Leishmania RNA virus-1 is similarly detected among metastatic and non-metastatic phenotypes in a prospective cohort of American Tegumentary Leishmaniasis.

American Tegumentary Leishmaniasis (ATL) is an endemic and neglected disease of South America. Here, mucosal leishmaniasis (ML) disproportionately affects up to 20% of subjects with current or previous localised cutaneous leishmaniasis (LCL). Preclinical and clinical reports have implicated the Leishmania RNA virus-1 (LRV1) as a possible determinant of progression to ML and other severe manifestations such as extensive cutaneous and mucosal disease and treatment failure and relapse. However, these associations were not consistently found in other observational studies and are exclusively based on cross-sectional designs. In the present study, 56 subjects with confirmed ATL were assessed and followed out for 24-months post-treatment. Lesion biopsy specimens were processed for molecular detection and quantification of Leishmania parasites, species identification, and LRV1 detection. Among individuals presenting LRV1 positive lesions, 40% harboured metastatic phenotypes; comparatively 58.1% of patients with LRV1 negative lesions harboured metastatic phenotypes (p = 0.299). We found treatment failure (p = 0.575) and frequency of severe metastatic phenotypes (p = 0.667) to be similarly independent of the LRV1. Parasite loads did not differ according to the LRV1 status (p = 0.330), nor did Leishmanin skin induration size (p = 0.907) or histopathologic patterns (p = 0.780). This study did not find clinical, parasitological, or immunological evidence supporting the hypothesis that LRV1 is a significant determinant of the pathobiology of ATL. Author summary: The Leishmania RNA virus-1 (LRV1) has been implicated as a possible modulator agent in the pathogenesis of leishmaniasis. In-vivo and in-vitro studies have depicted specific mechanisms of how LRV1 could lead to metastasis. Clinical studies and epidemiological evidence have both supported and rejected the hypothesis that LRV1 is a relevant determinant of progression, treatment failure and clinical severity of American Tegumentary Leishmaniasis (ATL). This lack of consistency between preclinical and clinical reports requires further longitudinal studies to clarify the role of LRV1 in ATL. Due to the complex nature of ATL, as other frequent human diseases, these studies should tackle multiple determinants of pathogenicity, including LRV1 status, parasite features, immune status, and prevalent comorbidities affecting individuals in endemic settings. Also, critical methodological aspects allowing for the reliable identification and quantification of LRV1 should be guaranteed. [ABSTRACT FROM AUTHOR]