Dengue diagnostics: serious inaccuracies are likely to occur if pre-analytical conditions are not strictly followed.

BACKGROUND: The heat-labile nature of Dengue virus (DENV) in serum samples must be considered when applying routine diagnostic tests to avoid issues that could impact the accuracy of test results with direct implications for case management and disease reporting. OBJECTIVES: To check if pre-analytical variables, such as storage time and temperature, have an impact on the accuracy of the main routine diagnostic tests for dengue. METHODS: Virus isolation, reverse transcription real-time polymerase chain reaction (RT-PCR) and NS1 enzyme-linked immunosorbent assay (ELISA) were evaluated using 84 samples submitted to different pre-analytical conditions. FINDINGS: Sensitivity and negative predictive value were directly affected by sample storage conditions. RT-PCR and virus isolation showed greater dependence on well-conserved samples for an accurate diagnosis. Interestingly, even storage at -30ºC for a relatively short time (15 days) was not adequate for accurate results using virus isolation and RT-PCR tests. On the other hand, NS1 ELISA showed no significant reduction in positivity for aliquots tested under the same conditions as in the previous tests. MAIN CONCLUSIONS: Our results support the stability of the NS1 marker in ELISA diagnosis and indicate that the accuracy of routine tests such as virus isolation and RT-PCR is significantly affected by inadequate transport and storage conditions of serum samples.

Characterization of dengue cases confirmed using the database linkage technique: assessment of virus circulation in Belo Horizonte, Brazil, 2009-2014. / Caracterização dos casos confirmados de dengue por meio da técnica de linkage de bancos de dados, para avaliar a circulação viral em Belo Horizonte, 2009-2014.

OBJECTIVE: to describe dengue virus circulation in Belo Horizonte, Brazil, from 2009 to 2014. METHODS: this is a series study of cases of dengue infected by different virus serotypes, identified by virus isolation or RT-PCR; database linkage was performed between the Notifiable Health Conditions Information System (SINAN), the Brazilian National Health System Hospital Information System (SIH/SUS) and the Laboratory Environment Manager (GAL). RESULTS: 91.1% of the records were linked (n=775); among the cases (n=851), 60.4% (n=514) were confirmed as DENV-1, 22.1% (n=188) DENV-4, 9.8% (n=83) as DENV-2, and 7.7% (n=66) as DENV-3; DENV-2 accounted for a higher percentage of severe cases (4.5%). CONCLUSION: DENV-1 prevailed and circulated in all evaluated years.

Prognostic factors associated with death from visceral leishmaniasis: a case-control study in Brazil.

BACKGROUND: The aim of this study was to identify the prognostic factors associated with death from visceral leishmaniasis (VL) considering the clinical evolution of patients through a case-control study. METHODS: We randomly selected 180 cases (death caused by VL) and 180 controls (cured) from Belo Horizonte's hospitals in Brazil, according to data found in the patients' medical records. Five models of multivariate logistic regression were performed following the chronological order of the variables between the onset of the symptoms and evolution of the VL cases. RESULTS: Considering the multivariate models and the stages of clinical evolution of VL, the prognostic factors associated with death are: age >60 y, minor hemorrhagic phenomena, increased abdominal volume, jaundice, dyspnea, malnutrition, TB, billirubin >2 mg/dL, Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) >100 U/L, leukocytes >7000/mm3, hemoglobin <7 g/dL, platelets <50 000/mm3 and infection without defined focus and bleeding. CONCLUSIONS: Knowledge regarding the prognostic factors associated with death from VL in different stages of the disease in large Brazilian urban centers such as Belo Horizonte may help optimize patient management strategies and contribute to reduce the high fatality rates in these cities.

Caracterização dos casos confirmados de dengue por meio da técnica de linkage de bancos de dados, para avaliar a circulação viral em Belo Horizonte, 2009-2014 / Características de los casos confirmados de dengue utilizando la técnica de enlace de bases de datos, para evaluar la circulación viral en la ciudad de Belo Horizonte, Brasil, 2009-2014 / Characterization of dengue cases confirmed using the database linkage technique: assessment of virus circulation in Belo Horizonte, Brazil, 2009-2014

Objetivo: descrever a circulação viral de dengue em Belo Horizonte, Brasil, de 2009 a 2014. Métodos: trata-se de estudo de série de casos de dengue infectados por diferentes sorotipos do vírus, identificados por isolamento viral ou RT-PCR; foi realizado linkage das bases de dados do Sistema de Informação de Agravos de Notificação (Sinan), do Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH/SUS) e do Gerenciador de Ambiente Laboratorial (GAL). Resultados: foram relacionados 91,1% dos registros (n=775); entre os casos (n=851), 60,4% (n=514) foram confirmados como DENV-1, 22,1% (n=188) como DENV-4, 9,8% (n=83) como DENV-2 e 7,7% (n=66) como DENV-3; DENV-2 apresentou maior percentual de casos graves (4,5%). Conclusão: DENV-1 prevaleceu e circulou em todos os anos avaliados.

Objetivo: describir la circulación viral del dengue en Belo Horizonte, Brasil, de 2009 a 2014. Métodos: se trata de estudio de una serie de casos de dengue infectados por diferentes serotipos del virus, identificados por aislamiento viral o RT-PCR; se realizó una conexión con las bases de datos del Sistema de Información para Enfermedades de Notificación (Sinan), el Sistema del Información Hospitalaria del Sistema Único de Salud (SIH/SUS) y el Gestor de Ambiente de Laboratorio (GAL). Resultados: fueron relacionados 91,1% de los registros (n=775); entre los casos (n=851), el 60,4% (n=514) fue confirmado como DENV-1, 22,1% (n=188) como DENV-4, 9,8% (n=83) como DENV-2 y 7,7% (n=66) como DENV-3; DENV-2 tuvo un mayor porcentaje de casos graves (4,5%). Conclusión: DENV-1 prevaleció y circuló en todos los años evaluados.

Objective: to describe dengue virus circulation in Belo Horizonte, Brazil, from 2009 to 2014. Methods: this is a series study of cases of dengue infected by different virus serotypes, identified by virus isolation or RT-PCR; database linkage was performed between the Notifiable Health Conditions Information System (SINAN), the Brazilian National Health System Hospital Information System (SIH/SUS) and the Laboratory Environment Manager (GAL). Results: 91.1% of the records were linked (n=775); among the cases (n=851), 60.4% (n=514) were confirmed as DENV-1, 22.1% (n=188) DENV-4, 9.8% (n=83) as DENV-2, and 7.7% (n=66) as DENV-3; DENV-2 accounted for a higher percentage of severe cases (4.5%). Conclusion: DENV-1 prevailed and circulated in all evaluated years.

Emergence of chikungunya and Zika in a municipality endemic to dengue, Santa Luzia, MG, Brazil, 2015-2017.

INTRODUCTION: The recent circulation of arboviruses transmitted by vectors, such as dengue, chikungunya, and Zika, is concerning due to the high morbidity rates, clinical complications, and increased demand on health services. The objective of this study was to analyze the clinical and epidemiological aspects of an epidemic caused by arboviruses in the municipality of Santa Luzia, Minas Gerais, Brazil. METHODS: Longitudinal study of patients with acute febrile disease and suspected arbovirus infection reported to Brazilian Notifiable Disease Information System (Sistema de Informação de Agravos de Notificação) from the epidemiological week 44 of 2015 to epidemiological week 52 of 2016. Patients with confirmed chikungunya were followed-up for 18 months and those with Zika for 15 months. Additionally, we analyzed and described the temporal distribution of confirmed cases of these arboviruses in this municipality. RESULTS: Overall 3,531 arboviruses cases, including 3,481 (98.7%) cases of dengue, 38 (1.0%) cases of chikungunya, and 12 (0.3%) cases of Zika were confirmed. The highest incidence of arbovirus infection occurred in the first quarter of 2016 (epidemiological week 7 to 14). The most frequent symptoms were for dengue, which included fever, headache, retro-orbital pain, and exanthema. Chikungunya infection was associated with fever, myalgia, arthralgia, and rash while Zika infection with pruritus and rash. CONCLUSIONS: Given the similarities in the initial clinical profiles of these arboviruses, it is important to perform a detailed clinical analysis, laboratory diagnosis, and patient follow-up.

Emergence of chikungunya and Zika in a municipality endemic to dengue, Santa Luzia, MG, Brazil, 2015-2017

Abstract INTRODUCTION: The recent circulation of arboviruses transmitted by vectors, such as dengue, chikungunya, and Zika, is concerning due to the high morbidity rates, clinical complications, and increased demand on health services. The objective of this study was to analyze the clinical and epidemiological aspects of an epidemic caused by arboviruses in the municipality of Santa Luzia, Minas Gerais, Brazil. METHODS: Longitudinal study of patients with acute febrile disease and suspected arbovirus infection reported to Brazilian Notifiable Disease Information System (Sistema de Informação de Agravos de Notificação) from the epidemiological week 44 of 2015 to epidemiological week 52 of 2016. Patients with confirmed chikungunya were followed-up for 18 months and those with Zika for 15 months. Additionally, we analyzed and described the temporal distribution of confirmed cases of these arboviruses in this municipality. RESULTS: Overall 3,531 arboviruses cases, including 3,481 (98.7%) cases of dengue, 38 (1.0%) cases of chikungunya, and 12 (0.3%) cases of Zika were confirmed. The highest incidence of arbovirus infection occurred in the first quarter of 2016 (epidemiological week 7 to 14). The most frequent symptoms were for dengue, which included fever, headache, retro-orbital pain, and exanthema. Chikungunya infection was associated with fever, myalgia, arthralgia, and rash while Zika infection with pruritus and rash. CONCLUSIONS: Given the similarities in the initial clinical profiles of these arboviruses, it is important to perform a detailed clinical analysis, laboratory diagnosis, and patient follow-up.

Thrombocytopenia as a marker of liver steatosis in a low-endemic area for schistosomiasis mansoni.

INTRODUCTION:: Thrombocytopenia is commonly found in patients living in highly endemic areas for Schistosoma mansoni. Recently, different degrees of liver steatosis have also been associated with low platelet counts worldwide. We investigated the association of platelet counts with hepatosplenic schistosomiasis and with liver steatosis in an area of low prevalence of schistosomiasis in Brazil. METHOD:: Pains, a city in the state of Minas Gerais, Brazil, had a population of 8,307 inhabitants and a schistosomiasis prevalence of 8%. Four micro-areas comprising 1,045 inhabitants were selected for this study. Blood sample was collected and a complete blood count (CBC) was performed. Eighty-seven (87) patients had low platelet counts (group 1 - 8.3%) and 94 volunteers presenting normal CBC were randomized (group 2 - 8.9%). They underwent clinical and ultrasound examinations. Liver steatosis was determined as either present or absent using abdominal ultrasound. A spleen > 12 cm in length, measured by ultrasound (US), was considered to be increased. Data collected were analyzed using SPSS software version 19.0. RESULTS:: Twenty-two patients (22/25.3%) in group 1 had liver steatosis compared with 11 volunteers (11.7%) in group 2 (p=0.02). Hepatosplenic schistosomiasis was diagnosed in two patients (p>0.05). CONCLUSION:: Thrombocytopenia was not a good marker of hepatosplenic schistosomiasis mansoni in a low prevalence area in Brazil. Liver steatosis was associated with thrombocytopenia in our study.

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.

Increase in the burden of dengue in Brazil and federated units, 2000 and 2015: analysis of the Global Burden of Disease Study 2015. / Aumento da carga de dengue no Brasil e unidades federadas, 2000 e 2015: análise do Global Burden of Disease Study 2015.

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.

Thrombocytopenia as a marker of liver steatosis in a low-endemic area for schistosomiasis mansoni / Trombocitopenia como marcador de esteatose hepática em áreas de baixa endemicidade de esquistossomose mansoni

Summary Introduction: Thrombocytopenia is commonly found in patients living in highly endemic areas for Schistosoma mansoni. Recently, different degrees of liver steatosis have also been associated with low platelet counts worldwide. We investigated the association of platelet counts with hepatosplenic schistosomiasis and with liver steatosis in an area of low prevalence of schistosomiasis in Brazil. Method: Pains, a city in the state of Minas Gerais, Brazil, had a population of 8,307 inhabitants and a schistosomiasis prevalence of 8%. Four micro-areas comprising 1,045 inhabitants were selected for this study. Blood sample was collected and a complete blood count (CBC) was performed. Eighty-seven (87) patients had low platelet counts (group 1 - 8.3%) and 94 volunteers presenting normal CBC were randomized (group 2 - 8.9%). They underwent clinical and ultrasound examinations. Liver steatosis was determined as either present or absent using abdominal ultrasound. A spleen > 12 cm in length, measured by ultrasound (US), was considered to be increased. Data collected were analyzed using SPSS software version 19.0. Results: Twenty-two patients (22/25.3%) in group 1 had liver steatosis compared with 11 volunteers (11.7%) in group 2 (p=0.02). Hepatosplenic schistosomiasis was diagnosed in two patients (p>0.05). Conclusion: Thrombocytopenia was not a good marker of hepatosplenic schistosomiasis mansoni in a low prevalence area in Brazil. Liver steatosis was associated with thrombocytopenia in our study.

Resumo Introdução: Trombocitopenia é um achado comum em pacientes que residem em áreas com alta endemicidade de esquistossomose mansônica. Recentemente, diferentes graus de esteatose hepática também têm sido associados a níveis baixos de plaquetas em todo o mundo. Investigamos a associação de níveis séricos de plaquetas com a forma grave da esquistossomose e com esteatose hepática em área de baixa prevalência de esquistossomose no Brasil. Método: Pains, cidade localizada no estado de Minas Gerais/Brasil, tem população de 8.307 habitantes e prevalência de esquistossomose de 8%. Em quatro microáreas dessa região, 1.045 habitantes foram avaliados para o estudo. Amostra de sangue foi coletada para realização do hemograma. Oitenta e sete (87) pessoas com níveis baixos de plaquetas formaram o grupo 1 (8,3%), e 94 voluntários com hemograma normal foram randomizados para compor o grupo 2 (8,9%). Todos os participantes dos grupos 1 e 2 foram submetidos a exame clínico e ultrassonografia (US) abdominal. Esteatose hepática foi caracterizada como presente ou ausente pela ultrassonografia (US) abdominal. Baços com mais de 12 cm de comprimento à US foram considerados aumentados. Os dados coletados foram analisados pelo programa de estatística SPSS 19.0. Resultados: Vinte e dois (22) indivíduos do grupo 1 (25,3%) e 11 do grupo 2 apresentaram esteatose hepática (11,7%) (p=0,02). Esquistossomose hepatoesplênica foi diagnosticada em dois pacientes (p>0,05). Conclusão: Trombocitopenia não foi um bom marcador de esquistossomose mansônica hepatoesplênica em área de baixa prevalência da esquistossomose no Brasil. Esteatose hepática foi associada com trombocitopenia no presente estudo.

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

Abstract 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 / Increase in the burden of dengue in Brazil and federated units, 2000 and 2015: analysis of the Global Burden of Disease Study 2015

RESUMO: Objetivo: Descrever as principais métricas 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. Métodos: As métricas descritas foram: taxas de incidência e de mortalidade por dengue, padronizadas por idade, years of life lost (YLL), years lived with disability (YLD) e disability adjusted life years (DALY) (frequência absoluta e taxas padronizadas por idade). As métricas estimadas foram apresentadas com intervalos de incerteza (II 95%) para 2000 e 2015, acompanhadas da variação relativa percentual. Resultados: Verificou-se aumento de 232,7% no número de casos e de 639,0% no número de mortes entre os anos de 2000 e 2015 no país. A taxa de incidência variou 184,3% e a taxa de mortalidade mostrou-se baixa, mas com aumento de 500,0% no período 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 federação. Conclusão: O aumento acentuado de dengue ao longo dos anos associa-se à introdução e/ou circulação de um ou mais sorotipos do vírus e crescente proporção de pacientes acometidos pela forma grave da doença. Apesar da baixa taxa de mortalidade, a dengue contribui para considerável perda de anos saudáveis de vida no Brasil por acometer elevado número de pessoas, de todas as faixas etárias, ocasionando algum grau de incapacidade durante a infecção sintomática, e em razão dos óbitos, principalmente, em crianças.

ABSTRACT: 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.

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.

Descentralização e expansão dos tratamentos de leishmaniose visceral (LV) com anfotericina B lipossomal em Minas Gerais, 2008-2012 / Decentralization and expansion of visceral leishmaniasis (VL) treatment with liposomal amphotericin B in Minas Gerais, 2008-2012

Descrever a descentralização e a expansão dos tratamentos da leishmaniose visceral (LV) com anfotericina B lipossomal em Minas Gerais, no período entre 2008 e 2012. Estudo descritivo que avaliou as fichas utilizadas para solicitar o tratamento com o medicamento e casos de LV no Sistema Nacional de Agravos de Notificação (SINAN). Foram avaliadas 646 solicitações de tratamento realizadas por 29 municípios, permitindo o tratamento de 577 pacientes, residentes em 97 municípios. A proporção de pacientes com LV tratados com anfotericina B lipossomal no Estado foi de 22,4%. As principais referências para o tratamento dos pacientes com LV foram as regiões Centro (URS Belo Horizonte) e Norte (URS Montes Claros). A descentralização e a expansão dos tratamentos refletem uma resposta positiva das equipes de assistência e vigilância do Estado e poderão contribuir favoravelmente para a evolução clínica dos casos de LV.

To describe the decentralization and expansion of VL treatment with liposomal amphotericin B in Minas Gerais between 2008 to 2012. This descriptive study evaluated forms used to request drug treatment and VL cases from the Reportable Disease Information System (SINAN). Were evaluated 646 treatment requests performed by 29 municipalities, allowing treatment of 577 patients residing in 97 municipalities. Proportion of patients with VL treated with lipossomal amphotericin B in the State was 22.4%. The main references for treatment of VL patients were Central (URS Belo Horizonte) and North (URS Montes Claros) regions. Decentralization and expansion of treatments reflect a positive response from assistance and surveillance teams of the State and may contribute favorably to clinical outcome of VL cases. Keywords: Visceral leishmaniasis, amphotericin B, decentralization.

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.

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

OBJECTIVES: 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. METHODS: Historical cohort study using data from the Brazilian Information System for Notifiable Diseases. A descriptive analysis of the DHF, DSS and complicated dengue cases and deaths was performed; the incidence, mortality and case-fatality rates were estimated. Logistic regression analysis was used to identify factors associated with death from dengue. Comorbidities were not included in the analysis because the information system does not contain such data. RESULTS: During the study period, 2214 DHF, DSS and complicated dengue cases were reported, including 156 deaths. The annual case-fatality rates for DHF/DSS and complicated dengue cases in the period of 2008-2010 were 7.3%, 4.8% and 7.9%, respectively. The factors associated with death from dengue included residence in a municipality with a population of fewer than 100,000 inhabitants [odds ratio (OR) 2.46; 95% confidence interval (CI) 1.71-3.55], age over 65 years (OR 3.05; 95% CI 1.99-4.68) and plasma leakage (OR 1.69; 95% CI 1.16-2.46). CONCLUSIONS: The results support the importance of plasma leakage as a warning sign associated with death from dengue as well as the signs and symptoms that allow the diagnosis of DHF. Moreover, our findings suggest that increased attention is necessary for individuals over 65 years of age and in municipalities with populations under 100,000 inhabitants to ensure a better quality of care during the management of severe patients of dengue in these locations. Differences in the interpretation of the DHF definition have hindered the comparison of data from different countries; it can improve from the WHO 2009 dengue classification.

Prognostic factors and scoring system for death from visceral leishmaniasis: an historical cohort study in Brazil.

BACKGROUND: In Brazil, case-fatality rates attributable to visceral leishmaniasis (VL) are high and knowledge of the risk factors associated with death may help reduce mortality. The aim of this study was to construct and validate a scoring system for prognosis of death from VL by using all cases reported in Brazil from 2007 to 2011. METHODOLOGY: In this historical cohort study, 18,501 VL cases were analyzed; of these, 17,345 cases were cured and 1,156 cases caused death. The database was divided into two series: primary (two-thirds of cases), to develop the model score, and secondary (one-third of cases), to validate the scoring system. Multivariate logistic regression models were performed to identify factors associated with death from VL, and these were included in the scoring system. PRINCIPAL FINDINGS: The factors associated with death from VL were: bleeding (score 3); splenomegaly (score 1); edema (score 1); weakness (score 1); jaundice (score 1); Leishmania-HIV co-infection (score 1); bacterial infection (score 1); and age (≤0.5 years [score 5]; >0.5 and ≤1 [score 2]; >19 and ≤50 [score 2]; >50 and <65 [score 3]; ≥65 [score 5]). It was observed that patients with a score of 4 had a probability of death of approximately 4.5% and had a worse prognosis. The sensitivity, specificity, and accuracy of this score were 89.4, 51.2, and 53.5, respectively. CONCLUSIONS/SIGNIFICANCE: The scoring system based on risk factors for death showed good performance in identifying patients with signs of severity at the time of clinical suspicion of VL and can contribute to improving the surveillance system for reducing case fatalities. The classification of patients according to their prognosis for death may assist decision-making regarding the transfer of the patients to hospitals more capable of handling their condition, admission to the intensive care unit, and adequate support and specific treatment.

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.

Fatal outcome o infection by dengue 4 in a patent with thrombocytopenic purpuura as a comorbid condition in Brazil / Óbito por dengue 4 no Brasil em paciente com púrpura trombocitopênica idiopática

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.

Dengue é atualmente um importante problema de saúde pública. O vírus da dengue (DENV) é classificado em quatro sorotipos distintos, DENV 1-4. Após 28 anos de ausência, o DENV-4 foi detectado novamente no Brasil em 2010 no Estado de Roraima, e um ano depois, o vírus foi identificado em outros estados do norte do país, Amazonas e Pará, seguido pelos estados do Rio de Janeiro e São Paulo. Em Minas Gerais, o primeiro caso confirmado de DENV-4 ocorreu no município de Frutal em 2011 e, desde então, o sorotipo foi isolado em um número crescente de pacientes. Apesar do DENV-2 estar associado a um maior risco de formas graves e morte, o DENV-4 também tem sido associado a casos graves e a risco aumentado de manifestações hemorrágicas. Neste relato, descrevemos o primeiro caso fatal confirmado por DENV-4 no Brasil. A paciente era uma menina de 11 anos do município de Montes Claros, no norte de Minas Gerais, Brasil. Apresentava púrpura trombocitopênica idiopática e evoluiu de forma fulminante durante a infecção por dengue, com óbito associado a complicações hemorrágicas. O diagnóstico foi confirmado pela detecção de anticorpos IgM específicos para dengue, por método imunoenzimático, e por semi-nested RT-PCR. Médicos e outros profissionais de saúde devem estar cientes que infecções por DENV-4 também podem resultar em formas graves da doença com complicações hemorrágicas e óbito, principalmente em pacientes com comorbidades.