24 research outputs found
Exacerbated leishmaniasis caused by a viral endosymbiont can be prevented by immunization with Its viral capsid
Recent studies have shown that a cytoplasmic virus called Leishmaniavirus (LRV) is present in some Leishmania species and acts as a potent innate immunogen, aggravating lesional inflammation and development in mice. In humans, the presence of LRV in Leishmania guyanensis and in L. braziliensis was significantly correlated with poor treatment response and symptomatic relapse. So far, no clinical effort has used LRV for prophylactic purposes. In this context, we designed an original vaccine strategy that targeted LRV nested in Leishmania parasites to prevent virus-related complications. To this end, C57BL/6 mice were immunized with a recombinant LRV1 Leishmania guyanensis viral capsid polypeptide formulated with a T helper 1-polarizing adjuvant. LRV1-vaccinated mice had significant reduction in lesion size and parasite load when subsequently challenged with LRV1+ Leishmania guyanensis parasites. The protection conferred by this immunization could be reproduced in naïve mice via T-cell transfer from vaccinated mice but not by serum transfer. The induction of LRV1 specific T cells secreting IFN-γ was confirmed in vaccinated mice and provided strong evidence that LRV1-specific protection arose via a cell mediated immune response against the LRV1 capsid. Our studies suggest that immunization with LRV1 capsid could be of a preventive benefit in mitigating the elevated pathology associated with LRV1 bearing Leishmania infections and possibly avoiding symptomatic relapses after an initial treatment. This novel anti-endosymbiotic vaccine strategy could be exploited to control other infectious diseases, as similar viral infections are largely prevalent across pathogenic pathogens and could consequently open new vaccine opportunities
Frequency and distribution of mixed Plasmodium falciparum-vivax infections in French Guiana between 2000 and 2008
Étude comparative rétrospective de l’amphotéricine B liposomale et de l’antimoniate de méglumine dans la leishmaniose cutanée américaine
American cutaneous leishmaniasis in French Guiana: a retrospective comparison between liposomal amphotericin B and meglumine antimoniate
American cutaneous leishmaniasis in French Guiana: a retrospective comparison between liposomal amphotericin B and meglumine antimoniate
The 2011 Cordón Caulle eruption triggered by slip on the Liquiñe-Ofqui fault system
International audienceDetermining the mechanisms that promote large silicic eruptions is one of the biggest challenges in volcanic hazard assessment. The 2011-2012 Cordón-Caulle eruption in Chile was one of the largest silicic eruptions of the 21st century and was characterized by a rapid change from explosive to effusive behavior. This eruption was preceded by inflation from 2007 to 2009, followed by two years of barely any ground deformation. Despite intensive monitoring by geodetic and seismological data, its trigger remains undetermined. Here, we benefit from SAR imagery over the Puyehue Cordón-Caulle Volcanic Complex acquired by ALOS-1, ENVISAT and SENTINEL-1 data, to analyze the temporal and spatial behavior of ground displacements before, during and after the eruption. First, we find that a similar prolate spheroidal source explains the ground deformation for the pre-eruptive and post-eruptive periods. Then, we use 3D numerical elasto-plastic models to assess the failure conditions resulting from the pre-eruptive magma injection. Our results show that such a magma injection was too small to trigger the eruption. Therefore we explore other eruption triggers. Analytical elastic inversion models show that the ground displacements observed during the explosive phase may have been produced by slip motion along a NNW-striking dextral-strike slip, double-branch fault of the north-trending Liquiñe-Ofqui Fault System (LOFS), or along a single southern branch fault of the LOFS and collapse of the caldera. When investigating the elasto-plastic deformation pattern resulting from dextral slip along this branch-fault system, we obtain a sub-vertical dilatational plastic zone that connects the reservoir wall to the surface in a location that coincides with that of the 2011 eruption. Hence, we propose that this LOFS branch-fault eventually destabilized (perhaps weakened by the 2007-2009 episode of magma injection), and then slipped in a way that opened channels for fluid migration from the magma reservoir up to the surface
Presence of Leishmania RNA Virus 1 in Leishmania guyanensis Increases the Risk of First-Line Treatment Failure and Symptomatic Relapse.
Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (TL). Such complications are seen frequently in Leishmania guyanensis infections, in which patients respond variously to first-line antileishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently, we reported that a double-stranded RNA virus, Leishmania RNA virus 1 (LRV1), nested within L. guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyperinflammatory 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 completion of first-line treatment. In our cohort of 75 patients with a diagnosis of primary localized American TL, the prevalence of LRV1-positive L. guyanensis infection was elevated to 58%. All patients infected with LRV1-negative L. guyanensis were cured after 1 dose (22 of 31 [71%]) or 2 doses (31 of 31 [100%]) of pentamidine. In contrast, 12 of 44 LRV1-positive patients (27%) presented with persistent infection and symptomatic relapse that required extended therapy and the use of second-line drugs. Finally, LRV1 presence was associated with a significant increase in levels of intra-lesional inflammatory markers. In conclusion, LRV1 status in L. guyanensis infection is significantly predictive (P = .0009) of first-line treatment failure and symptomatic relapse and has the potential to guide therapeutic choices in American TL