Development and validation of a clinical rule for the diagnosis of chikungunya fever in a dengue-endemic area.

Rio de Janeiro is a dengue-endemic city that experienced Zika and chikungunya epidemics between 2015 and 2019. Differential diagnosis is crucial for indicating adequate treatment and assessing prognosis and risk of death. This study aims to derive and validate a clinical rule for diagnosing chikungunya based on 3,214 suspected cases consecutively treated at primary and secondary health units of the sentinel surveillance system (up to 7 days from onset of symptoms) in Rio de Janeiro, Brazil. Of the total sample, 624 were chikungunya, 88 Zika, 51 dengue, and 2,451 were negative for all these arboviruses according to real-time polymerase chain reaction (RT-qPCR). The derived rule included fever (1 point), exanthema (1 point), myalgia (2 points), arthralgia or arthritis (2 points), and joint edema (2 points), providing an AUC (area under the receiver operator curve) = 0.695 (95% CI: 0.662-0.725). Scores of 4 points or more (validation sample) showed 74.3% sensitivity (69.0% - 79.2%) and 51.5% specificity (48.8% - 54.3%). Adding more symptoms improved the specificity at the expense of a lower sensitivity compared to definitions proposed by government agencies based on fever alone (European Center for Disease Control) or in combination with arthralgia (World Health Organization) or arthritis (Pan American Health Organization, Brazilian Ministry of Health). The proposed clinical rule offers a rapid, low-cost, easy-to-apply strategy to differentiate chikungunya fever from other arbovirus infections during epidemics.

Social inequalities in the temporal trend of mortality from sickle cell disease in Brazil, 1996-2019.

Contrary to international trends, the mortality rate of sickle cell disease increased in Brazil after the implementation of the neonatal screening program, probably due to improving access to diagnosis. This study aimed to assess differences in the temporal trend of the mortality rate and median age at death from sickle cell disease in Brazil, considering implemented measures to expand diagnosis, and improve health care access in-country and in the international scenario. Time series were extracted from the Brazilian Mortality Information System from 1996 to 2019. Changes in the mortality rate and median age at death were verified via segmented regression models, which were stratified by sex, region of residence, and age. Most deaths occurred in non-white people, young adults, and the Southeast and Northeast population. Sickle cell disease mortality rate increased until 2010 (13.31%; 95%CI: 6.37; 20.70), particularly in individuals aged 30 years or more (12.78%; 95%CI: 2.98; 23.53) and in the Northeast (12.27%; 95%CI: 8.92; 15.72). Most deaths occurred in the second decade of life (3.01 deaths/million), with a 59% increase in the median age of death in Brazil, from 27.6 to 30.3 years, more pronounced in females and the North Region. The observed gain in the survival of sickle cell disease in Brazil is still much lower than in developed countries and presents regional disparities, probably due to the lack of access to health care and recent treatments, such as hydroxyurea, still restricted to hematological referral centers in Brazilian capitals.

Social inequalities in the temporal trend of mortality from sickle cell disease in Brazil, 1996-2019 / Desigualdades sociais na tendência temporal de mortalidade por doença falciforme no Brasil, 1996-2019 / Desigualdades sociales en la tendencia temporal de la mortalidad por enfermedad de células falciformes en Brasil, 1996-2019

Contrary to international trends, the mortality rate of sickle cell disease increased in Brazil after the implementation of the neonatal screening program, probably due to improving access to diagnosis. This study aimed to assess differences in the temporal trend of the mortality rate and median age at death from sickle cell disease in Brazil, considering implemented measures to expand diagnosis, and improve health care access in-country and in the international scenario. Time series were extracted from the Brazilian Mortality Information System from 1996 to 2019. Changes in the mortality rate and median age at death were verified via segmented regression models, which were stratified by sex, region of residence, and age. Most deaths occurred in non-white people, young adults, and the Southeast and Northeast population. Sickle cell disease mortality rate increased until 2010 (13.31%; 95%CI: 6.37; 20.70), particularly in individuals aged 30 years or more (12.78%; 95%CI: 2.98; 23.53) and in the Northeast (12.27%; 95%CI: 8.92; 15.72). Most deaths occurred in the second decade of life (3.01 deaths/million), with a 59% increase in the median age of death in Brazil, from 27.6 to 30.3 years, more pronounced in females and the North Region. The observed gain in the survival of sickle cell disease in Brazil is still much lower than in developed countries and presents regional disparities, probably due to the lack of access to health care and recent treatments, such as hydroxyurea, still restricted to hematological referral centers in Brazilian capitals.

Ao contrário dos estudos internacionais, houve um aumento da taxa de mortalidade por doença falciforme no Brasil após a implantação do programa de triagem neonatal, provavelmente devido à melhoria do acesso ao diagnóstico. O objetivo deste estudo foi avaliar as diferenças na tendência temporal da taxa de mortalidade por doença falciforme e idade mediana ao morrer no Brasil, considerando as medidas implementadas para ampliar o diagnóstico e melhorar o acesso à saúde no país e no cenário internacional. As séries temporais foram extraídas do Sistema de Informação sobre Mortalidade de 1996 a 2019. Mudanças na magnitude da taxa de mortalidade e na idade mediana ao morrer foram verificadas via modelos de regressão segmentada, estratificados por sexo, região de residência e idade. A maioria dos óbitos ocorreu entre jovens, pretos ou pardos, e habitantes das regiões Sudeste e Nordeste. Houve um aumento da taxa de mortalidade por doença falciforme até 2010 (13,31%; IC95%: 6,37; 20,70), especialmente em indivíduos com 30 anos ou mais (12,78%; IC95%: 2,98; 23,53) e habitantes do Nordeste (12,27%; IC95%: 8,92; 15,72). A maioria dos óbitos ocorreu durante a segunda década de vida (3,01 óbitos/milhão), com um aumento de 59% na idade mediana ao morrer no Brasil (de 27,6 para 30,3 anos), mais acentuada entre mulheres e na Região Norte. O aumento observado na sobrevivência da doença falciforme no Brasil ainda é muito menor do que em países desenvolvidos e com disparidades regionais, provavelmente pela falta de acesso aos serviços de saúde e aos tratamentos recentes, como a hidroxiureia, que ainda é restrita aos centros de referência hematológicos das capitais brasileiras.

A diferencia de los estudios internacionales, en Brasil se produjo un aumento de la tasa de mortalidad por enfermedad de células falciformes tras la implantación del programa de tamizaje neonatal, probablemente debido a la mejora del acceso al diagnóstico. El objetivo del estudio es determinar las diferencias en la tendencia temporal de la tasa de mortalidad y la edad media de muerte por enfermedad de células falciformes en Brasil, teniendo en cuenta las medidas implementadas para ampliar el diagnóstico y mejorar el acceso a la atención sanitaria en el país y en el escenario internacional. Las series temporales fueron extraídas del Sistema de Información sobre de Mortalidad de 1996 a 2019. Los cambios en la magnitud de la tasa de mortalidad y la edad media de la muerte se identificaron con modelos de regresión segmentados, estratificados por sexo, región de residencia y edad. La mayoría de las muertes ocurrieron en personas de color, adultos jóvenes y los habitantes del sureste y noreste. Hubo un aumento de la tasa de mortalidad por enfermedad de células falciformes hasta 2010 (13,31%; IC95%: 6,37; 20,70), sobre todo en individuos de 30 años o más (12,78%; IC95%: 2,98; 23,53) y en el Noreste (12,27%; IC95%: 8,92; 15,72). La mayoría de las muertes ocurrió en la segunda década de la vida (3,01 muertes/millón), con un aumento del 59% en la edad media de muerte en Brasil, de 27,6 a 30,3 años, más pronunciado en las mujeres y en el Norte. La ganancia observada en la supervivencia de la enfermedad de células falciformes en Brasil es todavía muy inferior a la de los países desarrollados y con disparidades regionales, probablemente debido a la falta de acceso a la asistencia sanitaria y a los tratamientos recientes, como la hidroxiurea, todavía restringidos a los centros de referencia hematológica de las capitales brasileñas.

Prevalence of children with special healthcare needs: An epidemiological survey in Brazil.

PURPOSE: We aimed to estimate the prevalence and delineate the profile of children with special healthcare needs (CSHCN) in the three municipalities of Brazil's southern and southeastern regions from 2015 to 2017. DESIGN AND METHODS: This cross-sectional study included 6853 children aged 0-11 years. Participants were selected through complex sampling in 32 primary healthcare units. The Brazilian version of the Children with Special Healthcare Needs Screener© and a questionnaire were used to identify sociodemographic and family characteristics, health status, and health services utilization. Simple and multiple logistic regression models were used to evaluate the association between family and child characteristics and prevalence (P < 0.05). RESULTS: The prevalence of CSHCN was 25.3% (95% confidence interval: 21.0-30.0). Most participants required health services or were on long-term medication for a current chronic condition; approximately 53% of CSHCN had no formally recorded diagnoses. The most frequent health problems were respiratory conditions, asthma, and allergies. Approximately 60% of the CSHCN patients underwent follow-up examinations of the specialties pneumology, pediatrics, otorhinolaryngology, speech therapy, neurology, and psychology. Children of school age, of male sex, with premature birth, with a history of recurrent hospitalization, from non-nuclear families, and from underprivileged social classes were identified as risk factors for classification as CSHCN. PRACTICE IMPLICATION: These results contribute to the unprecedented mapping of these children in healthcare networks in Brazil. CONCLUSION: The high prevalence of CSHCN in medium and large municipalities in the southern and southeastern regions was associated with the child's previous health conditions and family structure.

Clinical profile of dengue in the elderly using surveillance data from two epidemics.

BACKGROUND: Population aging and mobility have increased the exposure of elderly individuals to dengue. This study evaluated the clinical features of dengue in the elderly during the epidemic (2008 and 2012) and interepidemic (2009 and 2010) periods. METHODS: This cross-sectional study was based on dengue surveillance data from Rio de Janeiro, Brazil: 2008 (n=31,210), 2009‒2010 (n=2,884), and 2012 (n=30,773). The analysis was stratified by age group (<60 and ≥60 years). RESULTS: Case-fatality rates were higher in the elderly. In 2008, elderly individuals were found to be more prone to hematuria and thrombocytopenia. CONCLUSIONS: These results can improve the understanding of dengue in elderly individuals who live in or travel to tropical regions.

Clinical profile of dengue in the elderly using surveillance data from two epidemics

ABSTRACT Background: Population aging and mobility have increased the exposure of elderly individuals to dengue. This study evaluated the clinical features of dengue in the elderly during the epidemic (2008 and 2012) and interepidemic (2009 and 2010) periods. Methods: This cross-sectional study was based on dengue surveillance data from Rio de Janeiro, Brazil: 2008 (n=31,210), 2009‒2010 (n=2,884), and 2012 (n=30,773). The analysis was stratified by age group (<60 and ≥60 years). Results: Case-fatality rates were higher in the elderly. In 2008, elderly individuals were found to be more prone to hematuria and thrombocytopenia. Conclusions: These results can improve the understanding of dengue in elderly individuals who live in or travel to tropical regions.

Clinical prediction rules for the diagnosis of neuritis in leprosy.

BACKGROUND: Diagnosing neuritis in leprosy patients with neuropathic pain or chronic neuropathy remains challenging since no specific laboratory or neurophysiological marker is available. METHODS: In a cross-sectional study developed at a leprosy outpatient clinic in Rio de Janeiro, RJ, Brazil, 54 individuals complaining of neural pain (single or multiple sites) were classified into two groups ("neuropathic pain" or "neuritis") by a neurological specialist in leprosy based on anamnesis together with clinical and electrophysiological examinations. A neurologist, blind to the pain diagnoses, interviewed and examined the participants using a standardized form that included clinical predictors, pain features, and neurological symptoms. The association between the clinical predictors and pain classifications was evaluated via the Pearson Chi-Square or Fisher's exact test (p < 0.05). RESULTS: Six clinical algorithms were generated to evaluate sensitivity and specificity, with 95% confidence intervals, for clinical predictors statistically associated with neuritis. The most conclusive clinical algorithm was: pain onset at any time during the previous 90 days, or in association with the initiation of neurological symptoms during the prior 30-day period, necessarily associated with the worsening of pain upon movement and nerve palpation, with 94% of specificity and 35% of sensitivity. CONCLUSION: This algorithm could help physicians confirm neuritis in leprosy patients with neural pain, particularly in primary health care units with no access to neurologists or electrophysiological tests.

[Methodological quality assessment of guidelines for surveillance and clinical management of dengue and chikungunya]. / Avaliação da qualidade metodológica de diretrizes de vigilância e manejo clínico de dengue e chikungunya.

The study aimed to assess the methodological quality of guidelines by the Brazilian Ministry of Health, Pan American Health Organization (PAHO), and World Health Organization (WHO) on surveillance and clinical management of dengue and chikungunya. This was a descriptive study in which the tool Appraisal of Guidelines for Research & Evaluation Reporting Checklist II (AGREE II) was applied by four evaluators in independent and masked fashion for six guidelines. Each evaluator assigned a score from 1 (disagree completely) to 7 (agree completely) to the 23 items in the AGREE II domains: scope and purpose; stakeholder involvement; rigor in the development; clarity of presentation; applicability; and editorial independence. The dengue guidelines by PAHO (mean = 5.2, SD = 0.8) and WHO (mean = 4.5, SD = 0.5) obtained the highest overall scores and were recommended with modifications by all the evaluators, while the Brazilian Ministry of Health guidelines (mean = 2.7, SD = 0.4) were not recommended by any of them. Meanwhile, the chikungunya guidelines scored low (means from 2.2 to 3.0) for all three agencies. The domains with the greatest conformity were "clarity of presentation" (median 84.7%) and "scope and purpose" (77.1%), while those with the lowest conformity were "editorial independence" (5.2%) and "rigor in development" (9.1%). The study identified gaps in the guidelines' methodological quality, mainly in transparency of the work processes, selection of scientific evidence, and formulation of recommendations, besides lack of clarity in financing and possible conflicts of interest.

Rapid immunochromatographic tests for the diagnosis of dengue: a systematic review and meta-analysis.

Dengue is an important arthropod-borne viral disease in terms of morbidity, mortality, economic impact and challenges in vector control. Benchmarks are expensive, time consuming and require trained personnel. Preventing dengue complications with rapid diagnosis has been based on the testing of easy-to-perform optimized immunochromatographic methods (ICT). This is a systematic meta-analysis review of the diagnostic accuracy of IgA, NS1, IgM and/or IgG ICT studies in suspected cases of acute or convalescent dengue, using a combination of RT-PCR, ELISA NS1, IgM IgG or viral isolation as a reference standard. This protocol was registered in PROSPERO (CRD42014009885). Two pairs of reviewers searched the PubMed, BIREME, Science Direct, Scopus, Web of Science, Ovid MEDLINE JBrigs, SCIRUS and EMBASE databases, selected, extracted, and quality-assessed by QUADAS 2. Of 3,783 studies, we selected 57, of which 40 in meta-analyses according to the analyte tested, with high heterogeneity (I2 > 90%), as expected for diagnostic tests. We detected higher pooled sensitivity in acute phase IgA (92.8%) with excellent (90%) specificity. ICT meta-analysis with NS1/IgM/IgG showed 91% sensitivity and 96% specificity. Poorer screening performance was for IgM/IgG ICT (sensitivity = 56%). Thus, the studies with NS1/IgM/IgG ICT showed the best combined performance in the acute phase of the disease.

Diagnostic parameters and reliability of four rapid immunochromatographic tests for dengue 4

ABSTRACT Background: Although performance of rapid immunochromatographic tests (RITs) for dengue virus (DENV) serotypes 1, 2 and 3 is relatively settled, evidence on accuracy of RITs for DENV-4 are based on studies with small sample sizes and with discrepant results. Objectives: To assess accuracy and inter-observer agreement of RITs targeting dengue nonstructural protein-1 (NS1) antigen - Dengue NS1-Bioeasy™, Dengue NS1 Ag Strip-Bio-Rad™, IVB Dengue Ag NS1-Orangelife™ and Dengue NS1-K130-Bioclin™ in DENV-4 samples. Methods: Study sample (n = 324) included adults presenting at an emergency unit in Rio de Janeiro, Brazil, with fever of ≤72 h and two or more dengue symptoms. A serum sample from each patient was tested by each RIT. A positive reverse-transcription polymerase chain reaction was considered as the reference standard for dengue diagnosis. The diagnostic parameters analyzed for each RIT were sensitivity, specificity, positive and negative predictive values, and likelihood ratios. Each RIT was read by homogeneous (two junior nurses) or heterogeneous (one junior nurse and one senior biologist) pairs. Agreement was estimated by simple kappa with 95% confidence interval, positive (Ppos) and negative (Pneg) proportion concordance and prevalence and bias adjusted kappa, rated from poor (k < 0.0) to almost perfect (0.8 < k < 1.0), and perfect (k = 1). Results: NS1 RITs for DENV-4 diagnosis showed high specificity (95.9%-99.4%), but low sensitivity (14.7%-45.4%). Bioeasy™ had the best performance, with a positive likelihood ratio of 26.0 (95% CI: 8.4;81.0). Inter-observer agreement was almost perfect for all evaluated RITs. Mismatches in confirmed dengue were more common for the Bioclin™ (Ppos 88.3-90.0 %) and Orangelife™ (Ppos 91.7-94.1 %) tests. Conclusions: For DENV-4, the tested RITs had high specificity, but lower sensitivity compared to published results for other serotypes. They should not be used for screening purposes. Different brands may have very different performances. This should be considered upon deciding of using RITs in DENV-4 outbreaks.

Diagnostic parameters and reliability of four rapid immunochromatographic tests for dengue 4.

BACKGROUND: Although performance of rapid immunochromatographic tests (RITs) for dengue virus (DENV) serotypes 1, 2 and 3 is relatively settled, evidence on accuracy of RITs for DENV-4 are based on studies with small sample sizes and with discrepant results. OBJECTIVES: To assess accuracy and inter-observer agreement of RITs targeting dengue nonstructural protein-1 (NS1) antigen - Dengue NS1-Bioeasy™, Dengue NS1 Ag Strip-Bio-Rad™, IVB Dengue Ag NS1-Orangelife™ and Dengue NS1-K130-Bioclin™ in DENV-4 samples. METHODS: Study sample (n = 324) included adults presenting at an emergency unit in Rio de Janeiro, Brazil, with fever of ≤72 h and two or more dengue symptoms. A serum sample from each patient was tested by each RIT. A positive reverse-transcription polymerase chain reaction was considered as the reference standard for dengue diagnosis. The diagnostic parameters analyzed for each RIT were sensitivity, specificity, positive and negative predictive values, and likelihood ratios. Each RIT was read by homogeneous (two junior nurses) or heterogeneous (one junior nurse and one senior biologist) pairs. Agreement was estimated by simple kappa with 95% confidence interval, positive (Ppos) and negative (Pneg) proportion concordance and prevalence and bias adjusted kappa, rated from poor (k < 0.0) to almost perfect (0.8 < k < 1.0), and perfect (k = 1). RESULTS: NS1 RITs for DENV-4 diagnosis showed high specificity (95.9%-99.4%), but low sensitivity (14.7%-45.4%). Bioeasy™ had the best performance, with a positive likelihood ratio of 26.0 (95% CI: 8.4;81.0). Inter-observer agreement was almost perfect for all evaluated RITs. Mismatches in confirmed dengue were more common for the Bioclin™ (Ppos 88.3-90.0 %) and Orangelife™ (Ppos 91.7-94.1 %) tests. CONCLUSIONS: For DENV-4, the tested RITs had high specificity, but lower sensitivity compared to published results for other serotypes. They should not be used for screening purposes. Different brands may have very different performances. This should be considered upon deciding of using RITs in DENV-4 outbreaks.

Avaliação da qualidade metodológica de diretrizes de vigilância e manejo clínico de dengue e chikungunya / Methodological quality assessment of guidelines for surveillance and clinical management of dengue and chikungunya / Evaluación de la calidad metodológica de directrices de vigilancia y manejo clínico del dengue y chikungunya

Resumo: A pesquisa objetivou avaliar a qualidade metodológica de diretrizes do Ministério da Saúde brasileiro, da Organização Pan-Americana da Saúde (OPAS) e da Organização Mundial da Saúde (OMS) sobre vigilância e manejo clínico de dengue e chikungunya. Trata-se de um estudo descritivo, no qual a ferramenta Appraisal of Guidelines for Research & Evaluation Reporting Checklist II (AGREE II) foi aplicada por quatro avaliadores, de forma independente e mascarada, para seis diretrizes. Cada avaliador atribuiu um escore de 1 (discordo totalmente) a 7 (concordo completamente) aos 23 itens dos domínios do AGREE II: escopo e propósito; envolvimento das partes interessadas; rigor no desenvolvimento; clareza da apresentação; aplicabilidade e independência editorial. As diretrizes de dengue da OPAS (média = 5,2, DP = 0,8) e da OMS (média = 4,5, DP = 0,5) obtiveram maiores pontuações globais, sendo recomendadas com modificações por todos os avaliadores, e a do Ministério da Saúde (média = 2,7, DP = 0,4) não foi recomendada por um deles. Já as pontuações das diretrizes de chikungunya foram baixas (médias variando de 2,2 a 3,0) independentemente do órgão que as elaborou. Os domínios com maior conformidade foram "clareza da apresentação" (mediana de 84,7%) e "escopo e propósito" (77,1%), e os de menor conformidade foram "independência editorial" (5,2%) e "rigor no desenvolvimento" (9,1%). O estudo identificou lacunas na qualidade metodológica das diretrizes relacionadas, principalmente, à transparência nos processos de busca, seleção das evidências científicas e formulação das recomendações, além de falta de clareza quanto ao financiamento e possíveis conflitos de interesses.

Abstract: The study aimed to assess the methodological quality of guidelines by the Brazilian Ministry of Health, Pan American Health Organization (PAHO), and World Health Organization (WHO) on surveillance and clinical management of dengue and chikungunya. This was a descriptive study in which the tool Appraisal of Guidelines for Research & Evaluation Reporting Checklist II (AGREE II) was applied by four evaluators in independent and masked fashion for six guidelines. Each evaluator assigned a score from 1 (disagree completely) to 7 (agree completely) to the 23 items in the AGREE II domains: scope and purpose; stakeholder involvement; rigor in the development; clarity of presentation; applicability; and editorial independence. The dengue guidelines by PAHO (mean = 5.2, SD = 0.8) and WHO (mean = 4.5, SD = 0.5) obtained the highest overall scores and were recommended with modifications by all the evaluators, while the Brazilian Ministry of Health guidelines (mean = 2.7, SD = 0.4) were not recommended by any of them. Meanwhile, the chikungunya guidelines scored low (means from 2.2 to 3.0) for all three agencies. The domains with the greatest conformity were "clarity of presentation" (median 84.7%) and "scope and purpose" (77.1%), while those with the lowest conformity were "editorial independence" (5.2%) and "rigor in development" (9.1%). The study identified gaps in the guidelines' methodological quality, mainly in transparency of the work processes, selection of scientific evidence, and formulation of recommendations, besides lack of clarity in financing and possible conflicts of interest.

Resumen: El objetivo de la investigación fue evaluar la calidad metodológica de las directrices del Ministerio de Salud (MS) brasileño, de la Organización Panamericana de la Salud (OPAS) y de la Organización Mundial de la Salud (OMS) sobre vigilancia y manejo clínico del dengue y chikungunya. Se trata de un estudio descriptivo, en el cual la herramienta Appraisal of Guidelines for Research & Evaluation Reporting Checklist II (AGREE II) fue aplicada por parte de cuatro evaluadores, de forma independiente y oculta, en seis directrices. Cada evaluador atribuyó una puntuación de 1 (en desacuerdo totalmente) a 7 (concuerdo completamente) a los 23 ítems de los dominios del AGREE II: alcance y propósito; implicando las partes interesadas; rigor en el desarrollo; claridad de la presentación; aplicabilidad e independencia editorial. Las directrices del dengue de la OPAS (media = 5,2, DP = 0,8) y OMS (media = 4,5, DP = 0,5) obtuvieron mayores puntuaciones globales, siendo recomendadas con modificaciones por todos los evaluadores, respecto a las del Ministerio de Salud (media = 2,7, DP = 0,4) no se recomendó por parte de uno de ellos. Ya las puntuaciones de las directrices de chikungunya fueron bajas (medias variando de 2,2 a 3,0), independientemente del órgano que las elaboró. Los dominios con mayor conformidad fueron "clareza de la presentación" (media de 84,7%) y "alcance y propósito" (77,1%), mientras que los de menor conformidad fueron "independencia editorial" (5,2%) y "rigor en el desarrollo" (9,1%). El estudio identificó lagunas en la calidad metodológica de las directrices relacionadas, principalmente, respecto a la transparencia en los procesos de búsqueda, selección de las evidencias científicas y formulación de las recomendaciones, además de la falta de claridad respecto a la financiación y posibles conflictos de intereses.

Rapid immunochromatographic tests for the diagnosis of dengue: a systematic review and meta-analysis / Testes imunocromatográficos rápidos para o diagnóstico da dengue: uma revisão sistemática e metanálise / Pruebas inmunocromatográficas rápidas para la diagnosis del dengue: una revisión sistemática y metaanálisis

Abstract: Dengue is an important arthropod-borne viral disease in terms of morbidity, mortality, economic impact and challenges in vector control. Benchmarks are expensive, time consuming and require trained personnel. Preventing dengue complications with rapid diagnosis has been based on the testing of easy-to-perform optimized immunochromatographic methods (ICT). This is a systematic meta-analysis review of the diagnostic accuracy of IgA, NS1, IgM and/or IgG ICT studies in suspected cases of acute or convalescent dengue, using a combination of RT-PCR, ELISA NS1, IgM IgG or viral isolation as a reference standard. This protocol was registered in PROSPERO (CRD42014009885). Two pairs of reviewers searched the PubMed, BIREME, Science Direct, Scopus, Web of Science, Ovid MEDLINE JBrigs, SCIRUS and EMBASE databases, selected, extracted, and quality-assessed by QUADAS 2. Of 3,783 studies, we selected 57, of which 40 in meta-analyses according to the analyte tested, with high heterogeneity (I2 > 90%), as expected for diagnostic tests. We detected higher pooled sensitivity in acute phase IgA (92.8%) with excellent (90%) specificity. ICT meta-analysis with NS1/IgM/IgG showed 91% sensitivity and 96% specificity. Poorer screening performance was for IgM/IgG ICT (sensitivity = 56%). Thus, the studies with NS1/IgM/IgG ICT showed the best combined performance in the acute phase of the disease.

Resumo: A dengue é uma importante arbovirose em termos de morbidade, mortalidade, impacto econômico e controle do vetor. Os testes de referência são dispendiosos e demorados e exigem pessoal capacitado. A prevenção das complicações da dengue com o diagnóstico rápido tem tomado como base a testagem com métodos imunocromatográficos (ICT). O estudo é uma revisão sistemática e meta-análise da acurácia diagnóstica de estudos de ICT de IgA, NS1, IgM e/ou IgG em casos suspeitos de dengue aguda ou convalescente, usando uma combinação de RT-PCR, ELISA NS1, IgM IgG ou isolamento viral como padrão de referência. O projeto foi registrado na base PROSPERO (CRD42014009885). Dois pares de revisores realizaram as buscas nas bases de dados PubMed, BIREME, Science Direct, Scopus, Web of Science, Ovid MEDLINE JBrigs, SCIRUS e EMBASE, além da seleção, extração e avaliação de qualidade com a ferramenta QUADAS 2. A partir de 3.783 estudos, selecionamos 57, dos quais 40 foram incluídos nas meta-análises de acordo com o analito testado, com alta heterogeneidade (I2 > 90%), conforme esperado para testes diagnósticos. Foi detectada a maior sensibilidade conjunta no IgA de fase aguda (92,8%), com excelente especificidade (90%). A meta-análise de ICT com NS1/IgM/IgG mostrou sensibilidade de 91% e especificidade de 96%. O pior desempenho para triagem foi com o ICT de IgM/IgG (sensibilidade = 56%). Portanto, os estudos de ICT com NS1/IgM/IgG mostraram o melhor desempenho combinado na fase aguda da doença.

Resumen: El dengue es una importante enfermedad arboviral, en términos de morbilidad, mortalidad, impacto económico y desafíos en el control del vector. Las mejores prácticas son caras, consumen mucho tiempo y requieren personal formado. Prevenir las complicaciones del dengue con un rápido diagnóstico se ha basado en pruebas con métodos inmunocromatográficos optimizados fáciles de realizar (ICT por sus siglas en inglés). Se trata de una revisión sistemática de metaanálisis sobre la precisión diagnóstica de estudios de IgA, NS1, IgM y/o IgG ICT en casos sospechosos de fases agudas o convalecientes de dengue, usando la combinación de RT-PCR, ELISA NS1, IgM IgG o el aislamiento viral como referencia estándar. Este proyecto se registró en PROSPERO (CRD42014009885). Dos parejas de revisores investigaron en las bases de datos de: PubMed, BIREME, Science Direct, Scopus, Web of Science, Ovid MEDLINE JBrigs, SCIRUS y EMBASE, seleccionaron, extrajeron, y realizaron la evaluación de calidad mediante QUADAS 2. De 3.783 estudios, se seleccionaron 57, de los cuales 40 fueron metaanálisis, según el analito probado, con una alta heterogeneidad (I2 > 90%), como se esperaba en las pruebas de diagnóstico. Detectamos una sensibilidad más alta combinada en la fase aguda IgA (92.8%) con una excelente (90%) especificidad. Los metaanálisis ICT con NS1/IgM/ IgG mostraron un 91% de sensibilidad y un 96% de especificidad. Se produjo un rendimiento más pobre en el diagnóstico IgM/IgG ICT (sensibilidad = 56%). De este modo, los estudios con NS1/IgM/IgG ICT mostraron un rendimiento mejor combinado en la fase aguda de la enfermedad.

Socio-demographic inequalities in the clinical characteristics of dengue haemorrhagic fever in the city of Rio de Janeiro, Brazil, 2007-2008.

In 2007-2008, the city of Rio de Janeiro underwent an epidemiological change, with increases in the incidence in children and in severe forms of dengue. To describe the clinical profile and spatial distribution of dengue we performed an ecological study based on dengue surveillance data using the Brazilian classification (2005): dengue fever, dengue haemorrhagic fever (DHF) and dengue with complications. χ 2 test was used to describe the clinical and socio-demographic variables (P < 0.05). Spatial distribution of incidence and case-fatality was explored with thematic maps, Moran and Geary indices (P < 0.05). Of the total of 151 527 dengue cases, 38 808 met the inclusion criteria; 42.4% <18 years; 22.9% dengue with complications and 2.7% DHF. Case-fatality was higher in infants (1.4%) and in DHF (7.7%). Bleeding was more frequent in adolescents and adults while plasma leakage was more common in preschoolers and schoolchildren. The highest incidence was found in the West Zone of the city, in a different area from that of the worst case-fatality (P < 0.05). Although the incidence of DHF was higher in schoolchildren, infants showed higher case-fatality. The area with the highest case-fatality did not present the highest incidence, which suggests problems in the organization of health services.

Effects of antiretroviral treatment and nadir CD4 count in progression to cardiovascular events and related comorbidities in a HIV Brazilian cohort: a multi-stage approach.

The use of highly active antiretroviral therapy has resulted in changes of comorbidity profile in people living with HIV (PLHIV), increasing non-AIDS-related events. The occurrence of cardiovascular events is greater in PLHIV, but the mechanism responsible for it is still controversial. This article aimed to investigate factors associated with the progression to cardiovascular events in PLHIV using HAART. A 15-years cohort study with 1135 PLHIV was conducted in Rio de Janeiro-Brazil. Clinical progression was stratified in five states: No comorbidities (s1), arterial hypertension (s2), lipid abnormalities (s3), hypertension and lipid abnormalities (s4) and major cardiovascular events (stroke, coronary artery disease, thrombosis or death) (s5). Semi-Markov models evaluated the effects of cardiovascular traditional factors, treatment and clinical covariates on transitions between these states. Hazard Ratios (HR) and 95% confidence intervals (CI) were provided. In addition to traditional factors (age, sex, educational level and skin color), the development of one comorbidity (lipid abnormalities or hypertension) increased in patients with low nadir CD4 (<50 cells/mm3), (HR = 1.59, CI 1.11-2.28 and 1.36, CI 1.11-1.66, respectively). The risk to experience a second comorbidity (s3→s4) increased 75% with low nadir CD4. Age was the only factor that increased the risk of major cardiovascular events once having lipid abnormalities with or without hypertension (s3,s4→s5). The prolonged use of certain antiretroviral drugs (abacavir, didanosine, ritonavir, lopinavir, amprenavir and fosamprenavir) increased the risk of direct transition (s1→s5) to major cardiovascular events (HR = 5.29, CI 1.16-24.05). This analysis suggests that prolonged use of certain antiretroviral drugs led directly to major cardiovascular events, while low nadir CD4 only affected the occurrence of lipid abnormalities and hypertension. Management strategies, including rational use of complex exams (such as, computed-tomography angiography), statins and antihypertensives, should be developed based on the distinct roles of antiretroviral use and of HIV infection itself on the progression to cardiovascular events.

Correction to: Accuracy and reliability of an NS1 rapid immunochromatographic test for DENV-1 diagnosis at point of care and in the laboratory.

An error occurred during the publication of the original article [1].

Detection of Zika Virus in April 2013 Patient Samples, Rio de Janeiro, Brazil.

We tested 210 dengue virus‒negative samples collected from febrile patients during a dengue virus type 4 outbreak in Rio de Janeiro in April 2013 and found 3 samples positive for Zika virus. Our findings support previously published entomological data suggesting Zika virus was introduced into Brazil during October 2012-May 2013.

Precisão e confiabilidade de um teste imuno-cromatográfico rápido NS1 para diagnóstico DENV-1 no ponto de atendimento e no laboratório.

BACKGROUND: Rapid immunochromatographic tests (ICT) for dengue non-structural protein 1 (NS1) have shown good performance for diagnosing acute-phase dengue in serum in laboratory settings, but rarely have been assessed in whole blood and at point of care (POC). This study compare the accuracy and inter- and intra-observer reliability of the NS1 Bioeasy™ ICT in whole blood at POC versus serum in the laboratory, during a DENV-1 epidemic. METHODS: Cross-sectional study involving 144 adults spontaneously demanding care in an emergency department within 4 days of onset of acute febrile illness. Accuracy of NS1 Bioeasy™ ICT was compared in whole blood and serum, both at 15 and 30 min, blinded to the reference RT-PCR or NS1 ELISA. Non-dengue patients were also tested for Zika virus with RT-PCR. Reliability of whole blood and serum readings by the same or different observers was measured by simple kappa (95% CI). RESULTS: At 15 min, sensitivity (Sn) of NS1 Bioeasy™ ICT in whole blood/POC was 76.7% (95% CI: 68.0-84.1) and specificity (Sp) was 87.0% (95% CI: 66.4-97.2). Sn in serum/laboratory was 82% (95% CI: 74.1-88.6) and Sp 100% (95% CI: 85.8-100). Positive likelihood ratio was 5.9 (95% CI: 2.0-17.0) for whole blood/POC and 19.8 (95% CI: 2.9-135.1) for serum/laboratory. Reliability of matched readings of whole blood/POC and serum/laboratory by the same observer (k = 0.83, 95% CI: 0.74-0.93) or different observers (k = 0.81, 95% CI: 0.72-0.92) was almost perfect, with higher discordant levels in the absence of dengue. Results did not differ statistically at 5%. CONCLUSIONS: NS1 Bioeasy™ ICT in DENV-1 epidemics is a potentially confirmatory test. Invalid results at 15 min should be reread at 30 min. To optimize impact of implementing ICT in the management of false-negatives it should be incorporated into an algorithm according to setting and available specimen. TRIAL REGISTRATION: UTN U1111-1145-9451 .

Severe infection in patients with rheumatoid arthritis taking anakinra, rituximab, or abatacept: a systematic review of observational studies.

A question is raised about an increased risk of severe infection from the use of biological drugs in patients with rheumatoid arthritis. This systematic review of observational studies aimed at assessing the risk of severe infection associated with the use of anakinra, rituximab, and abatacept in patients with rheumatoid arthritis. The following databases were searched: PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, Exerpta Medica Database, Scielo, and Lilacs up to July 2010. Severe infections were defined as those life-threatening ones in need of the use of parenteral antibiotics or of hospitalization. Longitudinal observational studies were selected without language restriction, involving adult patients diagnosed with rheumatoid arthritis and who used anakinra, rituximab, or abatacept. In four studies related to anakinra, 129 (5.1%) severe infections were related in 2896 patients, of which three died. With respect to rituximab, two studies reported 72 (5.9%) severe infections in 1224 patients, of which two died. Abatacept was evaluated in only one study in which 25 (2.4%) severe infections were reported in 1046 patients. The main site of infection for these three drugs was the respiratory tract. One possible explanation for the high frequency of severe infections associated with anakinra may be the longer follow-up time in the selected studies. The high frequency of severe infections associated with rituximab could be credited to the less strict inclusion criteria for the patients studied. Therefore, infection monitoring should be cautious in patients with rheumatoid arthritis in use of these three drugs.

Severe infection in patients with rheumatoid arthritis taking anakinra, rituximab, or abatacept: a systematic review of observational studies / Infecções graves em pacientes com artrite reumatoide em uso de anakinra, rituximab ou abatacept: revisão sistemática de estudos observacionais

ABSTRACT A question is raised about an increased risk of severe infection from the use of biological drugs in patients with rheumatoid arthritis. This systematic review of observational studies aimed at assessing the risk of severe infection associated with the use of anakinra, rituximab, and abatacept in patients with rheumatoid arthritis. The following databases were searched: PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, Exerpta Medica Database, Scielo, and Lilacs up to July 2010. Severe infections were defined as those life-threatening ones in need of the use of parenteral antibiotics or of hospitalization. Longitudinal observational studies were selected without language restriction, involving adult patients diagnosed with rheumatoid arthritis and who used anakinra, rituximab, or abatacept. In four studies related to anakinra, 129 (5.1%) severe infections were related in 2896 patients, of which three died. With respect to rituximab, two studies reported 72 (5.9%) severe infections in 1224 patients, of which two died. Abatacept was evaluated in only one study in which 25 (2.4%) severe infections were reported in 1046 patients. The main site of infection for these three drugs was the respiratory tract. One possible explanation for the high frequency of severe infections associated with anakinra may be the longer follow-up time in the selected studies. The high frequency of severe infections associated with rituximab could be credited to the less strict inclusion criteria for the patients studied. Therefore, infection monitoring should be cautious in patients with rheumatoid arthritis in use of these three drugs.

RESUMO Existe um questionamento sobre aumento do risco de infecções graves pelo uso de medicamentos biológicos por pacientes com artrite reumatoide. Esta revisão sistemática de estudos observacionais objetivou avaliar o risco de infecções graves associadas ao uso de anakinra, rituximab e abatacept em pacientes com artrite reumatoide. Foram pesquisadas as bases PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, Exerpta Medica Database, Scielo e Lilacs até julho/2010. Infecções graves foram definidas como aquelas com de risco de vida, necessidade de antibióticos parenterais ou de hospitalização. Foram selecionados estudos observacionais longitudinais, sem restrição de idioma, que envolviam pacientes adultos com diagnóstico de artrite reumatoide que usaram anakinra, rituximab, abatacept. Em quatro estudos relacionados ao anakinra, foram relatadas 129 (5,1%) infecções graves em 2.896 pacientes, dos quais três evoluíram para óbito. Sobre o rituximab, dois estudos relataram 72 (5,9%) infecções graves em 1.224 pacientes, dos quais dois evoluíram para óbito. O abatacept foi avaliado em apenas um estudo, no qual foram relatadas 25 (2,4%) infecções graves em 1.046 pacientes. O principal sítio de infecção para os três medicamentos foi o trato respiratório. Uma possível explicação para a frequência elevada de infecções graves associadas ao anakinra pode ser o maior tempo de acompanhamento nos estudos selecionados. A frequência elevada de infecções graves associadas ao rituximab poderia ser creditada ao critério menos restrito de inclusão de pacientes. Portanto, deve ser cautelosa a monitoração de infecções nos pacientes com artrite reumatoide que usam esses três medicamentos.