Clinical And Therapeutic Studies Of Human Filariasis and Related Diseases

National Institute Of Allergy And Infectious Diseases

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Abstract

Having developed both molecular and recombinant antigen-based approaches to sensitive and specific diagnosis for filarial and STH infections, we utilized these diagnostics around the world and have provided insights into parasite transmission dynamics in Kenya, Mali, Nigeria, Southeast Asia (Myanmar/Thailand), and American Samoa. A number of epidemiologic studies have been performed in Mali to both demonstrate the efficacy of yearly MDA programs to interrupt transmission of W. bancrofti and O. volvulus and to identify the extent of morbidity (i.e., lymphedema) associated with bancroftian filariasis. In addition, based on the development of the LoaScope, we have examined the feasibility of widescale use of this video-based microscopy for mapping L. loa infection in Onchocerca-co-endemic regions of the world and for the strategy of Test and not Treat (TaNT) as described in Project 4 below. Because the clinical expression of infection with most filarial infections in expatriates is significantly different from those exposed from birth to the parasite, pathogenesis underlying the clinical expression of disease and methods to approach and treat the returned traveler with filarial infection must differ as well. In a comprehensive analysis of 205 patients with loiasis, we extended our earlier observations related to immunologically-based clinical differences and shown that these immune perturbations move toward homeostasis following therapy. A similar comprehensive examination of patients with onchocerciasis has also been performed. Separate studies on migrants with subarachnoid neurocysticercosis and was shown to be mediated by local (CNS) inflammation, the nature of which could predict time to cure. Helping define the cause of the Nodding Syndrome (NS), a devastating syndrome associated with O. volvulus infection, has been a part of the work of the HIS over the past 6 years. Previously, we helped demonstrate the association of NS with the presence of O. volvulus -specific antibodies and had shown that these antibodies induce an autoreactive neurotoxic response that may be responsible for the syndrome. Over the past year, we have provided new insights into these cross-reactive autoantibodies by showing that they are not locally produced in the CNS and that, in a comprehensive family study of an extended kindred performed as part of the Undiagnosed Disease Service at the NIH, was not genetically based. As has been mentioned above, we have used molecular and bioinformatic approaches to identify diagnostic targets for many parasitic infections. Using methodologies to identify highly repetitive DNA short sequences, we have developed new molecular approaches for highly sensitive parasite detection in L. loa, W. bancrofti, O. volvulus, A. cantonensis, A. lumbricoides, S. stercoralis, and T. cruzi. Many of these assays can detect the parasite DNA as cell free circulating DNA (cfcDNA) in plasma, CSF, and/or urine.