Global population structure of Haemophilus influenzae serotype a (Hia) and emergence of invasive Hia disease: capsule switching or capsule replacement?

Abstract

The population structure of Haemophilus influenzae serotype a (Hia) was examined by interrogation of the H. influenzae MLST website. There were 196 entries of Hia with 55 sequence types (STs) identified (as of 3 September 2020). BURST analysis clustered related STs into four complexes with ST-23, ST-4, ST-21, and ST-62 identified as their ancestral STs. The majority of Hia entries (73.4%) and STs (65.5%) were identified as clonal division I (ST-23 and ST-4 complexes). Only 43 (21.9%) entries and 14 STs (25.5%) were identified as clonal division II (ST-62 and ST-21 complexes). Current data suggest that most invasive Hia belonged to clonal division I and the ST-23 complex, while most clonal division II Hia were respiratory isolates, with the exception of ST-62 which was common among invasive Hia in the US southwest. Comparison of the capsule bexABCD genes from clonal divisions I and II strains showed sequence diversity with variations following the pattern of clonal divisions. Evidence from the literature and the current study suggests that the recent emergence of invasive Hia might be related to capsule replacement subsequent to the implementation of the Hib conjugate vaccine and possibly exacerbated by other conjugate vaccines that may have altered the microbial flora of the human respiratory tract.