High prevalence and mortality due to Histoplasma capsulatum in the Brazilian Amazon: An autopsy study.

BACKGROUND: Histoplasmosis is acquired by inhalation of spores of the dimorphic fungus Histoplasma spp. Although this pathogen is distributed worldwide, it is more prevalent in the Americas. However, the real burden of histoplasmosis remains undefined in many endemic regions. METHODOLOGY: We conducted a series of 61 autopsies to individuals who died in a hospital in the Brazilian Amazon focused on infectious diseases. We performed a detailed histological and microbiological evaluation with genetic characterization of Histoplasma strains with the aim to evaluate the contribution of histoplasmosis to morbidity and mortality. Additionally, we assessed the clinicopathological correlation. PRINCIPAL FINDINGS: Evidence of Histoplasma infection was detected in 21 patients (34%). Eight cases were disseminated infections, all of them occurred in HIV-positive patients. Six cases were localized histoplasmosis, limited to the lungs. In seven patients Histoplasma DNA was detected by PCR in patients with no histological lesions. Histoplasma infection was detected in 38% of HIV-positive patients and was a major contributor to death in 22% of them. Lungs, liver and spleen were affected in all cases of disseminated histoplasmosis. Phylogenetic analysis of the strains suggested a high diversity of Histoplasma species circulating in the Brazilian Amazon. Histoplasmosis was clinically missed in 75% of the disseminated infections. CONCLUSIONS: The high incidence of histoplasmosis, the low index of clinical suspicion, and the severity of the disseminated disease highlight the need of proactively implementing sensitive routine screening methods for this pathogen in endemic areas. Antifungal prophylaxis against Histoplasma should be encouraged in the severely immunocompromised HIV patients in these areas. In conclusion, substantial mortality is associated with disseminated histoplasmosis among HIV-positive patients in the Brazilian Amazon.

HIV patients dying on anti-tuberculosis treatment: are undiagnosed infections still a problem in French Guiana?

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.

Treating progressive disseminated histoplasmosis in people living with HIV.

BACKGROUND: Progressive disseminated histoplasmosis (PDH) is a serious fungal infection that affects people living with HIV. The best way to treat the condition is unclear. OBJECTIVES: We assessed evidence in three areas of equipoise. 1. Induction. To compare efficacy and safety of initial therapy with liposomal amphotericin B versus initial therapy with alternative antifungals. 2. Maintenance. To compare efficacy and safety of maintenance therapy with 12 months of oral antifungal treatment with shorter durations of maintenance therapy. 3. Antiretroviral therapy (ART). To compare the outcomes of early initiation versus delayed initiation of ART. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane CENTRAL; MEDLINE (PubMed); Embase (Ovid); Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and BIOSIS Previews (all three in the Web of Science); the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the ISRCTN registry, all up to 20 March 2020. SELECTION CRITERIA: We evaluated studies assessing the use of liposomal amphotericin B and alternative antifungals for induction therapy; studies assessing the duration of antifungals for maintenance therapy; and studies assessing the timing of ART. We included randomized controlled trials (RCT), single-arm trials, prospective cohort studies, and single-arm cohort studies. DATA COLLECTION AND ANALYSIS: Two review authors assessed eligibility and risk of bias, extracted data, and assessed certainty of evidence. We used the Cochrane 'Risk of bias' tool to assess risk of bias in randomized studies, and ROBINS-I tool to assess risk of bias in non-randomized studies. We summarized dichotomous outcomes using risk ratios (RRs), with 95% confidence intervals (CI). MAIN RESULTS: We identified 17 individual studies. We judged eight studies to be at critical risk of bias, and removed these from the analysis. 1. Induction We found one RCT which compared liposomal amphotericin B to deoxycholate amphotericin B. Compared to deoxycholate amphotericin B, liposomal amphotericin B may have higher clinical success rates (RR 1.46, 95% CI 1.01 to 2.11; 1 study, 80 participants; low-certainty evidence). Compared to deoxycholate amphotericin B, liposomal amphotericin B has lower rates of nephrotoxicity (RR 0.25, 95% CI 0.09 to 0.67; 1 study, 77 participants; high-certainty evidence). We found very low-certainty evidence to inform comparisons between amphotericin B formulations and azoles for induction therapy. 2. Maintenance We found no eligible study that compared less than 12 months of oral antifungal treatment to 12 months or greater for maintenance therapy. For both induction and maintenance, fluconazole performed poorly in comparison to other azoles. 3. ART We found one study, in which one out of seven participants in the 'early' arm and none of the three participants in the 'late' arm died. AUTHORS' CONCLUSIONS: Liposomal amphotericin B appears to be a better choice compared to deoxycholate amphotericin B for treating PDH in people with HIV; and fluconazole performed poorly compared to other azoles. Other treatment choices for induction, maintenance, and when to start ART have no evidence, or very low certainty evidence. PDH needs prospective comparative trials to help inform clinical decisions.

Histoplasmosis en Argentina: serie de casos en niños / Histoplasmosis in Argentina: case series in children

ANTECEDENTES: La histoplasmosis es una micosis sistémica endémica en América con pocos casos reportados en pediatría. OBJETIVOS: Describir la epidemiología, formas clínicas y evolución de la histoplasmosis en niños de un hospital pediátrico en Argentina. MÉTODOS: El estudio, retrospectivo y descriptivo, se llevó a cabo entre enero de 2008 y diciembre de 2016 en el Hospital de Pediatría «Prof. Dr. Juan Pedro Garrahan», e incluyó pacientes menores de 18 años con cuadro clínico, serología, cultivos y/o hallazgos histológicos compatibles con histoplasmosis. Se estudiaron 13 pacientes (siete niños y seis niñas, con una mediana de edad de 9 años y rango intercuartílico de 3,4 a 13 años), de los cuales tres niños (23%) provenían de la provincia de Buenos Aires, tres de la provincia de Santa Fe (23%) y siete (54%) de otras provincias. RESULTADOS: Diez pacientes (77%) presentaron la forma diseminada de la enfermedad y tres (23%) la forma pulmonar (23%); ocho niños (62%) tenían otras comorbilidades. La serología fue positiva en siete casos (54%), los cultivos fueron positivos en nueve pacientes (69%) y en diez casos (77%) se identificaron hallazgos histológicos compatibles con histoplasmosis. Todos los pacientes recibieron anfotericina B (liposomal en siete casos y desoxicolato en seis). Diez pacientes (77%) continuaron el tratamiento con itraconazol y tres pacientes (23%) fallecieron por causas no relacionadas con la histoplasmosis. CONCLUSIONES: En la serie analizada predominaron los pacientes con histoplasmosis diseminada asociada a otra enfermedad. La mortalidad no estuvo directamente relacionada con la infección

BACKGROUND: Histoplasmosis is a fungal disease, endemic in South America, and seldom reported in paediatrics. AIMS: To report the epidemiology, clinical features and outcome of children diagnosed with histoplasmosis in an Argentinian Children's Hospital. METHODS: A retrospective and descriptive study was performed from January 2008 to December 2016 in Hospital de Pediatría 'Prof. Dr. Juan Pedro Garrahan'. Patients under 18 years with clinical features, serological tests, cultures and/or histological findings compatible with histoplasmosis were included. Thirteen patients were selected (seven male and six female; mean age was 9 years with interquartile range 3.4-13); three children (23%) were from Buenos Aires province, three (23%) from Santa Fe province, and seven (54%) from other provinces. RESULTS: In ten cases (77%) the clinical form was disseminated, and it was pulmonary in three (23%). Eight cases (62%) suffered other comorbidities. Serological tests were positive in seven patients (54%), with positive cultures obtained in nine patients (69%). Histological findings compatible with histoplasmosis were found in 10 cases (77%). All patients received treatment with amphotericin B (liposomal formulation in seven cases, deoxycholate in six), with 10 patients continuing with oral itraconazole. Three patients (23%) died from causes unrelated to histoplasmosis. CONCLUSIONS: The majority of children in the series had comorbidities and disseminated histoplasmosis. Mortality was not directly associated with histoplasmosis

Catheter based treatments for fibrosing mediastinitis.

Fibrosing mediastinitis is a rare, often debilitating and potentially lethal disease characterized by an exuberant fibroinflammatory response within the mediastinum. Patients typically present with insidious symptoms related to compression of adjacent structures including the esophagus, heart, airways, and cardiac vessels. Fibrosing mediastinitis is most often triggered by Histoplasmosis infection; however, antifungal and anti-inflammatory therapies are largely ineffective. While structural interventions aimed at alleviating obstruction can provide significant palliation, surgical interventions are challenging with high mortality and clinical experience with percutaneous interventions is limited. Here, we will review the presentation, natural history, and treatment of fibrosing mediastinitis, placing particular emphasis on catheter-based therapies.

Role of western blot assay for the diagnosis of histoplasmosis in AIDS patients from a National Institute of Infectious Diseases in Rio de Janeiro, Brazil.

BACKGROUND: Histoplasmosis is a frequent fungal infection in HIV/AIDS patients, with high morbimortality rates when diagnosis and treatment are delayed. Antibody detection, which is faster than the gold standard culture test, hastens the laboratory investigation. OBJECTIVES: To evaluate the role of WB for antibody detection in the diagnosis of histoplasmosis among HIV/AIDS patients. PATIENTS AND METHODS: Fifty patients with proven or probable histoplasmosis were included. Clinical, epidemiological and laboratory data were described in the same population after a review of their medical records. WB was performed using deglycosylated histoplasmin. RESULTS: About 82% of patients were adult males and the mean age was 39.3 years. CD4+ T lymphocyte count less than 150 cells/mm3 was observed in 62% patients. Antibodies against Histoplasma capsulatum M antigen were detected in 62% of patients, and against both M and H antigens in 28% of individuals. Sera from 10% of patients were nonreactive. Histoplasmosis was the first opportunistic infection in 38% of the cases. Disseminated and pulmonary histoplasmosis occurred in 84% and 16% of patients, respectively. The overall mortality was 16%. CONCLUSION: WB could be useful for the histoplasmosis diagnosis in HIV/AIDS patients because of its easefulness and good sensitivity in a population where antibody production is hampered.

Acute kidney injury and other factors associated with mortality in hiv-infected patients.

OBJECTIVE: HIV-related mortality is still high, especially in developed countries. The aim of this study is to investigate factors associated to death in HIV-infected patients. METHODS: This is a cross-sectional study with all HIV adult patients admitted to a tertiary infectious diseases hospital in Fortaleza, Northeast Brazil, from January 2013 to December 2014. Patients were divided into two groups: survivors and non-survivors. Demo-graphical, clinical and laboratory data were compared and a logistic regression was performed in order to investigate risk factors for death. P values ≤0.05 were considered statistically significant. RESULTS: A total of 200 patients with mean age of 39 years were including in the study, 69.5% males. Fifteen patients (7.5%) died. Non-survivors presented a higher percentage of males (93.3 vs. 67.3%, p = 0.037). Non-survivors presented AKI (73.3 vs. 10.3%, p < 0.001), liver dysfunction (33.3 vs. 11.5, p = 0.031), dyspnea (73.3 vs. 33.0%, p = 0.002) and disorientation (33.3 vs. 12.4%, p = 0.025) more frequently. Non-survivors also had higher levels of urea (73.8 ± 52.7vs. 36.1 ± 29.1 mg/dL, p < 0.001), creatinine (1.98 ± 1.65 vs. 1.05 ± 1.07 mg/dL, p < 0.001), aspartate aminotransferase (130.8 vs. 84.8 U/L, p = 0.03), alanine aminotransferase (115.6 vs. 85.4 U/L, p = 0.045) and lactate dehydrogenase (LDH) (1208 vs. 608 U/L, p = 0.012), as well as lower levels of bicarbonate (18.0 ± 4.7 vs. 21.6 ± 4.6 mEq/L, p = 0.016) and PCO2 (27.8 ± 7.7 vs. 33.0 ± 9.3 mmHg, p = 0.05). In multivariate analysis, disorientation (p = 0.035, OR = 5.523, 95%CI = 1.130 - 26.998), dyspnoea (p = 0.046, OR = 4.064, 95%CI = 1.028 - 16.073), AKI (p < 0.001, OR = 18.045, 95%CI = 4.308 - 75.596) and disseminated histoplasmosis (p = 0.016, OR = 12.696, 95%CI = 1.618 - 99.646) and LDH > 1000 U/L (p = 0.038, OR = 4.854, 95%CI = 1.093 - 21.739) were risk factors for death.]CONCLUSION: AKI and disseminated histoplasmosis (DH) were the main risk factors for death in the studied population. Neurologic and respiratory impairment as well as higher levels of LDH also increased mortality in HIV-infected patients.

Acute kidney injury and other factors associated with mortality in hiv-infected patients

SUMMARY OBJECTIVE: HIV-related mortality is still high, especially in developed countries. The aim of this study is to investigate factors associated to death in HIV-infected patients. METHODS: This is a cross-sectional study with all HIV adult patients admitted to a tertiary infectious diseases hospital in Fortaleza, Northeast Brazil, from January 2013 to December 2014. Patients were divided into two groups: survivors and non-survivors. Demo-graphical, clinical and laboratory data were compared and a logistic regression was performed in order to investigate risk factors for death. P values ≤0.05 were considered statistically significant. RESULTS: A total of 200 patients with mean age of 39 years were including in the study, 69.5% males. Fifteen patients (7.5%) died. Non-survivors presented a higher percentage of males (93.3 vs. 67.3%, p = 0.037). Non-survivors presented AKI (73.3 vs. 10.3%, p < 0.001), liver dysfunction (33.3 vs. 11.5, p = 0.031), dyspnea (73.3 vs. 33.0%, p = 0.002) and disorientation (33.3 vs. 12.4%, p = 0.025) more frequently. Non-survivors also had higher levels of urea (73.8 ± 52.7vs. 36.1 ± 29.1 mg/dL, p < 0.001), creatinine (1.98 ± 1.65 vs. 1.05 ± 1.07 mg/dL, p < 0.001), aspartate aminotransferase (130.8 vs. 84.8 U/L, p = 0.03), alanine aminotransferase (115.6 vs. 85.4 U/L, p = 0.045) and lactate dehydrogenase (LDH) (1208 vs. 608 U/L, p = 0.012), as well as lower levels of bicarbonate (18.0 ± 4.7 vs. 21.6 ± 4.6 mEq/L, p = 0.016) and PCO2 (27.8 ± 7.7 vs. 33.0 ± 9.3 mmHg, p = 0.05). In multivariate analysis, disorientation (p = 0.035, OR = 5.523, 95%CI = 1.130 - 26.998), dyspnoea (p = 0.046, OR = 4.064, 95%CI = 1.028 - 16.073), AKI (p < 0.001, OR = 18.045, 95%CI = 4.308 - 75.596) and disseminated histoplasmosis (p = 0.016, OR = 12.696, 95%CI = 1.618 - 99.646) and LDH > 1000 U/L (p = 0.038, OR = 4.854, 95%CI = 1.093 - 21.739) were risk factors for death.]CONCLUSION: AKI and disseminated histoplasmosis (DH) were the main risk factors for death in the studied population. Neurologic and respiratory impairment as well as higher levels of LDH also increased mortality in HIV-infected patients.

RESUMO INTRODUÇÃO: A mortalidade relacionada ao HIV ainda é alta, especialmente nos países em desenvolvimento. O objetivo deste estudo é investigar os fatores associados ao óbito em pacientes com HIV. MÉTODOS: Trata-se de um estudo transversal com todos os pacientes com HIV admitidos consecutivamente em um hospital terciário de doenças infecciosas em Fortaleza, Nordeste do Brasil, entre janeiro de 2013 e dezembro de 2014. Os pacientes foram divididos em dois grupos: sobreviventes e não sobreviventes. Dados demográficos, clínicos e laboratoriais foram comparados e análise de regressão logística foi feita para investigação dos fatores de risco para óbito. RESULTADOS: Um total de 200 pacientes, com média de idade de 39 anos, foi incluído no estudo, sendo 69,5% do sexo masculino. Óbito ocorreu em 15 pacientes (7,5%). Os não sobreviventes apresentaram maior percentual de homens (93,3 vs. 67,3%, p = 0,037) e um menor tempo de internação (8 ± 6 vs. 18 ± 15 dias, p = 0,005). Na análise multivariada, desorientação (p = 0,035, OR = 5,523), dispneia (p = 0,046, OR = 4,064), LRA (p < 0,001, OR = 18,045), histoplasmose disseminada (p = 0,016, OR = 12,696) e desidrogenase lática (LDH) > 1.000 U/L (p = 0,038, OR = 4,854) foram fatores de risco para óbito. CONCLUSÕES: LRA e histoplasmose disseminada foram os principais fatores de risco para óbito na população estudada. Distúrbios neurológicos e respiratórios, bem como níveis elevados de LDH, também estiveram associados com o aumento da mortalidade em pacientes com HIV.

Clinical outcomes and risk factors for death from disseminated histoplasmosis in patients with AIDS who visited a high-complexity hospital in Campo Grande, MS, Brazil.

INTRODUCTION: Disseminated histoplasmosis (DH) is a systemic mycosis caused by Histoplasma capsulatum (H. capsulatum) and is characterized by progressive and fatal evolution in immunocompromised patients. Moreover, it is considered an AIDS-defining disease. METHODS: We performed an observational, analytical, retrospective study to identify the clinical outcomes and risk factors for death from DH in patients with AIDS at an infectious diseases service facility in Brazil between September 2011 and July 2016. Patients with a positive serology for HIV and DH were diagnosed via direct examination and/or positive cultures for H. capsulatum. RESULTS: Twenty-three patients were included in this study. Approximately, 82.6% were men, with a mean age of 41.0±11.5 years, and 52.2% had a concomitant diagnosis of AIDS and DH. The median CD4+ T cell count was 19 cells/mm3, and 56.5% of the patients died. The most frequently observed symptoms were fever, dyspnea, and skin lesions. On the basis of a comparative analysis of those who died and survived, the absence of splenomegaly and hepatomegaly and the presence of H. capsulatum in the peripheral blood were considered as risk factors for death. Those who died had a higher leukocyte count; CRP, urea, and lactate dehydrogenase levels; AST index; and international normalized ratio prothrombin time. The serum total protein and albumin levels of the patients were lower. CONCLUSIONS: The mortality rate for DH is high among severely immunocompromised patients with AIDS. The risk factors for death were those traditionally associated with blood dyscrasia, inflammatory activity, as well as increased renal and nutritional impairment.

Concentration-dependent protein loading of extracellular vesicles released by Histoplasma capsulatum after antibody treatment and its modulatory action upon macrophages.

Diverse pathogenic fungi secrete extracellular vesicles (EV) that contain macromolecules, including virulence factors that can modulate the host immune response. We recently demonstrated that the binding of monoclonal antibodies (mAb) modulates how Histoplasma capsulatum load and releases its extracellular vesicles (EV). In the present paper, we addressed a concentration-dependent impact on the fungus' EV loading and release with different mAb, as well as the pathophysiological role of these EV during the host-pathogen interaction. We found that the mAbs differentially regulate EV content in concentration-dependent and independent manners. Enzymatic assays demonstrated that laccase activity in EV from H. capsulatum opsonized with 6B7 was reduced, but urease activity was not altered. The uptake of H. capsulatum by macrophages pre-treated with EV, presented an antibody concentration-dependent phenotype. The intracellular killing of yeast cells was potently inhibited in macrophages pre-treated with EV from 7B6 (non-protective) mAb-opsonized H. capsulatum and this inhibition was associated with a decrease in the reactive-oxygen species generated by these macrophages. In summary, our findings show that opsonization quantitatively and qualitatively modifies H. capsulatum EV load and secretion leading to distinct effects on the host's immune effector mechanisms, supporting the hypothesis that EV sorting and secretion are dynamic mechanisms for a fine-tuned response by fungal cells.

Clinical outcomes and risk factors for death from disseminated histoplasmosis in patients with AIDS who visited a high-complexity hospital in Campo Grande, MS, Brazil

Abstract INTRODUCTION: Disseminated histoplasmosis (DH) is a systemic mycosis caused by Histoplasma capsulatum (H. capsulatum) and is characterized by progressive and fatal evolution in immunocompromised patients. Moreover, it is considered an AIDS-defining disease. METHODS: We performed an observational, analytical, retrospective study to identify the clinical outcomes and risk factors for death from DH in patients with AIDS at an infectious diseases service facility in Brazil between September 2011 and July 2016. Patients with a positive serology for HIV and DH were diagnosed via direct examination and/or positive cultures for H. capsulatum. RESULTS: Twenty-three patients were included in this study. Approximately, 82.6% were men, with a mean age of 41.0±11.5 years, and 52.2% had a concomitant diagnosis of AIDS and DH. The median CD4+ T cell count was 19 cells/mm3, and 56.5% of the patients died. The most frequently observed symptoms were fever, dyspnea, and skin lesions. On the basis of a comparative analysis of those who died and survived, the absence of splenomegaly and hepatomegaly and the presence of H. capsulatum in the peripheral blood were considered as risk factors for death. Those who died had a higher leukocyte count; CRP, urea, and lactate dehydrogenase levels; AST index; and international normalized ratio prothrombin time. The serum total protein and albumin levels of the patients were lower. CONCLUSIONS: The mortality rate for DH is high among severely immunocompromised patients with AIDS. The risk factors for death were those traditionally associated with blood dyscrasia, inflammatory activity, as well as increased renal and nutritional impairment.

Central nervous system histoplasmosis: Multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment.

Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment.While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.

Multistate Epidemiology of Histoplasmosis, United States, 2011-2014

Histoplasmosis is one of the most common mycoses endemic to the United States, but it was reportable in only 10 states during 2016, when a national case definition was approved. To better characterize the epidemiologic features of histoplasmosis, we analyzed deidentified surveillance data for 2011-2014 from the following 12 states: Alabama, Arkansas, Delaware, Illinois, Indiana, Kentucky, Michigan, Minnesota, Mississippi, Nebraska, Pennsylvania, and Wisconsin. We examined epidemiologic and laboratory features and calculated state-specific annual and county-specific mean annual incidence rates. A total of 3,409 cases were reported. Median patient age was 49 (interquartile range 33-61) years, 2,079 (61%) patients were male, 1,273 (57%) patients were hospitalized, and 76 (7%) patients died. Incidence rates varied markedly between and within states. The high hospitalization rate suggests that histoplasmosis surveillance underestimates the true number of cases. Improved surveillance standardization and surveillance by additional states would provide more comprehensive knowledge of histoplasmosis in the United States.

Candidate prognostic indicators in cats with histoplasmosis treated with antifungal therapy.

Objectives The aim of this study was to retrospectively identify candidate prognostic indicators in cats with histoplasmosis treated with antifungal therapy. Methods Medical records of cats diagnosed with histoplasmosis were reviewed. Candidate prognostic indicators were assessed for an association with survival to hospital discharge and survival to 1 and 6 months after diagnosis. Potential indicators included easily obtained data at the time of the initial hospital visit derived from cat signalment, historical information, physical examination, laboratory data, form of disease and initial treatment. Results Approximately 88% of cats survived to discharge, with 77% and 67% surviving to 1 and 6 months, respectively. Clinical variables significantly associated with death at more than one outcome time point included the presence of dyspnea, adventitial lung sounds, fungemia, neurologic disease, neutropenia, lymphopenia, multiple cytopenias (anemia, neutropenia, thrombocytopenia), hyperbilirubinemia and increased creatinine kinase activity. Cats that did not survive were more likely to have received corticosteroids, oxygen supplementation and required hospitalization. In addition, cats that did not survive required significantly longer hospitalization. There was no significant difference between initial antifungal drug and survival. Conclusions and relevance Potential prognostic indicators were associated with more severe respiratory, hepatic, hematologic or neurologic disease. Prospective investigation concerning clinical indicators of disease severity of these body systems is indicated.

High Mortality and Coinfection in a Prospective Cohort of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome Patients with Histoplasmosis in Guatemala.

Histoplasmosis is one of the most common and deadly opportunistic infections among persons living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome in Latin America, but due to limited diagnostic capacity in this region, few data on the burden and clinical characteristics of this disease exist. Between 2005 and 2009, we enrolled patients ≥ 18 years of age with suspected histoplasmosis at a hospital-based HIV clinic in Guatemala City. A case of suspected histoplasmosis was defined as a person presenting with at least three of five clinical or radiologic criteria. A confirmed case of histoplasmosis was defined as a person with a positive culture or urine antigen test for Histoplasma capsulatum. Demographic and clinical data were also collected and analyzed. Of 263 enrolled as suspected cases of histoplasmosis, 101 (38.4%) were confirmed cases. Median time to diagnosis was 15 days after presentation (interquartile range [IQR] = 5-23). Crude overall mortality was 43.6%; median survival time was 19 days (IQR = 4-69). Mycobacterial infection was diagnosed in 70 (26.6%) cases; 26 (25.7%) histoplasmosis cases were coinfected with mycobacteria. High mortality and short survival time after initial symptoms were observed in patients with histoplasmosis. Mycobacterial coinfection diagnoses were frequent, highlighting the importance of pursuing diagnoses for both diseases.

Gastrointestinal Histoplasmosis: A Case Series.

Histoplasmosis is an invasive mycosis caused by inhalation of the spores of dimorphic fungi Histoplasma capsulatum. The disease manifests in the lung as acute or chronic pulmonary histoplasmosis and in severe cases gets disseminated in multiple organs like skin, adrenal gland, central nervous system, lymph node, liver, spleen, bone marrow, and gastrointestinal tract. It occurs most commonly in immunodeficient patients like HIV-positive patients and transplant recipients, while immunocompetent hosts are affected rarely. In cases of gastrointestinal histoplasmosis, the samples are collected for culture and biopsy should be sent for histopathological examination for definitive diagnosis. We conducted a retrospective study of colonic biopsies performed in the department of gastroenterology in a tertiary care hospital of north India from January 2014 to December 2015. Five cases of colonic histoplasmosis were diagnosed on histopathology out of which 4 patients were from north India while 1 patient was from Myanmar. The patients presented with various complaints, including loose stools, diarrhea, altered bowel habits, and gastrointestinal bleeding. The prognosis is very good after early and aggressive treatment while the disease is fatal if it remains untreated. In our study, 2 patients died within few days of diagnosis due to delay in the diagnosis, dissemination, and associated complications. Other patients were started on amphotericin B deoxycholate and are under follow-up. An early diagnosis of gastrointestinal histoplasmosis is important as appropriate treatment leads to long-term survival while untreated cases are almost fatal.

Prevalence and lethality among patients with histoplasmosis and AIDS in the Midwest Region of Brazil.

Histoplasmosis is a systemic mycosis that is considered an important public health problem. In this work, we performed a descriptive, observational, cross-sectional and retrospective study with a secondary data analysis of medical records from 2000 to 2012 at a tertiary hospital. The study sample consisted of 275 patients with laboratory-confirmed Disseminated Histoplasmosis (DH)/AIDS. The results showed that the prevalence of DH associated with AIDS was 4.4%. The majority of patients were young adult men with fever in 84.2%, cough in 63.4%, weight loss in 63.1%, diarrhoea in 44.8% and skin manifestations in 27.6% of patients. In the overall cohort, the CD4 counts were low, but not significantly different in survivors and non-survivors. Higher levels of urea and lower levels of haemoglobin and platelets were observed in non-survivor patients (<.05). The global lethality was 71.3% (196/275). The results with high prevalence and lethality highlight the need to adopt measures to facilitate early diagnosis, proper treatment and improved prognosis.

Mortality From Fungal Diseases in the US Air Force From 1970 to 2013.

We review a unique set of documents, death certificates, catalogued in the US Air Force Mortality Registry, which tracks deaths for current and retired Air Force service members. We screened the records for all deaths caused by fungal diseases between 1970 and 2013. There were 216 deaths caused by a variety of diseases such as aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, mucormycosis, pneumocystosis, sporotrichosis, and zygomycosis. The single most common identified cause of death was opportunistic candidiasis. Of the total 216 deaths, only 7 were active duty or active reserve personnel.

[Clinical comparative analysis for pulmonary histoplasmosis and progressive disseminated histoplasmosis].

OBJECTIVE: To compare clinical features, diagnosis and therapeutic effect between pulmonary histoplasmosis and progressive disseminated histoplasmosis.
 Methods: A retrospective analysis for 12 cases of hospitalized patients with histoplasmosis, who was admitted in Xiangya Hospital, Central South University during the time from February 2009 to October 2015, was carried out. Four cases of pulmonary histoplasmosis and 8 cases of progressive disseminated histoplasmosis were included. The differences of clinical features, imaging tests, means for diagnosis and prognosis were analyzed between the two types of histoplasmosis.
 Results: The clinical manifestations of pulmonary histoplasmosis were mild, such as dry cough. However, the main clinical symptoms of progressive disseminated histoplasmosis were severe, including recurrence of high fever, superficial lymph node enlargement over the whole body, hepatosplenomegaly, accompanied by cough, abdominal pain, joint pain, skin changes, etc.Laboratory examination showed pancytopenia, abnormal liver function and abnormal coagulation function. One pulmonary case received the operation of left lower lung lobectomy, 3 cases of pulmonary histoplasmosis and 6 cases of progressive disseminated histoplasmosis patients were given deoxycholate amphotericin B, itraconazole, voriconazole or fluconazole for antifungal therapy. One disseminated case discharged from the hospital without treatment after diagnosis of histoplasmosis, and 1 disseminated case combined with severe pneumonia and active tuberculosis died ultimately.
 Conclusion: As a rare fungal infection, histoplasmosis is easily to be misdiagnosed. The diagnostic criteria depends on etiology through bone marrow smear and tissues biopsy. Liposomeal amphotericin B, deoxycholate amphotericin B and itraconazole are recommended to treat infection for histoplasma capsulatum.