title: Efficacy and safety ofCarica papayaleaf extract in the dengue: A systematic review and meta-analysis.
abstract: BACKGROUND
  Dengue is an infectious disease associated with high mortality and morbidity. Being a viral disease, there is no specific drug available for treatment. There are some reports that Carica papaya leaf extract may improve the clinical condition of dengue patients; however, to support this, at present, there is no systematically searched and synthesized evidence available.
  
  
  OBJECTIVE
  This systematic review and meta-analysis was designed to search the available evidence related to the efficacy and safety ofC. papayaleaf extract in dengue and to synthesize the evidence in meaningful form through meta-analysis so that inference can be drawn.
  
  
  METHODS
  Randomized controlled trials related to the efficacy and safety ofC. papayaleaf extract in dengue were searched from PubMed, Cochrane Clinical Trial Registry and Google Scholar. The primary endpoint was mortality, and secondary endpoints were increase in platelet count, hospitalization days, and Grade 3 and 4 adverse events. Data related to primary and secondary endpoints were pooled together and analyzed by review manager (Review Manager (RevMan) Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, Denmark) software. The random effect model was used. The bias was analyzed by the Cochrane risk of bias tool.
  
  
  RESULTS
  Total four trials enrolling 439 subjects were included in the analysis. Of 439 subjects, data of 377 subjects were available for analysis.C. papayaleaf extract was found to be associated with increase in platelet count in the overall analysis (mean difference [MD] =20.27 [95% confidence interval (CI) 6.21-34.73;P= 0.005]) and analysis after 4thday (MD = 28.25 [95% CI 14.14-42.37;P< 0.0001]). After 48 h, there was no significant difference betweenC. papayaand control group (MD = 13.38 [95% CI - 7.71-34.51;P= 0.21]). There was significant decrease in hospitalization days in theC. papayagroup (MD = 1.90 [95% CI 1.62-2.18;P< 0.00001]). Because of nonavailability of data in published clinical trials, mortality, and adverse events cannot be pooled.
  
  
  CONCLUSIONS
  C. papayaleaf extract can be considered as a potential candidate for increase in platelet count in patients of dengue, however; there is need of high-quality evidence in the form of large clinical trials before a decision related to the use of such extract is made.
authors.affiliation: Department of Pharmacology, GMERS Medical College, Dharpur, Patan, India.
authors.forename: Jaykaran
authors.initials: J
authors.lastname: Charan
authors.affiliation: Indian Institute of Public Health, Gandhinagar, Gujarat, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Saxena
authors.affiliation: Department of Pediatrics, All India Institute of Medical Science, Rishikesh, Uttrakhand, India.
authors.forename: Jagdish Prasad
authors.initials: JP
authors.lastname: Goyal
authors.affiliation: Indian Institute of Public Health, Gandhinagar, Gujarat, India.
authors.forename: Sandul
authors.initials: S
authors.lastname: Yasobant
keywords: Dengue hemorrhagic fever; platelets; thrombocytopenia; vascular leakage