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Dengue is an emerging illness in India, where it is endemic in some areas and sometimes causes yearly epidemics. Each dengue outbreak starts with high death and morbidity, which has a significant socioeconomic impact. As of September 30, 2022, India had 63,280 dengue cases, according to information provided by the National Centre for Vector Borne Diseases Control. North India is most severely impacted by each outbreak. In Uttar Pradesh, the state with the most population in India, there have been 2060 confirmed cases of dengue and 1 mortality till September 2022 reported. Patients are being reported from semi-urban, rural, and urban areas. It is essential to properly monitor disease cases through disease surveillance in order to ensure prompt case management if dengue outbreak control is to be achieved. An efficient diagnostic approach for early diagnosis is urgently required to reduce the severity of the sickness, the length of the hospital stay, and clinical consequences.
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To determine the proportion of dengue non-structural protein 1 (NS1) positives among laboratory confirmed dengue IgM negative patients. Methods: Data for 1 732 samples received from January to October 2017 at the Virus Research and Diagnostic Laboratory (VRDL) for dengue diagnosis were downloaded from the National Institute of Epidemiology server. Samples that were previously reported as IgM negative for dengue diagnosis were identified and their NS1 status was determined using ELISA. Thus, 'missed out' NS1 positives were correlated with the duration of illness. Furthermore, an epidemic curve for the study period was constructed. The increase in positivity rate within and between the months was compared by McNemar's and Pearson's chi-square test, respectively. Results: The reported IgM-negatives were 813, of which, 22.5% (183) were retrospectively positive for NS1 antigen. The addition of NS1 positives revealed by this study has raised the reported positivity across the months that ranged from 8.1% to 29.6%. By analyzing the dengue positives per month and the epidemic curve, the period between January and September, 2017 was identified as non-epidemic while the epidemic started from the month of October, 2017. Conclusions: Acute dengue infection is widely confirmed by detecting NS1 antigen in serum. Missing out of NS1 positives happen due to shortened window period and such cases act as reservoir for further viral transmission. Hence, this study highly emphasizes performing all three tests for dengue diagnosis that warrants the accurate dengue proportion in India.
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To determine the proportion of dengue non-structural protein 1 (NS1) positives among laboratory confirmed dengue IgM negative patients. Methods: Data for 1 732 samples received from January to October 2017 at the Virus Research and Diagnostic Laboratory (VRDL) for dengue diagnosis were downloaded from the National Institute of Epidemiology server. Samples that were previously reported as IgM negative for dengue diagnosis were identified and their NS1 status was determined using ELISA. Thus, 'missed out' NS1 positives were correlated with the duration of illness. Furthermore, an epidemic curve for the study period was constructed. The increase in positivity rate within and between the months was compared by McNemar's and Pearson's chi-square test, respectively. Results: The reported IgM-negatives were 813, of which, 22.5% (183) were retrospectively positive for NS1 antigen. The addition of NS1 positives revealed by this study has raised the reported positivity across the months that ranged from 8.1% to 29.6%. By analyzing the dengue positives per month and the epidemic curve, the period between January and September, 2017 was identified as non-epidemic while the epidemic started from the month of October, 2017. Conclusions: Acute dengue infection is widely confirmed by detecting NS1 antigen in serum. Missing out of NS1 positives happen due to shortened window period and such cases act as reservoir for further viral transmission. Hence, this study highly emphasizes performing all three tests for dengue diagnosis that warrants the accurate dengue proportion in India.
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Objetivo: Se considera que el diagnóstico del dengue es fundamentalmente clínico; sin embargo, las pruebas rápidas basadas en la detección de IgM o NS1/IgM están siendo utilizadas en los servicios de salud. Este estudio determinó la contribución de las pruebas rápidas al diagnóstico de dengue en un área endémica antes de la introducción del virus zika. Metodología: Diseño de corte transversal de pruebas diagnósticas realizado a partir del análisis secundario de un estudio previo en 14 instituciones de salud del Valle del Cauca. Se obtuvo información de 632 participantes con resultados de prueba rápida, diagnóstico clínico y pruebas de referencia ELISA NS1, ELISA IgM y RT-PCR. Se compararon la sensibilidad, especificidad, valores predictivos y razones de verosimilitud del uso solo, en serie, y paralelo de los componentes NS1, IgM, NS1/IgM de la prueba rápida y el diagnóstico clínico con las pruebas Q de Cochran y McNemar para datos pareados. Resultados: La sensibilidad del diagnóstico clínico (61,4% IC95% 56%-66,7%) fue superior a la de las pruebas rápidas (37% IC95% 29,6%-44,7%) (P Conclusión: El diagnóstico clínico tiene una mayor sensibilidad que las pruebas rápidas, pero por si solo no es suficiente para confirmar o descartar dengue. Un resultado positivo en pruebas rápidas en pacientes con diagnóstico clínico de dengue es útil para confirmarlo, pero un resultado negativo no lo descarta.
Objective: Dengue diagnosis is considered to be mainly clinical; however, rapid tests that detect IgM or NS1/IgM are being used in health services. This study assessed the contribution of rapid tests to dengue diagnosis in an endemic area before the emergence of zika virus in Colombia. Methods: Cross-sectional study of diagnostic tests based on a secondary analysis of a previous study in 14 health care institutions in Valle del Cauca department. Results of dengue rapid test, clinical diagnosis, and reference tests ELISA NS1, ELISA IgM, and RT-PCR were obtained for 632 participants. The sensitivity, specificity, predictive values and likelihood ratios of the use alone, serial and parallel combinations of NS1, IgM, NS1/IgM of the rapid test and clinical diagnosis were compared using Cochran´s Q and MacNemar tests for paired data. Results: The sensitivity of clinical diagnosis (61.4% 95%IC 56-66.7) was higher than the sensitivity of rapid tests (37% 95% IC 29.6-44.7) (P<0.001). The serial used of NS1/IgM rapid test when clinical diagnosis was negative increased the sensitivity to 79.5% and, the serial use when clinical diagnosis was positive increased the specificity (from 66.3% to 98.7%). However, the latter decreased the sensitivity to 32.2%. While all negative likelihood ratios (LR-) were close to 1, the serial use of rapid tests when clinical diagnosis was positive had LR+ higher than 10. Conclusion: The clinical diagnosis is more sensitive than rapid tests, but by itself does not confirm or rule out dengue. A positive result in rapid tests is useful to confirm dengue but a negative result does not rule it out.
Subject(s)
Humans , Male , Female , Dengue , Dengue/diagnosis , Zika Virus , Sensitivity and Specificity , Viral Nonstructural Proteins/analysis , Colombia , Clinical Laboratory Techniques , Point-of-Care TestingABSTRACT
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.
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Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Algorithms , Dengue/diagnosis , Cross-Sectional Studies , Bayes Theorem , Sensitivity and Specificity , ColombiaABSTRACT
BACKGROUND The diagnosis of dengue is complex. Until recently, only specialised laboratories were able to confirm dengue infection. However, this has changed with the newly available immunochromatographic rapid tests. Early diagnosis is of great interest, and point-of-care rapid tests have been increasingly used in Brazil. Most of those tests have not undergone validation in the Brazilian population. In this context, we decided to evaluate a rapid test introduced in the Federal District (FD). OBJECTIVES To estimate the accuracy and reliability of the SD Bioeasy Dengue Duo rapid test and its components to detect dengue infections in a consecutive sample of symptomatic residents in the FD, Brazil. METHODS In total, 1353 venous blood samples were collected between 2013 and 2014. Two hundred and six positive samples (cases) and 246 negative samples (non cases) were required for sensitivity and specificity estimation, respectively; for agreement evaluation, we used 401 samples. The reference standard used was a composite of MAC-ELISA, virus isolation and real-time polymerase chain reaction (RT-qPCR). The evaluation was conducted prospectively under field conditions in the public health units of the FD. FINDINGS The results for the overall accuracy of the rapid test (NS1/IgM combined) showed 76% sensitivity and 98% specificity. The sensitivity for the NS1 component (67%) was better than that for the IgM component (35%). The positive likelihood ratio was 46, and the negative likelihood ratio was 0.24. The reliability of the test (NS1/IgM combined) demonstrated crude agreement of 98% (Kappa index 0.94). MAIN CONCLUSIONS The present phase III, large-scale validation study demonstrates that the rapid test SD Bioeasy Dengue Duo has moderate sensitivity (NS1/IgM combined) and high specificity. Therefore, the test is useful in confirming the diagnosis of dengue, but not enough to rule out the diagnosis. Our results also suggest that Dengue virus (DENV) viral load estimated through the RT-qPCR and antibody level measured through the MAC-ELISA could have had a direct influence on the accuracy of the rapid test.
Subject(s)
Humans , Immunoglobulin M/analysis , Dengue/diagnosis , Early Diagnosis , Brazil/epidemiology , Chile/epidemiology , Real-Time Polymerase Chain Reaction , Antibodies, Viral/bloodABSTRACT
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)
Subject(s)
Dengue/complications , Dengue/mortality , Comorbidity , Epidemiology, Descriptive , Retrospective StudiesABSTRACT
Purpose: To find out the most suitable serological investigative procedures to diagnose dengue cases effectively in the laboratory practice identifying primary and secondary cases as well as period of suffering. Materials and Methods: Dengue suspected cases sent to the laboratory in 2012 in central Kolkata by the local physicians were categorised into seven panels according to the investigations asked for such as (1) only dengue‑specific NS1 antigen (2) only IgM antibodies, (3) NS1 + IgM + IgG antibodies, (4) only IgM and IgG, (5) NS1 + IgM, (6) NS1 + IgG and (7) only IgG. Results: Out of 1892 suspected cases, dengue was diagnosed in 725 (38.3%). Through panels I, II, III, IV, V, VI and VII, it was possible to diagnose dengue in (I) 35.98% (435/1209), (II) 37.5% (24/60), (III) 49% (173/354), (IV) 30.8% (68/221), (V) 60.5% (23/38), (VI) 40% (2/5) and (VII) 0 of cases respectively. Detail information such as confirmed diagnosis, duration of the disease (whether early or prolonged) and classification of primary and secondary dengue in such early or prolonged stages would only be possible in panel III, which information would be helpful for effective monitoring and treatment of dengue patients. In all other panels, merely fragmentary information would be obtained. Conclusions: Serodiagnostic tests dengue‑specific NS1 antigen and IgM and IgG antibodies when conducted simultaneously would be able to diagnose confirmed dengue cases categorising primary and secondary dengue along with the duration of the disease, whether early or prolonged.
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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.