Marc Lipsitch (Director, Center for Communicable Disease Dynamics, Harvard School of Public Health, Department of Epidemiology, Harvard University; SFI External Professor)
Abstract. Streptococcus pneumoniae is a major human pathogen, responsible for ~800,000 deaths annually and much additional morbidity worldwide. Conjugate vaccines, introduced in 2000, provide protection against a subset of the ~94 serotypes of this organism, but only against that subset, and by removing their targeted serotypes they promote "serotype replacement," an increase in the prevalence and incidence of disease from serotypes not included in the vaccine. Serotype is determined by a genetic locus that encodes biosynthetic enzymes for a polysaccharide capsule that coats the organism; this capsule strongly affects many different biological properties of the organism. Understanding and addressing serotype replacement is a practical public health problem; to do so, one needs to understand the reason for the persistence of many serotypes in the first place – a pathogen equivalent of GE Hutchinson's famous Paradox of the Plankton.
This talk will describe experimental, epidemiologic and mathematical modeling efforts to understand serotype coexistence, its determinants and consequences. Pneumococcal serotypes range from rare (<<0.1% of children carry them) to somewhat common (~10% of children), and the same serotypes tend to be common across many different populations, and limited fluctuations in frequency over time. Our experimental and epidemiologic studies show that those serotypes that are most common tend to be better than their competitors on every fitness component that has been measured. Why do the "weak" serotypes not disappear? One possibility is that immunity is specific to particular serotypes, promoting persistence of rarer types. However we show that this type of immunity is weak, not strong enough by itself to produce observed patterns. Another form of immunity reduces the duration of carrying all serotypes, but disproportionately reduces the duration of the most fit (longest-carried) types. Using an individual-based transmission model, we show that these two types of immunity together (but not separately) are adequate to explain serotype coexistence and other features of pneumococcal serotype epidemiology. In the ecological debate over coexistence mechanisms, this system shows a need for both equalizing and niche-creating mechanisms to promote coexistence. Other coexistence problems in infectious disease epidemiology are even thornier and are the topic of current efforts.
(key collaborators: Sarah Cobey, Richard Malley, Daniel Weinberger, Krzysztof Trzcinski, Osman Abdullahi, Anthony Scott)