Three Outbreak-causing Neisseria meningitidis Serogroup C Clones, Brazil

During 2003–2012, 8 clusters of meningococcal disease were identified in Rio de Janeiro State, Brazil, all caused by serogroup C Neisseria meningitidis. The isolates were assigned to 3 clonal complexes (cc): cc11, cc32, and cc103. These hyperinvasive disease lineages were associated with endemic disease, outbreaks, and high case-fatality rates.

T he last epidemic of Neisseria meningitidis serogroup C meningococcal disease in Rio de Janeiro State, Brazil, occurred in 1994. It was caused by C:2b:P1.10 isolates that belonged to cluster A4 (1). Although the number of cases of serogroup C disease subsequently declined after a vaccination campaign, rates of serogroup C disease again began to increase in 2000. During 2003-2012, public health surveillance identified 8 clusters of serogroup C meningococcal disease in Rio de Janeiro State. We report the investigation of these meningococcal disease clusters and typing information of the causative agent.

The Study
Public health surveillance of meningococcal disease in Rio de Janeiro State is conducted by the Meningitis Advisory Committee of the State Department of Health, which uses data obtained from 2 surveillance sources: mandatory reports of meningococcal disease cases and reports of laboratory-confirmed N. meningitidis isolates collected by the Central Laboratory Noel Nutels and the Infectious Diseases State Institute São Sebastião, which are state reference laboratories, and 1 outsourced laboratory for bacterial meningitis (Cientificalab Laboratory Products and Systems, Rio de Janeiro, Brazil). Chemoprophylaxis with rifampin is currently recommended for close contacts of persons with confirmed or suspected cases of meningococcal disease.
A cluster was defined as ≥3 cases of meningococcal disease with a clear epidemiologic link and with N. meningitidis of the same serogroup recovered from either a normally sterile site or detected by PCR. Reports of invasive meningococcal disease during 2000-2012 were obtained from the Meningitis Advisory Committee and analyzed by using EpiInfo (version 3.5.3; Centers for Disease Control and Prevention, Atlanta, GA, USA). This study was approved by the Ethical Committee of the Evandro Chagas Research Institute of the Oswaldo Cruz Foundation.
Isolates assigned to clonal complex (cc) 11, cc32, and cc103 were associated with the clusters of meningococcal disease (online Technical Appendix; Figure); all were rifampin-susceptible (MICs, 0.006-0.19 μg/mL). The results of genotyping the 122 invasive isolates collected from 1990 through 2010 are shown in the Table. The Table also indicates when the cluster-associated clones were first observed.

Conclusions
Clusters of meningococcal disease were a prominent feature of N. meningitidis infections in several countries during the 1990s (4,5). These meningococcal clusters have been associated with educational institutions and particular clones of serogroup C. Clusters and community outbreaks of serogroup C disease have recently been observed in Brazil with increasing frequency outside the person's place of residence and involving teenagers and young adults, e.g., caused by the ST-3780 (cc103) isolates (6)(7)(8). A single cluster has been associated with the C:4,7:P1.19,15 phenotype (9).
Although the annual incidence rate remained stable (2-3 cases/100,000 population), clusters of meningococcal disease marked a change in the epidemiology of N. meningitidis infection during the 2000s in Rio de Janeiro State, while serogroup C disease and its case-fatality rate steadily increased. These clusters were caused by different clones, involved mostly children, and were accompanied by high case-fatality rates. The serogroup C clones found in this study seem to have emerged during the 2000s and are also now the major cause of endemic meningococcal disease. Some of these clones, namely, cc11 and cc32, have undergone capsular switching. For instance, the 2-2:P1.5-1,10- Chemoprophylaxis to control clusters has been ineffective in preventing new cases, possibly because transmission might have been occurring among social networks that did not receive chemoprophylaxis. In addition, it is not known whether chemoprophylaxis reduces risk in educational institutions (5). All of these clusters were potentially   vaccine preventable with monovalent serogroup C meningococcal vaccine, which was instituted in the state program of routine vaccination for children (<2 years) in October 2010. The implementation of molecular surveillance is advisable to both guide immunization programs and to monitor the effects of the immunization program and its consequences for the population biology of N. meningitidis associated with invasive disease.

Acknowledgments
We thank the staff of the National Meningitis Reference Center for serologictyping, the staff of the microbiology laboratories for providing meningococcal isolates, all health professionals involved in the investigation of communicable diseases, Mônica