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.

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.

Current situation of endemic mycosis in the Americas and the Caribbean: Proceedings of the first international meeting on endemic mycoses of the Americas (IMEMA).

BACKGROUND: The Americas are home to biologically and clinically diverse endemic fungi, including Blastomyces, Coccidioides, Emergomyces, Histoplasma, Paracoccidioides and Sporothrix. In endemic areas with high risk of infection, these fungal pathogens represent an important public health problem. OBJECTIVES: This report aims to summarise the main findings of the regional analysis carried out on the status of the endemic mycoses of the Americas, done at the first International Meeting on Endemic Mycoses of the Americas (IMEMA). METHODS: A regional analysis for the Americas was done, the 27 territories were grouped into nine regions. A SWOT analysis was done. RESULTS: All territories reported availability of microscopy. Seventy percent of territories reported antibody testing, 67% of territories reported availability of Histoplasma antigen testing. None of the territories reported the use of (1-3)-ß-d-glucan. Fifty two percent of territories reported the availability of PCR testing in reference centres (mostly for histoplasmosis). Most of the territories reported access to medications such as trimethoprim-sulfamethoxazole, itraconazole, voriconazole and amphotericin B (AMB) deoxycholate. Many countries had limited access to liposomal formulation of AMB and newer azoles, such as posaconazole and isavuconazole. Surveillance of these fungal diseases was minimal. CONCLUSIONS: A consensus emerged among meeting participants, this group concluded that endemic mycoses are neglected diseases, and due to their severity and lack of resources, the improvement of diagnosis, treatment and surveillance is needed.

Histoplasmosis Outbreaks in Brazil: Lessons to Learn About Preventing Exposure.

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.

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.

Validation of western blot for Histoplasma capsulatum antibody detection assay.

BACKGROUND: Histoplasmosis is worldwide systemic mycoses caused by the dimorphic fungus Histoplasma capsulatum. The isolation and identification of H. capsulatum in culture is the reference test for histoplasmosis diagnosis confirmation. However, in the absence of it, serology has been used as a presumptive diagnosis through antibody and antigen detection. The purpose of the present study was to validate an immunoassay method (western blot) for antibodies detection in the diagnosis of histoplasmosis. METHODS: To validate the western blot (WB) a study was conducted using 118 serum samples from patients with histoplasmosis and 118 serum controls collected from January 2000 to December 2013 in residents of the Rio de Janeiro State, Brazil. Diagnostic validation parameters were calculated based on the categorization of results obtained in a 2 × 2 table and subjected to statistical analysis. In addition, the viability of deglycosylated histoplasmin antigen (ptHMIN) onto nitrocellulose membranes previously sensitized was evaluated during the same period. RESULTS: The WB test showed sensitivity of 94.9 %, specificity of 94.1 %, positive predictive value of 94.1 %, negative predictive value of 94.9 %, accuracy of 94.5 %, and almost perfect precision. Besides, the strips have proved to be viable for using at least 5 years after ptHMIN antigen sensitization. CONCLUSION: Western blot test using ptHMIN provides sensitive, specific, and faster results. Therefore, could be considered a useful tool in the diagnosis of histoplasmosis being used by public health system, even in situations where laboratory facilities are relatively limited.

Disseminated histoplasmosis in HIV-infected patients: determinants of relapse and mortality in a north-eastern area of Brazil.

Many relapses and deaths resulting from disseminated histoplasmosis (DH) in acquired immunodeficiency syndrome (AIDS) patients have been observed in an endemic area in north-eastern Brazil. The objective of this study was to evaluate the risk factors associated with the clinical outcomes of DH/AIDS coinfection in patients from the state of Ceará, Brazil. A retrospective cohort of AIDS patients, after their hospital discharge due to first DH episode in the period 2002-2008, was followed until December 31, 2010, to investigate the factors associated with relapse and mortality. A total of 145 patients were evaluated in the study. Thirty patients (23.3%) relapsed and the overall mortality was 30.2%. The following variables were significantly (P < 0.05) associated with relapse and overall mortality (univariate analysis): non-adherence to highly active antiretroviral therapy (HAART), irregular use of an antifungal, non-recovery of the CD4+ count and having AIDS before DH; histoplasmosis relapse was also significantly associated with mortality. In the multivariate analysis, non-adherence to HAART was the independent risk factor that was associated with both relapse (Adj OR = 6.28) and overall mortality (Adj OR = 8.03); efavirenz usage was discovered to be significant only for the overall mortality rate (Adj OR = 4.50). Adherence to HAART was the most important variable that influenced the outcomes in this specific population.

The impact of immune recovery and treatment duration on disseminated histoplasmosis consolidation therapy in AIDS patients.

INTRODUCTION: The present study investigated the impact of immune recovery and the duration of antifungal adherence in the consolidation phase of disseminated histoplasmosis (DH) in acquired immune deficiency syndrome (AIDS) patients living in a hyperendemic area in northeastern Brazil. MATERIAL AND METHODS: Sixty-nine patients with DH/AIDS, admitted to the São José Hospital between 2010 and 2015, who continued histoplasmosis consolidation therapy at the outpatient clinic were studied. The follow-up duration was at least 24 months. RESULTS: Sixty-eight patients used itraconazole 200-400 mg/day or amphotericin B deoxycholate weekly during the consolidation phase, and six patients relapsed during follow-up. The overall median duration of consolidation antifungal use was 250 days [IQR 101 - 372]. Antifungal withdrawal by medical decision occurred in 41 patients (70.7 %) after a median of 293 days [IQR 128 - 372] of use; 16 patients discontinued by their own decision, with a median of 106 days [IQR 37 - 244] of therapy; three patients had no information available, and nine continued on AF therapy. The median CD4+ T-cell count in the group without relapse was 248 cells/µL [IQR 115-355] within 6 months after admission; conversely, in the relapse group, the median cell count remained below 100 cells/µL. Irregular adherence to highly active antiretroviral therapy (HAART) was the leading risk factor associated with relapse and death (p< 0.01). DISCUSSION: The regular use of HAART, combined with immune recovery, proved to be highly effective in preventing relapses in DH/AIDS patients, suggesting that long-term antifungal therapy may not be necessary.

A fatal case of COVID-19-associated meningoencephalitis in a patient coinfected with influenza A.

We report a case of COVID-19-associated meningoencephalitis with a fatal outcome in a male patient with concomitant influenza A, who had been hospitalized at the beginning of 2022, in the Northeastern region of Brazil. He died due to cardiopulmonary arrest after developing status epilepticus on the third day of hospitalization. The SARS-CoV-2 RNA was detected in cerebrospinal fluid and Influenza A was detected in the nasopharyngeal swab. Meningoencephalitis due to COVID-19 is a rare manifestation and physicians must be aware of this complication, mainly during the pandemic. In viral co-circulation situations, the possibility of respiratory coinfections should be remembered.

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.

Severe mpox in patients with advanced AIDS: long-term disease and fatal outcome.

Herein, we report two cases of severe mpox in patients with advanced acquired immunodeficiency syndrome from Brazil who developed atypical lesions and prolonged illness, one of whom had a fatal outcome. Both patients experienced serious complications involving the perianal and genital regions and prolonged disease with persistent viremia.

Prevalence of trachoma in the non-indigenous Baixo Jaguaribe micro-region, Ceará State, Northeast Brazil.

BACKGROUND: The aim of the current study was to estimate the population prevalence of trachoma in non-indigenous populations in the Baixo Jaguaribe micro-region, in the state of Ceará, northeast region of Brazil, 2021-2022. METHODS: A population-based prevalence survey focusing on detecting cases of trachomatous inflammation-follicular (TF) in children aged 1-9 y and trachomatous trichiasis (TT) 'unknown to the health system' in people aged ≥15 y, was conducted in rural areas of the Baixo Jaguaribe micro-region in the state of Ceará. Indigenous populations will be further researched. RESULTS: There was no detection of cases of TF and TT. In 900 households, 2234 people were examined. In the Baixo Jaguaribe micro-region, females (54.6%; 1219/2234) and the mixed/Pardo-Brazilian ethnicity (68.1%; 1521/2234) predominated. The most commonly reported educational level was elementary and middle school (41.8%; 702/1679). In 56.2% (506/900) of households, there was a source of water within the household. The monthly income range of 50%-100% of the minimum wage predominated in the families of the Baixo Jaguaribe micro-region (43.1%; 388/900). CONCLUSIONS: Although no cases of TF and TT were detected in the Baixo Jaguaribe micro-region in the state of Ceará during the study period, considering the historical endemicity, we emphasise the need for monitoring and sustainability of surveillance actions in areas at risk for trachoma, common contexts for neglected populations.

COVID-19-associated meningoencephalitis in a Brazilian patient: case report and literature review.

The global pandemic of COVID-19 is caused by the novel coronavirus SARS-CoV-2, which often causes flu-like symptoms and can progress to severe respiratory illness. Thus, as the disease spreads, COVID-19 cases have multiplied across the world, and manifestations involving multiple systems have been described. We report a case of COVID-19-associated meningoencephalitis in a Brazilian male patient who presented with seizures and altered mental status. To the best of our knowledge, this is the first reported case of COVID-19-associated meningoencephalitis in Brazil. COVID-19-associated meningoencephalitis is a rare manifestation of this viral infection and clinicians should be aware of this possible complication.

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.

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.

Mixed infection by Histoplasma capsulatum isolates with different mating types in Brazilian AIDS-patients.

Mixed infection by Histoplasma capsulatum isolates with different mating types, in AIDS-patients are described in this study. Morphological, mating type-specific PCR assay and multilocus sequencing type analysis of H. capsulatum isolates recovered from two Brazilian AIDS-patients were performed. Five H. capsulatum isolates were recovered at different times from the two patients. Three isolates were obtained from bone marrow (day 1 - CE0411) and buffy coat cultures (day 1 - CE0311; day 2 - CE0511) of patient 1, and two isolates were isolated from buffy coat cultures (day 3 - CE2813; day 12 - CE2513) of patient 2. The mycelial colonies depicted different textures and pigmentation features. Dimorphic conversion to the yeast-phase in ML-Gema medium was achieved in all isolates. MAT1-1 idiomorph was identified in CE0311, CE0411 and CE2813 isolates; MAT1-2 idiomorph was found in CE0511 and CE2513 isolates. These H. capsulatum isolates were grouped within LAm A clade, highlighting that CE0311 and CE0411 isolates formed a subgroup supported by a high bootstrap value. The CE0511, CE2513, and CE2813 isolates clustered together with a Brazilian H151 isolate. This research reports mixed infections caused by H. capsulatum isolates with different mating types in Brazilian AIDS-patients for the first time in the literature.

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.

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.

A fatal case of COVID-19-associated meningoencephalitis in a patient coinfected with influenza A

ABSTRACT We report a case of COVID-19-associated meningoencephalitis with a fatal outcome in a male patient with concomitant influenza A, who had been hospitalized at the beginning of 2022, in the Northeastern region of Brazil. He died due to cardiopulmonary arrest after developing status epilepticus on the third day of hospitalization. The SARS-CoV-2 RNA was detected in cerebrospinal fluid and Influenza A was detected in the nasopharyngeal swab. Meningoencephalitis due to COVID-19 is a rare manifestation and physicians must be aware of this complication, mainly during the pandemic. In viral co-circulation situations, the possibility of respiratory coinfections should be remembered.

Predictive factors for disseminated histoplasmosis in AIDS patients with fever admitted to a reference hospital in Brazil.

INTRODUCTION: In many settings, the lack of sensitive biomarkers of disseminated histoplasmosis (DH) leads to a clinical reliance on older diagnostic methods and delayed treatment initiation. The early recognition of DH is critical for survival, especially in patients with human immunodeficiency virus (HIV). This study aimed to identify clinical and laboratory findings associated with the definitive diagnosis of DH in low-income HIV patients in endemic areas. METHODS: Febrile AIDS patients with suspected DH who were admitted to a reference hospital in northeastern Brazil from January 2006 to January 2007 were evaluated for clinical and laboratory findings associated with DH diagnosis. RESULTS: One hundred seventeen patients with fever were included, and 48 (41%) cases of DH were determined by Histoplasma capsulatum identification. A higher fever (≥38.5ºC), maculopapular/papular rash, splenomegaly, hepatomegaly, wheezing, hemoglobin ≤9.5g/dL, platelets ≤80,000/µL, CD4 count ≤75/µL, aspartate aminotransferase (AST) level ≥2.5 times the upper limit of normal (ULN), lactate dehydrogenase (LDH) ≥5times the ULN; and international normalized ratio (INR) >2 times the ULN were significantly associated with DH. A multivariable analysis identified hepatomegaly [adjusted (a) prevalence ratio (PR)= 1.96; 95% confidence interval (CI): 1.21-3.16), CD4 count ≤75/µL (aPR = 2.02; 95% CI: 1.06-3.83), LDH ≥5 times the ULN (aPR = 2.23; 95% CI: 1.44-3.48), and maculopapular/papular rash (aPR = 1.70; 95% CI: 1.02-2.83) were independent risk factors for DH. CONCLUSIONS: These easily assessed parameters can facilitate clinical decision-making for febrile AIDS patients with suspected DH in low socioeconomic and Histoplasma-endemic regions.