European Journal of Cardiovascular Medicine

Dengue is derived from a Swahili term, “Ka-dinga pepo” which means a seizure caused by an evil spirit.1,2 One of the first infectious diseases to be ascribed to a virus, there are primarily five serotypes in the family of Flaviviridae. Dengue is transmitted by the bite of a mosquito, Aedes albopictus. The incubation period is around one week.3

The affliction with dengue virus has become endemic in more than 100 countries with a higher range of infectivity between August and November. In India, the total economic burden due to dengue in 2018 was USD 27.4 million. The case fatality rate was 2.6%. In 2019, the incidence of dengue cases in India was 157,315, with 16,986 in the state of Karnataka. 4

A single-stranded positive-sense ribonucleic acid (RNA) virus, belonging to the family Flaviviridae, is the cause of dengue fever. The viral genome consists of 11,000 bases, and codes for three structural proteins (C, prM and E) that form the virus particle and seven non-structural proteins (NS1, NS2a, NS2b, NS3, NS4a, NS4b and NS5).5

Patients with dengue must be evaluated thoroughly in a manner to prevent progression to severe disease. The

febrile phase consists of high-grade fever, headache, vomiting, myalgia, arthralgia and transient macular rash rarely. Recovery without complications is not uncommon in this phase. Anorexia, nausea, vomiting, abdominal pain, diarrhoea, haemorrhagic manifestations and respiratory symptoms may occur. Examination reveals conjunctival injection, pharyngeal erythema, lymphadenopathy, hepatomegaly, facial puffiness and petechiae.6

A small proportion of patients develop a systemic vascular syndrome characterised by bleeding, shock, encephalopathy, seizures and organ impairment. This is called the critical phase and lasts 24 to 48 hours. Hypotension usually occurs in this phase. Moderate to severe thrombocytopenia is observed with a temporary increase in the activated partial thromboplastin time and reduced fibrinogen levels. Hepatic failure, central nervous system involvement, myocarditis, acute kidney injury can occur in this phase.7

The convalescent phase starts only when there is a resolution of haemorrhage and plasma, stabilization of vital signs and reabsorption of fluid accumulation. This phase lasts two to four days.8 Reverse transcriptase-polymerase chain reaction assay positive during the first five days of illness or detection of viral antigen non-structural protein 1 positive during the initial seven days of illness are the standard for diagnosis.9

In terms of blood investigations, leucopenia is observed usually in the course of dengue fever. Thrombocytopenia is considered a predictor of dengue hemorrhagic fever (DHF).9 Haemoconcentration is also a common finding due to the concentration of plasma fluid leakage, causing an increase in the haemoglobin weight in a unit volume of blood.10

Mortality due to dengue fever occurs mainly in cases of severe dengue with complications, more frequently in patients with underlying comorbidities. The social determinants are increasing age, poor health-seeking behavior, low income and less education11.

Therefore, early indicators of prognosis, available and accessible even in resource-limited settings offering primary healthcare, are vital to reduce the fatality rate associated with dengue fever. The primary objective of this study is to investigate the value of a complete blood count (CBC) in determining the prognosis of dengue fever. The second objective is to observe the trends of recovery of white blood cells (WBCs) and platelets in dengue fever.

This is a prospective and cross-sectional study conducted in the Department of Pathology at Uma Nath Singh Autonomous State Medical College, Jaunpur, Uttar Pradesh over period of 1 year.

Inclusion Criteria: Patients diagnosed with dengue fever, dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS) based on WHO criteria. Patients of all age groups, or specify (e.g., ≥11 years). Cases confirmed by serological tests (NS1 antigen, IgM/IgG ELISA) or RT-PCR. Patients with recorded laboratory parameters, including hemoglobin, hematocrit, white blood cell count, platelet count, and peripheral blood smear findings.

Exclusion Criteria: Patients with previous DENV infection or other flaviviruses; (3) patients aged < 10 years, pregnant patients, chronic renal dysfunction, malignant tumor, liver cirrhosis, acquired immune deficiency, and other autoimmune and inflammatory diseases. All patients in the study were clinically diagnosed and treated according to the 2009 WHO dengue guideline as non-severe and severe dengue. The acute dengue infection was confirmed by the SD BIOLINE dengue duo rapid test (NS1 Ag and immunoglobulins IgM/IgG.

Data Collection

All data from the patients meeting the inclusion criteria were abstracted from the electronic medical records. Clinical parameter included age, sex, symptoms, and laboratory results were collected on admission (between second and eleventh day after symptom onset) for dengue

Statistical Analysis

Categorical data were represented in numbers and frequencies (%), and continuous variables were expressed as median and interquartile ranges (IQR). Gender and age-adjusted logistic regression was performed to calculate coefficients, adjusted odds ratios (OR), and 95% confidence intervals (95% CI). The MedCalc software version 19, R version 4.1.0 and Rstudio version 1.3 were used for the statistical analysis and statistical significance was set with a two-tailed p-value < 0.05.

A total of 560 patient data were analyzed in this study, comprising 280 males and 280 females. The mean age of the study population was 34.2 years, with a standard deviation of 13.7, and the age range was between 16 and 84 years. Among these patients, 245 did not develop DHF during hospitalization, while 315 progressed to DHF in the ward.

During the acute febrile phase (Days 2–3) of the illness, leucopenia (WBC < 5000 cells/mm³) was observed in 72.4% of the patients. The average WBC counts for DF and DHF patients were 4.22 and 4.57, respectively. Neutrophil counts showed mean values of 2.85 in DF patients and 3.21 in DHF patients. Lymphocyte counts were lower in DHF patients, with a mean of 0.92 compared to 1.07 in DF patients.

Hematocrit levels (PCV) averaged 42.3% in DF cases and 45.1% in DHF cases. Platelet counts were significantly lower in DHF patients, with an average of 112.47 × 10³ cells/mm³, compared to 151.82 × 10³ cells/mm³ in DF patients (p < 0.001). Hemoglobin levels were also higher in DHF patients, with a mean of 14.12 g/dL, compared to 13.54 g/dL in DF patients (p = 0.03)

Table 1: Summarizing the age distribution of the study population

Table 2: Distribution of Full Blood Count (FBC) During the Acute Febrile Phase (Days 2–3 of Illness)

During the acute febrile phase, hemoglobin levels ranged from 9.2 to 18.5 g/dL, with average values for DF and DHF being 13.54 and 14.12, respectively. Mean packed cell volume (PCV) values for DF and DHF were 42.30 and 45.10, respectively. Thrombocytopenia (platelet < 150,000 cells/mm³) was observed in 61.8% of patients during the acute febrile phase, and 34.5% had platelet counts below 100,000 cells/mm³. Mean platelet values for DF and DHF were 151.82 and 112.47, respectively (Table 2).

The blood samples from the 5th day of illness were analyzed similarly for peripheral blood parameters. When considering the 5th-day values, mean WBC values among leakers and non-leakers were 3.30 and 4.04, respectively. Mean neutrophil values for DF and DHF were 1.88and 2.12, respectively. Mean lymphocyte counts for DF and DHF were 1.69 and 2.48, respectively (Table 3).

Table 3: Distribution of Full Blood Count (FBC) on Day 5 of Illness

Table 4: Distribution of Full Blood Count (FBC) Parameters During the Acute Febrile Phase (Days 2–3 of Illness) and Day 5 of Illness by Gender (n=560)

Haemoglobin values ranged from 9.00 to 18.20 during the 5th day of illness with average values of 13.12 and 14.04 among DF and DHF patients, respectively. Mean PCV values for DF and DHF were 39.29 and 41.07, respectively. Mean platelet counts for DF and DHF were 108.50 and 47.49, respectively.

Analytical results showed that the leakers had significantly different mean values of haemoglobin and platelet counts during acute phase compared to non-leakers. There was significant difference between acute phase WBC, neutrophils, lymphocytes and PCV values between DF and DHF patients.

WBC and haemoglobin values were significantly higher among leakers compared to non-leakers during day 5 and platelet values were significantly lower among leakers. But no significant difference between day 5 neutrophils, lymphocyte and PCV values were observed.

The current study provides important insights into the characteristics and demographics of dengue-positive cases and their relationship with hematological parameters. The findings show that most dengue-positive cases were single positive, followed by dual-positive patients, and only a small percentage were triple positive. The median age of dengue-positive participants was found to be 30 years, with the age group 20-29 years having the most positive cases, followed by the 30-39 years age group. These findings are consistent with previous studies that found higher dengue incidence rates among young adults, possibly due to increased outdoor activities, mosquito bite exposure, and social behaviors that facilitate disease transmission.12 similarly, the study found that males had a slightly higher percentage of dengue-positive cases (51.8%) than females (48.2%). This gender difference in dengue infection has been observed in other studies and could be attributed to differences in male and female behavior, occupation, and exposure to mosquito bites.13

This study revealed variations in the hematological parameters in the study population. TLC was significantly lower in dengue hemorrhagic fever patients than in dengue positive. This result is consistent with earlier research that found dengue patients substantially decreased TLC.14 Similarly, our study observed a significantly lower platelet count in dengue patients concurrently with Rauniyar R et al.15 Previous studies revealed that increased platelet breakdown and decreased platelet formation during dengue fever are the main factors in thrombocytopenia in dengue infection.16 However, the higher RBC count, hematocrit, and MCV in patients with dengue were observed in our study, similar to other relevant studies from Ethiopia.17 

We analyzed routine hematological parameters that may be associated with dengue patients. According to the WHO, the two most significant tests evaluated during dengue infection are hematocrit and thrombocytopenia. Among the analyzed parameters, thrombocytopenia and leucopenia were significantly associated with dengue infection. Thrombocytopenia, which is well correlated with dengue infection as shown by various studies, also remained significant in our study.18 In a binary logistic regression analysis, RBC indices (MCH, MCHC), neutrophil count and lymphocyte count were independent predictors of dengue positivity. These findings are consistent with previous reports that show dengue infection causes changes in blood cell counts.19

DF is an increasing, global problem with a growing footprint on millions of lives. At this time, monitoring decreases in hemoglobin and increases in WBC counts, particularly neutrophils, through routine CBC testing in hospitalized patients with suspected DF may identify those young children at higher risk of severe DF and death in the DR. Our study’s significant percentage of excluded individuals without diagnostic testing highlights the need for screening algorithms utilizing laboratory and clinical symptoms to diagnose and guide care of patients with DF in low-resourced settings, where other forms of testing are either expensive, resource-intensive, or have long turnaround times..

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