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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. [ABSTRACT FROM AUTHOR]

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. Author summary: 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. 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. Hence, 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. [ABSTRACT FROM AUTHOR]

Objective: Despite scaling-up testing and antiretroviral treatment in Latin America, advanced HIV remains a significant public health problem. The objective of the present study was look for historical risk factors for death in French Guiana's HIV cohort taking into account the immunological status, the main opportunistic infections, and their treatment. A retrospective cohort study was conducted on data collected between 1992 and 2008 to identify factors associated with death in a cohort 2323 patients. Results: There were 370 deaths for a total 9608 patient-years. Being on tuberculosis treatment was associated with a greater hazard of death. The diagnosis of confirmed tuberculosis, of histoplasmosis, of toxoplasmosis, and pneumocystosis were independently associated with death. Interactions terms between cotrimoxazole treatment and pneumocystosis, or between confirmed tuberculosis and tuberculosis treatment showed a protective treatment-effect. All patients having received anti-tuberculosis treatment (n = 347) did not have a final diagnosis of tuberculosis (n = 93). For histoplasmosis, 199 patients received antifungal treatment while 141 were diagnosed as having histoplasmosis. The number of patients on anti-tuberculosis drugs was far greater that the number of patients with confirmed tuberculosis, and these patients on treatment without confirmed tuberculosis had a twofold greater risk of dying. [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]

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