Experts Call For New Pneumococcal Vaccine Strategies

Pneumococcal conjugate vaccines (PCVs) have been effective at reducing rates of invasive pneumococcal disease. The vaccines have led to reduction in not only pneumonia, but also sepsis and bacteremia in immunized populations.

Recently, the US Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices released updates to pneumococcal disease vaccination, suggesting clinicians should discuss conjugate vaccine with more of their older patients.

Yet despite the widespread use of PCVs, Streptococcus pneumoniae remains the leading cause of another invasive disease—bacterial meningitis—in the post-neonatal pediatric population.

An investigative duo from the University of Alabama at Birmingham published a review in The Pediatric Infectious Disease Journal highlighting the fact that amidst success in other areas, PCVs have done little to reduce disease incidence of meningitis caused by pneumococci colonization. The authors suggest it would be worthwhile to develop new vaccines capable of better preventing pneumococcal meningitis.

The investigators conducted searches in PubMed for relevant articles published from January 1930 to present.

The team explains that the proliferation of PCVs has changed the epidemiology of pneumococcal serotypes with a near-total replacement of PCV types in carriage and incomplete replacement in invasive disease.

“A Swedish study showed that before the introduction of PCV7 and PCV13, 38% and 18% of carriage isolates were non-PCV7 and non-PCV13 types, respectively, but after the introduction of the vaccines, the respective values were 95% and 89%, [respectively]” study authors wrote, providing an example of this trend.

This change in epidemiology manifests differently in various regions, but has globally led to large-scale strain replacement in adult meningitis.

In an Israeli study the authors refer to, a 70% decline in vaccine type meningitis was shown to have occurred alongside an overall increase in pneumococcal meningitis largely due to the emergence of serotypes 23A and 23B.

Rising cases of meningitis appear to be caused by non-PCV strains with capsule types that do not commonly lead to bacteremia or sepsis. Based on this, the authors infer that they may be reaching the brain through a nonhematogenous route.

“Indeed, several studies have supported the expectation that pneumococcal meningitis can be caused by a nonhematogenous route of infection, whereby the bacteria can travel directly from the nasopharynx or from ear infections to the brain,” they wrote.

Because these nonhematogenous routes likely require colonization of the nasopharynx, the authors argue that a vaccine which eradicates carriage may be able to prevent pneumococcal meningitis.

The authors also examined several ways to significantly reduce carriage. One option is the expansion of PCVs to increase the number of capsular types.

However, this approach may be difficult and costly due to the serotype diversity of newly prevalent strains. In addition, there is evidence that the introduction of new polysaccharide antigens decreases the antibody response the vaccine produces.

An alternative strategy would be identifying the virulence factors that predispose people to nasal colonization and target them in

“Either approach will be difficult,” David E. Briles, PhD, a study author and a member of the Department of Microbiology and Pediatrics at the University of Alabama at Birmingham told Contagion®.

For providers, though, there’s a simple and unfortunate takeaway.

“The main thing to know is that even if children get the PCV13 vaccine, they should still be prepared to see pneumococcal meningitis in some of their patients,” Briles concluded.