Desarrollo de algoritmos clínicos para el diagnóstico del dengue en Colombia / Development of clinical algorithms for the diagnosis of dengue in Colombia

Resumen Introducción. Dado el aumento de la incidencia y la mortalidad por dengue, su diagnóstico es relevante para los países endémicos. Las clasificaciones clínicas y las pruebas de laboratorio existentes tienen un desempeño variable en la práctica clínica, pues su sensibilidad fluctúa entre 45 y 98 %, y su especificidad, entre 4 y 98 %, lo cual se debe, en parte, a la diversidad de contextos en los que se utilizan. Objetivo. Desarrollar algoritmos clínicos para el diagnóstico del dengue en el contexto colombiano. Materiales y métodos. Se hizo un estudio transversal a partir de fuentes secundarias. Se construyeron algoritmos clínicos de diagnóstico del dengue con base en métodos bayesianos que combinaron síntomas, signos y parámetros del hemograma, y se comparó su exactitud diagnóstica con la de las pruebas de referencia. Se hizo una validación externa del algoritmo de mayor exactitud y sensibilidad, comparándolo con la clasificación clínica de la Organización Mundial de la Salud de 1997 y la del 2009, con la guía colombiana del 2010 y con la escala diagnóstica propuesta por el Ministerio de Salud y Protección Social de Colombia en el 2013. Resultados. Se generaron cuatro algoritmos, dos de signos y síntomas y dos que incluyeron el conteo de leucocitos (≤4.500/mm3) o de plaquetas (≤60.000/mm3). El algoritmo de mayor exactitud incluyó los parámetros del hemograma, con una sensibilidad de 76,5 % (IC95% 71,9-80,5) y una especificidad de 46,0 % (IC95% 37,6-54,7). En la validación externa, la sensibilidad fue de 11,1 % (IC95% 4,9-20,7) y la especificidad fue de 91,9 % (IC95% 87,5-93,9). La escala del Ministerio tuvo una sensibilidad de 76,4 % (IC95% 64,9-85,6) y una especificidad de 38,0 % (IC95% 32,8-43,4). Conclusión. La inclusión de los parámetros del hemograma mejoró la sensibilidad de los algoritmos de diagnóstico basados en los signos y los síntomas. Sin embargo, el diagnóstico clínico del dengue sigue siendo un reto para la investigación en salud.

Abstract Introduction: Due to the increase in dengue incidence and mortality, its diagnosis is relevant for endemic countries. Clinical classifications and laboratory tests have a variable performance in clinical practice with a sensitivity level between 45% and 98%, and a specificity level between 4% and 98% partly due to the variety of contexts where they are applied. Objective: To develop clinical algorithms for the diagnosis of dengue in the Colombian context. Materials and methods: A cross-sectional study was conducted based on secondary sources. We constructed clinical diagnostic algorithms of dengue based on Bayesian methods combining symptoms, signs, and blood count parameters, and then we compared them in terms of diagnostic accuracy with gold standard tests. In addition, an external validation of the algorithm with greater accuracy and sensibility was performed comparing it with the WHO-1997 and the WHO-2009 clinical classifications, the Colombian guide for 2010, and the diagnostic scale recommended by the Ministerio de Salud y Protección Social of Colombia for 2013. Results: Four algorithms were generated, two for signs and symptoms, and two that included leukocytes (≤4,500/mm3) and/or platelets (≤160,000/mm3) counts. The most accurate algorithm included blood count parameters with a sensitivity of 76.5% (95%CI: 71.9-80.5) and a specificity of 46.0% (95%CI: 37.6-54.7). In the external validation we found a sensitivity of 11.1% (95%CI: 4.9-20.7) and a specificity of 91.9% (95%CI: 87.5- 93.9). The scale of the Ministerio de Salud had a sensitivity of 76.4% (95%CI: 64.9-85.6) and a specificity of 38.0% (95%CI: 32.8-43.4). Conclusion: The inclusion of blood count parameters improved the sensitivity of diagnostics algorithms based on signs and symptoms. Clinical diagnosis of dengue remains a challenge for health research.

Formas de apresentação e evolução clínica dos óbitos por dengue em residentes no município do Rio de Janeiro em 2012 / Forms of clinical presentation and course of the deaths from dengue in the municipality of Rio de Janeiro in 2012

Objetivo: A dengue tem importância mundial por sua morbidadee abrangência. O presente artigo teve como objetivo descrever as principais características dos óbitos por dengue,ocorridos no Município do Rio de Janeiro (MRJ), durante aepidemia de 2012. Métodos: Foram descritos os 35 casosde óbitos por dengue ocorridos em 2012 neste município. Asvariáveis estudadas foram coletadas a partir das fichas de investigaçãode óbitos por dengue, padronizadas pelo Ministério daSaúde. Resultados: Encontrou-se maior proporção de óbitosentre 50 e 59 e acima de 70 anos, presença de comorbidadesem 77,8%, ligeiro predomínio do sexo masculino e da raça/corpreta. Principais achados hematológicos: leucopenia em 46,8%,leucocitose em 78,1%, hemoconcentração em 39,4% e plaquetopeniaem 87,9%. Na parte bioquímica: aumento de amilaseem 50%, gama GT em 92,8%, transaminase glutâmico oxaloacética(TGO) em 95,2%, transaminase glutâmico pirúvica(TGP) em 80,9%, bilirrubinas em 69,2%, creatina-fosfoquinase(CPK) em 50% e lactato desidrogenase (LDH) em 100%. Derramecavitário foi descrito em 64,3% e espessamento de parededa vesícula biliar em 37,5%. Manifestações atípicas evidenciadas:neurológicas 8,6%, insuficiência hepática 11,4%, insuficiênciarenal 25,7% e sangramento 22,8%. Conclusão: Oacompanhamento de exames laboratoriais e de imagem auxilia omanejo clínico e a predição da gravidade da dengue. Este acompanhamento,juntamente com a estabilização das morbidadespreexistentes, pode reduzir sua letalidade.(AU)

Objectives: Dengue has global significance for its morbidityand scope. This article aims to describe the main features of deathsdue to dengue, during the dengue epidemic in Rio de Janeiro(MRJ) in 2012. Methods: The 35 cases of obit by dengueoccurred in 2012 in this municipality were described. The studiedvariables were collected from the records of investigation of obitby dengue, standardized by the Ministry of Health. Results:Review of 35 deaths due to dengue that occurred in the city ofRio de Janeiro in 2012 showed a higher proportion between agesof 50 and 59 and also greater than 70 years old, the presence ofcomorbidities in 77.8% and a slight prevalence in male gender andin race/color black. Major hematologic findings were leukopenia(46.8%), leukocytosis (78.1%), hemoconcentration (39.4%)and thrombocytopenia (87.9%). Other lab abnormalities wereamylase (50%), gamma GT (92.8%), aspartate aminotransferase(AST) (95.2%), serum glutamate pyruvate transaminase (SGPT)alanine transferase (ALT) in 80.9%, bilirubin in 69.2%, creatinephosphokinase in 50% (5/10) and lactate dehydrogenase in100%. Cavity effusions were described in 60% and thickenedgallbladder in 37.5%. Atypical symptoms that were evident:neurological 8.6%, liver failure, 11.4%, kidney failure, 25.7%and bleeding 22.8%. Conclusion: Monitoring the levelsof hematocrit, platelets, aminotransferases and imaging tests helpthe clinical management and prediction of severity of dengueand, along with the stabilization of preexisting comorbidities,may reduce its lethality.(AU)

Determinación de Anticuerpos IgM contra Virus dengue partir de sangre absorbida en papel filtro: Un método alternativo y sencillo

Objetivo: Se propone como alternativa la obtención de muestras de sangre total en papel filtro, para la determinación de anticuerpos IgM contra dengue, por ser un método de recolección sencillo y no requerir de muchos cuidados en el envío al laboratorio. Materiales y métodos: De 100 pacientes con diagnóstico clínico de dengue clásico, se obtuvieron en forma simultánea, muestras de suero en tubos al vacío y de sangre total en papel filtro. Ambas muestras fueron evaluadas con el método serológico ELISA Captura de IgM a los 30 días de obtenida la muestra. Resultados: De las 100 muestras 25 fueron positivas y 75 negativas en suero, y 24 positivas y 74 negativas en papel filtro. Se obtuvo una concordancia por índice Kappa de 0,97, sensibilidad y especificidad de 96,0% y 98,0% respectivamente; el valor predictivo positivo fue 96,0%, y valor predictivo negativo fue 98,0%. Conclusión: Se evidencia muy buena sensibilidad, especificidad y concordancia en la determinación de IgM contra dengue, al utilizar papel filtro en la obtención de muestra de sangre.

Objective: This study proposes the use of filter paper, in whole blood samples to test for Dengue, as an alternate method, due to the fact that it is very simple and does not require of much detail for shipping samples to the laboratory. Materials and Methods: Using vacutainers and filter papers, whole blood sample obtained simultaneously from 100 patients diagnosed as classic dengue. All samples were tested using IgM capture ELISA. Findings: Out of 100 samples, 25 were positive and 75 were negative in sera, in filter paper 24 positive and 74 negative, with a Kappa concordance index of 0,97 and a sensitivity and specificity of 96,0% and 98,0% respectively: the positive predictive value was 96.0% and the negative predictive value was 98,0%. Conclusions: A very good sensitivity, specificity and concordance in the determination of IgM antibodies against Dengue is evidenced using filter paper when obtaining blood samples.