Clonal analysis of Neisseria meningitidis serogroup B strains in South Africa, 2002 to 2006: emergence of new clone ST-4240/6688

Abstract

From August 1999 through July 2002, hyperinvasive Neisseria meningitidis serogroup B (MenB) clonal complexes (CCs), namely, ST-32/ET-5 (CC32) and ST-41/44/lineage 3 (CC41/44), were predominant in the Western Cape Province of South Africa. This study analyzed MenB invasive isolates from a national laboratory-based surveillance system that were collected from January 2002 through December 2006. Isolates were characterized by pulsed-field gel electrophoresis (PFGE) (n = 302), and multilocus sequence typing (MLST) and PorA and FetA typing were performed on randomly selected isolates (34/302, 11%). In total, 2,400 cases were reported, with the highest numbers from Gauteng Province (1,307/2,400, 54%) and Western Cape Province (393/2,400, 16%); 67% (1,617/2,400) had viable isolates and 19% (307/1,617) were identified as serogroup B. MenB incidence remained stable over time (P = 0.77) (average incidence, 0.13/100,000 population [range, 0.10 to 0.16/100,000 population]). PFGE (302/307, 98%) divided isolates (206/302, 68%) into 13 clusters and 96 outliers. The largest cluster, B1, accounted for 25% of isolates (76/302) over the study period; its prevalence decreased from 43% (20/47) in 2002 to 13% (8/62) in 2006 (P < 0.001), and it was common in the Western Cape (58/76, 76%). Clusters B2 and B3 accounted for 10% (31/302) and 6% (19/302), respectively, and showed no significant change over time and were predominant in Gauteng. Randomly selected isolates from clusters B1, B2, and B3 belonged to CC32, CC41/44, and the new CC4240/6688, respectively. Overall, 15 PorA and 12 FetA types were identified. MenB isolates were mostly diverse with no single dominant clone; however, CC32 and CC41/44 accounted for 35% and the new CC4240/6688 was the third most prevalent clone.

Fig 1

Incidence of meningococcal disease in South Africa, by serogroup from 2002 to 2006 (n = 2,400). “Other” includes serogroups X (n = 7) and Z (n = 2) and nongroupable (n = 2) isolates.

Fig 2

Age-specific incidence for meningococcal disease, South Africa in 2006 (n = 667). Age was known for 632/667 (95%) reported cases; 474/667 (71%) cases were serogrouped, and 64/474 (14%) cases were identified as serogroup B. Age was unknown for 4 serogroup B cases.

Fig 3

PFGE dendrogram with MLST clonal complex information, representing the genetic relationships among serogroup B meningococci causing invasive disease in South Africa from 2002 to 2006 (n = 302).

Fig 4

Meningococcal serogroup B PFGE clusters in South Africa from 2002 to 2006 (n = 302). By inference, B1 represents ST-32/ET-5; B2, ST-41/44/lineage 3; B3, ST-4240/6688; B4, ST-41/44/lineage 3; B5, ST-865; B7, ST-41/44/lineage 3; B8, ST-41/44/lineage 3; B10, ST-269; and B12, ST-334. No isolates were selected for MLST from cluster B6, B9, B11, or B13.

Fig 5

Population snapshot of N. meningitidis serogroup B isolates in South Africa from 2002 to 2006 (n = 33). The size of the circle is proportional to the number of isolates. Pale blue lines connect double locus variants. eBURST groups are associated with the following clonal complexes: 1, ST-41/44/lineage 3; 2, ST-4240/6688; 3, ST32/ET-5; 4, ST-41/44/lineage 3; 5, not assigned to a clonal complex; and 6, ST-865.