Development of a Prognostic Prediction Model to Determine Severe Dengue in Children

Original Article
First Online:
Received:
Accepted:
  • 58 Downloads

Abstract

Objective

To develop a prognostic prediction model using the seven warning signs highlighted by WHO revised Dengue fever classification 2009 to determine severe dengue in children.

Methods

In this prospective analytical study conducted in a tertiary care centre, consecutive sampling of all children aged 1mo to 12y admitted with serologically confirmed Dengue was done from May 2015 through August 2016. After excluding 27 patients with co-infections and co-morbidities, 359 patients were followed up daily to assess clinical and laboratory progression till discharge/ death. Independent predictors were abdominal pain or tenderness, persistent vomiting, lethargy, mucosal bleed, clinical fluid accumulation, hepatomegaly >2 cm and rising hematocrit concurrent with platelet count <100 × 109/L. Outcome measure was severe dengue defined as per WHO guidelines 2009.

Results

Among 359 children, 93 progressed to severe dengue. In univariate analysis, significant predictors were clinical fluid accumulation (OR 4.773, p = 0.000, 95%CI 2.511–9.075), persistent vomiting (OR 1.944, p = 0.010, 95%CI 1.170–3.225), mucosal bleed (OR 2.045, p = 0.019, 95%CI 1.127–3.711) and hematocrit ≥0.40 concurrent with platelet count <100 × 109/L (OR 2.985, p = 0.000, 95%CI 1.783–4.997). The final multivariable model included clinical fluid accumulation (aOR 3.717, p = 0.000, 95%CI 1.901–7.269), hematocrit ≥0.40 concurrent with platelet count <100 × 109/L (aOR 2.252, p = 0.004, 95%CI 1.302–3.894) and persistent vomiting (p = 0.056) as predictors of severe dengue.

Conclusions

Among seven WHO warning signs, predictors of severe dengue as suggested by the present multivariable prediction model include clinical fluid accumulation, persistent vomiting and hematocrit ≥0.40 concurrent with platelet count <100 × 109/L.

Keywords

Dengue fever Pediatric Prediction model Severe dengue WHO 2009 classification Warning signs 

Abbreviations

AP/T

Abdominal Pain/ Tenderness

AST/ALT

Aspartate Transaminase/ Alanine Transaminase

CFA

Clinical Fluid Accumulation

DIC/MODS

Disseminated Intravascular Coagulation/ Multi Organ Dysfunction Syndrome

GCS

Glasgow Coma Scale

HM

Hepatomegaly

IVF

Intravenous Fluids

L/R

Lethargy/ Restlessness

MB

Mucosal Bleed

NSD

Non Severe Dengue

PC

Platelet Count

PCV

Packed Cell Volume

PV

Persistent Vomiting

SD

Severe Dengue

TRIPOD

Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis

WHO TDR

World Health Organization- Tropical Diseases Research

WS

Warning Signs

This is a preview of subscription content, log in to check access

Notes

Acknowledgements

The authors deeply acknowledge Kerala University of Health Sciences (KUHS) for granting permission for publication of this article, prepared as part of thesis work done in partial fulfilment of the requirements for Mphil (Clinical Epidemiology) degree course.

Contributions

PS: Conceived the concept, designed the protocol, collected, analyzed & interpreted the data and prepared the manuscript; GS: Guided conduct of the study, critically revised & approved the manuscript; SK: Designed the study methodology, analyzed & interpreted the data and approved the version to be published. Dr. Santhoshkumar A, Professor & Head of Department of Pediatrics, Government Medical College, Thiruvananthapuram will act as guarantor for this paper.

Compliance with Ethical Standards

Conflict of Interest

None.

References

  1. 1.
    World Health Organization. Dengue: Dengue factsheet. Available at: www.searo.who.int/entity/vector_borne_tropical_diseases/data/data_factsheet/en/. Accessed 30 April 2017.
  2. 2.
    National Vector Borne Disease Control Programme. Dengue. Dengue cases and deaths in the country since 2010. Available at: www.nvbdcp.gov.in/den-cd.html. Accessed 30 April 2017.
  3. 3.
    Alexander N, Balmaseda A, Coelho ICB, et al. Multicentre prospective study on dengue classification in four south-east Asian and three Latin American countries. Tropical Med Int Health. 2011;16:936–48.CrossRefGoogle Scholar
  4. 4.
    World Health Organization. Dengue guidelines for diagnosis, treatment, prevention and control: new edition 2009. Available at: www.who.int/rpc/guidelines/9789241547871/en/. Accessed 30 April 2017.
  5. 5.
    Barniol J, Gaczkowski R, Barbato EV, et al. Usefulness and applicability of the revised dengue case classification by disease: multicentre study in 18 countries. BMC Infect Dis. 2011;11:106.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Horstick O, Farrar J, Lum L, et al. Reviewing the development, evidence base and application of the revised dengue case classification. Pathog Glob Health. 2012;106:94–101.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Hadenegoro SRS. The revised WHO dengue case classification: does the system need to be modified? Paediatr Int Child Health. 2012;32:33–8.CrossRefGoogle Scholar
  8. 8.
    Jain A, Chaturvedi UC. Dengue in infants: an overview. FEMS Immunol Med Microbiol. 2010;59:119–30.CrossRefPubMedGoogle Scholar
  9. 9.
    Manakkadan A, Joseph I, Prasanna RR, Kunju RI, Kailas L, Sreekumar E. Lineage shift in Indian strains of dengue virus serotype-3 (genotype III), evidenced by detection of lineage IV strains in clinical cases from Kerala. Virol J. 2013;10:37.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Farrar JJ, Hien TT, Horstick O, et al. Dogma in classifying dengue disease. Am J Trop Med Hyg. 2013;89:198–201.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Moons KGM, Altman DG, Reitsma JB, et al. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): explanation and elaboration. Ann Intern Med. 2015;162:W1–73.CrossRefPubMedGoogle Scholar
  12. 12.
    Thein TL, Gan VC, Lye DC, et al. Utilities and limitations of the World Health Organization 2009 warning signs for adult dengue severity. PLoS Negl Trop Dis. 2013;7:e2023.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Leo YS, Gan VC, Ng EL, et al. Utility of warning signs in guiding admission and predicting severe disease in adult dengue. BMC Infect Dis. 2013;13:498.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Carrasco LR, Leo YS, Cook AR, et al. Predictive tool for severe dengue conforming to World Health Organization 2009 criteria. PLoS Negl Trop Dis. 2014;8:e2972.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Jayaratne SD, Atukorale V, Gomes L, et al. Evaluation of the WHO revised criteria for classification of clinical disease severity in acute adult dengue infection. BMC Res Notes. 2012;5:645.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Pongpan S, Wisitwong A, Tawichasri C, et al. Development of dengue infection severity score. ISRN Pediatr. 2013;2013:845876.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Zhang H, Zhou YP, Peng HJ, et al. Predictive symptoms and signs of severe dengue disease for patients with dengue fever: a meta analysis. Biomed Res Int. 2014:articleID359308.Google Scholar
  18. 18.
    Horstick O, Jaenisch T, Martinez E, et al. Comparing the usefulness of the 1997 and 2009 WHO dengue case classification: a systematic literature review. Am J Trop Med Hyg. 2014;91:621–34.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Jaenisch T, Tam DTH, Kieu NTT, et al. Clinical evaluation of dengue and identification of risk factors for severe disease: protocol for a multicentre study in 8 countries. BMC Infect Dis. 2016;16:120.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Thanachartwet V, Wattanathum A, Oer-areemitr N, et al. Diagnostic accuracy of peripheral venous lactate and the WHO 2009 warning signs for identifying severe dengue in Thai adults: a prospective observational study. BMC Infect Dis. 2016;16:46.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    National Vector Borne Disease Control Programme. National guidelines for clinical management of Dengue fever. Available at: http://pbhealth.gov.in/Dengue-National-Guidelines-2014%20Compressed.pdf. Accessed 23 February 2017.
  22. 22.
    Wills B, Ngoc TV, Van NTH, et al. Hemostatic changes in Vietnamese children with mild dengue correlate with the severity of vascular leakage rather than bleeding. Am J Trop Med Hyg. 2009;81:638–44.CrossRefPubMedGoogle Scholar
  23. 23.
    Krishnamurti C, Kalyanarooj S. Cutting MA, et al. mechanisms of hemorrhage in dengue without circulatory collapse. Am J Trop Med Hyg. 2001;65:840–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Halstead SB. Dengue: the syndromic basis to pathogenesis research. Inutility of the 2009 WHO case definition. Am J Trop Med Hyg. 2013;88:212–5.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Voung NL, Manh DH, Mai NT, et al. Criteria of “persistent vomiting” in the WHO 2009 warning for dengue case classification. Trop Med Health. 2016;44:14.CrossRefGoogle Scholar
  26. 26.
    Samanta J, Sharma V. Dengue and its effects on liver. World J Clin Cases. 2015;16:125–31.CrossRefGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2018

Authors and Affiliations

  1. 1.Department of PediatricsGovernment Medical College, ThiruvananthapuramThiruvananthapuram DistrictIndia
  2. 2.Clinical Epidemiology Research & Training Centre (CERTC)Government Medical CollegeThiruvananthapuramIndia

Personalised recommendations