Clinical And Therapeutic Studies Of Human Filariasis and Related Diseases

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

Because the clinical expression of filarial infections in expatriates is significantly different from that in those exposed from birth to the parasite, we have continued to define more precisely the differences between travelers (or long term residents) and those native to filarial-endemic regions. Thus, we have collated our long-term data to demonstrate quite definitively the differences in both risk of acquisition of these infections as well as the clinical manifestations of infection. Our data suggest that eosinophil-mediated processes are responsible for many of the differences seen. We have done a similar retrospective study of a large number of patients with onchocerciasis that suggests that the skin dwelling O. volvulus drives responses in both temporary residents and those with lifelong exposure that are very different than what has been seen for the blood-borne filarial infections (Showler, Nutman submitted). The role of O. volvulus-specific antigens in the pathogenesis of the Nodding Syndrome was demonstrated quite definitively. The mechanism underlying this appears to be a set of O. volvulus-induced antibodies that cross reacts with leimodin-1, a human CNS-expressed protein. These antibodies appear to be neurotoxic. Having previously developed a high throughput, highly sensitive and specific molecular diagnostic panel for the 8 most common gastrointestinal parasites of humans, we have expanded and improved this panel. This newer methodology was used both in a large cohort study in Kenya and as part of collaboration with the CDC Division of Quarantine in which >2000 Burmese refugees were studied while in refugee camps in Thailand and following re-settlement in the United States. Because of the severe post treatment reactions seen in loiasis, new methods of safer treatment have been sought. Unlike many of the other filarial infections Loa loa does not contain the intracellular Wolbachia endosymbiont. This and other data have suggested that it is the eosinophil activation and tissue eosinophilia that is mediating the severe post treatment inflammatory reactions. To understand better the pathogenesis of filarial infections (onchocerciasis, loiaisis, lymphatic filarasis) clinical assessments of patients with these and other related non-filarial (strongyloides, malaria) infections have been studied in detail. The influence that filarial infections have on the clinical expression of non-filarial infectious diseases have also been studied by performing clinical trials in filarial-endemic regions of the world that are co-endemic for malaria (Mali), tuberculosis (India) and HIV (India). New diagnostic approaches have been developed and utilized for the rapid and specific diagnosis of Strongyloidiasis, loiasis, and onchocerciasis. Rapid (almost point of care) diagnostics have been developed for surveillance of W. bancrofti and O. volvulus following mass drug distribution campaigns.