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Dynamics of lymphatic filarial infection at the cellular and molecular levels

Objective



Lymphatic filariasis is an active focus for tropical disease research in immunology, epidemiology and molecular biology. This major tropical disease,afflicting 90 million people, is typical of helminth infections, involving selective lymphocyte activation, immunogenetic predisposition, cytokine imbalance and isotype regulation, acquired immunity and immunopathology. our studies during STD-2 contributed to these developments with detailed cross-sectional studies of infected Populations. Longitudinal analysis of immunological processes in lymphatic filariasis as a function of infection in a dynamic context is now required. A field study will be set up to follow, over a period of 3 years, the parasitology status of selected individuals initially either infected or apparently free of infection. over this period, fluctuations in parasite load and/or status within the same individual will be closely monitored- These variables must be determined to verify our epidemiological categorisation of endemic populations, to validate diagnostic tools and to design strategies for developing immunoprophylactic agents. The study design will also focus on the acute stage of lymphatic filariasis by monitoring immunological parameters in patients experiencing short-term episodes of acute disease which cannot be followed by point prevalence studies.
T and B cell responses will be analysed to seek changes over time or concurrent with alterations of patients' clinical and parasitological status. T cells will be tested with adult and infective larval antigens in proliferative assays and IL4 and gIFN release, functions which are profoundly perturbed in filarial infection. Distinct profiles of antibody isotypes to Brugia exist in each disease state, and we will study the dynamics of these-isotypes over time. Responses will also be measured to recombinant antigens now available. Differential responses to L3 and adult antigens as well as stage-specific recombinant proteins will be
sought. T cell receptor (TCR) V Beta gene usage will be established for filarial-specific cells and compared over time and between clinical states. Finally, we will study changes in cytokine (IL6, TNF and ILIO) expression in the serum of exposed and infected individuals.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE
Address
Campus At Silwood Park, Road A329 (Virginia Water
SW7 2AZ London
United Kingdom

Participants (2)

LEIDEN UNIVERSITY
Netherlands
Address
62,Wassenaarseweg 62
2300 RC Leiden
UNIVERSITY OF INDONESIA
Indonesia
Address
6,Salemba Raya 6
10430 Jakarta