Utilities and Limitations of the World Health Organization 2009 Warning Signs for Adult Dengue Severity

<div><h3>Background</h3><p>In 2009, the World Health Organization (WHO) proposed seven warning signs (WS) as criteria for hospitalization and predictors of severe dengue (SD). We assessed their performance for predicting dengue hemorrhagic fever (DHF) and SD in adult dengue.</p> <h3>Method</h3><p>DHF, WS and SD were defined according to the WHO 1997 and 2009 dengue guidelines. We analyzed the prevalence, sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of WS before DHF and SD onset.</p> <h3>Results</h3><p>Of 1507 cases, median age was 35 years (5^th–95^th percentile, 17–60), illness duration on admission 4 days (5^th–95^th percentile, 2–6) and length of hospitalization 5 days (5^th–95^th percentile, 3–7). DHF occurred in 298 (19.5%) and SD in 248 (16.5%). Of these, WS occurred before DHF in 124 and SD in 65 at median of two days before DHF or SD. Three commonest warning signs were lethargy, abdominal pain/tenderness and mucosal bleeding. No single WS alone or combined had Sn >64% in predicting severe disease. Specificity was >90% for both DHF and SD with persistent vomiting, hepatomegaly, hematocrit rise and rapid platelet drop, clinical fluid accumulation, and any 3 or 4 WS. Any one of seven WS had 96% Sn but only 18% Sp for SD.</p> <h3>Conclusions</h3><p>No WS was highly sensitive in predicting subsequent DHF or SD in our confirmed adult dengue cohort. Persistent vomiting, hepatomegaly, hematocrit rise and rapid platelet drop, and clinical fluid accumulation, as well as any 3 or 4 WS were highly specific for DHF or SD.</p> </div

Prevalence of warning signs (WS) during the entire clinical course, and before the development of dengue hemorrhagic fever (DHF) and severe dengue (SD).

x<p>Years 2007 and 2008 cohorts only, Variables shown are numbers with percentage in parentheses.</p

Duration from the onset of warning signs to dengue hemorrhagic fever (DHF) and severe dengue (SD).

*<p>Median (5^th–95^th percentiles),</p>x<p>Years 2007 and 2008 cohorts only.</p

Performance of warning signs (WS) for predicting dengue hemorrhagic fever (DHF) (n = 1507).

<p>Sn = sensitivity, Sp = specificity, PPV = positive predictive value, NPV = negative predictive value,</p>x<p>Years 2007 and 2008 cohorts only,</p>*<p>Median number of WS before DHF was 1 (range, 1–4).</p

Performance of warning signs (WS) for predicting severe dengue (SD) (n = 1507).

<p>Sn = sensitivity, Sp = specificity, PPV = positive predictive value, NPV = negative predictive value,</p>x<p>Years 2007 and 2008 cohorts only,</p>*<p>Median number of WS before SD was 1 (range, 1–5).</p

Demographic and clinical characteristics, treatment and clinical outcomes of adult dengue patients with positive dengue polymerase chain reaction.

<p>Variables shown are numbers with percentage in parentheses unless otherwise stated.</p

Secondary multivariate analysis (excluding menorrhagia) of clinical variables predictive of CSB in (n = 4299) adult dengue patients.

<p>Secondary multivariate analysis (excluding menorrhagia) of clinical variables predictive of CSB in (n = 4299) adult dengue patients.</p

Demographic and clinical characteristics and outcomes among adult dengue patients with and without CSB.

<p>Demographic and clinical characteristics and outcomes among adult dengue patients with and without CSB.</p

Multivariate analysis of clinical factors on admission that were predictive of CSB according to the final model (N = 4383).

<p>Multivariate analysis of clinical factors on admission that were predictive of CSB according to the final model (N = 4383).</p

Multivariate analysis of clinical variables predictive of CSB in adult dengue patients (stratified by gender).

<p>Multivariate analysis of clinical variables predictive of CSB in adult dengue patients (stratified by gender).</p