Clinical And Therapeutic Studies Of Human Filariasis and Related Diseases

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

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. In the past year, we have shown the utility of rapid, point of contact (POC) tests in the context of coincident Loa loa/Onchocerca volvulus infection in Cameroon as well as driving the target product profiles for onchocerciasis mapping and MDA stopping decisions throughout Africa. In addition, we have provided clinical validity of a new recombinant antigen (SsIR/SsNIE)-based prototype ELISA that is in the process of being fully commercialized. 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. 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, T. cruzi and Schistotoma spp (mansoni, haematobium, intercalatum. 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.