Introduction
In tropical countries like India, the most common reasons for Acute febrile illness include Dengue, Malaria, Typhoid fever, Leptospirosis, and Rickettsial infection. Acute respiratory infections and viral exanthematous fevers also significantly affect children. Population density and urbanization may contribute to the emergence and re-emergence of some of these diseases in tropical regions. Vector-borne diseases account for more than 17% of all infectious diseases, causing more than 70,0000 deaths annually as per WHO estimates [2]. In 2021, India reported nearly 300,000 cases and approximately 30,000 fatalities due to vector-borne diseases, according to data from the National Vector Borne Disease Control Programme (NVBDCP). Dengue saw 193,245 reported cases, leading to 345 fatalities.
This study will provide a comprehensive description of clinico-pathological parameters in dengue fever, along with key predictors of mortality and morbidity in dengue fever.
Methods and Materials
This study was an observational, single-center study with prospective data collection. Conducted at the Post Graduate Institute of Child Health, NOIDA, in the Department of Pediatrics over 18 months, from May 2022 to November 2023. All children aged 1 month to 18 years who were confirmed cases of dengue fever were included in the study. Children who have co-morbid conditions such as immunodeficiency, chronic renal failure, chronic liver disease, hematological diseases, and other conditions that may affect the hematological and biochemical parameters were excluded from the study. Diagnosis of dengue was made by DENV non-structural protein 1 (NS1) antigen or IGM ELISA positivity with a compatible clinical history. Further severity classification was done as per the World Health Organization (WHO) criteria [4].
Anaemia was classified using the WHO cutoff of haemoglobin for various age groups. Leucopenia and leucocytosis were defined as counts of 12 × 109 /L in children and 10.5 × 109 /L in those >10 years. Thrombocytopenia was defined as a platelet count < 150 × 109 /L16 Elevated aspartate aminotransferase (AST) was defined as >60 U/L in children 50 U/L in children 3–9 years, and >40 U/L in children >9 years. Elevated alanine transaminase (ALT) was defined as >45 U/L, and serum albumin 44.2 µmol/ L in children 52 µmol/L in children 4–10 years; >78 µmol/L in children 10–14 years; >94 µmol/L in children >14 years of age [5].
Data was entered in Microsoft Excel and analyzed using SPSS version 25. Categorical variables were reported as frequencies and percentages. Kolmogorov-Smirnov test and Shapiro-Wilk tests were used to check the normality of the data. Mean ± Standard Deviation (SD) and median (Q1, Q3) were used for normal and skewed data, respectively.
An independent sample T test or Mann-Whitney U test was used to compare the two groups. One-way ANOVA or Kruskal-Wallis test was used to compare more than two groups. The chi-square test /Fisher's exact test was used to compare the categorical variables. A p-value less than 0.05 was considered statistically significant.
Results and Observations
We enrolled 249 children aged 1 month to 18 years with a confirmed case of dengue fever. The mean age (SD) of the children was 8 (5,11)years. Fever was the most common symptom present in all the patients, followed by gastrointestinal symptoms such as pain in the abdomen and vomiting. The median (IQR) duration of fever was 4 (3,5). [Table no. 1]
| Demographic characteristics | Dengue (n=249) | |
| Gender | Male | 174(69.9) |
| Female | 75(30.1) | |
| Age groups (in years) | <1 | 16(6.4) |
| 1-4 | 42(16.9) | |
| 5-9 | 103(41.4) | |
| 10-14 | 65(26.1) | |
| 15-18 | 23(9.2) | |
| Age (in completed years) | 8(5,11) | |
| Setting | Urban | 249(100.0) |
| Weight (in kgs) | 22(15,34) | |
| Height (in cm) | 123(102,142) | |
| W/H | Normal | 192(77.1) |
| SAM / Severe thinness | 18(7.2) | |
| Underweight / thinness | 20(8.0) | |
| Overweight | 18(7.2) | |
| Obese | 1(0.4) |
Disease characteristics significantly associated with disease severity in dengue fever were pain in the abdomen, vomiting, rash, respiratory distress, abdominal distension, and hepatomegaly. Pleural effusion and shock were seen more in patients with severe dengue. Laboratory parameters that were associated with disease severity in dengue fever were TLC, hematocrit, DLC, platelets, LFT, and KFT. Disease characteristics that were significantly associated with mortality in dengue were hemoglobin, total leucocyte count, albumin, urea, and PT-INR. [Table no. 2]
| Disease Characteristics | Dengue fever (N=249) | Dengue fever without warning signs (N=98) | Dengue fever without warning signs (N=83) | Severe Dengue (N=68) | p – value (for dengue patients) |
| Fever | 249 | 98 | 83 | 68 | 0.13 |
| Vomiting | 108 | 31 | 35 | 42 | <0.05 |
| Pain Abdomen | 160 | 51 | 54 | 55 | <0.05 |
| Rash | 73 | 19 | 17 | 37 | <0.05 |
| Bleeding | 58 | 0 | 23 | 37 | <0.05 |
| Respiratory distress | 27 | 1 | 2 | 24 | <0.05 |
| Abdominal distension | 23 | 2 | 8 | 13 | <0.05 |
| Hepatomegaly/Splenomegaly (Malaria patients) | 71 | 13 | 21 | 37 | <0.05 |
| Haemoglobin | 12.1 (10.9,13.6) | 11.90 (10.93, 13.0) | 12.60 (11.2, 13.9) | 12.0 (10.1, 13.8) | <0.05 |
| TLC | 7140 (4700,9800) | 6800 (4905, 9375) | 7040 (4270, 8850) | 8310 (5143, 13200) | <0.05 |
| Platelet | 64750 (34000,128500) | 120000 (43000, 149000) | 49600 (32300,117000) | 41500 (29125,74000) | <0.05 |
| Haematocrit | 38.4 (34,44) | 36.40 (33.70, 40.77) | 39.90 (35.4, 44.2) | 41.10 (34.6, 50) | <0.05 |
| SGOT | 117 (55,222) | 61 (45, 126) | 119 (60, 223.50) | 399 (140.50, 1185) | <0.05 |
| SGPT | 50 (27,115) | 34 (23, 58.75) | 50 (27, 97) | 177.50 (54, 524) | <0.05 |
| Bilirubin | 0.6 (0.5,0.8) | 0.5 (0.5, 0.7) | 0.5 (0.5, 0.7) | 0.8 (0.6, 1.425) | <0.05 |
| Albumin | 3.5 (3.2,4) | 3.8 (3.5, 4) | 3.5 (3.2, 4) | 3.1 (2.775, 3.425) | <0.05 |
| Urea | 29 (20,42) | 24 (17, 34) | 27 (21, 35.50) | 43.50 (25.75, 79.50) | <0.05 |
| Creatinine | 0.5 (0.4,0.6) | 0.5 (0.4, 0.6) | 0.5 (0.4, 0.6) | 0.6 (0.5, 1) | <0.05 |
The median (IQR) duration of hospital stay in children admitted with severe dengue was 7 (IQR- 4,10) while that of dengue fever with warning signs was 5 (IQR-3.5,8.2) and dengue fever without warning signs was 4 (IQR-3,6.4), respectively. Sixty-eight (28%) patients had a duration of hospital stay >7 days, and 181 (72%) patients had a duration of hospital stay less than 7 days.
Correlation of disease characteristics with mortality.
Respiratory distress at admission was associated with increased mortality; the rest of the parameters showed no correlation. [Table no. 3]
| Signs/Symptoms | Survivors 50 (%) | Mortality18 (%) | p-value |
| Duration of fever in days | 5 (4,6) | 4 (3,4) | 0.055 |
| Rash | 27 (54) | 10 (55) | 0.9 |
| Vomiting | 29 (58) | 13 (72) | 0.28 |
| Pain abdomen | 38 (76) | 17 (94) | 0.15 |
| Shock | 32 (64) | 15 (83) | 0.12 |
| Respiratory distress | 14 (28) | 10 (55) | < 0.05 * |
| Hepatomegaly | 27 (54) | 10 (55) | 0.8 |
Correlation of laboratory parameters with mortality
Haemoglobin, total leucocyte count, albumin, urea, and PT-INR
showed a correlation with mortality; the rest of the parameters showed no significance. [Table no. 4]
| Laboratory parameters | Survivors | Mortality | p-value |
| Haemoglobin | 12.8 ± 2.6 | 10.5 ± 3.0 | < 0.05* |
| Total leucocyte count | 7615 (4677,1047) | 10800 (7865,14650) | < 0.05 * |
| Platelet | 40500 (26250,78500) | 45000 (36250,60500) | 0.44 |
| Haematocrit | 40.9 ± 9.3 | 39.2 ± 11.9 | 0.95 |
| Urea | 34 (24,67.5) | 67 (49,102) | < 0.05 * |
| Albumin | 3.19 ± 0.5 | 2.83 ± 0.5 | < 0.05 * |
| SGOT | 240 (132,1088) | 890 (280,2148) | 0.09 |
| SGPT | 115 (54,490) | 401 (146,921) | 0.061 |
| PT-INR | 2.5 ±0.55 | 1.14±1.1 | <0.05* |
Discussions
Eight years old was the median (IQR) age of dengue patients hospitalised (5,11). Consistent with earlier Indian research, the age group most impacted was 5–9 years (41.4 percent), followed by 10–14 years (26%) [6]. which reported a similar age group and mean age affected their studies. This may be due to the children in this age group being more exposed to mosquitoes in schools and open playgrounds. A 2:1 male-to-female ratio indicated that men were more often impacted than females. Two studies that indicated men were more impacted than women had a comparable gender distribution. This could be because men are exposed to the outside world more than women [7]. All of the patients who were hospitalised with dengue fever had a fever, with a median (IQR) duration of 4 (3,5) days at admission. A similar mean (4.5 days) duration of fever at admission was reported in a study by Sahana et al.,[6] and Mittal et al.,[8]. The signs and symptoms associated with the increased severity of dengue in our study were pain in the abdomen[9], vomiting, hepatomegaly, pleural effusion, bleeding, and shock. Similar findings noted by various studies done in the past [10-13].
Clinical fluid accumulation in the form of ascites and pleural effusion was present in more than one-third of patients with severe dengue. Ascites and pleural effusion were associated with increased severity as reported in various studies [10,14,9]. The shock was present in more than one-third of patients with severe dengue. Shock with or without respiratory distress has been reported to be the most frequent complication in patients with severe dengue [15]. There was no association of past infection of dengue with disease severity in our study[16]. Respiratory distress, deranged KFT, hypoalbuminemia, total leucocyte count, and deranged coagulation profile were associated with increased mortality in patients with severe dengue, which are comparable to the results of the study conducted by Amancio et al.,[17] and Sachdev et al[18].
Conclusion
The following symptoms of dengue fever were shown to be substantially correlated with the disease's severity: rash, vomiting, abdominal distension, respiratory distress, and hepatomegaly. Patients with severe dengue were more likely to have shock and pleural effusion. The following laboratory measures were linked to the severity of dengue fever: TLC, haematocrit, DLC, platelets, LFT, and KFT. The following disease characteristics were substantially linked to death in dengue: PT-INR, albumin, urea, total leucocyte count, and haemoglobin.
Declaration
Ethical Statements
The ethical committee approved the study. [IRB Approval letter number and date (IEC-2022-06-IM-29) (25-06-2022)] Informed written consent was obtained from the parents/guardians of the children, and the ascent was obtained from children above ten years of age.
Conflicts of Interest
The authors have nothing to disclose.
Acknowledgement
We thank all the residents and staff who were involved in the care of this patient.
Financial Support and Sponsorship
Nil.