Cutaneous leishmaniasis has various outcomes, ranging from self-healing reddened papules to extensive open ulcerations that metastasise to secondary sites and are often resistant to standard ...therapies. In the case of L. guyanensis (L.g), about 5-10% of all infections result in metastatic complications. We recently showed that a cytoplasmic virus within L.g parasites (LRV1) is able to act as a potent innate immunogen, worsening disease outcome in a murine model. In this study, we investigated the immunophenotype of human patients infected by L.g and found a significant association between the inflammatory cytokine IL-17A, the presence of LRV1 and disease chronicity. Further, IL-17A was inversely correlated to the protective cytokine IFN-γ. These findings were experimentally corroborated in our murine model, where IL-17A produced in LRV1+ L.g infection contributed to parasite virulence and dissemination in the absence of IFN-γ. Additionally, IL-17A inhibition in mice using digoxin or SR1001, showed therapeutic promise in limiting parasite virulence. Thus, this murine model of LRV1-dependent infectious metastasis validated markers of disease chronicity in humans and elucidated the immunologic mechanism for the dissemination of Leishmania parasites to secondary sites. Moreover, it confirms the prognostic value of LRV1 and IL-17A detection to prevent metastatic leishmaniasis in human patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Progressive disseminated histoplasmosis remains a major but neglected cause of death among patients with advanced HIV. Recently, aiming to reduce avoidable deaths, the Pan American Health ...Organization issued the first diagnosis and treatment guidelines for HIV-associated histoplasmosis. But what proportion of progressive disseminated histoplasmosis in HIV-infected patients is severe is currently not known. Because this proportion influences treatment needs, we aimed to estimate this in a cohort of 416 patients in French Guiana. Methods We used the definition in the recent PAHO/WHO guidelines for severity. We used regression modelling to predict the impact of CD4 count on the proportion of severe cases. In a territory where treatment cost is not a limiting factor and where histoplasmosis is well known, we assumed that clinicians' initial treatment reflected their perception about the severity of the case and therefore, the needs for different treatments. Results Using these definitions, since the beginning, there were 274 (65.9%) severe/moderately severe cases and 142 (34.1%) mild cases. In practice 186 cases were treated with deoxycholate or liposomal amphotericin B (44.7%) and 230 (55.3%) cases treated with itraconazole as first line treatment. The Kappa concordance measure between the guideline definition and the actual treatment given was 0.22. There was a 9% risk difference for death within 30 days of antifungal treatment initiation between severe/moderately severe and mild cases. Over threequarters (77%) of early deaths were attributed to severe/moderately severe cases. Conclusions This is the only rigorous estimate of the proportion of severe/moderately severe cases of progressive disseminated histoplasmosis in symptomatic HIV patients on the largest published cohort. These numbers may help defend budget needs for rapid diagnostic tests and liposomal amphotericin B.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background In France, leishmaniasis is endemic in the Mediterranean region, in French Guiana and to a lesser extent, in the French West Indies. This study wanted to provide an updated picture of ...leishmaniasis epidemiology in metropolitan France and in its overseas territories. Methodology/Principal findings Leishmaniasis cases were collected by passive notification to the French National Reference Centre for Leishmaniases (NRCL) in Montpellier from 1998 to 2020 and at the associated Centre in Cayenne (French Guiana) from 2003 to 2020. In metropolitan France, 517 autochthonous leishmaniasis cases, mostly visceral forms due to Leishmania infantum (79%), and 1725 imported cases (French Guiana excluded), mainly cutaneous leishmaniasis from Maghreb, were recorded. A slight decrease of autochthonous cases was observed during the survey period, from 0.48 cases/100,000 inhabitants per year in 1999 (highest value) to 0.1 cases/100,000 inhabitants per year in 2017 (lowest value). Conversely, imported cases increased over time (from 59.7 in the 2000s to 94.5 in the 2010s). In French Guiana, 4126 cutaneous and mucocutaneous leishmaniasis cases were reported from 2003 to 2020. The mean incidence was 103.3 cases per 100,000 inhabitants/year but varied in function of the year (from 198 in 2004 to 54 in 2006). In Guadeloupe and Martinique (French West Indies), only sporadic cases were reported. Conclusions/Significance Because of concerns about disease expansion and outbreaks in other Southern Europe countries, and leishmaniasis monitoring by the NRCL should be continued and associated with a more active surveillance.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Disseminated histoplasmosis is one the main AIDS-defining opportunistic infections in HIV-infected patients, notably in Latin America. The non-specific and proteiform clinical presentation leads to ...diagnostic delays that may lead to fatal outcomes. This retrospective multicentric study aimed to describe the frequency and manifestations of gastrointestinal histoplasmosis in French Guiana, and to compare patients with disseminated histoplasmosis with or without gastrointestinal involvement. Between January 1, 1981 and October 1, 2014 co-infections with HIV and histoplasmosis were enrolled. Inclusion criteria were: age >18 years, confirmed HIV infection; first proven episode of histoplasmosis. Among 349 cases of disseminated histoplasmosis, 245 (70%) had a gastrointestinal presentation. Half of patients with gastrointestinal signs had abdominal pain or diarrhea, mostly watery. Half of patients with abdominal pain had diarrhea (63/124) and half of those with diarrhea (63/123) had abdominal pain. A significant proportion of patients also had hepatomegaly and, to a lesser degree, splenomegaly. After adjusting for potential confounding, the presence of lymphadenopathies >2cm (AOR = 0.2, IC95 = 0.04-0.7, P = 0.01), Haitian origin (AOR = 0.04, IC95 = 0.004-0.4, P = 0.006) were associated with a lower prevalence of gastrointestinal signs and positive gastrointestinal presence of H. capsulatum. Persons with a gastrointestinal H. capsulatum were more likely to have a decreased prothrombin time, lower ferritin, lower liver enzymes, and lower concentrations of LDH than those without gastrointestinal signs and symptoms. They also had a shorter interval between symptoms onset and diagnosis. Patients with a positive gastrointestinal identification of H. capsulatum were less likely to die at 1 month than those without a gastrointestinal presentation (respectively, 4.6% vs 18.5%, P = 0.01). Subacute or chronic gastrointestinal presentations are very frequent during disseminated histoplasmosis, they seem less severe, and should lead to suspect the diagnosis in endemic areas. There were populational or geographic differences in the frequency of gastrointestinal manifestations that could not be explained.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Disseminated histoplasmosis, a disease that often resembles and is mistaken for tuberculosis, is a major cause of death in patients with advanced HIV disease. Histoplasma antigen detection tests are ...an important addition to the diagnostic arsenal for patients with advanced HIV disease and should be considered for inclusion on the World Health Organization Essential Diagnostics List.
Our objective was to systematically review the literature to evaluate the diagnostic accuracy of Histoplasma antigen tests in the context of advanced HIV disease, with a focus on low- and middle-income countries.
A systematic review of the published literature extracted data on comparator groups, type of histoplasmosis, HIV status, performance results, patient numbers, whether patients were consecutively enrolled or if the study used biobank samples. PubMed, Scopus, Lilacs and Scielo databases were searched for published articles between 1981 and 2018. There was no language restriction.
Of 1327 screened abstracts we included a total of 16 studies in humans for further analysis. Most studies included used a heterogeneousgroup of patients, often without HIV or mixing HIV and non HIV patients, with disseminated or non-disseminated forms of histoplasmosis. Six studies did not systematically use mycologically confirmed cases as a gold standard but compared antigen detection tests against another antigen detection test. Patient numbers were generally small (19-65) in individual studies and, in most (7/10), no confidence intervals were given. The post test probability of a positive or negative test were good suggesting that this non invasive diagnostic tool would be very useful for HIV care givers at the level of reference hospitals or hospitals with the infrastructure to perform ELISA tests. The first results evaluating point of care antigen detection tests using a lateral flow assay were promising with high sensitivity and specificity.
Antigen detection tests are promising tools to improve detection of and ultimately reduce the burden of histoplasmosis mortality in patients with advanced HIV disease.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cutaneous Leishmaniasis (CL) is endemic in French Guiana but cases are usually sporadic. An outbreak signal was issued on May 15th 2020 with 15 suspected cases after a military training course in the ...rainforest. An outbreak investigation was carried out.
Thirty cases were confirmed. Leishmania guyanensis was the most frequent species (90%). The most frequent presentation was ulcerative (90%). Lesions on the face and hands were frequent (40% each). Eight cases (26%) presented a poor outcome after treatment with pentamidine and required a second line with amphotericin B. Three of them required further treatments with meglumine antimoniate or miltefosine. Two spots within the training area were deemed as likely sites of contamination, due to illegal logging. The isolated Leishmania strains did not form a separate cluster. Participation in Week 13 of year 2020 was associated with infection (OR = 4.59 1.10-19.83; p = 0.016) while undergoing only the "Fighting" exercise was protective (OR = 0.1 0-0.74; p = 0.021). There was no association between infection and other risk factors at the individual level. The attack rate of Regiment B (14/105 = 13.3%) was significantly higher (OR = 4.22 1.84-9.53, p = 0.0001) compared to Regiment A (16/507 = 3.2%). The attack rate during this training course (30/858 = 3.5%) was significantly higher (OR 2.29 1.28-4.13; p = 0.002) than for other missions in French Guiana during the same period (22/1427 = 1.5%).
This outbreak could be explained by a combination of factors: climatic conditions around week 13, at-risk activities including night trainings, absence of impregnation, a lesser experience of rainforest duties in Regiment B and illegal logging attracting sandflies on military training grounds.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Most emerging pathogens are zoonoses and have a wildlife origin. Anthropization and disruption of ecosystems favor the crossing of inter-species barriers. We hypothesize that the ...marginalized population of undocumented goldminers in the Amazon is at risk of acquiring zoonoses.
Method
A multicentric cross-sectional study included consenting gold-mining adult workers in 2019. A clinical examination recorded dermatological signs of leishmaniosis and past history of yellow fever vaccination. Biological tests were performed for yellow fever, Q fever and leptospirosis serologies. Additional blood samples from a previous study in 2015 were also tested for leptospirosis.
Results
In 2019, 380 individuals were included in the study, along with 407 samples from the 2015 biological collection. The seroprevalence of leptospirosis was 31.0% 95%CI = 26.4–35.5 in 2015 and 28.1% 23.5–32.7 in 2019. The seroprevalence of Q fever was 2.9% 1.2–4.6. The majority of participants reported being vaccinated against yellow fever (93.6%) and 97.9% had seroneutralizing antibodies. The prevalence of suspected active mucocutaneous leishmaniasis was 2.4% 0.8–3.9.
Discussion
These unique data shed new light on the transmission cycles of zoonoses still poorly understood in the region. They support the existence of a wild cycle of leptospirosis but not of Q fever. Leishmaniasis prevalence was high because of life conditions and tree felling. High yellow fever vaccine coverage was reassuring in this endemic area. In the era of global health, special attention must be paid to these vulnerable populations in direct contact with the tropical ecosystem and away from the health care system.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Given the great efforts put into the strategic objective of reducing the proportion of HIV-infected patients that are undiagnosed, the aim of the present study was to review the temporal trends ...between 1997 and 2016 for median estimates of infection duration and median CD4 count at diagnosis for the main patient origins in French Guiana.
CD4 cell count at HIV sero-conversion and square root of CD4 cell decline were obtained using the CD4 decline in a cohort of HIV-infected persons in the UK, fitting random effect (slope and intercept) multilevel linear regression models. Multivariate analysis used robust regression for modeling the delay between estimated HIV seroconversion and diagnosis and quantile regression for CD4 at HIV diagnosis.
The median interval between the estimated HIV seroconversion and HIV diagnosis was 8 years for patients fromBrazil, 4.5 years for those from Haiti, 6.6 years for those from Suriname, 3.3 years for patients from Guyana, and 3.1 years for French patients. A simple robust regression model with French patients as reference group adjusting for sex and age at the time of diagnosis showed that the interval was significantly longer for Brazilian (β = +3.7 years, P = 0.001), Surinamese (β = +4.2 years, P<0.0001), Haitian origins (β = +1.5 years, P = 0.049) but not for those originating from Guyana (β = -0.03 years, P = 0.9); Men independently had a longer interval than women (β = +3.5 years, P<0.0001).
Despite great efforts in French Guiana regarding HIV testing both in terms of diversification and intensification we still need to tailor the offer to better reach the communities in need. These results should help authorities scale up and optimize initiatives to reduce the proportion of patients who are unaware of their infection. They also raise the question of the role of stigma and discrimination as a barrier to HIV testing in small communities, and further emphasize the importance of reducing it.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In French Guiana, more than a third of the population, and nearly half of the adults, are of foreign origin. This immigration is explained by the French standard of living, which is attractive to ...nationals of surrounding countries. Infectious diseases remain in the top 10 causes of premature death, often in the most precarious populations. In this context we aimed to synthesize the state of the knowledge regarding immigration and infectious diseases in French Guiana and the general implications that follow this diagnosis.
For HIV, although the majority of patients are of foreign origin, estimates of the presumed date of infection based on CD4 erosion modelling and from molecular analyses suggest that the majority of transmissions in foreign-born individuals occur in French Guiana and that the Guiana shield has been a crossroad between Latin America and the Caribbean. Among key populations bridging these regions illegal gold miners are very mobile and have the greatest proportion B Caribbean HIV viruses. Gold miners have been a key vulnerable population for falciparum malaria and other tropical diseases such as leishmaniasis, leprosy, or leptospirosis. The complex history of migrations in French Guiana and on the Guiana Shield is also reflected in the fingerprinting of mycobacterium tuberculosis and the high incidence of tuberculosis in French Guiana, notably in immigrants, reflects the incidences in the countries of origin of patients. The high burden of infectious diseases in immigrants in French Guiana is first and foremost a reflection of the precarious living conditions within French Guiana and suggests that community-based proactive interventions are crucial to reduce transmission, morbidity, and mortality from infectious diseases.
•French Guiana, a French territory in South America, attracts numerous immigrants from countries endemic for a variety of infectious diseases.•Although there is circulation of infectious pathogens, most immigrants get infected after their arrival in French Guiana where they live in precarious conditions.•Proactive outreach efforts for vulnerable immigrants are key to reduce the burden of infectious diseases in these communities.
Histoplasmosis is the most frequent opportunistic infection and the first cause of mortality in HIV-infected patients in French Guiana and presumably in much of Latin America. Mucocutaneous lesions ...of histoplasmosis are considered as rare and late manifestations of the disease. It has been debated whether the greater proportion of cutaneo-mucous presentations in South America relative to the USA was the reflection of Histoplasma strains with increased dermotropism or simply delayed diagnosis and advanced immunosuppression. The objective of this study was to describe the clinical presentation, frequency, prognosis and temporal trends of cutaneomucous histoplasmosis in French Guiana. A retrospective study of patients with AIDS-related disseminated histoplasmosis followed in the three hospitals of French Guiana was performed between 1981 and 2014. Incident cases of histoplasmosis, proved by pathology and/or mycological examinations, were studied. Mucocutaneous histoplasmosis was confirmed by a positive cutaneous or mucosal biopsy. Mucocutaneous lesions were polymorphic. Ninety percent of patients were profoundly immunocompromised patients (CD4<50/mm3) and over 80% were not on antiretroviral treatment. The frequency of mucocutaneous forms and case fatality of disseminated histoplasmosis within one month of antifungal treatment significantly decreased over time (p<0,001). In this South American territory, diagnostic and therapeutic improvements have led to the quasi disappearance of cutaneous manifestations. There may be South American dermotropism in the laboratory but at the bedside early diagnosis seems to be the main parameter explaining the proportion of cutaneomucous presentations in South America relative to the USA.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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