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Prevalence and Lethality Among Patients with Histoplasmosis and AIDS in the Midwest Region of Brazil

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Prevalence and Lethality Among Patients with Histoplasmosis and AIDS in the Midwest Region of Brazil Received: 2 March 2016 | Revised: 30 May 2016 | Accepted: 19 July 2016 DOI: 10.1111/myc.12551 ORIGINAL ARTICLE Prevalence and lethality among patients with histoplasmosis and AIDS in the Midwest Region of Brazil Thaísa C. Silva1 | Carolina M. Treméa1 | Ana Laura S. A. Zara1 | Ana Flávia Mendonça2 | Cássia S. M. Godoy2 | Carolina R. Costa1 | Lúcia K. H. Souza1 | Maria R. R. Silva1 1Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiania, Summary Goiás, Brazil Histoplasmosis is a systemic mycosis that is considered an important public health 2 Hospital of Tropical Diseases “Dr. Anuar problem. In this work, we performed a descriptive, observational, cross- sectional and Auad”, Goiania, Goiás, Brazil retrospective study with a secondary data analysis of medical records from 2000 to Correspondence 2012 at a tertiary hospital. The study sample consisted of 275 patients with laboratory- Thaísa C. Silva, Setor Universitário, Goiânia, confirmed Disseminated Histoplasmosis (DH)/AIDS. The results showed that the Goiás, Brazil. Email: [email protected] 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. KEYWORDS AIDS, histoplasmosis, prevalence 1 | INTRODUCTION The disease is endemic in South America; in Brazil, it has been re- ported in the south, southeast and northeast regions.5,8–10 In the Disseminated histoplasmosis (DH) is near the top of the list of AIDS- Midwest Region, there have been reports of 30 cases of histoplasmosis defining illnesses and AIDS- related deaths.1 The estimated incidence in the Mato Grosso do Sul State,8 and although there are frequent medi- of DH varies from 5% to 25% in persons with AIDS and residents of cal reports of large numbers of histoplasmosis in Goiás (Midwest Region), endemic areas,2,3 with variable lethality throughout the world that there are no epidemiological studies about its occurrence in this State. ranges from approximately 10% in developed countries to 30% in To assess the prevalence, clinical characteristics, and laboratory areas with limited financial resources.4,5 and evolutionary data of histoplasmosis associated with AIDS in the Infection is characterised by a wide spectrum of manifestations Goiania, Goiás State, we performed a retrospective study of disease ranging from asymptomatic illness to severe disseminated histoplas- from January 2000 to June 2012. mosis.6 Symptoms of patients include fever, chills, non- productive cough, headaches and general malaise. However, in AIDS patients, 2 | MATERIALS AND METHODS the disease has non- specific symptoms and usually occurs with unexplained fever and weight loss. Laboratory findings, such as serum 2.1 | Patients creatinine level >2.1 mg/dL and LDH level of >400 U/L, have been associated with an increased risk of severe manifestations, such as A retrospective study was conducted to analyse the cases of histo- septic shock, respiratory failure and death.7 plasmosis in HIV patients from a reference hospital from January Mycoses 2017; 60: 59–65 wileyonlinelibrary.com/journal/myc © 2016 Blackwell Verlag GmbH | 59 60 | SILVA ET AL. 2000 to June 2012. This hospital is responsible for treating approxi- histoplasmosis, representing a prevalence of 4.4%, ranging from mately 90% of the HIV patients in Goiás. 0.9% in 2001 and 6.5% in 2011. The annual distribution of histo- The medical records of patients with AIDS (diagnosed according to plasmosis in AIDS patients showed an increased prevalence through the Brazilian Ministry of Health criteria) who had a diagnosis of histo- the years (Fig. 1). plasmosis were reviewed. Diagnosis of histoplasmosis was defined with Diagnostic confirmation occurred at a median of 10.5 days (per- standard mycologic examination methods from different fluids and tis- centiles 3–23) after admission, as defined by a positive culture in sues samples, including Giemsa stain and a positive culture in Sabouraud 64.1% of patients, cytology in 24.8% of patients and histopathology and Mycosel media, histoplasma antigen in urine and serum by immu- in 11.1% of patients. In this study, 40.1% (112/279) of patients were nological tests, or histopathologic consistent with H. capsulatum. diagnosed with DH and AIDS almost simultaneously, with interval less When available, the following information were collected: age, than 30 days. gender, occupation, residence area, clinical signs and symptoms, pres- The study population included 219 (78.5%) men and 60 (21.5%) ence of co- infections and treatment and evolution of the patients. women, with a median age of 37 years (range 30–49 years). Most of Laboratory data consisting of a full blood count, renal and hepatic func- the patients were born in the Goiás State (89.3%), came from urban tion tests and CD4+ cells count were recorded. Antifungal therapy for areas (82.1%), and did not have known risk activity for histoplasmosis, histoplasmosis was administered to 261 (93.6%) of the 279 patients. however, civil construction was the main activity for 23.3% of patients. Of the 279 patients study, four cases were excluded from the analysis because they had no record of the outcome death. 2.2 | Statistical analysis Epi- Info, version 3.5.1 (Center for Disease Control and Prevention, 3.2 | Clinical findings Atlanta, GA, USA), was used for data entry. Descriptive statistics included the mean ± standard deviation (SD) or the median (range) for Clinical symptoms and/or signs of histoplasmosis began at a me- quantitative variables as well as the absolute and relative frequency dian of 26 days before the diagnosis (percentiles 9–70 days). The for categorical variables. We used Student t- test to compare means. most frequent clinical symptoms included: fever (84.2%), weight Univariate analyses were performed using Fisher’s Exact test or χ2 loss (63.1%), weakness (53.8%), cough (63.4%), dyspnoea (56.3%), methods for categorical variables. Multivariable analysis was per- hepatomegaly (47.7%), diarrhoea (44.8%), vomiting (36.3%), sple- formed using stepwise logistic regression to determine the association nomegaly (33%) and skin lesions (27.6%). Chest radiographies of the predictor variables with lethality. For all tests, statistical signifi- were available in 157 (56.3%) patients, of which 127 (80.9%) had cance level was determined at α=0.05. Statistical analysis was con- interstitial infiltrates. ducted using PASW Statistics 18® (version 18.0.0, SPSS Inc., Chicago, Illinois, USA). The study was approved by the Ethical Committee of 3.3 | Laboratory findings reference protocol no. 023/2011. Clinical laboratory findings were not available for all patients and ranged in completeness for each exam. A summary of the 3 | RESULTS demographic characteristics and laboratory findings of survivors and non- survivors can be found in Tables 1 and 2. In the over- 3.1 | Sociodemographic data all cohort, the chance of death was higher among female patients Out of 6330 AIDS cases found from January 2000 to June (OR=2.74 [95% CI 1.28–5.89]; P<.05) (Table 2); CD4 counts were 2012 at the studied hospital, 279 patients were diagnosed with low (range, 1–702 cells/mm3) with 85.9% <150 cells/mm3, but FIGURE 1 Annual prevalence (2000– 2012 June) of histoplasmosis in patients with AIDS at Hospital of Tropical Diseases “Dr. Anuar Auad”. Goiânia, Goiás, Brazil SILVA ET AL. | 61 TABLE 1 Demographic characteristics vs death of patients with disseminated histoplasmosis and AIDS attended at Hospital of Tropical Diseases “Dr. Anuar Auad”. Goiania, Goiás, Brazil, 2000–2012 Non- survivors Survivors Demographic characteristics n=196 % n=79 % P-valuea Odds ratio (confidence interval 95%) Age group 196 71.3 79 28.7 .387 10–29 48 24.5 17 21.5 1 30–49 118 60.2 54 68.4 0.77 (0.41–1.47) 50–72 30 15.3 8 10.1 1.33 (0.51–3.45) Sex .008b Female 51 26.0 9 11.4 2.74 (1.28–5.89) Male 145 74.0 70 88.6 1 Marital status .816 Single/divorced/separated/widowed 123 65.4 46 63.9 1.07 (0.61–1.89) Married/stable union 65 34.6 26 36.1 1 Educational level .959 ≤8 years 110 75.3 45 75.0 1.02 (0.51–2.04) >8 years 36 24.7 15 25.0 1 Place of origin .747 Goiânia/Metropolitan Region 86 44.6 34 43.6 1 Others Municipalities of Goiás 87 45.1 38 48.7 0.91 (0.52–1.57) Others States of Country 20 10.2 6 7.7 1.32 (0.49–3.56) Residence area .112 Urban 172 90.5 55 83.3 1.91 (0.85–4.29) Rural 18 9.5 11 16.7 1 aChi- square test. bP<.05. were not significantly different in survivors and non- survivors 1.1% (n=3), tuberculosis 1.1% (n=3), and 56 cases (20.3%) had no data (P=.602) (Table 2). Higher levels of urea and lower levels of hae- available in the records. moglobin and platelets were observed in non- survivor patients (P<.05) (Table 2). In addition to DH, others opportunistic fungal infections were 4 | DISCUSSION observed in 58.1% of patients (162/279), 87.0% showed only one concomitant fungal infection DH and 13.0% of patients with over one Histoplasmosis continues to be an important opportunistic mycosis fungal infection.
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