Clonal distribution of disease-associated and healthy carrier isolates of Neisseria meningitidis between 1983 and 2005 in Cuba

Abstract

In response to epidemic levels of serogroup B meningococcal disease in Cuba during the 1980s, the VA-MENGOC-BC vaccine was developed and introduced into the National Infant Immunization Program in 1991. Since then the incidence of meningococcal disease in Cuba has returned to the low levels recorded before the epidemic. A total of 420 Neisseria meningitidis strains collected between 1983 and 2005 in Cuba were analyzed by multilocus sequence typing (MLST). The set of strains comprised 167 isolated from disease cases and 253 obtained from healthy carriers. By MLST analysis, 63 sequence types (STs) were identified, and 32 of these were reported to be a new ST. The Cuban isolates were associated with 12 clonal complexes; and the most common were ST-32 (246 isolates), ST-53 (86 isolates), and ST-41/44 (36 isolates). This study also showed that the application of VA-MENGOC-BC, the Cuban serogroup B and C vaccine, reduced the frequency and diversity of hypervirulent clonal complexes ST-32 (vaccine serogroup B type-strain) and ST-41/44 and also affected other lineages. Lineages ST-8 and ST-11 were no longer found during the postvaccination period. The vaccine also affected the genetic composition of the carrier-associated meningococcal isolates. The number of carrier isolates belonging to hypervirulent lineages decreased significantly after vaccination, and ST-53, a sequence type common in carriers, became the predominant ST.

FIG. 1.

Genetic relationships among STs of Cuban isolates by neighbor-joining analysis. (a) Phylogenetic relationships of 167 invasive meningococcal isolates; (b) phylogenetic relationships of 253 carrier isolates (the numbers of strains are given in parentheses). New STs are marked by asterisks, and the clonal complexes are indicated by brackets. Nodes with bootstrap support higher than 90% are indicated.

FIG. 2.

Splits graphs showing the relationships among STs in the two most common and diverse hypervirulent lineages present in Neisseria meningitidis in Cuba: ST-32 (246 isolates) and ST-41/44 (36 isolates) clonal complexes. (a and b) ST-32 complex; (c and d) ST-41/44 complex.