Visceral leishmaniasis is an understudied parasitic disease responsible for significant global morbidity and mortality. We are presently investigating a method of disease prevention termed paratransgenesis. In this approach, symbiotic or commensal bacteria are transformed to produce anti-Leishmania molecules. The transformed bacteria are delivered back to sand flies to inactivate the parasite within the vector itself. In this study, we identified 28 distinct gut microorganisms from Phlebotomus argentipes trapped from four visceral leishmaniasis-endemic sites in India. A significant percent of Staphylococcus spp., environmental bacteria, and Enterobacteriaceae were identified. Two non-pathogenic organisms, Bacillus megaterium and Brevibacterium linens, were also isolated. Both organisms are also used extensively in industry. Our results indicate that B. megaterium and B. linens are possible candidates for use in a model of paratransgenesis to prevent transmission of Leishmania.
Conventional methodologies to control vector borne diseases with chemical pesticides are often associated with environmental toxicity, adverse effects on human health and the emergence of insect resistance. In the paratransgenic strategy, symbiotic or commensal microbes of host insects are transformed to express gene products that interfere with pathogen transmission. These genetically altered microbes are re-introduced back to the insect where expression of the engineered molecules decreases the host's ability to transmit the pathogen. We have successfully utilized this strategy to reduce carriage rates of Trypanosoma cruzi, the causative agent of Chagas disease, in the triatomine bug, Rhodnius prolixus, and are currently developing this methodology to control the transmission of Leishmania donovani by the sand fly Phlebotomus argentipes. Several effector molecules, including antimicrobial peptides and highly specific single chain antibodies, are currently being explored for their anti-parasite activities in these two systems. In preparation for eventual field use, we are actively engaged in risk assessment studies addressing the issue of horizontal gene transfer from the modified bacteria to environmental microbes.
PurposeWest Nile Virus (WNV) is a mosquito-born RNA virus first recognized in Uganda in 1937. It has since emerged as an increasing threat across the United States. There have been 15,824 reported cases in the U.S. with 619 human deaths. Human disease manifestations range from a mild febrile illness to severe neurological disease with meningitis or encephalitis. Studies focusing on survivors of WNV have shown persistence of immunoglobulin M (IgM) against WNV. This study investigates whether or not the persistence of IgM can be explained by persistent viremia. Persistent viremia, if present, would have implications for increased blood and organ donation transmission and may explain persistent disease symptoms.MethodsPatients identified by the NM State Laboratory with acute WNV infection as demonstrated by positive IgM in serum or cerebrospinal fluid with persistent symptoms after acute infection were eligible for the study. Convalescent immunoglobulin levels were measured with Enzyme-Linked Immunoabsorbant Assay. Peripheral blood mononuclear cells (PBMCs) and serum were collected from eleven patients with persistent or equivocal IgM levels. RNA was extracted from PBMCs and serum. Reverse transcriptase polymerase chain reaction (RT-PCR) using specific WNV primers is presently underway. Agarose gel electrophoresis will be performed to evaluate RT-PCR product and viral sequencing will be performed for confirmation.ResultsOf the twenty-six WNV convalescent patients in the study, 23% remained IgM positive several months after initial diagnosis. An additional 19% of patients had equivocal IgM levels. All but two patients had persistence of IgG, one of which was equivocal.ConclusionNearly one-fourth of WNV patients with persistent symptoms months after acute infection have persistent IgM antibodies. RT-PCR presently underway will determine whether or not persistent viremia provides an explanation for persistent IgM levels. If RT-PCR indicates the presence of positive WNV RT-PCR products in PBMCs or serum of convalescent WNV patients, the natural history of the disease will be different than initially presumed, possibly increasing disease morbidity and increasing the transmission risk.
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