Clinical And Therapeutic Studies Of Human Filariasis and Related Diseases

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Having developed both molecular and recombinant antigen-based approaches to sensitive and specific diagnosis for filarial and STH infections, we have utilized these diagnostics around the world and many are in the throes of being commercialized. 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. In more recent studies, we have demonstrated that autoantibodies not only to Leiomodin-1 but also to DJ-1 are markedly higher in the CSF of patients with NS. 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, T. cruzi and Schistotoma spp (mansoni, haematobium, intercalatum), Leishmania spp. Many of these assays can detect the parasite DNA as cell free circulating DNA (cfcDNA) in plasma, CSF, and/or urine. Futhermore, we have developed recombinase polymerase assays (RPA) for both A. cantonensis and O. volvulus.