute to the susceptibility to meningococcal epidemics in the African meningitis belt.
Bacterial meningitis is a rare but often fatal infection of the meninges—the thin membrane around the brain and the spinal cord. It can be caused by several types of bacteria, but meningococcal meningitis, which is caused by Neisseria meningitidis, is the most common form of bacterial meningitis in children and the second most common form in adults. About 10% of healthy people have N. meningitidis growing in their nose and throat; the bacteria are spread by exposure to infected respiratory secretions. In these “carriers,” the immune system keeps the bug in check but sometimes this surveillance fails, N. meningitidis enters the bloodstream and travels to the brain, where it infects the meninges and causes inflammation. The symptoms of meningococcal meningitis are sudden fever, headache, and a stiff neck and, even if strong antibiotics are given quickly, 10%–15% of patients die.
Why Was This Study Done?
Outbreaks of meningococcal meningitis occur all over the world, but the highest burden of disease is in the African meningitis belt, which stretches across sub-Saharan Africa from Senegal to Ethiopia. Here, localized epidemics of meningococcal meningitis occur every eight to 12 years during the dry season. Control of these epidemics relies on their early detection followed by mass immunization. This approach can be hard to implement in countries with limited resources, but the introduction of other control measures (for example, routine childhood immunization) requires an understanding of how the spread of different strains of N. meningitides through the community causes periodic epidemics. In this study, the researchers have studied the long-term dynamics of colonization by N. meningitidis and the occurrence of meningococcal meningitis in one region of the African meningitis belt.
What Did the Researchers Do and Find?
The researchers took throat swabs twice a year from people living in rural northern Ghana for eight years. They tested each swab for N. meningitidis and determined the serogroup of the bacteria they found. Bacterial serogroups differ only in terms of the antigens (molecules recognized by the immune system) that they express; N. meningitidis is classified into 13 serogroups based on the sugars that coat its surface. The researchers also used DNA sequencing to group the bacterial isolates into genoclouds—genetically closely related groups of meningococci represented by a sequence type (ST) number. Finally, they monitored meningococcal disease throughout the study and determined the serogroup and genocloud of patient isolates. Their results show colonization of 6% of the study population by N. meningitidis and reveal three consecutive waves of colonization and disease characterized by the presence of a serogroup A ST5 genocloud, a serogroup X ST751 genocloud, and finally a serogroup A ST7 genocloud. Colonizing bacteria isolated in this study in Ghana, the researchers report, changed their genotype more frequently but were less genetically diverse than those isolated in industrialized countries. In addition, the commonest serogroups of N. meningitidis in carriers in Ghana were disease-causing serogroups, whereas in industrialized countries these serogroups are rarely seen in carriers. However, non-groupable bacteria (bacteria that lack surface sugars), although common in industrialized countries, were rare in Ghana.
What Do These Findings Mean?
These findings begin to explain why epidemics of meningococcal meningitis are common in the African meningitis belt. Because there isn't a stable, genetically diverse population of N. meningitidis in carriers, the immune systems of people living here may not be optimally prepared to deal with new bacterial clones that arrive in the region, and this lack of immunity could result in frequent epidemics. However, because the researchers took relatively few samples every six months from one small area of the meningitis belt, the genetic diversity of N. meningitidis over the whole region might be considerably greater than that colonizing the study population. Nevertheless, the description of successive waves of meningococci colonization in Ghana has important implications for the proposed introduction of childhood vaccination against meninogococcal disease in the African meningitis belt. If this vaccination program goes ahead, warn the researchers, it will be essential to monitor which strains of N. meningitidis are colonizing the population and to have emergency plans ready to deal with any emerging disease-causing serogroups that are not covered by the vaccine.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040101.
The Web sites of the institutions at which this research was performed, the Swiss Tropical Institute and the Navrongo Health Research Centre, provide more information about the programs
The World Health Organization provides information on meningococcal disease, including the African meningitis belt (in English, Spanish, Chinese, Russian, and Arabic)
Information on meningitis and vaccines and their potential use in Africa is available from the Meningitis Vaccine Project (in English and French)
Medline Plus has encyclopedia pages on meningococcal meningitis
The US Centers for Disease Control and Prevention provides information on meningococcal disease (in English and Spanish)