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.

Admission ultrasonography as a predictive tool for thrombocytopenia and disease severity in dengue infection.

BACKGROUND: Ultrasound (US) is an investigation available in many acute care settings. Thrombocytopenia is a well-described complication of dengue infection and has been shown to correlate with disease severity. The purpose of this study was to assess the utility of admission ultrasonography in predicting thrombocytopenia and disease severity in patients infected with dengue virus. METHODS: Data were collected prospectively on 176 patients (male, n=86; female, n=90) admitted to the Nawaloka Hospital, Sri Lanka with dengue infection between December 2016 and August 2018. All patients had an US scan on admission and disease severity was determined using the World Health Organization 2009 classification. RESULTS: There were 106 (60.2%) cases of dengue with/without warning signs and 70 (39.8%) cases of severe dengue. Patients with an abnormal US on admission were more likely to have severe dengue. Gallbladder wall thickening was the most common US abnormality. Abnormal US findings significantly correlated with more pronounced thrombocytopenia from day 2 of admission. CONCLUSIONS: An abnormal US scan on admission can aid in identification of patients at risk of developing severe dengue and can be used as a novel clinical tool to identify patients at risk of severe thrombocytopenia.

Rational use of ultrasonography with triaging of patients to detect dengue plasma leakage in resource limited settings: a prospective cohort study.

OBJECTIVES: To compare the traditional haematocrit-based criteria (>20% rise above baseline) with ultrasonography for diagnosing plasma leakage in dengue fever and to identify clinical indicators for triaging patients in resource-limited settings when the demand for ultrasonography is high. METHODS: The Colombo Dengue Study is a prospective observational cohort study recruiting dengue patients in the first three days of dengue fever, before plasma leakage. Serial haematocrit assessments and ultrasonography were performed in patients recruited from October 2017 to February 2020. Clinical signs/symptoms and laboratory investigation results independently associated with ultrasound detected plasma leakage were identified with a derivation cohort and confirmed in a validation cohort. RESULTS: 129 of 426 patients had ultrasonography-confirmed plasma leakage while 146 had a haematocrit rise >20%. Those positive on ultrasonography were also likely to fulfil the haematocrit-based criteria (OR: 4.42, 95% CI: 2.85-6.86), but the two groups did not overlap fully. In the derivation cohort (n = 317), platelet count <97 000/µl, AST/ALT > 51 IU/l and having abdominal pain in the first three days of fever were independent predictors of ultrasound-detected plasma leakage. In the validation cohort (n = 109), the combination of low platelet count and high aminotransferase level had better predictive capacity in terms of sensitivity and specificity. CONCLUSION: Dengue patients should be monitored with both serial haematocrit and ultrasonography whenever possible and plasma leakage should be diagnosed by either one of these criteria. If accessibility to scans is limited, platelet count, serum transaminase levels and presence of abdominal pain are useful to triage patients.

Ultrasound findings of plasma leakage as imaging adjunct in clinical management of dengue fever without warning signs.

INTRODUCTION: Plasma leakage is a major cause of morbidity and mortality in dengue fever. Few studies have shown the sensitivity of thoracoabdominal ultrasound in detecting plasma leakage in severe dengue, however its sensitivity in the early presentation of dengue fever without warning signs remains unknown. This study is aimed to determine the role of serial ultrasound in order to detect plasma leakage in dengue fever without warning signs. METHODS: This prospective cohort study was conducted at Hospital Universiti Sains Malaysia (USM) from 1st October 2016 to 30th November 2017. Serial bedside ultrasound procedures were performed for 83 patients who were diagnosed as having dengue fever without warning signs and were initially treated as outpatients. Ultrasonography evidence of plasma leakage either pleural effusion, thickened gallbladder wall, ascites or pericardial effusion were compared with clinical findings and laboratory parameters for plasma leakage. RESULTS: Of the 83 dengue patients, eventually 72.3% had dengue fever with warning signs and 6.0% had severe dengue fever. There were 38 patients who had subclinical plasma leakage at initial presentation, 84.2% and 7.9% of them then progressed to dengue fever with warning signs and severe dengue respectively. There was a minimal agreement between serial bedside ultrasound and haematocrit level in the detection of plasma leakage (observed kappa 0.135). CONCLUSIONS: Serial bedside ultrasound is an adjunct procedure to physical examination and may detect plasma leakage earlier compared to haemoconcentration. The early usage of serial ultrasound is of paramount importance in detecting dengue patients who are at risk of progressing to severe dengue.

Predictive and diagnostic test accuracy of ultrasonography in differentiating severe dengue from nonsevere dengue.

Diagnosing severe dengue from those who do not develop complication is important to prevent death. The objective of this systematic review was to evaluate the diagnostic test accuracy of ultrasonography in differentiating severe dengue from nonsevere dengue; and to assess if ultrasonography/ultrasound can be used as a predictive (screening) and diagnostic tool in the course of dengue infection. An electronic search was conducted in different databases via OvidSP platform. The included studies were cohort studies between 1995 and 2016 wherein cases were confirmed by dengue blood test. Severity of dengue was assessed and compared using standard WHO references. The methodological quality of the paper was assessed by two independent reviewers by using QUADAS-2 tool. In total 12 studies were included in this review after suitable screening. Overall, the studies included had a low and unclear risk of bias. Seven out of nine studies that compared severe dengue and nonsevere dengue, performed an ultrasonography on gallbladder (wall thickness cutoff-3 mm) with a sensitivity of 24.2-100% and a specificity of 13.2-98.7%. Other parameters such as splenic subcapsular fluid collection, pericardial fluid and hepatic subcapsular fluid collection had a specificity of >90%, though the sensitivity was poor. There were insufficient evidence that ultrasonography is able to differentiate severe dengue from nonsevere dengue accurately. The predictive and diagnostic value of ultrasonography could not be concluded due to insufficient reporting on the temporality of the ultrasonography performed with regard to the diagnosis. However, it might serve as an adjunct investigation to support the clinical diagnosis.

Ultrasonographic pattern of plasma leak in dengue haemorrhagic fever.

OBJECTIVE: To note ultrasonographic findings used for diagnosing plasma leakage in dengue haemorrhagic fever patients. METHODS: The observational retrospective study was conducted at the Holy Family Hospital, Rawalpindi and comprised records of patients with confirmed dengue infection who were screened for dengue haemorrhagic fever according to Dengue Expert Advisory Group criteria from July 1 to December 31, 2013. Each patient underwent ultrasonography for the detection of ascites, gall bladder wall thickness, pleural and/or pericardial effusion along with their quantification and localisation. RESULTS: Of the 240 patients, 166(69.2%) were men. The overall mean age was 28.9±12.4 years. Of the total, 215(89.5%) had ultrasonographic abnormalities, suggestive of plasma leakage. Quantification and localisation wise, mild abdominal ascites 68(47.2%), right pleural effusion 82(74.5%) and mild pleural effusion 98(89%) were commonly noted. None had pericardial effusion. CONCLUSIONS: Mild ascites and mild right pleural effusion were the commonest pattern of ultrasonographic leak in dengue haemorrhagic fever patients.

Is Ultrasound a Useful Tool to Predict Severe Dengue Infection?

OBJECTIVES: To study the role of ultrasound in children with dengue fever and determine its role in predicting the severity of the disease. METHODS: This was a retrospective hospital based study conducted from 1(st) August 2012 to January 31(st) 2015 at a tertiary care hospital in Puducherry. RESULTS: Two hundred and fifty four children were admitted with dengue fever and among them non-severe dengue and severe dengue were seen in 62.6 % and 37.4 % respectively. Mean age of presentation was 7.0 (3.3) years. M: F ratio was 1.2:1 Ultrasound was performed on all children with dengue fever during the critical period of illness as an early sign of plasma leakage and at the time of discharge. The diagnosis was confirmed by NS1 antigen and dengue serology. Ultrasonography showed positive findings in 156 cases (61.4 %) during the critical period of illness. Ultrasound findings were analyzed using logistic regression among severe and non-severe dengue and P value of <0.05 was taken as significant. The common ultrasound findings that were significantly associated with severe dengue infection on univariate analysis were gall bladder wall thickening, ascites, pleural effusion, pericardial effusion, pericholecystic fluid, hepatomegaly, splenomegaly and mesenteric adenopathy. On multivariate analysis, gall bladder thickening and hepatomegaly were significantly associated with severe dengue infection. Gall bladder wall thickening (GBWT) with honeycombing pattern was the most specific finding in severe dengue infection in the study and significantly associated with severe thrombocytopenia (Platelet count <50,000/mm(3)). The clinical improvement coincided with resolving of the ultrasound findings at the time of discharge. CONCLUSIONS: Ultrasound can be used as an early predictor as well as an important prognostic sign for severe dengue infection especially during an epidemic.

Serum angiopoietin-2 and soluble VEGF receptor 2 are surrogate markers for plasma leakage in patients with acute dengue virus infection.

BACKGROUND: Endothelial cell dysfunction is believed to play an important role in the pathogenesis of plasma leakage in patients with acute dengue virus (DENV) infection. Several factors, produced by activated endothelial cells, have been associated with plasma leakage or severe disease in patients with infectious diseases. OBJECTIVES: The aim of this study was to investigate which of these markers could serve as a surrogate marker for the occurrence of plasma leakage in patients with acute DENV infection. STUDY DESIGN: A case-control study was performed in patients with acute DENV infection in Santos, Brazil. Plasma leakage was detected with X-ray and/or ultrasound examination at admission. Serum levels of soluble endoglin, endothelin-1, angiopoietin-2, VEGF, soluble VEGFR-2, MMP-2, MMP-9, TIMP-1 and TIMP-2 were determined using commercially available ELISAs. RESULTS: Increased levels of angiopoietin-2, endothelin-1 and MMP-2 and decreased levels of soluble VEGFR-2 were significantly associated with the occurrence of plasma leakage. An unsupervised cluster analysis confirmed that angiopoietin-2 and soluble VEGFR-2 were strongly associated with clinical apparent vascular leakage. CONCLUSION: Angiopoietin-2 and soluble VEGFR-2 can serve as surrogate markers for the occurrence of plasma leakage in patients with acute DENV infection.

Left ventricular myocardial performance in patients with dengue hemorrhagic fever and thrombocytopenia as assessed by two-dimensional speckle tracking echocardiography.

OBJECTIVES: We obtained longitudinal, radial and circumferential strains in patients with dengue hemorrhagic fever (DhF) and thrombocytopenia using two-dimensional (2D) speckle tracking echocardiography to analyze left ventricular (LV) myocardial performance. METHODS: In this prospective study, 2D echocardiographic images of the left ventricle in the four-, three- and two-chamber views and parasternal short-axis views at the basal, mid and apical levels were obtained in 40 subjects: 20 patients (23 ± 8 years, 12 male) with DhF and thrombocytopenia and 20 healthy controls (23 ± 5 years, 11 male). Of the 20 patients, imaging was performed again in 19 at discharge after a hospital stay of 8 ± 1 days. Longitudinal, circumferential and radial strains were quantified and compared in an 18-segment model using a novel speckle tracking system. RESULTS: Left ventricular global ejection fraction was reduced in patients with DhF at presentation as compared with controls (51.25 ± 0.96% vs. 59.32 ± 1.26%; p = 0.032). Peak longitudinal strain in patients with DhF was significantly attenuated in the subendocardial region compared with normal controls (p < 0.001). A significant increase in circumferential strain for patients with DhF was evident only in the subepicardial region (p = 0.009). Patients with DhF showed significantly higher radial strain than controls (p < 0.001). On multivariate analysis, subendocardial longitudinal strain independently predicted the duration of hospital stay in patients with DhF. CONCLUSION: Assessment of speckle tracking echocardiography-derived LV mechanics helps in understanding myocardial mechanics in patients with DhF and thrombocytopenia. Identification of reduced LV longitudinal strain helps in understanding the mechanism of reduced LV myocardial performance seen in patients with DhF.

Dengue hemorrhagic fever in an adult traveler returning to Japan.

We report the case of a Japanese traveler who developed dengue hemorrhagic fever (DHF) with a probable secondary infection with dengue virus type 2 (DENV-2). DHF usually occurs in children, and rarely in adult travelers. Proper and timely interventions can markedly reduce the mortality rate of DHF patients. The expansion of endemic areas and increased frequency of travel to these areas may suggest increased incidence of DHF in non-endemic areas in the near future. Early recognition of reinfection with dengue virus and warning signs of circulatory failure are crucial to prevent a severe shock state.

Cardiac function in Vietnamese patients with different dengue severity grades.

OBJECTIVE: Dengue continues to cause significant global morbidity and mortality. Severe disease is characterized by cardiovascular compromise from capillary leakage. Cardiac involvement in dengue has also been reported but has not been adequately studied. SETTING: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. SUBJECTS AND DESIGN: Seventy-nine patients aged 8-6 yrs with different dengue severity grades were studied using echocardiography including tissue Doppler imaging. The patients were split into severity grades: dengue, dengue with warning signs, and severe dengue. Changes in cardiac functional parameters and hemodynamic indices were monitored over the hospital stay. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Patients with severe dengue had worse cardiac function compared with dengue in the form of left ventricular systolic dysfunction with increased left myocardial performance index (0.58 [0.26-0.80] vs. 0.38 [0.22-0.70], p = .006). Septal myocardial systolic velocities were reduced (6.4 [4.8-10] vs. 8.1 [6-13] cm/s, p = .01) as well as right ventricular systolic (11.4 [7.5-17] vs. 13.5 [10-17] cm/s, p = .016) and diastolic velocities (13 [8-23] vs. 17 [12-25] cm/s, p = .0026). In the severe group, these parameters improved from hospital admission to discharge; septal myocardial systolic velocities to 8.8 (7-11) cm/s (p = .002), right ventricular myocardial systolic velocities to 15.0 (11.8-23) cm/s, (p = .003), and diastolic velocity to 21 (11-25) cm/s (p = .002). Patients with cardiac impairment were more likely to have significant pleural effusions. CONCLUSIONS: Patients with severe dengue have evidence of systolic and diastolic cardiac impairment with septal and right ventricular wall being predominantly affected.

Clinical, laboratory and radiological parameters in children with dengue fever and predictive factors for dengue shock syndrome.

This article is a prospective study of the clinical, laboratory and radiological picture of children satisfying the case definition criteria of dengue by WHO admitted at Sri Ramachandra Medical College and Research Institute, a suburban tertiary referral centre, to determine the predictive factors for dengue shock syndrome (DSS). Data were analyzed by Chi-squared test and Student's t-test for significance after dividing the patients into two groups, those with and those without DSS for the same. Bleeding manifestations, presence of effusion on USG/X-ray, haematocrit >35%, WBC <4000/cumm, Na < or =130 meq/l, bicarbonate level of <18 mmol/l, deranged coagulation profile and serum glutamic pyruvic transaminase (SGPT) > or =40 IU were predictive of DSS.

Chest radiographic presentation in patients with dengue hemorrhagic Fever.

There has been no previously reported case series study regarding chest radiographic (CXR) presentations in dengue hemorrhagic fever (DHF) patients. We retrospectively studied 363 DHF patients from June to December 2002 in southern Taiwan, and a total of 468 CXRs were obtained and reviewed. More than 50% of these showed abnormalities after the 3rd day, with infiltration only and small pleural effusion as the major findings. Progressive changes during the first week and improvements during the second week were observed in these abnormal CXRs. The CXR presentation was also significantly correlated with laboratory findings (white blood cell count, platelet levels, activated partial thromboplastin time, and alanine aminotransferase and albumin levels), as well as the clinical course (renal insufficiency, liver function impairment, upper gastrointestinal bleeding, combination bacterial infection, and duration of admission) and outcome (mortality). The CXR may therefore be a modality for evaluating the clinical course of DHF and should be made during first week after the onset of illness.