Frederico Figueiredo Amâncio

Clinical Profiles and Factors Associated with Death in Adults with Dengue Admitted to Intensive Care Units, Minas Gerais, Brazil

The purpose of our study was to describe the clinical profile of dengue-infected patients admitted to Brazilian intensive care units (ICU) and evaluate factors associated with death. A longitudinal, multicenter case series study was conducted with laboratory-confirmed dengue patients admitted to nine Brazilian ICUs situated in Minas Gerais state, southeastern Brazil from January 1, 2008, to December 31, 2013. Demographic, clinical and laboratory data; disease severity scores; and mortality were evaluated. A total of 97 patients were studied. The in-ICU and in-hospital mortality rates were 18.6% and 19.6%, respectively. Patients classified as having severe dengue according to current World Health Organization classifications showed an increased risk of death in a univariate analysis. Nonsurvivors were older, exhibited lower serum albumin concentrations and higher total leukocyte counts and serum creatinine levels. Other risk factors (vomiting, lethargy/restlessness, dyspnea/respiratory distress) were also associated with death in a univariate analysis. Multivariate analysis indicated that in-hospital mortality was significantly associated with Acute Physiology and Chronic Health Evaluation II and the Sequential Organ Failure Assessment score. The ICU and in-hospital mortality observed in this study were higher than values reported in similar studies. An increased frequency of ICU admission due to severe organ dysfunction, higher severity indices and scarcity of ICU beds may partially explain the higher mortality.

Predictors of the short- and long-term survival of HIV-infected patients admitted to a Brazilian intensive care unit.

The outcomes of HIV-infected patients requiring critical care have improved. However, in developing countries, information about HIV-infected patients admitted to intensive care units (ICUs) is scarce. We describe the prognosis of HIV-infected patients admitted to a Brazilian ICU and the factors predictive of short- and long-term survival. A historical cohort study, including HIV-infected patients admitted to a Brazilian ICU at an HIV/AIDS reference hospital, was conducted. Survivors were followed up for 24 months after ICU discharge. Demographic, clinical and laboratory data, disease severity scores and mortality were evaluated. Data were analysed using survival and regression models. One hundred and twenty-five patients were studied. In-ICU and in-hospital mortality rates were 46.4% and 68.0%, respectively. Multivariate analysis showed that the in-ICU mortality was significantly associated with APACHE (Acute Physiology and Chronic Health Evaluation) II scores (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.03–1.11), mechanical ventilation (OR, 6.39; 95% CI, 1.29–31.76), tuberculosis treatment (OR, 2.62; 95% CI, 1.03–6.71), use of antiretroviral therapy (OR, 0.19; 95% CI, 0.05–0.77) and septic shock (OR, 4.38; 95% CI, 1.78–10.76). Septic shock was also associated with long-term survival (hazard ratio, 3.0; 95% CI, 1.31–6.90). In-hospital and in-ICU mortality were higher than those reported for developed countries. ICU admission mostly due to AIDS-related diseases may explain these differences.

Epidemiological characteristics of Brazilian spotted fever in Minas Gerais State, Brazil, 2000-2008

Brazilian spotted fever is the most common rickettsiosis in Brazil, most prevalent in the States of São Paulo and Minas Gerais. The aim of this study was to describe the epidemiological characteristics of Brazilian spotted fever in Minas Gerais from 2000 to 2008. Of the 132 cases of Brazilian spotted fever, 53 patients died, representing a case-fatality rate of 40.2%. Males predominated, with 78.8% of confirmed cases, and median age was 26.5 years. Absence of rash was associated with increased risk of death (p = 0.005). Greater Metropolitan Belo Horizonte, Rio Doce Valley, and Zona da Mata accounted for 70.6% of the cases, which occurred mainly from May to November. There was an increase in the number of cases, which could suggest an expansion of the disease, but probably resulted from an increase in the health systems diagnostic capacity and sensitivity. Despite this improvement, the case-fatality rate remains high and with no apparent tendency to decrease, thus indicating the need for improved prevention and patient care.

Factors associated with death from dengue in the state of Minas Gerais, Brazil: historical cohort study

To analyse the clinical and epidemiological profiles of dengue haemorrhagic fever (DHF), dengue shock syndrome (DSS) and complicated dengue cases and deaths from 2008 to 2010 that occurred in the state of Minas Gerais, south‐eastern Brazil, and to identify factors associated with death from dengue.

Dengue virus serotype 4 in a highly susceptible population in Southeast Brazil.

In Minas Gerais, Brazil, almost 500,000 dengue fever cases were reported to the State Surveillance System between November 2012 and July 2013. An analysis of the laboratory-confirmed cases revealed a higher age-specific incidence in adults and a higher case fatality rate in people aged ≥50. Dengue virus serotypes 1 and 4 (the latter of which is an emerging serotype in Brazil) were responsible for the outbreak.

FATAL OUTCOME OF INFECTION BY DENGUE 4 IN A PATIENT WITH THROMBOCYTOPENIC PURPURA AS A COMORBID CONDITION IN BRAZIL

Dengue is currently a major public-health problem. Dengue virus (DENV) is classified into four distinct serotypes, DENV 1-4. After 28 years of absence, DENV-4 was again detected in Brazil in 2010 in Roraima State, and one year later, the virus was identified in the northern Brazilian states of Amazonas and Pará, followed by Rio de Janeiro and São Paulo. In Minas Gerais, the first confirmed case of DENV-4 occurred in the municipality of Frutal in 2011 and has now been isolated from a growing number of patients. Although DENV-2 is associated with the highest risk of severe forms of the disease and death due to the infection, DENV-4 has also been associated with severe forms of the disease and an increasing risk of hemorrhagic manifestations. Herein, the first fatal case of confirmed DENV-4 in Brazil is reported. The patient was an 11-year-old girl from the municipality of Montes Claros in northern Minas Gerais State, Brazil. She had idiopathic thrombocytopenic purpura as a comorbid condition and presented with a fulminant course of infection, leading to death due to hemorrhagic complications. Diagnosis was confirmed by detection of Dengue-specific antibodies using IgM capture enzyme-linked immunosorbent assay and semi-nested RT-PCR. Primary care physicians and other health-care providers should bear in mind that DENV-4 can also result in severe forms of the disease and lead to hemorrhagic complications and death, mainly when dengue infection is associated with coexisting conditions.

Sensitivity and specificity of the circulating cathodic antigen rapid urine test in the diagnosis of Schistosomiasis mansoni infection and evaluation of morbidity in a low- endemic area in Brazil.

INTRODUCTION: The Kato-Katz technique is the standard diagnostic test for Schistosoma mansoni infection in rural areas. However, the utility of this method is severely limited by the day-to-day variability in host egg excretion in the stool. In high-transmission areas, the point-of-care circulating cathodic antigen (POC-CCA) urine assay has proven to be a reliable test. However, investigations of the reliability of the POC-CCA assay in low-transmission regions are under way. This study aimed to evaluate the sensitivity and specificity of the POC-CCA assay and the morbidity of schistosomiasis in a low-endemic area in Brazil. METHODS: Pains City is a low-transmission zone for schistosomiasis. A total of 300 subjects aged 7-76 years were randomly selected for the POC-CCA cassette test. For S. mansoni diagnosis, three stool samples on six slides were compared with one urine sample for each subject. The sensitivity and specificity in the absence of a gold standard were calculated using latent class analysis. Clinical examinations and abdominal ultrasounds were performed in 181 volunteers to evaluate morbidity associated with schistosomiasis. RESULTS: The sensitivity and specificity of the Kato-Katz technique were 25.6% and 94.6%, respectively. By contrast, the sensitivity and specificity of the POC-CCA assay were 68.1% and 72.8%, respectively. Hepatosplenic schistosomiasis was diagnosed in two patients (1.1%). CONCLUSIONS: Overall, the POC-CCA urine assay proved to be a useful test for diagnosing S. mansoni in a low-endemic area in Brazil. Severe clinical forms of schistosomiasis can be present even in such low-endemic areas.

Aumento da carga de dengue no Brasil e unidades federadas, 2000 e 2015: análise do Global Burden of Disease Study 2015

RESUMO: Objetivo: Descrever as principais metricas sobre dengue geradas pelo Global Burden of Disease (GBD) Study 2015, para o Brasil e suas 27 unidades federadas, nos anos de 2000 e 2015. Metodos: As metricas descritas foram: taxas de incidencia e de mortalidade por dengue, padronizadas por idade, years of life lost (YLL), years lived with disability (YLD) e disability adjusted life years (DALY) (frequencia absoluta e taxas padronizadas por idade). As metricas estimadas foram apresentadas com intervalos de incerteza (II 95%) para 2000 e 2015, acompanhadas da variacao relativa percentual. Resultados: Verificou-se aumento de 232,7% no numero de casos e de 639,0% no numero de mortes entre os anos de 2000 e 2015 no pais. A taxa de incidencia variou 184,3% e a taxa de mortalidade mostrou-se baixa, mas com aumento de 500,0% no periodo avaliado. As taxas de YLL, YLD e DALY aumentaram 420,0, 187,2 e 266,1%, respectivamente. Em 2015, DALY foi semelhante entre mulheres e homens (21,9/100.000). O DALY aumentou mais que o dobro em todas as unidades da federacao. Conclusao: O aumento acentuado de dengue ao longo dos anos associa-se a introducao e/ou circulacao de um ou mais sorotipos do virus e crescente proporcao de pacientes acometidos pela forma grave da doenca. Apesar da baixa taxa de mortalidade, a dengue contribui para consideravel perda de anos saudaveis de vida no Brasil por acometer elevado numero de pessoas, de todas as faixas etarias, ocasionando algum grau de incapacidade durante a infeccao sintomatica, e em razao dos obitos, principalmente, em criancas.Objective: To describe the main metrics on dengue generated by Global Burden of Disease (GBD) Study 2015, for Brazil and its 27 federated units, in the years 2000 and 2015. Methods: The metrics described were: incidence and mortality rates by dengue, standardized by age, years of life lost (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY) (in absolute frequency and age-standardized rates). The estimated metrics were presented with uncertainty intervals (UI 95%) for the years 2000 and 2015, accompanied by the relative percentages of changes. Results: The number of cases increased 232.7% and the number of deaths increased 639.0% between 2000 and 2015 in the country. The incidence rate varied 184.3% and the mortality rate was low, but with an increase of 500.0% in the period evaluated. The YLL, YLD, and DALY rates increased 420.0, 187.2, and 266.1%, respectively. In 2015, DALY was similar among women and men (21.9/100,000). The DALY increased more than double in all the Brazilian federated units. Conclusion: The marked increase in dengue over the years is associated with the introduction and/or circulation of one or more serotypes of the transmitter virus and an increasing proportion of patients affected by the severe form of the disease. Despite the low mortality rate of the disease in comparison between the years of study, the disease contributes to the loss of healthy years of life in Brazil as it affects a large number of people, from all age groups, causing some degree of disability during the infection and deaths, especially, in children.

Prognostic factors for death from visceral leishmaniasis in patients treated with liposomal amphotericin B in an endemic state in Brazil.

Objective To characterize the clinical and epidemiological profiles of patients with visceral leishmaniasis (VL) treated with liposomal amphotericin B (LAmB) and to identify prognostic factors for death from VL in 2008-2012 in the state of Minas Gerais, Brazil. Methods A historical cohort study was conducted using data obtained from treatment requests forms, Brazilian Notifiable Disease Information System and the Mortality Information System. Case-fatality rates of patients with VL treated with LAmB were compared with patients treated with other therapies. Logistic regression analysis was used to identify prognostic factors for death. Results The overall case-fatality rate of the 577 patients treated with LAmB was 19.4%. Prognostic factors for death from VL were age between 35 and 49 years (OR 2.7; 95% CI 1.3-5.4) and above 50 years (OR 2.6; 95% CI 1.3-4.9), jaundice (OR 2.2; 95% CI 1.2-3.7), kidney disease (OR 2.8; 95% CI 1.6-4.9), presence of other infections (OR 2.4; 95% CI 1.5-4.1), edema (OR 2.0; 95% CI 1.1-3.4), platelet count below 50.000/mm3 (OR 3.6; 95% CI 2.1-6.0), AST higher than 100 U/L (OR 2.2; 95% CI 1.3-3.8), and assistance in non-specialized institutions (OR 1.9; 95% CI 1.0-3.5). Conclusions Case-fatality rates were higher than that observed among patients with VL treated with other therapies. Identification of prognostic factors of death from VL may allow early diagnosis of patients prone to such outcome and prompt an expeditious and appropriate management of VL to reduce fatality rates.

Osteopontin Is Upregulated in Human and Murine Acute Schistosomiasis Mansoni.

Background Symptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection. Methodology/Principal Findings Serum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7–11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells. Conclusions/Significance S. mansoni egg antigens induce the production of OPN by macrophages in the necrotic-exudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and murine acute schistosomiasis and could be a non-invasive biomarker of this form of disease.