This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Microsporidia were sporadically identified in humans prior to 1985 and then emerged as causes of opportunistic infections associated with diarrhea and systemic disease in persons with AIDS. Enterocytozoon bieneusi is the most commonly-reported microsporidian species that infects humans, but it is also the least-characterized microsporidian. Unlike most of the other commonly-detected species of microsporidia, E. bieneusi can not be grown in tissue culture and does not naturally or experimentally infect small laboratory animals (eg. rodents and rabbits). This has severely limited studies on the natural history, epidemiology, pathogenesis, chemotherapy, and immunology of E. bieneusi infections. Non-human primates, however, are susceptible to natural and experimental E. bieneusi infections, and these simian infections simulate what is known about human infections. Preliminary studies have shown that by nested PCR using E. bieneusi-specific primers on fecal specimens, positive results were obtained from 84 of 188 (44.7%) rhesus macaques, 30 of 88 (34.1%) pigtail macaques, and 26 of 72 (36.1%) baboons that were housed in the outdoor corrals. From 70 NHPs that were necropsied during a four-month period of the current year that could be accessed for specimens, 19 (27%) were positive for E. bieneusi by PCR in bile and/or feces. Of these NHPs, 14 had been sacrificed as part of their experimental protocols and 5 were euthanized due to diarrhea, weight loss, and dehydration. Furthermore, bile specimens of the E. bieneusi-infected animals were uniformly less pigmented than those of the uninfected NHPs with diarrhea and correspondingly higher billirubin levels. A statistically significant association was observed between poor pregnancy outcome and E. bieneusi spore shedding among the dams compared with uninfected dams in a retrospective study, and prospective studies are planned corroboration. These early observations support continued studies to better understand the pathogenesis of E. bieneusi infections in NHPs as a contributor to GI disease.
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