Meningococcal disease is a serious, rapidly developing, and potentially fatal disease affecting people worldwide with varying incidence depending on the geographical area.1 Around 1.2 million cases of meningococcal infection occur annually with 135,000 related deaths.2Neisseria meningitidis is one of the major causes of bacterial meningitis globally.3 Pharyngeal carriage of N. meningitidis has been considered to be a prerequisite for the development of invasive meningococcal disease (IMD) and known to be essential for transmission.4 The exact mechanism by which a pharyngeal colonization changes into an invasive disease status is not entirely clear. The possible mechanisms that have been suggested are bacterial virulence factors, host susceptibility, including age, prior viral infection, and smoking may ultimately lead to invasive meningococcal disease.5,6N. meningitidis serogroups A, B, C, W, Y, and X account for the majority of IMD cases.2 Globally, meningococcal carriage rates between 5% and 24% have been reported for children and adolescents.7

Meningococcal disease is endemic in Brazil and 1.5–2.0 cases per 100,000 inhabitants were reported during 2000–2009.8 Outbreaks of IMD caused by various serogroups have been reported.9,10 Since 2002, the proportion of cases attributed to meningococcal serogroup C has increased significantly and it is now the most frequent serogroup.1,11,12 After this serogroup C epidemic, Brazil included the meningococcal C conjugate vaccine into the National Immunization Program in 2010.1,12 In addition, studies describing meningococci carriage in Brazil are limited, with few specific studies in adolescents and young adults.8,12–14 No recent data are available on carriage across different age groups from infancy to adulthood and this remains a key knowledge gap. Further data are needed to help understand both the serogroup distribution and disease transmission as they may be useful to help identifying the age groups with higher carriage prevalence rates that could be targeted for vaccination against meningococcal disease and to assess the impact of current vaccination strategies. This information is crucial to support the use of monovalent meningococcal C conjugate vaccine and to gauge if there is a need for another meningococcal vaccine in the country. In this perspective, this cross-sectional study was conducted to assess the prevalence of N. meningitidis carriage and associated factors in among children and adolescents aged 1–24 years.

Four epidemic outbreaks have been reported in São Paulo in the last century. The first two outbreaks, occurring in 1920 and 1944, were caused by meningococcal serogroup A.18,19 The third (serogroup C – 1971) and fourth (serogroup A – 1974) outbreaks were characterized by two overlapping epidemic waves. Until then, the prevalence of serogroup C had not been associated with major outbreaks. This epidemic provided the impetus for first major mass testing of polysaccharide A and C vaccines resulting in control of the epidemic by 1975.9,18,19 In the late 1980s, epidemics due to serogroup B occurred in several locations across the country, demonstrating the highly variable and unpredictable epidemiology of this disease.

Since 2002, a significant increase in the proportion of cases attributed to serogroup C has been observed in São Paulo20 and other regions21 across Brazil making it in 2010 the most frequent serogroup causing meningococcal disease in the country.8,9 A meningococcal C conjugate vaccine (MCC) was introduced to the Brazilian Immunization Program in December 2010 for children under two years of age.

Despite the importance of N. meningitidis carriage for transmitting the disease, limited data describing N. meningitidis carriage in Brazil are available.8,12,13 Looking for covering this gap, this study assessed the N. meningitidis carriage in a wider age range, from childhood to young adult from a selected city of São Paulo state.

In this study, the overall carriage prevalence observed was similar to those observed in other studies.8,11,13 Although the carriage rate in children was not negligible, the highest carriage prevalence was observed in adolescents 10–19 years old.

Two years after the introduction of meningococcal C conjugate vaccination program in Brazil (2011–2012), high vaccine coverage (90–95%) was achieved, and a 50% reduction in the incidence of disease in the vaccinated cohort was demonstrated. However, no impact was observed in other age groups.12 Clearly, vaccinating only young children, who are not the main reservoir of N. meningitidis, will not result in herd protection.12,22,23 Our study results show that the highest carriage prevalence has been observed in older adolescents and young adults, similar to other studies.7,13,24 This age group should be included in a catch-up vaccination program, to achieve herd protection and successful meningococcal C disease control.

This study started 10 months after the introduction of the MCC vaccine in the National Immunization Program for children under two and some of the participants have received MCC vaccine. We observed a higher prevalence of pharyngeal carriage among unvaccinated (8.5%) than among vaccinated subjects (4.8%). MCC vaccination prevents acquisition of carriage, which is not observed with polysaccharide vaccines.8

In our study sample, serogroup C was the dominant serogroup followed by serogroup B. These results are aligned with another recent study on 11–19 year-old adolescents in Campinas, Brazil where serogroup C was also the most prevalent serogroup.25 However, differences in prevalence of serogroups across geographical regions have been observed. While recent studies on meningococcal carriage in Europe24 and particularly in United Kindom26 have identified serogroup B as the most prevalent serogroup, in another study conducted in Africa it was serogroup W.27,28 These data suggest a regional variation in serogroup meningococcal carriage.

In this study the pharyngeal carriage prevalence of N. meningitidis was also evaluated on the basis of different risk factors. Higher pharyngeal carriage prevalence was observed in previously unvaccinated subjects, who used the public health system, and attended public educational institutions. Higher pharyngeal carriage prevalence was also seen in subjects with no previous history of meningitis, those with a previous history of contact with a meningitis-affected patient, and those who had not used antibiotics previously. However, no significant association (p≤0.05) was observed between carriage prevalence and risk factors in the multivariate analysis. Nonetheless, an increase in the number of household members was found to be independently associated with an increased risk of meningococcal carriage in the logistic regression analyses.

The strength of this study is that it was population-based where subjects across a wide age-range were recruited from different facilities like health care centers, day care centers and schools thereby covering a wider population and giving better surveillance. Further, qPCR, a sensitive technique, was used in this study for detection of different serogroups. A limitation of this study is that the selected population constitutes a convenience sample and the results cannot be extrapolated to all communities in Brazil and its external validity may be subject to criticism. However, the results found by age-group are consistent with those reported in the literature.29–31 A low sample size in some age groups could have also been a limitation of this study. The fact that we did not assessed the association between smoking habits of older subjects (or household members) and risk of N. meningitidis carriage constitutes another limitation. As mentioned earlier, 60.9% of meningococci carriers (n=53) identified in the current study remained non-groupable, i.e. not capsulated. However, this should not be seen as a limitation of the study. In fact, most carrier isolates have been shown to lack capsule production. Approximately 50% of the strains isolated from carriers lack capsule and are therefore serologically not groupable.32,33 In one of the studies on meningococcal carriage prevalence in Chile, 65% of isolated strains were non-groupable.34 Similar high percentages of non-groupable strains have been reported in other studies.8,35

This was the first study in Brazil evaluating the meningococcal carrier state in a wide age range. This study revealed that both the age groups 10–14 and 15–19 years had similarly high pharyngeal carriage prevalence of N. meningitidis in Embu das Artes. Vaccination programs should consider the inclusion of catch-up cohorts to achieve herd protection with direct and indirect effects of vaccination. Serogroup C was the most predominant, followed by serogroup B, and to a lesser extent serogroups Y and W. Due to the impact of meningococcal C vaccination and highly variable and unpredictable epidemiology of meningococcal disease, a constant surveillance is required. This study will further add to our understanding of meningococcal disease epidemiology in Brazil and may assist in developing future vaccination strategies.

All authors participated in the design or implementation or analysis, and interpretation of the study and in the development of this manuscript. All authors had full access to the data and gave final approval before submission. The corresponding author was responsible for submission of the publication.

L.Y. Weckx received Institutional grants from the GSK group of companies during the conduct of the study. E. Ortega-Barria, R Colindres, E.N.C. Barros and R. Devadiga are employees of the GSK group of companies. E. de Barros, E. Ortega-Barria and R Colindres own stock options in the GSK group of companies. S.H. Tuboi was a former employee of the GSK group of companies at the time of the study and owns restricted shares in the GSK group of companies. M.G. Gonçalves, R.F. Puccini and A.M.O. Machado have nothing to disclose.