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

Outbreak of Leishmania braziliensis cutaneous leishmaniasis, Saül, French Guiana [letter]

New World cutaneous leishmaniasis (CL), a zoonotic disease, is increasingly seen among travelers returning from Latin American countries, particularly from Bolivia, Belize, and French Guiana (1). The epidemiology of CL in the Americas is heterogeneous and has complex variations in transmission cycles, reservoir hosts, and sandfly vectors. Changing human activities that affect these factors may have resulted in the emergence of species with distinct pathogenic potentials and responses to therapy. In the Guianan ecoregion complex, leishmaniasis is endemic, and 5 coexisting Leishmania parasite species are known to infect humans: L. guyanensis, L. braziliensis, L. amazonensis, L. naiffi, and L. lainsoni. Among these species, L. guyanensis accounts for ≈85% of CL cases (2). We report an outbreak of 7 cases of L. braziliensis CL that occurred among 24 scientists who participated in a field mission at Limonade Creek in Saül, French Guiana, during October 10–25, 2013. Saül is an isolated village in the Amazonian rainforest (3°55′18′′N, 53°18′02′′W)

Approche épidémiologique, clinique et biologique des formes sévères de toxoplasmose acquise du sujet adulte immunocompétent en Guyane française

This thesis in a focus on medical knowledge and scientific work which helped to describe since 1998 a special from of acquired toxoplasmosis especially reported in French Guiana and in a Surinamese border village. It presents as a clinical and pathophysiological approach of criteria of pathogenicity of Toxoplasma gondii that circulate in French Guiana. The document is organized into three main parts ; the first one reports the clinical, epidemiological and biological features of this form of toxoplasmosis, called Amazonian toxoplasmosis or AT ; the second part develops the arguments for the existence of a forest base cycle of atypical strains of T.gondii, and the third part determines the virulence criteria on mice for one T.gondii involved in AT.General review of published articles associated with the analysis of 35 cases of AT reported from 2002 to 2009 clearly highlight the experience of this clinical entity that is remarkable for its morbidity and its clinical heterogeneity. Ethnicity, place of residence and some biological parameters seems to be aggravating factors. The initial hypothesis that AT involves unsuitable T.gondii strains to humans led to study the circulation of the parasite in wildlife and recent studies confirms this hypothesis. The third part of this document really concretizes the virulence on mice of one atypical T.gondii strain involved in an AT case by the determination od the letal dose, LD50 and LD100 and the description of of the histological features. This part initiates a discussion about the pathophysiolgical mechanisms of this entityCette thèse fait une mise au point sur les connaissances médicales et les travaux scientifiques qui ont contribué à mettre en lumière depuis 1998 une forme particulière de toxoplasmose acquise décrite principalement en Guyane Française et à sa frontière Surinamaise. Elle s organise en une double approche clinique et physiopathologique des critères de pathogénicité des Toxoplasma gondii circulant en Guyane et se décline en 3 volets ; le premier rapportant les aspects cliniques, épidémiologique et biologiques de cette forme de toxoplasmose, dénommée toxoplasmose amazonienne ou TA ; le deuxième expose les arguments pour l existence d un cycle forestier impliquant des souches T.gondii atypiques et à l origine de ces formes ; et le troisième volet détermine des critères de virulence d une souche atypique responsable de TA chez la souris.Le travail de synthèse des articles publiés couplé à l exploitation de 35 cas entre 2002 et 2009 met bien en évidence l existence de cette entité clinique remarquable de part sa morbidité, sévérité et son hétérogénéité clinique. Le caractère ethnique et le lieu de résidence pourraient être des facteurs aggravants de même que certains paramètres biologiques. L hypothèse initiale d une inadaptation de souches de T.gondii à l homme à conduit à explorer la circulation du parasite dans la faune sauvage et les enquêtes réalisées sur ce biotope confortent cette idée. La troisième partie de ce document rapporte bien par i) des critères chiffrés au travers de la DL 50 et DL100, ii) par des critères anatomopathologiques, la virulence particulière d une souche. Elle initie une réflexion sur les mécanismes physiopathologiques de cette entité.CAYENNE-BU (973022101) / SudocSudocFranceFrench GuianaFRG

Hyperparasitaemia during bouts of malaria in French Guiana.

International audienceUNLABELLED: ABSTRACT: BACKGROUND: High circulating parasite load is one of the WHO criteria for severe falciparum malaria. During a period of 11 years (2000-2010), the frequency of hyperparasitaemia (HP) (≥4% infected erythrocytes) during bouts of malaria due to Plasmodium falciparum, Plasmodium vivax and Plasmodium malariae in patients referred to Cayenne General Hospital (CGH) in French Guiana and the frequency of their admission to the Intensive Care Unit (ICU) were evaluated. METHODS: A mean of 1,150 malaria cases were referred to the Parasitology Laboratory of CGH each year over the last decade. During this period, malaria diagnostic (microscopy) and parasitaemia evaluation have remained unchanged: determination of the parasitized erythrocytes percentage with asexual forms on thin blood smears for all cases of parasitaemia exceeding 0.1%. Patients admitted to the ICU can be counted by origin of the request for malaria testing. All the data collected retrospectively were anonymized in a standardized case report form and in database. RESULTS: Between 2000 and 2010, 12,254 bouts of malaria were confirmed at the Parasitology Laboratory of CHG: P. vivax: 56.2%, P. falciparum: 39.5%, co-infection with both species: 3.4%, P. malariae: 0.9%. HP was observed in 262 cases, at a frequency of 4.9% for P. falciparum and only 0.041% for P. vivax, with no recorded cases for P. malariae. The need for intensive care was correlated with P. falciparum parasite load: 12.3% of cases for parasitaemia of 4-9%, 21.2% for parasitaemia 10-19%, 50% for parasitaemia 20-29% and 77.8% for parasitaemia ≥30% (n=9). The patient with the highest parasitaemia (75% infected erythrocytes with asexual form) presented a major concomitant lupus flare-up treated with corticoids. He survived without obvious sequelae. CONCLUSIONS: In French Guiana during bouts of malaria, HP was observed at a frequency of ~ 5% for P. falciparum and two orders of magnitude less frequent for P. vivax. HP is a severity criterion for falciparum malaria in this endemic area. However, two of the patients with HP ≥30% were not admitted to the ICU and sequel-free cure in malaria patients with 75% parasitaemia is, therefore, possible

Plasmodium falciparum malaria in splenectomized patients: two case reports in French Guiana and a literature review.

International audienceSome of the immunologic mechanisms involved in malaria physiopathology remain unclear. In animals, the spleen seems to play a key role in protecting the host against malaria. However, little is known about the effect of spleen dysfunction on human malaria. We report two severe cases of Plasmodium falciparum infection with unusual clinical and parasitologic features in two splenectomized men living in French Guiana. The peripheral blood of these cases showed hyperparasitemia, with a high proportion of mature parasites and leukocytes with malaria pigment. Despite appropriate treatment and adequate absorption, hyperparasitemia persisted. Parasite clearance was delayed and one patient died. Only the patient who died had the merozoite surface protein 1 allele B-K1 and the varD gene genotype, which is considered to be a probable parasite virulence factor. These uncommon cases differ from most of those described in the literature, illustrating the complexity of the mechanisms underlying the protective function of the spleen in human malaria

Disseminated Histoplasmosis: Fighting a neglected killer of patients with advanced HIV disease in Latin America

International audienc

Virulence des souches atypiques de Toxoplasma gondii isolées en Guyane française chez un modèle murin

International audienc

Atypical Toxoplasma gondii strain from a free-living jaguar (Panthera onca) in French Guiana

International audienceLike domestic cats, wild felids are involved in the complete infective cycle of Toxoplasma gondii because they can host in their gastrointestinal tract sexually mature parasites and shed infective oocysts in their feces. We report, to our knowledge, the first isolation and molecular characterization of a T. gondii strain from the heart tissue of a free-living jaguar (Panthera onca) in French Guiana. Sequencing at six polymorphic markers indicated that the jaguar isolate had an atypical genotype, including an allele at TgM-A previously found only in isolates from South America, and an allele at GRA6, which was previously reported only in Californian sea otter isolates. These findings are consistent with the recent description of atypical T. gondii strains involved in severe toxoplasmoses in immunocompetent patients in French Guiana that seemed to be linked to a neotropical forest-based cycle involving wild cats and their prey

Virulence of atypical Toxoplasma gondii strains isolated in French Guiana in a murine model

International audienceBACKGROUND: Toxoplasma gondii is an obligate intracellular protozoan parasite of warm-blooded vertebrates. Most infections in immunocompetent patients are asymptomatic. However, since 2000s, strains with particular genetic profiles that differ from the known clonal type (type I, II, III), have been described. In French Guiana, these strains are highly pathogenic in immunocompetent patients. They have defined a new clinical entity called Amazonian Toxoplasmosis. The present study aims to further improve our knowledge on the pathogenicity of these Amazonian T. gondii strains in comparison with three reference strains using Swiss strain mice. With these data, we tried to establish a predictive virulence score to classify these strains, but also to correlate this virulence with the severity of the disease in infected patients.RESULTS: All the virulence indicators revealed that the Amazonian strains isolated in French Guiana presented a high virulence profile, but lower than the highly virulent type I reference RH strain. The findings reveal differences in virulence between human and animal strains, but also between anthropized and wild strains.CONCLUSION: In addition to being a clinically relevant animal model of Amazonian Toxoplasmosis, this model could also provide a solid experimental basis for future studies aiming to investigate the underlying mechanisms of Amazonian Toxoplasmosis disease.Virulence des souches atypiques de Toxoplasma gondii isolées en Guyane française chez un modèle murin. Contexte. Toxoplasma gondii est un parasite protozoaire intracellulaire obligatoire des vertébrés à sang chaud. La plupart des infections chez les patients immunocompétents sont asymptomatiques. Cependant, depuis les années 2000, des souches avec des profils génétiques particuliers qui diffèrent du type clonal connu (type I, II, III) ont été décrites. En Guyane française, ces souches sont hautement pathogènes chez les patients immunocompétents. Elles ont défini une nouvelle entité clinique appelée Toxoplasmose Amazonienne. La présente étude vise à approfondir nos connaissances sur le pouvoir pathogène de ces souches amazoniennes de T. gondii par rapport à 3 souches de référence en utilisant des souris de souche Swiss. Avec ces données, nous avons tenté d'établir un score de virulence prédictif pour classer ces souches mais également de corréler cette virulence avec la gravité de la maladie chez les patients infectés. Résultats. Tous les indicateurs de virulence ont révélé que les souches amazoniennes isolées en Guyane française présentaient une virulence élevée mais plus faible que la souche de référence RH très virulente de type I. Les résultats ont mis en évidence les différences de virulence entre les souches humaines et animales mais aussi entre les souches anthropisées et les souches sauvages. Conclusion. En plus d'être un modèle animal cliniquement pertinent de la toxoplasmose amazonienne, ce modèle pourrait également fournir une base expérimentale solide à de futurs travaux qui chercheront à approfondir les mécanismes sous-jacents de la toxoplasmose amazonienne