| dc.description.abstract | Previous attempts to determine the interactions between filariasis transmission intensity, infection and chronic disease have been limited by a lack of a theoretical framework that allows the explicit examination of mechanisms that may link these variables at the community level.
Here, we show how deterministic mathematical models, in conjunction with analyses of standardized field data from communities with varying parasite transmission intensities, can provide a particularly powerful framework for investigating this topic. These models were based on adult worm population dynamics, worm initiated chronic disease and two major forms of acquired immunity (larvalversus
adult-worm generated) explicitly linked to community
transmission intensity as measured by the Annual
Transmission Potential (ATP). They were then fitted to data from low, moderate and moderately high transmission
communities from East Africa to determine the mechanistic
relationships between transmission, 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 transmission, community-specific microfilarial rates may increase proportionately with transmission intensity until moderated by the generation of herd immunity. This supports recent suggestions that acquired immunity in filariasis is transmission driven and may be significant only in areas of high transmission. In East Africa, this transmission threshold is likely to be
higher than an ATP of at least 100. A new finding from the analysis of the disease data is that per capita worm
pathogenicity could increase with transmission intensity
such that the prevalences of both hydrocele and lymphoedema, even without immunopathological involvement, may increase disproportionately with transmission intensity. For lymphoedema, this rise may be further accelerated with the onset of immunopathology. An intriguing finding is that
there may be at least two types of immunity operating in
filariasis: one implicated in anti-infection immunity and
generated by past experience of adult worms, the other
involved in immune-mediated pathology and based on
cumulative experience of infective larvae. If confirmed,
these findings have important implications for the new
global initiative to achieve control of this disease | en |
