Centre d'Investigation Clinique Antilles Guyane

Endemic mycoses such as histoplasmosis, coccidioidomycosis, blastomycosis, paracoccidioidomycosis, and talaromycosis are well-known causes of focal and systemic disease within specific geographic areas of known endemicity. However, over the past few decades, there have been increasingly frequent reports of infections due to endemic fungi in areas previously thought to be "non-endemic." There are numerous potential reasons for this shift such as increased use of immune suppressive medications, improved diagnostic tests, increased disease recognition, and global factors such as migration, increased travel, and climate change. Regardless of the causes, it has become evident that our previous understanding of endemic regions for these fungal diseases needs to evolve. The epidemiology of the newly described Emergomyces is incomplete; our understanding of it continues to evolve. This review will focus on the evidence underlying the established areas of endemicity for these mycoses as well as new data and reports from medical literature that support the re-thinking these geographic boundaries. Updating the endemic fungi maps would inform clinical practice and global surveillance of these diseases.

BACKGROUND: In French Guiana, a French overseas territory in South America, 6 to 10 thousands undocumented persons work illegally in gold mining sites in the Amazonian forest. Precarious life conditions lead to poor health but few data exist on the health status of illegal gold miners in French Guiana. The objective of this article was to describe the sociodemographic and health status of this vulnerable population. METHOD: A prospective cross-sectional survey was conducted in 2015 on gold mine supply sites at the border between French Guiana and Suriname. Health status was assessed through medical examination, past medical history, haemoglobin concentration, and HIV and malaria testing. A questionnaire was used to collect data about the migration itinerary and life conditions on mining sites. RESULTS: Among the 421 adults included in the study, 93.8% (395/421) were Brazilian, mainly from Maranhão (55.7%, 220/395), the poorest Brazilian state. The sex ratio was 2.4. Overall, 48% of persons never went to school or beyond the primary level. The median time spent in gold mining was quite long (10 years), with a high turn-over. One third of the surveyed population (37.1%, 156/421) had high blood pressure, and only two had a medical follow-up. Most persons had experienced malaria (89.3%, 376/421). They declared frequent arboviroses and digestive disorders. Active leishmaniasis was observed in 8.3% of gold miners. Among women, 28.5% were anemic. Concerning HIV, 36.6% (154/421) of persons, mainly men, never got tested before and 6 were tested positive, which represented an HIV prevalence of 1.43% (95%CI =0.29-2.5). CONCLUSION: These findings support the hypothesis that mining in remote areas is linked to several specific illnesses. Theoretically, gold miners would be presumed to start their economical migration to French Guiana as a healthy group. However, their strenuous working and living conditions there lead to poor health caused by infectious and non infectious diseases. This description of their health status is precious for health policy planners in French Guiana given the importance of controlling communicable disease, and the severity and range of specific illnesses acquired by this neglected population. TRIAL REGISTRATION: Clinical trial registration PRS N° NCT02903706 . Retrospectively registered 09/13/2016.

Abstract Purpose of Review Following Paraguay and Argentina, several countries from the Amazon region aim to eliminate malaria. To achieve this, all key affected and vulnerable populations by malaria, including people working on gold mining sites, must be considered. What is the situation of malaria in these particular settings and what are the challenges? This literature review aims to compile knowledge to answer these questions. Recent Findings The contexts in which gold miners operate are very heterogeneous: size and localization of mines, links with crime, administrative status of the mines and of the miners, mobility of the workers or national regulations. The number of malaria cases has been correlated with deforestation (Brazil, Colombia), gold production (Colombia), gold prices (Guyana), or location of the mining region (Peru, Colombia, Venezuela, Guyana). The burden of malaria in gold mines differs between territories: significant in Guyana, French Guiana, or Venezuela; lower in Brazil. Although P lasmodium vivax causes 75% of malaria cases in the Americas, P. falciparum is predominant in several gold mining regions, especially in the Guiana Shield. Because of the remoteness from health facilities, self-medication with under-the-counter antimalarials is frequent. This constitutes a significant risk for the emergence of new P. falciparum parasites resistant to antimalarial drugs. Summary Because of the workers’ mobility, addressing malaria transmission in gold mines is essential, not only for miners, but also to prevent the (re-)emergence of malaria. Strategies among these populations should be tailored to the context because of the heterogeneity of situations in different territories. The transnational environment favoring malaria transmission also requires transborder and regional cooperation, where innovative solutions should be considered and evaluated.

AIMS: Indications for surgery in acute infective endocarditis (IE) are detailed in guidelines, but their application is not well known. We analysed the agreement between the patient's attending physicians and European Society of Cardiology guidelines regarding indications for surgery. We also assessed whether surgery was performed in patients who had an indication. METHODS AND RESULTS: From the 2008 prospective population-based French survey on IE, 303 patients with definite left-sided native IE were identified. For each case, we prospectively recorded (i) indication for surgery according to the attending physicians and (ii) indication for surgery according to guidelines. Surgery was indicated in 194 (65%) patients according to attending physicians and in 221 (73%) according to guidelines, while 139 (46%) underwent surgery. Agreement was moderate between attending physicians and guidelines (kappa 0.41-0.59) and between indication according to guidelines and the performance of surgery (kappa 0.38). Of the 90 (30%) patients not operated despite indication, contraindication to surgery was reported by the attending physicians in 42 (47%), and indication was not identified in 48 (53%). One-year survival was 76% in patients with indication and surgery performed (n = 131), 69% in patients without indication and no surgery (n = 74), 56% in patients with identified indication and contraindication to surgery (n = 42), and 60% in patients with no identified indication (n = 48; P = 0.059). CONCLUSION: Cardiac surgery during acute IE was recommended in almost three out of four patients, although fewer than half were actually operated. Indication was not acknowledged by the attending physicians in one out of six patients.

In disease-endemic areas, histoplasmosis is the main differential diagnosis for tuberculosis among human immunodeficiency virus (HIV)-infected patients. However, no study has compared the two diseases. Thus, the objective of this study was to compare tuberculosis and histoplasmosis in HIV-infected patients. A population of 205 HIV-infected patients (99 with tuberculosis and 106 with histoplasmosis) hospitalized in Cayenne, French Guiana during January 1, 1997-December 31, 2008 were selected retrospectively from the French Hospital Database on HIV. Multivariate analysis showed that tuberculosis was associated with cough (adjusted odds ratio [AOR] = 0.20, 95% confidence interval [CI] = 0.05-0.73) and a C-reactive protein level > 70 mg/L (AOR = 0.98, 95% CI = 0.97-0.99). Variables associated with disseminated histoplasmosis were a γ-glutamyl transferase level > 72 IU/L (AOR = 4.99, 95% CI = 1.31-18.99), origin from French Guiana (AOR = 5.20, 95% CI = 1.30-20.73), disseminated localization (AOR = 6.40, 95% CI = 1.44-28.45), a concomitant opportunistic infection (AOR = 6.71, 95% CI = 1.50-29.96), a neutrophil count < 2,750 cells/mm(3) (AOR = 10.54, 95% CI = 2.83-39.24), a CD4 cell count < 60 cells/mm(3) (AOR = 11.62, 95% CI = 2.30-58.63), and a platelet count < 150,000/mm(3) (AOR = 19.20, 95% CI = 3.35-110.14). Tuberculosis and histoplasmosis have similarities, but some factors show a greater association with one of these diseases. Thus, adapted therapeutic choices can be made by using simple clinical and paraclinical criteria.

The incidence of dengue worldwide is increasing rapidly. A better understanding of dengue transmission may help improve interventions against this major public health problem. The virus is mostly transmitted by vectors. There are, however, other modes of transmission, notably mother-to-child transmission or vertical transmission. We studied a prospective cohort of 54 women who had dengue while pregnant during the 2012-2013 epidemic in French Guiana to estimate the mother-to-child transmission rate and assess the clinical and biological presentation of neonatal dengue. The rate of vertical transmission was between 18.5% (95% confidence interval [CI]: 9.25-31.4) and 22.7% (95% CI: 11.5-37.8), depending on the calculation method used. Mother-to-child transmission occurred both in early and late pregnancy. There were 52 births, including three newborns who presented neonatal dengue with warning signs requiring platelet transfusion. This quantification of the mother-to-child transmission of dengue highlights three points: first, vertical transmission of dengue is not negligible; second, it is more frequent when maternal dengue occurs late during pregnancy near delivery; and third, reliable diagnostic tests must be used to allow the diagnosis of vertical transmission. Our findings indicate that if there is a known history of maternal dengue during pregnancy, or if there is fever during the 15 days before term, cord blood and placenta should be sampled after delivery and tested for the virus, and the newborn should be closely monitored during the postpartum period.

BACKGROUND: Illegal gold miners in French Guiana, a French overseas territory ('département') located in Amazonia, often carry malaria parasites (up to 46.8%). While the Guiana Shield Region aims at malaria elimination, the high prevalence of Plasmodium in this hard-to-reach population in conjunction with frequent incorrect use of artemisinin-based anti-malarials could favour the emergence of resistant parasites. Due to geographical and regulatory issues in French Guiana, usual malaria control strategies cannot be implemented in this particular context. Therefore, new strategies targeting this specific population in the forest are required. METHODS: Numerous discussions among health institutions and scientific partners from French Guiana, Brazil and Suriname have led to an innovative project based on the distribution of kits for self-diagnosis and self-treatment of Plasmodium infections. The kit-distribution will be implemented at "resting sites", which are areas across the border of French Guiana regularly frequented by gold miners. The main objective is to increase the appropriate use and complete malaria treatment after a positive malaria diagnosis with a rapid test, which will be evaluated with before-and-after cross-sectional studies. Monitoring indicators will be collected from health mediators at the time of kit distribution and during subsequent visits, and from illegal gold miners themselves, through a smartphone application. The project funding is multisource, including Ministries of Health of the three countries, WHO/PAHO, and the European Union. RESULTS: This project will start in April 2018 as a 18 month pilot study led by the Clinical Investigation Centre of Cayenne. Results should be available at the end of 2019. DISCUSSION: This innovative approach may have several limitations which should be taken into account, as potential side effects, kit misuse or resale, declarative main criteria, or no Plasmodium vivax curative treatment. Close monitoring is thus needed. CONCLUSIONS: This project may be the best available solution to a specific and important public health challenge in the Guiana Shield. If the use of self-diagnosis and self-treatment approach is effective, this strategy could be sustained by health institutions in the region.

Arthropod-borne viruses or arbovirus, are most commonly associated with acute infections, resulting on various symptoms ranging from mild fever to more severe disorders such as hemorrhagic fever. Moreover, some arboviral infections can be associated with important neuroinflammation that can trigger neurological disorders including encephalitis, paralysis, ophthalmological impairments, or developmental defects, which in some cases, can lead to long-term defects of the central nervous system (CNS). This is well illustrated in Zika virus-associated congenital brain malformations but also in West Nile virus-induced synaptic dysfunctions that can last well beyond infection and lead to cognitive deficits. Here, we summarize clinical and mechanistic data reporting on cognitive disturbances triggered by arboviral infections, which may highlight growing public health issues spanning the five continents.

Background: Illegal gold miners are currently key hosts for malaria in French Guiana (FG), with a risk of emergence of resistance linked to improper use of artemisinin-based combination therapy (ACT). The remoteness of the mines and regulatory issues hinder their access to health care. Methods: A quasi-experimental researched project (Malakit) implemented in FG borders with Brazil and Suriname aimed at determining the effectiveness of distributed kits for self-diagnosis and self-treatment to illegal gold miners, after training, at strategic border staging areas. Evaluation relied on questionnaires at inclusion and follow-up visits, and pre/post intervention surveys. The primary outcome was the proportion of persons reporting a use of certified ACT after a positive malaria diagnosis. The secondary outcomes assessed antimalarial adherence, kit use and impact on malaria epidemiology. Findings: The proportion of patients reporting a use of certified ACT after a positive diagnosis increased after the intervention (OR 1.8, 95%CI [1.1-3.0]). From April 2018 to March 2020, 3,733 persons participated in the intervention. The kit was used correctly by 71.7% [65.8-77.7] of the 223 persons reporting having used a malakit during the follow-up visits. No serious adverse events related to the misuse of malakit have been reported. The intervention appears to have accelerated the decline in malaria incidence in the region by 42.9%. Interpretation: This innovative international project showed that people with low education can correctly self-manage their malaria symptoms. This strategy could be integrated in the malaria control programs of the countries involved and considered in other regions with residual malaria in remote areas. Funding: This project was funded by the European Union, the Global Fund, Brazil MoH, Cayenne Hospital and FG Health Regional Agency. Editor's note: This translation in French was submitted by the authors and we reproduce it as supplied. It has not been peer reviewed. Our editorial processes have only been applied to the original abstract in English, which should serve as reference for this manuscript. The Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations. Contexte: Les chercheurs d'or illégaux sont actuellement un réservoir clé du paludisme en Guyane, avec un risque d'émergence de résistance lié à une mauvaise utilisation des combinaisons thérapeutiques à base d'artémisinine (ACT). L'isolement de ces sites miniers clandestins et des contraintes règlementaires entravent leur accès aux soins. Méthodes: Un projet de recherche opérationnelle quasi-expérimental (Malakit) a été mis en œuvre aux frontières de la Guyane avec le Brésil et le Suriname. Il visait à déterminer l'efficacité de la distribution de kits d'autodiagnostic et d'autotraitement à des orpailleurs illégaux, après une formation adaptée, dans des zones stratégiques transfrontalières. L'évaluation s'est appuyée sur des questionnaires lors des visites d'inclusion et de suivi, et sur des enquêtes pré/post intervention. L'indicateur principal était la proportion de personnes déclarant avoir utilisé une ACT certifiée après un diagnostic positif de paludisme. Les indicateurs secondaires reposaient sur l'adhérence aux traitements antipaludiques, l'utilisation des kits et l'impact sur l'épidémiologie du paludisme. Résultats: La proportion de patients déclarant une utilisation d'ACT certifiée après un diagnostic positif a augmenté après l'intervention (OR 1,8, 95%CI [1,1-3,0]). D'avril 2018 à mars 2020, 3 733 personnes ont participé à l'intervention. Le kit a été utilisé correctement par 71,7% [65,8-77,7] des 223 personnes revues en visites de suivi ayant déclaré avoir utilisé un malakit. Aucun événement indésirable grave lié à une mauvaise utilisation du malakit n'a été signalé. L'intervention semble avoir accéléré la diminution de l'incidence du paludisme dans la région de 42,9%. Interprétation: Ce projet international innovant a montré que les personnes ayant un faible niveau d'éducation peuvent se prendre en charge par eux-mêmes pour des symptômes de paludisme. Cette stratégie pourrait être intégrée dans les programmes de lutte contre le paludisme des pays impliqués et envisagée dans d'autres régions où du paludisme résiduel persiste dans des zones isolées. Financement: Ce projet a été financé par l'Union Européenne, le Fonds Mondial, le Ministère de la santé du Brésil, le Centre Hospitalier de Cayenne et l'Agence Régionale de Santé de Guyane.

BACKGROUND: Malaria is endemic in French Guiana (FG), South America. Despite the decrease in cases in the local population, illegal gold miners are very affected by malaria (22.3% of them carried Plasmodium spp.). Self-medication seems to be very common, but its modalities and associated factors have not been studied. The aim of this study was to evaluate parasite susceptibility to drugs and to document behaviours that could contribute to resistance selection in illegal gold miners. METHODS: This multicentric cross-sectional study was conducted in resting sites along the FG-Surinamese border. Participating gold miners working in FG completed a questionnaire and provided a blood sample. RESULTS: From January to June 2015, 421 illegal gold miners were included. Most were Brazilian (93.8%) and 70.5% were male. During the most recent malaria attack, 45.5% reported having been tested for malaria and 52.4% self-medicated, mainly with artemisinin derivatives (90%). Being in FG during the last malaria attack was the main factor associated with self-medication (adjusted OR = 22.1). This suggests that access to malaria diagnosis in FG is particularly difficult for Brazilian illegal gold miners. Treatment adherence was better for persons who reported being tested. None of the 32 samples with Plasmodium falciparum presented any mutation on the pfK13 gene, but one isolate showed a resistance profile to artemisinin derivatives in vitro. CONCLUSIONS: The risk factors for the selection of resistance are well known and this study showed that they are present in FG with persons who self-medicated with poor adherence. Interventions should be implemented among this specific population to avoid the emergence of artemisinin resistance.

BACKGROUND: Lymphomatoid papulosis (LyP) is classified as an indolent cutaneous lymphoma, but outcome dramatically worsens if LyP is associated with lymphoma. The frequency of this association remains unclear in the literature. Here, we assess the frequency and risk factors of association between LyP and another lymphoma in an 11-year retrospective study conducted in 8 dermatology departments belonging to the French Study Group on Cutaneous Lymphoma (FSGCL). PATIENTS AND METHODS: Patients with LyP were identified and data extracted from the FSGCL registry between 1991 and 2006. Patients were followed up to January 2014. Age, sex, number of skin lesions, histologic subtype, and genotype were recorded at baseline. Risk factors were determined using univariate and multivariate analysis. Cumulative probability of association was calculated using the Kaplan-Meier method. RESULTS: We observed 52 cases of lymphomas (cutaneous, n = 38; systemic, n = 14) in 44 of 106 patients (41%). Lymphoma diagnosis was concomitant with or prior to LyP diagnosis in 31 cases and occurred during the course of LyP in 21 cases (cutaneous, n = 14; systemic, n = 7; median delay: 5 years; interquartile range: 1.5-7 years). In multivariate analysis, main prognostic factors for association between LyP and another lymphoma were older age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.01-1.08; p = .011) and presence of a T-cell clone in LyP lesions (OR: 7.55; 95% CI: 2.18-26.18; p = .001). CONCLUSION: Older age and presence of a T-cell clone in LyP lesions are risk factors for associated lymphomas in patients with LyP. These findings should help to identify patients who require close management in clinical practice. IMPLICATIONS FOR PRACTICE: The management of lymphomatoid papulosis (LyP) is that of an indolent cutaneous lymphoma, based on its excellent prognosis. However, this good prognosis is altered if LyP is associated with lymphoma. Furthermore, risk factors for and frequency of this association remain unclear in the literature. The results presented here demonstrate a high rate of association between LyP and other lymphomas (41%) as well as a long median delay of occurrence (5 years), which emphasizes the need for prolonged follow-up of patients with LyP. Moreover, two main risk factors (i.e., older age and presence of a T-cell clone in LyP lesions) are highlighted, which should help clinical practitioners to identify patients who require close management.

To implement future malaria elimination strategies in French Guiana, a characterization of the infectious reservoir is recommended. A cross-sectional survey was conducted between October and December 2017 in the French Guianese municipality of St Georges de l’Oyapock, located along the Brazilian border. The prevalence of Plasmodium spp . was determined using a rapid diagnostic test (RDT) and a polymerase chain reaction (PCR). Demographic, house locations, medical history, and biological data were analyzed. Factors associated with Plasmodium spp. carriage were analyzed using logistic regression, and the carriage localization was investigated through spatial cluster analysis. Of the 1,501 samples analyzed with PCR, positive results totaled 90 and 10 for Plasmodium vivax and Plasmodium falciparum , respectively. The general PCR prevalence was 6.6% [5.3–7.9], among which 74% were asymptomatic. Only 13/1,549 were positive by RDT. In multivariate analysis, participants older than 15 years, living in a remote neighborhood, with a prior history of malaria, anemia, and thrombocytopenia were associated with an increased odds of Plasmodium spp. carriage. High-risk clusters of P. vivax carriage were detected in the most remote neighborhoods on the village outskirts and two small foci in the village center. We also detected a hot spot for both P. vivax and P. falciparum symptomatic carriers in the northwestern part of the village. The present study confirms a wide-scale presence of asymptomatic P. falciparum and P. vivax carriers in this area. Although they were more often located in remote areas, their geographic distribution was spatially heterogeneous and complex.

French Guiana (FG), a French overseas territory in South America, is susceptible to tropical diseases, including arboviruses. The tropical climate supports the proliferation and establishment of vectors, making it difficult to control transmission. In the last ten years, FG has experienced large outbreaks of imported arboviruses such as Chikungunya and Zika, as well as endemic arboviruses such as dengue, Yellow fever, and Oropouche virus. Epidemiological surveillance is challenging due to the differing distributions and behaviors of vectors. This article aims to summarize the current knowledge of these arboviruses in FG and discuss the challenges of arbovirus emergence and reemergence. Effective control measures are hampered by the nonspecific clinical presentation of these diseases, as well as the Aedes aegypti mosquito’s resistance to insecticides. Despite the high seroprevalence of certain viruses, the possibility of new epidemics cannot be ruled out. Therefore, active epidemiological surveillance is needed to identify potential outbreaks, and an adequate sentinel surveillance system and broad virological diagnostic panel are being developed in FG to improve disease management.

BACKGROUND: In utero exposure to Zika virus (ZIKV) is known to be associated with birth defects. The impact of in utero ZIKV exposure on neurodevelopmental outcomes in early childhood remains unclear. The objective of this study was to determine the impact of in utero ZIKV exposure on neurodevelopment at 24 months of age among toddlers who were born normocephalic to women who were pregnant during the 2016 ZIKV outbreak in French territories in the Americas. METHODS: We conducted a population-based mother-child cohort study of women whose pregnancies overlapped with the 2016 ZIKV epidemic in Guadeloupe, Martinique, and French Guiana. Infants were included in this analysis if maternal ZIKV infection during pregnancy could be determined, the newborn had a gestational age ≥ 35 weeks, there were no abnormal transfontanelle cerebral ultrasound findings after delivery or no abnormal ultrasound findings on the last ultrasound performed during the third trimester of the mother's pregnancy, there was an absence of microcephaly at birth, and the parent completed the 24-month neurodevelopment assessment of the infant at 24 months (± 1 month) of age. ZIKV exposure of the toddler was determined by evidence of maternal ZIKV infection during pregnancy. Neurodevelopment assessments included the Ages and Stages Questionnaire (ASQ) for five dimensions of general development-communication, gross motor, fine motor, problem solving, and personal-social skills; the Modified Checklist for Autism on Toddlers (M-CHAT) for behavior; and the French MacArthur Inventory Scales (IFDC) for French language acquisition. RESULTS: Between June 2018 and August 2019, 156 toddlers with and 79 toddlers without in utero ZIKV exposure completed neurodevelopment assessments. Twenty-four (15.4%) ZIKV-exposed toddlers and 20 (25.3%) ZIKV-unexposed toddlers had an ASQ result below the reference - 2SD cut-off (P = 0.10) for at least one of the five ASQ dimensions. CONCLUSION: In one of the largest population-based cohorts of in utero ZIKV-exposed, normocephalic newborns to date, there were minimal differences apparent in neurodevelopment outcomes at 24 months of age compared to ZIKV-unexposed toddlers at 24 months of age. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02810210 . Registered 20 June 2016.

Nowhere to be seen Histoplasma capsulatum is endemic in the Americas [1,2]. It has been an AIDS-defining infection since 1987 [3]. In the USA, it is a well known pathogen that can be promptly diagnosed and treated. In South and Central America, and may be the Caribbean, it is another story. Since the onset of the HIV epidemic, there have been a number of convergent reports that suggest that disseminated histoplasmosis is one of the major AIDS-defining infections and a major killer of HIV-infected patients [4–8]. However, most hospitals still have no way of diagnosing the disease and often lack the best treatments for the disease. There is thus a double tragedy, with clinicians failing to diagnose what is killing their patients, and public health authorities failing to tackle one of the major burdens of disease. Mycologic diagnosis rests on direct examination and culture of tissue samples that is often invasive and may take weeks to reveal H. capsulatum[9]. Molecular biology is not commercially available and thus not available in most hospitals. The detection of H. capsulatum antigens in urine or serum by enzyme immune assays remains a simple, noninvasive, sensitive method, with an increasing number of alternatives that are being evaluated but are still distributed on a small scale in Latin America [9]. The future diagnostic tests that could radically change the picture should be ASSURED, that is affordable, sensitive, specific, user friendly, rapid, equipment free, and delivered to those who need it [10]. Connecting the dots Histoplasmin skin test studies show how widespread histoplasmosis is [1,2]. Mycologists have long been aware that the disease is there, but they often do not receive samples from clinicians in charge of HIV patients. Therefore, reports mention that a large proportion of histoplasmoses are HIV positive. However, this perspective is not likely to enhance histoplasmosis in HIV programmes. A more fruitful question, and one whose answer should get clinicians, public health authorities, and international authorities to act is how does histoplasmosis rank compared with other opportunistic infections? or what proportion of AIDS cases are in fact histoplasmosis cases? To answer requires sustained collaboration between mycologists and HIV clinics. A few teams have answered this question – in Panama, 7.65% of patients with HIV infection had culture-positive H. capsulatum[6]; in Guatemala, histoplamosis is the second opportunistic infection just after tuberculosis, but with a greater mortality [8]; in Venezuela, before the highly active antiretroviral therapy era, among 200 patients with AIDS, histoplasmosis was diagnosed in 43 (21.5%) [7], and in one study it was documented in 29 of 66 (44%) autopsies performed [1]; in Fortaleza Brazil, in 378 consecutively admitted HIV patients, 164 (43%) had disseminated histoplasmosis [5]; in French Guiana, histoplasmosis is the first AIDS-defining infection and has long been the first cause of AIDS-related death [4,11]; and a recent study showed that 42% of HIV patients admitted with CD4+ cell counts less than 200 and 85% of those with CD4+ cell counts less than 50 had disseminated histoplasmosis [12]. One may argue that these are focal hotspots of histoplasmosis; however, this does not fit with the spread of endemic regions for histoplasmosis. On the contrary, if one connects the dots, the picture is staggering. Histoplasmosis inflating tuberculosis statistics Reducing tuberculosis deaths, and notably HIV-associated tuberculosis, is a major objective for the Joint United Nations programme on HIV/AIDS (UNAIDS), the Pan American Health Organization (PAHO), and numerous AIDS programmes. Recently, data from Latin America showed a 60% increase in culture-negative relative to culture-positive tuberculosis [13]. The conclusion was that culture-negative cases were possibly because of other causes. Presumably, a large proportion of these deadly cases were disseminated histoplasmosis misdiagnosed as tuberculosis [14,15]. A staggering invisible burden There are an estimated 1 600 000 HIV patients in the Americas. If we apply the incidence rate of 1.5 per 100 person-years measured in French Guiana [4], this suggests that there are 24 000 histoplasmosis cases in the Americas per year. The historical death rate of 40% [16] of deaths in histoplasmosis would mean there are 9600 deaths per year. In addition, it is arguable that the incidence rate is a low estimate of that of other regions in the Americas. Indeed in this French territory, 30% of patients have less than 200 CD4+ cell counts when tested and over 85% of the patients are on treatment, a situation that is probably more favourable than in other countries where up to 60% of patients are at stage C, where treatment initiation is still delayed and a large proportion of the HIV population is not yet on antiretroviral treatment [17]. In addition, for undiagnosed histoplasmosis, mortality is likely to be far greater than 40%. For the Americas, the estimated annual number of malaria deaths for 2013 was 84 [18]; HIV–tuberculosis annual deaths are estimated 6000 [19], and AIDS, without specification, is estimated 47 000 annual deaths [17]. So the number of deaths from tuberculosis in AIDS patients is at a similar level than HIV-associated histoplasmosis deaths (Fig. 1). However, one is a strategic objective of UNAIDS/PAHO/the CDC/GATES foundation's HIV/AIDS strategic plans, and the other is nowhere to be seen.Fig. 1: Estimated number of deaths per year for different major infectious diseases in Latin America.How could 9600 deaths a year – approximately the equivalent number of deaths as 70 Boeing 737 plane crashes a year – have gone unnoticed? The extrapolation of this to the 34 years since the AIDS epidemic was recognized puts the cumulated number of deaths in Latin America well over 100 000. We concede that such estimates are gross approximations, that histoplasmosis incidence may be more heterogeneous than we portray, but the order of magnitude is plausible. Correcting the lethal blind spot The fact that a network of independent HIV care and mycology specialists reaches the same conclusion should be taken seriously. So far, the scattered scientific publications do not seem to have percolated up towards the upper spheres of public health decision making. The expanding and earlier access to antiretroviral treatments should have a substantial impact on the mortality of histoplasmosis [20,21]. However, despite efforts to promote early HIV testing and to put greater numbers of persons on antiretroviral treatment, histoplasmosis still has a bright future because late testing, adherence and follow-up difficulties are still common. The international public health system and numerous HIV programmes have a blind spot; we believe a huge global health tragedy has been overlooked, and apathy to change when the stakes are so high would be unacceptable. Mycology is a neglected specialty [22], often struggling to keep functioning; innovation is hampered by financial anaemia. Recently, PAHO has funded technical cooperation on histoplasmosis at a level of 50 000 dollars, a good start but it represents less than one dollar per estimated histoplasmosis death. We need simple diagnostic tests, and we need to lobby for affordable liposomal amphotericin B in endemic countries, teach clinicians to adapt diagnostic and treatment algorithms and get histoplasmosis on board of the HIV/AIDS strategic plans. Surely, major funders have the power to make things right, by funding and inciting national AIDS programmes to correct this gap and avoid more unnecessary deaths. Acknowledgements Writing committee: Mathieu Nachera,b, Antoine Adenisa,b, Eduardo Arathoonc, Blanca Samayoac, Dalia Lau-Bonillac, Beatriz L. Gomezd, Angela Tobond, Diego Caceresd, Silvia Marques da Silvae, Maurimelia Mesquita da Costae, Rosely Zancopef, Terezinha Silva Leitãog, Margarete Do Socorro Mendonca Gomesh, Ivina Lopes Limah, Rosilene Malcher Leiteh, Stephen Vredeni, Marja Van Eerj, Sigrid Mac Donaldi, Sandra Hermelini, Magalie Demarb,k, Denis Blanchetb,k, Felix Djossoub,l, Vincent Vantilckem, Maria Mercedez Panizon, Maribel Dolanden, Christina Canteroso, Marcus Lacerdap,q, Pierre Couppiébr, Angela Restrepod. aCentre d’Investigation Clinique Antilles Guyane, CIC INSERM 1424, Centre Hospitalier de Cayenne, Cayenne, French Guiana. bEA3593 Ecosystèmes Amazoniens et Pathologie Tropicale, Université de Guyane, Cayenne, French Guiana. cClínica Familiar ‘Luis Angel García’, Asociación de Salud Integral, Guatemala city, Guatemala. dSchool of Medicine and Health Sciences, Universidad Rosario, Bogotá and Corporacion para Investigationnes Biologicas, Medellin, Colombia. eInstituto Evandro Chagas – IEC/SVS/MS Seção de Bacteriologia e Micologia – SABMI Laboratório de Micologia, Belem, Brazil. fLaboratório de Micologia, Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro, Brazil. gFederal University of Ceará, Fortaleza, Brazil. hLaborató rio Central de Saude Publica do Amapá, Macapa, Brazil. iAcademic Hospital Paramaribo, Suriname. jDiakonessenhuis, Paramaribo, Suriname. kLaboratoire Hospitalo-Universitaire de parasitologie mycologie, Centre Hospitalier de Cayenne, Cayenne, French Guiana. lService des Maladies Infectieuses et Tropicales, Centre Hospitalier de Cayenne, Cayenne, French Guiana. mService de Médecine, Centre Hospitalier de l’Ouest Guyanais,Saint Laurent du Maroni, French Guiana. nDepartamento de Micología, Instituto Nacional de Higiene Rafael Rangel, Caracas, Venezuela. oINEI-ANLIS ‘Dr Carlos G. Malbran,’ Buenos Aires, Argentina. pInstituto Leônidas e Maria Deane (Fiocruz – Amazônia). qFundação de Medicina Tropical Dr Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil. rService de Dermatologie-Vénéréologie, Centre Hospitalier de Cayenne, French Guiana. Authors’ contributions: M.N. wrote the first draft, and all authors amended and endorsed the final version. In memory: We wish to dedicate this article to the memory of Maurimelia Mesquita da Costa, a wonderful person and a great mycologist. Funding: This work has benefited from an ‘Investissement d’Avenir’ grant managed by Agence Nationale de la Recherche (CEBA, ref. ANR-10-LABX-25-01). Conflicts of interest There are no conflicts of interest.

BACKGROUND: Since 2013, 3 successive arbovirus outbreaks, dengue (DENV), chikungunya (CHIKV), and Zika virus, have occurred in French Guiana (FG). The primary objective of this study was to describe the socioeconomic indicators of the first patients infected with CHIKV during the outbreak of 2014. The secondary objective was to compare those patients with patient infected by DENV and with the local population. METHODS: A monocentric, retrospective, case-control study was conducted in Cayenne hospital in FG comparing a group of patients infected with CHIKV in 2014 with a group infected with DENV in 2013. Children aged less than 15 years and pregnant women were excluded. RESULTS: A total of 168 CHIKV patients were compared with 168 DENV patients. Factors associated with CHIKV were living in poor neighborhoods (82% vs 44%; odds ratio [OR], 5.81; 95% confidence interval [CI], 3.35-10.2), having a precarious status (54% vs 33%; OR, 2.37; 95% CI, 1.49-3.78), and being born abroad (70% vs 35%; OR, 4.35; 95% CI, 2.69-7.06). CONCLUSIONS: The present results suggest that early in the epidemic, the populations most at risk for CHIKV infection were the most socially vulnerable populations in the poorest neighborhoods, whereas DENV appeared to have affected a richer population and richer areas.

Dengue fever is an increasing problem worldwide, but consequences during pregnancy remain unclear. Much of the available literature suffers from methodological biases that compromise the validity of clinical recommendations. We conducted a matched cohort study during an epidemic in French Guiana to compare events and pregnancy outcomes between two paired groups of pregnant women: women having presented with symptomatic dengue during pregnancy (n = 73) and women having had neither fever nor dengue during pregnancy (n = 219). Women in each arm were matched by place of follow up, gestation weeks at inclusion, and place of residence. Dengue infection was considered to be confirmed if viral RNA, N S1 antigen, the seroconversion of IgM antibodies or the presence of IgM was detected in collected samples. According to the 2009 WHO classification, 27% of the women with symptomatic dengue had at least one clinical or biological warning sign. These complications occurred after the 28th week of gestation in 55% of cases. The medical history, socioeconomic status and demographic characteristics were included in multivariate analysis. Exposure to dengue during pregnancy was not significantly associated with prematurity, small for gestational age infants, hypertension or emergency caesarian section. Maternal dengue with warning signs was a risk factor for peripartum hemorrhage with adjusted relative risk = 8.6(95% CI = 1.2-62). There was a near significant association between dengue and in utero death (p = 0.09). This prospective comparative study underlined the importance of taking into account potential confounders between exposure to dengue and the occurrence of obstetrical events. It also confirms the need for increased vigilance for pregnant women with dengue, particularly for women who present with severe dengue.

While general lockdowns have proven effective to control SARS-CoV-2 epidemics, they come with enormous costs for society. It is therefore essential to identify control strategies with lower social and economic impact. Here, we report and evaluate the control strategy implemented during a large SARS-CoV-2 epidemic in June-July 2020 in French Guiana that relied on curfews, targeted lockdowns, and other measures. We find that the combination of these interventions coincided with a reduction in the basic reproduction number of SARS-CoV-2 from 1.7 to 1.1, which was sufficient to avoid hospital saturation. We estimate that thanks to the young demographics, the risk of hospitalisation following infection was 0.3 times that of metropolitan France and that about 20% of the population was infected by July. Our model projections are consistent with a recent seroprevalence study. The study showcases how mathematical modelling can be used to support healthcare planning in a context of high uncertainty.

BACKGROUND: This multicentre phase II trial (DOVIGIST) evaluated the antitumour activity of dovitinib as second-line treatment of patients with gastrointestinal stromal tumour (GIST) refractory to imatinib or who do not tolerate imatinib. METHODS: , 5 days on/2 days off, until GIST progression or unacceptable toxicity, with an objective to evaluate efficacy, assessed as the disease control rate (DCR) at 12 weeks. Tumour assessment and response to dovitinib therapy were evaluated by Response Evaluation Criteria In Solid Tumours (RECIST v1.1) and the Choi criteria. Secondary objectives included assessment of progression-free survival (PFS), safety and tolerability, and DCR at the end of treatment. RESULTS: Thirty-eight of the 39 patients enrolled had histologically confirmed GIST. The DCR at 12 weeks was 52.6% (90% confidence interval (CI), 38.2-66.7%) meeting the preset efficacy criterion for the primary end point. The objective response rate (complete response+partial response) was 2.6% (1 of 38; 90% CI, 0.1-11.9%), and 5.3% (n=2; 90% CI, 0.9-15.7%) at the end of the study. The median PFS was 4.6 months (90% CI, 2.8-7.4 months). Dose interruption was required in 26 patients (66.7%), of which 18 (69.2%) were due to adverse events. The most frequently observed grade 3 adverse events included hypertension (n=7), fatigue (n=5), vomiting (n=4), hypertriglyceridaemia (n=4), and γ-glutamyltransferase increase (n=4). CONCLUSIONS: Dovitinib is an active treatment for patients with GIST who are intolerant to imatinib or whose GIST progresses on imatinib.

BACKGROUND: Histoplasmosis is among the main acquired immunodeficiency syndrome (AIDS)-defining conditions in endemic areas. Although histoplasmosis has a worldwide distribution, histoplasmosis-associated immune reconstitution inflammatory syndrome (IRIS) in people living with human immunodeficiency virus (PLHIV) is rarely reported.This study aimed to describe the incidence and features of histoplasmosis-associated IRIS in a cohort of PLHIV. METHODS: A retrospective multicenter study was conducted in French Guiana from 1 January 1997 to 30 September 2017. The target population was represented by PLHIV who presented an episode of histoplasmosis within 6 months after antiretroviral therapy initiation. We used a consensual IRIS case definition, submitted to the agreement of 2 experts. Each case was described using a standardized questionnaire, and all patients gave informed consent. RESULTS: Twenty-two cases of histoplasmosis-associated IRIS were included (14 infectious/unmasking and 8 paradoxical), with an overall incidence rate of 0.74 cases per 1000 HIV-infected person-years (95% confidence interval, 0.43-1.05). Mean age was 40.5 years. The ratio of males to females was 1:4. Median time to IRIS was 11 days (interquartile range 7-40 days) after antiretroviral therapy initiation. The main clinical presentation was fever, without any specific pattern, and disseminated disease. We reported 2 severe cases and partial or complete recovery at 1 month was the rule. Twenty-two cases were identified in the literature with similar characteristics. CONCLUSIONS: Histoplasmosis-associated IRIS incidence was low but generated significant morbidity in PLHIV. In endemic areas, screening for latent or subclinical histoplasmosis should be implemented before antiretroviral therapy initiation.