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Among 1107 cryptococcosis cases from the French surveillance network (2005–2020), the proportion of HIV-seronegative individuals has recently surpassed that of HIV-seropositive individuals. We observed marked differences in patient characteristics, disease presentations, cryptococcal antigen results, infecting species, and mortality according to HIV serostatus. [ABSTRACT FROM AUTHOR]

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. [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]

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. [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]

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]

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/mm3 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. [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 was first described in Panama in 1906 in a patient presenting miliary tuberculosis-like symptoms. Hence, in Panama, 7.6% of patients had culture-proven histoplasmosis [[9]]; in Venezuela, histoplasmosis was documented in 43 of 200 (21.3%) [[10]]; in Fortaleza, Brazil, of 378 consecutive hospitalized HIV patients, 164 (43.4%) had disseminated histoplasmosis [[11]]; A recent screening study in hospitalized HIV patients in Brazil found high I Histoplasma i antigen prevalence, ranging from 8.8% in Porto Alegre to 44.8% in Natal. [[18]] However, these data originate from histoplasmosis-aware centers, and in most hospitals across Latin America, histoplasmosis is not diagnosed and not treated, often being mistaken for tuberculosis, thereby leading to unnecessary deaths and inflated tuberculosis statistics. [Extracted from the article]

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. [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]

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. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

• Histoplasmosis case fatality score (HFS) predicts mortality at 30 days of treatment. • HFS is the first HIV-associated histoplasmosis prognostic score. • The criteria are performance and mental status, dyspnea, C-reactive protein, cytopenia, and chest X-ray. • An HFS <5 is associated with 30-day mortality <5% and >33% when HFS ≥5. • HFS may help clinicians optimize antifungal induction and reduce early mortality. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]