Clinical evaluation of dengue and identification of risk factors for severe disease: protocol for a multicentre study in 8 countries

Background: The burden of dengue continues to increase globally, with an estimated 100 million clinically apparent infections occurring each year. Although most dengue infections are asymptomatic, patients can present with a wide spectrum of clinical symptoms ranging from mild febrile illness through to severe manifestations of bleeding, organ impairment, and hypovolaemic shock due to a systemic vascular leak syndrome. Clinical diagnosis of dengue and identification of which patients are likely to develop severe disease remain challenging. This study aims to improve diagnosis and clinical management through approaches designed a) to differentiate between dengue and other common febrile illness within 72 h of fever onset, and b) among patients with dengue to identify markers that are predictive of the likelihood of evolving to a more severe disease course. Method/Design: This is a prospective multi-centre observational study aiming to enrol 7–8000 participants aged ≥ 5 years presenting with a febrile illness consistent with dengue to outpatient health facilities in 8 countries across Asia and Latin America. Patients presenting within 72 h of fever onset who do not exhibit signs of severe disease are eligible for the study. A broad range of clinical and laboratory parameters are assessed daily for up to 6 days during the acute illness, and also at a follow up visit 1 week later. Discussion: Data from this large cohort of patients, enrolled early with undifferentiated fever, will be used to develop a practical diagnostic algorithm and a robust clinical case definition for dengue. Additionally, among patients with confirmed dengue we aim to identify simple clinical and laboratory parameters associated with progression to a more severe disease course. We will also investigate early virological and serological correlates of severe disease, and examine genetic associations in this large heterogeneous cohort. In addition the results will be used to assess the new World Health Organization classification scheme for dengue in practice, and to update the guidelines for “Integrated Management of Childhood Illness” used in dengue-endemic countries. Trial registration: NCT01550016. Registration Date: March 7, 201

C-reactive protein as a potential biomarker for disease progression in dengue: a multi-country observational study.

BACKGROUND: Dengue infection can cause a wide spectrum of clinical outcomes. The severe clinical manifestations occur sufficiently late in the disease course, during day 4-6 of illness, to allow a window of opportunity for risk stratification. Markers of inflammation may be useful biomarkers. We investigated the value of C-reactive protein (CRP) measured early on illness days 1-3 to predict dengue disease outcome and the difference in CRP levels between dengue and other febrile illnesses (OFI). METHOD: We performed a nested case-control study using the clinical data and samples collected from the IDAMS-consortium multi-country study. This was a prospective multi-center observational study that enrolled almost 8000 participants presenting with a dengue-like illness to outpatient facilities in 8 countries across Asia and Latin America. Predefined severity definitions of severe and intermediate dengue were used as the primary outcomes. A total of 281 cases with severe/intermediate dengue were compared to 836 uncomplicated dengue patients as controls (ratio 1:3), and also 394 patients with OFI. RESULTS: In patients with confirmed dengue, median (interquartile range) of CRP level within the first 3 days was 30.2 mg/L (12.4-61.2 mg/L) (uncomplicated dengue, 28.6 (10.5-58.9); severe or intermediate dengue, 34.0 (17.4-71.8)). Higher CRP levels in the first 3 days of illness were associated with a higher risk of severe or intermediate outcome (OR 1.17, 95% CI 1.07-1.29), especially in children. Higher CRP levels, exceeding 30 mg/L, also associated with hospitalization (OR 1.37, 95% CI 1.14-1.64) and longer fever clearance time (HR 0.84, 95% CI 0.76-0.93), especially in adults. CRP levels in patients with dengue were higher than patients with potential viral infection but lower than patients with potential bacterial infection, resulting in a quadratic association between dengue diagnosis and CRP, with levels of approximately 30 mg/L associated with the highest risk of having dengue. CRP had a positive correlation with total white cell count and neutrophils and negative correlation with lymphocytes, but did not correlate with liver transaminases, albumin, or platelet nadir. CONCLUSIONS: In summary, CRP measured in the first 3 days of illness could be a useful biomarker for early dengue risk prediction and may assist differentiating dengue from other febrile illnesses

EDITORIAL: Innovación y Tecnología en Ciencias de la Salud.

Hemos estado últimamente, sorprendidos por una serie de informaciones sobre avances en la ciencia médica. Estas informaciones representan opciones para aquello que, al momento, no visualizan con esperanza, volver a vivir con la calidad de vida que experimentaron en años pasados

EDITORIAL: Ejercicio académico

Presentamos este nuevo volumen de Crea Ciencia, nuestra vía académico-científica oficial de comunicación. Ofrecemos a lo profesionales del área de la salud espacios para que sus investigaciones sean publicadas. Todo proceso de investigación no es completo si los resultados que resuelven problemas, y agregan conocimiento antes no imaginado, no publicados

Innovación y Tecnología en Ciencias de la Salud.

Crea Ciencia ofrece hacer del conocimiento de la comunidad científica internacional, las investigaciones de salvadoreños que han tomado en serio el camino del desarrollo.Universidad Evangélica de El Salvado

EDITORIAL, Crea Ciencia: Una opción válida

Con mucha alegría estamos entregando un nuevo número de la Revista Científica Crea Ciencia. Nuestra satisfacción se debe a que estamos ofreciendo a toda la comunidad del área de la salud, una revista indexada, inscrita en bases de datos internacionales y ahora con la novedad de tener nuestro propio sello editorial

Association between Nutritional Status and Severity of Dengue Infection in Children in El Salvador

Clinical observations and some studies suggest that dengue virus infection is more severe among children with better nutritional status. We examined the nutritional status of children in El Salvador and its relationship between this and the severity of dengue infection. Z-scores for weight-for-age, height-for-age, and body mass index (BMI)-for-age of children with dengue fever (66), dengue hemorrhagic fever (62), and healthy controls (74) were compared. There were no differences in weight-for-age or BMI-for-age Z-scores between the three groups. Children with dengue fever had a greater height-for-age than healthy controls but no significant differences in rates of stunting. There was no difference in height between children with dengue fever and dengue hemorrhagic fever. Excess nutrition does not appear to be a risk factor for severe forms of dengue infection in El Salvador, nor does malnutrition appear to be predictive of good outcomes

C-reactive protein as a potential biomarker for disease progression in dengue: a multi-country observational study.

BACKGROUND: Dengue infection can cause a wide spectrum of clinical outcomes. The severe clinical manifestations occur sufficiently late in the disease course, during day 4-6 of illness, to allow a window of opportunity for risk stratification. Markers of inflammation may be useful biomarkers. We investigated the value of C-reactive protein (CRP) measured early on illness days 1-3 to predict dengue disease outcome and the difference in CRP levels between dengue and other febrile illnesses (OFI). METHOD: We performed a nested case-control study using the clinical data and samples collected from the IDAMS-consortium multi-country study. This was a prospective multi-center observational study that enrolled almost 8000 participants presenting with a dengue-like illness to outpatient facilities in 8 countries across Asia and Latin America. Predefined severity definitions of severe and intermediate dengue were used as the primary outcomes. A total of 281 cases with severe/intermediate dengue were compared to 836 uncomplicated dengue patients as controls (ratio 1:3), and also 394 patients with OFI. RESULTS: In patients with confirmed dengue, median (interquartile range) of CRP level within the first 3 days was 30.2 mg/L (12.4-61.2 mg/L) (uncomplicated dengue, 28.6 (10.5-58.9); severe or intermediate dengue, 34.0 (17.4-71.8)). Higher CRP levels in the first 3 days of illness were associated with a higher risk of severe or intermediate outcome (OR 1.17, 95% CI 1.07-1.29), especially in children. Higher CRP levels, exceeding 30 mg/L, also associated with hospitalization (OR 1.37, 95% CI 1.14-1.64) and longer fever clearance time (HR 0.84, 95% CI 0.76-0.93), especially in adults. CRP levels in patients with dengue were higher than patients with potential viral infection but lower than patients with potential bacterial infection, resulting in a quadratic association between dengue diagnosis and CRP, with levels of approximately 30 mg/L associated with the highest risk of having dengue. CRP had a positive correlation with total white cell count and neutrophils and negative correlation with lymphocytes, but did not correlate with liver transaminases, albumin, or platelet nadir. CONCLUSIONS: In summary, CRP measured in the first 3 days of illness could be a useful biomarker for early dengue risk prediction and may assist differentiating dengue from other febrile illnesses

C-reactive protein as a potential biomarker for disease progression in dengue: a multi-country observational study

Abstract: Background: Dengue infection can cause a wide spectrum of clinical outcomes. The severe clinical manifestations occur sufficiently late in the disease course, during day 4–6 of illness, to allow a window of opportunity for risk stratification. Markers of inflammation may be useful biomarkers. We investigated the value of C-reactive protein (CRP) measured early on illness days 1–3 to predict dengue disease outcome and the difference in CRP levels between dengue and other febrile illnesses (OFI). Method: We performed a nested case-control study using the clinical data and samples collected from the IDAMS-consortium multi-country study. This was a prospective multi-center observational study that enrolled almost 8000 participants presenting with a dengue-like illness to outpatient facilities in 8 countries across Asia and Latin America. Predefined severity definitions of severe and intermediate dengue were used as the primary outcomes. A total of 281 cases with severe/intermediate dengue were compared to 836 uncomplicated dengue patients as controls (ratio 1:3), and also 394 patients with OFI. Results: In patients with confirmed dengue, median (interquartile range) of CRP level within the first 3 days was 30.2 mg/L (12.4–61.2 mg/L) (uncomplicated dengue, 28.6 (10.5–58.9); severe or intermediate dengue, 34.0 (17.4–71.8)). Higher CRP levels in the first 3 days of illness were associated with a higher risk of severe or intermediate outcome (OR 1.17, 95% CI 1.07–1.29), especially in children. Higher CRP levels, exceeding 30 mg/L, also associated with hospitalization (OR 1.37, 95% CI 1.14–1.64) and longer fever clearance time (HR 0.84, 95% CI 0.76–0.93), especially in adults. CRP levels in patients with dengue were higher than patients with potential viral infection but lower than patients with potential bacterial infection, resulting in a quadratic association between dengue diagnosis and CRP, with levels of approximately 30 mg/L associated with the highest risk of having dengue. CRP had a positive correlation with total white cell count and neutrophils and negative correlation with lymphocytes, but did not correlate with liver transaminases, albumin, or platelet nadir. Conclusions: In summary, CRP measured in the first 3 days of illness could be a useful biomarker for early dengue risk prediction and may assist differentiating dengue from other febrile illnesses