Abstract
Background Neisseria meningitidis serogroup B has been predominant in Brazil, but no broadly effective vaccine is available to prevent endemic meningococcal disease. To understand genetic diversity among serogroup B strains in Brazil, we selected a nationally representative sample of clinical disease isolates from 2004, and a temporally representative sample for the state of São Paulo (1988–2006) for study (n = 372).MethodsWe performed multi-locus sequence typing (MLST) and sequence analysis of five outer membrane protein (OMP) genes, including novel vaccine targets fHbp and nadA.ResultsIn 2004, strain B:4:P1.15,19 clonal complex ST-32/ET-5 (cc32) predominated throughout Brazil; regional variation in MLST sequence type (ST), fetA, and porB was significant but diversity was limited for nadA and fHbp. Between 1988 and 1996, the São Paulo isolates shifted from clonal complex ST-41/44/Lineage 3 (cc41/44) to cc32. OMP variation was associated with but not predicted by cc or ST. Overall, fHbp variant 1/subfamily B was present in 80% of isolates and showed little diversity. The majority of nadA were similar to reference allele 1.ConclusionsA predominant serogroup B lineage has circulated in Brazil for over a decade with significant regional and temporal diversity in ST, fetA, and porB, but not in nadA and fHbp.
Highlights
Neisseria meningitidis causes severe invasive disease which occurs sporadically or as outbreaks and which is characterized by rapid onset, high case fatality ratio and devastating sequelae
Our goal was to determine the genetic diversity of outer membrane proteins (OMPs) among a representative sample of invasive serogroup B clinical isolates from all major geographic regions of Brazil in 2004, and among additional isolates from Sao Paulo from the years 1988, 1996, and 2006, which span the initiation, peak and decline of the most recent epidemic at its epicenter [2]
Sixty-seven (23.7%) of those had one of 62 new sequence type (ST) not previously reported; an additional 19 had an ST not previously reported from Brazil
Summary
Neisseria meningitidis causes severe invasive disease which occurs sporadically or as outbreaks and which is characterized by rapid onset, high case fatality ratio and devastating sequelae. The incidence peaked in 1996 at 7.8 cases per 100,000 persons, and the epicenter was Sao Paulo State, Brazil where 80% of cases were caused by serogroup B strains [2]. Polysaccharide and polysaccharide-protein conjugate vaccines are effective and available for prevention of meningococcal serogroups A, C, W-135, and Y, but not for serogroup B because that capsule is poorly immunogenic. Outer membrane vesicle vaccines have been used in epidemic situations [3] but vaccines to prevent genetically diverse endemic serogroup B disease are needed. Neisseria meningitidis serogroup B has been predominant in Brazil, but no broadly effective vaccine is available to prevent endemic meningococcal disease. To understand genetic diversity among serogroup B strains in Brazil, we selected a nationally representative sample of clinical disease isolates from 2004, and a temporally representative sample for the state of Sao Paulo (1988–2006) for study (n = 372)
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