European Journal of Cardiovascular Medicine

Dengue fever is an acute febrile illness caused by the dengue virus (DENV), a single-stranded RNA virus of the family Flaviviridae, transmitted to humans predominantly by the bite of infected female Aedes aegypti and, to a lesser extent, Aedes albopictus mosquitoes. Four antigenically distinct but closely related serotypes (DENV-1 to DENV-4) are known to circulate, and infection with one serotype confers lifelong homotypic immunity but only transient heterotypic protection, so that sequential infection with a different serotype increases the risk of severe disease [1].

Globally, dengue is regarded as the most rapidly spreading mosquito-borne viral disease, with the World Health Organization estimating that nearly half of the world's population now lives in areas at risk of dengue transmission and that approximately 390 million infections occur every year, of which about 96 million manifest clinically [2]. The disease is endemic in more than 100 countries across South-East Asia, the Western Pacific, the Americas and Africa, with South-East Asia and the Western Pacific bearing the largest share of the global disease burden [3].

India contributes substantially to the global dengue burden, with outbreaks being reported from nearly every state, and children constitute a particularly vulnerable group because of their comparatively immature immune and vascular systems and their limited ability to compensate for capillary leakage [4]. Data from the National Vector Borne Disease Control Programme (NVBDCP) have shown a rising trend in the number of reported dengue cases and deaths over the past two decades, with a disproportionately high case fatality rate among children below 14 years of age in several state-level analyses [5].

The clinical spectrum of dengue in children is notably broader and often more difficult to recognise than in adults, ranging from an asymptomatic infection or a mild undifferentiated febrile illness to classic dengue fever, and in a minority of cases progressing to dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), which are potentially fatal if not identified and managed promptly [6]. The World Health Organization revised its classification in 2009 to a two-tier system of "dengue without warning signs," "dengue with warning signs" and "severe dengue," specifically to improve early triage and reduce case fatality in resource-limited settings [7].

Several Indian studies from tertiary care centres in Delhi, Chennai, Kolkata, Pune and other cities have documented the changing clinical and epidemiological pattern of paediatric dengue, including a shift towards younger age groups, an increasing proportion of expanded dengue syndrome with atypical organ involvement, and a rising incidence of dengue with warning signs [8,9]. A study from North India reported thrombocytopenia and hepatic dysfunction as the most consistent laboratory abnormalities in children with dengue, while a study from South India highlighted the diagnostic value of the NS1 antigen assay in the early febrile phase [10,11].

Despite the availability of national and WHO guidelines, under-recognition of warning signs, delayed presentation to hospital, and inappropriate fluid management continue to contribute to avoidable morbidity and mortality in children, particularly in resource-constrained tertiary care settings that receive a large volume of referred and critically ill patients [12]. Continuous hospital-based surveillance of the clinical profile and outcome of paediatric dengue is therefore essential to identify local patterns of disease severity, to sensitise clinicians to early warning signs, and to guide resource allocation during seasonal outbreaks.

With this background, the present study was undertaken to describe the demographic characteristics, clinical presentation, laboratory profile, severity spectrum and treatment outcome of children with serologically confirmed dengue fever admitted to the Department of Paediatrics of a tertiary care teaching hospital, and to compare the findings with other studies conducted in India and elsewhere.

Aims and Objectives

To study the clinical profile, laboratory parameters, severity spectrum and outcome of serologically confirmed dengue fever in children admitted to a tertiary care teaching hospital.

Study Design and Setting

This was a hospital-based, prospective, observational study conducted in the Department of Paediatrics of a tertiary care teaching hospital, which serves as a referral centre for a large urban and surrounding rural population.

Study Period

The study was carried out over a period of 18 months, from January 2022 to June 2023, encompassing two dengue transmission seasons so as to capture seasonal variation in disease incidence and severity.

Study Population and Sample Size

All children aged between 1 and 12 years admitted with an acute febrile illness and found to be positive for dengue NS1 antigen and/or dengue-specific IgM antibody by enzyme-linked immunosorbent assay (ELISA) were considered for enrolment. Using an expected prevalence of severe dengue of 12% among paediatric dengue admissions (based on regional data), a 95% confidence interval and 5% absolute precision, a minimum sample size of 162 was calculated; the sample was extended to 250 children to allow for more robust sub-group analysis.

Inclusion Criteria

• Children aged 1 to 12 years of either sex; (2) acute febrile illness of less than 7 days' duration; (3) laboratory confirmation of dengue infection by NS1 antigen and/or IgM ELISA; (4) parents/guardians willing to provide written informed consent.

Exclusion Criteria

• Children with a concurrent confirmed diagnosis of malaria, enteric fever, or other definable cause of fever; (2) children with pre-existing haematological disorders, chronic liver or renal disease; (3) children whose parents did not consent to participate; (4) incomplete case records.

Ethical Considerations

The study protocol was approved by the Institutional Ethics Committee prior to commencement. Written informed consent was obtained from parents or legal guardians of all participating children, and assent was obtained from children above 7 years of age where appropriate. Confidentiality of patient data was maintained throughout the study.

Data Collection

A pre-tested, structured proforma was used to record demographic details, presenting symptoms, duration of illness prior to admission, general and systemic examination findings, and day-wise haematological and biochemical parameters. Vital signs, capillary refill time, and evidence of plasma leakage (pleural effusion, ascites, rising haematocrit) were monitored at least twice daily and more frequently in children with warning signs.

Laboratory Investigations

All children underwent a complete blood count with platelet count on admission and thereafter as clinically indicated, dengue NS1 antigen and IgM/IgG ELISA, liver function tests, renal function tests, and coagulation profile where indicated. Serial haematocrit monitoring was performed in children with warning signs or severe dengue. Chest radiograph and abdominal ultrasonography were performed selectively to look for pleural effusion and ascites.

Definitions and Classification

Cases were classified according to the WHO 2009 revised classification into (a) dengue without warning signs, (b) dengue with warning signs (abdominal pain/tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy, liver enlargement >2 cm, and a rising haematocrit with a rapid decrease in platelet count), and (c) severe dengue (severe plasma leakage leading to shock or fluid accumulation with respiratory distress, severe bleeding, or severe organ impairment). The older 1997 WHO classification (DF/DHF grades I-IV/DSS) was also applied for comparability with earlier Indian healthcare [7,13].

Treatment Protocol

All children were managed as per the National Vector Borne Disease Control Programme (NVBDCP) and WHO dengue case management guidelines, with supportive care, antipyretics (paracetamol only), judicious isotonic fluid therapy guided by haematocrit and clinical status, and platelet or blood product transfusion reserved for significant bleeding or extremely low platelet counts with active bleeding, rather than for prophylaxis alone.

Statistical Analysis

Data were entered in Microsoft Excel and analysed using SPSS software (version 26.0). Continuous variables were expressed as mean ± standard deviation (SD) and categorical variables as frequency and percentage. The Chi-square test was used to compare categorical variables between severity groups, and a p-value of less than 0.05 was considered statistically significant.

A total of 250 children with serologically confirmed dengue fever were enrolled over the 18-month study period. The results are presented under demographic, clinical, laboratory, severity and outcome parameters.

Demographic Profile

Of the 250 children studied, 146 (58.4%) were boys and 104 (41.6%) were girls, giving a male-to-female ratio of 1.4:1. The mean age of the study population was 7.3 ± 2.9 years, with the maximum number of cases (36.4%) occurring in the 6-9 year age group (Table 1). A seasonal clustering of cases was observed, with 68% of admissions occurring between July and October, coinciding with the post-monsoon period.

Table 1: Age and Sex Distribution of Study Participants (n = 250)

Clinical Presentation

Fever was present in 100% of children, and was typically high-grade and continuous. The other common presenting symptoms in decreasing order of frequency were myalgia/arthralgia, headache, vomiting, abdominal pain, retro-orbital pain, and rash (Table 2). Bleeding manifestations of any type were noted in 57 children (22.8%), the commonest being petechiae/skin rash with bleeding tendency (11.6%) followed by gum bleeding (6.4%) and epistaxis (3.2%); gastrointestinal bleeding (malena/haematemesis) was seen in 4 children (1.6%).

Table 2: Clinical Features at Presentation (n = 250)

 Percentages calculated out of total n = 250; more than one feature could be present in the same child.

Laboratory Profile

Thrombocytopenia (platelet count <1,00,000/mm³) was the most consistent laboratory abnormality, observed in 179 children (71.6%), with severe thrombocytopenia (<20,000/mm³) in 21 children (8.4%). Leukopenia was present in 46.8% and haemoconcentration (rise in haematocrit ≥ 20% above baseline) in 34.8% of children. Elevated liver transaminases (AST/ALT more than twice the upper limit of normal) were seen in 38.4% of children, generally more marked in those with warning signs and severe dengue (Table 3).

Table 3: Laboratory Parameters of the Study Population (n = 250)

 ULN = upper limit of normal; Hct = haematocrit.

Severity Classification

Based on the WHO 2009 classification, 155 children (62.0%) had dengue without warning signs, 62 children (24.8%) had dengue with warning signs, and 33 children (13.2%) had severe dengue; of these, 24 children (9.6% of total) met criteria for dengue haemorrhagic fever with plasma leakage and 9 children (3.6% of total) developed dengue shock syndrome (Table 4). A statistically significant association was observed between age less than 5 years and progression to severe dengue (p = 0.02), as well as between secondary dengue infection (IgG positive at presentation) and severe disease (p = 0.01).

Table 4: Severity Classification of Dengue Cases (WHO 2009 Criteria, n = 250)

 Classified as per WHO 2009 revised dengue classification.

Treatment and Complications

Most children (86.4%) were managed with oral rehydration and antipyretics alone or with a period of maintenance intravenous fluids; 13.6% required fluid resuscitation with isotonic crystalloids for warning signs or shock. Platelet transfusion was required in 19 children (7.6%), all of whom had either active bleeding or a platelet count below 10,000/mm³ with clinical concern. Fresh frozen plasma was administered in 8 children (3.2%) with coagulopathy and bleeding. Complications encountered included pleural effusion (11.2%), ascites (8.0%), acute kidney injury (2.0%), myocarditis (1.2%) and encephalopathy (0.8%) (Table 5).

Table 5: Complications Observed Among Study Participants (n = 250)

Some children had more than one complication.

Outcome

Of the 250 children, 235 (94.0%) recovered completely and were discharged in a stable condition, 12 children (4.8%) required transfer to the paediatric intensive care unit (PICU) for further management of severe dengue/shock, and 3 children (1.2%) succumbed to the illness, giving a case fatality rate of 1.2%. All three deaths occurred in children who presented late (more than 5 days after onset of fever) and who were already in decompensated shock with multiorgan dysfunction at the time of admission. The mean duration of hospital stay for the entire cohort was 5.4 ± 2.1 days, and was significantly longer in children with severe dengue (8.9 ± 2.6 days) compared to those without warning signs (4.1 ± 1.4 days) (p < 0.001) (Table 6).

Table 6: Outcome of Study Participants by Severity Category (n = 250)

This hospital-based prospective study of 250 children with confirmed dengue infection provides a comprehensive picture of the clinical profile, laboratory abnormalities, severity spectrum and outcome of paediatric dengue in a tertiary care teaching hospital setting, and its findings are broadly consistent with, while also adding nuance to, existing Indian and international healthcare.

In the present study, a male preponderance was noted (58.4% boys versus 41.6% girls), with a male-to-female ratio of 1.4:1. A similar male predominance has been reported by Gupta et al. from New Delhi and by Kumar et al. from a tertiary centre in North India, who attributed the higher male attack rate to greater outdoor exposure of boys during peak mosquito-biting hours [8,14]. The mean age of 7.3 ± 2.9 years and peak incidence in the 6-9 year age group in our study is comparable to the findings of Narayanan et al. from South India, who also reported the highest burden of dengue in school-going children [9]. This pattern reinforces the observation that school-going children, who spend considerable time both indoors and outdoors in areas of vector breeding, are at particularly high risk.

Fever was a universal finding in our cohort, consistent with its role as a mandatory diagnostic criterion, while myalgia, headache, vomiting and abdominal pain were the other predominant symptoms, mirroring the clinical pattern described in classical dengue fever by the WHO and by several Indian case series [1,7]. The relatively high frequency of abdominal pain (52.8%) and hepatomegaly (31.6%) in our study is in agreement with the findings of Sharma et al. from a tertiary hospital in Rajasthan, who reported hepatic involvement, including hepatomegaly and transaminitis, as a common and often under-recognised feature of paediatric dengue [15]. Bleeding manifestations were seen in 22.8% of our patients, a figure comparable to the 18-25% range reported in most Indian paediatric dengue series, with skin petechiae and gum bleeding being the most frequent forms, and major bleeding (gastrointestinal or intracranial) being distinctly uncommon [10,16].

Thrombocytopenia was the single most consistent laboratory abnormality in our study, present in 71.6% of children, which is in close agreement with rates of 65-80% reported by Kumar et al. and Cherian et al. from other Indian tertiary centres [14,17]. Leukopenia (46.8%) and haemoconcentration (34.8%) were also frequently observed, supporting the well-established role of serial complete blood counts, and particularly trend monitoring of platelet count and haematocrit together, in early identification of children at risk of plasma leakage [18]. Elevated liver transaminases were noted in 38.4% of our patients, a finding that parallels international reports describing the liver as one of the most commonly affected extra-vascular organs in dengue infection, presumably related to direct viral hepatotropism as well as immune-mediated injury [19].

When classified according to the WHO 2009 criteria, 62.0% of our patients had dengue without warning signs, 24.8% had dengue with warning signs and 13.2% had severe dengue (9.6% DHF with plasma leakage and 3.6% DSS). These proportions are comparable to those reported by Gupta et al. (severe dengue in 10-15% of hospitalised children) and by Chaudhary et al. from Uttar Pradesh, who documented a similar distribution across warning-sign categories in a large paediatric dengue cohort [8,20]. The observed association between age below 5 years and progression to severe disease in our study aligns with the hypothesis, supported by other Indian and South-East Asian studies, that very young children may present later or have less specific symptoms, delaying recognition of warning signs and appropriate fluid management [21]. Similarly, the association between secondary infection (IgG positivity at presentation) and severe dengue in our cohort supports the widely accepted antibody-dependent enhancement hypothesis, wherein pre-existing heterotypic antibodies from a prior dengue infection may paradoxically enhance viral entry into Fc-receptor-bearing cells during a subsequent infection with a different serotype [1,22].

Complications such as pleural effusion (11.2%), ascites (8.0%) and acute kidney injury (2.0%) reflect the systemic capillary leak that characterises severe dengue, and are broadly in keeping with complication rates reported from other Indian tertiary care series [16,23]. Rare but serious complications such as myocarditis and encephalopathy, though infrequent in our cohort (1.2% and 0.8% respectively), have also been described in Indian and international healthcare as part of the "expanded dengue syndrome," underscoring the importance of a high index of suspicion for atypical organ involvement in any child with confirmed or probable dengue who deteriorates unexpectedly [9,24].

The overall case fatality rate of 1.2% in our study is comparable to rates of 1-2% reported from other Indian tertiary care teaching hospitals, and considerably lower than the case fatality rates exceeding 5% reported from some peripheral or first-referral centres, highlighting the impact of timely referral, continuous haemodynamic monitoring and protocol-based fluid management available at a tertiary care level [13,25]. Notably, all deaths in our cohort occurred in children who presented late in an already decompensated state, a finding echoed by multiple Indian audits of dengue mortality, which consistently identify delayed presentation and delayed recognition of shock as the single most important preventable factor in dengue-related paediatric deaths [12,26]. This observation reinforces the public health importance of community awareness programmes, especially during the monsoon and post-monsoon months, to encourage early care-seeking for febrile illness.

Certain limitations of the present study merit consideration. Being a single-centre, hospital-based study conducted at a tertiary referral centre, our cohort may over-represent more severe cases referred from peripheral facilities, which could inflate the apparent proportion of warning-sign and severe dengue relative to the true community burden. Serotype-specific reverse transcriptase polymerase chain reaction (RT-PCR) and viral load estimation, which could have provided additional insight into serotype-specific severity, were not performed in all cases due to resource constraints. Longer-term follow-up to document post-dengue convalescent symptoms was also beyond the scope of the present study. Despite these limitations, the relatively large sample size, prospective design and standardised WHO-based classification lend robustness to our findings and allow meaningful comparison with other published Indian series.

Dengue fever continues to be an important cause of acute febrile illness and hospitalisation among children in India, with a clinical spectrum ranging from a self-limiting febrile illness to life-threatening shock. In the present study, the majority of children had an uncomplicated course, but nearly one in eight developed severe dengue, and thrombocytopenia, haemoconcentration and hepatic dysfunction emerged as the most useful and consistent laboratory markers for risk-stratifying children at the bedside. Younger age and evidence of secondary infection were significant risk factors for progression to severe disease, while delayed presentation was the single most important determinant of mortality. These findings emphasise the need for early clinical suspicion, judicious and protocol-based use of NS1/IgM testing, close monitoring of warning signs, and prompt, guideline-based fluid management, particularly during peak transmission months. Strengthening primary and secondary level referral pathways, together with sustained community-level vector control and health education, is likely to further reduce dengue-related morbidity and mortality in children.

1. World Health Organization. Dengue and severe dengue. Comprehensive guidelines for prevention and control of dengue and dengue haemorrhagic fever. Geneva: WHO Press; 2011.
2. World Health Organization. Global strategy for dengue prevention and control 2012-2020. Geneva: WHO Press; 2012.
3. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature. 2013;496(7446):504-7.
4. Gupta E, Dar L, Kapoor G, Broor S. The changing epidemiology of dengue in Delhi, India. Virol J. 2006;3:92.
5. National Vector Borne Disease Control Programme (NVBDCP), Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India. Dengue/DHF situation in India. New Delhi: NVBDCP; 2022.
6. Halstead SB. Dengue. Lancet. 2007;370(9599):1644-52.
7. World Health Organization. Dengue: guidelines for diagnosis, treatment, prevention and control. New edition. Geneva: WHO/TDR; 2009.
8. Gupta P, Khare V, Tripathi S, Nag VL, Kumar V, Khan F, et al. Assessment of World Health Organization definition of dengue re-classification and its application in children. J Trop Pediatr. 2016;62(1):5-12.
9. Narayanan M, Aravind MA, Thilothammal N, Prema R, Sargunam CS, Ramamurty N. Dengue fever epidemic in Chennai: a study of clinical profile and outcome. Indian Pediatr. 2002;39(11):1027-33.
10. Kabra SK, Verma IC, Arora NK, Jain Y, Kalra V. Dengue haemorrhagic fever in children in Delhi. Bull World Health Organ. 1992;70(1):105-8.
11. Rajajee S, Boobalan J, Rathnam S. Clinico-hematological profile and outcome of dengue fever in children. Indian J Pediatr. 2005;72(6):469-73.
12. Vikram K, Nagpal BN, Pande V, Srivastava A, Saxena R, Anvikar A, et al. An epidemiological study of dengue in Delhi, India. Acta Trop. 2016;153:21-7.
13. World Health Organization. Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. 2nd ed. Geneva: WHO; 1997.
14. 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(3):386-90.
15. Sharma S, Sharma SK, Rai A, Kumar V. Hepatic involvement in dengue fever in children: a hospital-based study. J Clin Diagn Res. 2019;13(6):SC01-SC04.
16. Kalayanarooj S. Clinical manifestations and management of dengue/DHF/DSS. Trop Med Health. 2011;39(4 Suppl):83-7.
17. Cherian T, Ponnuraj E, Kuruvilla T, Kirubakaran C, John TJ, Raghupathy P. An epidemic of dengue haemorrhagic fever & dengue shock syndrome in and around Vellore. Indian J Med Res. 1994;100:51-6.
18. Srikiatkhachorn A, Rothman AL, Gibbons RV, Sittisombut N, Malasit P, Ennis FA, et al. Dengue: how best to classify it. Clin Infect Dis. 2011;53(6):563-7.
19. Samanta J, Sharma V. Dengue and its effects on liver. World J Clin Cases. 2015;3(2):125-31.
20. Chaudhary V, Kumar V, Kumar S, Kant A, Kumar R. Clinical and laboratory profile of dengue infection in children: a study from a tertiary care hospital in Uttar Pradesh, India. Int J Contemp Pediatr. 2019;6(2):600-5.
21. Anders KL, Nguyet NM, Chau NVV, Hung NT, Thuy TT, Lien LB, et al. Epidemiological factors associated with dengue shock syndrome and mortality in hospitalized dengue patients in Ho Chi Minh City, Vietnam. Am J Trop Med Hyg. 2011;84(1):127-34.
22. Guzman MG, Alvarez M, Halstead SB. Secondary infection as a risk factor for dengue hemorrhagic fever/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection. Arch Virol. 2013;158(7):1445-59.
23. Kabra SK, Jain Y, Pandey RM, Madhulika, Singhal T, Tripathi P, et al. Dengue haemorrhagic fever in children in the 1996 Delhi epidemic. Trans R Soc Trop Med Hyg. 1999;93(3):294-8.
24. Verma R, Sahu R, Holla V. Neurological manifestations of dengue infection: a review. J Neurol Sci. 2014;346(1-2):26-34.
25. Karyanti MR, Uiterwaal CS, Kusriastuti R, Hadinegoro SR, Rovers MM, Heesterbeek H, et al. The changing incidence of dengue haemorrhagic fever in Indonesia: a 45-year registry-based analysis. BMC Infect Dis. 2014;14:412.
26. Rigau-Perez JG. Severe dengue: the need for new case definitions. Lancet Infect Dis. 2006;6(5):297-302.