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Reinfection thresholds and the management of recurrent infections


Infectious disease is the leading cause of morbidity and mortality in developing countries, and one of the leading causes worldwide. The twentieth century witnessed spectacular decays in infectious disease. Vaccines have eliminated smallpox, and have dramatically reduced the incidence of childhood diseases. A major concern is that the success of vaccination and other control measures is far from uniform. Interventions aimed at reducing tuberculosis, malaria, and several respiratory and diarrhoeal diseases have generally failed.

The management of recurrent infections is a major global challenge for biomedical science and public health in the twenty-first century. Recurrent infections occur as pathogens evolve a variety of ways to circumvent immunity: persisting at reduced activity (Mycobacterium tuberculosis, Plasmodium spp), or confusing the immune system by change in appearance (influenza virus, respiratory syncytial virus). Empirical relationships between such elaborate host-pathogen interactions and the observed epidemiological patterns are difficult to deduce.

Simple mathematical models are useful conceptual tools, but the potential for unwanted artefacts increases dramatically as each layer of complexity is introduced. These will be paralleled by more flexible computer models, combining the dynamics of infection, immunity, and pathogen ecology. Intervention design will be explored in the presence of reinfection, space, stochasticity, and resonance effects.

Many high impact diseases (tuberculosis, malaria and respiratory diseases) are considered in depth, and the results given a broad perspective. Theoretical models will be developed in coordination with laboratory and fieldwork, with two complementary roles: (1) assess the epidemiological impact of mechanisms of infection and immunity; (2) set targets for future interventions. The control of complex infectious disease problems is currently a major challenge where integrated approaches are in great demand.

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