Fan Zhang1, Christine V Kramer. 1. School of Public Health and Management, Chongqing Medical University, No. 1, Yi Xue Yuan Road, Chongqing, China, 400016.
Abstract
BACKGROUND: Dengue is a common and important mosquito-borne viral infection. In many low- and middle-income countries it is endemic and is an important public health problem. Severe dengue is an important cause of death in children. There is no specific treatment for dengue, but observational studies suggest corticosteroids may have a benefit in dengue-related shock, and some people believe corticosteroids may prevent the progression to severe illness if given early in the course of the illness. OBJECTIVES: To compare treatment of dengue with and without use of corticosteroids or placebo in relation to preventing shock-related death and disease progression in children and adults. SEARCH METHODS: We searched the Cochrane Infectious Disease Group Centralized Register; CENTRAL; MEDLINE; EMBASE; and LILACS, up to 6 January 2014. We screened reference lists and contacted the relevant study authors for additional information where required. SELECTION CRITERIA: Randomized controlled trials or quasi-randomized controlled trials comparing corticosteroids with placebo or no corticosteroids in patients diagnosed with dengue-related shock, or patients in an early symptomatic state of dengue with positive serology. DATA COLLECTION AND ANALYSIS: Two researchers independently screened eligibility of records, extracted data and assessed quality of the studies. We presented findings in meta-analysis and summary of findings tables and evaluated the quality of evidence using GRADE. MAIN RESULTS: We included eight studies enrolling 948 participants in this review. Paitents with dengue-related shock Four studies enrolled children younger than 15 years with dengue-related shock at hospitals in Southeast Asia and evaluated intravenous corticosteroids. The trials did not detect an effect on death (four trials, 284 participants, very low quality evidence), the need for blood transfusion (two trials, 89 participants, very low quality evidence), pulmonary haemorrhage (one trial, 63 participants, very low quality evidence), convulsions (one trial, 63 participants, very low quality evidence), or duration of hospitalization (one trial, 63 participants, very low quality evidence). The body of evidence is too small to confidently prove or exclude clinically important effects. Furthermore, the trials are more than 20 years old with several methodological limitations. Patients with dengue at an early stage Four studies enrolled 664 children and adults with dengue at an early stage of infection (without shock) in Columbia, India, Sri Lanka and Vietnam. In these participants there were no evidence of effects of oral or intravenous corticosteroids on mortality (four trials, 664 participants, low quality evidence), or on the development of complications of severe dengue such as shock (two trials, 286 participants, very low quality evidence), severe bleeding (two trials, 425 participants, very low quality evidence), severe thrombocytopaenia (one trial, 225 participants, very low quality evidence), ascites (one trial, 178 participants, very low quality evidence) and intensive care unit (ICU) admissions (two trials, 286 participants, very low quality evidence). AUTHORS' CONCLUSIONS: The evidence from trials using corticosteroids in dengue is inconclusive and the quality of evidence is low to very low. This applies to both the use of corticosteroids in dengue-related shock and for dengue at an early stage. There is insufficient evidence to evaluate the effects of corticosteroids in the treatment of early stage dengue fever and dengue-related shock outside of the context of a randomized controlled trial.
BACKGROUND: Dengue is a common and important mosquito-borne viral infection. In many low- and middle-income countries it is endemic and is an important public health problem. Severe dengue is an important cause of death in children. There is no specific treatment for dengue, but observational studies suggest corticosteroids may have a benefit in dengue-related shock, and some people believe corticosteroids may prevent the progression to severe illness if given early in the course of the illness. OBJECTIVES: To compare treatment of dengue with and without use of corticosteroids or placebo in relation to preventing shock-related death and disease progression in children and adults. SEARCH METHODS: We searched the Cochrane Infectious Disease Group Centralized Register; CENTRAL; MEDLINE; EMBASE; and LILACS, up to 6 January 2014. We screened reference lists and contacted the relevant study authors for additional information where required. SELECTION CRITERIA: Randomized controlled trials or quasi-randomized controlled trials comparing corticosteroids with placebo or no corticosteroids in patients diagnosed with dengue-related shock, or patients in an early symptomatic state of dengue with positive serology. DATA COLLECTION AND ANALYSIS: Two researchers independently screened eligibility of records, extracted data and assessed quality of the studies. We presented findings in meta-analysis and summary of findings tables and evaluated the quality of evidence using GRADE. MAIN RESULTS: We included eight studies enrolling 948 participants in this review. Paitents with dengue-related shock Four studies enrolled children younger than 15 years with dengue-related shock at hospitals in Southeast Asia and evaluated intravenous corticosteroids. The trials did not detect an effect on death (four trials, 284 participants, very low quality evidence), the need for blood transfusion (two trials, 89 participants, very low quality evidence), pulmonary haemorrhage (one trial, 63 participants, very low quality evidence), convulsions (one trial, 63 participants, very low quality evidence), or duration of hospitalization (one trial, 63 participants, very low quality evidence). The body of evidence is too small to confidently prove or exclude clinically important effects. Furthermore, the trials are more than 20 years old with several methodological limitations. Patients with dengue at an early stage Four studies enrolled 664 children and adults with dengue at an early stage of infection (without shock) in Columbia, India, Sri Lanka and Vietnam. In these participants there were no evidence of effects of oral or intravenous corticosteroids on mortality (four trials, 664 participants, low quality evidence), or on the development of complications of severe dengue such as shock (two trials, 286 participants, very low quality evidence), severe bleeding (two trials, 425 participants, very low quality evidence), severe thrombocytopaenia (one trial, 225 participants, very low quality evidence), ascites (one trial, 178 participants, very low quality evidence) and intensive care unit (ICU) admissions (two trials, 286 participants, very low quality evidence). AUTHORS' CONCLUSIONS: The evidence from trials using corticosteroids in dengue is inconclusive and the quality of evidence is low to very low. This applies to both the use of corticosteroids in dengue-related shock and for dengue at an early stage. There is insufficient evidence to evaluate the effects of corticosteroids in the treatment of early stage dengue fever and dengue-related shock outside of the context of a randomized controlled trial.
Authors: Kay M Tomashek; Aidsa Rivera; Brenda Torres-Velasquez; Elizabeth A Hunsperger; Jorge L Munoz-Jordan; Tyler M Sharp; Irma Rivera; Dario Sanabria; Dianna M Blau; Renee Galloway; Jose Torres; Rosa Rodriguez; Javier Serrano; Carlos Chávez; Francisco Dávila; Janice Perez-Padilla; Esther M Ellis; Gladys Caballero; Laura Wright; Sherif R Zaki; Carmen Deseda; Edda Rodriguez; Harold S Margolis Journal: PLoS Negl Trop Dis Date: 2016-10-11