Histoplasmosis in non-immunosuppressed patients from an endemic area in Northeastern Brazil.

Differently from immunocompromised patients, very little information is available in the literature regarding the clinical presentation, epidemiology, and outcomes of histoplasmosis in non-immunosuppressed individuals living in endemic areas. This retrospective case series study was carried out by reviewing the medical records of non-immunocompromised patients with histoplasmosis, residents in a hyperendemic area in northeastern Brazil, between 2011 and 2022. Thirty HIV-negative patients were identified with histoplasmosis, and 19 cases met the inclusion criteria: three had acute, five subacute and one chronic pulmonary forms; two with mediastinal picture and eight had disseminated disease (two with severe symptoms). The median age of our sample was 32.7 years old [interquartile range: 24-45]. Most of the patients were male (male-to-female ratio = 15:4) and resided in the state capital (n = 9). The majority had a previous history of exposure to well-known risk factors for Histoplasma infection. Pulmonary nodules were observed in all subacute form, two patients (acute and subacute forms) were initially treated empirically for pulmonary tuberculosis; one death was registered in the subacute form. The chronic pulmonary form of histoplasmosis was diagnosed in one patient only after the symptoms persisted despite specific treatment. The primary clinical manifestations of the moderate form of DH were enlarged lymph nodes, with histopathology being the main diagnostic method. The cases were detected as isolated occurrences and not as an outbreak, suggesting that exposure to Histoplasma can be more widespread than presumed. Despite the self-limiting nature of the disease, death can occur even in previously heathy patients.

This study aimed to describe the presentation of histoplasmosis outside the context of immunosuppression, including the diagnostic methods, epidemiology, and main radiological and clinical features. A better understanding of the various forms of this disease will help improve case management.

Cryptococcal meningoencephalitis: Risk factors associated to death in a hospital in Northeastern Brazil.

INTRODUCTION: Cryptococcosis is an opportunistic systemic mycosis caused by pathogenic encapsulated yeasts of the genus Cryptococcus. The objective of the present study was to evaluate the risk factors associated with death of patients diagnosed with meningitis due to Cryptococcus spp. METHODS: This retrospective cohort study included patients admitted to the São José Hospital (SJH) with Cryptococcal Meningoencephalitis (CM) who were diagnosed between 2010 and 2018. Data collection was carried out by reviewing the patients' medical records. Death during hospitalization was considered the primary outcome. RESULTS: From 2010 to 2018, 21,519 patients were admitted to the HSJ, 124 of whom were hospitalized due to CM. The CM incidence rate was 5.8 cases/103 hospitalizations. We included 112 patients in the study. Male patients were the most affected (82.1%), and the median age was 37 years [IQR: 29-45]. HIV coinfection occurred in 79.4% of the patients. Fever (65.2%) and headache (88.4%) were the most frequent symptoms. Greater cellularity in the CSF was the most related factor to CM in non-HIV individuals (p < 0.05). Death during hospitalization occurred in 28.6% (n = 32) of the patients. The independent risk factors associated with death during the hospitalization were women (p = 0.009), age > 35 years (p = 0.046), focal neurological deficits (p = 0.013), altered mental status (p = 0.018) and HIV infection (p = 0.040). The twelve-month survival was lower in HIV-positive patients (p < 0.05). CONCLUSION: Early diagnosis, optimal treatment, and clinical follow-up strategies, especially in HIV patients, should be prioritized.

Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial.

BACKGROUND: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. METHODS: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. RESULTS: A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82). CONCLUSIONS: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.

Impact of a computer system as a triage tool in the management of pulmonary tuberculosis in a HIV reference center in Brazil.

BACKGROUND: The Neural Clinical Score for tuberculosis (NCS-TB) is a computer system developed to improve the triage of presumed pulmonary TB (pPTB). METHODS: A study was performed with cohorts of pPTB patients cared for at a reference hospital in Northeast Brazil. RESULTS: The NCS-TB sensitivity was 76.5% for TB diagnosis, which shortened the time from triage to smear microscopy results (3.3 to 2.5 days; p<0.001) and therapy initiation (6.7 to 4.1 days; p=0.045). CONCLUSIONS: Although the NCS-TB was not suitable as a screening tool, it was able to optimize laboratory diagnosis and shorten the time to treatment initiation.

Progressive disseminated histoplasmosis in HIV-positive patients.

BACKGROUND: Histoplasmosis is the most common endemic mycosis among people living with advanced HIV infection. PURPOSE: Describe general aspects and challenges of this disease and its association with HIV. RESEARCH DESIGN: Review of literature. STUDY SAMPLE: Articles found using different combinations of terms including "disseminated histoplasmosis" and AIDS/HIV or immunosuppression in PubMed, Scopus, WHO Global health library, and Scielo database. ANALYSIS: We look for information on epidemiology, pathogenesis, diagnosis, and treatment of histoplasmosis in AIDS patients. RESULTS: Histoplasmosis is caused by Histoplasma capsulatum, a dimorphic fungus encountered throughout the world, mainly in soil enriched with bat and bird excreta. Progressive disseminated histoplasmosis is the main presentation of this mycosis in people living with advanced HIV and is fatal if left untreated. Symptoms include a systemic disease characterized by fever, weight loss, night sweats, skin manifestations, hepatomegaly, splenomegaly, and septic shock. Diagnostic tests include culture, visualization of H. capsulatum by direct and histopathological examination, serology, antigen, molecular, and skin testing. Patients with disseminated disease require aggressive and prolonged treatment to eradicate the pathogen and include amphotericin B and itraconazole. In many low income countries of endemic regions, histoplasmosis in HIV-positive patients is often undiagnosed or misdiagnosed as another opportunistic infection, due to the similarity in clinical manifestations and to the paucity of better diagnostic tests. CONCLUSION: Histoplasmosis remains a neglected disease. Few studies about the disease and expensive treatments make it difficult to reduce the morbidity and mortality of this condition. Public health services and physicians must be aware of histoplasmosis' burden among the HIV-positive population.

Impact of a computer system as a triage tool in the management of pulmonary tuberculosis in a HIV reference center in Brazil

ABSTRACT Background: The Neural Clinical Score for tuberculosis (NCS-TB) is a computer system developed to improve the triage of presumed pulmonary TB (pPTB). Methods: A study was performed with cohorts of pPTB patients cared for at a reference hospital in Northeast Brazil. Results: The NCS-TB sensitivity was 76.5% for TB diagnosis, which shortened the time from triage to smear microscopy results (3.3 to 2.5 days; p<0.001) and therapy initiation (6.7 to 4.1 days; p=0.045). Conclusions: Although the NCS-TB was not suitable as a screening tool, it was able to optimize laboratory diagnosis and shorten the time to treatment initiation.

Prevalence and associated factors of tuberculosis treatment abandonment. / Prevalência e fatores associados ao abandono do tratamento da tuberculose.

OBJECTIVE: To estimate the prevalence of tuberculosis treatment abandonment and its associated factors. METHOD: Cross-sectional study which used cases of tuberculosis in the System of Information on Notification Aggravations (Sistema de Informação de Agravos de Notificação) from 2001 to 2017 in Ceará state. This study included 74,006 cases and the outcome was the closing situation "treatment abandonment". A multivariate analysis was performed to estimate the association between the variables with abandonment. RESULTS: Throughout the period, the abandonment rate was 12.54%. A higher abandonment prevalence was verified among people who live in the urban zone (PR = 2.45; 95%CI: 2.20-2.74), who are readmitted after abandonment (PR = 2.84; 95%CI: 2.68-3.01), among those notified as recurrent (PR = 1.22; 95%CI: 1.10-1.35) and among drinkers (PR = 1.50; 95%CI: 1.42-1.58). Those who were sputum smear-positive (PR = 1.11; 95%CI: 1.03-1.19) or for whom sputum smear was unperformed (PR = 1.30; 95%CI: 1.20-1.40), coinfection (PR = 2.04; CI95%: 1.89-2.21) and who were not submitted to serology (PR = 1.62; 95%CI: 1.53-1.71) have also a higher prevalence of tuberculosis treatment abandonment. CONCLUSION: Tuberculosis treatment abandonment is associated to biological and social factors, habits, and health service structure.

Prevalência e fatores associados ao abandono do tratamento da tuberculose / Prevalencia y factores asociados al abandono del tratamiento de la tuberculosis / Prevalence and associated factors of tuberculosis treatment abandonment

RESUMO Objetivo Estimar a prevalência de abandono do tratamento da tuberculose e seus fatores associados. Método Estudo transversal que utilizou os casos de tuberculose do Sistema de Informação de Agravos de Notificação entre 2001 e 2017 no Ceará. Fizeram parte desse estudo 74.006 casos e o desfecho foi a situação de encerramento "abandono do tratamento". Foi realizada análise multivariada para estimar associação entre as variáveis com o abandono. Resultados Durante todo o período, a taxa de abandono foi de 12,54%. Verificou-se maior prevalência de abandono entre as pessoas que residem na zona urbana (RP = 2,45; IC95%: 2,20-2,74), que dão entrada como reingresso pós-abandono (RP = 2,84; IC95%: 2,68-3,01), entre aqueles notificados como recidiva (RP = 1,22; IC95%: 1,10-1,35) e entre os etilistas (RP = 1,50; IC95%: 1,42-1,58). Aqueles que apresentaram baciloscopia de escarro positiva (RP = 1,11; IC95%: 1,03-1,19) ou não realizada (RP = 1,30; IC95%: 1,20-1,40), coinfecção (RP = 2,04; IC95%: 1,89-2,21) e que não realizaram sorologia (RP = 1,62; IC95%: 1,53-1,71) também possuem maior prevalência de abandono do tratamento para tuberculose. Conclusão O abandono do tratamento da tuberculose está associado a fatores biológicos, sociais, hábitos e à estrutura dos serviços de saúde.

RESUMEN Objetivo Estimar la prevalencia del abandono del tratamiento de la tuberculosis y sus factores asociados. Método Estudio transversal que utilizó los casos de tuberculosis del Sistema de Información de Agravios de Notificación entre 2001 y 2017 en Ceará, Brasil. Un total de 74.006 casos fueron incluidos en este estudio y el resultado fue la conclusión "abandono del tratamiento". Se realizó un análisis multivariante para estimar la asociación entre las variables con el abandono. Resultados Durante todo el periodo, la tasa de abandono fue del 12,54%. Se encontró una mayor prevalencia de abandono entre las personas que viven en zonas urbanas (RP = 2,45; IC95%: 2,20-2,74), los que ingresan como reingreso tras el abandono (RP = 2,84; IC95%: 2,68-3,01), los que se declararon reincidentes (RP = 1,22; IC95%: 1,10-1,35) y los alcohólicos (RP = 1,50; IC95%: 1,42-1,58). Los que tenían una baciloscopia de esputo positiva (RP = 1,11; IC95%: 1,03-1,19) o para los cuales no se realizó baciloscopia de esputo (RP = 1,30; IC95%: 1,20-1,40), coinfección (RP = 2,04; IC95%: 1,89-2,21) y que no se sometieron a serología (RP = 1,62; IC95%: 1,53-1,71) también presentaron una mayor prevalencia de abandono del tratamiento de la tuberculosis. Conclusión El abandono del tratamiento de la tuberculosis está asociado a factores biológicos y sociales, a los hábitos y a la estructura de los servicios sanitarios.

ABSTRACT Objective To estimate the prevalence of tuberculosis treatment abandonment and its associated factors. Method Cross-sectional study which used cases of tuberculosis in the System of Information on Notification Aggravations (Sistema de Informação de Agravos de Notificação) from 2001 to 2017 in Ceará state. This study included 74,006 cases and the outcome was the closing situation "treatment abandonment". A multivariate analysis was performed to estimate the association between the variables with abandonment. Results Throughout the period, the abandonment rate was 12.54%. A higher abandonment prevalence was verified among people who live in the urban zone (PR = 2.45; 95%CI: 2.20-2.74), who are readmitted after abandonment (PR = 2.84; 95%CI: 2.68-3.01), among those notified as recurrent (PR = 1.22; 95%CI: 1.10-1.35) and among drinkers (PR = 1.50; 95%CI: 1.42-1.58). Those who were sputum smear-positive (PR = 1.11; 95%CI: 1.03-1.19) or for whom sputum smear was unperformed (PR = 1.30; 95%CI: 1.20-1.40), coinfection (PR = 2.04; CI95%: 1.89-2.21) and who were not submitted to serology (PR = 1.62; 95%CI: 1.53-1.71) have also a higher prevalence of tuberculosis treatment abandonment. Conclusion Tuberculosis treatment abandonment is associated to biological and social factors, habits, and health service structure.

Trends and patterns of mortality arising from fungal infections in Brazil in a period of 11 years / Tendências e padrões de mortalidade em decorrência de infecções fúngicas no Brasil, em um período de 11 anos

Objective: To investigate the mortality attributed to fungal infections, in Brazil between 2003 and 2013. Methods: This ecological study relied on official data collected from the Sistema de Informação Sobre Mortalidade ­ Mortality Information System database. The mycoses were identified by the 10th revision of the International Classification of Diseases, which included categories B35­B49 in its first chapter. Results: Overall, 11,991,935 deaths were reported in the aforementioned period. The deaths of 4,192 individuals were primarily attributed to mycoses. High annual mortality rates were observed in all Brazilian regions, except in the Northeast. The main recorded mycoses were paracoccidioidomycosis (35.6%) and cryptococcosis (24.1%). There was a downward trend in the number of deaths due to paracoccidioidomycosis. In addition, 10,925 death certificates listed mycoses as an associated cause of death. Cryptococcosis (89.7%) and histoplasmosis (89.4%) were the most common mycoses associated with deaths in HIV patients. Conclusions: There was a downward trend in the number of deaths stemming from invasive fungal infections. However, opportunistic mycoses follow been a significant cause of death, especially in HIV patients.

Objetivo: Investigar a mortalidade atribuída para as infecções fúngicas, no Brasil, entre 2003 e 2013. Métodos: Trata-se de um estudo ecológico, em que os dados foram obtidos do Sistema de Informação sobre Mortalidade (SIM), disponíveis na plataforma do DATASUS. As micoses foram identificadas por meio da 10ª revisão da Classificação Internacional de Doenças (CID-10), a qual incluiu as categorias B35-B49 no primeiro capítulo da CID-10. Resultados: No total, 11.991.935 óbitos foram notificados no período do estudo. Os óbitos de 4,192 indivíduos foram atribuídos às micoses. Foram observadas elevadas taxas de mortalidade em todas as regiões brasileiras, com exceção do Nordeste. As principais micoses registradas foram paracoccidioidomicose (35,6%) e criptococose (24,1%). Houve uma tendência na redução do número de óbitos em relação à paracoccidioidomicose. Além disso, em 10.925 declarações de óbitos informavam que as micoses foram causas associadas ao óbito. Criptococose (89,7%) e Histoplasmose (89,4%) foram as micoses mais comumente associadas ao óbito, principalmente em pacientes HIV positivos. Conclusões: Houve uma tendencia na diminuição dos óbitos por infecções fúngicas invasivas. Entretanto, micoses oportunistas continuam sendo importantes causas de morte, especialmente em indivíduos HIV positivos.

Prevalência de tuberculose drogarresistente e fatores associados / Prevalence of drug-resistant tuberculosis and associated factors

RESUMO Objetivo estimar a prevalência de tuberculose drogarresistente e os fatores a ela associados. Métodos estudo retrospectivo que avaliou 74.006 casos de tuberculose registrados no Sistema de Informação de Agravos de Notificação. Na análise multivariada, utilizou-se da variável desfecho "resistência medicamentosa" para estimar a razão de prevalência dos fatores associados à drogarresistência. Resultados estimou-se taxa de 0,5% de drogarresistência (n=388). Observou-se maior prevalência nos casos classificados como recidiva, reingresso pós-abandono e transferência. Houve aumento de 53,0% quando a baciloscopia de escarro foi positiva e de 6,5 vezes para cultura de escarro positiva. Efeito contrário foi observado mediante a não realização do exame diagnóstico para vírus da imunodeficiência humana. Conclusão estimou-se baixa prevalência de tuberculose drogarresistente comparada a cenários internacionais. Os principais fatores associados à doença estiveram ligados aos retratamentos e ao resultado positivo da baciloscopia e cultura de escarro.

ABSTRACT Objective to estimate the prevalence of drug-resistant tuberculosis and associated factors. Methods a retrospective study that evaluated 74,006 cases of tuberculosis registered in the Notifiable Diseases Information System. In the multivariate analysis, the outcome variable "drug resistance" was used to estimate the prevalence ratio of factors associated with drug resistance. Results a rate of 0.5% of drug resistance was estimated (n=388). A higher prevalence was observed in cases classified as relapse, post-dropout re-entry, and transfer. There was a 53.0% increase when sputum smear microscopy was positive and a 6.5 increase for positive sputum culture. The opposite effect was observed when the diagnostic test for human immunodeficiency virus was not performed. Conclusion a low prevalence of drug-resistant tuberculosis was estimated compared to international scenarios. The main factors associated with the disease were related to retreatments and positive sputum smear and culture results.

Postpartum histoplasmosis in an HIV-negative woman: a case report and phylogenetic characterization by internal transcribed spacer region analysis.

The present report describes the first case of postpartum disseminated histoplasmosis in a 24-year-old HIV-negative woman. On the tenth day after vaginal delivery, the patient presented with dyspnea, fever, hypotension, tachycardia, and painful hepatomegaly. Yeast-like Histoplasma capsulatum features were isolated in the buffy coat. The phylogenetic analysis demonstrated that the fungal isolate was similar to other H. capsulatum isolates identified in HIV patients from Ceará and Latin America. Thus, histoplasmosis development in individuals with transitory immunosuppression or during the period of immunological recovery should be carefully examined.

Postpartum histoplasmosis in an HIV-negative woman: a case report and phylogenetic characterization by internal transcribed spacer region analysis

Abstract The present report describes the first case of postpartum disseminated histoplasmosis in a 24-year-old HIV-negative woman. On the tenth day after vaginal delivery, the patient presented with dyspnea, fever, hypotension, tachycardia, and painful hepatomegaly. Yeast-like Histoplasma capsulatum features were isolated in the buffy coat. The phylogenetic analysis demonstrated that the fungal isolate was similar to other H. capsulatum isolates identified in HIV patients from Ceará and Latin America. Thus, histoplasmosis development in individuals with transitory immunosuppression or during the period of immunological recovery should be carefully examined.

An autochthonous case of paracoccidioidomycosis in a new area of Ceara State, Northeastern Brazil.

The largest endemic areas of paracoccidioidomycosis (PCM) in Brazil comprise the humid agricultural regions of the Southeast, South, and, recently, the Midwest and North regions. The Ceara State, located in the Brazilian Northeast region, presents semi-arid climate in most of its territory, characterized by high temperatures, scarce vegetation and low humidity. The objective of the present study was to describe a new autochthonous case of paracoccidioidomycosis from a distinct area of Ceara and review the characteristics of PCM occurrence in Northeastern Brazil. The patient was a 65-year-old male farmer who denied traveling outside the Ceara State or living in other locations. He was born and lived in the rural area known as Camara, bordering the municipalities of Itapaje and Itapipoca. Camara is one of the highest areas (around 720 m of altitude) of the Uruburetama mountains that exhibits tropical forests and is located in Northern Ceara, distant 139 km from the capital, Fortaleza. The patient sought for care, complaining of an oral lesion that appeared over the past three years. The hard palate lesion biopsy revealed multinucleated cells with cytoplasmic inclusions, compatible with PCM. After culture, P. brasiliensis was identified by polymerase chain reaction. Serological testing for PCM was reagent. The patient was treated with itraconazole for approximately 17 months, persisting free of symptoms after 15 months of follow-up. Regarding this new autochthonous case in the Ceara State, PCM should be considered in the differential diagnosis of patients with suggestive clinical manifestations, proceeding from the mountainous areas of Ceara.

Novel clinical and dual infection by Histoplasma capsulatum genotypes in HIV patients from Northeastern, Brazil.

Histoplasmosis is a worldwide-distributed deep mycosis that affects healthy and immunocompromised hosts. Severe and disseminated disease is especially common in HIV-infected patients. At least 11 phylogenetic species are recognized and the majority of diversity is found in Latin America. The northeastern region of Brazil has one of the highest HIV/AIDS prevalence in Latin America and Ceará State has one of the highest death rates due to histoplasmosis in the world, where the mortality rate varies between 33-42%. The phylogenetic distribution and population genetic structure of 51 clinical isolates from Northeast Brazil was studied. For that morphological characteristics, exoantigens profile, and fungal mating types were evaluated. The genotypes were deduced by a MSLT in order to define local population structure of this fungal pathogen. In addition, the relationships of H. capsulatum genotypes with clinically relevant phenotypes and clinical aspects were investigated. The results suggest two cryptic species, herein named population Northeast BR1 and population Northeast BR2. These populations are recombining, exhibit a high level of haplotype diversity, and contain different ratios of mating types MAT1-1 and MAT1-2. However, differences in phenotypes or clinical aspects were not observed within these new cryptic species. A HIV patient can be co-infected by two or more genotypes from Northeast BR1 and/or Northeast BR2, which may have significant impact on disease progression due to the impaired immune response. We hypothesize that co-infections could be the result of multiple exposure events and may indicate higher risk of disseminated histoplasmosis, especially in HIV infected patients.

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 in Medellin; 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.

Accuracy of Buffy Coat in the Diagnosis of Disseminated Histoplasmosis in AIDS-Patients in an Endemic Area of Brazil.

The buffy coat is obtained routinely for disseminated histoplamosis (DH) diagnosis in Ceará, Brazil. The aim of this study is to describe the accuracy of staining smears for Histoplasma in the buffy coat of AIDS-patients with DH. From 2012-2013, all results of stained buffy coat smears and culture for fungi performed at São José Hospital were recorded. In total, 489 buffy coats of 361 patients were studied; 19/361 (5.3%; 95%CI = 2.9-7.6%) had positive direct examination stained smears for Histoplasma and 61/361 (16.9%; 95%CI = 13.0-20.8%) had growth in culture. For those with positive Histoplasma cultures, the CD4 count was significantly lower (139.3 vs. 191.7cells/µL; p = 0.014) than others, and death was 18%. The sensitivity and specificity of stained smears was 25.9% and 100%, respectively. A second test, performed up to 36 days from the first one, increased the sensitivity of stained smears to 32.2%. Stained smears of buffy coat have low accuracy; nonetheless, they are easy to perform and can give a quick diagnosis in low-resource endemic areas. Despite the decrease in mortality, it is not yet to the low levels observed in areas that have better and more efficient methods.

Histoplasmosis, An Underdiagnosed Disease Affecting People Living With HIV/AIDS in Brazil: Results of a Multicenter Prospective Cohort Study Using Both Classical Mycology Tests and Histoplasma Urine Antigen Detection.

BACKGROUND: Histoplasmosis is highly endemic in the American continent. This condition is associated with a high mortality, particularly in people living with HIV/AIDS (PLWHA). Diagnosis of histoplasmosis is usually late in South America, as Histoplasma antigen detection is rarely available. Here we determined the prevalence, risk factors, and outcome of histoplasmosis in PLWHA in Brazilian hospitals. METHODS: This was a prospective cohort study (2016-2018) involving 14 tertiary medical centers in Brazil. We included hospitalized PLWHA presenting with fever and additional clinical findings. Patients were investigated at each participant center with classical mycology methods. Also, Histoplasma antigen detection was performed in urine samples (IMMY). Probable/proven histoplasmosis was defined according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group/National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria. RESULTS: From 616 eligible patients, 570 were included. Histoplasmosis was identified in 21.6% (123/570) of patients. Urine antigen testing increased the diagnostic yield in 53.8%, in comparison with standard mycology methods. Variables independently associated with histoplasmosis were CD4+ count <50 cells/mm3, use of an antiretroviral (protective effect), and sample collection in the Northeast region of Brazil. Dyspnea at presentation was independently associated with death. Histoplasmosis was more frequent than tuberculosis in patients with low CD4+ counts. Overall 30-day mortality was 22.1%, decreasing to 14.3% in patients with antigen-based diagnosis. CONCLUSIONS: Histoplasmosis is a very frequent condition affecting PLWHA in Brazil, particularly when CD4+ counts are lower than 50 cells/mm3. Antigen detection may detect earlier disease, with a probable impact on outcomes. Access to this diagnostic tool is needed to improve clinical management of PLWHA in endemic countries.