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

Justin T Lana,Mathilde Chantry,Andrea K Boggild,Alejandro Llanos-Cuentas,Ana Pilar Ramos,Ruwandi Kariyawasam,Walderez O Dutra,Marlene Jara,Braulio Mark Valencia,Rachel Lau

doi:10.1371/journal.pntd.0010162

Abstract

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.

Highlights

Clinical studies and epidemiological evidence have both supported and rejected the hypothesis that Leishmania RNA virus-1 (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
American Tegumentary Leishmaniasis (ATL), a neglected tropical disease predominantly caused by New World Leishmania Viannia pathogens, represents almost one-third of the global cutaneous leishmaniasis burden [1]

Summary

Introduction

American Tegumentary Leishmaniasis (ATL), a neglected tropical disease predominantly caused by New World Leishmania Viannia pathogens, represents almost one-third of the global cutaneous leishmaniasis burden [1]. (L.) Donovani [10,11,12,13] It is unclear if the emergence of the non-L.(V.) braziliensis ML cases have occurred because of changes in pathobiological mechanisms, improved epidemiological reports, or improved access to species identification through molecular biology. Of the infecting pathogen, the predominance of LCL cases over ML—or even the less common phenotypes of disseminated leishmaniasis (DL) or diffuse cutaneous leishmaniasis (DCL)— suggest that pathogen determinants are not solely explaining the diversity of clinical manifestations and phenotypes. The predominance of subclinical or mild manifestations over severe or unusual phenotypes is frequently reported in many other infectious diseases where unusual phenotypes represent a lower proportion of the disease burden [14]

Results

Discussion

Conclusion