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Predictive markers for the early prognosis of dengue severity: A systematic review and meta-analysis

Author

Listed:
  • Tran Quang Thach
  • Heba Gamal Eisa
  • AlMotsim Ben Hmeda
  • Hazem Faraj
  • Tieu Minh Thuan
  • Manal Mahmoud Abdelrahman
  • Mario Gerges Awadallah
  • Ha Xuan Nam
  • Michael Noeske
  • Jeza Muhamad Abdul Aziz
  • Nguyen Hai Nam
  • Mohamed El Nile
  • Shyam Prakash Dumre
  • Nguyen Tien Huy
  • Kenji Hirayama

Abstract

Background: Predictive markers represent a solution for the proactive management of severe dengue. Despite the low mortality rate resulting from severe cases, dengue requires constant examination and round-the-clock nursing care due to the unpredictable progression of complications, posing a burden on clinical triage and material resources. Accordingly, identifying markers that allow for predicting disease prognosis from the initial diagnosis is needed. Given the improved pathogenesis understanding, myriad candidates have been proposed to be associated with severe dengue progression. Thus, we aim to review the relationship between the available biomarkers and severe dengue. Methodology: We performed a systematic review and meta-analysis to compare the differences in host data collected within 72 hours of fever onset amongst the different disease severity levels. We searched nine bibliographic databases without restrictive criteria of language and publication date. We assessed risk of bias and graded robustness of evidence using NHLBI quality assessments and GRADE, respectively. This study protocol is registered in PROSPERO (CRD42018104495). Principal findings: Of 4000 records found, 40 studies for qualitative synthesis, 19 for meta-analysis. We identified 108 host and viral markers collected within 72 hours of fever onset from 6160 laboratory-confirmed dengue cases, including hematopoietic parameters, biochemical substances, clinical symptoms, immune mediators, viral particles, and host genes. Overall, inconsistent case classifications explained substantial heterogeneity, and meta-analyses lacked statistical power. Still, moderate-certainty evidence indicated significantly lower platelet counts (SMD -0.65, 95% CI -0.97 to -0.32) and higher AST levels (SMD 0.87, 95% CI 0.36 to 1.38) in severe cases when compared to non-severe dengue during this time window. Conclusion: The findings suggest that alterations of platelet count and AST level—in the first 72 hours of fever onset—are independent markers predicting the development of severe dengue. Author summary: The major concern in dengue fever is the abrupt occurrence of severe complications, for which only close monitoring of patients is the treatment scheme. Thus, the markers managing to predict the subsequent progression of complications—in the early stage of disease course—could alleviate the clinical management burden. Ideally, the predictors foretell the outcomes before the severe complications occur—usually on days 4–7 following fever onset. In this study, therefore, we reviewed the available markers collected during the first 3 days of fever onset. We found robust evidence of significantly lower platelet counts and higher AST levels in those who subsequently developed severe dengue than those who did not. In this regard, platelet count could serve as an independent warning sign rather than combining with hematocrit—as seen in the current classification—which remains unaltered during this time window. Also, abdominal pain and vomiting could predict the outcomes, but using these signs is arduous when their manifestations vary as per the patient without cutoffs. Hepatomegaly rate is substantially higher in severe dengue, but likely yields a high false-negative prediction rate. There is a need for larger studies to confirm the relatedness of hyaluronan in severe dengue.

Suggested Citation

  • Tran Quang Thach & Heba Gamal Eisa & AlMotsim Ben Hmeda & Hazem Faraj & Tieu Minh Thuan & Manal Mahmoud Abdelrahman & Mario Gerges Awadallah & Ha Xuan Nam & Michael Noeske & Jeza Muhamad Abdul Aziz & , 2021. "Predictive markers for the early prognosis of dengue severity: A systematic review and meta-analysis," PLOS Neglected Tropical Diseases, Public Library of Science, vol. 15(10), pages 1-25, October.
  • Handle: RePEc:plo:pntd00:0009808
    DOI: 10.1371/journal.pntd.0009808
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    References listed on IDEAS

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    1. Hope H Biswas & Oscar Ortega & Aubree Gordon & Katherine Standish & Angel Balmaseda & Guillermina Kuan & Eva Harris, 2012. "Early Clinical Features of Dengue Virus Infection in Nicaraguan Children: A Longitudinal Analysis," PLOS Neglected Tropical Diseases, Public Library of Science, vol. 6(3), pages 1-9, March.
    2. Phung Khanh Lam & Tran Van Ngoc & Truong Thi Thu Thuy & Nguyen Thi Hong Van & Tran Thi Nhu Thuy & Dong Thi Hoai Tam & Nguyen Minh Dung & Nguyen Thi Hanh Tien & Nguyen Tan Thanh Kieu & Cameron Simmons , 2017. "The value of daily platelet counts for predicting dengue shock syndrome: Results from a prospective observational study of 2301 Vietnamese children with dengue," PLOS Neglected Tropical Diseases, Public Library of Science, vol. 11(4), pages 1-20, April.
    3. Sangshin Park & Anon Srikiatkhachorn & Siripen Kalayanarooj & Louis Macareo & Sharone Green & Jennifer F Friedman & Alan L Rothman, 2018. "Use of structural equation models to predict dengue illness phenotype," PLOS Neglected Tropical Diseases, Public Library of Science, vol. 12(10), pages 1-14, October.
    4. Nguyen Tien Huy & Tran Van Giang & Dinh Ha Duy Thuy & Mihoko Kikuchi & Tran Tinh Hien & Javier Zamora & Kenji Hirayama, 2013. "Factors Associated with Dengue Shock Syndrome: A Systematic Review and Meta-Analysis," PLOS Neglected Tropical Diseases, Public Library of Science, vol. 7(9), pages 1-15, September.
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