A total of 9,448 (male 4,759, female 4,689) person-years were followed in the 3 years study period. There were 2,591 febrile episodes attended RH during this period. These represented 71% of the total febrile episodes occurring in the recruited subjects. Fifty-two percent of febrile episodes not attending RH were mild and were self-treated without medical attention. The remaining febrile patients who did not attend RH had attended either private clinics or hospitals. None of them were diagnosed as dengue infection because a study requirement was that a diagnosis of dengue outside RH would prompt a visit to RH. Our study follow-up team tracked all febrile patients to a conclusion and prompted all with a dengue diagnosis to visit RH. Among those who attended RH, 313 febrile episodes (12.1%) were due to dengue infections as diagnosed by ELISA test, including 41(13.1%) primary antibody responses and 272 (86.9%) secondary antibody responses. Dengue serotypes were identified by either mosquito inoculation or RT-PCR in 259 cases (82.7%) including 115 (36.7%), 80 (25.6%), 41 (13.1%), and 23 (7.3%) cases of DEN1, 2, 3, and 4, respectively. There were 156 cases (49.8%) of UF, 123 cases (39.3%) of DF, and 34 cases (10.9%) of DHF including 22 cases (7.0%), 5 cases (1.6%), and 7 cases (2.2%) of DHF grade 1, 2 and 3, respectively. Among 41 cases with primary antibody responses, 26 cases had UF (63.4%), 14 cases had DF (34.2%) and 1 case had DHF grade 1 (2.4%). There was no significant association among infecting dengue serotypes and types of antibody response (data not shown).
The detailed data on clinical manifestations (i.e. daily symptoms until recovery) of 71 UF cases were not obtained. Therefore only 85 UF cases are used for analysis. The clinical diagnosis of these 71 and 85 UF cases are shown in . Significantly more cases in the group whose data were obtained were diagnosed as acute febrile illness/suspected viral infection (p<0.001). However, there was no statistically significant difference in other clinical diagnosis between groups. There was also no statistically significant difference by age and gender [8.9 (SD 2.2) vs 9.2 (SD 2.2) years and 46.5% vs 61.2% male gender, respectively] although the male proportions were rather skewed.
Clinical diagnosis of UF cases.
The median age (interquatile range [IQR]) and percentage of males in the cases who had UF, DF and DHF were 9.3 (3.3), 9.6 (3.3), 10.0 (3.3) years, and 55.1, 55.3, 58.8 percent, respectively. There was no statistically significant difference in the age and gender among different disease spectra.
The symptoms of overall dengue infection and each specific disease spectrum (UF, DF, DHF) are presented in . Headache, anorexia, nausea/vomiting and myalgia were common symptoms occurring in more than half of the patients. It was found that nausea/vomiting, abdominal pain, rash, diarrhea and petechiae were statistically more common in DHF compared to DF and UF. shows symptoms and disease severity from different dengue serotypes. DEN4 was found to cause only UF, DF and DHF grade 1 and seemed to have less headache, anorexia, nausea/vomiting and rash compared to other DEN serotypes. However, these differences are not statistically significant.
Symptoms of dengue infection [n (%)].
Symptoms and disease severity from different dengue serotypes [n (%)].
Regarding fever, the median (IQR) value of the peak temperature and duration of fever in UF, DF, and DHF were 38.4 (1.6), 39.0 (1.5), and 39.0 (1.7) degree Celsius and 5 (3), 6 (2), and 6 (1) days, respectively. It was found that UF had both lower peak temperature and shorter duration of fever compared to DF and DHF (p<0.001).
The prevalence of common symptoms in each day of illness is shown in . It was noted that the prevalence of most of the symptoms was highest during the first 2 days of illness and then slowly declined. The exceptions are for anorexia, nausea/vomiting, abdominal pain and diarrhea that tended to increase in prevalence in DHF during day 3–5 of illness. It was also revealed that most symptoms were more common in DHF and, specifically, DHF cases had significantly higher prevalence of anorexia, nausea/vomiting and abdominal pain during day 3–6 and diarrhea during day 4–6 of illness (Chi-square test; p<0.05). Conversely, drowsiness/lethargy was significantly more common in UF during day 2–5 of illness.
The prevalence of common symptoms in dengue infection by the day of illness.
It was also revealed that a higher proportion of DHF had prolonged (3 or more days) anorexia, nausea/vomiting, abdominal pain, retro-orbital pain and petechiae. In contrast, a higher proportion of UF had prolonged drowsiness/lethargy. It is worth noting that very few cases had prolonged hemorrhagic manifestation ().
The number of dengue infected patients who had prolonged symptom (for 3 or more days) [n (%)].
shows physical findings in dengue infection. Positive tourniquet test was found in 72% and flushed face was found in approximately half of the dengue infected patients. Hepatomegaly was found in approximately 40% of DHF. This proportion was significantly higher than that found in UF and DF. Clinical jaundice was found only in one DHF (2.9%). shows the occurrence of selected clinical manifestations and their predictive value for DHF among symptomatic dengue infected cases. It was found that all of these clinical manifestations had low positive predictive value but high negative predictive value for DHF.
Physical findings in dengue infection [n/number observed (%)].
Occurrence of selected clinical manifestations [n/total] and their predictive value (%) for DHF among dengue infected cases.
Complete blood count were done in 43, 11, 8, 2, 2, 2 UF and in 113, 69, 32, 20, 7, 4 DF, and 32, 19, 12, 8, 2, 2 DHF cases on day 1, 2, 3, 4, 5, 6 of illness, respectively. shows the median value of hematocrit, peripheral white blood cell and platelet count in these dengue-infected patients. It was revealed that DHF cases had higher median hematocrit during the later days of illness and the median hematocrit in DHF was significantly higher than DF and UF during day 4–6 of illness. All of the 3 spectra of dengue infection had lower median peripheral white blood cell (WBC) count during the later days of illness and cases with UF had significantly higher median WBC count compared to DF and DHF. All spectra of dengue also had lower median peripheral platelet count during the later days of illness, although the median value in DF and UF did not meet the WHO's criterion for thrombocytopenia, i.e. lower than 100,000/mm3. Moreover, the level of platelet count showed reverse correlation with the disease severity, i.e. highest in UF and lowest in DHF. The median platelet count in DHF was significantly lower than the other 2 groups during day 3–6 of illness, while DF had significantly lower median platelet count compared to UF only during day 3–5 of illness.
Hematocrit, peripheral white blood cell and platelet count in dengue infected patients.