Outcomes of adult severe dengue in a tertiary care centre of Bangladesh: a cross-sectional retrospective observation

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Understanding the factors influencing disease severity and outcomes is crucial for improving clinical management and reducing the disease burden. This retrospective observational study aimed to identify clinical patterns, risk factors, complications, and outcomes among adult severe dengue patients admitted to BIRDEM General Hospital, Dhaka, Bangladesh. Hospital records of admitted patients were analyzed to find the prevalence of severe dengue and explore the potential risk factors contributing to the severity of dengue outcomes. Key parameters included patient demographics, comorbidities, clinical manifestations, laboratory findings, and treatment outcomes. This retrospective study analyzed 330 adult dengue fever cases, identifying 26 (7.9%) as severe dengue. Severe dengue patients were significantly older (mean ~ 59 years), and showed a higher occurrence in pre-existing diabetes (84.6%), hypertension (69.2%), and chronic kidney disease (26.9%). Alteration of consciousness was significantly associated with severity, enhancing the odds of progressing to severe dengue by 51 times. Laboratory findings included significantly lower mean hematocrit (32.86%), hemoglobin (11.02 mg/dl), elevated liver enzymes (mean ALT 467.79 U/L, AST 865.3 U/L, ALP 146.41 U/L), lower serum albumin (31.7 mg/dL), elevated BUN (61.68 mg/dL), creatinine (2.71 mg/dL), and LDH (3007.33 U/L). A logistic regression model demonstrated good predictive ability (AUC = 0.8302), with alteration of consciousness and higher AST as independent risk factors of severe dengue. Based on the available data, despite high rates of complications (81% including plasma leakage, organ impairment, and concurrent co-infections), 16 (62%) were cured, and minimal mortality was reported (n = 3). By identifying high-risk populations and predictors of severe outcomes, this research aims to improve patient care and reduce dengue-related mortality. Dengue outcome Risk factors Bangladesh Predictors of severity Tropical diseases Figures Figure 1 1 Introduction Being one of the leading neglected tropical diseases, dengue infection is regarded as the most important arthropod-transmitted human viral disease (WHO 2019) and constitutes a significant global health threat. The worldwide challenge of dengue as a significant public health issue, particularly in the tropical and subtropical regions, has been widely investigated, emphasizing its epidemiology, clinical symptoms, and treatment approaches. Nonetheless, there is a scarcity of studies concentrating on the unique socio-environmental conditions in low and middle-income countries (LMICs) such as Bangladesh, which is situated in the dengue endemic zone of the southeastern region. Throughout Bangladesh, given the impact of climate change globally, the unusual changing monsoon pattern along with the elevated humidity, rising under-construction sites, and the water stagnation in unkempt containers being potential breeding sites for the proliferation have overall contributed to the increasing population of mosquitoes in Bangladesh, causing an acute upsurge of cases, over time. Dense populations, swift urban growth, and scarce healthcare resources worsen the disease's effects [ 1 ] . Earlier research has pinpointed key risk factors for progression to severe dengue as age [ 2 ] , pre-existing conditions (diabetes and hypertension), host immunity, genetic predisposition [ 3 ] , and delays in treatment [ 4 ] as crucial factors leading to unfavorable outcomes; however, localized data remains insufficient [ 1 ] . Despite ongoing control measures, the burden of the disease remains substantial, highlighting the need for in-depth research into clinical outcomes and contributing factors. Bangladesh requires immediate and long-term approaches to minimize dengue-related deaths in the coming days. This study aimed to identify the proportion of severe dengue among the hospitalized adult dengue fever patients, to explore the possible risk factors that cause progression to severe dengue, evaluated the demographics, clinical, and laboratory parameters of the adult dengue patients, and analyzed the outcome of severe dengue in BIRDEM General Hospital, Dhaka, Bangladesh, using retrospective data. The findings of our study will provide evidence-based insights in understanding the burden of severe dengue and identifying the associated risk factors, to guide efficient healthcare interventions and improve outcomes of the patients. Early identification of at-risk patients, early intervention with optimal supportive care, close observation, and judicious parenteral fluid therapy, it is possible to reduce the mortality rates to less than 1%, even among cases of Dengue shock syndrome (DSS) [ 5 ] . Timely and appropriate monitoring and management, principally with fluid intervention, and awareness of progression to severe dengue are critical in the reduction of morbidity and mortality [ 6 , 7 ] . Less than 1% with viremia progress to potentially fatal form of severe dengue, due to risk factors as age, comorbidities, host genetics, and virus strain, heterotypic secondary infections being the most conspicuous one [ 8 ] . Identifying the predictive factors for severe dengue is of potential importance for the effective management of dengue patients by healthcare providers [ 9 ] . 2 Materials and Methods Study design and population This retrospective cross-sectional study was conducted at BIRDEM General Hospital, Dhaka, Bangladesh. (BIRDEM, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders). The target population included all adult dengue fever patients admitted to the study site from January 1, 2023, to December 31, 2024. The study’s inclusion criteria were: (1) adults 18 years and above, of both genders, and (2) admitted with a history of suspected dengue infection with at least one of the following confirmed laboratory tests: (a) positive dengue NS1 antigen, or (b) positive dengue IgM and IgG, or (c) positive dengue IgM with negative dengue IgG, or (d) positive dengue PCR. Those in whom the final diagnosis of severe dengue could not be established or the outcome of dengue could not be determined were excluded. The retrospective data was extracted from the stored database of electronic medical records (EMR) and paper-based documented medical records at the study site. Using a structured case record form (CRF), the demographic data, clinical presentation, laboratory findings, outcomes, and complications of all adult dengue patients were recorded. The severity of dengue was assessed according to the WHO 2009 classification. Case definition of dengue As per the 2009 dengue case definition by the WHO, dengue patients were classified into severe and non-severe dengue [ 10 ] . Patients with non-severe dengue were further sub-categorized based on the presence or absence of warning signs. Non-severe dengue without warning signs was defined as acute fever with at least two of the following: nausea, vomiting, rash, myalgia, arthralgia, a positive tourniquet test, or leukopenia. Warning signs included: 1. abdominal pain, 2. persistent vomiting ( ≥ 3 episodes of vomiting in 12 hours) [ 11 ] , 3. clinical fluid accumulation, 4. lethargy, 5. liver span > 15cm, 6. bleeding from mucosal areas, including nose, gums, gastrointestinal tract, or vagina, or 7. an elevated hematocrit of ≥ 20% with concurrent thrombocytopenia. Severe dengue was classified as having: (1) severe plasma leakage with shock or with respiratory distress (i.e., respiratory rate ≥ 24 breaths/min. with oxygen saturation < 95% in room air, and/or requiring oxygen therapy), (2) severe clinical bleeding, defined as spontaneous bleeding from mucosal areas or in vital organs, that necessitates blood transfusion, (3) severe organ impairment, defined as AST > 1000 U/L and/or ALT > 1000 U/L, encephalitis, myocarditis, and/or serum creatinine ≥ 1.3 mg/dL) [ 2 , 11 ] . Sample size calculation Based on a cross-sectional observational study conducted at Dhaka Medical College Hospital and Chittagong Medical College Hospital of Bangladesh, 17% of patients experienced severe dengue, and 89% of those with non-severe cases exhibited at least one warning sign [ 3 , 12 ] . We used the formula to estimate the required sample size: n = p(1-p)/(E/1.96)^2 . So, we assumed a 17% (0.17) prevalence from the previous study, allowed for a 5% (0.05) margin of error, and to estimate the prevalence of severe dengue with 95% confidence interval, we needed to study a minimum of 217 adult patients with dengue. Statistical analyses The proportion of severe dengue was estimated and expressed as a percentage (%). The 95% confidence intervals for the proportion of severe dengue were computed and reported. Mean and standard deviations for continuous variables - age, symptoms, and laboratory investigations were done. To compare the mean between severe and non-severe dengue, student’s T-test was used. For categorical variables, Pearson’s chi-square (χ2) or Fisher’s exact test was used. Logistic regression was used to assess the risk factors associated with severe dengue. The odds ratios (OR) and 95% Confidence intervals for odds ratios were reported. Univariate analyses and multivariable analyses in logistic regression model were performed for binary outcome (severe dengue vs. non-severe dengue). Data analysis was conducted using SPSS for Mac OS and STATA. 3 Results For this retrospective observational study, the hospital records from 1st January 2023 to 31st December 2024 were reviewed. During this period, 457 cases were diagnosed or classified as dengue fever in the electronic discharge summaries and the in-patient documented hospital admission files. Of these screened 457 cases, initially 45 cases had to be excluded as they were < 18 years, had not presented with fever on admission, in terms of dengue serology had only dengue IgG positive or all negative serology results. For the remaining 412 cases, additional 82 cases had to be further excluded, as the duration of the fever was not mentioned or the cases had sub-acute duration of febrile illness (i.e., ≥ 8 days and longer); hence, based on our inclusion criteria, these cases could also not be included in this study and thus, had to be further excluded. Ultimately, 330 cases met the inclusion criteria and were enrolled in our study. (Figure A1 ) 3.1 Proportion of severe dengue The proportion of severe dengue among the dengue fever cases in adults admitted at BIRDEM General Hospital was found to be 26/330 (7.9%). The corresponding 95% confidence interval (CI) was 0.496–0.108. Of the enrolled cases (n = 330), 26 (7.9%) were severe dengue, and 304 of the patients were non-severe dengue (92.4%). Amidst the non-severe dengue (n = 304), 46 (15.1%) were dengue with warning signs, and 258 (84.9%) were dengue without warning signs. (Table 1 ) Table 1 Severe and non-severe dengue, with and without warning signs. Severity n % Severe dengue 26 7.9 Non-severe dengue • Dengue with warning signs • Dengue without warning signs 46 258 15.1 84.9 According to the 2009 WHO dengue classification, severe dengue presented as: 2/26 (7.7%) adult severe dengue patients developed severe plasma leakage with shock 3/26 (11.5%) adult severe dengue patients had severe plasma leakage in the form of ascites (n = 2, 7.7%) and pleural effusion (n = 1, 4%) (as evidenced radiologically). 9 (34.6%) of the patients had severe clinical bleeding – in the form of melaena (n = 2), hemoptysis with per-rectal bleeding, and bleeding from left ear (n = 1), hematemesis with melaena (n = 1), melaena with hematuria (n = 1), hematuria (n = 2), per-vaginal bleeding (n = 1), and hypermenorrhea (n = 1). Severe organ impairment was found in 12 patients (46%), as follows: Liver involvement (as transaminitis): 4 patients (15.4%), CNS involvement (as encephalitis): 3 patients (11.5%), cardiac involvement (as myocarditis): 1 patient (4%), acute kidney injury (serum creatinine > 3 times above baseline): 4 patients (15.4%). For comparison of the demographic data, clinical characteristics, and laboratory investigations, the population was divided into: severe dengue and non-severe dengue – which included dengue fever both with or without warning signs. 3.1.1 Demographic data The overall study population (n = 330) consisted of 137 (41.5%) males and 193 females (58.5%), among whom 10 males (38.5%) and 16 females (61.5%) had severe dengue, while 127 (41.8%) males and 177 (58.2%) females, had non-severe dengue. The mean age group in severe dengue was 58.8 ( ± 13.6) years, and for the non-severe dengue, the mean age group 50.6 ( ± 17.2) years. There was a statistically significant difference in the mean age between patients with severe dengue and those with non-severe dengue (p = 0.018). (Table 2 ) Table 2 Baseline demographics of cases with severe and non-severe dengue. Parameters Severe dengue (n = 26) Non-severe dengue (n = 304) P-value GENDER - Male - Female 10 (38.5%) 127 (41.8%) 0.837 16 (61.5%) 177 (58.2%) AGE (mean ± S.D.) 58.8 ± 13.6 50.6 ± 17.2 0.018 UNDERLYING DISEASES • Diabetes mellitus • Hypertension • Ischemic heart disease • Asthma • Chronic kidney disease • Chronic liver disease • Hypothyroidism • Hyperthyroidism • Dyslipidemia 22 (84.6%) 190 (62.5%) 0.031 18 (69.2%) 141 (46.4%) 0.039 4 (15.4%) 43 (14.1%) 1 3 (11.5%) 16 (5.3%) 0.180 7 (26.9%) 37 (12.2%) 0.042 3 (11.5%) 16 (5.3%) 0.180 5 (19.2%) 32 (10.5%) 0.191 - 7 (2.3%) 0.658 2 (7.7%) 19 (6.3%) 1 All the enrolled cases were aware of their underlying disease status. (See Supplementary Figure S1 , Additional File 1) The associated underlying diseases that were commonly found were: diabetes mellitus (n = 22, 84.6%), hypertension (n = 18, 69.2%), ischemic heart disease (IHD) (n = 4, 15.4%), asthma (n = 3, 11.5%), chronic kidney disease (CKD) (n = 7, 26.9%), chronic liver disease (CLD) (n = 3, 11.5%), hypothyroidism (n = 5, 19.2%), hyperthyroidism (none with severe dengue), and dyslipidemia (n = 2, 7.7%). None of the cases were evaluated for underlying thalassemia or G-6-PD (glucose-6-phosphate dehydrogenase) deficiency in this study. 3.1.2 Clinical manifestations As shown in Table 3 (also see Supplementary Figure S2 , Additional File 2), fever was the most predominant presenting complaint in all the cases with severe dengue, followed by vomiting being the second most common (n = 8, 30.8%). The mean duration of fever was similar in both severe (3.5 days) & in non-severe (3.3 days) dengue patients. There was no statistically significant difference in the duration of fever between the two groups. Interestingly, 7 (26.9%) of the severe dengue patients had presented with alteration of consciousness on admission, which was observed in the form of drowsiness in one case, one with grade II unconsciousness, one unconscious with poor Glasgow Coma Scale (GCS) of 5/15, & one with convulsion and poor GCS of 3/15. There was a statistically significant (p < 0.001) association between alteration of consciousness and severe dengue. In contrary, n = 11, 3.6%) non-severe dengue patients had presented with confusion or drowsiness. The classical presentation with retro-orbital pain, joint pain, myalgia, were not present in any of the patients with severe dengue. One patient presented with headache, one with generalized non-petechial rash, two cases with nausea, one with anorexia & another case with diarrhea. Neither of the patients with severe dengue had any congested conjunctiva, blurred vision, low back pain, or loss of appetite, and had no statistically significant difference with the non-severe dengue patients. ( Figure S2 ) While in patients with non-severe dengue, fever was the most common presenting complaint on admission, followed by vomiting being the second most common (n = 101, 33.3%) complaint; same as noticed in severe dengue cases. A statistically significantly (p < 0.033) higher proportion (n = 84, 27.6%) of non-severe dengue patients experience body ache, as compared to severe dengue patients (n = 2). Headache (n = 57, 18.8%), nausea (n = 42, 13.8%), anorexia (n = 39, 12.8%) were also common symptoms in non-severe dengue. Retro-orbital pain was present in 8 (2.6%), joint pain in 6 (2%), and myalgia in 3 (1%) of the non-severe dengue patients. Rash was present in 4 (1.3%) patients, of whom 3 had maculopapular rash, but the nature of the rash was not specified in one patient. In terms of nausea, vomiting, rash, lethargy, constipation, and diarrhea, there was no statistically significant difference observed between the severe dengue and the non-severe dengue patients. Table 3 Clinical presentation of cases with severe and non-severe dengue. Parameters Severe dengue (n = 26) Non-severe dengue (n = 304) CHIEF COMPLAINT • Fever • Headache • Alteration of consciousness 26 (100%) 304 (100%) 1 (3.8%) 57 (18.8%) 7 (26.9%) - CLINICAL MANIFESTATIONS Fever • Duration of fever (days) Headache Retro-orbital pain Congested conjunctiva/conjunctivitis Joint pain Myalgia Body ache Low back pain Rash Nausea Vomiting Anorexia Loss of appetite Constipation Diarrhea Confusion and drowsiness 26 (100%) 304 (100%) 3.5 ± 2.08 1 (3.8%) 3.3 ± 1.73 57 (18.8%) - 8 (2.6%) - 2 (0.7%) - 6 (2%) - 3 (1%) 2 (7.7%) 84 (27.6%) - 7 (2.3%) 1 (3.8%) 4 (1.3%) 2 (7.7%) 42 (13.8%) 8 (30.8%) 101 (33.3%) 1 (3.8%) 39 (12.8%) - 10 (3.3%) - 3 (1%) 1 (3.8%) 22 (7.2%) - 11 (3.6%) * (mean + S.D.) Warning signs : 12 (46.2%) of the severe dengue patients exhibited warning signs. (Table 4) Abdominal pain was present in 4 patients (15.4%), and in non-severe dengue patients, it was a frequent symptom (n = 31, 10.2%). Persistent vomiting was found in 3 patients (11.5%) in severe dengue, while on the other hand, in 12 patients (3.9%) in non-severe dengue. 6 of the severe dengue patients presented with bleeding manifestations, in the form of hematemesis (n = 1, 3.8%), melaena (n = 4, 15.4%), and hypermenorrhea (n = 1, 3.8%). For melaena, there was a highly statistically significant (p < 0.001) difference, thus implying it was a strong indicator of severity in this study. None of the severe dengue cases presented with gum bleeding or epistaxis. (See Supplementary Figure S3 , Additional File 3) Table 4 Warning signs in severe and non-severe dengue. Warning signs Severe dengue (n = 26) Non-severe dengue (n = 304) Abdominal pain Persistent vomiting Bleeding manifestations ♣ Gum bleeding ♣ Epistaxis ♣ Hematemesis ♣ Melaena ♣ Hypermenorrhea ♣ Restlessness 4 (15.4%) 31 (10.2%) 3 (11.5%) 12 (3.9%) - 3 (1%) - 1 (0.3%) 1 (3.8%) - 4 (15.4%) - 1 (3.8%) - 1 (3.8%) 1 (0.3%) 3.1.3 Laboratory findings The baseline laboratory investigations on the day of admission, including hematology, liver function tests, and biochemistry, were analyzed (Table 5 ) . Patients with severe dengue had a significantly lower mean hematocrit (32.86%) compared to those with non-severe dengue (36.08%). Those with severe dengue also had a significantly lower mean hemoglobin (11.02 mg/dl), compared to non-severe dengue (12.13 mg/dl). The patients with severe dengue had a significantly higher mean WBC count (9,790/mm 3 ). In the differential count of the whole blood count, there was no statistically significant difference. While the mean platelet count was lower in the severe dengue patients (130.55 x 10 9 /mm 3 ) compared to non-severe (133.66 x 10 9 /mm 3 ), this difference was not statistically significant. Patients with severe dengue had significantly higher (p < 0.001) mean alanine transferase (467.79 U/L), mean aspartate transferase (865.3 U/L), and mean alkaline phosphatase (146.41 U/L) levels, compared to non-severe dengue. This indicated significant liver involvement or damage in severe dengue. Patients with severe dengue had significantly lower mean serum albumin levels compared to non-severe dengue. Hypoalbuminemia is a common finding in severe dengue due to plasma leakage. There was no statistically significant difference in total protein, total or direct bilirubin levels in severe and non-severe dengue patients. Patients with severe dengue had significantly higher (p < 0.001) mean BUN levels compared to non-severe dengue. Elevated BUN could indicate impaired renal function or dehydration, both of which can be complications of severe dengue. Patients with severe dengue also had a significantly higher (p < 0.001) mean serum creatinine level compared to non-severe dengue. Elevated creatinine is a strong indicator of acute kidney injury, which is a severe complication of dengue. No statistically significant difference was seen in the mean sodium, chloride, TCO2, mean serum ferritin, and mean serum LDH levels between severe and non-severe dengue patients in this study. Table 5 Baseline laboratory findings of patients with severe and non-severe dengue. Parameters Severe dengue (n = 26) Non-severe dengue (n = 304) P-value 95% CI HEMATOLOGY (mean ± S.D.) Hematocrit (%) 32.86 ± 9.59 36.08 ± 5.41 0.023 0.46–5.99 Hemoglobin (mg/dl) 11.02 ± 3.27 12.13 ± 1.87 0.019 0.18–2.04 WBC count (x 10 3 /cu mm) 9,790 ± 8,492.12 6,476.18 ± 4,381.15 0.005 -5596.92 – (-1030.72) • Neutrophils (%) 74.06 ± 12.43 69.67 ± 15.2 0.223 -11.48–2.70 • Lymphocytes (%) 18.61 ± 10.3 23.53 ± 14.23 0.143 -1.68–11.51 • Monocytes (%) 4.1 ± 2.29 5.47 ± 2.88 0.046 0.02–2.70 • Eosinophils (%) 0.53 ± 0.62 0.71 ± 1.27 0.541 -0.40–0.76 Platelet count (x 10 9 /mm 3 ) 130.55 ± 99.38 133.66 ± 84.96 0.878 -150.52–213.02 LIVER FUNCTION TESTS* ALT (U/L) 467.79 ± 926.02 89.47 ± 236.54 < 0.001 -520.91 - (-235.73) AST (U/L) 865.3 ± 1553.89 119.5 ± 209.32 < 0.001 -948.97 - (-542.65) ALP (U/L) 146.41 ± 82.96 91.38 ± 65.8 < 0.001 -84.7 - (-25.37) Total protein (g/L) 63.71 ± 9.7 66.65 ± 8.99 0.195 -1.52–7.41 serum albumin (g/L) 31.7 ± 7.06 36.28 ± 4.8 < 0.001 2.36–6.8 Total bilirubin (mg/dl) 1.25 ± 2.0 0.92 ± 3.18 0.638 -1.72–1.06 Direct bilirubin (mg/dl) 0.93 0.53 ± 0.23 0.275 -1.54–0.75 BIOCHEMISTRY (mean ± S.D.) Blood urea nitrogen (BUN) 61.68 ± 54.24 38.29 ± 32.44 0.007 -40.38 - (-6.4) Serum creatinine (mg/dl) 2.71 ± 3.25 1.28 ± 1.15 < 0.001 -2.04 - (-0.84) Serum electrolytes (mmol/l) • Na 134.88 ± 7.79 134.37 ± 5.29 0.658 -2.77–1.75 • K 4.18 ± 0.96 4.02 ± 0.62 0.235 -0.43–0.11 • Cl 100.56 ± 6.67 99.09 ± 5.36 0.200 -3.71–0.78 • TCO2 22.88 ± 4.48 23.54 ± 3.17 0.333 -0.68–2.01 Serum ferritin 1944.25 ± 1048.8 3312.78 ± 5851.2 0.647 -4617.89–7354.94 Serum lactate dehydrogenase 3007.33 ± 1325.67 1210.67 ± 1012.87 0.032 -3404.91 - (-188.42) * (mean + S.D.) 3.1.4 Possible risk factors of severe dengue Logistic regression model was used to assess the risk factors associated with severe dengue, by univariate and multivariate analyses. The odds ratios (OR) and the corresponding 95% confidence intervals for the odds ratios were reported (as shown in Table 6 ). For univariate analysis, the independent association of severe dengue with each of the following variables was analyzed: AGE : Age was a statistically significant (p = 0.021 ) predictor of severe dengue in this study, suggesting that older age was associated with increased odds of severe dengue. For every one-year increase in age, the odds of severe dengue increased by 3.1% (OR = 1.031). SYMPTOM – ALTERATION OF CONSCIOUSNESS : Patients with alteration of consciousness had approximately ~ 10 times higher odds of having severe dengue, compared to those without this symptom. This was a highly statistically significant (p < 0.001) and strong predictor of severe dengue. SYMPTOM – BODY ACHE : Patients with body ache had 0.22 times the lower odds of severe dengue, which was statistically significant (p = 0.042), suggesting that it was more common in non-severe cases. UNDERLYING DISEASES : Those with underlying diabetes, hypertension, and chronic kidney disease had approximately 3 times higher odds of having severe dengue. LAB INVESTIGATIONS - HEMATOCRIT : For every one-unit increase in hematocrit, the odds of severe dengue decreased by about 10% (i.e., 1–0.896). This indicated that higher hematocrit was significantly (p = 0.025) associated with lower odds of severe dengue in the univariate analysis. This was an unusual finding, as higher hematocrit (hemoconcentration) is typically associated with severe dengue. ASPARTATE TRANSAMINASE (AST), ALKALINE PHOSPHATASE (ALP) : were highly statistically significant (p < 0.001) predictors of severe dengue. LOWER SERUM ALBUMIN : consistent with plasma leakage in severe cases. SERUM CREATININE : indicating that impaired renal function was strongly associated with severe dengue. There was no statistical significance between WBC count and severe dengue (p = 0.013, OR = 1). Based on the multivariate analysis (which is more robust for identifying independent predictors), only alteration of consciousness, hematocrit, and AST remained significant after multivariate adjustment of the listed variables in the model. Hematocrit (lower values) and AST (higher values) were statistically significant independent predictors of severe dengue. The logistic regression model, as indicated by the ROC (receiver operating characteristic) curve AUC (area under ROC curve) of 0.8834, showed good overall predictive ability (goodness-of-fit test) of 88.3% for severe dengue. (Fig. 1 ) Table 6 Logistic regression model for severe dengue. VARIABLES UNIVARIATE ANALYSIS MULTIVARIATE ANALYSIS OR 95% CI P-value adjusted OR (aOR) 95% CI P-value Age 1.031 1.005–1.058 0.021 SYMPTOMS Alteration of consciousness 9.813 3.417–28.187 < 0.001 51.254 8.245–318.613 < 0.001 Body ache 0.218 0.05–0.944 0.042 UNDERLYING DISEASES Diabetes mellitus 3.3 1.109–9.189 0.032 Hypertension 2.601 1.098–6.164 0.03 Chronic kidney disease 2.659 1.047–6.754 0.04 LABORATORY INVESTIGATIONS Hematocrit 0.896 0.814–0.987 0.025 0.829 0.728–0.9444 0.005 White blood cell count 1 1 0.013 AST 1.002 1.001–1.002 < 0.001 1.005 1.002–1.008 0.002 ALP 1.007 1.002–1.011 0.004 Serum albumin 0.853 0.782–0.931 < 0.001 Serum creatinine 1.368 1.138–1.645 < 0.001 3.1.5 Complications of severe dengue Twenty-one (80.8%) out of the 26 patients with severe dengue had developed complications. 2 (7.7%) of the patients with severe dengue had developed septic and cardiogenic shock. 6 (23.1%) had respiratory failure; among them, 4 required respiratory support by endotracheal intubation with airway protection and mechanical ventilation. 4 (15.4%) of these patients had also developed pulmonary edema, along with respiratory failure. 8 (30.8%) patients had abnormal bleeding. One (4%) patient with severe dengue developed viral myocarditis, while 2 (7.7%) patients developed acute left ventricular failure. 3 (11.5%) patients had developed encephalitis. Findings in MRI brain of one showed bilateral hyperintense signal change in both cerebral cortices. 2 of them had received steroids during hospitalization and improved. 4 (15.4%) of them had acute kidney injury, had prior chronic kidney disease (CKD), and were on hemodialysis. 8 (30.8%) of the patients had electrolyte imbalance. Coinfection was present in 14 (53.8%) of the patients. The concomitant coinfections seen in our severe dengue cases ranged from pneumonia (n = 5), sepsis (n = 2), urinary tract infection (n = 3), pneumonia with pleural effusion, along with concurrent urinary tract infection (n = 1), rickettsial fever with urosepsis (n = 1), and acute gastroenteritis (n = 2). 3.1.6 Outcomes of severe dengue Outcome at the end-of-care was defined in this study as the following: cured and discharged with advice, required transfer to the intensive care unit (ICU), was discharged on risk bond (i.e. the patient was in a very critical state but despite being aware of the risks, wanted discharge due to financial constraints), was discharged on request (i.e. the patient was relatively well but did not recover entirely; needed to be observed by the clinician but wanted to be discharged upon request), or death. 16 (61.5%) out of the 26 adult severe dengue patients were cured and were discharged with advice. 3 (11.5%) patients had to be transferred to the intensive care unit (ICU), primarily due to respiratory and multi-organ failure, necessitating close monitoring and for further management. 2 (7.7%) of the patients were discharged on risk bond due to financial constraints. 2 (7.7%) patients wanted to be discharged on request, and 3 (11.5%) patients died. (See Supplementary Figure S4 , Additional File 4) The ultimate outcome of those who were transferred to the ICU, were discharged on risk bond or upon request, were unknown (n = 7, 29.2%). 4 Discussion Our study site BIRDEM General Hospital of Dhaka, Bangladesh, is a non-government tertiary care specialized hospital especially for treating those with underlying diabetes mellitus, endocrine and metabolic disorders; thus, diabetes or endocrine diseases, such as hypothyroidism, could have been confounding factors in our study population of severe dengue. In contrast to the vast patient turnover in the public hospitals of Bangladesh, the findings of this study may not be reflective of the actual real-time scenario of severe dengue in Bangladesh. However, in the public hospital settings of Bangladesh, there are insufficient beds, limited diagnostic facilities, lack of manpower, and an inadequate referral system. Due to the unfortunate lack of proper documentation and data preservation, conducting our retrospective study in public hospitals could not be considered. From this study, the proportion of adult severe dengue patients in the study site was 7.9%. In contrast, the cross-sectional observational study conducted in 2023 at two government medical college hospitals in Bangladesh found ∼17% developed severe dengue [ 12 ] . Our study indicated that out of the total enrolled cases (n = 330), 26 were severe dengue (7.9%), and the majority of the 304 patients were non-severe dengue (92.4%), which included 46 patients of dengue with warning signs (15.1%) and 258 patients of dengue without warning signs (84.9%). A prospective study done at the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University in Bangkok, Thailand, showed that out of the 153 patients with confirmed dengue infection, 13.7% (21 patients) had severe dengue while 86.3% (132 patients) had non-severe dengue, which included 94.7% dengue with warning signs (125 patients) and dengue without warning signs in 5.3% (7 patients). Of those with severe dengue, 16 (76.2%) had severe plasma leakage, 8 (38.1%) had severe clinical bleeding, and 16 (76.2%) had severe organ involvement. 12 out of the 16 patients (75%) had severe plasma leakage with shock, and 8 (50%) had plasma leakage with respiratory distress. Out of the 16 patients with severe organ involvement, 9 (56.2%) had AST > 1,000 IU/L and/or ALT > 1,000 IU/L, 9 (56.2%) had serum creatinine ≥ 3 times above baseline, 1 (6.2%) had myocarditis, and 1 (6.2%) had encephalitis [ 13 ] . Whereas, in our study, out of the 26 patients with severe dengue, 2 (7.7%) developed plasma leakage with shock, 3 (11.5%) had plasma leakage in the form of ascites (n = 2) and pleural effusion (n = 1) (radiological evidence), and 9 (34.6%) had severe clinical bleeding. Among the 12 patients (56%) who had severe organ impairment, 4 (15.4%) had liver involvement (i.e. AST > 1,000 IU/L and/or ALT > 1,000 IU/L), 3 (11.5%) had CNS involvement (as encephalitis), 1 (4%) had cardiac involvement (as myocarditis), and 4 (15.4%) had acute kidney injury (serum creatinine ≥ 3 times above baseline). On the contrary, a prospective observational study conducted in four government hospitals in Dhaka, Bangladesh, in 2022 showed severe organ involvement in dengue infection as myocarditis (cardiac involvement) in 0.6% cases and neurologic involvement in the form of meningitis and Guillain-Barré syndrome (GBS) in 0.6% cases as well [ 14 ] . In our study, the affected population of adult severe dengue were predominantly females (n = 16, 61.5%), and 177 females (58.2%) had non-severe dengue. There was no specific reason as to why the affected population was mostly females. Regarding gender distribution, there was a male predominance in all the dengue outbreaks that were previously reported in Bangladesh, including a study done at our study site in 2019 [ 15 – 24 ] . A cross-sectional observational study conducted in 450 confirmed dengue patients at two government medical college hospitals of Bangladesh in 2023, also showed that the male-to-female ratio was nearly equal. The above-mentioned study also showed that the patients with severe dengue were older compared to those with non-severe dengue (36.6 years versus 32.6 years) [ 12 ] . In the prospective study done in Thailand, as mentioned above, also showed that the development of severe dengue was significantly associated with patients aged > 40 years [ 13 ] . In our study, the mean age group in severe dengue was 58.8 years, and for the non-severe dengue, the mean age group was 50.6 years. Whereas the study in our same study site in 2023 found the mean age of the dengue patients was 33 ± 14.6 years (± SD), and almost half of them were young adults age 18 to 30 years, found the least number (1.90%) of cases in the > 60 years age group, and about 15.24% cases in the age group of 41–60 years [ 24 ] . The study population of severe dengue patients had underlying diseases including diabetes mellitus (n = 22, 84.6%), hypertension (n = 18, 69.2%), ischemic heart disease (n = 4, 15.4%), chronic kidney disease (n = 7, 26.9%), chronic liver disease (n = 3, 11.5%), hypothyroidism (n = 5, 19.2%), and dyslipidemia (n = 2, 7.7%). Diabetes mellitus (84.6%) and hypertension (69.2%) showed higher percentages in severe dengue, and were statistically significant (DM: p = 0.031; HTN: p = 0.039) in both severe and non-severe dengue. While chronic kidney disease was more prevalent in severe dengue (26.9% vs. 12.2%, this difference was statistically significant (p = 0.042), suggesting it as a potential predisposing factor for severe outcomes. The prospective observational study conducted in four government hospitals in Dhaka, Bangladesh, in 2022 showed 15.8% (p 0.03) of their study population were diabetic and 19.7% (p 0.01) were hypertensive, in the severe category of dengue fever [ 14 ] . Another cross-sectional study done in 3 hospitals in Dhaka, Bangladesh, showed hypertension (90, 4.5%) as the most common associated comorbidity along with diabetes mellitus (DM) (70, 3.5%) and CKD (10, 0.5%), in those with severe disease [ 25 ] . The study in our same study site in 2023 also found diabetes mellitus (DM) as the major comorbidity (75, 25.7%), followed by hypertension (16.1, 47%), dyslipidemia (21, 7.2%), hypothyroidism (4.8, 14%), ischemic heart disease (3, 1%), and CKD (n = 4, 1.4%) [ 24 ] . For the development of acute kidney injury, some independent risk factors are advanced age, male gender, obesity, hemorrhagic fever, multiple organ dysfunction, diabetes mellitus, concomitant bacterial infection, rhabdomyolysis, delay in hospital consultation, and use of nephrotoxic drugs [ 26 – 29 ] . Our study demonstrated fever as the sole consistent presenting complaint, universally present (100%), while vomiting was the second most common, observed in 30.8% (n = 8) of patients upon admission. Differing from classical dengue presentations, symptoms such as retro-orbital pain, joint pain, and myalgia were absent. Furthermore, specific complaints like congested conjunctiva, blurred vision, loss of appetite, constipation, or lethargy were also not reported, and had no statistically significant difference with the non-severe dengue patients. The mean duration of fever was nearly the same (∼3 days) in both severe and non-severe dengue, which implied that there was no statistically significant difference between severe and non-severe dengue. Warning signs were evident in a considerable portion (n = 12, 46.2%) of patients. 6 individuals presented with bleeding manifestations, comprising hematemesis (n = 1, 3.8%), melena (n = 4, 15.4%), and hypermenorrhea (n = 1, 3.8%). Remarkably, gum bleeding or epistaxis were not observed. Additional warning signs included abdominal pain (n = 4, 15.4%), persistent vomiting (n = 3, 11.5%), and restlessness (n = 1, 3.8%). A notable finding from the crosstabulation analysis was that, contrary to common expectations, a substantial portion of severe dengue cases (54%) did not present with the specified warning signs, and a considerable proportion (15.8%) of non-severe cases did. This suggested that reliance solely on these particular warning signs may have been insufficient for identifying all severe dengue cases in this study population. While in contrast to the prospective observational study done in Dhaka in 2022 displayed that severe dengue patients reported fever in all the cases (100%), followed by body aches (72.1%), and reported a higher number of nausea (80.3%, p 0.008), cough (57.9%, p < 0.001), abdominal pain (56.6%, p 0.21), persistent vomiting (53.9%), dyspnea (35.5%, p < 0.001), diarrhea (28.9%, p 0.45), skin rash (27.6%, p < 0.001), and joint pain (26.3%, p 0.91). Also, hematemesis (2.3%), hematochezia (1.3%), and melena (1.6%) were present only in severe dengue cases [ 14 ] . On the other hand, the prospective study of Hospital of Tropical Diseases, Bangkok, Thailand, in severe dengue patients showed myalgia (20, 95.2%), lethargy (19, 90.5%), headache (18, 87.5%), fever (17, 80%), mucosal bleeding (14, 66.7%), skin bleeding (13, 61.9%), retro-orbital pain (11, 52.4%), rash (10, 47.6%), abdominal pain and persistent vomiting (9, 42.9%) patients, and diarrhea (5, 23.8%) [ 13 ] . A particularly striking finding in our study was the occurrence of altered consciousness in 7 (26.9%) patients at presentation, with documented cases of drowsiness, grade II unconsciousness, and profoundly low Glasgow Coma Scale scores (3/15 and 5/15, respectively), including one case with convulsion. This aligns with a multi-center retrospective cohort study done in Taiwan between 2002–2019, where altered consciousness was found in 12.2% severe dengue patients [ 30 ] . From our study, the laboratory findings suggested that in severe dengue, compared to non-severe dengue, there was significantly (p = 0.023) lower hematocrit (32.86%) level and significantly (p 0.019) lower hemoglobin (11.02 mg/dL) levels. In liver function tests, significantly (p < 0.001) higher ALT: 467.79 U/L, AST: 865.3 U/L, and ALP levels: 146.41 U/L, implying hepatocellular damage, and significantly (p < 0.001) lower serum albumin (31.7 g/L) levels. Biochemistry results indicated significantly (p < 0.001) higher serum creatinine (2.71 mg/dL) and blood urea nitrogen (BUN): 61.68 mg/dL, suggesting possible impairment of renal function. Furthermore, a marker of organ dysfunction as serum LDH (3007.33 IU) was elevated, which aligns with the pathology of severe dengue. The findings of this study for hematocrit (lower in severe dengue) and platelet count (no significant difference) were opposed to the typical clinical presentation and WHO guidelines for severe dengue, where hemoconcentration (elevated hematocrit) and significant thrombocytopenia were expected hallmarks. These specific results suggested a possibility of potential confounding factors within this specific study. It could also be possible that the sample size for severe dengue (n = 26) was too small to consistently capture these changes, or there was some unique characteristic of this study. A retrospective study conducted at Teaching Hospital Peradeniya of Kandy district of Sri Lanka, showed that during the acute febrile phase (2nd and 3rd day) of dengue virus infection, hemoglobin levels ranged from 9.5–18.8 mg/dL, also platelet count < 150,000 cells/mm 3 in 63.1% and < 100,000 cells/mm 3 in about 33.2% patients. Besides, the decline in the mean hematocrit values on the 5th day of illness (compared to the 3rd day) in both plasma leakers and in non-leakers could be due to dilution of plasma during fluid replenishment [ 31 ] . In those with lower mean hematocrit and hemoglobin levels, there was occurrence of bleeding manifestations in 3 of the severe dengue patients. Based on the multivariate logistic regression analysis, alteration of consciousness, hematocrit, and elevated AST levels were significantly associated with increased odds of severe dengue. While other variables like age, body ache, diabetes mellitus, hypertension, chronic kidney disease, WBC, ALP, serum albumin, and serum creatinine were all individually significant predictors in univariate analyses, their independent significance was not maintained or not presented in the final multivariate model. The overall derived predictive model, as previously indicated by an Area Under the ROC Curve (AUC) of 0.8302, demonstrated a good to very good ability (goodness-to-fit-test) to discriminate between severe and non-severe dengue cases. In a cross-sectional study done in two of the academic hospitals of Bangladesh in 2023, their laboratory parameters reflected that > 48% hematocrit was present in 5% of the patients, 13% in severe dengue, and 3.5% in non-severe dengue, which was statistically significant (P = 0.001) in their study. Leukopenia was reported in ∼46%, and thrombocytopenia in 56% of their patients. Increased AST and ALT levels (> 40 IU/L) were reported in 42% and 67% of the patients, respectively. Serum AST was associated with severe dengue. 2% of their patients also had a serum creatinine value of > 2 mg/dL, mostly seen in the patients with severe dengue (P = 0.001) of their study [ 12 ] . Laboratory findings in the prospective study in Thailand showed patients with severe dengue had significantly greater white blood cell (WBC) (p = 0.034); absolute lymphocytes > 2,000 cells per µL, alanine transaminase (ALT) levels (p = 0.003), and aspartate transaminase (AST) levels (p < 0.001). In their study, multivariate regression indicated that the following clinical and laboratory characteristics upon admission were independently associated with the development of severe dengue: (1) age > 40 years, (2) persistent vomiting, (3) absolute atypical lymphocyte > 300 cells per µL, and (4) lactate level ≥ 2.0 mmol/L [ 13 ] . The study done in pediatric severe dengue patients in Puerto Rico concluded severe dengue cases had more frequent hemoconcentration (11%, p < 0.001), leucopenia (77%, p < 0.001), thrombocytopenia (74%, p < 0.001), and low albumin (86%, p < 0.001) levels [ 32 ] . Our severe dengue cases exhibited a range of concomitant coinfections, including pneumonia, sepsis, urinary tract infection, and acute gastroenteritis. More complex coinfections also occurred, such as one case of pneumonia with pleural effusion and concurrent urinary tract infection, and one case of rickettsial fever with urosepsis. The most common complications in the severe dengue cases that were observed in the prospective observational study in Dhaka, Bangladesh, in 2022 were pneumonia (2.3%), followed by hepatitis (1.6%), and pancreatitis (1.3%) [ 14 ] . While in the retrospective cohort study done in Taiwan, among the severe dengue patients, 35% experienced acute kidney injury, 18.4% had pneumonia, and 6.5% had bacteremia [ 30 ] . A relatively uncommon yet serious complication in severe dengue is bacterial co-infection. Although only approximately 7% dengue patients have concurrent bacteremia, 44% dengue-related deaths are related to bacterial co-infection, like pneumonia, urinary tract infection, enteric fever, etc. [ 33 ] . In a prospective cohort in Latin America found patients with warning signs were hospitalized (99%), while 33% critical dengue patients needed admission to the ICU, primarily due to vascular leakage with respiratory distress or profound thrombocytopenia, that needed close observation and monitoring [ 34 ] . Out of the 26 adult severe dengue patients in this study, 16 patients (62%) recovered and were discharged with follow-up advice. 3 patients (11.5%) required transfer to the ICU due to complications such as respiratory and multi-organ failure, requiring intensive monitoring and management. 2 patients (8%) were discharged on a risk bond due to financial limitations, 2 patients (8%) were discharged on request, and death of 3 patients (11.5%) were reported. 5 Conclusion This retrospective observational study highlighted that the adult severe dengue patients belonged to the older age group and significantly more prevalent in those with underlying diabetes mellitus, hypertension, and chronic kidney disease. Clinical indicators of severe dengue included alteration of consciousness and melena, while body ache was more frequent in non-severe cases. Laboratory derangements including unexpectedly reduced hematocrit and hemoglobin levels, elevated liver enzymes (AST, ALT, ALP), renal function tests (creatinine, BUN), markers of systemic damage (reduced albumin, elevated LDH), were strongly associated with disease severity. The multivariate logistic regression model highlighted alteration of consciousness and elevated AST as independent predictors of severe dengue, emphasizing their crucial role in risk assessment. The finding regarding lower hematocrit being associated with severe dengue in the univariate analysis was counter-intuitive to the established understanding of hemoconcentration in severe dengue. However, the developed logistic regression model offered good predictive capability for identifying severe dengue. But the small sample size for severe dengue (n = 26) could have impacted the statistical power, when interpreting the strength of associations. The findings of this study also emphasized that the absence of classical warning signs should not preclude vigilance for severe dengue, indicating a need for patients requiring hospitalization to be accurately identified by physicians. Although a large group of non-severe dengue patients were admitted to the hospital, they could possibly be managed with ambulatory care and followed up afterwards on an outpatient basis with daily follow-up physically or via telemedicine, to reduce the burden on hospitals. Despite the severity of illness, complexity of manifestations, and complications like severe organ impairment and bleeding, the study observed a favorable positive outcome with minimal reported mortality, indicating effective clinical management protocols within the hospital setting. These findings provide valuable insights and emphasize the importance of clinical and laboratory markers for early recognition, risk stratification, and timely intervention to improve outcomes in dengue management. Limitations Bangladesh, being a resource-limited low- to middle-income country (LMIC), had certain limitations in our research. As the hospital health information system (HIS) and laboratory information system (LIS) database was not designed with the ICD-10 (International Classification of Diseases 10th revision) coding system, to trace and identify the dengue cases specifically, the screening and enrolment had to be done manually, by cross-checking the raw laboratory data (especially in case of Dengue serology – Dengue NS1, IgM, IgG), and comparing them with the electronic discharge summaries. Also, there was a backlog in the archiving system of the hospital admission records, and unfortunately, ~ 50% of the archived records could not be retrieved, thus leading to missing data, which could not be recorded and completely analyzed further. An initiative for improved documentation of cases is warranted. Besides, the atypical lymphocytes were not generated in the profile of complete blood count (CBC) panel. The diagnostic facility for dengue PCR (polymerase chain reaction) test was not available at the study site and therefore, could not be recorded. Abbreviations The following abbreviations are used in this manuscript: aOR Adjusted Odd’s ratio HIS Health information system ALT Alanine aminotransferase ICU Intensive care unit AST Aspartate aminotransferase ICD-10 International Classification of Diseases 10 th revision coding system ALP Alkaline phosphatase IgG Immunoglobulin G AUC Area under ROC curve IgM Immunoglobulin M BIRDEM Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders LDH Lactate dehydrogenase CNS Central Nervous System LIS Laboratory information system CFR Case fatality rate LMICs Low and middle-income countries CBC Complete blood count NS1 Non-structural protein 1 CI Confidence interval OR Odd’s ratio CKD Chronic kidney disease PCR polymerase chain reaction CLD Chronic liver disease ROC Receiver operating characteristic GCS Glasgow Coma Scale WHO World Health Organization G6-PD Gluose-6-phosphate dehydrogenase Declarations Supplementary information. This article has accompanying supplementary files. Ethical approval declaration Institutional Review Board Statement:The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Mahidol University (TMEC 25-008 and 26 March 2025) and of the Diabetic Association of Bangladesh (ERC/EC/25/40 and 13 February 2025). Informed Consent Statement: Patient consent was waived as this study was retrospective observational study, accessing secondary medical data (medical records. There was no intervention to the human subjects. Any information leading to the identification of the subjects was not recorded and the confidentiality of their records was maintained. Consent for publication: Not applicable. Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests. Funding: This research was funded by Mahidol University, under the Masters of Clinical Tropical Medicine program. CRediT Authors Contributions: Fariha Fairouz: Conceptualization, Methodology, Data curation, Formal analysis, Writing - original draft preparation; Wirongrong Chierakul: Conceptualization, Methodology, Investigation, Resources, Formal analysis, Funding acquisition, Validation, Supervision, Writing - review and editing; Chayasin Mansanguan: Conceptualization, Methodology, Formal analysis, Validation, Supervision, Writing - review and editing; Hisham Ahmed Imad: Conceptualization, Methodology, Formal analysis, Validation, Supervision, Writing - review and editing; Janjira Thaipadungpanit: Conceptualization, Methodology, Formal analysis, Validation, Supervision, Writing - review and editing; Jamal Uddin Ahmed: Conceptualization, Methodology, Investigation, Resources, Supervision, Writing - review and editing; Prakaykaew Charunwatthana: Conceptualization, Methodology, Investigation, Resources, Formal analysis, Funding acquisition, Project administration, Validation, Visualization, Supervision, Writing - review and editing. All authors who deserve to be credited on the manuscript are indeed identified, that no authors are listed who do not deserve authorship credit, and that author contributions, where they are provided, are expressed accurately. The authors have reviewed and edited the final manuscript and take full responsibility for the content of this publication. Acknowledgements. The authors would like to sincerely acknowledge the IT department of BIRDEM General Hospital for facilitating data collection for the research. References Kayesh MEH, Khalil I, Kohara M, Tsukiyama-Kohara K. Increasing Dengue Burden and Severe Dengue Risk in Bangladesh: An Overview. Trop Med Infect Dis. 2023;8(1). Egger JR, Coleman PG. Age and clinical dengue illness. Emerg Infect Dis. 2007;13(6):924–5. Guzman MG, Gubler DJ, Izquierdo A, Martinez E, Halstead SB. Dengue infection. Nat Rev Dis Primers. 2016;2:16055. Martina BE, Koraka P, Osterhaus AD. Dengue virus pathogenesis: an integrated view. 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Prognostic factors in severe dengue patients: A multi-center retrospective cohort study. PLoS Negl Trop Dis. 2025;19(1):e0012846. Ralapanawa U, Alawattegama ATM, Gunrathne M, Tennakoon S, Kularatne SAM, Jayalath T. Value of peripheral blood count for dengue severity prediction. BMC Res Notes. 2018;11(1):400. Paz-Bailey G, Sanchez-Gonzalez L, Torres-Velasquez B, Jones ES, Perez-Padilla J, Sharp TM, et al. Predominance of Severe Plasma Leakage in Pediatric Patients With Severe Dengue in Puerto Rico. J Infect Dis. 2022;226(11):1949–58. Tejo AM, Hamasaki DT, Menezes LM, Ho YL. Severe dengue in the intensive care unit. J Intensive Med. 2024;4(1):16–33. Gomez-Zambrano M, Torres-Hernandez D, Murillo-Ortiz MA, Hurtado IC, Davalos DM, Cantor E, et al. Different Clinical Severity and Outcomes in a Cohort of Patients With Dengue With Warning Signs in an Endemic Latin American City. Open Forum Infect Dis. 2025;12(4):ofaf227. Additional Declarations No competing interests reported. Supplementary Files Additionalfile1FigureS1Underlyingdiseasesinseveredenguen26.png Additional file 1: Figure S1, Underlying diseases in severe dengue (n=26), .png Additionalfile2FigureS2Clinicalfeaturesindengueinfectionn330.png Additional file 2: Figure S2, Clinical features in dengue infection (n=330), .png Additionalfile3FigureS3Warningsignsindengueinfection.png Additional file 3: Figure S3, Warning signs in dengue infection, .png Additionalfile4FigureS4Outcomesofseveredengue.png Additional file 4: Figure S4, Outcomes of severe dengue, .png AppendixA.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7844350","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":534029206,"identity":"c9deb012-e7a6-4564-a79b-4f89ffadd9c3","order_by":0,"name":"Fariha 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University","correspondingAuthor":false,"prefix":"","firstName":"Wirongrong","middleName":"","lastName":"Chierakul","suffix":""},{"id":534029210,"identity":"54706d1e-35be-44ae-8389-454081c1da0b","order_by":2,"name":"Chayasin Mansanguan","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Chayasin","middleName":"","lastName":"Mansanguan","suffix":""},{"id":534029211,"identity":"211ddf93-f441-4067-bdd0-b4865ba858c1","order_by":3,"name":"Hisham Ahmed Imad","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Hisham","middleName":"Ahmed","lastName":"Imad","suffix":""},{"id":534029212,"identity":"749a5063-f87a-4eb3-be38-9e145453ad97","order_by":4,"name":"Janjira Thaipadungpanit","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Janjira","middleName":"","lastName":"Thaipadungpanit","suffix":""},{"id":534029213,"identity":"4cf4280e-522c-4ff1-8756-f424b169cac7","order_by":5,"name":"Jamal Uddin Ahmed","email":"","orcid":"","institution":"BIRDEM General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jamal","middleName":"Uddin","lastName":"Ahmed","suffix":""},{"id":534029214,"identity":"8b125f77-cd24-40e6-b272-d1f2697cbc12","order_by":6,"name":"Prakaykaew Charunwatthana","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Prakaykaew","middleName":"","lastName":"Charunwatthana","suffix":""}],"badges":[],"createdAt":"2025-10-13 04:38:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7844350/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7844350/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":94874340,"identity":"ff0cd76c-dfe6-429c-93ac-d535688942cc","added_by":"auto","created_at":"2025-10-31 15:30:50","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":8002353,"visible":true,"origin":"","legend":"","description":"","filename":"BMCManuscriptamendedv1.1submission141025.docx","url":"https://assets-eu.researchsquare.com/files/rs-7844350/v1/c677d26e6a32a2f7ba275095.docx"},{"id":94874329,"identity":"d2737191-ab97-4f3d-919b-df74d757669d","added_by":"auto","created_at":"2025-10-31 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15:30:50","extension":"html","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":162088,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7844350/v1/e7a9dd05bac5c161f02f00a6.html"},{"id":94874326,"identity":"f2ff9a2b-4869-4636-923c-a49eee8df1fd","added_by":"auto","created_at":"2025-10-31 15:30:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":15358,"visible":true,"origin":"","legend":"\u003cp\u003eROC (receiver operating characteristic) curve of predictors of severe dengue.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7844350/v1/60b151a090cb4d8f1c5622e2.png"},{"id":99864417,"identity":"ef40d512-3bfc-49cc-8034-f6cab1a06046","added_by":"auto","created_at":"2026-01-09 07:40:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1135318,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7844350/v1/aaabd4d9-7114-4a4f-8291-7fb8010fc188.pdf"},{"id":94874327,"identity":"1a8a5e0e-70f3-48b5-a7eb-c24445dc0758","added_by":"auto","created_at":"2025-10-31 15:30:50","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":124116,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 1: Figure S1, Underlying diseases in severe dengue (n=26), .png\u003c/p\u003e","description":"","filename":"Additionalfile1FigureS1Underlyingdiseasesinseveredenguen26.png","url":"https://assets-eu.researchsquare.com/files/rs-7844350/v1/5984920494be8f4d3b4674b0.png"},{"id":94986177,"identity":"46bafe15-cdbb-42c3-af44-c5c7fc51343d","added_by":"auto","created_at":"2025-11-03 07:00:00","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":263160,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 2: Figure S2, Clinical features in dengue infection (n=330), .png\u003c/p\u003e","description":"","filename":"Additionalfile2FigureS2Clinicalfeaturesindengueinfectionn330.png","url":"https://assets-eu.researchsquare.com/files/rs-7844350/v1/7afd65542b1a5c020523b35f.png"},{"id":94986502,"identity":"bb83e2c2-f7ae-4ecf-8ad1-3885a298f108","added_by":"auto","created_at":"2025-11-03 07:00:22","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":174608,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 3: Figure S3, Warning signs in dengue infection, .png\u003c/p\u003e","description":"","filename":"Additionalfile3FigureS3Warningsignsindengueinfection.png","url":"https://assets-eu.researchsquare.com/files/rs-7844350/v1/cff2dded447dd73553ce9530.png"},{"id":94874338,"identity":"166180aa-32a1-401b-bc55-b17d4e913ed5","added_by":"auto","created_at":"2025-10-31 15:30:50","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":99960,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 4: Figure S4, Outcomes of severe dengue, .png\u003c/p\u003e","description":"","filename":"Additionalfile4FigureS4Outcomesofseveredengue.png","url":"https://assets-eu.researchsquare.com/files/rs-7844350/v1/f2550ea9c3d5bb3883a4c8e7.png"},{"id":94986835,"identity":"24dd3d53-f892-4c69-8905-bc6488c62e9b","added_by":"auto","created_at":"2025-11-03 07:00:51","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":822248,"visible":true,"origin":"","legend":"","description":"","filename":"AppendixA.docx","url":"https://assets-eu.researchsquare.com/files/rs-7844350/v1/0a699d76ac5d660c742b9007.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Outcomes of adult severe dengue in a tertiary care centre of Bangladesh: a cross-sectional retrospective observation","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eBeing one of the leading neglected tropical diseases, dengue infection is regarded as the most important arthropod-transmitted human viral disease (WHO 2019) and constitutes a significant global health threat. The worldwide challenge of dengue as a significant public health issue, particularly in the tropical and subtropical regions, has been widely investigated, emphasizing its epidemiology, clinical symptoms, and treatment approaches. Nonetheless, there is a scarcity of studies concentrating on the unique socio-environmental conditions in low and middle-income countries (LMICs) such as Bangladesh, which is situated in the dengue endemic zone of the southeastern region. Throughout Bangladesh, given the impact of climate change globally, the unusual changing monsoon pattern along with the elevated humidity, rising under-construction sites, and the water stagnation in unkempt containers being potential breeding sites for the proliferation have overall contributed to the increasing population of mosquitoes in Bangladesh, causing an acute upsurge of cases, over time. Dense populations, swift urban growth, and scarce healthcare resources worsen the disease's effects\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eEarlier research has pinpointed key risk factors for progression to severe dengue as age\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e, pre-existing conditions (diabetes and hypertension), host immunity, genetic predisposition\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e, and delays in treatment\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e as crucial factors leading to unfavorable outcomes; however, localized data remains insufficient\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Despite ongoing control measures, the burden of the disease remains substantial, highlighting the need for in-depth research into clinical outcomes and contributing factors. Bangladesh requires immediate and long-term approaches to minimize dengue-related deaths in the coming days.\u003c/p\u003e\u003cp\u003eThis study aimed to identify the proportion of severe dengue among the hospitalized adult dengue fever patients, to explore the possible risk factors that cause progression to severe dengue, evaluated the demographics, clinical, and laboratory parameters of the adult dengue patients, and analyzed the outcome of severe dengue in BIRDEM General Hospital, Dhaka, Bangladesh, using retrospective data. The findings of our study will provide evidence-based insights in understanding the burden of severe dengue and identifying the associated risk factors, to guide efficient healthcare interventions and improve outcomes of the patients.\u003c/p\u003e\u003cp\u003eEarly identification of at-risk patients, early intervention with optimal supportive care, close observation, and judicious parenteral fluid therapy, it is possible to reduce the mortality rates to less than 1%, even among cases of Dengue shock syndrome (DSS)\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Timely and appropriate monitoring and management, principally with fluid intervention, and awareness of progression to severe dengue are critical in the reduction of morbidity and mortality\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Less than 1% with viremia progress to potentially fatal form of severe dengue, due to risk factors as age, comorbidities, host genetics, and virus strain, heterotypic secondary infections being the most conspicuous one\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Identifying the predictive factors for severe dengue is of potential importance for the effective management of dengue patients by healthcare providers\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"2 Materials and Methods","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u003cem\u003eStudy design and population\u003c/em\u003e\u003c/p\u003e\u003cp\u003eThis retrospective cross-sectional study was conducted at BIRDEM General Hospital, Dhaka, Bangladesh. (BIRDEM, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders). The target population included all adult dengue fever patients admitted to the study site from January 1, 2023, to December 31, 2024. The study\u0026rsquo;s inclusion criteria were: (1) adults 18 years and above, of both genders, and (2) admitted with a history of suspected dengue infection with at least one of the following confirmed laboratory tests: (a) positive dengue NS1 antigen, or (b) positive dengue IgM and IgG, or (c) positive dengue IgM with negative dengue IgG, or (d) positive dengue PCR. Those in whom the final diagnosis of severe dengue could not be established or the outcome of dengue could not be determined were excluded.\u003c/p\u003e\u003cp\u003eThe retrospective data was extracted from the stored database of electronic medical records (EMR) and paper-based documented medical records at the study site. Using a structured case record form (CRF), the demographic data, clinical presentation, laboratory findings, outcomes, and complications of all adult dengue patients were recorded. The severity of dengue was assessed according to the WHO 2009 classification.\u003c/p\u003e\u003cp\u003e\u003cem\u003eCase definition of dengue\u003c/em\u003e\u003c/p\u003e\u003cp\u003eAs per the 2009 dengue case definition by the WHO, dengue patients were classified into severe and non-severe dengue\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Patients with non-severe dengue were further sub-categorized based on the presence or absence of warning signs. Non-severe dengue without warning signs was defined as acute fever with at least two of the following: nausea, vomiting, rash, myalgia, arthralgia, a positive tourniquet test, or leukopenia. Warning signs included: 1. abdominal pain, 2. persistent vomiting (\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;3 episodes of vomiting in 12 hours)\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e, 3. clinical fluid accumulation, 4. lethargy, 5. liver span\u0026thinsp;\u0026gt;\u0026thinsp;15cm, 6. bleeding from mucosal areas, including nose, gums, gastrointestinal tract, or vagina, or 7. an elevated hematocrit of \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;20% with concurrent thrombocytopenia. Severe dengue was classified as having: (1) severe plasma leakage with shock or with respiratory distress (i.e., respiratory rate\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;24 breaths/min. with oxygen saturation\u0026thinsp;\u0026lt;\u0026thinsp;95% in room air, and/or requiring oxygen therapy), (2) severe clinical bleeding, defined as spontaneous bleeding from mucosal areas or in vital organs, that necessitates blood transfusion, (3) severe organ impairment, defined as AST\u0026thinsp;\u0026gt;\u0026thinsp;1000 U/L and/or ALT\u0026thinsp;\u0026gt;\u0026thinsp;1000 U/L, encephalitis, myocarditis, and/or serum creatinine\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;1.3 mg/dL)\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e\u003cem\u003eSample size calculation\u003c/em\u003e\u003c/p\u003e\u003cp\u003eBased on a cross-sectional observational study conducted at Dhaka Medical College Hospital and Chittagong Medical College Hospital of Bangladesh, 17% of patients experienced severe dengue, and 89% of those with non-severe cases exhibited at least one warning sign\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. We used the formula to estimate the required sample size: \u003cem\u003en\u0026thinsp;=\u0026thinsp;p(1-p)/(E/1.96)^2\u003c/em\u003e. So, we assumed a 17% (0.17) prevalence from the previous study, allowed for a 5% (0.05) margin of error, and to estimate the prevalence of severe dengue with 95% confidence interval, we needed to study a minimum of 217 adult patients with dengue.\u003c/p\u003e\u003cp\u003e\u003cem\u003eStatistical analyses\u003c/em\u003e\u003c/p\u003e\u003cp\u003eThe proportion of severe dengue was estimated and expressed as a percentage (%). The 95% confidence intervals for the proportion of severe dengue were computed and reported. Mean and standard deviations for continuous variables - age, symptoms, and laboratory investigations were done. To compare the mean between severe and non-severe dengue, student\u0026rsquo;s T-test was used. For categorical variables, Pearson\u0026rsquo;s chi-square (χ2) or Fisher\u0026rsquo;s exact test was used. Logistic regression was used to assess the risk factors associated with severe dengue. The odds ratios (OR) and 95% Confidence intervals for odds ratios were reported. Univariate analyses and multivariable analyses in logistic regression model were performed for binary outcome (severe dengue vs. non-severe dengue). Data analysis was conducted using SPSS for Mac OS and STATA.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"3 Results","content":"\u003cp\u003eFor this retrospective observational study, the hospital records from 1st January 2023 to 31st December 2024 were reviewed. During this period, 457 cases were diagnosed or classified as dengue fever in the electronic discharge summaries and the in-patient documented hospital admission files. Of these screened 457 cases, initially 45 cases had to be excluded as they were \u0026lt;\u0026thinsp;18 years, had not presented with fever on admission, in terms of dengue serology had only dengue IgG positive or all negative serology results. For the remaining 412 cases, additional 82 cases had to be further excluded, as the duration of the fever was not mentioned or the cases had sub-acute duration of febrile illness (i.e., \u003cspan class=\"Underline\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;8 days and longer); hence, based on our inclusion criteria, these cases could also not be included in this study and thus, had to be further excluded. Ultimately, 330 cases met the inclusion criteria and were enrolled in our study. (Figure \u003cspan class=\"InternalRef\"\u003eA1\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003e3.1 Proportion of severe dengue\u003c/h2\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n\u003cp\u003eThe proportion of severe dengue among the dengue fever cases in adults admitted at BIRDEM General Hospital was found to be 26/330 (7.9%). The corresponding 95% confidence interval (CI) was 0.496\u0026ndash;0.108.\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eOf the enrolled cases (n\u0026thinsp;=\u0026thinsp;330), 26 (7.9%) were severe dengue, and 304 of the patients were non-severe dengue (92.4%). Amidst the non-severe dengue (n\u0026thinsp;=\u0026thinsp;304), 46 (15.1%) were dengue with warning signs, and 258 (84.9%) were dengue without warning signs. (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eSevere and non-severe dengue, with and without warning signs.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSeverity\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003en\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e%\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSevere dengue\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\"\u003e\n\u003cp\u003e7.9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNon-severe dengue\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026bull; Dengue with warning signs\u003c/p\u003e\n\u003cp\u003e\u0026bull; Dengue without warning signs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e46\u003c/p\u003e\n\u003cp\u003e258\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15.1\u003c/p\u003e\n\u003cp\u003e84.9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAccording to the 2009 WHO dengue classification, severe dengue presented as:\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003e2/26 (7.7%) adult severe dengue patients developed severe plasma leakage with shock\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e3/26 (11.5%) adult severe dengue patients had severe plasma leakage in the form of ascites (n\u0026thinsp;=\u0026thinsp;2, 7.7%) and pleural effusion (n\u0026thinsp;=\u0026thinsp;1, 4%) (as evidenced radiologically).\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e9 (34.6%) of the patients had severe clinical bleeding \u0026ndash; in the form of melaena (n\u0026thinsp;=\u0026thinsp;2), hemoptysis with per-rectal bleeding, and bleeding from left ear (n\u0026thinsp;=\u0026thinsp;1), hematemesis with melaena (n\u0026thinsp;=\u0026thinsp;1), melaena with hematuria (n\u0026thinsp;=\u0026thinsp;1), hematuria (n\u0026thinsp;=\u0026thinsp;2), per-vaginal bleeding (n\u0026thinsp;=\u0026thinsp;1), and hypermenorrhea (n\u0026thinsp;=\u0026thinsp;1).\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eSevere organ impairment was found in 12 patients (46%), as follows: Liver involvement (as transaminitis): 4 patients (15.4%), CNS involvement (as encephalitis): 3 patients (11.5%), cardiac involvement (as myocarditis): 1 patient (4%), acute kidney injury (serum creatinine\u0026thinsp;\u0026gt;\u0026thinsp;3 times above baseline): 4 patients (15.4%).\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eFor comparison of the demographic data, clinical characteristics, and laboratory investigations, the population was divided into: severe dengue and non-severe dengue \u0026ndash; which included dengue fever both with or without warning signs.\u003c/p\u003e\n\u003cdiv id=\"Sec5\" class=\"Section3\"\u003e\n\u003ch2\u003e3.1.1 \u003cem\u003eDemographic data\u003c/em\u003e\u003c/h2\u003e\n\u003cp\u003eThe overall study population (n\u0026thinsp;=\u0026thinsp;330) consisted of 137 (41.5%) males and 193 females (58.5%), among whom 10 males (38.5%) and 16 females (61.5%) had severe dengue, while 127 (41.8%) males and 177 (58.2%) females, had non-severe dengue.\u003c/p\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n\u003cp\u003eThe mean age group in severe dengue was 58.8 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;13.6) years, and for the non-severe dengue, the mean age group 50.6 (\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;17.2) years. There was a statistically significant difference in the mean age between patients with severe dengue and those with non-severe dengue (p\u0026thinsp;=\u0026thinsp;0.018). (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab2\" style=\"width: 439px;\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eBaseline demographics of cases with severe and non-severe dengue.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 148px;\" align=\"left\"\u003e\n\u003cp\u003eParameters\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cp\u003eSevere dengue (n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 95.6343px;\" align=\"left\"\u003e\n\u003cp\u003eNon-severe\u003c/p\u003e\n\u003cp\u003edengue (n\u0026thinsp;=\u0026thinsp;304)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 39.3657px;\" align=\"left\"\u003e\n\u003cp\u003eP-value\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 148px;\" rowspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eGENDER\u003c/p\u003e\n\u003cp\u003e- Male\u003c/p\u003e\n\u003cp\u003e- Female\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 95.6343px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 39.3657px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cp\u003e10 (38.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 95.6343px;\" align=\"char\"\u003e\n\u003cp\u003e127 (41.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 39.3657px;\" align=\"left\"\u003e\n\u003cp\u003e0.837\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cp\u003e16 (61.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 95.6343px;\" align=\"char\"\u003e\n\u003cp\u003e177 (58.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 39.3657px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 148px;\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAGE\u003c/strong\u003e (mean\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;S.D.)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cp\u003e58.8\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;13.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 95.6343px;\" align=\"char\"\u003e\n\u003cp\u003e50.6\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;17.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 39.3657px;\" align=\"left\"\u003e\n\u003cp\u003e0.018\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 148px;\" rowspan=\"10\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eUNDERLYING DISEASES\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026bull; Diabetes mellitus\u003c/p\u003e\n\u003cp\u003e\u0026bull; Hypertension\u003c/p\u003e\n\u003cp\u003e\u0026bull; Ischemic heart disease\u003c/p\u003e\n\u003cp\u003e\u0026bull; Asthma\u003c/p\u003e\n\u003cp\u003e\u0026bull; Chronic kidney disease\u003c/p\u003e\n\u003cp\u003e\u0026bull; Chronic liver disease\u003c/p\u003e\n\u003cp\u003e\u0026bull; Hypothyroidism\u003c/p\u003e\n\u003cp\u003e\u0026bull; Hyperthyroidism\u003c/p\u003e\n\u003cp\u003e\u0026bull; Dyslipidemia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 95.6343px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"width: 39.3657px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cp\u003e22 (84.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 95.6343px;\" align=\"char\"\u003e\n\u003cp\u003e190 (62.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 39.3657px;\" align=\"left\"\u003e\n\u003cp\u003e0.031\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cp\u003e18 (69.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 95.6343px;\" align=\"char\"\u003e\n\u003cp\u003e141 (46.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 39.3657px;\" align=\"left\"\u003e\n\u003cp\u003e0.039\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cp\u003e4 (15.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 95.6343px;\" align=\"char\"\u003e\n\u003cp\u003e43 (14.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 39.3657px;\" align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cp\u003e3 (11.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 95.6343px;\" align=\"char\"\u003e\n\u003cp\u003e16 (5.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 39.3657px;\" align=\"left\"\u003e\n\u003cp\u003e0.180\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cp\u003e7 (26.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 95.6343px;\" align=\"char\"\u003e\n\u003cp\u003e37 (12.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 39.3657px;\" align=\"left\"\u003e\n\u003cp\u003e0.042\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cp\u003e3 (11.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 95.6343px;\" align=\"char\"\u003e\n\u003cp\u003e16 (5.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 39.3657px;\" align=\"left\"\u003e\n\u003cp\u003e0.180\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cp\u003e5 (19.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 95.6343px;\" align=\"char\"\u003e\n\u003cp\u003e32 (10.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 39.3657px;\" align=\"left\"\u003e\n\u003cp\u003e0.191\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 95.6343px;\" align=\"char\"\u003e\n\u003cp\u003e7 (2.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 39.3657px;\" align=\"left\"\u003e\n\u003cp\u003e0.658\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 131px;\" align=\"left\"\u003e\n\u003cp\u003e2 (7.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 95.6343px;\" align=\"char\"\u003e\n\u003cp\u003e19 (6.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 39.3657px;\" align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAll the enrolled cases were aware of their underlying disease status. (See Supplementary Figure \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e, Additional File 1) The associated underlying diseases that were commonly found were: diabetes mellitus (n\u0026thinsp;=\u0026thinsp;22, 84.6%), hypertension (n\u0026thinsp;=\u0026thinsp;18, 69.2%), ischemic heart disease (IHD) (n\u0026thinsp;=\u0026thinsp;4, 15.4%), asthma (n\u0026thinsp;=\u0026thinsp;3, 11.5%), chronic kidney disease (CKD) (n\u0026thinsp;=\u0026thinsp;7, 26.9%), chronic liver disease (CLD) (n\u0026thinsp;=\u0026thinsp;3, 11.5%), hypothyroidism (n\u0026thinsp;=\u0026thinsp;5, 19.2%), hyperthyroidism (none with severe dengue), and dyslipidemia (n\u0026thinsp;=\u0026thinsp;2, 7.7%). None of the cases were evaluated for underlying thalassemia or G-6-PD (glucose-6-phosphate dehydrogenase) deficiency in this study.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section3\"\u003e\n\u003ch2\u003e3.1.2 \u003cem\u003eClinical manifestations\u003c/em\u003e\u003c/h2\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n\u003cp\u003eAs shown in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e (also see Supplementary \u003cstrong\u003eFigure S2\u003c/strong\u003e, Additional File 2), fever was the most predominant presenting complaint in all the cases with severe dengue, followed by vomiting being the second most common (n\u0026thinsp;=\u0026thinsp;8, 30.8%). The mean duration of fever was similar in both severe (3.5 days) \u0026amp; in non-severe (3.3 days) dengue patients. There was no statistically significant difference in the duration of fever between the two groups. Interestingly, 7 (26.9%) of the severe dengue patients had presented with alteration of consciousness on admission, which was observed in the form of drowsiness in one case, one with grade II unconsciousness, one unconscious with poor Glasgow Coma Scale (GCS) of 5/15, \u0026amp; one with convulsion and poor GCS of 3/15. There was a \u003cem\u003estatistically significant\u003c/em\u003e (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) association between alteration of consciousness and severe dengue. In contrary, n\u0026thinsp;=\u0026thinsp;11, 3.6%) non-severe dengue patients had presented with confusion or drowsiness.\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eThe classical presentation with retro-orbital pain, joint pain, myalgia, were not present in any of the patients with severe dengue. One patient presented with headache, one with generalized non-petechial rash, two cases with nausea, one with anorexia \u0026amp; another case with diarrhea. Neither of the patients with severe dengue had any congested conjunctiva, blurred vision, low back pain, or loss of appetite, and had no statistically significant difference with the non-severe dengue patients. (\u003cstrong\u003eFigure \u003cspan class=\"InternalRef\"\u003eS2\u003c/span\u003e\u003c/strong\u003e)\u003c/p\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n\u003cp\u003eWhile in patients with non-severe dengue, fever was the most common presenting complaint on admission, followed by vomiting being the second most common (n\u0026thinsp;=\u0026thinsp;101, 33.3%) complaint; same as noticed in severe dengue cases. A\u0026nbsp;\u003cem\u003estatistically significantly\u003c/em\u003e (p\u0026thinsp;\u0026lt;\u0026thinsp;0.033) higher proportion (n\u0026thinsp;=\u0026thinsp;84, 27.6%) of non-severe dengue patients experience body ache, as compared to severe dengue patients (n\u0026thinsp;=\u0026thinsp;2). Headache (n\u0026thinsp;=\u0026thinsp;57, 18.8%), nausea (n\u0026thinsp;=\u0026thinsp;42, 13.8%), anorexia (n\u0026thinsp;=\u0026thinsp;39, 12.8%) were also common symptoms in non-severe dengue. Retro-orbital pain was present in 8 (2.6%), joint pain in 6 (2%), and myalgia in 3 (1%) of the non-severe dengue patients. Rash was present in 4 (1.3%) patients, of whom 3 had maculopapular rash, but the nature of the rash was not specified in one patient. In terms of nausea, vomiting, rash, lethargy, constipation, and diarrhea, there was no statistically significant difference observed between the severe dengue and the non-severe dengue patients.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eClinical presentation of cases with severe and non-severe dengue.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eParameters\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSevere dengue (n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNon-severe\u003c/p\u003e\n\u003cp\u003edengue (n\u0026thinsp;=\u0026thinsp;304)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eCHIEF COMPLAINT\u003c/p\u003e\n\u003cp\u003e\u0026bull; Fever\u003c/p\u003e\n\u003cp\u003e\u0026bull; Headache\u003c/p\u003e\n\u003cp\u003e\u0026bull; Alteration of consciousness\u003c/p\u003e\n\u003c/td\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26 (100%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e304 (100%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e57 (18.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (26.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"17\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eCLINICAL MANIFESTATIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFever\u003c/p\u003e\n\u003cp\u003e\u0026bull; Duration of fever (days)\u003c/p\u003e\n\u003cp\u003eHeadache\u003c/p\u003e\n\u003cp\u003eRetro-orbital pain\u003c/p\u003e\n\u003cp\u003eCongested conjunctiva/conjunctivitis\u003c/p\u003e\n\u003cp\u003eJoint pain\u003c/p\u003e\n\u003cp\u003eMyalgia\u003c/p\u003e\n\u003cp\u003eBody ache\u003c/p\u003e\n\u003cp\u003eLow back pain\u003c/p\u003e\n\u003cp\u003eRash\u003c/p\u003e\n\u003cp\u003eNausea\u003c/p\u003e\n\u003cp\u003eVomiting\u003c/p\u003e\n\u003cp\u003eAnorexia\u003c/p\u003e\n\u003cp\u003eLoss of appetite\u003c/p\u003e\n\u003cp\u003eConstipation\u003c/p\u003e\n\u003cp\u003eDiarrhea\u003c/p\u003e\n\u003cp\u003eConfusion and drowsiness\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26 (100%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e304 (100%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.5\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.08\u003c/p\u003e\n\u003cp\u003e1 (3.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.3\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.73\u003c/p\u003e\n\u003cp\u003e57 (18.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (2.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (0.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (7.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e84 (27.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (2.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (1.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (7.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42 (13.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (30.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e101 (33.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39 (12.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (3.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22 (7.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (3.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\"\u003e* (mean\u0026thinsp;+\u0026thinsp;S.D.)\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cem\u003eWarning signs\u003c/em\u003e: 12 (46.2%) of the severe dengue patients exhibited warning signs. (Table 4) Abdominal pain was present in 4 patients (15.4%), and in non-severe dengue patients, it was a frequent symptom (n\u0026thinsp;=\u0026thinsp;31, 10.2%). Persistent vomiting was found in 3 patients (11.5%) in severe dengue, while on the other hand, in 12 patients (3.9%) in non-severe dengue. 6 of the severe dengue patients presented with bleeding manifestations, in the form of hematemesis (n\u0026thinsp;=\u0026thinsp;1, 3.8%), melaena (n\u0026thinsp;=\u0026thinsp;4, 15.4%), and hypermenorrhea (n\u0026thinsp;=\u0026thinsp;1, 3.8%). For melaena, there was a highly \u003cem\u003estatistically significant\u003c/em\u003e (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) difference, thus implying it was a strong indicator of severity in this study. None of the severe dengue cases presented with gum bleeding or epistaxis. (See Supplementary\u0026nbsp;\u003cstrong\u003eFigure S3\u003c/strong\u003e, Additional File 3)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eWarning signs in severe and non-severe dengue.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWarning signs\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSevere dengue (n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNon-severe\u003c/p\u003e\n\u003cp\u003edengue (n\u0026thinsp;=\u0026thinsp;304)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"8\" align=\"left\"\u003e\n\u003cp\u003eAbdominal pain\u003c/p\u003e\n\u003cp\u003ePersistent vomiting\u003c/p\u003e\n\u003cp\u003eBleeding manifestations\u003c/p\u003e\n\u003cp\u003e\u0026clubs; Gum bleeding\u003c/p\u003e\n\u003cp\u003e\u0026clubs; Epistaxis\u003c/p\u003e\n\u003cp\u003e\u0026clubs; Hematemesis\u003c/p\u003e\n\u003cp\u003e\u0026clubs; Melaena\u003c/p\u003e\n\u003cp\u003e\u0026clubs; Hypermenorrhea\u003c/p\u003e\n\u003cp\u003e\u0026clubs; Restlessness\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (15.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31 (10.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (11.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12 (3.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (0.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (15.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (0.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section3\"\u003e\n\u003ch2\u003e3.1.3 \u003cem\u003eLaboratory findings\u003c/em\u003e\u003c/h2\u003e\n\u003cp\u003eThe baseline laboratory investigations on the day of admission, including hematology, liver function tests, and biochemistry, were analyzed (Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e.\u003c/p\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n\u003cp\u003ePatients with severe dengue had a significantly lower mean hematocrit (32.86%) compared to those with non-severe dengue (36.08%). Those with severe dengue also had a significantly lower mean hemoglobin (11.02 mg/dl), compared to non-severe dengue (12.13 mg/dl). The patients with severe dengue had a significantly higher mean WBC count (9,790/mm\u003csup\u003e3\u003c/sup\u003e). In the differential count of the whole blood count, there was no statistically significant difference. While the mean platelet count was lower in the severe dengue patients (130.55 x 10\u003csup\u003e9\u003c/sup\u003e/mm\u003csup\u003e3\u003c/sup\u003e) compared to non-severe (133.66 x 10\u003csup\u003e9\u003c/sup\u003e/mm\u003csup\u003e3\u003c/sup\u003e), this difference was not statistically significant. Patients with severe dengue had \u003cem\u003esignificantly\u003c/em\u003e higher (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) mean alanine transferase (467.79 U/L), mean aspartate transferase (865.3 U/L), and mean alkaline phosphatase (146.41 U/L) levels, compared to non-severe dengue. This indicated significant liver involvement or damage in severe dengue. Patients with severe dengue had \u003cem\u003esignificantly\u003c/em\u003e lower mean serum albumin levels compared to non-severe dengue. Hypoalbuminemia is a common finding in severe dengue due to plasma leakage. There was no statistically significant difference in total protein, total or direct bilirubin levels in severe and non-severe dengue patients.\u003c/p\u003e\n\u003cp\u003ePatients with severe dengue had \u003cem\u003esignificantly\u003c/em\u003e higher (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) mean BUN levels compared to non-severe dengue. Elevated BUN could indicate impaired renal function or dehydration, both of which can be complications of severe dengue. Patients with severe dengue also had a \u003cem\u003esignificantly\u003c/em\u003e higher (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) mean serum creatinine level compared to non-severe dengue. Elevated creatinine is a strong indicator of acute kidney injury, which is a severe complication of dengue. No statistically significant difference was seen in the mean sodium, chloride, TCO2, mean serum ferritin, and mean serum LDH levels between severe and non-severe dengue patients in this study.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab5\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eBaseline laboratory findings of patients with severe and non-severe dengue.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eParameters\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSevere dengue (n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNon-severe\u003c/p\u003e\n\u003cp\u003edengue (n\u0026thinsp;=\u0026thinsp;304)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP-value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e95% CI\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eHEMATOLOGY\u003c/strong\u003e (mean\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;S.D.)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHematocrit (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32.86\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;9.59\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36.08\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5.41\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.023\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.46\u0026ndash;5.99\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHemoglobin (mg/dl)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.02\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;3.27\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.13\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.87\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.019\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.18\u0026ndash;2.04\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWBC count (x 10\u003csup\u003e3\u003c/sup\u003e/cu mm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9,790\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;8,492.12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6,476.18\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;4,381.15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-5596.92 \u0026ndash; (-1030.72)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026bull; Neutrophils (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e74.06\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;12.43\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e69.67\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;15.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.223\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-11.48\u0026ndash;2.70\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026bull; Lymphocytes (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.61\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;10.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.53\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;14.23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.143\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-1.68\u0026ndash;11.51\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026bull; Monocytes (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.1\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.47\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.88\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.046\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.02\u0026ndash;2.70\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026bull; Eosinophils (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.53\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.62\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.71\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.27\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.541\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.40\u0026ndash;0.76\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePlatelet count (x 10\u003csup\u003e9\u003c/sup\u003e/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e130.55\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;99.38\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e133.66\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;84.96\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.878\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-150.52\u0026ndash;213.02\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eLIVER FUNCTION TESTS*\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALT (U/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e467.79\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;926.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e89.47\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;236.54\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-520.91 - (-235.73)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAST (U/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e865.3\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1553.89\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e119.5\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;209.32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-948.97 - (-542.65)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALP (U/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e146.41\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;82.96\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e91.38\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;65.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-84.7 - (-25.37)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal protein (g/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e63.71\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;9.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66.65\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;8.99\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.195\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-1.52\u0026ndash;7.41\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eserum albumin (g/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31.7\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;7.06\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36.28\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;4.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.36\u0026ndash;6.8\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal bilirubin (mg/dl)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.25\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.92\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;3.18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.638\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-1.72\u0026ndash;1.06\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDirect bilirubin (mg/dl)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.93\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.53\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.275\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-1.54\u0026ndash;0.75\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eBIOCHEMISTRY\u003c/strong\u003e (mean\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;S.D.)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBlood urea nitrogen (BUN)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e61.68\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;54.24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38.29\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;32.44\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.007\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-40.38 - (-6.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSerum creatinine (mg/dl)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.71\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;3.25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.28\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-2.04 - (-0.84)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSerum electrolytes (mmol/l)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026bull; Na\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e134.88\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;7.79\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e134.37\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5.29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.658\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-2.77\u0026ndash;1.75\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026bull; K\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.18\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.96\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.02\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.62\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.235\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.43\u0026ndash;0.11\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026bull; Cl\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100.56\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;6.67\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e99.09\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5.36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.200\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-3.71\u0026ndash;0.78\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026bull; TCO2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.88\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;4.48\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.54\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;3.17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.333\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.68\u0026ndash;2.01\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSerum ferritin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1944.25\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1048.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3312.78\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;5851.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.647\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-4617.89\u0026ndash;7354.94\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSerum lactate dehydrogenase\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3007.33\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1325.67\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1210.67\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1012.87\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.032\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-3404.91 - (-188.42)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003e* (mean\u0026thinsp;+\u0026thinsp;S.D.)\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section3\"\u003e\n\u003ch2\u003e3.1.4 \u003cem\u003ePossible risk factors of severe dengue\u003c/em\u003e\u003c/h2\u003e\n\u003cp\u003eLogistic regression model was used to assess the risk factors associated with severe dengue, by univariate and multivariate analyses. The odds ratios (OR) and the corresponding 95% confidence intervals for the odds ratios were reported (as shown in Table \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n\u003cp\u003eFor univariate analysis, the independent association of severe dengue with each of the following variables was analyzed:\u003c/p\u003e\n\u003c/div\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cem\u003eAGE\u003c/em\u003e: Age was a \u003cem\u003estatistically significant\u003c/em\u003e (p\u0026thinsp;=\u0026thinsp;0.021\u003cstrong\u003e)\u003c/strong\u003e predictor of severe dengue in this study, suggesting that older age was associated with increased odds of severe dengue. For every one-year increase in age, the odds of severe dengue increased by 3.1% (OR\u0026thinsp;=\u0026thinsp;1.031).\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cem\u003eSYMPTOM \u0026ndash; ALTERATION OF CONSCIOUSNESS\u003c/em\u003e: Patients with alteration of consciousness had approximately\u0026thinsp;~\u0026thinsp;10 times higher odds of having severe dengue, compared to those without this symptom. This was a highly \u003cem\u003estatistically significant\u003c/em\u003e (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and strong predictor of severe dengue.\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cem\u003eSYMPTOM \u0026ndash; BODY ACHE\u003c/em\u003e: Patients with body ache had 0.22 times the lower odds of severe dengue, which was \u003cem\u003estatistically significant\u003c/em\u003e (p\u0026thinsp;=\u0026thinsp;0.042), suggesting that it was more common in non-severe cases.\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cem\u003eUNDERLYING DISEASES\u003c/em\u003e: Those with underlying diabetes, hypertension, and chronic kidney disease had approximately 3 times higher odds of having severe dengue.\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cem\u003eLAB INVESTIGATIONS - HEMATOCRIT\u003c/em\u003e: For every one-unit increase in hematocrit, the odds of severe dengue decreased by about 10% (i.e., 1\u0026ndash;0.896). This indicated that higher hematocrit was \u003cem\u003esignificantly\u003c/em\u003e (p\u0026thinsp;=\u0026thinsp;0.025) associated with lower odds of severe dengue in the univariate analysis. This was an unusual finding, as higher hematocrit (hemoconcentration) is typically associated with severe dengue. \u003cem\u003eASPARTATE TRANSAMINASE (AST), ALKALINE PHOSPHATASE (ALP)\u003c/em\u003e: were highly \u003cem\u003estatistically significant\u003c/em\u003e (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) predictors of severe dengue. \u003cem\u003eLOWER SERUM ALBUMIN\u003c/em\u003e: consistent with plasma leakage in severe cases. \u003cem\u003eSERUM CREATININE\u003c/em\u003e: indicating that impaired renal function was strongly associated with severe dengue. There was no statistical significance between WBC count and severe dengue (p\u0026thinsp;=\u0026thinsp;0.013, OR\u0026thinsp;=\u0026thinsp;1).\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n\u003cp\u003eBased on the multivariate analysis (which is more robust for identifying independent predictors), only alteration of consciousness, hematocrit, and AST remained significant after multivariate adjustment of the listed variables in the model. Hematocrit (lower values) and AST (higher values) were \u003cem\u003estatistically significant\u003c/em\u003e independent predictors of severe dengue. The logistic regression model, as indicated by the ROC (receiver operating characteristic) curve AUC (area under ROC curve) of 0.8834, showed good overall predictive ability (goodness-of-fit test) of 88.3% for severe dengue. (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab6\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eLogistic regression model for severe dengue.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eVARIABLES\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eUNIVARIATE ANALYSIS\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003eMULTIVARIATE ANALYSIS\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOR\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e95% CI\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP-value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eadjusted OR (aOR)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e95% CI\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP-value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.031\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.005\u0026ndash;1.058\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.021\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSYMPTOMS\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlteration of consciousness\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.813\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.417\u0026ndash;28.187\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e51.254\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e8.245\u0026ndash;318.613\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBody ache\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.218\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.05\u0026ndash;0.944\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.042\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eUNDERLYING DISEASES\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDiabetes mellitus\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.109\u0026ndash;9.189\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.032\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHypertension\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.601\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.098\u0026ndash;6.164\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.03\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChronic kidney disease\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.659\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.047\u0026ndash;6.754\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.04\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eLABORATORY INVESTIGATIONS\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHematocrit\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.896\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.814\u0026ndash;0.987\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.025\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.829\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.728\u0026ndash;0.9444\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWhite blood cell count\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.013\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAST\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.002\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.001\u0026ndash;1.002\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.002\u0026ndash;1.008\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.007\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.002\u0026ndash;1.011\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.004\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSerum albumin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.853\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.782\u0026ndash;0.931\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSerum creatinine\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.368\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.138\u0026ndash;1.645\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section3\"\u003e\n\u003ch2\u003e3.1.5 \u003cem\u003eComplications of severe dengue\u003c/em\u003e\u003c/h2\u003e\n\u003cp\u003eTwenty-one (80.8%) out of the 26 patients with severe dengue had developed complications. 2 (7.7%) of the patients with severe dengue had developed septic and cardiogenic shock. 6 (23.1%) had respiratory failure; among them, 4 required respiratory support by endotracheal intubation with airway protection and mechanical ventilation. 4 (15.4%) of these patients had also developed pulmonary edema, along with respiratory failure. 8 (30.8%) patients had abnormal bleeding. One (4%) patient with severe dengue developed viral myocarditis, while 2 (7.7%) patients developed acute left ventricular failure. 3 (11.5%) patients had developed encephalitis. Findings in MRI brain of one showed bilateral hyperintense signal change in both cerebral cortices. 2 of them had received steroids during hospitalization and improved. 4 (15.4%) of them had acute kidney injury, had prior chronic kidney disease (CKD), and were on hemodialysis. 8 (30.8%) of the patients had electrolyte imbalance. Coinfection was present in 14 (53.8%) of the patients. The concomitant coinfections seen in our severe dengue cases ranged from pneumonia (n\u0026thinsp;=\u0026thinsp;5), sepsis (n\u0026thinsp;=\u0026thinsp;2), urinary tract infection (n\u0026thinsp;=\u0026thinsp;3), pneumonia with pleural effusion, along with concurrent urinary tract infection (n\u0026thinsp;=\u0026thinsp;1), rickettsial fever with urosepsis (n\u0026thinsp;=\u0026thinsp;1), and acute gastroenteritis (n\u0026thinsp;=\u0026thinsp;2).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section3\"\u003e\n\u003ch2\u003e3.1.6 \u003cem\u003eOutcomes of severe dengue\u003c/em\u003e\u003c/h2\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n\u003cp\u003eOutcome at the end-of-care was defined in this study as the following: cured and discharged with advice, required transfer to the intensive care unit (ICU), was discharged on risk bond (i.e. the patient was in a very critical state but despite being aware of the risks, wanted discharge due to financial constraints), was discharged on request (i.e. the patient was relatively well but did not recover entirely; needed to be observed by the clinician but wanted to be discharged upon request), or death.\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003e16 (61.5%) out of the 26 adult severe dengue patients were cured and were discharged with advice. 3 (11.5%) patients had to be transferred to the intensive care unit (ICU), primarily due to respiratory and multi-organ failure, necessitating close monitoring and for further management. 2 (7.7%) of the patients were discharged on risk bond due to financial constraints. 2 (7.7%) patients wanted to be discharged on request, and 3 (11.5%) patients died. (See Supplementary \u003cstrong\u003eFigure S4\u003c/strong\u003e, Additional File 4) The ultimate outcome of those who were transferred to the ICU, were discharged on risk bond or upon request, were unknown (n\u0026thinsp;=\u0026thinsp;7, 29.2%).\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eOur study site BIRDEM General Hospital of Dhaka, Bangladesh, is a non-government tertiary care specialized hospital especially for treating those with underlying diabetes mellitus, endocrine and metabolic disorders; thus, diabetes or endocrine diseases, such as hypothyroidism, could have been confounding factors in our study population of severe dengue. In contrast to the vast patient turnover in the public hospitals of Bangladesh, the findings of this study may not be reflective of the actual real-time scenario of severe dengue in Bangladesh. However, in the public hospital settings of Bangladesh, there are insufficient beds, limited diagnostic facilities, lack of manpower, and an inadequate referral system. Due to the unfortunate lack of proper documentation and data preservation, conducting our retrospective study in public hospitals could not be considered.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eFrom this study, the proportion of adult severe dengue patients in the study site was 7.9%. In contrast, the cross-sectional observational study conducted in 2023 at two government medical college hospitals in Bangladesh found \u0026sim;17% developed severe dengue\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur study indicated that out of the total enrolled cases (n\u0026thinsp;=\u0026thinsp;330), 26 were severe dengue (7.9%), and the majority of the 304 patients were non-severe dengue (92.4%), which included 46 patients of dengue with warning signs (15.1%) and 258 patients of dengue without warning signs (84.9%). A prospective study done at the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University in Bangkok, Thailand, showed that out of the 153 patients with confirmed dengue infection, 13.7% (21 patients) had severe dengue while 86.3% (132 patients) had non-severe dengue, which included 94.7% dengue with warning signs (125 patients) and dengue without warning signs in 5.3% (7 patients). Of those with severe dengue, 16 (76.2%) had severe plasma leakage, 8 (38.1%) had severe clinical bleeding, and 16 (76.2%) had severe organ involvement. 12 out of the 16 patients (75%) had severe plasma leakage with shock, and 8 (50%) had plasma leakage with respiratory distress. Out of the 16 patients with severe organ involvement, 9 (56.2%) had AST\u0026thinsp;\u0026gt;\u0026thinsp;1,000 IU/L and/or ALT\u0026thinsp;\u0026gt;\u0026thinsp;1,000 IU/L, 9 (56.2%) had serum creatinine\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;3 times above baseline, 1 (6.2%) had myocarditis, and 1 (6.2%) had encephalitis\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Whereas, in our study, out of the 26 patients with severe dengue, 2 (7.7%) developed plasma leakage with shock, 3 (11.5%) had plasma leakage in the form of ascites (n\u0026thinsp;=\u0026thinsp;2) and pleural effusion (n\u0026thinsp;=\u0026thinsp;1) (radiological evidence), and 9 (34.6%) had severe clinical bleeding. Among the 12 patients (56%) who had severe organ impairment, 4 (15.4%) had liver involvement (i.e. AST\u0026thinsp;\u0026gt;\u0026thinsp;1,000 IU/L and/or ALT\u0026thinsp;\u0026gt;\u0026thinsp;1,000 IU/L), 3 (11.5%) had CNS involvement (as encephalitis), 1 (4%) had cardiac involvement (as myocarditis), and 4 (15.4%) had acute kidney injury (serum creatinine\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;3 times above baseline). On the contrary, a prospective observational study conducted in four government hospitals in Dhaka, Bangladesh, in 2022 showed severe organ involvement in dengue infection as myocarditis (cardiac involvement) in 0.6% cases and neurologic involvement in the form of meningitis and Guillain-Barr\u0026eacute; syndrome (GBS) in 0.6% cases as well\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn our study, the affected population of adult severe dengue were predominantly females (n\u0026thinsp;=\u0026thinsp;16, 61.5%), and 177 females (58.2%) had non-severe dengue. There was no specific reason as to why the affected population was mostly females. Regarding gender distribution, there was a male predominance in all the dengue outbreaks that were previously reported in Bangladesh, including a study done at our study site in 2019\u003csup\u003e[\u003cspan additionalcitationids=\"CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. A cross-sectional observational study conducted in 450 confirmed dengue patients at two government medical college hospitals of Bangladesh in 2023, also showed that the male-to-female ratio was nearly equal. The above-mentioned study also showed that the patients with severe dengue were older compared to those with non-severe dengue (36.6 years versus 32.6 years)\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. In the prospective study done in Thailand, as mentioned above, also showed that the development of severe dengue was significantly associated with patients aged\u0026thinsp;\u0026gt;\u0026thinsp;40 years\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. In our study, the mean age group in severe dengue was 58.8 years, and for the non-severe dengue, the mean age group was 50.6 years. Whereas the study in our same study site in 2023 found the mean age of the dengue patients was 33\u0026thinsp;\u0026plusmn;\u0026thinsp;14.6 years (\u0026plusmn;\u0026thinsp;SD), and almost half of them were young adults age 18 to 30 years, found the least number (1.90%) of cases in the \u0026gt;\u0026thinsp;60 years age group, and about 15.24% cases in the age group of 41\u0026ndash;60 years\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe study population of severe dengue patients had underlying diseases including diabetes mellitus (n\u0026thinsp;=\u0026thinsp;22, 84.6%), hypertension (n\u0026thinsp;=\u0026thinsp;18, 69.2%), ischemic heart disease (n\u0026thinsp;=\u0026thinsp;4, 15.4%), chronic kidney disease (n\u0026thinsp;=\u0026thinsp;7, 26.9%), chronic liver disease (n\u0026thinsp;=\u0026thinsp;3, 11.5%), hypothyroidism (n\u0026thinsp;=\u0026thinsp;5, 19.2%), and dyslipidemia (n\u0026thinsp;=\u0026thinsp;2, 7.7%). Diabetes mellitus (84.6%) and hypertension (69.2%) showed higher percentages in severe dengue, and were \u003cem\u003estatistically significant\u003c/em\u003e (DM: p\u0026thinsp;=\u0026thinsp;0.031; HTN: p\u0026thinsp;=\u0026thinsp;0.039) in both severe and non-severe dengue. While chronic kidney disease was more prevalent in severe dengue (26.9% vs. 12.2%, this difference was statistically significant (p\u0026thinsp;=\u0026thinsp;0.042), suggesting it as a potential predisposing factor for severe outcomes.\u003c/p\u003e\u003cp\u003eThe prospective observational study conducted in four government hospitals in Dhaka, Bangladesh, in 2022 showed 15.8% (p 0.03) of their study population were diabetic and 19.7% (p 0.01) were hypertensive, in the severe category of dengue fever\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. Another cross-sectional study done in 3 hospitals in Dhaka, Bangladesh, showed hypertension (90, 4.5%) as the most common associated comorbidity along with diabetes mellitus (DM) (70, 3.5%) and CKD (10, 0.5%), in those with severe disease\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. The study in our same study site in 2023 also found diabetes mellitus (DM) as the major comorbidity (75, 25.7%), followed by hypertension (16.1, 47%), dyslipidemia (21, 7.2%), hypothyroidism (4.8, 14%), ischemic heart disease (3, 1%), and CKD (n\u0026thinsp;=\u0026thinsp;4, 1.4%)\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. For the development of acute kidney injury, some independent risk factors are advanced age, male gender, obesity, hemorrhagic fever, multiple organ dysfunction, diabetes mellitus, concomitant bacterial infection, rhabdomyolysis, delay in hospital consultation, and use of nephrotoxic drugs\u003csup\u003e[\u003cspan additionalcitationids=\"CR27 CR28\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur study demonstrated fever as the sole consistent presenting complaint, universally present (100%), while vomiting was the second most common, observed in 30.8% (n\u0026thinsp;=\u0026thinsp;8) of patients upon admission. Differing from classical dengue presentations, symptoms such as retro-orbital pain, joint pain, and myalgia were absent. Furthermore, specific complaints like congested conjunctiva, blurred vision, loss of appetite, constipation, or lethargy were also not reported, and had no statistically significant difference with the non-severe dengue patients. The mean duration of fever was nearly the same (\u0026sim;3 days) in both severe and non-severe dengue, which implied that there was no statistically significant difference between severe and non-severe dengue. Warning signs were evident in a considerable portion (n\u0026thinsp;=\u0026thinsp;12, 46.2%) of patients. 6 individuals presented with bleeding manifestations, comprising hematemesis (n\u0026thinsp;=\u0026thinsp;1, 3.8%), melena (n\u0026thinsp;=\u0026thinsp;4, 15.4%), and hypermenorrhea (n\u0026thinsp;=\u0026thinsp;1, 3.8%). Remarkably, gum bleeding or epistaxis were not observed. Additional warning signs included abdominal pain (n\u0026thinsp;=\u0026thinsp;4, 15.4%), persistent vomiting (n\u0026thinsp;=\u0026thinsp;3, 11.5%), and restlessness (n\u0026thinsp;=\u0026thinsp;1, 3.8%). A notable finding from the crosstabulation analysis was that, contrary to common expectations, a substantial portion of severe dengue cases (54%) did not present with the specified warning signs, and a considerable proportion (15.8%) of non-severe cases did. This suggested that reliance solely on these particular warning signs may have been insufficient for identifying all severe dengue cases in this study population.\u003c/p\u003e\u003cp\u003eWhile in contrast to the prospective observational study done in Dhaka in 2022 displayed that severe dengue patients reported fever in all the cases (100%), followed by body aches (72.1%), and reported a higher number of nausea (80.3%, p 0.008), cough (57.9%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), abdominal pain (56.6%, p 0.21), persistent vomiting (53.9%), dyspnea (35.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), diarrhea (28.9%, p 0.45), skin rash (27.6%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and joint pain (26.3%, p 0.91). Also, hematemesis (2.3%), hematochezia (1.3%), and melena (1.6%) were present only in severe dengue cases\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. On the other hand, the prospective study of Hospital of Tropical Diseases, Bangkok, Thailand, in severe dengue patients showed myalgia (20, 95.2%), lethargy (19, 90.5%), headache (18, 87.5%), fever (17, 80%), mucosal bleeding (14, 66.7%), skin bleeding (13, 61.9%), retro-orbital pain (11, 52.4%), rash (10, 47.6%), abdominal pain and persistent vomiting (9, 42.9%) patients, and diarrhea (5, 23.8%)\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. A particularly striking finding in our study was the occurrence of altered consciousness in 7 (26.9%) patients at presentation, with documented cases of drowsiness, grade II unconsciousness, and profoundly low Glasgow Coma Scale scores (3/15 and 5/15, respectively), including one case with convulsion. This aligns with a multi-center retrospective cohort study done in Taiwan between 2002\u0026ndash;2019, where altered consciousness was found in 12.2% severe dengue patients\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eFrom our study, the laboratory findings suggested that in severe dengue, compared to non-severe dengue, there was significantly (p\u0026thinsp;=\u0026thinsp;0.023) lower hematocrit (32.86%) level and significantly (p 0.019) lower hemoglobin (11.02 mg/dL) levels. In liver function tests, significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) higher ALT: 467.79 U/L, AST: 865.3 U/L, and ALP levels: 146.41 U/L, implying hepatocellular damage, and significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) lower serum albumin (31.7 g/L) levels. Biochemistry results indicated significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) higher serum creatinine (2.71 mg/dL) and blood urea nitrogen (BUN): 61.68 mg/dL, suggesting possible impairment of renal function. Furthermore, a marker of organ dysfunction as serum LDH (3007.33 IU) was elevated, which aligns with the pathology of severe dengue. The findings of this study for hematocrit (lower in severe dengue) and platelet count (no significant difference) were opposed to the typical clinical presentation and WHO guidelines for severe dengue, where hemoconcentration (elevated hematocrit) and significant thrombocytopenia were expected hallmarks. These specific results suggested a possibility of potential confounding factors within this specific study. It could also be possible that the sample size for severe dengue (n\u0026thinsp;=\u0026thinsp;26) was too small to consistently capture these changes, or there was some unique characteristic of this study. A retrospective study conducted at Teaching Hospital Peradeniya of Kandy district of Sri Lanka, showed that during the acute febrile phase (2nd and 3rd day) of dengue virus infection, hemoglobin levels ranged from 9.5\u0026ndash;18.8 mg/dL, also platelet count\u0026thinsp;\u0026lt;\u0026thinsp;150,000 cells/mm\u003csup\u003e3\u003c/sup\u003e in 63.1% and \u0026lt;\u0026thinsp;100,000 cells/mm\u003csup\u003e3\u003c/sup\u003e in about 33.2% patients. Besides, the decline in the mean hematocrit values on the 5th day of illness (compared to the 3rd day) in both plasma leakers and in non-leakers could be due to dilution of plasma during fluid replenishment\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e. In those with lower mean hematocrit and hemoglobin levels, there was occurrence of bleeding manifestations in 3 of the severe dengue patients.\u003c/p\u003e\u003cp\u003eBased on the multivariate logistic regression analysis, alteration of consciousness, hematocrit, and elevated AST levels were significantly associated with increased odds of severe dengue. While other variables like age, body ache, diabetes mellitus, hypertension, chronic kidney disease, WBC, ALP, serum albumin, and serum creatinine were all individually significant predictors in univariate analyses, their independent significance was not maintained or not presented in the final multivariate model. The overall derived predictive model, as previously indicated by an Area Under the ROC Curve (AUC) of 0.8302, demonstrated a good to very good ability (goodness-to-fit-test) to discriminate between severe and non-severe dengue cases.\u003c/p\u003e\u003cp\u003eIn a cross-sectional study done in two of the academic hospitals of Bangladesh in 2023, their laboratory parameters reflected that \u0026gt;\u0026thinsp;48% hematocrit was present in 5% of the patients, 13% in severe dengue, and 3.5% in non-severe dengue, which was statistically significant (P\u0026thinsp;=\u0026thinsp;0.001) in their study. Leukopenia was reported in \u0026sim;46%, and thrombocytopenia in 56% of their patients. Increased AST and ALT levels (\u0026gt;\u0026thinsp;40 IU/L) were reported in 42% and 67% of the patients, respectively. Serum AST was associated with severe dengue. 2% of their patients also had a serum creatinine value of \u0026gt;\u0026thinsp;2 mg/dL, mostly seen in the patients with severe dengue (P\u0026thinsp;=\u0026thinsp;0.001) of their study\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Laboratory findings in the prospective study in Thailand showed patients with severe dengue had significantly greater white blood cell (WBC) (p\u0026thinsp;=\u0026thinsp;0.034); absolute lymphocytes\u0026thinsp;\u0026gt;\u0026thinsp;2,000 cells per \u0026micro;L, alanine transaminase (ALT) levels (p\u0026thinsp;=\u0026thinsp;0.003), and aspartate transaminase (AST) levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In their study, multivariate regression indicated that the following clinical and laboratory characteristics upon admission were independently associated with the development of severe dengue: (1) age\u0026thinsp;\u0026gt;\u0026thinsp;40 years, (2) persistent vomiting, (3) absolute atypical lymphocyte\u0026thinsp;\u0026gt;\u0026thinsp;300 cells per \u0026micro;L, and (4) lactate level\u0026thinsp;\u0026ge;\u0026thinsp;2.0 mmol/L\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. The study done in pediatric severe dengue patients in Puerto Rico concluded severe dengue cases had more frequent hemoconcentration (11%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), leucopenia (77%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), thrombocytopenia (74%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and low albumin (86%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) levels\u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur severe dengue cases exhibited a range of concomitant coinfections, including pneumonia, sepsis, urinary tract infection, and acute gastroenteritis. More complex coinfections also occurred, such as one case of pneumonia with pleural effusion and concurrent urinary tract infection, and one case of rickettsial fever with urosepsis.\u003c/p\u003e\u003cp\u003eThe most common complications in the severe dengue cases that were observed in the prospective observational study in Dhaka, Bangladesh, in 2022 were pneumonia (2.3%), followed by hepatitis (1.6%), and pancreatitis (1.3%)\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. While in the retrospective cohort study done in Taiwan, among the severe dengue patients, 35% experienced acute kidney injury, 18.4% had pneumonia, and 6.5% had bacteremia\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. A relatively uncommon yet serious complication in severe dengue is bacterial co-infection. Although only approximately 7% dengue patients have concurrent bacteremia, 44% dengue-related deaths are related to bacterial co-infection, like pneumonia, urinary tract infection, enteric fever, etc.\u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn a prospective cohort in Latin America found patients with warning signs were hospitalized (99%), while 33% critical dengue patients needed admission to the ICU, primarily due to vascular leakage with respiratory distress or profound thrombocytopenia, that needed close observation and monitoring\u003csup\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOut of the 26 adult severe dengue patients in this study, 16 patients (62%) recovered and were discharged with follow-up advice. 3 patients (11.5%) required transfer to the ICU due to complications such as respiratory and multi-organ failure, requiring intensive monitoring and management. 2 patients (8%) were discharged on a risk bond due to financial limitations, 2 patients (8%) were discharged on request, and death of 3 patients (11.5%) were reported.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThis retrospective observational study highlighted that the adult severe dengue patients belonged to the older age group and significantly more prevalent in those with underlying diabetes mellitus, hypertension, and chronic kidney disease. Clinical indicators of severe dengue included alteration of consciousness and melena, while body ache was more frequent in non-severe cases. Laboratory derangements including unexpectedly reduced hematocrit and hemoglobin levels, elevated liver enzymes (AST, ALT, ALP), renal function tests (creatinine, BUN), markers of systemic damage (reduced albumin, elevated LDH), were strongly associated with disease severity. The multivariate logistic regression model highlighted alteration of consciousness and elevated AST as independent predictors of severe dengue, emphasizing their crucial role in risk assessment. The finding regarding lower hematocrit being associated with severe dengue in the univariate analysis was counter-intuitive to the established understanding of hemoconcentration in severe dengue. However, the developed logistic regression model offered good predictive capability for identifying severe dengue. But the small sample size for severe dengue (n\u0026thinsp;=\u0026thinsp;26) could have impacted the statistical power, when interpreting the strength of associations. The findings of this study also emphasized that the absence of classical warning signs should not preclude vigilance for severe dengue, indicating a need for patients requiring hospitalization to be accurately identified by physicians. Although a large group of non-severe dengue patients were admitted to the hospital, they could possibly be managed with ambulatory care and followed up afterwards on an outpatient basis with daily follow-up physically or via telemedicine, to reduce the burden on hospitals. Despite the severity of illness, complexity of manifestations, and complications like severe organ impairment and bleeding, the study observed a favorable positive outcome with minimal reported mortality, indicating effective clinical management protocols within the hospital setting. These findings provide valuable insights and emphasize the importance of clinical and laboratory markers for early recognition, risk stratification, and timely intervention to improve outcomes in dengue management.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003cp\u003eBangladesh, being a resource-limited low- to middle-income country (LMIC), had certain limitations in our research. As the hospital health information system (HIS) and laboratory information system (LIS) database was not designed with the ICD-10 (International Classification of Diseases 10th revision) coding system, to trace and identify the dengue cases specifically, the screening and enrolment had to be done manually, by cross-checking the raw laboratory data (especially in case of Dengue serology \u0026ndash; Dengue NS1, IgM, IgG), and comparing them with the electronic discharge summaries. Also, there was a backlog in the archiving system of the hospital admission records, and unfortunately, ~\u0026thinsp;50% of the archived records could not be retrieved, thus leading to missing data, which could not be recorded and completely analyzed further. An initiative for improved documentation of cases is warranted. Besides, the atypical lymphocytes were not generated in the profile of complete blood count (CBC) panel. The diagnostic facility for dengue PCR (polymerase chain reaction) test was not available at the study site and therefore, could not be recorded.\u003c/p\u003e\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eThe following abbreviations are used in this manuscript:\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eaOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAdjusted Odd’s ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHealth information system\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eALT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAlanine aminotransferase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIntensive care unit\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAspartate aminotransferase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eICD-10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eInternational Classification of Diseases 10\u003csup\u003eth\u003c/sup\u003e revision coding system\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eALP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAlkaline phosphatase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIgG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eImmunoglobulin G\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAUC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eArea under ROC curve\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIgM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eImmunoglobulin M\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBIRDEM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLDH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLactate dehydrogenase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCentral Nervous System\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLaboratory information system\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCFR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCase fatality rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLMICs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLow and middle-income countries\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComplete blood count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNS1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNon-structural protein 1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eConfidence interval\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOdd’s ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCKD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eChronic kidney disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003epolymerase chain reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCLD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eChronic liver disease\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eROC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eReceiver operating characteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGCS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGlasgow Coma Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWHO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWorld Health Organization\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eG6-PD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGluose-6-phosphate dehydrogenase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eSupplementary information. \u0026nbsp; \u0026nbsp;This article has accompanying supplementary files.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval declaration\u003c/p\u003e\n\u003cp\u003eInstitutional Review Board Statement:The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Mahidol University (TMEC 25-008 and 26 March 2025) and of the Diabetic Association of Bangladesh (ERC/EC/25/40 and 13 February 2025).\u003c/p\u003e\n\u003cp\u003eInformed Consent Statement: Patient consent was waived as this study was retrospective observational study, accessing secondary medical data (medical records. There was no intervention to the human subjects. Any information leading to the identification of the subjects was not recorded and the confidentiality of their records was maintained.\u003c/p\u003e\n\u003cp\u003eConsent for publication: Not applicable.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials:\u0026nbsp;The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests:\u0026nbsp;The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding: This research was funded by Mahidol University, under the Masters of Clinical Tropical Medicine program.\u003c/p\u003e\n\u003cp\u003eCRediT Authors Contributions:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFariha Fairouz: Conceptualization, Methodology, Data curation, Formal analysis, Writing - original draft preparation;\u003c/p\u003e\n\u003cp\u003eWirongrong Chierakul: Conceptualization, Methodology, Investigation, Resources, Formal analysis, Funding acquisition, Validation, Supervision, Writing - review and editing;\u003c/p\u003e\n\u003cp\u003eChayasin Mansanguan: Conceptualization, Methodology, Formal analysis, Validation, Supervision, Writing - review and editing;\u003c/p\u003e\n\u003cp\u003eHisham Ahmed Imad: Conceptualization, Methodology, Formal analysis, Validation, Supervision, Writing - review and editing;\u003c/p\u003e\n\u003cp\u003eJanjira Thaipadungpanit:\u0026nbsp;Conceptualization, Methodology, Formal analysis, Validation, Supervision, Writing - review and editing;\u003c/p\u003e\n\u003cp\u003eJamal Uddin Ahmed: Conceptualization, Methodology, Investigation, Resources, Supervision, Writing - review and editing;\u003c/p\u003e\n\u003cp\u003ePrakaykaew Charunwatthana: Conceptualization, Methodology, Investigation, Resources, Formal analysis, Funding acquisition, Project administration, Validation, Visualization, Supervision, Writing - review and editing.\u003c/p\u003e\n\u003cp\u003eAll authors who deserve to be credited on the manuscript are indeed identified, that no authors are listed who do not deserve authorship credit, and that author contributions, where they are provided, are expressed accurately.\u0026nbsp;The authors have reviewed and edited the final manuscript and take full responsibility for the content of this publication.\u003c/p\u003e\n\u003cp\u003eAcknowledgements. The authors would like to sincerely acknowledge the IT department of BIRDEM General Hospital for facilitating data collection for the research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKayesh MEH, Khalil I, Kohara M, Tsukiyama-Kohara K. Increasing Dengue Burden and Severe Dengue Risk in Bangladesh: An Overview. Trop Med Infect Dis. 2023;8(1).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEgger JR, Coleman PG. Age and clinical dengue illness. Emerg Infect Dis. 2007;13(6):924\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGuzman MG, Gubler DJ, Izquierdo A, Martinez E, Halstead SB. Dengue infection. Nat Rev Dis Primers. 2016;2:16055.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMartina BE, Koraka P, Osterhaus AD. Dengue virus pathogenesis: an integrated view. 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J Infect Dis. 2022;226(11):1949\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTejo AM, Hamasaki DT, Menezes LM, Ho YL. Severe dengue in the intensive care unit. J Intensive Med. 2024;4(1):16\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGomez-Zambrano M, Torres-Hernandez D, Murillo-Ortiz MA, Hurtado IC, Davalos DM, Cantor E, et al. Different Clinical Severity and Outcomes in a Cohort of Patients With Dengue With Warning Signs in an Endemic Latin American City. Open Forum Infect Dis. 2025;12(4):ofaf227.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Dengue outcome, Risk factors, Bangladesh, Predictors of severity, Tropical diseases","lastPublishedDoi":"10.21203/rs.3.rs-7844350/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7844350/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWith an alarmingly high case fatality rate (CFR) of 0.56% in 2024, marking the consecutive year to report its devastating outbreak on record in 2023 with 1,705 fatalities, dengue fever presents a major public health challenge in Bangladesh, with seasonal outbreaks causing morbidity, mortality, and strain on the healthcare system. Understanding the factors influencing disease severity and outcomes is crucial for improving clinical management and reducing the disease burden. This retrospective observational study aimed to identify clinical patterns, risk factors, complications, and outcomes among adult severe dengue patients admitted to BIRDEM General Hospital, Dhaka, Bangladesh. Hospital records of admitted patients were analyzed to find the prevalence of severe dengue and explore the potential risk factors contributing to the severity of dengue outcomes. Key parameters included patient demographics, comorbidities, clinical manifestations, laboratory findings, and treatment outcomes. This retrospective study analyzed 330 adult dengue fever cases, identifying 26 (7.9%) as severe dengue. Severe dengue patients were significantly older (mean\u0026thinsp;~\u0026thinsp;59 years), and showed a higher occurrence in pre-existing diabetes (84.6%), hypertension (69.2%), and chronic kidney disease (26.9%). Alteration of consciousness was significantly associated with severity, enhancing the odds of progressing to severe dengue by 51 times. Laboratory findings included significantly lower mean hematocrit (32.86%), hemoglobin (11.02 mg/dl), elevated liver enzymes (mean ALT 467.79 U/L, AST 865.3 U/L, ALP 146.41 U/L), lower serum albumin (31.7 mg/dL), elevated BUN (61.68 mg/dL), creatinine (2.71 mg/dL), and LDH (3007.33 U/L). A logistic regression model demonstrated good predictive ability (AUC\u0026thinsp;=\u0026thinsp;0.8302), with alteration of consciousness and higher AST as independent risk factors of severe dengue. Based on the available data, despite high rates of complications (81% including plasma leakage, organ impairment, and concurrent co-infections), 16 (62%) were cured, and minimal mortality was reported (n\u0026thinsp;=\u0026thinsp;3). By identifying high-risk populations and predictors of severe outcomes, this research aims to improve patient care and reduce dengue-related mortality.\u003c/p\u003e","manuscriptTitle":"Outcomes of adult severe dengue in a tertiary care centre of Bangladesh: a cross-sectional retrospective observation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-31 15:30:45","doi":"10.21203/rs.3.rs-7844350/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d476e14e-8dd8-4fb6-84c3-f32afe7ea72e","owner":[],"postedDate":"October 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-09T07:40:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-31 15:30:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7844350","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7844350","identity":"rs-7844350","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}