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Objectives: Histoplasmosis is a systemic mycosis, present globally. We aimed to describe cases of histoplasmosis (Hc) and to establish a risk profile associated with Hc in HIV-infected patients (HIV+). Methods: This was a retrospective study of patients with a clinical laboratory diagnosis of Hc. Data were fed into REDCap, and statistical analysis was performed with R. Results: We included 99 records, 65 HIV+ and 34 HIV-. Average age was 39 years. Median time from onset to diagnosis was 8 weeks in HIV- and 22 weeks in HIV+. Disseminated histoplasmosis occurred in 79.4% of HIV+, vs. 36.4% of HIV- patients. Median CD4 count was 70. Co-infection with tuberculosis was present in 20% of HIV+ patients. Blood cultures were positive in 32.3% of HIV+ vs. 11.8% of HIV- (p = 0.025) patients; bone marrow culture was positive in 36.9% vs. 8.8% (p = 0.003). Most HIV+ patients (71.4%) were hospitalized. On univariate analysis, anemia, leukopenia, intensive care, use of vasopressors and mechanical ventilation were associated with death in HIV+ patients. Conclusions: Most of our patients with histoplasmosis were HIV+, presenting advanced AIDS. Diagnosis was late in HIV+ patients, and they frequently presented disseminated Hc, required hospitalization, and died. Early screening for Hc in HIV+ and drug-induced immunosuppressed patients is crucial.
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Wild animals infected with Paracoccidioides brasiliensis represent important indicators of this fungal agent presence in the environment. The detection of this pathogen in road-killed wild animals has shown to be a key strategy for eco-epidemiological surveillance of paracoccidioidomycosis (PCM), helping to map hot spots for human infection. Molecular detection of P. brasiliensis in wild animals from PCM outbreak areas has not been performed so far. The authors investigated the presence of P. brasiliensis through nested-PCR in tissue samples obtained from road-killed animals collected nearby a human PCM outbreak spot, Rio de Janeiro state, Brazil and border areas. Eighteen species of mammals were analyzed: Dasypus novemcinctus (nine-banded armadillo, n = 6), Cerdocyon thous (crab-eating fox, n = 4), Coendou spinosus (hairy dwarf porcupine, n = 2), Lontra longicaudis (Neotropical river otter, n = 1), Procyon cancrivorus (crab-eating raccoon, n = 1), Galactis cuja (lesser grison, n = 1), Tamandua tetradactyla (collared anteater, n = 1), Cuniculus paca (paca, n = 1), and Bradypus variegatus (brown-throated three-toed sloth, n = 1). Specific P. brasiliensis sequences were detected in the liver, spleen, and lymph node samples from 4/6 (66.7%) D. novemcinctus, reinforcing the importance of these animals on Paracoccidioides ecology. Moreover, lymph nodes samples from two C. thous, as well as lung samples from the C. paca were also positive. A literature review of Paracoccidioides spp. in vertebrates in Brazil indicates C. thous and C. paca as new hosts for the fungal pathogen P. brasiliensis.
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Canidae/microbiologia , Cuniculidae/microbiologia , Mamíferos/microbiologia , Paracoccidioides/isolamento & purificação , Animais , Animais Selvagens/microbiologia , Brasil , DNA Fúngico/química , DNA Fúngico/metabolismo , Feminino , Fígado/microbiologia , Linfonodos/microbiologia , Masculino , Paracoccidioides/genética , Análise de Sequência de DNA , Baço/microbiologiaRESUMO
BACKGROUND: Pulmonary mycoses resemble clinically and radiologically chronic pulmonary tuberculosis. Studies describing the prevalence, etiology and clinical features of pulmonary mycosis are of crucial importance in the Brazilian Amazon. AIMS: To estimate the frequency of pulmonary mycoses in smear-negative tuberculosis patients; to describe their demographic, epidemiological, and clinical characteristics; and to evaluate diagnostic methods. METHODS: A cross-sectional study was conducted at two tuberculosis reference institutions in Amazonas, Brazil. We included 213 patients and collected clinical data, blood and induced sputum to perform serological, direct microscopy, microbiologic culture and PCR-based assays to identify infections caused by Aspergillus fumigatus, Paracoccidioides brasiliensis, Histoplasma capsulatum, Cryptococcus, and HIV. Chest computed tomography was also performed. RESULTS: Pulmonary mycoses were diagnosed in 7% (15/213) of the cases, comprising ten aspergillosis cases, three cases of paracoccidioidomycosis and one case each of histoplasmosis and cryptococcosis. Among the patients with pulmonary mycoses, 86.7% were former tuberculosis patients. The most significant clinical characteristics associated with pulmonary mycoses were cavity-shaped lung injuries, prolonged chronic cough and hemoptysis. CONCLUSIONS: Our study confirmed the high prevalence of pulmonary mycoses in smear-negative tuberculosis patients in the Brazilian Amazon.
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Micoses , Tuberculose , Brasil/epidemiologia , Estudos Transversais , Humanos , PrevalênciaRESUMO
Cryptococcosis is a life-threatening fungal infection caused by the Cryptococcus neoformans/Cryptococcus gattii species complex. Most cases are recorded in patients suffering from HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome). However, this infection also occurs in non-HIV patients with a proportion of 10-30% of all cases. The study aimed at the clinical and molecular characterization of non-HIV patients diagnosed with cryptococcosis at the Tropical Medicine Foundation (FMT-HVD) from July 2016 to June 2019. Medical records of respective patients were analyzed to describe the course of cryptococcosis in non-HIV patients. In addition, multi-locus sequence typing (MLST) was applied to identify the sequence types of the isolated Cryptococcus strains, to perform phylogenetic analysis, and to evaluate the isolates' genetic relationship to global reference strains. Antifungal susceptibility profiles to amphotericin B, fluconazole, and itraconazole were assessed by broth microdilution. From a total of 7 patients, 4 were female, the age range varied between 10 and 53 years (median of 36.3 years). Cryptococcal meningitis was the common clinical manifestation (100%). The period between onset of symptoms and confirmed diagnosis ranged from 15 to 730 days (mean value of 172.9 days), and the observed mortality was 57.1%. Of note, comorbidities of the assessed cryptococcosis patients comprised hypertension, diabetes mellitus, and intestinal tuberculosis. Genotyping applying PCR-RFLP of the URA5 gene identified all clinical isolates as C. gattii genotype VGII. Using MLST, it was possible to discriminate the sequence types ST20 (n = 4), ST5 (n = 3), and the newly identified sequence type ST560 (n = 1). The antifungals amphotericin B, fluconazole, and itraconazole showed satisfactory inhibitory activity (microdilution test) against all C. gattii VGII strains.
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Cryptococcus gattii/genética , Cryptococcus neoformans/genética , Meningite Criptocócica/epidemiologia , Adolescente , Adulto , Antifúngicos/farmacologia , Brasil/epidemiologia , Criança , Cryptococcus gattii/classificação , Cryptococcus gattii/efeitos dos fármacos , Cryptococcus gattii/patogenicidade , Cryptococcus neoformans/classificação , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/patogenicidade , Feminino , Geografia , Infecções por HIV , Humanos , Masculino , Meningite Criptocócica/microbiologia , Meningite Criptocócica/mortalidade , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Técnicas de Tipagem Micológica , Filogenia , Estudos Prospectivos , Adulto JovemRESUMO
Objetivos: Investigar o surto de histoplasmose em bombeiros no Distrito federal/DF, ocorrido em junho de 2017. Métodos: Realizou-se um estudo de coorte por meio das entrevistas realizadas com os bombeiros mediante um questionário semiestruturado. Considerou-se infectado o bombeiro que apresentou tomografia de tórax sugestiva de histoplasmose ou reagente nos testes de imunodifusão e/ou Western blot. Coletou-se amostra ambiental e realizou-se Nested PCR específico para Histoplasma capsulatum. Resultados: Entre 35 bombeiros, 94,3% eram homens; com a mediana de idade de 37 (24-45) anos, 28 foram classificados como infectados. A média de permanência dentro da caverna foi 25 minutos. O fator de risco associado à infecção foi o ato de entrar na caverna (RR=3,86; RA=71,6; p<0,02). Entre 14 amostras ambientais, 50% foram positivas para H. capsulatum. Conclusão: Confirmou-se o surto de histoplasmose de bombeiros em Brazlândia-DF, e foram tomadas ações como a interdição da caverna e o tratamento dos bombeiros.
Objectives: To nvestigate the outbreak of histoplasmosis in firefighters in Federal District/DF, which occurred in June 2017. Methods: A cohort study was conducted through interviews with firefighters by means of a semi-structured questionnaire. Firefighters who presented chest tomography suggestive of histoplasmosis or reacted to immunodiffusion and/or Western blot tests were considered infected. Environmental samples were collected and Nested PCR specific for Histoplasma capsulatum was performed. Results: Among 35 firefighters, 94.3% were men; with a median age of 37 (24-45) years, 28 were classified as infected. The average length of stay inside the cave was 25 minutes. The risk factor associated with infection was the act of entering the cave (RR = 3.86, RA = 71.6, p <0.02). Among 14 environmental samples, 50% were positive for H. capsulatum. Conclusion: The outbreak of histoplasmosis in firefighters in Brazlândia-DF was confirmed, and actions were taken such as banning the cave and treating the firefighters
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Histoplasma , Histoplasmose , Surtos de Doenças , Fatores de Risco , Estudos de Coortes , BombeirosRESUMO
Paracoccidioides spp. isolation from environmental samples is rare and hardly reproducible. Molecular techniques have facilitated the fungal detection. However, it can be still difficult. Some strategies to enhance the capacity of DNA detection have been adopted, including the analysis of soil samples belonging to the habitat of animals from which Paracoccidioides spp. have already been isolated, notably armadillo burrows. To date, the detection of Paracoccidioides spp. has not yet been reported from outbreak hotspots. Clusters and outbreaks of acute paracoccidioidomycosis (PCM), usually a more severe clinical form, have currently occurred in urban areas being associated to climate changes, deforestation, and great constructions. These occurrences potentially signalise the fungus' environmental niche, a riddle not yet solved. The authors performed an environmental investigation in a deeply disturbed area, after a highway construction in Rio de Janeiro, Brazil, where a recent outbreak of acute PCM occurred. Specific DNA sequences of Paracoccidioides brasiliensis were detected in shallow soil samples around the highway, reinforcing the association between the road construction and this PCM outbreak.
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Tatus , DNA Fúngico/genética , Paracoccidioides/isolamento & purificação , Paracoccidioidomicose/microbiologia , Animais , Sequência de Bases , Brasil , Ecossistema , Paracoccidioides/genética , Paracoccidioides/crescimento & desenvolvimento , Análise de Sequência de DNA , Microbiologia do SoloRESUMO
Cryptococcosis, a potentially fatal mycosis in humans, is acquired via exposure to exogenous environmental sources. This study aimed to investigate the frequency, genetic diversity, and virulence of cryptococcal strains isolated from indoor dust in the Rio Negro micro-region of the Brazilian Amazon. A total of 8.9% of the studied houses were positive, recovering nine Cryptococcus neoformans VNI and 16 C. gattii VGII isolates, revealing an endemic pattern in domestic microenvironments. The International Society for Human and Animal Mycology (ISHAM) consensus multilocus sequence typing (MLST) scheme for the C. neoformans/C. gattii species complexes identified two sequence types (STs), ST93 and ST5, amongst C. neoformans isolates and six STs amongst C. gattii isolates, including the Vancouver Island Outbreak ST7 (VGIIa) and ST20 (VGIIb), the Australian ST5, and ST264, ST268 and ST445, being unique to the studied region. Virulence studies in the Galleria mellonella model showed that five C. gattii strains and one C. neoformans strain showed a similar pathogenic potential to the highly virulent Vancouver Island outbreak strain CDR265 (VGIIa). The findings of this study indicate that humans can be exposed to the agents of cryptococcosis via house dust, forming the basis for future studies to analyze the impact of early and continuous exposure to indoor dust on the development of subclinical or clinical infections.
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Cryptococcal meningitis is a several disease common in late stage of HIV infection. Detection of cryptococcal antigen (CrAg) is an important for early diagnosis of this invasive mycosis. The pre-emptive treatment for isolated antigenemia prevents the onset of meningoencephalitis. Screening CrAg in patients with low CD4 count is cost-effective in countries with prevalence of antigenemia above 3%. However, in Brazil, the number of prevalence studies on cryptococcosis and HIV is insufficient. The objective of this study is to estimate the prevalence of CrAg and describe clinical characteristics from a cohort of patients followed at a reference center in Brazil. CrAg screening was performed in 89 inpatients with CD4 count ≤200 cells/mm3 or WHO stage III/IV from the National Institute of Infecttious Disease, Rio de Janeiro. Patients with isolated antigenemia received pre-emptive therapy with fluconazole and patients with meningoencephalitis were treated with Amphotericin B. Individuals were followed up for 12 months. Prevalence of serum CrAg was 11.23%, cryptococcal meningoencephalitis 6.74% and isolated antigenemia 4.81%. None of the patients with isolated antigenemia developed meningoencephalitis during the follow up. Signs and symptoms of meningoencephalitis were unspecific or absent. Our study suggests the need of CrAg screening in Brazil and highlights that lumbar puncture is mandatory in all individuals CrAg positive to exclude asymptomatic meningoencephalitis.
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Criptococose/complicações , Infecções por HIV/complicações , Adulto , Antígenos de Fungos/sangue , Brasil/epidemiologia , Criptococose/epidemiologia , Criptococose/imunologia , Criptococose/mortalidade , Cryptococcus/imunologia , Feminino , Seguimentos , Humanos , Masculino , Meningite Criptocócica/líquido cefalorraquidiano , Meningite Criptocócica/complicações , Meningite Criptocócica/epidemiologia , Meningite Criptocócica/imunologia , Pessoa de Meia-Idade , Prevalência , Tuberculose/complicações , Tuberculose/mortalidadeRESUMO
Histoplasmosis is considered the most common invasive opportunistic fungal disease in the Americas, with outbreaks and micro-epidemics reported for over 80 years. In Brazil, this disease has been described since 1946, reaching a remarkable incidence in the population, especially during the HIV-AIDS pandemic. In this study, published and unpublished outbreaks and micro-epidemics of histoplasmosis in Brazil were revisited by accessing different database sources and evaluating epidemiological and clinical features. We have found reports spanning 1946-2017, across 10 Brazilian states and with involvement of 370 humans and 2 dogs, and 13 disseminated cases and 3 deaths were reported. Rio de Janeiro had the largest number of outbreaks (n = 20/40; 50%) reported in this study. The majority of outbreaks and micro-epidemics was reported in caves (n = 21/40; 52.5%), followed by reports in abandoned/deactivated sites (n = 6/40; 15%), mines (n = 5/40; 12.5%), chicken coops (n = 4/40; 10%). Histoplasmosis is a serious health issue in Brazil considering the attractive and growing market of ecotourism throughout more than 7000 caves, and all levels of poultry farming activity are important to raise awareness about how dangerous this neglected disease can be and establish ways to decrease exposure to contaminated environmental sources through adequate preventive measures.