We performed a multi-center retrospective observational study of adult dengue deaths at all five major adult public hospitals in Singapore from 1 January 2004 to 31 December 2008. Cases were identified through matching positive dengue diagnostic test results with hospital mortality records. Patients tested positive by dengue PCR or NS1 as previously described [9, 10], and died within the same hospital admission, were included. Probable dengue diagnosed with rapid dengue serology was excluded due to lack of specificity .
Demographic, epidemiological, co-morbidity, serial clinical and laboratory, radiological, treatment and outcome data were obtained, and principal and secondary discharge diagnoses were recorded. The duration of acute illness was determined from the onset of fever, and from the onset of symptoms preceding hospitalization if fever was absent.
Institutional review boards of National Healthcare Group (Tan Tock Seng Hospital, National University Hospital and Alexandra Hospital) and Singhealth Group (Singapore General Hospital and Changi General Hospital), Singapore, approved the study, which was funded by the National Medical Research Council, Singapore. All records examined were anonymized.
According to the WHO 1997 guideline, DF clinically required the presence of fever and two or more of headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations and leukopenia; DHF the presence of all of fever, thrombocytopenia ≤100 × 10^9/L, any bleeding, and plasma leakage manifesting as either hematocrit change of ≥20%, clinical fluid accumulation (e.g. pleural effusion or ascites), or hypoproteinemia; and DSS the presence of one of rapid and weak pulse with narrow pulse pressure <20 mmHg, or hypotension for age in a patient with DHF.
Minor modifications to the WHO 2009 criteria were made in this study. Probable dengue was defined as fever and two of nausea or vomiting, rash, aches and pain, leukopenia, and any warning sign. The tourniquet sign was not performed in Singapore. Warning signs were determined as: abdominal pain or tenderness, persistent vomiting on at least two consecutive hospital days, clinical fluid accumulation (pleural effusion or ascites), mucosal bleed, lethargy or restlessness, any hepatomegaly (instead of greater than 2 cm), and hematocrit change of ≥20% with concurrent platelet nadir < 20 × 10^9/L or 50 × 10^9/L (instead of the qualitative rapid change in hematocrit with rapid drop in platelet count).
Severe dengue was present if any one of the following was recorded:
(1) Plasma leakage evidenced by hematocrit change of ≥20%, pleural effusion or ascites, or hypoproteinemia, leading to
(a) DSS (tachycardia, cold and clammy extremities, capillary refill time greater than three seconds, weak or undetectable pulse, narrow pulse pressure ≤20 mmHg, or systolic blood pressure <90 mmHg or unrecordable blood pressure), or
(b) Fluid accumulation with respiratory distress (respiratory rate ≥30/minute, oxygen saturation ≤92% on room air, or mechanical ventilation); or
(2) Severe bleeding manifesting as gastro-intestinal bleeding or menorrhagia, or requirement for transfusion of packed red blood cells or whole blood; or
(3) Severe organ involvement as follows:
(a) Serum alanine or aspartate transaminase ≥1000 units/L;
(b) Impaired consciousness;
(c) Acute renal impairment defined as serum creatinine > two times upper limit of normal ; or
(d) Myocarditis or encephalopathy/encephalitis.
For the statistical analysis, Fisher's exact test was applied to detect statistical difference between dichotomous variables, while the Kruskal-Wallis test was used to test for significant trend for continuous data. The analysis was performed in SPSS version 16 (SPSS Inc., Chicago, IL, USA), with the level of significance set at a two-tailed p value of <0.05.