Determinants of Invasiveness Beneath the Capsule of the Pneumococcus

Abstract

Interventions provide unique opportunities to learn about the natural history of infectious diseases, and one such intervention is the global rollout of pneumococcal conjugate vaccine. This is a vast experiment in natural selection, during which specific capsular types contained in 10–13-valent vaccines are increasingly being prevented from circulating in the human population. These types were chosen on the basis of their prevalence among invasive pneumococcal disease isolates, so by definition they represent a selection of the dominant invasive pneumococcal serotypes. The remaining ≥80 serotypes are then increasingly free to compete in an environment without their most invasive competitors. We can measure the invasive potential of these “replacement” strains most simply by comparing their prevalence in collections of carriage strains versus invasive strains. This allows the development of an invasiveness index [1–6],which has until now been based entirely on capsular types. Thus, serotypes 1, 5, and 7F, which are rarely detected among carriage isolates and almost exclusively found in collections of invasive disease isolates, have the highestinvasivepotential, whichissimply a ratio of their occurrence in collections ofinvasiveversuscarriagestrains.Acaveat ofthisapproachisthatthesestudiesoncarriage have used culture only, so as molecular or immunologic methods are developed to identify low density carriage, these invasive indices may change. There are some further caveats to these comparisons, such as taking the invasive strains and carriage strains from the same population in time and place, and these fundamentals are met in the article by Browall et al [7], from the Karolinska Institute in Sweden. They examined a collection of 550 carriage strains and 165 invasive strains, all recovered from children <18 years of age in the Stockholm area between 1997 and 2004, presumably before the introduction conjugate vaccine in much of that population. The mean age of 2.5 years among subjects with invasive pneumococci and 3.3 years among those carrying pneumococci meansthat onlyafraction of the subjects in each group were <1 year old, the age when most mortality due to pneumococcal infection occurs in children in developing countries. Nonetheless, these data offer a useful comparison between invasiveandcarriagestrainsinthe samecommunity in a developed country.