Transmission intensity and the immunoepidemiology of bancroftian filariasis in East Africa

Previous attempts to determine the interactions between filariasis transmis sion intensity, infection and chronic disease have been limited by a lack o f a theoretical framework that allows the explicit examination of mechanism s that may link these variables at the community level. Here, we show how d eterministic mathematical models, in conjunction with analyses of standardi zed field data from communities with varying parasite transmission intensit ies, can provide a particularly powerful framework for investigating this t opic. These models were based on adult worm population dynamics, worm initi ated chronic disease and two major forms of acquired immunity (larval- vers us adult-worm generated) explicitly linked to community transmission intens ity as measured by the Annual Transmission Potential (ATP). They were then fitted to data from low, moderate and moderately high transmission communit ies from East Africa to determine the mechanistic relationships between tra nsmission, infection and observed filarial morbidity. The results indicate a profound effect of transmission intensity on patent infection and chronic disease, and on the generation and impact of immunity on these variables. For infection, the analysis indicates that in areas of higher parasite tran smission, community-specific microfilarial rates may increase proportionate ly with transmission intensity until moderated by the generation of herd im munity. This supports recent suggestions that acquired immunity in filarias is is transmission driven and may be significant only in areas of high tran smission. In East Africa, this transmission threshold is likely to be highe r than an ATP of at least 100. A new finding from the analysis of the disea se data is that per capita worm pathogenicity could increase with transmiss ion intensity such that the prevalences of both hydrocele and lymphoedema, even without immunopathological involvement, may increase disproportionatel y with transmission intensity. For lymphoedema, this rise may be further ac celerated with the onset of immunopathology. An intriguing finding is that there may be at least two types of immunity operating in filariasis: one im plicated in anti-infection immunity and generated by past experience of adu lt worms, the other involved in immune-mediated pathology and based on cumu lative experience of infective larvae. If confirmed, these findings have im portant implications for the new global initiative to achieve control of th is disease.