Spectrum of Liver Injury in Dengue Fever: Cause or Effect of Severe Dengue?

The study aimed to determine if deranged liver function tests (LFTs) can predict severe dengue or mortality. It included 135 dengue patients, with a mean age of 30.9 ± 12.09 years. Among the patients, 82 (60.7%) were under 30 years of age. Nearly half of the patients (64, 47. 4%) had some degree of liver damage indicated by deranged LFTs, 27 (42.1%) had elevated alanine transaminase (ALT), 7 (10.9%) had increased bilirubin, and 30 (46.9%) had high values of alkaline phosphatase (ALP). However, only elevated ALP levels were positively correlated with mortality (Pearson's R = 0.282, p = <0.05). The mean bilirubin was 11.711 ± 8.602 umol/l, and the mean values of ALT and ALP were 107 ± 240 and 113.571 ± 59.91 IU/L, respectively, which were higher than the normal. The study findings suggested that hepatic derangement is a common occurrence in dengue patients, and increased ALP levels could be an indicator of a higher risk of mortality. These findings can help improve patient care by identifying the potential risk factors for mortality. Key Words: Dengue, Liver function tests, Alanine transaminase, Alkaline phosphatase.

Harness risk stratification of diabetic patients with dengue in a cohort study.

BACKGROUND: Identifying predictors of severe dengue (SD) is key for triage and management of patients as well as for advising travellers to countries where dengue is endemic. In this, meta-analyses have raised diabetes mellitus as a risk factor for SD and a prognostic factor for dengue-related mortality. The purpose of this study was to assess whether diabetic patients (DPs) are at increased risk for SD in comparison to non-diabetic patients (NDPs) in a setting of high prevalence of type 2 diabetes mellitus and increasing endemicity for dengue. METHODS: In a cohort study conducted during the 2019 dengue epidemic on Reunion Island, we estimated the risk ratios (RR) of DPs for SD (WHO 2009 definition), hospitalisation, intensive care unit (ICU) admission, critical care need or death in the ICU, and scales rating severity or multiple organ dysfunction syndrome (MODS), among confirmed cases of dengue (positive RT-PCR or NS1 antigen). RESULTS: In a Poisson regression model adjusted for age, gender and comorbidity, DPs were more likely to develop SD (adjusted RR: 1.46, 95%CI 1.10-1.95), to be hospitalised, admitted to the ICU, and need critical care or die in the ICU. Subgroup analyses identified female DPs, non-elderly DPs (< 65 years) and DPs with low Charlson score (< 3) to be at higher risk for SD, the two first subgroups trough more severe presentation (higher Simplified Acute Physiology Score-2 values; higher MODS scores, respectively). Male gender, age less than 65 years and mixed comorbidity were identified as prognostic factors for critical care need or death in the ICU, male and non-elderly DPs being more likely to develop MODS than their non-diabetic counterparts. CONCLUSIONS: Together, these data highlight the role of diabetes mellitus in the progression from dengue to SD through higher severity per se or the event of MODS.

A curious case of expanded dengue syndrome.

Dengue fever (DF) primarily presents with fever, headache, malaise, bleeding manifestations and haemoconcentration. World Health Organization (WHO) classifies DF according to levels of severity: (a) without warning signs; (b) with warning signs, such as abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, increasing haematocrit and thrombocytopenia; and (c) severe dengue with severe plasma leakage, severe bleeding or organ failure. Atypical clinical presentations of DF are defined as expanded dengue syndrome: this includes renal, cardiac, hepatic or cerebral damage. We report such a severe case where a young man developed acute kidney injury, acute fulminant liver failure and acute pancreatitis secondary to DF, but recovered.

Spontaneous Intracranial Hemorrhage and Acute Respiratory Distress Syndrome Associated with Dengue: A Case Report.

BACKGROUND: Dengue is a major health burden worldwide, notably in tropical and subtropical countries, with symptoms ranging from asymptomatic infection to severe hemorrhagic or shock syndrome. The clinical and biochemical profile of dengue has been shown in the literature to be expanding as more atypical signs have been added over the past few decades. Most dengue-related symptoms are typically mild to moderate and self-limited. However, intracranial hemorrhage and acute respiratory distress syndrome in severe dengue is an event that has been encountered uncommonly. CASE PRESENTATION: A 30-year-old female presented with complaints of fever, headache, cough, and altered sensorium. Later, she was diagnosed with severe dengue fever complicated by dengue hemorrhagic fever, which manifested as subarachnoid and subdural bleeding and acute respiratory distress syndrome. She was managed conservatively with a positive outcome. CONCLUSION: Atypical manifestation, though rare, should be kept in mind while dealing with severe dengue patients, as early detection based on anticipated risk factors and timely treatment have the potential to save lives.

Descriptive and comparative analysis of mucocutaneous manifestations in patients with dengue fever: A prospective study.

BACKGROUND: Dengue is an arbovirosis affecting nearly 4 billion people worldwide. Since 2018, dengue has been re-emerging in Reunion Island. The incidence of mucocutaneous manifestations varies according to the studies and is generally called 'rash'. OBJECTIVES: To assess the prevalence of different mucocutaneous symptoms and describe the characteristics of patients developing these symptoms and the clinical signs associated with severe dengue. METHODS: A prospective study was conducted in 2019 at the University Hospital of La Réunion, in patients presenting a positive PCR for dengue. Descriptive analyses were performed. All cases in the prospective study were examined by a dermatologist. RESULTS: A total of 163 cases were included. The prevalence of mucocutaneous signs was 80.4%. A pruritus was reported in 33.7% cases, an erythematous rash in 29.4% and a mouth involvement including lip, tongue, cheek, angular cheilitis, pharyngitis, mouth ulcer and gingivitis in 31.3%. Most of symptoms appeared in the first days, but some of them could disappear only after the 3rd week. Mucocutaneous signs were not associated with a severe dengue fever (p = 0.54), but ecchymotic purpura was (p = 0.037). In multivariate analysis, skin involvement was associated with flu-like syndrome (headache, pharyngitis, rachis pain) and patient required rehydration but not invasive reanimation. CONCLUSION: This work confirms the high prevalence of skin symptoms in dengue disease, but also their wide diversity. The mucocutaneous involvement of dengue fever appears to be accompanied by a pronounced flu-like syndrome in people without severity, but careful examination to identify ecchymotic purpura or sign of dehydration in the mucous membranes would better identify cases that may worsen.

The continuum of liver injury with severity of dengue fever: A retrospective observational study.

BACKGROUND: Dengue is a major international health concern prevalent in tropical and sub-tropical countries. There are a paucity of studies on the relationship of hepatic complications with inflammatory parameters in dengue infection. METHODS: Single-centre observational study was conducted at the tertiary care centre in North India. Patients (>12 years) diagnosed with dengue infection between August and November 2021 were enrolled in the study. The frequency of hepatic derangements and their associations with inflammatory severity was analysed. RESULTS: Based on the clinical symptoms, 170 patients were classified into three categories, namely, dengue fever, warning dengue and severe dengue. Higher incidence of liver dysfunction was observed in severe dengue patients with median values of aspartate aminotransferase (AST) (3051 U/L, p < 0.001), alanine aminotransferase (ALT) (1792 U/L, p = 0.009), alkaline phosphatase (172 U/L, p = 0.001), T.Bil (34.2 µmol/L, p < 0.001), albumin (30 g/L, <0.001), and gamma-glutamyl transferase (152 U/L, p < 0.001) along with inflammatory marker C-reactive protein (CRP) (43 mg/dL, p < 0.001) highly deranged, in comparison to patients with/without warning signs. Median levels of CRP were found to be positively and significantly correlated with the median levels of AST and ALT (p < 0.05, r = 0.99) in all three categories of dengue patients. Liver injury was noted in 107 (63%) of the cohort, and mixed type of liver injury involving both hepatocellular and cholestatic patterns was observed as the most common type of injury (n = 50, 29.4%). Liver injury correlated with the severity of dengue illness as about 85% of severe dengue patients had significant liver injury (p = 0.014). CONCLUSION: In dengue patients, the association of the liver injury with inflammatory severity suggests that the mechanism of liver injury may be related to inflammatory response apart from the hepatotropic nature of the virus.

Association of cardiovascular disease with severe dengue: A systematic review and meta-analysis.

BACKGROUND: Cardiovascular disease (CVD) and dengue are both significant global health concerns, and their intersection presents a growing clinical challenge. Emerging evidence suggests that individuals with pre-existing CVD may face an elevated risk of severe dengue outcomes. The present study aims to perform a systematic review to assess the relationship between CVD and the severity of dengue. METHODS: We conducted a literature search across multiple databases from inception to November 25, 2023. Primary studies reporting the number of dengue patients with CVD in severe dengue and non-severe dengue groups were included. Quality assessment was performed using the Newcastle-Ottawa Scale, and a meta-analysis was conducted using R software version 4.2 to determine the pooled Relative Risk (RR). The study protocol has been registered in PROSPERO. RESULTS: Based on data from 5 studies involving 274,576 dengue patients, our meta-analysis revealed a significant association between CVD and an increased risk of severe dengue, with a calculated RR of 2.71 (95  % CI: 1.03 to 7.10). However, substantial heterogeneity was observed among the included studies (I2 = 79  %). CONCLUSION: The current evidence suggests an association between CVD and severe dengue, emphasizing the importance of closely monitoring individuals with pre-existing cardiovascular disease and providing them with targeted interventions upon dengue diagnosis to mitigate the risk of severe outcomes.

Associations of obesity and dengue-associated mortality, acute liver failure and mechanical ventilation in children with dengue shock syndrome.

Dengue-associated complications, including dengue shock syndrome, severe respiratory distress, and pediatric acute liver failure (PALF), are associated with high mortality rates in patients with dengue. There is increasing prevalence of overweight and obesity among children worldwide. Obesity may activate inflammatory mediators, leading to increased capillary permeability and plasma leakage in patients with dengue. Several studies have shown a correlation between obesity and DSS, but did not include dengue fatality or PALF. Therefore, we hypothesized possible associations between obesity and critical dengue-associated clinical outcomes among PICU-admitted children with DSS, including dengue-related mortality, mechanical ventilation (MV) requirements, and dengue-associated PALF. The nutritional status of the participants was assessed using World Health Organization growth charts. A total of 858 participants with complete nutritional data were enrolled in this study. Obesity was significantly associated with risk of severe respiratory failure and MV support (odds ratio = 2.3, 95% CI: 1.31-4.06, P < .01); however, it was not associated with dengue-associated mortality or acute liver failure. Obese pediatric patients with DSS should be closely monitored for severe respiratory distress and the need for high-flow oxygenation support, particularly MV, soon after hospitalization.

Severity of Dengue Viral Infection Based on Clinical and Hematological Parameters among Pakistani Patients.

The global burden of dengue infections has increased dramatically. Early diagnosis of dengue infection is critical to proper medical management to avoid further complications in patients. This study was geared to assess the severity of dengue infections based on clinical and hematological examinations. A cross-sectional study was conducted among febrile patients with dengue infection in a teaching hospital in Pakistan. Blood samples were investigated for dengue-specific antibodies (IgM and IgG) and the nonstructural 1 antigen. The clinical findings of each subject were noted to assess the severity of the infection. Tests for hematological parameters were performed. Of 130 patients with confirmed dengue infection, 23 had severe and 107 had nonsevere dengue. Patients with severe dengue experienced mucosal bleeding (71.4%), fluid accumulation (57.1%), shock (35.7%), and gastrointestinal bleeding (28.6%). The most significant hematological findings among severe and nonsevere patients with dengue infection were thrombocytopenia, leukopenia, and a raised hematocrit level (P < 0.001). Patients with severe dengue infection showed marked thrombocytopenia, with a mean platelet count of 49.96 × 109 platelets/L. The clinical presentation of patients with dengue infection along with hematological markers are the most important clues for the diagnosis of, prognosis of, and therapy for dengue infection. Thrombocytopenia, leukopenia, and raised hematocrit levels were the most significant hematological parameters when assessing the severity of dengue infection.

Dengue Myocarditis: A Case Report and Major Review.

Dengue is a viral disease transmitted by the bite of a female arthropod, prevalent primarily in tropical and subtropical regions. Its manifestations include asymptomatic infections, dengue fever, and a severe form called hemorrhagic dengue or dengue shock syndrome. Atypical manifestations can also occur, called expanded dengue syndrome. We describe the case of a 43-year-old man with an unusual presentation of dengue, demonstrating a workup suggestive of myocardial and pericardial damage. Symptoms and markers indicative of cardiac compromise improved after five days on anti-inflammatory treatment. Dengue myocarditis is considered an uncommon complication of dengue, although its reported incidence is likely an underestimation. In general, most cases of dengue myocarditis are self-limited, with only a minority at risk of progressing to heart failure. In order to improve recognition and prevent progression, healthcare providers should maintain a high degree of suspicion regarding potential cardiac complications in patients with dengue.

Unique Immune Blood Markers Between Severe Dengue and Sepsis in Children.

BACKGROUND: Pediatric dengue and sepsis share clinical and pathophysiologic aspects. Multiple inflammatory and regulatory cytokines, decoy receptors and vascular permeability factors have been implicated in the pathogenesis of both diseases. The differential pattern and dynamic of these soluble factors, and the relationship with clinical severity between pediatric dengue and sepsis could offer new diagnosis and therapeutic strategies. METHODS: We evaluated the concentration levels of 11 soluble factors with proinflammatory, regulatory and vascular permeability involvement, in plasma from children with dengue or sepsis, both clinically ranging from mild to severe, in the early, late and convalescence phases of the disease. RESULTS: During early acute infection, children with sepsis exhibited specific higher concentration levels of IL-6, vascular endothelial growth factor (VEGF), and its soluble decoy receptor II (sVEGFR2) and lower concentration levels of IL-10 and the soluble tumor necrosis factor receptor 2 (sTNFR2), in comparison with children with severe dengue. In addition, the circulating amounts of soluble ST2, and VEGF/sVEGFR2 were widely associated with clinical and laboratory indicators of dengue severity, whereas secondary dengue virus infections were characterized by an enhanced cytokine response, relative to primary infections. In severe forms of dengue, or sepsis, the kinetics and the cytokines response during the late and convalescence phases of the disease also differentiate. CONCLUSIONS: Dengue virus infection and septic processes in children are characterized by cytokine responses of a specific magnitude, pattern and kinetics, which are implicated in the pathophysiology and clinical outcome of these diseases.

Obesity as a clinical predictor for severe manifestation of dengue: a systematic review and meta-analysis.

BACKGROUND: Severe dengue often leads to poor clinical outcomes and high mortality; as a result, it is of vital importance to find prognostic factors associated with the severe form of dengue. Obesity is known to deteriorate many infectious diseases due to impaired immune responses. Several studies have suggested that obese patients with dengue infection tend to have more severe manifestations with poorer prognosis. However, a firm conclusion could not be drawn due to the varied results of these studies. Here, we aimed to conduct a systematic review and meta-analysis to investigate the association between obesity and dengue severity. METHODS: A literature search for relevant studies was conducted in PubMed, Embase, Ovid Medline and Cochrane from inception to September 9, 2022. The two main keywords were "dengue" and "obesity". Mantel-Haenszel method and random effects model was used to analyze the pooled odds ratio with 95% confidence intervals. RESULTS: A total of 15 article involving a total of 6,508 patients were included in the meta-analysis. Included patients in most studies were hospitalized pediatric patients. Only one study included adulthood data. Three cohort studies, four case-control studies, and one cross-sectional studies found a significant association between obesity and dengue severity. In contrast, three cohort studies, three case-control studies, and one cross-sectional study reported no significant relationship between obesity and dengue severity. Our analysis results showed that patient with obesity is 50% (OR = 1.50; 95%CI: 1.15-1.97) more likely to develop severe manifestation of dengue. CONCLUSION: This meta-analysis revealed that overweight could be a clinical predictor for severe disease for pediatric patients with dengue infection.

Prevalence, Characteristics, and Outcomes Associated with Acute Kidney Injury among Adult Patients with Severe Dengue in Mainland China.

Acute kidney injury (AKI) can occur in adult patients with severe dengue (SD) and have serious clinical outcomes. This study aimed to determine the prevalence, characteristics, risk factors, and clinical outcomes of AKI in adult patients with SD; the correlation of dengue virus (DENV) serological and virological profiles with AKI; and the clinical features of patients with severe AKI who received renal replacement treatment (RRT). This multicenter study was conducted in Guangdong Province, China, between January 2013 and November 2019. A total of 242 patients were evaluated, of which 85 (35.1%) developed AKI and 32 (13.2%) developed severe AKI (stage 3). Patients with AKI had a higher fatality rate (22.4% versus 5.7%; P < 0.001) and longer length of hospital stay (median: 13 versus 9 days; P < 0.001). Independent risk factors for AKI were hypertension (odds ratio [OR]: 2.03; 95% CI: 1.10-3.76), use of nephrotoxic drugs (OR: 1.90; 95% CI: 1.00-3.60), respiratory distress (OR: 4.15; 95% CI: 1.787-9.632), high international normalized ratio (INR) levels (OR: 6.44; 95% CI: 1.89-21.95), and hematuria (OR: 2.12; 95% CI: 1.14-3.95). There was no significant association between DENV serological and virological profiles and the presence or absence of AKI. Among patients with severe AKI, those who received RRT had a longer length of hospital stay and similar fatality rate. Hence, adult patients with SD should be closely monitored for the development of AKI to enable timely and appropriate therapy.

Dengue hemorrhagic fever with bleeding and fluid overload in a patient with active lupus nephritis: a case report of diagnostic and therapeutic challenges.

BACKGROUND: Diagnosis and management of dengue hemorrhagic fever (DHF) can be challenging in the presence of confounding comorbidities. Important confounders are conditions that alter hematological parameters and intra/extra vascular fluid distribution. We report the case of a patient with active lupus nephritis, who developed DHF with subsequent bleeding and fluid overload. This is the first case report to highlight a unique set of diagnostic and therapeutic challenges in DHF in this context. CASE PRESENTATION: A seventeen-year-old girl with lupus nephritis class IV developed a renal flare of lupus and subsequently developed DHF with bleeding per vaginum. Due to acute kidney injury, she was managed with a restrictive fluid approach during the ascending limb with blood transfusion when required, and close monitoring for hemodynamic instability. During the descending limb, hourly input was transiently increased due to a rise in hematocrit. This precipitated nephrogenic pulmonary edema, which was managed with mechanical ventilation and continuous renal replacement therapy. CONCLUSIONS: This patient posed two diagnostic challenges: diagnosis of dengue in a patient with lupus-related bicytopenia, and diagnosis of dengue leakage in a patient with nephrotic syndrome-related ascites. There were three therapeutic difficulties: deciding the fluid quota for DHF in the presence of renal impairment, and balancing the risks and benefits of steroids and anticoagulation in lupus nephritis with dengue. As decisions in such instances are patient-specific, sharing of individual experiences will help guide management decisions.

Frequency of pleural effusion in dengue patients by severity, age and imaging modality: a systematic review and meta-analysis.

BACKGROUND: Identification of pleural effusion (PE) in dengue infection is an objective measure of plasma leakage and may predict disease progression. However, no studies have systematically assessed the frequency of PE in patients with dengue, and whether this differs across age and imaging modality. METHODS: We searched Pubmed, Embase Web of Science and Lilacs (period 1900-2021) for studies reporting on PE in dengue patients (hospitalized and outpatient). We defined PE as fluid in the thoracic cavity detected by any imaging test. The study was registered in PROSPERO (CRD42021228862). Complicated dengue was defined as hemorrhagic fever, dengue shock syndrome or severe dengue. RESULTS: The search identified 2,157 studies of which 85 studies were eligible for inclusion. The studies (n = 31 children, n = 10 adults, n = 44 mixed age) involved 12,800 patients (30% complicated dengue). The overall frequency of PE was 33% [95%CI: 29 to 37%] and the rate of PE increased significantly with disease severity (P = 0.001) such that in complicated vs. uncomplicated dengue the frequencies were 48% and 17% (P < 0.001). When assessing all studies, PE occurred significantly more often in children compared to adults (43% vs. 13%, P = 0.002) and lung ultrasound more frequently detected PE than conventional chest X-ray (P = 0.023). CONCLUSIONS: We found that 1/3 of dengue patients presented with PE and the frequency increased with severity and younger age. Importantly, lung ultrasound demonstrated the highest rate of detection. Our findings suggest that PE is a relatively common finding in dengue and that bedside imaging tools, such as lung ultrasound, potentially may enhance detection.

Hemophagocytic lymphohistiocytosis as a rare complication of dengue haemorrhagic fever: a case report.

BACKGROUND: Haemophagocytic lymphohistiocytosis (HLH) is an uncommon systemic inflammatory syndrome that can happen secondary to numerous conditions. It rarely occurs due to dengue infection causing significant mortality and morbidity even with appropriate treatment. The outcome is further poor if the diagnosis of HLH is delayed or left untreated. Therefore, a high degree of clinical suspicion is paramount in diagnosing HLH. CASE PRESENTATION: A 17-year-old Sinhalese boy was admitted to a tertiary care hospital in Sri Lanka with a 4-day history of fever, headache, nausea, vomiting, and diarrhea. He was hemodynamically stable, and the serological investigation confirmed a dengue infection. On the fifth day of fever, he entered the critical phase of dengue infection, confirmed by ultrasound evidence of plasma leaking. However, he had ongoing high fever spikes during the critical phase, and even after the critical phase was over, the fever spikes continued. Simultaneously, hepatosplenomegaly was noticed, and he showed persistent thrombocytopenia, neutropenia, and anemia despite the resolution of the critical phase. Further, the workup revealed a serum ferritin level of > 3000 ng/mL triglyceride level of 314 mg/dL, and the bone marrow biopsy revealed an increased haemophagocytic activity. Secondary HLH was diagnosed on the basis of criteria used in the HLH-2004 trial and successfully managed with intravenous dexamethasone 10 mg/body surface area/day for the first 2 weeks, followed by a tapering regimen over 8 weeks. CONCLUSION: This case emphasizes the need to consider HLH as a potential complication when persistent fever and cytopenias are present after recovering from dengue fever, particularly in patients with unusual clinical features like hepatosplenomegaly. Early recognition and prompt treatment with appropriate immunosuppressive therapy, such as intravenous dexamethasone, can lead to a successful response and good prognosis.

Spontaneous splenic rupture during dengue fever.

Dengue fever is one of the most frequent arboviral diseases in the world. Dengue is known to cause myocarditis, hepatitis, and neurological illustrations but one of the established presentations is leakage of plasma resulting in circulatory failure. Spontaneous rupture of the spleen is one of the most infrequent but known outcome of dengue fever which has been reported from time to time in literature. We present, here, the case of a 50-year-old patient who developed this condition during dengue fever and was managed in our department successfully. This complication must be kept in mind while treating any case of dengue fever so that it can be avoided or if not then treated timely.

Clinical and Laboratory Characteristics of Hemophagocytic Lymphohistiocytosis in Children With Severe Dengue During the 2019-2020 Outbreak in Southern Colombia.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled activation of inflammatory cells and an exaggerated release of cytokines. It can be triggered by different factors, including viruses, such as dengue. The objective of this study was to characterize the clinical and laboratory profiles of children with severe dengue and HLH, and to identify the risk factors for this clinical complication. METHODS: An analytical study was conducted in children with severe dengue who were treated in an intensive care unit between January 2019 and March 2020. Clinical and laboratory factors were compared between patients with and without HLH. RESULTS: HLH represented 13.4% (15/112) of children with severe dengue. Patients with HLH had a long-lasting fever (10.1 vs. 5.8 days; P = 0.012), low hemoglobin levels (7.6 vs. 10.8 g/dL; P = 0.000) and high aspartate aminotransferase values (4443 vs. 1061 U/L; P = 0.002), alanine transaminase (1433 vs. 487 U/L; P = 0.004), partial thromboplastin time (80.6 vs. 51.8 seconds; P = 0.010), prothrombin time (23.5 vs. 19.6 seconds; P = 0.024), triglycerides (333.7 vs. 223.2 mg/dL; P = 0.005), lactate dehydrogenase (4209 vs. 1947 U/L; P = 0.006), soluble CD25 (3488 vs. 1026 pg/mL; P = 0.014), and presented with higher frequency of myocarditis (66.7% vs. 38.3%; P = 0.048), hepatitis (5.3% vs. 1.3%; P = 0.014), bacterial coinfection (73.3% vs. 26.7%; P = 0.010) and fatal outcome (26% vs. 5%; P = 0.037). CONCLUSIONS: HLH is a serious life-threatening clinical complication of dengue virus infection that must be considered, particularly during outbreaks.

Demographic characteristics, clinical symptoms, biochemical markers and probability of occurrence of severe dengue: A multicenter hospital-based study in Bangladesh.

Establishing reliable early warning models for severe dengue cases is a high priority to facilitate triage in dengue-endemic areas and optimal use of limited resources. However, few studies have identified the complex interactive relationship between potential risk factors and severe dengue. This research aimed to assess the potential risk factors and detect their high-order combinative effects on severe dengue. A structured questionnaire was used to collect detailed dengue outbreak data from eight representative hospitals in Dhaka, Bangladesh, in 2019. Logistic regression and machine learning models were used to examine the complex effects of demographic characteristics, clinical symptoms, and biochemical markers on severe dengue. A total of 1,090 dengue cases (158 severe and 932 non-severe) were included in this study. Dyspnoea (Odds Ratio [OR] = 2.87, 95% Confidence Interval [CI]: 1.72 to 4.77), plasma leakage (OR = 3.61, 95% CI: 2.12 to 6.15), and hemorrhage (OR = 2.33, 95% CI: 1.46 to 3.73) were positively and significantly associated with the occurrence of severe dengue. Classification and regression tree models showed that the probability of occurrence of severe dengue cases ranged from 7% (age >12.5 years without plasma leakage) to 92.9% (age ≤12.5 years with dyspnoea and plasma leakage). The random forest model indicated that age was the most important factor in predicting severe dengue, followed by education, plasma leakage, platelet, and dyspnoea. The research provides new evidence to identify key risk factors contributing to severe dengue cases, which could be beneficial to clinical doctors to identify and predict the severity of dengue early.