Association of the Endobiont Double-Stranded RNA Virus LRV1 With Treatment Failure for Human Leishmaniasis Caused by Leishmania braziliensis in Peru and Bolivia

Cutaneous and mucosal leishmaniasis, caused in South America byLeishmania braziliensis, is difficult to cure by chemotherapy (primarily pentavalent antimonials [Sb-V]). Treatment failure does not correlate well with resistance in vitro, and the factors responsible for treatment failure in patients are not well understood. Many isolates ofL. braziliensis (> 25%) contain a double-stranded RNA virus namedLeishmaniavirus 1 (LRV1), which has also been reported inLeishmania guyanensis, for which an association with increased pathology, metastasis, and parasite replication was found in murine models. Here we probed the relationship of LRV1 to drug treatment success and disease in 97L. braziliensis-infected patients from Peru and Bolivia. In vitro cultures were established, parasites were typed asL. braziliensis, and the presence of LRV1 was determined by reverse transcription-polymerase chain reaction, followed by sequence analysis. LRV1 was associated significantly with an increased risk of treatment failure (odds ratio, 3.99;P = .04). There was no significant association with intrinsic Sb-V resistance among parasites, suggesting that treatment failure arises from LRV1-mediated effects on host metabolism and/or parasite survival. The association of LRV1 with clinical drug treatment failure could serve to guide more-effective treatment of tegumentary disease caused byL. braziliensis.