Dengue fever is a mosquito-borne viral illness caused by the dengue virus (DENV), which exists in four distinct serotypes (DENV-1 to DENV-4). It is transmitted primarily by the Aedes aegypti mosquito and poses a significant public health burden in tropical and subtropical regions worldwide. The World Health Organization (WHO) classifies dengue into three categories: dengue without warning signs, dengue with warning signs, and severe dengue, based on clinical and laboratory parameters that help predict disease severity and guide management strategies [1]. India is hyperendemic for dengue, with multiple serotypes co-circulating, leading to frequent outbreaks, increased hospitalization rates, and challenges in clinical management [2].

Dengue with warning signs, as per the WHO 2009 classification, includes symptoms such as abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, liver enlargement >2 cm, and an increase in hematocrit with a concurrent rapid decrease in platelet count [3]. These signs are considered predictors of progression to severe dengue, which can manifest as severe plasma leakage, severe bleeding, or severe organ involvement. However, the predictive value of these warning signs is still debated, and not all patients with warning signs progress to severe disease [4]. On the other hand, some patients without warning signs may deteriorate rapidly, underscoring the need for close monitoring and timely intervention.

The clinical profile of dengue patients with warning signs may differ significantly from those without, in terms of hematological parameters, liver enzyme elevations, and the need for interventions like intravenous fluids, blood transfusions, or intensive care unit (ICU) admission [5]. Studies have shown that patients with warning signs often present with higher hematocrit levels, lower platelet counts, and more pronounced hepatic transaminase elevations compared to those without warning signs [6]. The evaluation of short-term outcomes, including duration of hospital stay, need for ICU care, complications, and mortality, is crucial for assessing the effectiveness of early warning signs as prognostic indicators and for optimizing resource allocation in healthcare facilities.

Timely identification of patients at risk of developing severe disease is pivotal in reducing mortality. The WHO classification aims to facilitate early triage and appropriate clinical decisions. Nevertheless, studies in different populations have reported varied sensitivity and specificity of warning signs in predicting disease severity and outcomes [7,8]. Therefore, understanding the regional clinical patterns and validating the usefulness of warning signs in local settings is essential for tailoring dengue management protocols.

This study aims to compare the clinical profile and short-term outcomes of dengue patients with and without warning signs in a tertiary care setting. By analyzing differences in demographic characteristics, clinical symptoms, laboratory findings, and in-hospital outcomes such as duration of hospitalization, complications, and need for critical care, we hope to identify markers that can help stratify risk more effectively. Such data can aid clinicians in refining triage criteria, improving patient outcomes, and ensuring more efficient use of hospital resources, especially during seasonal epidemics when healthcare systems are overwhelmed [9,10]. This study aims to compare the clinical profiles and short-term outcomes of dengue patients presenting with warning signs versus those without.

Study Design: This was a hospital-based observational, prospective, comparative study conducted to evaluate the clinical profile and short-term outcomes of dengue patients with warning signs versus those without warning signs.

Study Place: Department of Medicine, Government Medical College and Hospital, Baramati, Pune, Maharashtra.

Study Duration: 1 year

Study Population: Patients admitted to the Department of Medicine with a clinical and serological diagnosis of dengue fever were screened and included as per eligibility criteria.

Sample Size: A total of 100 patients were enrolled in the study, divided into two groups:

• Group A (With Warning Signs) – 50 patients
• Group B (Without Warning Signs) – 50 patients

Inclusion Criteria

• Patients aged ≥18 years.
• Confirmed diagnosis of dengue infection based on NS1 antigen or IgM antibody positivity.
• Admission within the first 7 days of onset of symptoms.
• Patients giving written informed consent for participation.

Exclusion Criteria

• Patients diagnosed with co-infections (malaria, leptospirosis, typhoid, etc.).
• Known chronic liver disease, renal failure, or heart disease.
• Immunocompromised individuals (e.g., HIV, on chemotherapy/steroids).
• Pregnant women.

Statistical Analysis:- For statistical analysis, data were initially entered into a Microsoft Excel spread sheet and then analysed using SPSS (version 27.0; SPSS Inc., Chicago, IL, USA) and Graph Pad Prism (version 5). Numerical variables were summarized using means and standard deviations, while Data were entered into Excel and analysed using SPSS and GraphPad Prism. Numerical variables were summarized using means and standard deviations, while categorical variables were described with counts and percentages. Two-sample t-tests were used to compare independent groups, while paired t-tests accounted for correlations in paired data. Chi-square tests (including Fisher’s exact test for small sample sizes) were used for categorical data comparisons. P-values ≤ 0.05 were considered statistically significant.

Table 1: Demographic & Symptoms

Table 2: Comparison of Clinical, Laboratory Parameters, Interventions, and Outcomes in Dengue Patients with and Without Warning Signs

Table 3: Warning Signs Distribution

Table 4: Complications Developed

Table 5: Correlation of Platelet Count with Complications

The study included 100 patients, divided equally into groups with (n=50) and without (n=50) warning signs. The mean age was slightly higher in patients with warning signs (28.4 ± 10.2 years) compared to those without (26.1 ± 9.8 years), though the difference was not statistically significant (p = 0.21). Gender distribution was comparable between the groups, with males comprising 60% in the warning signs group and 64% in the group without warning signs (p = 0.68). Fever was present in all patients across both groups. However, symptoms such as abdominal pain (64% vs. 20%, p < 0.001) and vomiting (60% vs. 24%, p < 0.001) were significantly more frequent among patients with warning signs. In contrast, headache (50% vs. 60%, p = 0.31) and myalgia (56% vs. 68%, p = 0.20) did not differ significantly between the groups.

 Comparison of clinical and laboratory parameters between patients with and without warning signs revealed several significant differences. Hemoglobin levels were comparable between the groups (13.1 ± 1.4 vs. 13.5 ± 1.3 g/dL; p = 0.15). However, patients with warning signs had significantly lower platelet counts (48.6 ± 22.3 vs. 96.4 ± 30.1 ×10⁹/L; p < 0.001) and higher hematocrit levels (43.2 ± 5.5% vs. 40.1 ± 4.8%; p = 0.002). White blood cell counts were also lower in the warning signs group (4.1 ± 1.8 vs. 4.8 ± 1.6 ×10⁹/L; p = 0.04).

Liver function tests showed significantly elevated levels in patients with warning signs, including SGOT (102 ± 34 vs. 78 ± 29 IU/L; p = 0.001), SGPT (95 ± 30 vs. 70 ± 26 IU/L; p = 0.001), and serum bilirubin (1.3 ± 0.4 vs. 0.9 ± 0.3 mg/dL; p < 0.001). Additionally, hospital stay was significantly longer in the warning signs group (6.8 ± 2.1 vs. 4.2 ± 1.4 days; p < 0.001).

Regarding interventions, IV fluid resuscitation (96% vs. 80%; p = 0.02), platelet transfusion (30% vs. 4%; p < 0.001), and ICU admission (12% vs. 2%; p = 0.05) were significantly more common among those with warning signs. While all patients without warning signs recovered, recovery was slightly lower in the warning signs group (94%), though not statistically significant (p = 0.08). Referral (4% vs. 0%; p = 0.15) and death (2% vs. 0%; p = 0.31) were observed only in the warning signs group, without significant difference.

 Among the 50 patients with warning signs, the most frequently observed clinical features were abdominal pain (64%) and persistent vomiting (60%). Mucosal bleeding was present in 30% of patients, while hepatomegaly greater than 2 cm was noted in 20%. Clinical fluid accumulation was observed in 16% of cases.

 Complications were significantly more common among patients with warning signs compared to those without. Shock occurred in 24% of patients with warning signs versus 4% in those without (p = 0.004). Bleeding manifestations were also significantly higher in the warning signs group (28% vs. 6%; p = 0.003). Similarly, pleural effusion (16% vs. 2%; p = 0.03) and hepatic dysfunction (36% vs. 12%; p = 0.005) were observed more frequently in patients presenting with warning signs.

 A significant association was observed between lower platelet counts and the occurrence of complications (p < 0.001). Among patients with platelet counts <20 ×10⁹/L, 60% (9/15) experienced complications. This decreased to 40% (8/20) in those with platelet counts between 20–50 ×10⁹/L, and only 3% (2/65) in patients with counts >50 ×10⁹/L.

In the present study, dengue patients with warning signs exhibited a more severe clinical and laboratory profile compared to those without warning signs. Symptoms such as abdominal pain and persistent vomiting were significantly more frequent among patients with warning signs, consistent with the World Health Organization's (WHO) 2009 criteria for early recognition of potential disease progression [11]. Our findings align with those of Kalayanarooj et al., who reported that abdominal pain and vomiting were strong predictors of severe dengue in a cohort of Thai children [12].

The platelet count and hematocrit levels were significantly different between the two groups in our study, reflecting increased capillary permeability and plasma leakage in patients with warning signs. Similar hematological trends were noted by Srikiatkhachorn et al., who observed that thrombocytopenia and hemoconcentration were reliable indicators of disease severity [13]. Our finding that lower platelet counts were significantly associated with complications supports previous observations by Thein et al., who identified platelet count <50 ×10⁹/L as a strong predictor of adverse outcomes in hospitalized dengue patients [14].

Liver enzyme elevations (SGOT, SGPT) and serum bilirubin levels were significantly higher in patients with warning signs, indicating hepatic involvement. This observation is consistent with the study by Trung et al., which showed that elevated liver enzymes correlated with disease severity and warning signs, especially in secondary dengue infections [15]. Similarly, Sharma et al. noted that hepatic dysfunction was significantly more prevalent in patients with dengue hemorrhagic fever compared to those with classic dengue fever [16].

The duration of hospital stay, as well as the requirement for interventions like IV fluids, platelet transfusions, and ICU admission, were significantly greater among patients with warning signs. These findings are supported by studies from India and Southeast Asia, where warning signs were associated with prolonged hospitalization and increased resource utilization [17,18]. ICU admission and complications such as shock and bleeding were also notably higher in our study’s warning sign group, similar to the results reported by Alexander et al. in a multicentric study on dengue classification and severity [19].

Mortality in our study was low (2%) and observed only in the warning signs group, which mirrors outcomes from studies in tertiary care settings with early identification and supportive care [20]. Importantly, our results emphasize that early recognition of warning signs can guide prompt interventions, potentially reducing mortality and morbidity.

Though our findings support the clinical utility of WHO's 2009 classification, it is essential to note that not all patients with warning signs progressed to severe disease, and a few without warning signs did develop complications. This suggests that while warning signs are valuable indicators, continuous monitoring and individualized assessment remain critical.

The present study highlights that dengue patients with warning signs exhibit a significantly more severe clinical course compared to those without warning signs. Key findings include a higher incidence of gastrointestinal symptoms, profound thrombocytopenia, hem concentration, hepatic dysfunction, and increased hospital resource utilization, including IV fluid therapy, platelet transfusions, and ICU admissions. Complications such as shock, bleeding, pleural effusion, and hepatic dysfunction were also markedly more common in the warning signs group. Although the overall recovery rate was high in both groups, the warning signs group experienced higher rates of referral and mortality, albeit not statistically significant.A strong inverse correlation was noted between platelet count and the risk of complications, reaffirming its value as a prognostic indicator. The study reinforces the clinical relevance of the WHO 2009 warning signs in identifying patients at greater risk for adverse outcomes and underscores the need for early recognition, close monitoring, and timely intervention in these patients to prevent progression to severe dengue and reduce morbidity and mortality.

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