Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
IntroductionLeishmania RNA virus type 1 (LRV1) is an endosymbiont of some Leishmania (Vianna) species in South America. Presence of LRV1 in parasites exacerbates disease severity in animal models and humans, related to a disproportioned innate immune response, and is correlated with drug treatment failures in humans. Although the virus was identified decades ago, its genomic diversity has been overlooked until now.Methodology/Principles findingsWe subjected LRV1 strains from 19 L. (V.) guyanensis and one L. (V.) braziliensis isolates obtained from cutaneous leishmaniasis samples identified throughout French Guiana with next-generation sequencing and de novo sequence assembly. We generated and analyzed 24 unique LRV1 sequences over their full-length coding regions. Multiple alignment of these new sequences revealed variability (0.5%±23.5%) across the entire sequence except for highly conserved motifs within the 5' untranslated region. Phylogenetic analyses showed that viral genomes of L. (V.) guyanensis grouped into five distinct clusters. They further showed a species-dependent clustering between viral genomes of L. (V.) guyanensis and L. (V.) braziliensis, confirming a long-term co-evolutionary history. Noteworthy, we identified cases of multiple LRV1 infections in three of the 20 Leishmania isolates.Conclusions/SignificanceHere, we present the first-ever estimate of LRV1 genomic diversity that exists in Leishmania (V.) guyanensis parasites. Genetic characterization and phylogenetic analyses of these viruses has shed light on their evolutionary relationships. To our knowledge, this study is also the first to report cases of multiple LRV1 infections in some parasites. Finally, this work has made it possible to develop molecular tools for adequate identification and genotyping of LRV1 strains for diagnostic purposes. Given the suspected worsening role of LRV1 infection in the pathogenesis of human leishmaniasis, these data have a major impact from a clinical viewpoint and for the management of Leishmania-infected patients.
ISSN: 1935-2727

pasteur-01583523
https://hal-riip.archives-ouvertes.fr/pasteur-01583523
DOI : 10.1371/journal.pntd.0005764
PUBMED : 28715422

Éditeur(s) : HAL CCSD American Society of Tropical Medicine and Hygiene
Résumé : International audience
In South America, the presence of the Leishmania RNA virus type 1 (LRV1) was described in Leishmania guyanensis and Leishmania braziliensis strains. The aim of this study was to determine the prevalence distribution of LRV1 in Leishmania isolates in French Guiana given that, in this French overseas department, most Leishmania infections are due to these parasite species. The presence of the virus was observed in 74% of Leishmania spp. isolates, with a highest presence in the internal areas of the country.
ISSN: 0002-9637

pasteur-01583614
https://hal-riip.archives-ouvertes.fr/pasteur-01583614
https://hal-riip.archives-ouvertes.fr/pasteur-01583614/document
https://hal-riip.archives-ouvertes.fr/pasteur-01583614/file/2016%20Ginouves%20et%20al.%20ajtmh.pdf
PUBMED : 26598572

Éditeur(s) : HAL CCSD American Society of Tropical Medicine and Hygiene
Résumé : International audience
Anti-leishmaniasis drug resistance is a common problem worldwide. The aim of this study was to inventory the general in vitro level of sensitivity of Leishmania isolates circulating in French Guiana and to highlight potential in vitro pentamidine-resistant isolates. This sensitivity study was conducted on 36 patient-promastigote isolates for seven drugs (amphotericin B, azithromycin, fluconazole, meglumine antimoniate, miltefosine, paromomycin, and pentamidine) using the Cell Counting Kit-8 viability test. The IC50 values obtained were heterogeneous. One isolate exhibited high IC50 values for almost all drugs tested. Pentamidine, which is the first-line treatment in French Guiana, showed efficacy at very low doses (mean of 0.0038 μg/mL). The concordance of the in vitro pentamidine results with the patients' clinical outcomes was 94% (K = 0.82).
ISSN: 0002-9637

inserm-01481512
http://www.hal.inserm.fr/inserm-01481512
http://www.hal.inserm.fr/inserm-01481512/document
http://www.hal.inserm.fr/inserm-01481512/file/2017%2C%20Ginouves%20-%20In%20vitro%20sensitivity%20of%20cutaneous%20leishmania.pdf
DOI : 10.4269/ajtmh.16-0373

Éditeur(s) : HAL CCSD
Résumé : International audience
Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (ATL). Such complications are seen frequently in L.guyanensis infections where patients respond variously to first-line anti-leishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently ,: we reported that a dsRNA virus (LRV1) nested within L.guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyper-inflammatory response. This report investigates the prevalence of LRV1 in human L.guyanensis infection and its effect on treatment efficacy as well as its correlation to symptomatic relapses after the first-line treatment. In our cohort of 75 patients diagnosed with primary-localised ATL, the prevalence of LRV1+ infection was elevated to 58%. All patients infected with LRV1-negative L.guyanensis were cured after one (22/31 i.e.71%) or two (31/31 i.e.100%) doses of pentamidine. Oppositely, 12 out of the 44 LRV1-positive patients presented with persistent infection and symptomatic relapse required extended therapy and the use of second-line drugs. Finally, LRV1 presence was associated with a significant increase in intra-lesional inflammatory markers. In conclusion, LRV1 status in L.guyanensis infection is significantly predictive (p=0.0009) of first-line treatment failure and symptomatic relapse, and could stand to guide therapeutic choices in ATL
Journal of Infectious Diseases

hal-01175528
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01175528
DOI : 10.1093/infdis/jiv355
PUBMED : 26123564