Abstract
Introduction:
Analyzing dengue disease patterns from different parts of the world should help us formulate more evidence based treatment guidelines and appropriately allocate limited healthcare resources. Therefore, we described the disease characteristics of hospitalised pediatric patients with dengue infections from Sri Lanka during the 2017 dengue epidemic.
Methods:
Clinical and biochemical characteristics of pediatric dengue patients treated at a secondary care hospital in Sri Lanka from 1 June 2017 to 31 August 2017 were analyzed. Our findings were compared with previous pediatric dengue studies in Asia.
Results: A total of 305
patients (number of males = 184(60%); mean age = 8.6 years) were analyzed. DF (Dengue Fever)—245 (80.3%), DHF (Dengue Hemorrhagic fever)—I:52 (17%), DHF—II:7 (2.3%), and DHF—III:1 (0.3%). Significant associations were found between DHF and abdominal symptoms/signs and overt bleeding manifestations (P < .001). Time of onset of the critical phase was variable (Day 3: 12%, Day 4-5: 78%, Day 6: 5%, and Day 7: 5%). Platelet and white-cell counts (WBC) were significantly lower in DHF than DF; liver enzyme derangement was mild and was similar in the DHF and DF subgroups. None had cardiac, renal, or neurological manifestations and all recovered uneventfully.
Conclusion:
In Sri Lankan pediatric dengue patients, we found abdominal symptoms and signs, decreased WBC and platelet counts and bleeding manifestations were to be significantly associated with DHF. Liver enzyme derangement did not predict DHF. The time of onset of the critical phase was difficult to predict due to the considerable variations noted.
Keywords: dengue virus infections, children, Sri Lanka, dengue epidemic, dengue fever
Introduction
Dengue viral infections are common in children and cause high morbidity and increased financial burden to the health system.1 Around 500,000 people with Dengue Hemorrhagic Fever (DHF) need hospitalization each year, the majority being children aged less than 5 years.1 Reports from different parts of the world suggest a changing pattern in the incidence of dengue infections and associated organ involvement such as respiratory, cardiac, gastrointestinal, hepatic, renal and neurological.2-9
In Sri Lanka, dengue epidemics occur regularly and cause considerable financial burden to the health care sector and economy of the country.10,11 Although children are commonly affected by dengue, published data on dengue infections in children living in Sri Lanka are limited.12-14 Following the study by Malavige et al, no study in Sri Lanka has described the patterns of dengue infections specifically in the pediatric population.12 In 2017, Sri Lanka faced its largest dengue epidemic, requiring reallocation of resources and specialized dengue treatment units to combat the large epidemic.15-17 Systematically collected demographic and clinical data during such dengue epidemics is essential for evidence based practice. Lack of such information will lead health policy makers and clinicians to rely on personal experience and knowledge as opposed to tangible evidence when basing their decisions related to allocation of resources and individual patient management. Therefore, we conducted a follow up study to identify patterns of clinical, demographic and biochemical findings of hospitalized pediatric dengue patients during the Sri Lankan dengue epidemic in 2017 and compared our findings with similar pediatric dengue data in Sri Lanka and other regional Asian countries.
Materials and Methods
All children with fever who were admitted to the 2 pediatric wards at a secondary care hospital in Sri Lanka (Base Hospital Panadura) from 1 June 2017 to 31 August 2017 and who fulfilled a locally revised criteria based on the 1997-WHO dengue case classifications were recruited (see Supplementary File). Ethical clearance was received from the National Hospital of Sri Lanka- ethical review committee (No: AAJ/ETH/COM/2017-21) and institutional approval was obtained from the director of the hospital. Informed written consents were obtained before inclusion to the study. Categorization of patients into DF or DHF was based on the 1997 and 2009 WHO case definitions.18,19 The clinical, demographic and biochemical findings were collected from the clinical records using a standardized questionnaire. In those with severe infections, hematological parameters such as white blood cell (WBC), hematocrit and platelet counts were recorded 8 hourly. Biochemical parameters such as serum creatinine, liver enzymes and serum electrolytes were performed till discharge on a daily basis. In stable patients with mild infections, we collected hematological parameters daily and biochemical parameters every other day. Ultrasonographic assessments were initiated from day 3 onwards, or if the platelets were less than 100,000 × 103/µL. Ultrasonographic assessment was routinely performed twice daily until a clinical improvement was detected with a concomitant rise in platelet counts. If patients had any features of fluid leakage with or without shock, they were classified as having DHF irrespective of bleeding manifestations. DHF was sub-classified into 4 grades (grade I, grade II, grade III, and grade IV) as described in the 2007 WHO dengue case definitions. The critical phase was defined as the period of fluid leakage in DHF associated with defervescence and rise in hematocrit.
Data were analyzed using SPSS (version 17) and data were described as frequency and percentages. Possible predictive or associated factors in relation to DHF were described using the Pearson Chi square test and Student’s T test. A p value less than 0.05 was deemed statistically significant. Furthermore, subgroup analyses were performed between DF and DHF patients and also DHF-I and DHF-II/DHF-III.
Results
A total of 305 children who were diagnosed with dengue viral infections were studied. The majority were male—184(60.3%). The mean age was 8.6(Standard deviation [SD] = 3.3) years and 154 (50.5%) got admitted on the 3rd and 4th days of their illnesses. The mean duration of symptoms at presentation was 3.9(SD: 1.4) days and the mean duration of hospitalization was 3.8 (SD: 1.3) days (for DF: 3.5 (SD: 1.2) and DHF: 4.9 (SD: 1.3), P < .001). Fever was present in all patients during the onset of the infection (mean duration of fever: 4.0 days, SD: 1.4). Symptoms, such as headache 55% (n = 168), body aches 52.5% (n = 160), vomiting 43.1% (n = 131), abdominal pain 21.6% (n = 66), nausea 21.3% (n = 65), and diarrhea 15.4% (n = 47) were commonly associated with dengue. Bleeding manifestations were present in 2.6% (n = 8) and was more prevalent in DHF patients (5.1% vs 2%, P = .18) but the difference noted was not statistically significant. Around 38% (n = 116) and 6.9% (n = 21) had tenderness over the right hypochondrium and epigastrium, respectively. Around 80% of patients had DF (DF-245 (80.3%), DHF grade I-52 (17%), DHF grade II-7 (2.3%), and DHF grade III–1 (0.3%)). Clinically detectable ascites and pleural effusion were present among 71.6% (n = 43) and 26.7% (n = 16) of the DHF patients. Table 1 shows the comparison between the clinical features of DF and DHF. Compared with DF patients, a significantly greater proportion of DHF patients had abdominal symptoms (vomiting 64.4% vs 38%, diarrhea 27.1% vs 12.6%, and abdominal pain 32.2% vs 19.1%, P < .001). Furthermore, right hypochondrial tenderness was significantly higher in the DHF group compared to DF (84.7% vs 26.8%, P < .001). According to the 2009 dengue case classifications, 245 children had warning signs and 3 patients had severe dengue. The comparison between the 1997 and 2009 dengue case classifications is given in Table 2.
Table 1.
Clinical Characteristics of DF and DHF.
| Total |
DF |
DHF |
Odds ratio (95% CI) | P value | |||||
|---|---|---|---|---|---|---|---|---|---|
| N | % | N | % | N | % | ||||
| Gender | Male | 184 | 60.3 | 146 | 59.6 | 38 | 63.3% | 1.1 (0.7-1.8) | 0.60 |
| Female | 121 | 39.7 | 99 | 40.4 | 22 | 36.7% | |||
| Age | 8.6 ± SD3.2 | 8.6 ± SD3.3 | 8.7 ± SD2.9 | — | 0.92 | ||||
| Headache | Yes | 168 | 55.1 | 127 | 51.8 | 41 | 68.3 | 1.8 (1.1-2.9) | 0.02 |
| No | 137 | 44.9 | 118 | 48.2 | 19 | 31.7 | |||
| Body aches | Yes | 160 | 52.5 | 122 | 49.8 | 38 | 63.3 | 1.6 (0.9-2.5) | 0.60 |
| No | 145 | 47.5 | 123 | 50.2 | 22 | 36.7 | |||
| Vomiting | Yes | 131 | 43.0 | 93 | 38.1 | 38 | 63.3 | 2.3 (1.4-3.7) | <0.001 |
| No | 174 | 57.0 | 152 | 61.9 | 22 | 36.7 | |||
| Right hypochondrial tenderness | Yes | 116 | 38.0 | 65 | 26.5 | 51 | 85.0 | 9.2 (4.7-18.0) | <0.001 |
| No | 189 | 62.0 | 180 | 73.5 | 9 | 15.0 | |||
| Abdominal pain | Yes | 66 | 21.6 | 47 | 19.2 | 19 | 31.7 | 1.7 (1.1-2.7) | 0.035 |
| No | 239 | 78.4 | 198 | 80.8 | 41 | 68.3 | |||
| Nausea | Yes | 65 | 21.3 | 53 | 21.6 | 12 | 20.0 | 0.9 (0.5-1.6) | 0.78 |
| No | 240 | 78.7 | 192 | 78.4 | 48 | 80.0 | |||
| Diarrhea | Yes | 47 | 15.4 | 31 | 12.7 | 16 | 26.7 | 2.0 (1.2-3.2) | 0.007 |
| No | 258 | 84.6 | 214 | 87.3 | 44 | 73.3 | |||
| Epigastric tenderness | Yes | 21 | 6.9 | 17 | 6.9 | 4 | 6.7 | 0.9 (0.4-2.4) | 0.94 |
| No | 284 | 93.1 | 228 | 93.1 | 56 | 93.3 | |||
| Bleeding manifestations | Yes | 8 | 2.6 | 5 | 2.0 | 3 | 5.0 | 1.9 (0.8-5.0) | 0.2 |
| No | 297 | 97.4 | 240 | 98.0 | 57 | 95.0 | |||
| Retro orbital pain | Yes | 7 | 2.3 | 4 | 1.6 | 3 | 5.0 | 2.2 (0.9-5.4) | 0.12 |
| No | 298 | 97.7 | 241 | 98.4 | 57 | 95.0 | |||
Table 2.
WHO Classification 1997 vs 2009.
| Dengue |
Severe dengue |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| With warning signs | Without warning signs | Yes | No | ||||||
| N | % | N | % | N | % | N | % | ||
| DF/DHF | DF | 185 | 75.5 | 60 | 100.0 | 0 | 0.0% | 245 | 81.1 |
| DHF-I | 52 | 21.2 | 0 | 0.0 | 0 | 0.0% | 52 | 17.2 | |
| DHF-II | 7 | 2.9 | 0 | 0.0 | 2 | 66.7% | 5 | 1.7 | |
| DHF-III | 1 | 0.4 | 0 | 0.0 | 1 | 33.3% | 0 | 0.0 | |
| DF/DHF overall | DF | 185 | 75.5 | 60 | 100.0 | 0 | 0.0% | 245 | 81.1 |
| DHF | 60 | 24.5 | 0 | 0.0 | 3 | 100.0% | 57 | 18.9 | |
Among the DHF patients, the onset of the critical phase was noted following a mean duration of illness of 4.6 days (SD 0.9). The majority of children went into the critical phase on day 4 and day 5 (Day 4%-28.3%, n = 17 and Day 5%-50.0%, n = 30). However, 7 patients (11.9%) went into the critical phase on day 3. Furthermore, three patients each went into critical phase on day 6 and day 7 of the illness. Around 52% (n = 159) required crystalloids and 5.2% (n = 16) required colloids (boluses of dextran). Only two patients (0.7%) required blood transfusion.
Among DHF patients, a significantly lower WBC and platelet counts were noted as expected (Table 3). The lowest platelet count was less than 25,000 × 103/µL among 45% of DHF patients, compared to 2.0% of DF patients. The lowest platelet count of less than 50,000 × 103/µL was seen among 76.7% of DHF patients. The mean platelet count at the beginning of critical phase was 94 × 103/µL. The mean white cell count at the beginning of critical phase was 4.7 × 109/L. More importantly, the onset of critical phase was detected while the platelet count was more than 100,000/µL in around 32% of patients.
Table 3.
Laboratory Findings of DF and DHF.
| DF |
DHF |
||||
|---|---|---|---|---|---|
| N | % | N | % | P value | |
| Lowest platelet count (Mean ± SD)/µL | 104 ± SD46 | 39 ± SD28 | <.001 | ||
| <25000 | 5 | 2.0 | 27 | 45.0% | <.001 |
| 25 000–50 000 | 14 | 5.7% | 19 | 31.7% | |
| 50 000–75 000 | 39 | 15.9% | 6 | 10.0% | |
| 75 000–100 000 | 62 | 25.3% | 6 | 10.0% | |
| >100 000 | 125 | 51.0% | 2 | 3.3% | |
| Lowest WBC (Mean ± SD) × 109/L | 3.5 ± SD1.6 | 3.7 ± SD1.7 | .68 | ||
| <2 | 31 | 12.7% | 10 | 16.7% | .003 |
| 2–4 | 143 | 58.4% | 34 | 56.7% | |
| >4 | 71 | 29.0% | 16 | 26.7% | |
| Highest AST (Mean ± SD) IU/L | 85.4 ± SD51.4 | 93.5 ± SD45.3 | .33 | ||
| mild | 149 | 60.9% | 42 | 69.5% | .96 |
| moderate | 7 | 2.8% | 2 | 3.4% | |
| Severe | 0 | 0 | 0 | 0 | |
| Highest ALT (Mean ± SD) IU/L | 53.1 ± SD42.1 | 52.3 ± SD43.3 | .91 | ||
| mild | 108 | 44.3% | 25 | 40.7% | .87 |
| moderate | 8 | 3.3% | 2 | 3.4% | |
| severe | 0 | 0 | 0 | 0 | |
| Serum creatinine (Mean ± SD) mmol/L | 41.3 ± SD16.5 | 40.7 ± SD15.1 | .90 | ||
| Serum sodium (Mean ± SD) mEq/L | 135 ± SD2.5 | 133.5 ± SD3.3 | .001 | ||
| Serum potassium (Mean ± SD) mEq/L | 4.0 ± SD.44 | 3.9 ± SD.5 | .31 | ||
Liver enzyme derangements were subclassified as mild, moderate and marked.20 Mild (less than 5-fold rise), moderate (5-10 fold rise) and marked (greater than 10-fold rise) derangement of aspartate transaminase (AST) were noted in 62.6% (n = 191), 3.0% (n = 9), and none, respectively. Whereas mild, moderate and marked derangement of alanine transaminase (ALT) were present in 43.6% (n = 133), 3.3% (n = 10), and none, respectively. There was no significant different in the proportion of patients with liver enzyme derangement among the DHF and DF subgroups (Table 3). None of the patients developed renal or cardiac involvement and there were no neurological complications. None required intensive care unit (ICU) treatment and all patients had an uncomplicated recovery.
Discussion
In 2017, Sri Lanka experienced its largest dengue epidemic, with an overwhelming number of dengue patients being managed in secondary and tertiary care hospitals.15 We found that the onset of the critical phase was unpredictable due to the considerable variations noted. Although, most patients went into critical phase on the 4th and 5th days of the illness, approximately 12% went into critical phase on day 3. Thus, patients should be monitored to detect features of fluid leakage from the third day of illness irrespective of the platelet count.
Around 10% (n = 6) of children went into critical phases on the 6th day or later, which usually corresponds to the time of discharge after recovering from uncomplicated dengue infections. Thus, the treating physicians should take careful decision when discharging patients with suspected dengue infections and there should be acceptable evidence to suggest clinical recovery.
In this study, around 81% had DF and 19% had DHF. Furthermore, a considerable proportion with dengue fever had abdominal signs and symptoms which were vomiting (43%), tenderness over the right hypochondrium (38%) diarrhea (15%) and abdominal pain (22%). Moreover, the abdominal symptoms and signs were more associated with DHF compared with DF (P < .001). In certain instances, the abdominal complaints were one of the predominant symptoms during admission. Therefore, the clinical presentation may mimic an acute abdomen which is usually treated in a surgical unit. Furthermore, inadequate resuscitation or over resuscitation in this context and delay in detecting fluid leakage may result in detrimental outcomes. Similar studies have also shown dengue patients with significant gastro-intestinal manifestations.21,22 Therefore, a patient with predominant gastrointestinal symptoms in a dengue endemic area, especially during an epidemic should alert the healthcare personnel to consider the possibility of dengue.
The bleeding manifestation observed in our study was considerably low compared to previous studies.21-23 In our study, only 2.6% of patients had overt bleeding manifestations. However, analyzing the changes in the hematocrit levels (comparing the hematocrit level following clinical recovery and another stable recording during the course of the illness) revealed that 8% (n = 24) of the dengue patients showed a drop in the hematocrit level of more than 5%. Though, this analysis is a crude assessment, the possibility of concealed bleeding is a possibility.
Several studies have described a considerable rise in liver enzymes such as AST and ALT in DHF cases than DF, with higher rise in AST more than ALT. Moreover, a surge in aminotransferases, predominantly AST has been described in association with the severity of the illness.24,25 In the present study, we did not detect any significant difference in the AST/ALT in the DHF cohort compared to DF group (Table 3).
Table 412,13,26-28 summarizes the data presented in similar pediatric dengue publications from Sri Lanka. The distribution of gender was comparable. The prevalence of DHF was comparatively lower in our study. Proportion of patients with abdominal symptoms such as abdominal pain and vomiting was similar. High percentage had liver impairment but the majority were mild. Moderate liver impairment was only seen in 3%. Lower WBC and platelet cell counts were described in our study. However, the bleeding manifestations described in the present study were considerably lower compared to previous Sri Lankan studies. Table 529-41 compared the findings of our study with similar studies from South Asia. The distribution of gender was comparable. The proportion of DHF to DF was seen to vary between studies where some studies had lower proportion of DHF similar to our study. The proportion of patients with lower platelet count was higher in other studies. Table 623,42-48 shows the comparison of our data with previous pediatric dengue publications from Southeast Asia. The proportion of DHF to DF, and liver involvement were variable. Compared to South Asian and South East Asian studies, the gastrointestinal symptoms including abdominal pain and vomiting were lower in our study and furthermore, the prevalence of bleeding manifestations was considerably lower.
Table 4.
Comparison With Similar Studies in Sri Lanka.
| Author (year) | Present study (2017) | Sirisena (2014) | Murugananthan (2014) | Messer (2012) | Malavige (2006) | Lucas (2000) |
|---|---|---|---|---|---|---|
| Country | Sri Lanka | Sri Lanka | Sri Lanka | Sri Lanka | Sri Lanka | Sri Lanka |
| Study design | Retrospective | Cross sectional pilot study | Retrospective study | N/A | Prospective study | Retrospective study |
| Sample size | 305 children | 147 (254 with adult cases) | 288 (1085 with adult cases) | 65 (357 with adult cases) | 104 children | 177 children |
| Male % | 60.30% | 62.6% | 49.3% | 57.7% | 41.3% | N/A |
| Female % | 39.70% | 37.4% | 50.7% | 42.3% | 58.7% | N/A |
| Mean duration of fever (days) | 3.9 | N/A | 4.5 | N/A | N/A | N/A |
| DF | 80.70% | 68.9% | 55.4% | 79.8% | 17.3% | 19.2% |
| DHF | 19.30% | 30.3% | 12.2% | 31.4% | 82.7% | 80.8% |
| Cardiac | None | N/A | N/A | N/A | 2.9% | N/A |
| Neurological | None | N/A | N/A | N/A | 6.7% | 6.2% |
| Renal | None | N/A | N/A | N/A | N/A | N/A |
| Hepatic | Mild = 62.6%, moderate = 3% | 1.2% | 26.2% | 7.7% | N/A | 78.0% |
| Headache | 55.10% | 90.2% | 54.0% | 50.8% | 71.2% | 16.4% |
| Bodyache | 52.50% | 79.1% | 26.4% | 53.8% | N/A | 15.3% |
| Nausea | 21.30% | N/A | N/A | N/A | N/A | N/A |
| Vomiting | 43.10% | N/A | 50.1% | 42.5% | 74.0% | 82.5% |
| Diarrhea | 15.40% | N/A | N/A | N/A | 17.3% | N/A |
| Abdominal pain | 21.60% | N/A | N/A | 29.8% | N/A | 43.5% |
| Bleeding manifestations | 2.60% | 18.9% | 24.7% | N/A | 38.5% | 42.9% |
| Right hypochandrial tenderness | 38.00% | N/A | N/A | N/A | N/A | 57.1% |
| Epigastric tenderness | 6.90% | N/A | N/A | N/A | N/A | N/A |
| Platelet count | Count < 25 × 109/L = 10.5%; Count < 100 × 109/L = 58.4%; | Count < 100 × 109/L = 65.4; Count < 20 × 109/L = 2.4% | N/A | Count < 100 × 109/L = 53.6% | Count < 100 × 109/L = 70.2%, count < 20 × 109/L = 9.6% | Count < 100 × 109/L = 39.0% |
| WBC count | Count < 4 × 106/L = 71.5% | Count < 4 × 106/L = 76.0% | N/A | N/A | Count < 4 × 109/L = 15.4% | N/A |
| Mortality | None | 1 | Percentage = 0.9% (absolute count N/A) | N/A | 0 | 2 |
Note. N/A: not available.
Table 5.
Comparison with Similar Studies in South Asia.
| Author (Year) | Present study(2017) | Banerjee (2018) | Ramachandran (2016) | Pai Jakribettu (2015) | Kumar (2010) | Kamath (2006) | Ratageri (2005) | Shah (2004) | Narayanan (2002) | Sajid (2012) | Ahmed (2008) | Alam (2010) | Pervin (2004) | Ahmed (2001) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Country | Sri Lanka | India | India | India | India | India | India | India | India | Pakistan | Pakistan | Bangladesh | Bangladesh | Bangladesh |
| Study design | Retrospective | Prospective | Retrospective | Retrospective | Retrospective | Retrospective | Retrospective | Prospective | Prospective | Prospective | Prospective | Prospective | Prospective | Prospective |
| Sample size | 305 | 200 | 69 | 69 | 359 adults (≥15) and 107 pediatric (<15) cases | 109 DHF III-IV/DSS cases | 23 | 39 | 59 | 35 | 35 | 54 | 97 | 72 |
| Male% | 60.30% | 58.00% | 62.3% | 69.57% | 64.6% | 50.46% | 48% | N/A | 52.54% | 57.14% | 54.29% | 50.00% | N/A | 58.33% |
| Female% | 39.70% | 42.00% | 37.7% | 30.43% | 35.4% | 49.54% | 52% | N/A | 47.46% | 42.86% | 45.71% | 50.00% | N/A | 41.67% |
| Mean duration of fever (days) | 3.9 | N/A | N/A | N/A | 6-10 days | N/A | N/A | 7.7 | 4.9 | N/A | N/A | 4.9 | N/A | 8.2 |
| DF | 80.70% | N/A | N/A | N/A | 83.9% | N/A | 17% | 2.6% | 72.88% | N/A | 31.43% | 40% | N/A | 36.11% |
| DHF | 19.30% | N/A | N/A | N/A | 8.8% | 100.00% | 83% | 97.4% | 27.12% | N/A | 68.57% | 59.3% | 18.56% | 63.89% |
| Cardiac | None | N/A | N/A | N/A | N/A | 4.59% | N/A | N/A | Bradycardia = 10.17% | N/A | N/A | N/A | N/A | N/A |
| Neurological | None | N/A | N/A | N/A | Altered sensorium = 10.3% | 22.02% | 22% | 48.7% | 23.73% | N/A | 2.86% | N/A | N/A | N/A |
| Renal | None | N/A | 39.1% | N/A | Renal failure = 0.2% | 4.59% | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Hepatic | Mild = 62.6%, Moderate = 3% | N/A | 50.7% | 4.35% | 53.2% | 36.70% | 87% | 97.4% | 52.54% | 54.29% | 37.14% | 31.48% | 13.40% | 50.00% |
| Headache | 55.10% | 55.50% | N/A | 52.17% | 47.6% | N/A | 22% | N/A | 28.81% | N/A | 40.00% | 31.48% | 82.47% | 77.78% |
| Bodyache | 52.50% | 63.00% | N/A | 100.00% | 64.6% | N/A | N/A | N/A | 54.24% | 5.71% | 34.29% | 46.30% | 84.54% | 76.39% |
| Nausea | 21.30% | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Vomiting | 43.10% | N/A | 63.8% | 42.03% | 47.6% | N/A | 82% | 86.6% | 83.05% | 34.29% | 68.57% | N/A | 36.08% | 12.50% |
| Diarrhea | 15.40% | N/A | N/A | 8.69% | 13.9% | N/A | 13% | 48.7% | N/A | 17.14% | N/A | 9.26% | N/A | 19.44% |
| Abdominal pain | 21.60% | N/A | 71.0% | 11.59% | 37.5% | N/A | 61% | N/A | 23.73% | 51.43% | 68.57% | 59.26% | 6.19% | N/A |
| Bleeding manifestations | 2.60% | 13.00% | Mucosal bleeding = 39.1% | N/A | Petechiae 67.2%, ecchymosis 6.2%, gum bleeding 5.2%, hematuria 4.9%, melena 4.7%, hematemesis 3%, and epistaxis 2.6% | N/A | N/A | 53.8% | 66.10% | 5.71% | 62.86% | 59.26% | N/A | 86.11% |
| Right hypochondrial tenderness | 38.00% | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Epigastric tenderness | 6.90% | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Platelet count | Count < 25 × 109/L = 10.5%; Count < 100 × 109/L = 58.4% | N/A | Count<100 × 109/L = 82.6% | N/A | N/A | N/A | Count<100 × 10^9/L=82% | “Thrombocytopenia” = 92.3% | Count < 100 × 109/L = 72.88%; Count < 50 × 109/L = 20.34% | Count < 50 × 109/L = 11.43% | Count < 150 × 109/L = 85.71% | Count < 50 × 109/L = 68.52%; Count < 20 × 109/L = 9.26% | Count < 100 × 109/L = 22.68% | Count < 100 × 109/L = 37.5% |
| WBC count | Count < 4 × 106/L = 71.5% | N/A | N/A | N/A | N/A | N/A | Count<5 × 106/L=26% | N/A | Lymphocyte count > 50% = 30.51% | Count < 4 × 106/L = 14.29% | Count < 4 × 106/L = 42.86%; Neutrophils > 60% = 20.00% | Count < 4 × 106/L = 9.26% | N/A | Leucopenia = 12.5% |
| Mortality | None | N = 3 | N = 4 | N = 2 | N = 11 | N = 9 | N = 0 | N = 3 | N = 2 | N = 0 | N = 1 | 6% | N/A | N = 5 |
Note. N/A: not available.
Table 6.
Comparison with Similar Studies in Southeast Asia.
| Author (Year) | Present study (2017) | Hanafusa (2008) | Wichmann (2004) | Sawasdivorn (2001) | Kalayanarooj (1997) | Lam (2017) | Thu (2012) | Phuong (2004) | Chairulfatah (1995) |
|---|---|---|---|---|---|---|---|---|---|
| Country | Sri Lanka | Thailand | Thailand | Thailand | Thailand | Vietnam | Vietnam | Vietnam | Indonesia |
| Study design | Retrospective | Retrospective | Retrospective | Retrospective | Prospective | Prospective, observational study | Prospective | Prospective | Prospective |
| Sample size | 305 | 147 | 60 adults and 287 pediatric cases | 45 | 60 | 2301 pediatric cases (5 - 15 years) | 647 adults and 881 pediatric cases | 712 | 128 DHF cases |
| Male% | 60.30% | 51.70% | 50.7% | 58.33% | 53.33% | 59.0% | 55.4% | 52.53% | N/A |
| Female% | 39.70% | 48.30% | 49.3% | 41.67% | 46.67% | 41.0% | 44.6% | 47.47% | N/A |
| Mean duration of fever (days) | 3.9 | N/A | 5.4 | N/A | N/A | N/A | N/A | N/A | N/A |
| DF | 80.70% | 53.74% | 36.9% | 100.00% | 53.33% | N/A | 61.1% | 43.82% | 0% |
| DHF | 19.30% | 46.26% | 63.1% | 0.00% | 46.67% | N/A | 38.9% | 44.80% | 100% |
| Cardiac | None | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Neurological | None | 10.88% | 0.9% | N/A | N/A | N/A | 0.7% | N/A | 3% |
| Renal | None | N/A | N/A | N/A | N/A | N/A | 0.2% | N/A | N/A |
| Hepatic | Mild = 62.6%, moderate = 3% | 82.05% | 40.3% | N/A | N/A | 10.0% | 38.2% | 36.52% | 47% |
| Headache | 55.10% | 51.02% | 15.0% | 80.48% | 77.19% | N/A | 63.2% | 37.68% | N/A |
| Bodyache | 52.50% | 12.24% | 8.4% | 41.46% | N/A | N/A | N/A | 9.90% | N/A |
| Nausea | 21.30% | N/A | 57.0% | N/A | 67.80% | N/A | N/A | N/A | N/A |
| Vomiting | 43.10% | 72.79% | 59.0% | N/A | 70.00% | 36.0% | 52.1% | 64.33% | 56% |
| Diarrhea | 15.40% | N/A | N/A | N/A | N/A | N/A | N/A | 9.70% | 4% |
| Abdominal pain | 21.60% | 68.03% | N/A | N/A | 33.90% | 20.0% | 36.9% | 62.31% | N/A |
| Bleeding manifestations | 2.60% | N/A | 35.7% | 100.00% | 13.33% | 42.0% | 69.7% | 15.31% | N/A |
| right hypochondrial tenderness | 38.00% | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Epigastric tenderness | 6.90% | N/A | N/A | N/A | N/A | N/A | N/A | N/A | 62% |
| Platelet count | Count < 25 × 109/L = 10.5%; Count < 100 × 109/L = 58.4%; | N/A | N/A | N/A | N/A | N/A | N/A | Count < 100 × 109/L = 80.59% | Count < 100 × 109/L = 15.3% |
| WBC count | Count < 4 × 106/L = 71.5% | N/A | N/A | Count < 5 × 106/L = 62.22% | N/A | N/A | N/A | N/A | N/A |
| Mortality | None | N = 0 | N = 1 | N/A | N/A | N/A | N = 8 | N = 0 | 3% |
Note. N/A: not available.
We did a parallel study on adult dengue patients and during comparison with this adult cohort (n = 1167), we noted several differences.49 The proportion of DHF was significantly lower among the children (19.3% vs 33.6%, P < .001). A Sri Lankan study by Malavige et al in 2006 noted that children had a higher tendency for fluid leakage than the adults. However, the pattern observed in the current epidemic was different.12,21 Children had more gastrointestinal symptoms and signs such as vomiting (43.1% vs 19.7%, P < .001), tenderness in the right hypochondrium (38.0% vs 26.0%, P < x.001) and abdominal pain (21.6% vs 15.0%, P = .005), compared to adults.
Conclusion
We have comprehensively analyzed the clinical and biochemical characteristics among a group of hospitalized pediatric dengue patients during a large Sri Lankan dengue epidemic. We found that abdominal symptoms and signs, low WBC and low platelet counts to be significantly associated with DHF. Liver enzyme derangement did not predict DHF. Considerable variations were noted in relation to the onset of the critical phase. Furthermore, we noted several differences in the pattern of dengue infections in children compared with previous publications from Sri Lanka. Moreover, considerable differences in the clinical and biochemical measurements were seen when compared with hospitalized adult dengue patients during the same epidemic.
Supplemental Material
Supplemental material, sj-pdf-1-gph-10.1177_2333794X20974207 for Clinical and Biochemical Characteristics of Dengue Infections in Children From Sri Lanka by Umesh Jayarajah, Manohari Madarasinghe, Damayanthi Hapugoda, Upul Dissanayake, Lakshika Perera, Vibhavee Kannangara, Champika Udayangani, Ranga Peiris, Pamodh Yasawardene, Ishan De Zoysa and Suranjith L. Seneviratne in Global Pediatric Health
Appendix
List of Abbreviations
DF dengue fever
DHF dengue hemorrhagic fever
WHO World health Organization
SD standard deviation
WBC white blood cell
AST aspartate transaminase
ALT alanine transaminase
Footnotes
Authors’ Contributions: UJ: contributed to conception and design; contributed to acquisition, analysis, and interpretation; drafted manuscript; critically revised manuscript; gave final approval; agrees to be accountable for all aspects of work ensuring itegrity and accuracy.
MM: contributed to conception and design; contributed to acquisition; drafted manuscript; gave final approval; agrees to be accountable for all aspects of work ensuring itegrity and accuracy.
DH: contributed to conception and design; contributed to acquisition; drafted manuscript; gave final approval; agrees to be accountable for all aspects of work ensuring itegrity and accuracy.
UD: contributed to conception and design; contributed to acquisition; drafted manuscript; critically revised manuscript; gave final approval; agrees to be accountable for all aspects of work ensuring itegrity and accuracy.
LP: contributed to conception and design; contributed to acquisition, analysis, and interpretation; drafted manuscript; gave final approval; agrees to be accountable for all aspects of work ensuring itegrity and accuracy.
VK: contributed to conception and design; contributed to acquisition, analysis, and interpretation; drafted manuscript; gave final approval; agrees to be accountable for all aspects of work ensuring itegrity and accuracy.
CU: contributed to conception and design; contributed to acquisition, analysis, and interpretation; drafted manuscript; gave final approval; agrees to be accountable for all aspects of work ensuring itegrity and accuracy.
RP: contributed to conception and design; contributed to acquisition, analysis, and interpretation; drafted manuscript; gave final approval; agrees to be accountable for all aspects of work ensuring itegrity and accuracy.
PY: contributed to conception and design; contributed to acquisition, analysis, and interpretation; drafted manuscript; critically revised manuscript; gave final approval; agrees to be accountable for all aspects of work ensuring itegrity and accuracy.
IDZ: contributed to conception and design; contributed to acquisition, analysis, and interpretation; drafted manuscript; critically revised manuscript; gave final approval; agrees to be accountable for all aspects of work ensuring itegrity and accuracy.
SLS: contributed to conception and design; contributed to acquisition, analysis, and interpretation; drafted manuscript; critically revised manuscript; gave final approval; agrees to be accountable for all aspects of work ensuring itegrity and accuracy.
Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
Ethics Approval and Informed Consent: Ethical approval was obtained from Ethical Review Committee of National of Sri Lanka to conduct the study (No: AAJ/ETH/COM/2017-21). Informed written consent was obtained from parents/guardians and assent from children where appropriate before including in the study.
ORCID iDs: Umesh Jayarajah 
https://orcid.org/0000-0002-0398-5197
Pamodh Yasawardene
https://orcid.org/0000-0002-5210-5141
Availability of Data and Materials: The datasets and materials generated and analyzed during the current study are available from the corresponding author on reasonable request.
Supplemental Material: Supplemental material for this article is available online.
References
- 1. World Health Organization. Dengue and dengue haemorrhagic fever 2017. http://www.who.int/mediacentre/factsheets/fs117/en/
- 2. Seneviratne S, Malavige G, De Silva H. Pathogenesis of liver involvement during dengue viral infections. Trans R Soc Trop Med Hyg. 2006;100:608-614. [DOI] [PubMed] [Google Scholar]
- 3. Kabra S, Juneja R, Jain Y, et al. Myocardial dysfunction in children with dengue haemorrhagic fever. Natl Med J India. 1998;11:59-61. [PubMed] [Google Scholar]
- 4. Malavige G, Ranatunga P, Jayaratne S, Wijesiriwardana B, Seneviratne S, Karunatilaka D. Dengue viral infections as a cause of encephalopathy. Indian J Med Microbiol. 2007;25:143. [DOI] [PubMed] [Google Scholar]
- 5. Jayarajah U, Seneviratne SL, Gurugama P, Wanigasuriya KP. Microalbuminuria and dengue viral infections. Southeast Asian J Trop Med Public Health. 2017;48:938. [Google Scholar]
- 6. Gurugama P, Jayarajah U, Wanigasuriya K, Wijewickrema A, Perera J, Seneviratne SL. Renal manifestations of dengue virus infections. J Clin Virol. 2018;101C:1-6. [DOI] [PubMed] [Google Scholar]
- 7. Jayarajah U, Basnayake O, Nagodavithane K, Jayasinghe J, Samarasekera DN. Atypical presentation of severe dengue in a patient following a major abdominal surgery. Case Rep Infect Dis. 2020;2020:2916107. doi: 10.1155/2020/2916107 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Perera L, De Zoysa N, Jayarajah U, Senanayake N, De Zoysa I, Seneviratne SL. Transfusion-transmissible dengue infections. Trans R Soc Trop Med Hyg 2020; 114:traa075. doi: 10.1093/trstmh/traa075 [DOI] [PubMed] [Google Scholar]
- 9. Jayarajah U, Lahiru M, De Zoysa I, Seneviratne SL. Dengue infections and the surgical patient. Am J Trop Med Hyg. 2020. doi:10.4269/ajtmh.20-0983 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Malavige GN, Fernando S, Fernando DJ, Seneviratne SL. Dengue viral infections. Postgrad Med J 2004;80:588-601. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Jayarajah U, Dissanayake U, Abeysuriya V, et al. Comparing the 2009 and 1997 World Health Organization dengue case classifications in a large cohort of South Asian patients. J Infect Dev Ctries. 2020;14:781-787 [DOI] [PubMed] [Google Scholar]
- 12. Malavige GN, Ranatunga PK, Velathanthiri VGNS, et al. Patterns of disease in Sri Lankan dengue patients. Arch Dis Child. 2006;91:396-400. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Sirisena P, Noordeen F, Fernando L. A preliminary study on clinical profiles of dengue and dengue haemorrhagic fever suspected patients from two hospitals in the Western Province of Sri Lanka. Sri Lankan J Infect Dis 2014;4:99-107. [Google Scholar]
- 14. Lucas GN, Amerasinghe A, Sriranganathan S. Dengue haemorrhagic fever in Sri Lanka. Indian J Pediatr 2000; 67:503-504. [DOI] [PubMed] [Google Scholar]
- 15. Epidemiology Unit, Ministry of Health Sri Lanka. Dengue. http://www.epid.gov.lk
- 16. Jayarajah U, Faizer S, de Zoysa I, Seneviratne SL. A large dengue epidemic affects Sri Lanka in 2017. Int J Prog Sci Technol. 2017;6:84-85. [Google Scholar]
- 17. de Silva P, Jayawardena P, Jayarajah U, et al. Improving clinical outcomes through setting up of a specialised dengue treatment unit. Int J Adv Res. 2017;5:1152-1153. [Google Scholar]
- 18. Hadinegoro SRS. The revised WHO dengue case classification: does the system need to be modified? Paediatr Int Child Health. 2012;32:33-38. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Jayarajah U, Dissanayake U, Edirisinghe K, Seneviratne SL. The World Health Organization dengue case classifications. Galle Med J. 2020;25:74-79. [Google Scholar]
- 20. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ. 2005;172:367-379. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Malavige GN, Velathanthiri VGNS, Wijewickrama ES, et al. Patterns of disease among adults hospitalized with dengue infections. QJM 2006;99:299-305. [DOI] [PubMed] [Google Scholar]
- 22. Seet RC, Ooi EE, Wong HB, Paton NI. An outbreak of primary dengue infection among migrant Chinese workers in Singapore characterized by prominent gastrointestinal symptoms and a high proportion of symptomatic cases. J Clin Virol. 2005;33:336-340. [DOI] [PubMed] [Google Scholar]
- 23. Wichmann O, Hongsiriwon S, Bowonwatanuwong C, Chotivanich K, Sukthana Y, Pukrittayakamee S. Risk factors and clinical features associated with severe dengue infection in adults and children during the 2001 epidemic in Chonburi, Thailand. Trop Med Int Health. 2004;9:1022-1029. [DOI] [PubMed] [Google Scholar]
- 24. Mahmuduzzaman M, Chowdhury AS, Ghosh DK, Kabir IM, Rahman MA, Ali MS. Serum transaminase level changes in dengue fever and its correlation with disease severity. Mymensingh Med J. 2011;20:349-355. [PubMed] [Google Scholar]
- 25. Chhina RS, Goyal O, Chhina DK, Goyal P, Kumar R, Puri S. Liver function tests in patients with dengue viral infection. Dengue Bull. 2008;32:110-117. [Google Scholar]
- 26. Murugananthan K, Kandasamy M, Rajeshkannan N, Noordeen F. Demographic and clinical features of suspected dengue and dengue haemorrhagic fever in the Northern Province of Sri Lanka, a region afflicted by an internal conflict for more than 30 years—a retrospective analysis. Int J Infect Dis. 2014;27:32-36. [DOI] [PubMed] [Google Scholar]
- 27. Messer W, Kanakaratne N, Thevanesam V, Ranawaka G, Shahani A, De Silva A. Clinical features of hospitalized dengue patients in Sri Lanka from 2004 to 2006. Sri Lankan J Infect Dis. 2012;2:9–18. [Google Scholar]
- 28. Lucas GN, Amerasinghe A, Sriranganathan S. Dengue haemorrhagic fever in Sri Lanka. Indian J Pediatr. 2000; 67:503-504. [DOI] [PubMed] [Google Scholar]
- 29. Banerjee A, Barik KL, Bandyopadhyay A, Paul UK. A study on the clinical features of dengue virus infected pediatric patients. Int J Contemp Pediatrics. 2018;5:368-371. [Google Scholar]
- 30. Ramachandran S, Gera A, Kamal M, Gera R, Roy MP. Changing trends in clinicopathological parameters in dengue with evaluation of predictors of poor outcome in children. Int J Contemp Pediatrics. 2016;3:1411-1415. [Google Scholar]
- 31. Kumar A, Rao CR, Pandit V, Shetty S, Bammigatti C, Samarasinghe CM. Clinical manifestations and trend of dengue cases admitted in a Tertiary Care Hospital, Udupi District, Karnataka. Indian J Community Med. 2010;35: 386-390. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Kamath SR, Ranjit S. Clinical features, complications and atypical manifestations of children with severe forms of dengue hemorrhagic fever in South India. Indian J Pediatr. 2006;73:889-895. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Ratageri VH, Shepur T, Wari P, Chavan S, Mujahid I, Yergolkar P. Clinical profile and outcome of dengue fever cases. Indian J Pediatr. 2005;72:705-706. [DOI] [PubMed] [Google Scholar]
- 34. Shah I, Deshpande G, Tardeja P. Outbreak of dengue in Mumbai and predictive markers for dengue shock syndrome. J Trop Pediatr. 2004;50:301-305. [DOI] [PubMed] [Google Scholar]
- 35. Narayanan M, Aravind M, Thilothammal N, Prema R, Sargunam CR, Ramamurty N. Dengue fever epidemic in Chennai-a study of clinical profile and outcome. Indian Pediatr. 2002;39:1027-1033. [PubMed] [Google Scholar]
- 36. Pai Jakribettu R, Boloor R, Thaliath A, Yesudasan George S, George T, Ponadka Rai M, et al. Correlation of clinicohaematological parameters in paediatric dengue: a retrospective study. J Trop Med. 2015;2015:647162. doi: 10.1155/2015/647162 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Sajid A, Ikram A, Ahmed M. Dengue fever outbreak 2011: clinical profile of children presenting at Madina teaching hospital Faisalabad. J Univ Med Dent Coll. 2012;3:42-47. [Google Scholar]
- 38. Ahmed S, Arif F, Yahya Y, Rehman A, Abbas K, Ashraf S, et al. Dengue fever outbreak in Karachi 2006–a study of profile and outcome of children under 15 years of age. J Pak Med Assoc. 2008;58:4. [PubMed] [Google Scholar]
- 39. Alam AS, Sadat SA, Swapan Z, Ahmed AU, Karim MN, Paul H, et al. Clinical profile of dengue fever in children. Bangladesh J Child Health. 2009;33:55-58. [Google Scholar]
- 40. Pervin M, Tabassum S, Ali M, Mamun KZ, Islam M. Clinical and laboratory observations associated with the 2000 dengue outbreak in Dhaka, Bangladesh. Dengue Bull. 2004;28:96-106. [Google Scholar]
- 41. Ahmed FU, Mahmood CB, Sharma JD, Hoque SM, Zaman R, Hasan MS. Dengue and dengue haemorrhagic fever in children during the 2000 outbreak in Chittagong, Bangladesh. Dengue Bull. 2001;25:33-39. [Google Scholar]
- 42. Hanafusa S, Chanyasanha C, Sujirarat D, Khuankhunsathid I, Yaguchi A, Suzuki T. Clinical features and differences between child and adult dengue infections in Rayong Province, southeast Thailand. Southeast Asian J Trop Med Public Health. 2008;39:252. [PubMed] [Google Scholar]
- 43. Sawasdivorn S, Vibulvattanakit S, Sasavatpakdee M, Iamsirithavorn S. Efficacy of clinical diagnosis of dengue fever in paediatric age groups as determined by WHO case definition 1997 in Thailand. Dengue Bull. 2001;25: 56-64. [Google Scholar]
- 44. Kalayanarooj S, Vaughn DW, Nimmannitya S, et al. Early clinical and laboratory indicators of acute dengue illness. J Infect Dis. 1997;176:313-321. [DOI] [PubMed] [Google Scholar]
- 45. Lam PK, Van Ngoc T, Thuy TTT, et al. The value of daily platelet counts for predicting dengue shock syndrome: results from a prospective observational study of 2301 Vietnamese children with dengue. PLoS Negl Trop Dis. 2017;11:e0005498. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46. Thu TLT, Minh DN, Van NT, et al. Clinical features of dengue in a large Vietnamese cohort: intrinsically lower platelet counts and greater risk for bleeding in adults than children. PLoS Negl Trop Dis. 2012;6:e1679. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47. Phuong CXT, Nhan NT, Kneen R, et al. Clinical diagnosis and assessment of severity of confirmed dengue infections in Vietnamese children: is the World Health Organization classification system helpful? Am J Trop Med Hyg. 2004;70:172-179. [PubMed] [Google Scholar]
- 48. Chairulfatah A, Setiabudi D, Ridad A, Colebunders R. Clinical manifestations of dengue haemorrhagic fever in children in Bandung, Indonesia. Ann Soc Belg Med Trop. 1995;75:291-295. [PubMed] [Google Scholar]
- 49. Jayarajah U, de Silva PK, Jayawardena P, et al. Pattern of dengue virus infections in adult patients from Sri Lanka. Trans R Soc Trop Med Hyg. 2018;112:144-153. [DOI] [PubMed] [Google Scholar]
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Supplementary Materials
Supplemental material, sj-pdf-1-gph-10.1177_2333794X20974207 for Clinical and Biochemical Characteristics of Dengue Infections in Children From Sri Lanka by Umesh Jayarajah, Manohari Madarasinghe, Damayanthi Hapugoda, Upul Dissanayake, Lakshika Perera, Vibhavee Kannangara, Champika Udayangani, Ranga Peiris, Pamodh Yasawardene, Ishan De Zoysa and Suranjith L. Seneviratne in Global Pediatric Health