Clinical signs and symptoms associated with WHO severe dengue classification: a systematic review and meta-analysis.

ABSTRACTThe World Health Organization (WHO) introduced the new dengue classification in 2009. We aimed to assess the association of clinical signs and symptoms with WHO severe dengue classification in clinical practice. A systematic literature search was performed using the databases of PubMed, Embase, and Scopus between 2009 and 2018 according to PRISMA guideline. Meta-analysis was performed with the RevMan software. A random or fixed-effect model was applied to pool odds ratios and 95% confidence intervals of important signs and symptoms across studies. Thirty nine articles from 1790 records were included in this review. In our meta-analysis, signs and symptoms associated with higher risk of severe dengue were comorbidity, vomiting, persistent vomiting, abdominal pain or tenderness, pleural effusion, ascites, epistaxis, gum bleeding, GI bleeding, skin bleeding, lethargy or restlessness, hepatomegaly (>2 cm), increased HCT with decreased platelets, shock, dyspnea, impaired consciousness, thrombocytopenia, elevated AST and ALT, gall bladder wall thickening and secondary infection. This review shows new factors comorbidity, epistaxis, GI and skin bleeding, dyspnea, gall bladder wall thickening and secondary infection may be useful to refine the 2009 classification to triage severe dengue patients.

Comparison of dengue case classification schemes and evaluation of biological changes in different dengue clinical patterns in a longitudinal follow-up of hospitalized children in Cambodia.

BACKGROUND: The World Health Organization (WHO) proposed guidelines on dengue clinical classification in 1997 and more recently in 2009 for the clinical management of patients. The WHO 1997 classification defines three categories of dengue infection according to severity: dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Alternative WHO 2009 guidelines provide a cross-sectional classification aiming to discriminate dengue fever from dengue with warning signs (DWWS) and severe dengue (SD). The primary objective of this study was to perform a comparison of two dengue classifications. The secondary objective was to describe the changes of hematological and biochemical parameters occurring in patients presenting with different degrees of severity during the course of the disease, since progression to more severe clinical forms is unpredictable. METHODOLOGY/PRINCIPAL FINDINGS: We performed a prospective, monocentric, cross-sectional study of hospitalized children in Cambodia, aged from 2 to 15 years old with severe and non-severe dengue. We enrolled 243 patients with acute dengue-like illness: 71.2% were dengue infections confirmed using quantitative reverse transcription PCR or NS1 antigen capture ELISA, of which 87.2% and 9.0% of DF cases were respectively classified DWWS and SD, and 35.9% of DHF were designated SD using an adapted WHO 2009 classification for SD case definition. Systematic use of ultrasound at patient admission was crucial for detecting plasma leakage. No difference was observed in the concentration of secreted NS1 protein between different dengue severity groups. Lipid profiles were different between DWWS and SD at admission, characterized by a decrease in total cholesterol, HDL cholesterol, and LDL cholesterol, in SD. CONCLUSIONS/SIGNIFICANCE: Our results show discrepancies between the two classifications, including misclassification of severe dengue cases as mild cases by the WHO 1997 classification. Using an adapted WHO 2009 classification, SD more precisely defines the group of patients requiring careful clinical care at a given time during hospitalization.

Severe dengue categories as research endpoints-Results from a prospective observational study in hospitalised dengue patients.

Severe dengue was perceived as one clinical disease entity until the WHO 2009 classification stratified it into severe vascular leakage, severe bleeding, and severe organ dysfunction. The objectives of this study were to investigate the potential use of severe dengue categories as endpoints for intervention research. 271 patients with severe dengue among 1734 confirmed dengue patients were followed prospectively in this hospital-based observational study in Latin America and Asia. We compared the distribution of severe dengue categories according to gender and age (below/above 15y), and determined the relative frequency and the overlap of severe dengue categories in the same patients. In a next step, we extended the analysis to candidate moderate severity categories, based on recently suggested definitions which were adapted for our purposes. Severe vascular leakage occurred in 244 (90%), severe bleeding in 39 (14%), and severe organ dysfunction in 28 (10%) of 271 severe dengue patients. A higher frequency of severe leakage was seen in children or adolescents (<15y) compared to adults. More than 80% of the severe leakage cases, and 30-50% of the cases with severe bleeding or severe organ dysfunction, were defined as severe on the basis of that feature alone. In 136 out of 213 patients with severe leakage alone, neither moderate bleeding manifestation nor hepatic involvement was recorded. On the other hand, moderate leakage manifestations were detected in 4 out of 12 cases that were classified as severe based on bleeding alone. A major proportion of severe dengue patients exhibited clinical manifestations of severe vascular leakage only, which may constitute a useful endpoint for intervention research or pathophysiology studies. Severe bleeding and severe organ manifestation were recorded less frequently and exhibited a higher degree of overlap with severe leakage. Severe bleeding without leakage may be associated with individual predisposition or the presence of comorbidities. More detailed assessments are needed to explore this hypothesis. Candidate moderate disease endpoints were investigated and need to be further validated.

Assessment of the new World Health Organization's dengue classification for predicting severity of illness and level of healthcare required.

The objective of this study was to assess the validity of the new dengue classification proposed by the World Health Organization (WHO) in 2009 and to develop pragmatic guidelines for case triage and management. This retrospective study involved 357 laboratory-confirmed cases of dengue infection diagnosed at King Abdulaziz University Hospital, Jeddah, Saudi Arabia over a 4-year period from 2014 to 2017. The sensitivity of the new classification for identifying severe cases was limited (65%) but higher than the old one (30%). It had a higher sensitivity for identifying patients who needed advanced healthcare compared to the old one (72% versus 32%, respectively). We propose adding decompensation of chronic diseases and thrombocytopenia-related bleeding to the category of severe dengue in the new classification. This modification improves sensitivity from 72% to 98% for identifying patients who need advanced healthcare without altering specificity (97%). It also improves sensitivity in predicting severe outcomes from 32% to 88%. In conclusion, the new classification had a low sensitivity for identifying patients needing advanced care and for predicting morbidity and mortality. We propose to include decompensation of chronic diseases and thrombocytopenia-related bleeding to the category of severe dengue in the new classification to improve the sensitivity of predicting cases requiring advanced care.

Aplicación y aceptabilidad de la Guía Clínica de Dengue OMS-2009: la percepción de Ecuador / Aplicability and Aceptability and of the Dengue Clinical Guidelines WHO 2009: Ecuador's perception

Introducción: la infección por virus dengue se ha diseminado a más de 100 países a nivel mundial, con un cambio en su patrón que hizo que la clasificación OMS 1997 no sea aplicable. Objetivo: determinar la aceptabilidad y aplicabilidad de la guía OMS-2009. Materiales y métodos: fue conducido un estudio de corte transversal con diseño mixto, entre abril a noviembre del 2009 posterior a una intervención formativa dirigida a médicos, para lo cual se aplicó un cuestionario previamente elaborado y se realizó un trabajo de grupos focales. Resultados: los médicos mostraron una aceptación del 91,9% por la clasificación OMS-2009. El 100% realiza monitoreo de los signos vitales, considerando plaquetas (98,4%) y hematocrito (96.9%). El 96,9% utiliza las plaquetas como signos de alarma, seguido de letargia o inquietud (95,3%), dolor abdominal (95,3%), vómitos persistentes (92,2%). Los participantes refieren que es útil en la clasificación de los pacientes, especialmente los graves (30,56%), fácil de entender y manejar (30,56%), y como una ventaja que ayuda en el manejo y tratamiento de los casos (44,4%). El 80% considera que es necesaria su difusión a través de capacitaciones. De los grupos focales se considera que es sencilla, practica y didáctica para los niveles de severidad, orienta al triage de los pacientes y permite mejor su clasificación. Conclusiones: la guía OMS-2009 tiene una amplia aceptación por el personal de salud (AU).

Introduction: dengue virus infection has spread to more than 100 countries worldwide, with a change in its pattern that made the 1997 WHO classification not applicable. Objective: to determine the acceptability and applicability of the WHO-2009 guide. Materials and methods: a cross-sectional study with a mixed design was conducted between April and November 2009 following a training intervention directed at physicians, for which a previously elaborated questionnaire was applied and a focus group work was carried out. Results: physicians showed an acceptance of 91.9% for the WHO-2009 classification. 100% performed vital signs monitoring, considering platelets (98.4%) and hematocrit (96.9%). 96.9% used platelets as warning signs, followed by lethargy or restlessness (95.3%), abdominal pain (95.3%), persistent vomiting (92.2%). Participants report that it is useful in the classification of patients, especially severe (30.56%), easy to understand and manage (30.56%), and as an aid to the management and treatment of cases (44.4%). Eighty percent consider it necessary to disseminate it through training. Conclusions: gráficothe WHO-2009 guide has a wide acceptance by the health personnel, the health professionals, the health professionals, the health professionals (AU).

Aplicación y aceptabilidad de la Guía Clínica de Dengue OMS-2009: la percepción de Ecuador / Aplicability and Aceptability and of the Dengue Clinical Guidelines WHO 2009: Ecuador's perception

Introducción: la infección por virus dengue se ha diseminado a más de 100 países a nivel mundial, con un cambio en su patrón que hizo que la clasificación OMS 1997 no sea aplicable. Objetivo: determinar la aceptabilidad y aplicabilidad de la guía OMS-2009. Materiales y métodos: fue conducido un estudio de corte transversal con diseño mixto, entre abril a noviembre del 2009 posterior a una intervención formativa dirigida a médicos, para lo cual se aplicó un cuestionario previamente elaborado y se realizó un trabajo de grupos focales. Resultados: los médicos mostraron una aceptación del 91,9% por la clasificación OMS-2009. El 100% realiza monitoreo de los signos vitales, considerando plaquetas (98,4%) y hematocrito (96.9%). El 96,9% utiliza las plaquetas como signos de alarma, seguido de letargia o inquietud (95,3%), dolor abdominal (95,3%), vómitos persistentes (92,2%). Los participantes refieren que es útil en la clasificación de los pacientes, especialmente los graves (30,56%), fácil de entender y manejar (30,56%), y como una ventaja que ayuda en el manejo y tratamiento de los casos (44,4%). El 80% considera que es necesaria su difusión a través de capacitaciones. De los grupos focales se considera que es sencilla, practica y didáctica para los niveles de severidad, orienta al triage de los pacientes y permite mejor su clasificación. Conclusiones: la guía OMS-2009 tiene una amplia aceptación por el personal de salud (AU).

Introduction: dengue virus infection has spread to more than 100 countries worldwide, with a change in its pattern that made the 1997 WHO classification not applicable. Objective: to determine the acceptability and applicability of the WHO-2009 guide. Materials and methods: a cross-sectional study with a mixed design was conducted between April and November 2009 following a training intervention directed at physicians, for which a previously elaborated questionnaire was applied and a focus group work was carried out. Results: physicians showed an acceptance of 91.9% for the WHO-2009 classification. 100% performed vital signs monitoring, considering platelets (98.4%) and hematocrit (96.9%). 96.9% used platelets as warning signs, followed by lethargy or restlessness (95.3%), abdominal pain (95.3%), persistent vomiting (92.2%). Participants report that it is useful in the classification of patients, especially severe (30.56%), easy to understand and manage (30.56%), and as an aid to the management and treatment of cases (44.4%). Eighty percent consider it necessary to disseminate it through training. Conclusions: gráficothe WHO-2009 guide has a wide acceptance by the health personnel, the health professionals, the health professionals, the health professionals (AU).

Metformin Use and Severe Dengue in Diabetic Adults.

Diabetes mellitus is a risk factor for severe dengue in adults, but few studies have examined the association between metformin use and disease severity in dengue. In addition to its effect on glucose control, metformin has been associated with pleiotropic properties in preclinical studies. Using a cohort of laboratory-confirmed adult (≥21 years) dengue patients with diabetes mellitus admitted to Tan Tock Seng Hospital, we conducted a retrospective cohort study involving 131 (58.7%) metformin users and 92 (41.3%) non-users. Dengue severity was categorized as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) in World Health Organization (WHO) 1997 criteria and severe dengue (SD) in WHO 2009 criteria. Multivariable Poisson regression with robust error variance was used to estimate risk ratio (RR). Compared with non-use, metformin use was associated with a decreased risk of developing severe dengue (adjusted risk ratio [aRR] = 0.60, 95% confidence interval [CI]: 0.37-0.98, P = 0.04). Additionally, there was an inverse dose-response relationship (aRR = 0.69, 95% CI: 0.49-0.98, P = 0.04) with dengue severity as classified by WHO 2009 criteria. Use of metformin, however, was not associated with dengue severity based on WHO 1997 criteria; and no dose-response relationship was noted. Our results suggest metformin use could attenuate disease severity in dengue-infected diabetes mellitus individuals.

The Clinical and Serological Profile of Pediatric Dengue.

OBJECTIVE: To classify suspected dengue into dengue, dengue with warning signs and severe dengue, based on clinical features as per the revised WHO guidelines with special emphasis on serology. METHODS: It was a prospective cross-sectional study for five years from 2011-2016 in a tertiary care medical college hospital in Bangalore. All cases of fever of three to five days duration with symptoms like dengue were enrolled for the study. They were categorized into three groups as per the Revised WHO 2012 criteria. Laboratory parameters, serology, ultrasound abdomen and X-ray were done in almost all patients. Data was analysed by SPSS software, version 16, and different groups were compared with Chi square test. RESULTS: Five hundred sixty eight children were diagnosed to have dengue fever; 4.2% of the sample belonged to infancy. Majority were in the age group of 5-10 y (42.6%). Fever and flushing were present in majority of the children. Gastrointestinal bleed was more commonly seen in the severe dengue group. Dengue nonstructural protein antigen (NS1Ag) was positive in 78%, immunoglobulin M (IgM) in 15.8% and immunoglobulin G (IgG) in 14.6%. Children with IgG had more complications, though not statistically significant. Mortality was reported in 1.2%. Dengue serology helped to confirm the diagnosis, however did not help in patient management. CONCLUSIONS: There is a considerable overlap in the symptomatology of dengue with warning signs and severe dengue. More studies are required on the severity and type of response to treatment in infants and obese adoloscents with severe dengue.

REPORTING PROGRESS ON THE USE OF THE WHO 2009 DENGUE CASE CLASSIFICATION: A REVIEW.

This review reports on the progress in the use of the WHO 2009 dengue case classification--dengue and severe dengue--following up on a previous review (Horstick et al, 2012). The previous review detailed Steps 1 - 5 in developing the 2009 WHO case classification. As a further step, a systematic review of published studies comparing the two classifications has been published with 12 studies and a further 10 expert opinion papers that recommend the use of the 2009 WHO dengue case classification for clinical management, epidemiology, and clinical research. Furthermore, a formal expert consensus was reached in La Habana, Cuba in 2013 with dengue experts from the Americas, sharing experiences that applied the 2009 WHO dengue case classification. The expert panel recommended to 1) update ICD10, 2) include the 2009 WHO case classification in country epidemiological reports globally, and 3) implement studies improving sensitivity/specificity of the dengue case definition.

Dengue importado: arbovirosis emergente en Espa˜na / Imported dengue: An emerging arbovirosis in Spain

El dengue es causado por uno de 4 serotipos del virus dengue. En España, solo se han comunicado casos importados. Las manifestaciones clínicas más frecuentes son fiebre y exantema, aunque puede haber formas graves, especialmente en infecciones secundarias. Presentamos a 5 niños con dengue no grave, infección primaria, diagnosticados por sospecha clínica y antecedente epidemiológico mediante inmunocromatografía y ELISA. Evolución favorable en todos los casos. Es importante considerar este diagnóstico en todo viajero internacional que presenta fiebre dentro de los 14 días tras volver de un área endémica, para un diagnóstico precoz, un adecuado tratamiento y un buen pronóstico

Dengue is caused by one of 4 serotypes of dengue virus. Only imported cases have been reported in Spain. The main clinical findings are fever and exanthema, although there may be severe forms, particularly in secondary infections. Five children with a primary, non severe dengue infection are presented. The diagnosis was based on clinical suspicion and epidemiological history, and confirmed by immunochromatography and ELISA tests. The outcome was favourable in all cases. It is important to consider this diagnosis in international travellers that present with fever within the 14 days of returning from an endemic area, in order to get an early diagnosis, adequate treatment and a good prognosis

An evaluation of the World Health Organization's 1997 and 2009 dengue classifications in hospitalized dengue patients in Malaysia.

INTRODUCTION: The latest revised version of the World Health Organization's dengue classification was released in 2009. A handful of studies have taken initiatives to evaluate the old and revised guidelines to determine early signs and symptoms of severe dengue. This retrospective study aimed to compare the classification of dengue using both the 1997 and 2009 guidelines in a selected cohort of dengue patients from Peninsular Malaysia between 2008 and 2012. METHODOLOGY: Adult dengue patients were recruited from tertiary hospitals in two different states, Selangor and Kelantan, in Peninsular Malaysia. Their clinical manifestations were assessed. RESULTS: A total of 281 confirmed dengue patients were enrolled; the mean duration of illness at admission was five days. Of these, 88.6%, 10.7%, and 0.7% were classified according to the 1997 guidelines as having dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS), respectively. When the WHO 2009 guidelines were applied, 17.1%, 78.3%, and 4.6% were classified as dengue without warning signs, dengue with warning signs, and severe dengue, respectively. CONCLUSIONS: Our data suggests that the revised WHO 2009 guidelines stratify a much larger proportion of patients into a category that requires a higher level of medical and nursing care.

Comparing the usefulness of the 1997 and 2009 WHO dengue case classification: a systematic literature review.

The 1997 and 2009 WHO dengue case classifications were compared in a systematic review with 12 eligible studies (4 prospective). Ten expert opinion articles were used for discussion. For the 2009 WHO classification studies show: when determining severe dengue sensitivity ranges between 59-98% (88%/98%: prospective studies), specificity between 41-99% (99%: prospective study) - comparing the 1997 WHO classification: sensitivity 24.8-89.9% (24.8%/74%: prospective studies), specificity: 25%/100% (100%: prospective study). The application of the 2009 WHO classification is easy, however for (non-severe) dengue there may be a risk of monitoring increased case numbers. Warning signs validation studies are needed. For epidemiological/pathogenesis research use of the 2009 WHO classification, opinion papers show that ease of application, increased sensitivity (severe dengue) and international comparability are advantageous; 3 severe dengue criteria (severe plasma leakage, severe bleeding, severe organ manifestation) are useful research endpoints. The 2009 WHO classification has clear advantages for clinical use, use in epidemiology is promising and research use may at least not be a disadvantage.

Sensitivity and specificity of the World Health Organization dengue classification schemes for severe dengue assessment in children in Rio de Janeiro.

BACKGROUND: The clinical definition of severe dengue fever remains a challenge for researchers in hyperendemic areas like Brazil. The ability of the traditional (1997) as well as the revised (2009) World Health Organization (WHO) dengue case classification schemes to detect severe dengue cases was evaluated in 267 children admitted to hospital with laboratory-confirmed dengue. PRINCIPAL FINDINGS: Using the traditional scheme, 28.5% of patients could not be assigned to any category, while the revised scheme categorized all patients. Intensive therapeutic interventions were used as the reference standard to evaluate the ability of both the traditional and revised schemes to detect severe dengue cases. Analyses of the classified cases (n = 183) demonstrated that the revised scheme had better sensitivity (86.8%, P<0.001), while the traditional scheme had better specificity (93.4%, P<0.001) for the detection of severe forms of dengue. CONCLUSIONS/SIGNIFICANCE: This improved sensitivity of the revised scheme allows for better case capture and increased ICU admission, which may aid pediatricians in avoiding deaths due to severe dengue among children, but, in turn, it may also result in the misclassification of the patients' condition as severe, reflected in the observed lower positive predictive value (61.6%, P<0.001) when compared with the traditional scheme (82.6%, P<0.001). The inclusion of unusual dengue manifestations in the revised scheme has not shifted the emphasis from the most important aspects of dengue disease and the major factors contributing to fatality in this study: shock with consequent organ dysfunction.

Prospective applicability study of the new dengue classification system for clinical management in children.

BACKGROUND: To evaluate the efficacy of the 2009 revised dengue classification system proposed by the World Health Organization (WHO) for early detection of dengue cases requiring intervention. METHODS: Children <15 years of age with dengue [confirmed by laboratory testing (IgM enzyme-linked immunosorbent assay, NS1 Ag or reverse transcriptase polymerase chain reaction) or by epidemiologic link] who were admitted to the Institute of Tropical Medicine during the 2011 dengue outbreak in Paraguay were prospectively included. Each case was classified according to the 1997 WHO dengue criteria and by the 2009 WHO revised criteria, which categorize dengue patients using a set of clinical finding into dengue with/without warning signs and severe dengue. The management of all cases followed the new recommendations. RESULTS: During the 2011 dengue outbreak, 123 children were admitted with a mean age of 11 ± 3 years. By the 2009 classification system, 119 cases (97%) were classified as dengue requiring intervention [89 patients (75%) with warning signs and 30 patients (25%) with severe signs], whereas by the old system 67 patients (54%) were classified as dengue requiring intervention (P < 0.001). Further, by the 1997 classification, only 13 patients (10%) were classified as dengue hemorrhagic fever III/IV (severe cases), whereas with the 2009 classification 30 patients (24%) were considered as having severe dengue infection (P < 0.05) CONCLUSIONS:: This study confirms that the 2009 WHO dengue classification provides better detection of severe cases of dengue than the earlier 1997 WHO dengue system.

Evaluation of the WHO classification of dengue disease severity during an epidemic in 2011 in the state of Ceará, Brazil.

In 2009, the World Health Organization (WHO) issued a new guideline that stratifies dengue-affected patients into severe (SD) and non-severe dengue (NSD) (with or without warning signs). To evaluate the new recommendations, we completed a retrospective cross-sectional study of the dengue haemorrhagic fever (DHF) cases reported during an outbreak in 2011 in northeastern Brazil. We investigated 84 suspected DHF patients, including 45 (53.6%) males and 39 (46.4%) females. The ages of the patients ranged from five-83 years and the median age was 29. According to the DHF/dengue shock syndrome classification, 53 (63.1%) patients were classified as having dengue fever and 31 (36.9%) as having DHF. According to the 2009 WHO classification, 32 (38.1%) patients were grouped as having NSD [4 (4.8%) without warning signs and 28 (33.3%) with warning signs] and 52 (61.9%) as having SD. A better performance of the revised classification in the detection of severe clinical manifestations allows for an improved detection of patients with SD and may reduce deaths. The revised classification will not only facilitate effective screening and patient management, but will also enable the collection of standardised surveillance data for future epidemiological and clinical studies.

Evaluation of the WHO classification of dengue disease severity during an epidemic in 2011 in the state of Ceara, Brazil

In 2009, the World Health Organization (WHO) issued a new guideline that stratifies dengue-affected patients into severe (SD) and non-severe dengue (NSD) (with or without warning signs). To evaluate the new recommendations, we completed a retrospective cross-sectional study of the dengue haemorrhagic fever (DHF) cases reported during an outbreak in 2011 in northeastern Brazil. We investigated 84 suspected DHF patients, including 45 (53.6%) males and 39 (46.4%) females. The ages of the patients ranged from five-83 years and the median age was 29. According to the DHF/dengue shock syndrome classification, 53 (63.1%) patients were classified as having dengue fever and 31 (36.9%) as having DHF. According to the 2009 WHO classification, 32 (38.1%) patients were grouped as having NSD [4 (4.8%) without warning signs and 28 (33.3%) with warning signs] and 52 (61.9%) as having SD. A better performance of the revised classification in the detection of severe clinical manifestations allows for an improved detection of patients with SD and may reduce deaths. The revised classification will not only facilitate effective screening and patient management, but will also enable the collection of standardised surveillance data for future epidemiological and clinical studies.

Implications of discordance in world health organization 1997 and 2009 dengue classifications in adult dengue.

BACKGROUND: Revised dengue guidelines were published by the World Health Organization (WHO) in 2009 addressing severe dengue cases not classified by dengue hemorrhagic fever (DHF) and shock syndrome (DSS). METHODS AND PRINCIPAL FINDINGS: We conducted a retrospective cohort study to compare WHO 2009 and 1997 classifications using 1278 adult dengue cases confirmed by polymerase chain reaction assay from Singapore epidemics in 2004 and 2007 (predominantly serotype 1 and 2 respectively).DHF occurred in 14.3%, DSS 2.7% and severe dengue 16.0%. The two WHO dengue classifications were discordant in defining severe disease (p<0.001). Five DSS patients (15%) were classified as non-severe dengue without warning signs. Of severe dengue patients, 107 did not fulfil DHF criteria. Of these, 14.9% had self-resolving isolated elevated aminotransferases, 18.7% gastrointestinal bleeding without hemodynamic compromise and 56.1% plasma leakage with isolated tachycardia. We compared both guidelines against requirement for intensive care including the single death in this series: all six had severe dengue; only four had DHF as two lacked bleeding manifestations but had plasma leakage. Increasing length of hospitalization was noted among severe cases with both classifications but the trend was only statistically significant for WHO 2009. Length of hospitalization was significantly longer for severe plasma leakage compared with severe bleeding or organ impairment. Requirement for hospitalization increased using WHO 2009 from 17.0% to 51.3%. CONCLUSIONS: While the WHO 2009 dengue classification is clinically useful, we propose retaining criteria for plasma leakage and hemodynamic compromise from WHO 1997, and refining definitions of severe bleeding and organ impairment to improve clinical relevance having found that differences in these accounted for the discordance between classifications. Findings from our retrospective study may be limited by the study site - a tertiary referral center in a hyperendemic country - and should be evaluated in a wider range of geographic settings.

Timing, predictors, and progress of third space fluid accumulation during preliminary phase fluid resuscitation in adult patients with dengue.

BACKGROUND: Fluid leakage remains the hallmark of dengue hemorrhagic fever (DHF). The applicability of currently recommended predictors of DHF for adults with dengue is questionable as these are based on studies conducted in children. METHODS: One hundred and two adults with dengue were prospectively followed up to investigate whether home-based or hospital-based early phase fluid resuscitation has an impact on clinical and hematological parameters used for the diagnosis of early or critical phase fluid leakage. RESULTS: In the majority of subjects, third space fluid accumulation (TSFA) was detected on the fifth and sixth days of infection. The quantity and quality of fluids administered played no role in TSFA. A reduction in systolic blood pressure appeared to be more helpful than a reduction in pulse pressure in predicting fluid leakage. TSFA occurred with lower percentage rises in packed cell volume (PCV) than stated in the current recommendations. A rapid reduction in platelets, progressive reduction in white blood cells, percentage rises in Haemoglobin (Hb), and PCV, and rises in aspartate aminotransferase and alanine aminotransferase were observed in patients with TSFA and therefore with the development of severe illness. CONCLUSIONS: Clinicians should be aware of the limitations of currently recommended predictors of DHF in adult patients who are receiving fluid resuscitation.

Clasificación de dengue hemorrágico utilizando árboles de decisión en la fase temprana de la enfermedad / Classification of dengue hemorrhagic fever using decision trees in the early phase of the disease

Introducción: el dengue es una enfermedad viral con comportamiento epidémico, a su inicio no es posible saber qué pacientes evolucionarón desfavorablemente, sin embargo, pueden presentar signos de alarma que anuncian deterioro clínico. Objetivo: aplicar la técnica de árboles de decisión a la búsqueda de signos de alarma de gravedad en la fase temprana de la enfermedad. Métodos: la muestra de estudio la constituyeron 230 pacientes ingresados con dengue en el Instituto de Medicina Tropical Pedro Kourí en 2001. Las variables consideradas para la clasificación fueron los signos, síntomas y exámenes de laboratorio al tercer día de evolución de la enfermedad. Se aplicó el algoritmo de árboles de clasificación y regresión utilizando el índice de Gini. Se consideraron diferentes matrices de pérdida para mejorar la sensibilidad. Resultados: el algoritmo ARC, correspondiente a la mejor pérdida, tuvo una sensibilidad de 98,68 por ciento y error global de 0,36. Sin considerar pérdida, el árbol resultante obtuvo una sensibilidad de 74 por ciento con un error de 0,25. En ambos casos las variables de mayor importancia fueron plaqueta y hemoglobina. Conclusiones: se proponen reglas de decisión con alta sensibilidad y valor predictivo negativo de utilidad en la práctica clínica. Las variables de laboratorio resultan tener mayor importancia que las clínicas para discriminar las formas clínicas de dengue(AU)

Introduction: dengue is a viral disease with endemic behavior. At the beginning of the illness it is not possible to know which patients will have an unfavorable evolution and develop a severe form of dengue. However, some warning symptoms and signs may be present. Objective: to apply decision tree techniques to the exploration of signs of severity in the early phase of the illness. Methods: the study sample was made up of 230 patients admitted with dengue to Pedro Kourí Institute of Tropical Medicine in 2001. The variables considered for the classification were the signs, symptoms and laboratory exams on the third day of evolution of the illness. The algorithm of classification and regression trees using the Gini's index was applied. Different loss matrices to improve the sensitivity were considered. Results: the algorithm CART, corresponding to the best loss, had a sensitivity of 98.68 percent and global error of 0.36. Without considering loss, it obtained its sensitivity reached 74 percent with an error of 0.25. In both cases, the most important variables were platelets and hemoglobin. Conclusions: the study submitted rules of decision with high sensitivity and negative predictive value of utility in the clinical practice. The laboratory variables resulted more important from the informational viewpoint than the clinical ones to discriminate clinical forms of dengue(AU)

Clasificación de dengue hemorrágico utilizando árboles de decisión en la fase temprana de la enfermedad / Classification of dengue hemorrhagic fever using decision trees in the early phase of the disease

Introducción: el dengue es una enfermedad viral con comportamiento epidémico, a su inicio no es posible saber qué pacientes evolucionarán desfavorablemente, sin embargo, pueden presentar signos de alarma que anuncian deterioro clínico. Objetivo: aplicar la técnica de árboles de decisión a la búsqueda de signos de alarma de gravedad en la fase temprana de la enfermedad. Métodos: la muestra de estudio la constituyeron 230 pacientes ingresados con dengue en el Instituto de Medicina Tropical "Pedro Kourí" en 2001. Las variables consideradas para la clasificación fueron los signos, síntomas y exámenes de laboratorio al tercer día de evolución de la enfermedad. Se aplicó el algoritmo de árboles de clasificación y regresión utilizando el índice de Gini. Se consideraron diferentes matrices de pérdida para mejorar la sensibilidad. Resultados: el algoritmo ARC, correspondiente a la mejor pérdida, tuvo una sensibilidad de 98,68 por ciento y error global de 0,36. Sin considerar pérdida, el árbol resultante obtuvo una sensibilidad de 74 por ciento con un error de 0,25. En ambos casos las variables de mayor importancia fueron plaqueta y hemoglobina. Conclusiones: se proponen reglas de decisión con alta sensibilidad y valor predictivo negativo de utilidad en la práctica clínica. Las variables de laboratorio resultan tener mayor importancia que las clínicas para discriminar las formas clínicas de dengue.

Introduction: dengue is a viral disease with endemic behavior. At the beginning of the illness it is not possible to know which patients will have an unfavorable evolution and develop a severe form of dengue. However, some warning symptoms and signs may be present. Objective: to apply decision tree techniques to the exploration of signs of severity in the early phase of the illness. Methods: the study sample was made up of 230 patients admitted with dengue to "Pedro Kourí" Institute of Tropical Medicine in 2001. The variables considered for the classification were the signs, symptoms and laboratory exams on the third day of evolution of the illness. The algorithm of classification and regression trees using the Gini's index was applied. Different loss matrices to improve the sensitivity were considered. Results: the algorithm CART, corresponding to the best loss, had a sensitivity of 98.68 percent and global error of 0.36. Without considering loss, it obtained its sensitivity reached 74 percent with an error of 0.25. In both cases, the most important variables were platelets and hemoglobin. Conclusions: the study submitted rules of decision with high sensitivity and negative predictive value of utility in the clinical practice. The laboratory variables resulted more important from the informational viewpoint than the clinical ones to discriminate clinical forms of dengue.