European Journal of Cardiovascular Medicine

Dengue fever is caused by dengue viruses that are transmitted by Aedes mosquitoes. The World Health Organization estimates that 2.5 billion people in tropical and subtropical regions worldwide are at risk of infection¹ . Approximately 50–100 million cases are reported annually, of which 500,000 require hospital admission ². A significant 71.4% of the cases are children at the age of 2–17 years. The occurrence of dengue fever presents a substantial burden for public health care in developing countries. During epidemiological week 24 of 2022, 1494 dengue cases were reported, leading to a total of 21,689 cumulative reported dengue cases in 2022. This is an increase of 68.7% compared to 12,854 cases reported during the same period (epidemiological week 1 to week 24) in 2021³. Data from Thailand’s surveillance reported 166,680 cases from 2017 to 2022, approximately 27,780 per year. The change of infection was 41.87/100,000 population, with a mortality rate of 0.11%.Currently, there are no drugs for the causative treatment of dengue diseases, and therapies are therefore mainly symptomatic [4]. Nevertheless, the morbidity rate of this disease has been reduced from 5% to about 2% in ten countries in Southeast Asia ⁴. Patients with symptoms of a severe infection usually demonstrate hemorrhage followed by shock^5,6. Common causes of death among children with dengue infection are delayed diagnosis and untimely medical attention, eventually resulting in internal bleeding due to severe hemorrhage and multi-organ failure⁷. The early detection of markers valuable for the diagnosis of disease severity could be imperative for proper medical treatment, preventing the risk of hemorrhagic complications. Laboratory data were shown to support a correct diagnosis of dengue virus infection, thus facilitating treatment and appropriate care plans⁸. Clinical risk factors and laboratory data were recently studied to explore their usefulness for the prediction of dengue disease severity^9,10. A decision tree algorithm that differentiates dengue fever from other types of fever was recently proposed .

AIM

The aim of this study is to identify and evaluate clinical and laboratory prognostic indicators that can predict the severity of dengue infection at an early stage

This hospital-based prospective observational study was conducted at at Department of General Medicine, Govt Medical College, Jhunjhunu, Rajasthan, India over a period of 6 months, from June 2025 to Nov 2025, to evaluate prognostic indicators associated with the severity of dengue infection. All patients presenting during the study period with acute febrile illness suggestive of dengue and subsequently confirmed by laboratory testing were assessed for eligibility. Patients of either sex aged  ≥18 years (as applicable) with laboratory-confirmed dengue infection based on NS1 antigen and/or dengue IgM antibody positivity, who were admitted within the first seven days of illness and whose parents or guardians provided informed consent, were included in the study. Patients with febrile illnesses due to other infectious causes such as malaria, typhoid, leptospirosis, or scrub typhus, as well as those with coexisting chronic systemic diseases including chronic liver disease, chronic kidney disease, hematological disorders, or immunodeficiency states, were excluded. Patients with incomplete clinical records, insufficient laboratory data, or those who had received prior treatment at another healthcare facility that could alter laboratory parameters were also excluded. Detailed demographic information, clinical features, vital signs, and warning signs were recorded using a structured proforma at the time of admission. Laboratory parameters including complete blood count, hematocrit, platelet count, liver function tests, and other relevant investigations were documented and monitored during the hospital stay. Based on the World Health Organization classification, patients were categorized into dengue fever, dengue with warning signs, and severe dengue. The collected data were systematically analyzed using appropriate statistical methods to identify clinical and laboratory parameters significantly associated with disease severity, with a p-value of less than 0.05 considered statistically significant

Table 1: Age Distribution of Dengue Patients According to Disease Severity

The majority of dengue patients belonged to the 31–40 years age group (91 cases), followed by 18–30 years (66 cases). Severe dengue was more commonly observed in the younger and middle-aged adults, with no cases reported above 61 years, and the age distribution showed no statistically significant association with disease severity (p > 0.05).

Table 2:Sex distribution of patients According to Disease Severity

Male patients constituted the majority of dengue cases (170), with higher numbers seen in dengue without warning signs and dengue with warning signs. Severe dengue was proportionally more common among females, and the association between sex and disease severity was statistically significant (p < 0.05).

Table 3: Distribution according to area of residence

Urban residents constituted the majority of dengue cases (183) compared to rural residents (67). Severe dengue was more frequently observed among urban patients, and area of residence showed an association with disease severity.(p<0.0001)

Table 4: Signs and symptoms

Fever was the most common presenting symptom (210 cases), followed by myalgia and headache, and was seen across all categories of dengue severity. Warning signs such as abdominal pain, oedema, dehydration, and neurological symptoms were more frequent in dengue with warning signs and severe dengue, indicating progressive disease severity.(p<0.0001)

Table 5: Bleeding manifestation

Bleeding manifestations were observed more frequently in dengue with warning signs and severe dengue compared to dengue without warning signs. Conjunctival suffusion and rash were the most common bleeding manifestations, while gastrointestinal bleeding and hematuria were predominantly seen in patients with severe disease.(p>0.05)

Table 6:Hematological Parameter

Progressive thrombocytopenia with increasing disease severity was observed, with severe dengue showing the highest proportion of platelet counts below 20,000/mm³. Rising hematocrit, leukopenia, and relatively higher hemoglobin levels were more common in dengue with warning signs and severe dengue.

Table 7: Biological parameters

Elevated AST and ALT levels were increasingly observed with worsening dengue severity, with marked transaminase elevation predominantly seen in severe dengue cases. Hypoalbuminemia and raised serum creatinine were more frequent in dengue with warning signs and severe dengue.

A total of 250 patients were included in the study and were categorized into dengue without warning signs, dengue with warning signs, and severe dengue. The most commonly affected age group was 31–40 years, accounting for 91 patients, followed by the 18–30 years age group with 66 patients. Dengue without warning signs was predominant across all age groups, while severe dengue was more frequently observed in the younger and middle-aged population. Patients above 60 years had the least number of severe dengue cases, with none reported in this age group.Khan MI et¹¹ al Among 977 confirmed dengue illness, ages  with a mean + SD age of 39.9 + 6.7 years

 Among the 250 dengue patients studied, males constituted the majority with 170 cases, while females accounted for 80 cases. Dengue without warning signs was more commonly seen in males (116 cases) compared to females (44 cases). Dengue with warning signs was also more frequent among males (45 cases) than females (21 cases). However, severe dengue showed a higher proportion among females (15 cases) compared to males (9 cases).

The majority of dengue patients belonged to urban areas, accounting for 183 cases, compared to 67 cases from rural areas. Dengue without warning signs was more commonly observed in urban residents than rural residents. Patients with dengue with warning signs were also predominantly from urban areas. Severe dengue cases were higher among urban residents compared to rural residents.

Fever was the most common presenting symptom, observed in 210 patients across all severity groups, followed by myalgia and headache. Classical dengue symptoms such as headache and retro-orbital pain were seen more frequently in patients with warning signs and severe dengue. Gastrointestinal symptoms, including dehydration and abdominal pain, showed a rising trend with increasing disease severity. Oedema was predominantly noted in dengue with warning signs and severe dengue, suggesting plasma leakage. Neurological manifestations were uncommon overall but were more frequently associated with severe dengue.Jelia et al¹² The most common presenting symptoms were fever (100.0%) followed by myalgia (77.0%), nausea and vomiting (56.0%).

Bleeding manifestations were observed across all categories of dengue severity, with a clear increase in frequency among patients with warning signs and severe dengue. Rash and conjunctival suffusion were the most common manifestations, seen in a substantial proportion of cases. Epistaxis and oral bleeding were more frequent in dengue with warning signs, reflecting underlying platelet dysfunction and capillary fragility. Gastrointestinal bleeding in the form of hematemesis or melena was predominantly seen in patients with warning signs and severe dengue. Hematuria and hemoptysis were less common but occurred mainly in more severe forms of the disease.

Hematological abnormalities showed a clear progression with increasing severity of dengue infection. Thrombocytopenia was common across all groups, with severe thrombocytopenia (<20,000/mm³) predominantly seen in severe dengue patients. Rising hematocrit, especially a rise of more than 20%, was mainly observed in dengue with warning signs and severe dengue, indicating significant plasma leakage. Leukopenia was frequently noted in all categories, but was most pronounced in severe dengue cases. Hemoglobin levels were largely within the normal range in most patients, with lower values seen in a smaller proportion, particularly in severe dengue.Jelia et al¹² Hemoglobin level and hematocrit values did not show a significant correlation with hemorrhagic manifestations. There was an increased white blood cell count, and absolute neutrophil count in patients with bleeding (P<0.001), but there was no correlation of monocyte and lymphocyte counts with bleeding symptoms. The decreased number of platelets was significant for bleeding (P=0.003). The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) also showed a statistically significant correlation with hemorrhagic manifestations (P<0.001).

Derangement of biochemical parameters increased progressively with the severity of dengue infection. Elevation of AST and ALT was mild in dengue without warning signs, moderate in dengue with warning signs, and marked in severe dengue, with AST levels consistently higher than ALT. Hypoalbuminemia was uncommon in dengue without warning signs but became increasingly prevalent in dengue with warning signs and severe dengue, indicating plasma leakage. Most patients without warning signs had normal serum creatinine levels, whereas rising creatinine was more frequently observed in dengue with warning signs. Severe dengue showed the highest proportion of patients with significantly elevated creatinine, reflecting renal involvement. Srisuphanunt M, et al¹³ age (>17 years), anorexia, hematocrit (>40%), neutrophils (≤51%), atypical lymphocyte (>3%), platelet count (≤97 × 103/µL), albumin (≤2.7 g/dL), AST (>104 U/I), ALT (>141 U/I).

The present study highlights that dengue infection predominantly affected young and middle-aged adults, with dengue without warning signs being the most common presentation, while severe dengue constituted a smaller but clinically significant proportion. Males and urban residents formed the majority of cases; however, severe dengue showed a relatively higher proportion among females, indicating possible gender-related vulnerability. Clinical manifestations progressed from classical symptoms such as fever, myalgia, and headache to gastrointestinal, bleeding, and plasma leakage features with increasing severity. Hematological abnormalities, particularly thrombocytopenia and rising hematocrit, showed a strong association with disease severity, while leukopenia was common across all groups. Biochemical derangements, including progressive elevation of AST and ALT with AST predominance, hypoalbuminemia, and rising serum creatinine, correlated well with severe dengue and organ involvement.

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