WHO 2009 Warning Signs as Predictors of Time Taken for Progression to Severe Dengue in Children

Objective To identify WHO 2009 warning signs that can predict time taken for progression to severe dengue in a pediatric population. Design Prospective analytical study over 1 year and 2 months. Setting Tertiary care center. Participants 350 children aged 1 mo-12 y with serologically confirmed dengue without co-morbidities/co-infections; consecutive sampling. Procedure At admission, clinical and laboratory details were noted. Disease progression, time of onset of each warning sign, hematocrit, and platelet counts were recorded daily till discharge/death. If progressing to severe dengue, its time of onset was noted. Time to event analysis with Log Rank test, Kaplan Meier plots and Cox Proportional Hazards Model was done. Outcome Measures Primary outcome was time interval from onset of first warning sign to onset of severe dengue (defined as per WHO 2009 guidelines). Predictors were WHO 2009 warning signs: abdominal pain, lethargy, persistent vomiting, mucosal bleed, clinical fluid accumulation, hepatomegaly >2 cm, hematocrit ≥0.40 and platelet count <100×10 9 /L. Results Among 350 children followed up completely till discharge/death, 90 developed severe dengue (event) while 260 did not (censored). Median age of study population was 7.75 y. Clinical fluid accumulation [( P =0.002, Hazard Ratio (HR) 2.19, 95% CI 1.33–3.60)] and hematocrit ≥0.40 [( P =0.009, HR (95%CI) 1.715, (1.13–2.60)] were significant in univariate analysis. Final multivariate model includes clinical fluid accumulation [( P =0.02, HR (95%CI) 1.89, (1.116–3.202)], hematocrit ≥0.40 ( P =0.07), mucosal bleed ( P =0.56) and persistent vomiting ( P =0.32). Conclusion WHO warning signs that predict time taken for progression to severe dengue in children include clinical fluid accumulation, hematocrit ≥0.40, persistent vomiting and mucosal bleed. Study results have implications in policy making and practice guidelines to triage children attending a health care facility with or without warning signs.