The sample constituted 205 males (58.6%) and 145 females (41.4%). The females were older (mean 37.6, SD 17 years) than the males (mean 30.8, SD 12.8 years). There was no significant difference in age between those with DF and DHF. Of the 350 subjects, 257 (73.4%) were diagnosed as dengue fever (DF, non leakers) and 93 (26.5%) as DHF with plasma leakage.
Most patients with DF and DHF were admitted on day 3 of the illness. Patients with DHF had a longer stay in hospital compared to DF patients (DF: mean 4.1, median 4. DHF: mean 4.76, median 5, P<0.01). Most patients with DHF had plasma leakage on day 5 (Mean 5.01 SD 1.3; median 5; range day 2-8) (Table 1).
Twenty-seven (29%) patients with DHF had evidence of plasma leakage at time of admission to hospital on ultrasonography.
Serial platelet, white cell counts and transaminases
The platelet counts done on day 1 and 2 of fever remained above 150,000/mm3 in both groups and the difference was not significant. The platelet count gradually dropped in both groups from day 3 of fever reaching a lowest mean of 97,000/mm3 in DF by day 6 and 40,000/ mm3 in DHF on day 7. The platelet count dropped to less than 50,000/mm3 on day 5 in DHF patients. The platelet counts remained significantly lower in DHF patients compared to DF patients from day 3 to day 7 (P=0.000) (Table-2). The counts gradually started to improve from day 7 in both groups.
The mean percentage drop in absolute platelet count from day prior to leaking to day of leaking was 47.8% (SD 22.9). When serial platelet counts were analyzed against the day of plasma leakage, the platelet count was less than 50,000/mm3 at time of leaking irrespective of the day of the illness (table 3).
The total white cell count (WCC) dropped in both groups from day 1 to day 4 and then gradually recovered and was significantly higher among leakers compared to non-leakers from day 6 to day 9(P<0.01, Table 2).
Hepatic transaminases showed progressive elevation from day 1 to day 6 of illness and a gradual decline thereafter in both groups, with AST being higher than ALT. The AST and ALT were significantly higher in patients with DHF compared to those with DF (P<0.01). The highest mean AST (157.5IU/L) was observed on day 6 and highest mean ALT (112IU/L) was observed on day 5 in patients with DHF (Table 2).
Platelet count <50,000/mm3 (OR 23.7; 95% CI 12.2-45.9), AST> twice, upper limit of normal (OR 7.5; 95% CI 3.9-14.3) and ALT> twice, upper limit of normal (OR 2.4; 95%CI 1.4-3.6) increased the likelihood of DHF (Table 4).
There was no significant difference between C-Reactive protein (CRP) and rise in haematocrit between the groups.
Correlation and predictive association between markers
Strength of relationships between markers as determined by Pearson r and their respective predictive associations as represented by R 2 are shown in table 5.
Plasma leakage had significant correlation with platelet count (r- 0.59) and a moderate predictive association (R2 0.35) at time of leakage. The correlation with AST (r 0.271) was less and the association weaker (R2 0.069). The correlation of leaking with ALT, hematocrit and CRP was much weaker (r< 0.16) and the associations negligible. AST and ALT showed excellent correlation with each other (r 0.89) at time of leaking. There was moderate correlation between platelet count and ALT and AST (table 5).
Logistic regression was performed selecting the laboratory variables with p<.05 in the univariate and bivariate analysis, utilizing the forward step-wise selection method. The platelet count and AST at time of leakage emerged as significant independent predictors of DHF. The Hosmer-Lemeshow goodness of fit test showed a good fit in the 2 independent predictors of DHF/plasma leakage (P=0.85).
Predictive platelet count and AST from ROC
Receiver operated characteristic (ROC) curves for the platelet count and AST at time of plasma leakage were performed separately to obtain a predictive value for DHF. The area under the curve (AUC) for the platelet count was 0.89 (figure 1). We propose a cut-off value of 50,000/cumm3 as reasonable value giving a sensitivity of 87% and specificity of 79% for detecting DHF in adult dengue patients.
AUC for the ROC curve for AST was 0.73 (figure 2). We propose an AST value of 93IU/L with a sensitivity of 85% and a specificity of 60% as a reasonable predictive value for DHF.