A Narrative Review of the Molecular Epidemiology and Laboratory Surveillance of Vaccine Preventable Bacterial Meningitis Agents: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae and Streptococcus agalactiae

Abstract

This narrative review describes the public health importance of four most common bacterial meningitis agents, Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, and S. agalactiae (group B Streptococcus). Three of them are strict human pathogens that normally colonize the nasopharynx and may invade the blood stream to cause systemic infections and meningitis. S. agalactiae colonizes the genito-gastrointestinal tract and is an important meningitis agent in newborns, but also causes invasive infections in infants or adults. These four bacteria have polysaccharide capsules that protect them against the host complement defense. Currently licensed conjugate vaccines (against S. pneumoniae, H. influenza, and N. meningitidis only but not S. agalactiae) can induce protective serum antibodies in infants as young as two months old offering protection to the most vulnerable groups, and the ability to eliminate carriage of homologous serotype strains in vaccinated subjects lending further protection to those not vaccinated through herd immunity. However, the serotype-specific nature of these vaccines have driven the bacteria to adapt by mechanisms that affect the capsule antigens through either capsule switching or capsule replacement in addition to the possibility of unmasking of strains or serotypes not covered by the vaccines. The post-vaccine molecular epidemiology of vaccine-preventable bacterial meningitis is discussed based on findings obtained with newer genomic laboratory surveillance methods.

Keywords: H. influenzae; N. meningitidis; S. agalactiae; S. pneumoniae; bacterial meningitis; conjugate vaccines; post-vaccine surveillance.

Figure 1

(a) Depiction of capsule switching between a genetic lineage 1* strain with a vaccine-type capsule (colored green) and a genetic lineage 2* strain with a non-vaccine type capsule (colored red). Diagram based on information from Swartley et al. [48]. (b) Illustration of capsule replacement when the vaccine capsule type (colored green) strain of genetic lineage 1* is removed by the vaccine, leaving the strain of genetic lineage 2* with non-vaccine capsule (colored red) to remain and proliferate. Diagram based on information from Lipstich M [49]. (c) Another scenario of capsule replacement when strain of genetic lineage 1* with both vaccine (colored green) and non-vaccine (colored red) capsule types are present before vaccine introduction and after vaccine use, only the non-vaccine capsule type of genetic lineage 1* strain remains. Diagram based on information from Lipstich M [49].