Search

Background: Histoplasmosis is mainly described as a disseminated disease in people living with HIV (PLHIV). Compared to historical descriptions in immunocompetent individuals, knowledge is lacking on the detailed clinical and radiological findings and outcomes of pulmonary histoplasmosis (PH). Overlooked or misdiagnosed with other AIDS-defining condition, prognostic of PLHIV may be at risk because of inappropriate care., Methods: A retrospective multicentric study was conducted in PLHIV from French Guiana between January 1988 and October 2019. Proven PH were documented through mycological direct examination, culture, or histology. Patients with concomitant respiratory infections were excluded., Results: Among 65 patients, sex ratio M:F was 2.4 with a median age of 39 years [IQR 25-75%: 34-44]. Median CD4 count was 24 cells/mm 3 [11-71], with histoplasmosis as the AIDS-defining condition in 88% and concomitant AIDS-defining conditions in 29%. Clinical findings were fever (89%), cough (58%), dyspnea (35%), expectoration (14%), and hemoptysis (5%). Sixty-one X-rays and 24 CT-scans were performed. On X-rays, an interstitial lung disease was mainly found (77%). On CT-scans, a nodular pattern was predominant (83%): mostly miliary disease (63%), but also excavated nodules (35%). Consolidations were present in 46%, associated with miliary disease in 21%. Thoracic lymphadenopathies were found in 58%, mainly hilar and symmetric (33%). Despite antifungal treatment, case-fatality rate at one month was 22%., Conclusion: When faced with an interstitial lung disease on X-rays or a miliary pattern on CT-scans in advanced PLHIV, physicians in endemic areas, apart from tuberculosis or pneumocystosis, should include histoplasmosis as part of their differential diagnoses., (© 2023. The Author(s).)

Objectives: The burden of histoplasmosis is as great as that of tuberculosis in Latin America and the attributable mortality is even higher. A better assessment of severity could help reduce mortality., Methods: From the French Guiana HIV-histoplasmosis database, we attempted to identify factors associated with 30-day death after antifungal drug initiation and constructed a prognostic score. We evaluated its discrimination performance using several resampling methods., Results: Of the 415 patients included, 56 (13.5%) died within 30 days of treatment. The fatality-associated factors were performance status ≥3, altered mental status, dyspnea, C-reactive protein ≥75 mg/l, hemoglobin <9 g/dl and/or a platelet <100000/ml, and an interstitial lung pattern on chest X-ray. We constructed a 12-point prognostic score. A threshold ≥5 classified patients as alive or dead at 30 days with a sensitivity of 84%, a specificity of 81%, a positive predicted value of 40%, and a negative predicted value of 97%. The area under the curve of the receiver operating characteristic curves from the different resamples were stable between 0.88 and 0.93., Conclusion: The histoplasmosis case fatality score, which is easy and inexpensive to perform, is a good tool for assessing severity and helping in the choice of induction therapy. An external validation remains necessary to generalize these results., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Source of many myths, French Guiana represents an exceptional territory due to the richness of its biodiversity and the variety of its communities. The only European territory in Amazonia, surrounded by the Brazilian giant and the little-known Suriname, Ariane 6 rockets are launched from Kourou while 50% of the population lives below the poverty line. This paradoxical situation is a source of health problems specific to this territory, whether they be infectious diseases with unknown germs, intoxications or chronic pathologies.Some infectious diseases such as Q fever, toxoplasmosis, cryptococcosis or HIV infection are in common with temperate countries, but present specificities leading to sometimes different management and medical reasoning. In addition to these pathologies, many tropical diseases are present in an endemic and / or epidemic mode such as malaria, leishmaniasis, Chagas disease, histoplasmosis or dengue. Besides, Amazonian dermatology is extremely varied, ranging from rare but serious pathologies (Buruli ulcer, leprosy) to others which are frequent and benign such as agouti lice (mites of the family Trombiculidae) or papillonitis. Envenomations by wild fauna are not rare, and deserve an appropriate management of the incriminated taxon. Obstetrical, cardiovascular and metabolic cosmopolitan pathologies sometimes take on a particular dimension in French Guiana that must be taken into account in the management of patients. Finally, different types of intoxication are to be known by practitioners, especially due to heavy metals.European-level resources offer diagnostic and therapeutic possibilities that do not exist in the surrounding countries and regions, thus allowing the management of diseases that are not well known elsewhere.Thanks to these same European-level resources, research in Guyana occupies a key place within the Amazon region, despite a smaller population than in the surrounding countries. Thus, certain pathologies such as histoplasmosis of the immunocompromised patient, Amazonian toxoplasmosis or Q fever are hardly described in neighboring countries, probably due to under-diagnosis linked to more limited resources. French Guiana plays a leading role in the study of these diseases.The objective of this overview is to guide health care providers coming to or practicing in French Guiana in their daily practice, but also practitioners taking care of people returning from French Guiana., (Copyright © 2023 SFMTSI.)

Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Nacher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Disseminated histoplasmosis is a major killer of HIV-infected persons in Latin America. Antigen detection, fungal culture and Polymerase Chain Reaction are often not available, but cytology and histology are present in most hospitals and may offer a diagnostic alternative. In this study, we review 34 years of clinical experience to describe the roles of cytology and histology in diagnosing disseminated histoplasmosis., Methods: Retrospective multicentric study of 349 patients between 1 January 1981 and 1 October 2014 with confirmed disseminated histoplasmosis., Results: Around 32/214 (14.9%) of samples were screened using cytopathology, as were 10/101 (9.9%) bronchoalveolar lavage samples and 5/61 (8.2%) of spinal fluid samples. The samples most commonly sent to pathology were liver biopsies, lower digestive tract and lymphnode biopsies; the greatest proportion of positive results were found in lower digestive tract (43/59 (72.9%) positives), lymph node (39/63 (66.1%)), and liver (38/75 (50.7%)) samples. Overall, 97.2% of bone marrow and 97% of bronchoalveolar lavage samples were directly examined by a mycologist. Positive direct examination was independently associated with death (aHR = 1.5 (95%CI = 1-2.2))., Conclusions: Opportunities for a rapid diagnosis were regularly missed, notably for bone marrow samples, which could have been examined using staining methods complementary to those of the mycologist., (© 2021 John Wiley & Sons Ltd.)

Disseminated histoplasmosis is the most frequent acquired immunodeficiency syndrome-defining illness in French Guiana. Paradoxically, central nervous system (CNS) involvement has been scarcely described. We aimed to identify CNS histoplasmosis in our territory. We conducted an observational, multicentric, descriptive, and retrospective study including patients with proven or probable CNS histoplasmosis according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MGS). The study population consisted of patients admitted in one of the hospitals of French Guiana between January 1, 1990 and December 31, 2019. During the study period, 390 cases of HIV-associated histoplasmosis were recorded, in which six of them had CNS infections with Histoplasma capsulatum. The male to female sex ratio was 0.25, and the median age at diagnosis was 37.5 years. The median CD4 count was 42 cells/mm3 ([IQR: 29-60]). All patients had disseminated histoplasmosis. Usual signs of meningitis were observed in three patients and focal signs in four patients. One patient had no neurological signs. The median time between the first cerebral symptoms and diagnosis was 22.4 days (IQR 9.5-36.2). Two patients died within a month after diagnosis. In conclusion, few proven CNS localizations of histoplasmosis were observed on 30-year study in French Guiana. This low proportion suggests that the documentation of CNS involvement is often not ascertained for lack of awareness of this particular presentation, and for lack of rapid and sensitive diagnostic tools.

Adrenal histoplasmosis and primary adrenal insufficiency are mostly described in immunocompetent patients. This particular tropism is attributed to the presence of cortisol within the adrenal gland, a privileged niche for Histoplasma growth. In French Guiana, disseminated histoplasmosis is the main opportunistic infection in HIV patients. Our objective was to search in our HIV-histoplasmosis cohorts to determine how frequent adrenal insufficiency was among these patients. Between January 1, 1981 and October 1, 2014, a multicentric retrospective, observational study of histoplasmosis was conducted. Patients co-infected by HIV and histoplasmosis were enrolled in French Guiana's histoplasmosis and HIV database. Among 349 cases of disseminated histoplasmosis between 1981 and 2014, only 3 had adrenal insufficiency (0.85%). Their respective CD4 counts were 10, 14 and 43 per mm3. All patients had regular electrolyte measurements and 234/349 (67%) had abdominal ultrasonography and 98/349 (28%) had abdominopelvic CT scans. None of these explorations reported adrenal enlargement. Overall, these numbers are far from the 10% reports among living patients and 80-90% among histoplasmosis autopsy series. This suggests 2 conflicting hypotheses: First, apart from acute adrenal failure with high potassium and low sodium, less advanced functional deficiencies, which require specific explorations, may have remained undiagnosed. The second hypothesis is that immunosuppression leads to different tissular responses that are less likely to incapacitate the adrenal function. Furthermore, given the general immunosuppression, the adrenal glands no longer represent a particular niche for Histoplasma proliferation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nacher, Alsibai, Valdes, Abboud, Adenis, Blaizot, Blanchet, Demar, Djossou, Epelboin, Misslin, Ntab, Sabbah and Couppié.)

Background: Disseminated histoplasmosis is a major killer of patients with advanced HIV. It is proteiform and often hard to diagnose in the absence of diagnostic tests. We aimed to describe disseminated histoplasmosis with lymphadenopathies in French Guiana and to compare survival and severity of those patients to patients without lymphadenopathies., Methods: A retrospective cohort study was performed on data records collected between January 1, 1981 and October 1, 2014., Results: Among 349 cases of disseminated histoplasmosis 168 (48.3%) had superficial lymphadenopathies and 133(38.1%) had deep lymphadenopathies. The median LDH concentration, ferritin concentration, TGO concentration, and WHO performance status were lower among patients with deep lymphadenopathies than those without deep lymphadenopathies. There was a significant decrease in the risk of early death (<1 month) among those with deep lymphadenopathies relative to those without (OR=0.26 (95%CI=0.10-0.60), P=0.0006) and in the overall risk of death (OR=0.33 (95%CI=0.20-0.55), P<0.0001). These associations remained strongly significant after adjusting for time period, CD4 counts, age, delay between beginning of symptoms and hospital admission, antifungal and antiretroviral treatment., Conclusions: The present data show that in patients with advanced HIV and disseminated histoplasmosis, the presence of deep lymphadenopathies is associated with fewer markers of severity and a lower risk of death. To our knowledge it is the first study to show this. The presence of deep lymphadenopathies is hypothesized to reflect the patient's partially effective defense against H. capsulatum ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nacher, Alsibai, Adenis, Blaizot, Abboud, Demar, Djossou, Epelboin, Misslin, Ntab, Valdes and Couppié.)

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., Competing Interests: The authors have declared that no competing interests exist.

Background: Disseminated histoplasmosis remains a major killer of immunocompromised patients in Latin America. Cytological and histological methods are usually present in most hospitals and may represent a precious diagnostic method. We report 15 years of experience of the department of pathology of the Centre Hospitalier de Cayenne Andrée Rosemon in French Guiana., Methods: Specimens from live patients from January 2005 to June 2020 with the presence of H. capsulatum on cytological and/or histological analysis were analyzed. All specimens were examined by an experienced pathologist. The analysis was descriptive., Results: Two hundred two cytological and histological samples were diagnosed with histoplasmosis between January 2005 and June 2020. The 202 samples included 153 (75.7%) histopathological formalin-fixed and paraffin-embedded tissues (biopsy or surgical specimens) and 49 (24.3%) cytological analysis from all organs. One hundred thirty-four patients (82.7%) were HIV-positive, 15 patients (9.3%) had immunosuppressant treatment, and 13 patients (8%) were immunocompetent. Seventy-eight of 202 (38.5%) were samples from the digestive tract, mostly the colon (53/78 cases, 70%) and small intestine (14/78 cases, 18%). Microorganisms were more numerous in digestive samples (notably the colon) than in other organs. Lymphocyte and histiocyte inflammation of moderate to marked intensity were observed in all positive specimens. Tuberculoid epithelioid granuloma were present in 16/78 (20,5%) specimens including 14 colon and 2 small intestine specimens. There were 11/202 cases of liver histoplasmosis, 26/202 (12,8%) cases of pulmonary histoplasmosis. Bone marrow involvement was diagnosed in 14 (2%) specimens (8 aspiration and 6 biopsies). Lymph nodes were positive in 42 specimens (31 histology and 11 cytology). Histopathological analysis of the 31 lymph nodes showed a variable histological appearance. Tuberculoid forms were most frequent (24/31, 77,4%)., Conclusions: From the pathologist perspective, this is the largest series to date showing that digestive involvement was the most frequent, usually with a tuberculoid form and a greater load of Histoplasma . With awareness and expertise, cytology and pathology are widely available methods that can give life-saving results in a short time to help orient clinicians facing a potentially fatal infection requiring prompt treatment., (Copyright © 2020 Drak Alsibai, Couppié, Blanchet, Adenis, Epelboin, Blaizot, Louvel, Djossou, Demar and Nacher.)

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., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Haemophagocytic Lymphohistiocytosis (HLH), during HIV infection is a rare complication with a poor prognosis. There are few data on HLH within the Amazon region. The objective was to describe epidemiological, clinical and therapeutic features of HIV-related HLH in French Guiana. Methods: A retrospective analysis of adult HIV patients at Cayenne hospital with HLH between 2012 and 2015. A diagnosis of HLH was given if the patient presented at least 3 of 8 criteria of the HLH-2004 classification. Results: Fourteen cases of HLH were tallied during the study period. The mean age was 46 years with a sex ratio of 1.8. The most frequent etiology of HLH was an associated infection (12/14). Confirmed disseminated histoplasmosis, was found in 10 of 14 cases, and it was suspected in 2 other cases. The CD4 count was below 200/mm 3 in 13/14 cases. An HIV viral load >100,000 copies/ml was observed in 13/14 cases. An early treatment with liposomal amphotericin B was initiated in 12/14 cases. The outcome was favorable in 12/14 of all cases and in 10/12 cases involving histoplasmosis. Case fatality was 2/14 among all cases (14.3%) et 1/10 among confirmed disseminated histoplasmosis with HLH (10%). During the study period 1 in 5 cases of known HIV-associated disseminated histoplasmosis in French Guiana was HLH. Conclusion: Histoplasmosis was the most frequent etiology associated with HLH in HIV-infected patients in French Guiana. The prognosis of HLH remains severe. However, a probabilistic empirical first line treatment with liposomal amphotericin B seemed to have a favorable impact on patient survival., (Copyright © 2020 Nguyen, Nacher, Epelboin, Melzani, Demar, Blanchet, Blaizot, Drak Alsibai, Abboud, Djossou, Couppié and Adenis.)

Introduction: In the past decade, new diagnostic methods and strategies have appeared, HIV testing efforts and the generalization of antiretroviral therapy may have influenced the number of opportunistic diagnoses and mortality of HIV-infected patients. To test this hypothesis we compiled data on the top opportunistic infections and causes of early death in the HIV cohort of French Guiana., Methods: HIV-infected persons followed in Cayenne, Kourou, and Saint Laurent du Maroni hospitals from 2010 to 2019 were studied. Annual incidence of different opportunistic infections and annual deaths are compiled. For patients with opportunistic infections we calculated the proportion of early deaths., Results: At the time of analysis, among 2 459 patients, (treated and untreated) 90% had a viral load <400 copies, 91% of the patients in the cohort were on antiretroviral treatment, and 94.2% of patients on treatment for over 6 months had undetectable viral loads. Only 9% of patients had CD4 counts under 200 per mm3. Histoplasmosis clearly remained the most frequent (128 cases) opportunistic infection among HIV-infected persons followed by cerebral toxoplasmosis (63 cases) and esophageal candidiasis (41 cases). Cryptococcal meningitis was ranked 5th most frequent opportunistic infection as was tuberculosis (31 cases). The trend for a sharp decline in early deaths continued (3.9% of patients)., Conclusions: Despite the successes of antiretrovirals, patients presenting with advanced HIV are still common and they are still at risk of dying. Improved diagnosis, and notably systematic screening with appropriate tools are still important areas of potential progress., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: The authors have declared that no competing interests exist.

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., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: 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., Objective: 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., Methods: 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., Results: 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., Conclusions: Antigen detection tests are promising tools to improve detection of and ultimately reduce the burden of histoplasmosis mortality in patients with advanced HIV disease., Competing Interests: The authors have declared that no competing interests exist.

In South America, disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum (H. capsulatum), is a severe and frequent opportunistic infection in AIDS patients. In areas outside the USA where specific-Histoplasma antigen detection is not available, the diagnosis is difficult. With the galactomannan antigen (GM) detection, a test commonly used for invasive aspergillosis diagnosis, there is a cross-reactivity with H. capsulatum that can be helpful for the diagnosis of histoplasmosis. The aim of this study was to evaluate the GM detection for the diagnosis of disseminated histoplasmosis in AIDS patients. The performance of the GM detection was evaluated with serum collected in French Guiana where H. capsulatum is highly endemic. Sera from AIDS patients with disseminated histoplasmosis occurring from 2002 to 2009 and from control HIV-positive patients without histoplasmosis were tested with the GM detection and Histoplasma-specific antibody detection (IEP). In 39 AIDS patients with proven disseminated histoplasmosis, the sensitivity of the Histoplasma IEP was only 35.9% and was linked to the TCD4+ lymphocyte level. For the GM detection, the sensitivity (Se) was 76.9% and specificity (Sp) was 100% with the recommended threshold for aspergillosis diagnosis (0.5). The test was more efficient with a threshold of 0.4 (Se: 0.82 [95% CI: 0.66-0.92], Sp: 1.00 [95% CI: 0.86-1.00], LR+: >10, LR-: 0.18). This study confirms that the GM detection can be a surrogate marker for the diagnosis of disseminated histoplasmosis in AIDS patients in endemic areas where Histoplasma EIA is not available., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Background: Histoplasmosis is an endemic fungal infection in French Guiana. It is the most common AIDS-defining illness and the leading cause of AIDS-related deaths. Diagnosis is difficult, but in the past 2 decades, it has improved in this French overseas territory which offers an interesting model of Amazonian pathogen ecology. The objectives of the present study were to describe the temporal trends of incidence and mortality indicators for HIV-associated histoplasmosis in French Guiana., Methods: A retrospective study was conducted to describe early mortality rates observed in persons diagnosed with incident cases of HIV-associated Histoplasma capsulatum var. capsulatum histoplasmosis admitted in one of the three main hospitals in French Guiana between 1992 and 2011. Early mortality was defined by death occurring within 30 days after antifungal treatment initiation. Data were collected on standardized case report forms and analysed using standard statistical methods., Results: There were 124 deaths (45.3%) and 46 early deaths (16.8%) among 274 patients. Three time periods of particular interest were identified: 1992-1997, 1998-2004 and 2005-2011. The two main temporal trends were: the proportion of early deaths among annual incident histoplasmosis cases significantly declined four fold (χ2, p<0.0001) and the number of annual incident histoplasmosis cases increased three fold between 1992-1997 and 1998-2004, and subsequently stabilized., Conclusion: From an occasional exotic diagnosis, AIDS-related histoplasmosis became the top AIDS-defining event in French Guiana. This was accompanied by a spectacular decrease of early mortality related to histoplasmosis, consistent with North American reference center mortality rates. The present example testifies that rapid progress could be at reach if awareness increases and leads to clinical and laboratory capacity building in order to diagnose and treat this curable disease.

Human immunodeficiency virus (HIV)-associated disseminated Histoplasma capsulatum capsulatum infection often mimics tuberculosis. This disease is well know in the United States but is dramatically underdiagnosed in Central and South America. In the Amazon region, given the available incidence data and the regional HIV prevalence, it is expected that, every year, 1,500 cases of histoplasmosis affect HIV patients in that region alone. Given the mortality in undiagnosed patients, at least 600 patients would be expected to die from an undiagnosed but treatable disease. The lack of a simple diagnostic tool and the lack of awareness by clinicians spiral in a vicious cycle and made a major problem invisible for 30 years. The HIV/acquired immunodeficiency syndrome community should tackle this problem now to prevent numerous avoidable deaths from HIV-associated histoplasmosis in the region and elsewhere.

Disseminated histoplasmosis is the first AIDS-defining infection in French Guiana. A retrospective cohort study studied predictive factors of disseminated histoplasmosis in HIV-infected patients between 1996 and 2008. Cox proportional hazards models were used. The variables studied were age, sex, last CD4/CD8 count, CD4 nadir, herpes or pneumocystosis, cotrimoxazole and fluconazole use, antiretroviral treatment and the notion of recent initiation of HAART. A total of 1404 patients were followed for 6833 person-years. The variables independently associated with increased incidence of disseminated histoplasmosis were CD4 count<50 per mm3, CD4 count between 50 and 200 per mm3, a CD4 nadir <50 per mm3, CD8 count in the lowest quartile, herpes infection, and recent antiretroviral treatment initiation (less than 6 months). The variables associated with decreased incidence of histoplasmosis were antiretroviral treatment for more than 6 months, fluconazole treatment, and pneumocystosis. There were 13.5% of deaths at 1 month, 17.5% at 3 months, and 22.5% at 6 months after the date of diagnosis of histoplasmosis. The most important predictive factors for death within 6 months of diagnosis were CD4 counts and antiretroviral treatment. The present study did not study environmental/occupational factors but provides predictive factors for disseminated histoplasmosis and its outcome in HIV patients in an Amazonian environment during the HAART era.

Objective: Histoplasma capsulatum var. capsulatum infection is a major AIDS-defining illness in French Guiana. Although it affects South and Central American countries, the number of published cases is low. We present the largest series of AIDS-related histoplasmosis. The aim of this work is to describe clinical features and to help optimize investigations in settings where antigen detection methods are not available., Design: Two hundred cases of AIDS-related histoplasmosis, diagnosed in the hospitals of French Guiana, were included retrospectively between 1982 and 2007., Results: At the time of diagnosis, 92% of patients did not receive highly active antiretroviral therapy. CD4 cell count was less than 100 cells/microl for 80% of them. Most patients had fever, lymphadenopathies, and pulmonary and digestive symptoms. Neurological signs and skin/mucosal locations were less common. Other opportunistic infections were associated in 36.6% of cases (mostly tuberculosis). In most of the patients, lactic dehydrogenase was at least four times the normal value, and there was a moderate increase of aspartate aminotransaminase but not alanine aminotransaminase levels. Bone marrow aspirations were useful, but cultures of liver and lymphadenopathy specimens were the most contributive. Following treatment initiation, 17.5% died within a month. Presumptive treatment was started before diagnostic confirmation in 14.3% of the cases., Conclusion: In high prevalence settings, histoplasmosis often revealed AIDS in severely immunodeficient and poorly followed patients. In the absence of a quick sensitive technique, skin smear and fungal tissue cultures are contributive. Nevertheless, given the diagnostic delays and the poor prognosis, presumptive treatment with amphotericin B-containing regimens should be recommended when clinical and epidemiological contexts are evocative.

(1) Background: Only a few studies on histoplasmosis in immunocompetent patients have been reported in French Guiana. Therefore, we conducted a detailed clinical description of hospitalized patients suffering with histoplasmosis among non-HIV patients. (2) Methods: This is a single-center, retrospective study conducted at Cayenne Hospital Center between 2008 and 2022. (3) Results: Our cohort was composed of 31 (91%) adults (>18 years of age) and 3 (9%) children, with a sex ratio, M:F, of 1:2. The median age was higher among the women than among the men (70 versus 54 years). The collection of respiratory samples constituted the majority of the performed examinations (38%). Fever (>37 °C) was found in 56% of patients. Surprisingly, the histoplasmosis was disseminated in 82% of patients with an overall case fatality rate of 14.7%. However, immunosuppressive conditions were found in 52% (16/31) of the adult patients, including lymphoid hemopathies, diabetes and immunosuppressive drugs. Conclusions: This disease, though rare and usually considered a mostly benign disease in non-HIV patients, presented a relatively high mortality rate in our cohort. Thus, histoplasmosis should be suspected, screened and investigated as a first line of defense in highly endemic areas, even in immunocompetent and non-HIV patients, especially those with fever or chronic respiratory symptoms. [ABSTRACT FROM AUTHOR]

Disseminated histoplasmosis is a major cause of mortality in HIV-infected patients. Rapid and efficient diagnosis of Histoplasma capsulatum is crucial. Cytopathology is available in most hospitals and represents a rapid diagnostic alternative. In this study, we reviewed 12 years of experience to describe the cytology of histoplasmosis diagnosed by bronchoalveolar lavage (BAL) in relation to patient characteristics. BAL-diagnosed pulmonary histoplasmosis concerned 17 patients (14 HIV+). BAL cellularity ranged from 76,000 to 125,000 cells/mL in HIV patients, and 117,000 to 160,000 cells/mL in non-HIV patients. Macrophages predominated in all HIV patients (from 60% to 88%), lymphocytic infiltrates ranged from 5% to 15%, and neutrophils were very heterogeneous (from 2% to 32%). The number of H. capsulatum at hot spots seemed greater in HIV-infected than in immunocompetent patients (9 to 375 vs. 4 to 10) and were inversely proportional to the CD4 counts. Yeasts were both intracellular and extracellular in 85.7% of the HIV patients. This is the most comprehensive series detailing the cytological aspects of BAL in the diagnosis of H. capsulatum, focusing on the number of yeasts and their clustering pattern. The cytological examination of the Gomori-Grocott-stained BAL allows a reliable diagnosis of histoplasmosis. [ABSTRACT FROM AUTHOR]

Although the burden of histoplasmosis in patients with advanced HIV has been the focus of detailed estimations, knowledge about invasive fungal infections in patients living with HIV in an Amazonian context is somewhat scattered. Our goal was thus to adopt a broader view integrating all invasive fungal infections diagnosed over a decade in French Guiana. All patients hospitalized at Cayenne hospital from 1 January 2009 to 31 December 2018 with a proven diagnosis of invasive fungal infection were included (n = 227). Histoplasmosis was the most common (48.2%), followed by Cryptococcus infection (26.3%), and pneumocystosis (12.5%). For cryptococcal infection, there was a discordance between the actual diagnosis of cryptococcal meningitis n = (26) and the isolated presence of antigen in the serum (n = 46). Among the latter when the information was available (n = 34), 21(65.6%) were treated with antifungals but not coded as cryptococcocosis. Most fungal infections were simultaneous to the discovery of HIV (38%) and were the AIDS-defining event (66%). The proportion of major invasive fungal infections appeared to remain stable over the course of the study, with a clear predominance of documented H. capsulatum infections. Until now, the focus of attention has been histoplasmosis, but such attention should not overshadow other less-studied invasive fungal infections. [ABSTRACT FROM AUTHOR]

Identifying prognostic factors is important in order to guide the choice of first-line therapy for disseminated histoplasmosis. Our objective was to identify factors associated with death among a cohort of 330 patients compiled over 34 years of clinical practice in French Guiana. Survival analysis was performed with death as the failure event and date of symptom onset as the origin event. Incidence rates were and Cox proportional hazards models were computed. Overall, 330 HIV-infected patients with disseminated histoplasmosis were included in the analysis, with 126 deaths occurring. One-quarter of all patients died within 6 months of the first symptoms. Patients with dyspnea, renal failure, arterial blood pressure <90 mmHG, and a WHO performance score >2 had a greater incidence of death. Bivariate analyses showed that patients with increased LDH, low hemoglobin, low serum protein, low CD4 counts, and low platelets tended to have a greater incidence of death. After adjusting for potential confounders, patients with dyspnea, a WHO performance score >2, serum protein <60 g/L, and hemoglobin <8.9 g/dL had an increased risk of dying. The interaction terms showed that patients treated with liposomal amphotericin B had a marked reduction in death among patients with renal failure; among renal failure patients, the elevation of LDH was associated with a significant risk of death. [ABSTRACT FROM AUTHOR]

We aimed to describe the ways patients with disseminated histoplasmosis—a multifaceted and often lethal disease—present themselves and are explored. A retrospective, observational, multicentric study spanned the period between 1 January 1981 and 1 October 2014. Principal component analysis was performed for the sampling sites and for the clinical signs and symptoms. The factor loadings of the principal components were selected for eigenvalues > 1. The most frequent signs and symptoms were an alteration of the WHO general performance status, fever, digestive tract, respiratory signs and symptoms and lymphadenopathies. The most common sites sampled were bone marrow, respiratory tract, blood, lymph node and liver biopsies, with significant variations in the number of sites from which samples were taken to try to identify the pathogen. The principal component analysis clinical signs and symptoms leading to the diagnosis showed four main lines of variation. The factor loadings of the four main components were compatible with four broad types of clinical presentations and four types of exploration strategies. Extracting simple algorithms was difficult, emphasizing the importance of clinical expertise when diagnosis depends on obtaining a sample where Histoplasma can be seen or grown. Histoplasma antigen detection tests will help simplifying the algorithms. [ABSTRACT FROM AUTHOR]

Disseminated histoplasmosis is the main AIDS-defining infection of French Guiana. We aim to describe our therapeutic experience for 349 patients with disseminated histoplasmosis between 1 January 1981 and 10 January 2014 in French Guiana. Survival, delays for treatment initiation, duration of induction therapy, and associated initial treatments are described. The death rate was 14.9 per 100 person-years, with an early drop in survival. Among those who died, >1/3 died within a year of HIV diagnosis, and ¾ of all patients with histoplasmosis had been diagnosed for HIV within a year. As induction treatment, 29% received liposomal amphotericin B, 12.9% received deoxycholate amphotericin B, 54% received itraconazole alone, and 21.8% received liposomal amphotericin B and itraconazole. The median delay between symptoms-onset and hospitalization was 19.5 days (IQR = 5–105). Liposomal amphotericin B or itraconazole was initiated shortly after admission. Treatment initiation was often presumptive for liposomal amphotericin B (27%) and itraconazole (20%). The median duration of liposomal amphotericin B treatment was 7 days (IQR = 5–11 days). The present study shows that ¾ of the patients were profoundly immunocompromised and had been diagnosed for HIV within the past year. Antifungal treatment was often initiated presumptively on admission. Over time there was a significant gradual decline in early death. [ABSTRACT FROM AUTHOR]

Introduction: Histoplasmosis is the main opportunistic infection and cause of death in HIV-infected persons living with HIV in French Guiana and probably in most of Latin America. The objective of the present study was to compare cutaneomucous histoplasmosis to non-cutaneomucous histoplasmosis in French Guiana. Methods: Between 1981 and 2014 AIDS-related disseminated histoplasmosis patients followed in the three hospitals of French Guiana were retrospectively studied. Only proven incident cases of histoplasmosis, either by pathology and/or mycological analysis, were considered. Mucocutaneous histoplasmosis was ascertained by a positive mucosal or cutaneous biopsy. Results: Thirty-one patients had mucocutaneous lesions, and 318 had no mucocutaneous lesions. Patients with cutaneomucous lesions were more likely to have had prior opportunistic infections (35.5%) than those who did not have cutaneomucous lesions (19.5%). They were more likely to be very severely immunocompromised (CD4 count < 50) (90.3% versus 62.8%) and less likely to have digestive signs (32.3% versus 74.1%) and superficial adenopathies (29% versus 50.2%) than those without cutaneomucous lesions. In terms of simple biological examinations, patients with cutaneomucous lesions had fewer signs of cholestasis. The diagnosis was significantly more likely to be performed by direct examination and pathology in those with cutaneomucous lesions than in those without such lesions. On the contrary, patients with cutaneomucous lesions were less likely to be diagnosed by fungal culture than those without cutaneomucous lesions. There was a greater but non-significant risk of early death in those with cutaneomucous lesions relative to those without (OR = 2.28 (95%CI = 0.83–5.7), p = 0.056. Conclusions: Mucocutaneous forms were associated with more profound immunosuppression and perhaps risk of early death. They are easily accessible for diagnosis. [ABSTRACT FROM AUTHOR]

Histoplasmosis is a common but neglected AIDS-defining condition in endemic areas for Histoplasma capsulatum. At the advanced stage of HIV infection, the broad spectrum of clinical features may mimic other frequent opportunistic infections such as tuberculosis and makes it difficult for clinicians to diagnose histoplasmosis in a timely manner. Diagnosis of histoplasmosis is difficult and relies on a high index of clinical suspicion along with access to medical mycology facilities with the capacity to implement conventional diagnostic methods (direct examination and culture) in a biosafety level 3 laboratory as well as indirect diagnostic methods (molecular biology, antibody, and antigen detection tools in tissue and body fluids). Time to initiation of effective antifungals has an impact on the patient's prognosis. The initiation of empirical antifungal treatment should be considered in endemic areas for Histoplasma capsulatum and HIV. Here, we report on 30 years of experience in managing HIV-associated histoplasmosis based on a synthesis of clinical findings in French Guiana with considerations regarding the difficulties in determining its differential diagnosis with other opportunistic infections. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Disseminated histoplasmosis is a common differential diagnosis of tuberculosis in disease-endemic areas. We aimed to find a predictive score to orient clinicians towards disseminated histoplasmosis or tuberculosis when facing a non-specific infectious syndrome in patients with advanced HIV disease. We reanalyzed data from a retrospective study in Cayenne Hospital between January 1997–December 2008 comparing disseminated histoplasmosis and tuberculosis: 100 confirmed disseminated histoplasmosis cases and 88 confirmed tuberculosis cases were included. A simple logit regression model was constructed to predict whether a case was tuberculosis or disseminated histoplasmosis. From this model, a score may be obtained, where the natural logarithm of the probability of disseminated histoplasmosis/tuberculosis = +3.917962 × WHO performance score (1 if >2, 0 if ≤2) −1.624642 × Pulmonary presentation (1 yes, 0 no) +2.245819 × Adenopathies > 2 cm (1 yes, 0 no) −0.015898 × CD4 count − 0.001851 × ASAT − 0.000871 × Neutrophil count − 0.000018 × Platelet count + 6.053793. The area under the curve was 98.55%. The sensitivity of the model to distinguish between disseminated histoplasmosis and tuberculosis was 95% (95% CI = 88.7–98.3%), and the specificity was 93% (95% CI = 85.7.3–97.4%). In conclusion, we here present a clinical-biological predictive score, using simple variables available on admission, that seemed to perform very well to discriminate disseminated histoplasmosis from tuberculosis in French Guiana in well characterized patients. [ABSTRACT FROM AUTHOR]

Histoplasmosis and tuberculosis are common AIDS-defining illnesses in the Amazon region. While tuberculosis is well-known and included in public health programs, disseminated histoplasmosis is often neglected in South and Central America. Both diseases can be fatal if left untreated, and diagnosis can be slow. In French Guiana, where HIV is a major public health problem, clinicians often need to consider both diseases when treating severely immunocompromised patients. Longitudinal data from the French Hospital Database on HIV infection in French Guiana showed that histoplasmosis had a higher incidence than tuberculosis, and histoplasmosis-related deaths were more common. Therefore, clinicians may be better off starting treatment with amphotericin B for patients with CD4 counts below 200 and a tuberculosis-like syndrome. [Extracted from the article]