Selective Expression of the Vβ14 T Cell Receptor on Leishmania guyanensis-Specific CD8+ T Cells during Human Infection

Peripheral blood mononuclear cells from subjects never exposed to Leishmania were stimulated with Leishmania guyanensis. We demonstrated that L. guyanensis-stimulated CD8+ T cells produced interferon (IFN)-γ and preferentially expressed the Vb14 T cell receptor (TCR) gene family. In addition, these cells expressed cutaneous lymphocyte antigen and CCR4 surface molecules, suggesting that they could migrate to the skin. Results obtained from the lesions of patients with localized cutaneous leishmaniaisis (LCL) showed that Vβ14 TCR expression was increased in most lesions (63.5%) and that expression of only a small number of Vb gene families (Vβ1, Vβ6, Vβ9, Vβ14, and Vβ24) was increased. The presence of Vβ14 T cells in tissue confirmed the migration of these cells to the lesion site. Thus, we propose the following sequence of events during infection with L. guyanensis. After initial exposure to L. guyanensis, CD8+ T cells preferentially expressing the Vb14 TCR and secreting IFN-γ develop and circulate in the periphery. During the infection, these cells migrate to the skin at the site of the parasitic infection. The role of these Vβ14 CD8+ T cells in resistance to infection remains to be determined conclusivel

The fight against HIV-associated disseminated histoplasmosis in the Americas: Unfolding the different stories of four centers

Disseminated histoplasmosis is a major opportunistic infection of HIV-infected patients, killing thousands in Latin America each year. Yet, it remains a neglected disease that is often confused with tuberculosis, for lack of simple, affordable, and rapid diagnostic tools. There is great heterogeneity in the level of histoplasmosis awareness. The purpose of this report was to describe how the historical “awakening” to the threat of histoplasmosis came to be in four different centers that have actively described this disease: In Brazil, the Sao José hospital in Fortaleza; in Colombia, the Corporación para Investigaciones Biológicas inMedellin; in French Guiana, Cayenne Hospital; and in Guatemala, the Association de Salud Integral in Guatemala city. In Brazil and French Guiana, the search for leishmaniasis on the buffy coat or skin smears, respectively, led to the rapid realization that HIV patients were suffering from disseminated histoplasmosis. With time and progress in fungal culture, the magnitude of this problem turned it into a local priority. In Colombia and Guatemala, the story is different because for these mycology centers, it was no surprise to find histoplasmosis in HIV patients. In addition, collaborations with the CDC to evaluate antigen-detection tests resulted in researchers and clinicians developing the capacity to rapidly screen most patients and to demonstrate the very high burden of disease in these countries. While the lack of awareness is still a major problem, it is instructive to review the ways through which different centers became histoplasmosis-aware. Nevertheless, as new rapid diagnostic tools are becoming available, their implementation throughout Latin America should rapidly raise the level of awareness in order to reduce the burden of histoplasmosis deaths. © 2019 by the authors

First Detection of Mycobacterium ulcerans DNA in Environmental Samples from South America

The occurrences of many environmentally-persistent and zoonotic infections are driven by ecosystem changes, which in turn are underpinned by land-use modifications that alter the governance of pathogen, biodiversity and human interactions. Our current understanding of these ecological changes on disease emergence however remains limited. Buruli ulcer is an emerging human skin disease caused by the mycobacterium, Mycobacterium ulcerans, for which the exact route of infection remains unclear. It can have a devastating impact on its human host, causing extensive necrosis of the skin and underlying tissue, often leading to permanent disability. The mycobacterium is associated with tropical aquatic environments and incidences of the disease are significantly higher on floodplains and where there is an increase of human aquatic activities. Although the disease has been previously diagnosed in South America, until now the presence of M. ulcerans DNA in the wild has only been identified in Australia where there have been significant outbreaks and in western and central regions of Africa where the disease is persistent. Here for the first time, we have identified the presence of the aetiological agent's DNA in environmental samples from South America. The DNA was positively identified using Real-time Polymerase Chain Reaction (PCR) on 163 environmental samples, taken from 23 freshwater bodies in French Guiana (Southern America), using primers for both IS2404 and for the ketoreductase-B domain of the M. ulcerans mycolactone polyketide synthase genes (KR). Five samples out of 163 were positive for both primers from three different water bodies. A further nine sites had low levels of IS2404 close to a standard CT of 35 and could potentially harbour M. ulcerans. The majority of our positive samples (8/14) came from filtered water. These results also reveal the Sinnamary River as a potential source of infection to humans. © 2014 Morris et al

Qualifications et parcours - Qualification des parcours. XXVèmes journées du longitudinal, Nantes, 20 et 21 juin 2019

International audienceLes XXVèmes journées du longitudinal (JDL) se proposaient de questionner deux notions : la qualification et les parcours ainsi que leur articulation. Elles furent l'occasion d'évoquer les parcours biographiques et de saisir la qualification des personnes comme un construit dans le temps, dans une perspective de « formation tout au long de la vie ». Ces journées ont permis de discuter de la polarisation des parcours tels les parcours d'exclusion et parcours d'accès aux qualifications les plus socialement valorisées mais aussi de la multiplication des parcours atypiques remettant en cause les relations directes entre réussite ou échec scolaire d'une part, insertion professionnelle durable ou précaire d'autre part. À cet égard, les JDL ont permis de discuter des méthodes statistiques permettant d'identifier des parcours-types, notamment à travers les techniques de classification

Staphylococcal Panton-Valentine Leucocidin as a Major Virulence Factor Associated to Furuncles

Panton-Valentine Leucocidin (PVL), one of the β-barrel pore-forming staphylococcal leucotoxins, is known to be associated to furuncles and some severe community pneumonia. However, it is still uncertain how many other virulence factors are also associated to furuncles and what the risk factors of furuncles are in immuno-compromised status of patients, especially the HIV (+) patients. In this paper, we use antigen immunoprecipitation and multiplex PCR approach to determine the presence of 19 toxins, 8 adhesion factors and the PFGE profiles associated to furuncles in three independent patient study groups of S. aureus (SA) isolates collected from the Cayenne General Hospital (French Guiana). The patient groups were made of: 16 isolates from HIV (−) patients, 9 from HIV (+) patients suffering from furuncles, and 30 control isolates from patients with diverse secondary infected dermatitis. Our data reveals that the majority (96%) of SA strains isolated from HIV patient-derived furuncles significantly produced PVL (p<10−7), whereas only 10% of SA strains produced this toxin in secondary infected dermatosis. A high prevalence of LukE-LukD-producing isolates (56 to 78%) was recorded in patient groups. Genes encoding clumping factor B, collagen- and laminin-binding proteins (clfB, cna, lbp, respectively) were markedly frequent (30 to 55%), without being associated to a specific group. Pulse field gel electrophoresis evidenced 24 overall pulsotypes, whereas the 25 PVL-producing isolates were distributed into 15 non clonal fingerprints. These pulsotypes were not specific PVL-producing isolates. PVL appears to be the major virulence factor associated to furuncles in Europe and in South America regardless of the immune status of the HIV patients

Comparison of Tetrazolium Salt Assays for Evaluation of Drug Activity against Leishmania spp.

International audienc

Disseminated Histoplasmosis Seasonal Incidence Variations: A Supplementary Argument for Recent Infection?

International audienceBackground: In French Guiana, a recent study has shown that a major part of the histoplasmosis incidence temporal fluctuations could be explained by climatic factors and thus postulated that disseminated histoplasmosis cases could be in a large proportion due to new infections. The description of the seasonal pattern of histoplasmosis could potentially help to test this new hypothesis. Patients and methods: A study using prospective data from the French Hospital Database for HIV was conducted in order to determine seasonal variations of the incidence of first cases of disseminated histoplasmosis in HIV persons in Cayenne, French Guiana. Single failure Cox proportional hazards models were used. Results: After adjusting for CD4 counts and antiretroviral treatment, the incidence of disseminated histoplasmosis was significantly higher during the Short Wet Season-Long Dry Season than during the Short Dry Season-Long Wet Season (Adjusted Hazard ratio 1.7 (1.1-2.5), P= 0.01). Conclusion: This result gives both valuable epidemiologic information to clinicians and a supplementary argument in favour of the hypothesis that an important proportion of cases were due to recent exposure. Therefore, the use of a primary prophylaxis must be discussed in French Guiana

Hierarchy of Determinants Underlying Death among HIV-Infected Patients in French Guiana

International audienceObjective: In order to determine how risk factors of death among HIV-infected patients in French Guiana interact with one another and to define high risk population segments, an alternative statistical method to Cox proportional hazards models was used. Patients and methods: Data from HIV+ patients followed in the three main hospitals of French Guiana were used. Data were extracted from the prospective French Hospital Database for HIV (FHDH). To examine the nature of the relationships between time of death since the first consultation and a set of predictor variables (age at enrolment, gender, nationality, CD4 count at enrolment, presence or absence of HAART at enrolment, a declared addiction, and mode of acquisition of the virus) a survival tree analysis was used. Survival rates at 5 years and 10 years and their 95% confidence interval were also calculated. Results: This analysis permitted to reveal a new specific subgroup of HIV+ patients particularly at risk in French Guiana not already mentioned in the literature: the HIV+ female patients with a declared addiction. Conclusions: Prevention and care in this vulnerable segment of the HIV+ population identified by this methodology should be reinforced

In Vitro Sensitivity of Cutaneous Leishmania Promastigote Isolates Circulating in French Guiana to a Set of Drugs.

International audienceAnti-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)