Simple clinical and laboratory predictors of Chikungunya versus dengue infections in adults

Abstract

Background: Dengue and chikungunya are co-circulating vector-borne diseases with substantial overlap in clinical presentations. It is important to differentiate between them during first presentation as their management, especially for dengue hemorrhagic fever (DHF), is different. This study compares their clinical presentation in Singapore adults to derive predictors to assist doctors in diagnostic decision-making.

Methods: We compared 117 patients with chikungunya infection diagnosed with reverse transcription-polymerase chain reaction (RT-PCR) with 917 dengue RT-PCR-positive adult patients (including 55 with DHF). We compared dengue fever (DF), DHF, and chikungunya infections by evaluating clinical characteristics of dengue and chikungunya; developing classification tools via multivariate logistic regression models and classification trees of disease etiology using clinical and laboratory factors; and assessing the time course of several clinical variables.

Findings: At first presentation to hospital, significantly more chikungunya patients had myalgia or arthralgia, and fewer had a sore throat, cough (for DF), nausea, vomiting, diarrhea, abdominal pain, anorexia or tachycardia than DF or DHF patients. From the decision trees, platelets <118 × 10(9)/L was the only distinguishing feature for DF versus chikungunya with an overall correct classification of 89%. For DHF versus chikungunya using platelets <100 × 10(9)/L and the presence of bleeding, the overall correct classification was 98%. The time course analysis supported platelet count as the key distinguishing variable.

Interpretation: There is substantial overlap in clinical presentation between dengue and chikungunya infections, but simple clinical and laboratory variables can predict these infections at presentation for appropriate management.

Figure 1. Univariate anaylsis of variables at first presentation to hospital.

The analysis compared between Dengue fever (DF), dengue hemorraghic fever (DHF), and chikungunya (Chik). For binomial variables (first column on the left), bars denote mean percentage with whiskers denoting 95% confidence intervals. For continuous variables (right 2 columns), the box shows the median values (in white) with the interquartile ranges, while the whiskers denote the central 95^th percentiles. The red brackets to the left of the bars denote statistically significant comparisons between DF and chikungunya (upper brackers), and DHF and chikungunya (lower brackets). Uniformly distributed jitter of up to ±12 h has been added to the days since onset and duration of fever for graphical purposes. Five DF patients with no temperature measurement are excluded from the maximum temperature panel.

Figure 2. Decision tree models for discrimination.

Models discriminate between dengue fever (DF) or dengue hemorrhagic fever (DHF) and chikungunya (Chik) for well-resourced (laboratory data included) and resource-limited (laboratory data excluded) settings. A and B discriminate between chikungunya and DF in a resource-limited and well-resourced setting respectively. C and D discriminate between chikungunya and DHF in a resource-limited and well-resourced setting respectively. Final classifications as chikungunya are shaded in grey, while classifications for DF/DHF are unshaded.

Figure 3. Time course analysis of selected variables.

Analysis shows platelet counts (A), serum hematocrit (B), leukocyte (C), and temperature (D) for dengue fever (DF), dengue hemorrhagic fever (DHF) and chikungunya. Individual data are indicated in semi-transparent red (chikungunya), black (DF), and blue(DHF) lines. Overall means are indicated as solid lines, with 95% credible intervals as dashed lines. The bar on X-axis indicates in black days with a ‘significant’ difference (defined as 95% credible interval for the difference between the two disease means not crossing zero) between chikungunya and DF, and the blue bar between chikungunya and DHF.