A systematic review of ultrasound to predict severe disease in patients with dengue and other viral infections associated with hemorrhagic fevers
8 affiliations
- 1Division of Internal Medicine – Pediatrics, David Geffen School of Medicine at the University of California (Los Angeles), Los Angeles, United States of America
- 2Department of Emergency Medicine, Hospital das Clínicas da Faculdade de Medicina de Marília, São Paulo, Brazil
- 3Emergency and Trauma Department, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
- 4Ministry of Health, Putrajaya, Malaysia
- 5Lighthouse Clinic Trust, Lilongwe, Malawi
- 6Institute of Infectious Diseases and Tropical Medicine, LMU University Hospital, Munich, Germany
- 7Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
- 8Hypertension Center, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
Abstract
Background: Viral infections associated with hemorrhagic fevers (VaHFs) cause millions of cases each year across a broad geography with severity ranging from asymptomatic cases to clinical disease with a high case fatality rate. Commonalities in pathophysiology across VaHFs include vascular damage and plasma leakage with the possibility of hemorrhage, organ failure, shock, and death. These changes are seen on autopsy, and evidence of plasma leakage can be readily detected on ultrasound. Methods: We conducted a systematic review to assess ultrasound findings in VaHFs and their ability to predict severe disease (PROSPERO CRD42024620862). PubMed was searched through May 2025. Any articles presenting original, patient-level findings on ultrasound in VaHFs with serologic and/or molecular confirmation were included. Case series and duplicative datasets were excluded. A QUADAS-2 tool was used to assess bias. Study level characteristics and patient-level data on the ultrasound findings were extracted. The crude proportions of ultrasound findings were reported, and weighted meta-analysis using a random-effects model was performed and displayed in forest plots when the data allowed. Sensitivity, specificity, and positive/negative likelihood ratios for severe disease were calculated and visualized using a random effects model in SROC plots when the data allowed. Results: In total, 457 unique publications were screened for inclusion, and 56 publications comprising 6979 participants were included in the review, including 44 publications (6189 participants) on dengue, six (494 participants) on Crimean-Congo hemorrhagic fever, three (134 participants) on hantavirus disease, two (116 participants) on yellow fever, and one (46 participants) on Lassa fever. Participants were most often recruited while acutely sick during periods of high transmission at tertiary care centers. Ultrasound findings included gallbladder wall thickening, ascites, pleural effusions and abnormal lung ultrasound, pericardial effusions, abdominal lymphadenopathy, splenomegaly, abnormal pancreatic ultrasound, and hyperechoic kidneys or liver. Pericardial effusions and several other findings were associated with severe disease. Conclusions: Common pathophysiology leading to plasma leakage results in sonographic signs across viral infections associated with hemorrhagic fevers, and some findings can help predict severe disease. Important limitations included reliance on a single database and possibility of missing manuscripts from local journals, the small number of publications on non-dengue VaHFs, patient recruitment overwhelmingly from the in-hospital setting at tertiary referral centers during high-transmission periods, high degree of heterogeneity, and bias in the timing domain among the studies on dengue. We first propose ultrasound findings be incorporated into new definitions of severity for VaHFs and then introduce an Ultrasound-based assessment of Plasma leakage Severity (UPS) as a hypothesis generating framework to help guide future, prospective research. We discuss some virus and organ-specific considerations and conclude with detailed considerations for future research. Author summary: Viral infections associated with hemorrhagic fevers (VaHFs) may lead to vascular damage and plasma leakage with the possibility of hemorrhage, organ failure, shock, and death. Plasma leakage can be readily detected on ultrasound, and in this review, the authors assess the frequency of gallbladder wall thickening, ascites, pleural effusions and abnormal lung ultrasound, pericardial effusions, abdominal lymphadenopathy, splenomegaly, abnormal pancreatic ultrasound, and hyperechoic kidneys or liver in VaHFs, as well as the ability of these findings to predict severe disease. The review was dominated by studies on dengue, and there was great heterogeneity in the frequency of ultrasound findings in part related to variability in the era the study was completed, the age of participants, and the location of the original study. Several findings were associated with severe disease, and the authors raise many important considerations for future research. The authors recommend ultrasound findings be incorporated into definitions of severity for VaHFs and then propose an ultrasound-based grading scale for plasma leakage severity (UPS) as a hypothesis generating framework to help spark future research.
Related
- Seroprevalence of viral hemorrhagic fevers and arboviral infections among febrile patients in Forest Guinea
- Associated Factors of Hemorrhagic Transformation in Patients Undergoing Anterior Circulation Thrombectomy: Data from a Comprehensive Stroke Center in Vietnam
- Burden and associated factors of urinary tract infections among pregnant women in Ghana: a systematic review and meta-analysis
- Screening for rheumatoid arthritis-associated interstitial lung disease using lung ultrasound: a systematic review and quality appraisal of recent studies
- Bloodstream Infections in Patients with Malignancy: Microbiological Epidemiology, Antimicrobial Resistance, and Factors Associated with Mortality in a Nine-Year Single-Center Retrospective Cohort
BibTeX
@article{hodson2026systematic,
title = {{A systematic review of ultrasound to predict severe disease in patients with dengue and other viral infections associated with hemorrhagic fevers}},
author = {Daniel Z. Hodson and Renato A. Tambelli and Mahathar A. Wahab and Claudia Wallrauch and Hans-Michael Steffen and Benno Kreuels and Sabine Bélard and Tom Heller},
journal = {PLOS Neglected Tropical Diseases},
year = {2026},
month = sep,
doi = {10.1371/journal.pntd.0014609},
url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014609},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A systematic review of ultrasound to predict severe disease in patients with dengue and other viral infections associated with hemorrhagic fevers
AU - Daniel Z. Hodson
AU - Renato A. Tambelli
AU - Mahathar A. Wahab
AU - Claudia Wallrauch
AU - Hans-Michael Steffen
AU - Benno Kreuels
AU - Sabine Bélard
AU - Tom Heller
PY - 2026
DA - 2026/09/17
JO - PLOS Neglected Tropical Diseases
DO - 10.1371/journal.pntd.0014609
UR - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014609
AB - Background: Viral infections associated with hemorrhagic fevers (VaHFs) cause millions of cases each year across a broad geography with severity ranging from asymptomatic cases to clinical disease with a high case fatality rate. Commonalities in pathophysiology across VaHFs include vascular damage and plasma leakage with the possibility of hemorrhage, organ failure, shock, and death. These changes are seen on autopsy, and evidence of plasma leakage can be readily detected on ultrasound. Methods: We conducted a systematic review to assess ultrasound findings in VaHFs and their ability to predict severe disease (PROSPERO CRD42024620862). PubMed was searched through May 2025. Any articles presenting original, patient-level findings on ultrasound in VaHFs with serologic and/or molecular confirmation were included. Case series and duplicative datasets were excluded. A QUADAS-2 tool was used to assess bias. Study level characteristics and patient-level data on the ultrasound findings were extracted. The crude proportions of ultrasound findings were reported, and weighted meta-analysis using a random-effects model was performed and displayed in forest plots when the data allowed. Sensitivity, specificity, and positive/negative likelihood ratios for severe disease were calculated and visualized using a random effects model in SROC plots when the data allowed. Results: In total, 457 unique publications were screened for inclusion, and 56 publications comprising 6979 participants were included in the review, including 44 publications (6189 participants) on dengue, six (494 participants) on Crimean-Congo hemorrhagic fever, three (134 participants) on hantavirus disease, two (116 participants) on yellow fever, and one (46 participants) on Lassa fever. Participants were most often recruited while acutely sick during periods of high transmission at tertiary care centers. Ultrasound findings included gallbladder wall thickening, ascites, pleural effusions and abnormal lung ultrasound, pericardial effusions, abdominal lymphadenopathy, splenomegaly, abnormal pancreatic ultrasound, and hyperechoic kidneys or liver. Pericardial effusions and several other findings were associated with severe disease. Conclusions: Common pathophysiology leading to plasma leakage results in sonographic signs across viral infections associated with hemorrhagic fevers, and some findings can help predict severe disease. Important limitations included reliance on a single database and possibility of missing manuscripts from local journals, the small number of publications on non-dengue VaHFs, patient recruitment overwhelmingly from the in-hospital setting at tertiary referral centers during high-transmission periods, high degree of heterogeneity, and bias in the timing domain among the studies on dengue. We first propose ultrasound findings be incorporated into new definitions of severity for VaHFs and then introduce an Ultrasound-based assessment of Plasma leakage Severity (UPS) as a hypothesis generating framework to help guide future, prospective research. We discuss some virus and organ-specific considerations and conclude with detailed considerations for future research. Author summary: Viral infections associated with hemorrhagic fevers (VaHFs) may lead to vascular damage and plasma leakage with the possibility of hemorrhage, organ failure, shock, and death. Plasma leakage can be readily detected on ultrasound, and in this review, the authors assess the frequency of gallbladder wall thickening, ascites, pleural effusions and abnormal lung ultrasound, pericardial effusions, abdominal lymphadenopathy, splenomegaly, abnormal pancreatic ultrasound, and hyperechoic kidneys or liver in VaHFs, as well as the ability of these findings to predict severe disease. The review was dominated by studies on dengue, and there was great heterogeneity in the frequency of ultrasound findings in part related to variability in the era the study was completed, the age of participants, and the location of the original study. Several findings were associated with severe disease, and the authors raise many important considerations for future research. The authors recommend ultrasound findings be incorporated into definitions of severity for VaHFs and then propose an ultrasound-based grading scale for plasma leakage severity (UPS) as a hypothesis generating framework to help spark future research.
SN - 1935-2735
ER -