Dengue, a vector-borne disease, has witnessed a concerning surge in incidence over recent decades, becoming a commonly neglected global health issue. 

The underreporting of cases is pervasive due to a significant proportion of asymptomatic and mild self-limiting illnesses. Researchers have estimated an astonishing 390 million annual infections, of which 96 million manifested clinical symptoms, highlighting the substantial burden of the disease. [1] Notably, 70% of these infections were concentrated in Asia, underlining the region's vulnerability to dengue outbreaks. The gravity of the situation is further emphasized by the alarming increase in mortality rates, rising from 960 to 4,032 in 2015. [2] India, in particular, has been grappling with dengue since its first recorded epidemic in 1963-1964 in Calcutta and the eastern coastal region. The persistent outbreaks in the country are attributed to the widespread invasion of Aedes aegypti, especially in rural areas undergoing rapid urbanization. [3] Recent data from 2022 indicates that India documented 110,473 dengue cases between January and October, resembling figures reported in 2018 (101,192). However, the preceding years witnessed substantially higher case numbers: 188,401 in 2017, 157,315 in 2019, and 193,245 in 2021. [4] On a global scale, dengue prevalence is notably concentrated in South Asia (3546.9 [2128.5–5429.5]), Southeast Asia (2940.6 [1787.3–4457.0]), and the Caribbean (2510.4 [1656.1–3578.7]) [5]. Dengue is caused by the dengue virus (DENV), which comprises four serotypes (DENV-1, DENV-2, DENV-3, and DENV-4). Transmission occurs primarily through the bite of the female Aedes aegypti mosquito and, to a lesser extent, by A. albopictus. Clinical manifestations range from a flu-like illness to severe dengue, with no specific treatment available. Early detection and management of severe cases can significantly reduce mortality from 20% to 1%. Additionally, infection with a single serovar type confers lifelong complete immunity to that serovar, alongside transient and partial immunity to other serovars [6]. The multifaceted challenges posed by dengue underscore the critical need for global health efforts and research to curb its impact. This comprehensive overview of dengue's global impact emphasizes its increasing incidence, particularly in Asia, and the need for heightened awareness, early detection, and effective management to address the escalating public health threat. Hence, we aimed to examine the clinical profile and identify the atypical presentations of dengue fever cases.

This retrospective observational study was conducted in the Department of Medicine at F.H. Medical College in Agra, India, from 2021 to 2023. Before participation, each patient provided informed consent, and the study received approval from the Institutional Ethical Committee. Serum samples were systematically collected from individuals clinically suspected of dengue, subsequently confirmed using NS1 antigen, IgM, and IgG antibody assays via ELISA (Human Anti-Dengue Virus IgG ELISA Kit (ab108728)). Rigorous procedures included a thorough patient history, detailed clinical examinations for all positive cases, and documentation of key haematological parameters, encompassing platelet count, haemoglobin levels, hematocrit (HCT) levels, complete blood count (CBC), and white blood cell count (WBC). The data obtained from the study was subjected to comprehensive statistical analysis, with results presented in both tabular and graphical formats to facilitate a comprehensive understanding. Descriptive statistics, including the number (n) and corresponding percentages (%), were utilized to present the distribution of key variables.

In the present study, 1423 cases were screened for dengue. In 2021, 83 cases were recorded, with 97.59% identified as positive cases for dengue. Subsequent years exhibited fluctuating numbers of positive cases depicted in Table 1. Out of the total positive cases (804), the majority of them were males (59.95%), and the rest of them were females (40.05%). Most cases were aged between 18-44 years (38.56%). [figure-1] The most prominent clinical feature observed was fever, reported in 93.53% of the cases. Headache was also common, noted in 77.74%, followed by myalgia (62.94%), body pain (50.12%), vomiting (42.04%), joint pain (32.84%), dry cough (20.27%), nausea (14.68%) and abdominal pain (9.83%). [table-2] In the present study, a total of 177 cases exhibited atypical clinical manifestations, where Hepatomegaly was the most common clinical feature (8.08%), followed by Splenomegaly (5.60%), Bradycardia (4.35%) and Meningitis (2.11%). [table-3] Based on specific markers, including NS1 Ag, IgM, IgG, and the combination of IgG + IgM in the dengue-positive patients, it was found that 63.56% of the cases tested positive for the NS1 antigen. Additionally, 12.06% were positive for IgM antibodies. Furthermore, 18.03% tested positive for IgG antibodies, and 6.34% exhibited positivity for both IgG and IgM antibodies. [figure-2] The Haematological parameters of dengue-positive cases showed that Thrombocytopenia, characterized by a platelet count below 150,000/mm³, was observed in 524 cases. Leucopenia, defined by a white blood cell count below 4000/mm³, was identified in 221 cases. Additionally, 59 cases displayed a raised hematocrit level. [table-4] These findings suggest a high prevalence of thrombocytopenia among the dengue-positive cases, potentially indicating platelet depletion commonly associated with dengue infections. Leucopenia, another common haematological manifestation in dengue, was also present but to a lesser extent. In a smaller percentage of cases, the observation of raised hematocrit may indicate hemoconcentration, a characteristic feature of severe dengue.

TABLE-1: Year-wise distribution of dengue cases during the study period

TABLE-2: Clinical features of dengue-positive cases (n=804)

TABLE-3: Atypical clinical manifestations in dengue patients (n=177)

TABLE-4: Haematological parameters of dengue-positive cases (n=464)

FIGURE-1: Age and sex-wise distribution of dengue cases.

FIGURE-2: Distribution of dengue-specific markers in dengue-positive cases.

Dengue is emerging as a significant public health concern, with recurrent outbreaks observed across India. [7,8] Providing effective care to individuals suspected of dengue within primary care settings necessitates proficient clinical assessment, appropriate laboratory testing, and knowledgeable healthcare professionals capable of recognizing warning signs and offering guidance to mitigate the severity of the disease. Factors contributing to the escalating incidence of dengue include rapid urbanization, globalization, a burgeoning population, suboptimal solid waste management, and inadequate water control, collectively fostering conducive environments for mosquito breeding and consequently amplifying the prevalence of cases and associated fatalities. [9,10] The identification of dengue cases is facilitated through distinct clinical features, with studies highlighting those atypical manifestations in dengue fever manifest as multisystemic and intricate, involving organs such as the liver, brain, heart, kidney, and central nervous system. [11]

The incidence of dengue positivity has exhibited a consistent upward trend over the preceding years. Notably, the present study reveals a peak in the number of dengue-positive cases in 2021, followed by 2020, 2019, and 2022. This aligns with similar observations by Mohan K et al. [12] and other researchers. [13] Investigations further indicated that a substantial proportion of cases fell within the 15–44 age group, consistent with existing literature. Within this study, the majority of cases were in the age group of 18-44 years, constituting 38.56% of the total. Additionally, a notable male preponderance was observed, with 59.95% of cases being males. This gender distribution corresponds with the findings of Mohan K et al. [12], where males constituted 57.7%, surpassing females at 42.2%. These trends are in concordance with the observations made by Chandralekha et al. [14]

The predominant clinical presentation in the present study was fever, evident in 93.53% of all presenting patients, followed by headache (77.74%) and myalgia (62.94%). Additional common symptoms included body pain (50.12%), vomiting (42.04%), joint pain (32.84%), dry cough (20.27%), nausea (14.68%), abdominal pain (9.83%), diarrhoea (6.22%), retro-orbital pain (5.10%), burning micturition (3.23%), and rashes (1.49%). These findings align with the observations of Hasan SR et al. [15] and other researchers. [12,16] Retro-orbital pain, recognized as a cardinal feature of dengue fever, has been consistently reported in prior studies. [12,17,18]

The present study recorded the atypical symptoms, where Hepatomegaly emerged as the most prevalent atypical clinical manifestation (8.08%), followed by Splenomegaly (5.60%), Bradycardia (4.35%), Meningitis (2.11%), Hemoptysis (0.62%), Acalculous cholecystitis (1.00%), and Acute pancreatitis ranking as the least common (0.25%). Notably, Hepatomegaly demonstrated high specificity for the development of both dengue hemorrhagic fever and dengue shock syndrome. These findings are consistent with observations made by Mohan K et al. [12], Rowe E et al. [19], and others [20], highlighting Hepatomegaly as a prominent atypical feature. However, this contrasts with studies where bradycardia, meningitis, hemoptysis, and acalculous cholecystitis were identified in higher percentages of confirmed dengue fever cases. [21-23] Conversely, Nagarajan N et al. [24] reported febrile diarrhoea (85.5%), gall bladder edema (28.3%), abdominal pain (90.9%), myositis (77.9%), and rhabdomyolysis (3.6%) as observed atypical manifestations. Other atypical features, such as encephalitis, acute pancreatitis, acute renal failure, disseminated intravascular coagulation, cardiac conduction disturbances, and ischemic heart disease, were also reported. [18,24]

Among the 1423 samples from clinically suspected dengue cases, 804 (23%) were confirmed positive through ELISA. Specific markers, including NS1 Ag, IgM, IgG, and the combination of IgG + IgM, were utilized to delineate the characteristics of dengue-positive patients. Results revealed that 63.56% of cases tested positive for the NS1 antigen, indicating an ongoing active dengue infection. Additionally, 12.06% displayed positivity for IgM antibodies, signifying recent exposure to the dengue virus. Furthermore, 18.03% tested positive for IgG antibodies, suggesting a previous dengue infection. Notably, 6.34% exhibited positivity for both IgG and IgM antibodies, indicative of a combination of recent and past infections. These findings closely align with a study conducted by Anand et al. [25] and other researchers [12]. On the contrary, Jisamerin J et al. [18] showed that the IgM antibody was positive in all patients (100%), and NS 1 antigen was positive in only 9.3%. 

In the present study, the haematological parameters of dengue-positive cases revealed that Thrombocytopenia, characterized by a platelet count below 150,000/mm³, was prevalent in 65.17% of cases. Leucopenia, defined as a white blood cell count below 4000/mm³, was identified in 27.49% of cases. Additionally, 7.34% of cases displayed a raised hematocrit level. [24,26] These findings indicate a notable prevalence of thrombocytopenia among dengue-positive cases, suggesting platelet depletion commonly associated with dengue infections. While leucopenia, another common haematological manifestation in dengue, was present, it occurred to a lesser extent. Observing raised hematocrit in a smaller percentage of cases may suggest hemoconcentration, a characteristic feature of severe dengue. It is worth noting that other studies, such as those conducted by Ahmed et al. [27] and Mohan et al. [12], have reported fewer cases with thrombocytopenia. Furthermore, studies have established a hematocrit level exceeding 40% as a prognostic factor for severe dengue. [25,27,28]

A comprehensive understanding of disease progression, identification of risk factors, recognition of warning signs, and vigilance for clinical complications throughout different phases of dengue fever is crucial for primary care physicians. This knowledge empowers them to manage the disease appropriately and timely, ultimately reducing morbidity and mortality. Primary care physicians play a pivotal role in regularly imparting health education about dengue fever to rural communities, employing methods such as health camps or interpersonal communication-based health awareness programs. [29] Therefore, the presence of atypical presentations should prompt thorough investigations for dengue, especially during ongoing epidemics. Emphasizing primary care and effective management is paramount in preventing the progression of expanded dengue syndrome.

While this study provides valuable insights into the changing clinical profile of dengue fever cases, certain limitations should be acknowledged. The retrospective nature of the analysis may introduce biases in data collection and reporting. Additionally, variations in healthcare infrastructure and reporting practices across different regions could impact the consistency and reliability of the findings. The study's reliance on historical data might not fully capture the real-time dynamics of atypical manifestations, and potential confounding factors, such as co-infections or comorbidities, may not have been comprehensively considered.

In conclusion, the evolving clinical profile of dengue fever cases across various epidemics, even within consistent regions and over time, underscores the dynamic nature of the disease. Primary care physicians should maintain a heightened awareness to promptly identify and manage atypical manifestations of dengue fever, which are becoming increasingly prevalent. Recognizing these atypical presentations is essential, as they are no longer rare occurrences and are expected to rise, emphasizing the importance of vigilant screening in dengue patients. This study highlights the necessity for ongoing seroepidemiological surveillance to effectively and promptly identify clinical features and atypical manifestations of dengue infection. To address the limitations, it is recommended to conduct prospective studies with a standardized and uniform data collection methodology.

CONFLICT OF INTEREST- All authors declare no conflict of interest.

SOURCE OF FUNDING- None

CONSENT:

As per international or university standards, the authors have collected and preserved written participant consent.

ETHICAL APPROVAL:

As per international or university standards, the author(s) has collected and preserved written ethical permission.

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