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J Pediatr Infect Dis 2022; 17(03): 119-125
DOI: 10.1055/s-0042-1745838
Original Article

Warning Signs in Predicting Severe Pediatric Dengue Infection

Andry Juliansen
1   Department of Pediatric, Faculty of Medicine, Universitas Pelita Harapan, Karawaci, Tangerang, Indonesia
,
Rivaldo S. Heriyanto 
2   Faculty of Medicine, Universitas Pelita Harapan, Karawaci, Tangerang, Indonesia
,
Charista L. Budiputri
2   Faculty of Medicine, Universitas Pelita Harapan, Karawaci, Tangerang, Indonesia
,
Fellisa Meliani
2   Faculty of Medicine, Universitas Pelita Harapan, Karawaci, Tangerang, Indonesia
,
Michelle P. Muljono
2   Faculty of Medicine, Universitas Pelita Harapan, Karawaci, Tangerang, Indonesia
,
Shally Chandra
2   Faculty of Medicine, Universitas Pelita Harapan, Karawaci, Tangerang, Indonesia
,
Gilbert S. Octavius
2   Faculty of Medicine, Universitas Pelita Harapan, Karawaci, Tangerang, Indonesia
› Author Affiliations Funding None.
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Abstract

Objective The uncertainty of dengue's progression from infection to its severe form represents a major health care challenge, especially in children. Clinical identification of impending clinical manifestations of severe dengue (SD), along with proper and immediate management, is crucial. Thus, this study assesses the ability of warning signs to predict SD infection in pediatric patients.

Methods This cross-sectional study utilized purposive sampling using medical records from January 2015 to December 2020. Children aged 0 to 18 years diagnosed with dengue fever and SD according to the World Health Organization's 2009 criteria were included.

Discussion Multivariate analysis revealed that abdominal pain (odds ratio [OR]: 16.34; 95% confidence interval [CI]: 3.78–70.64; p < 0.001), fluid accumulation (OR: 10.51, 95% CI: 1.17–94.3; p = 0.036), mucosal bleeding (OR: 4.77; 95% CI: 1.27–17.91; p = 0.021), lethargy (OR: 94.37; 95% CI: 4.92–180.79; p = 0.003), hepatomegaly (OR: 17.57; 95% CI: 2.14–144.13; p = 0.008), and increased hematocrit concurrent with a rapid decrease in platelets (OR: 6.89; 95% CI: 1.79–26.51, p = 0.005) were associated with SD infection, with a high quality of discrimination (area under the curve [AUC] = 0.96) and a high quality of fit (p = 0.73). Receiver operating characteristic analysis demonstrated that 1.5 warning signs was the optimal cut-off for predicting SD infection, with a sensitivity of 90.9 and a specificity of 89.8%.

Conclusion All six warning signs were significantly associated with SD infection. The optimal cut-off for predicting SD was 1.5 warning signs.

Keywords

dengue infection - severe dengue - warning signs - pediatrics

Authors' Contributions

Conceptualization: A.J. and G.S.O.


Methodology: R.S.H. and G.S.O.


Formal analysis, investigation, data curation: R.S.H., C.L.B., F.M., M.P.M., and S.C.


Supervision: A.J.


Writing—original draft: A.J., R.S.H., C.L.B., F.M., M.P.M., S.C., and G.S.O.


Writing—review and editing: A.J., R.S.H., G.S.O.




Publication History

Received: 22 December 2021

Accepted: 24 February 2022

Article published online:
30 May 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 World Health Organization. Dengue and severe dengue. Accessed October 18, 2021 at: https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue
    PubMedGoogle Scholar
  • 2 Dengue guidelines for diagnosis, treatment, prevention and control: new edition 2009. Available at: DHF_guidelines_COVER.indd (who.int). Accessed March 9, 2022
    PubMedGoogle Scholar
  • 3 Bhatt S, Gething PW, Brady OJ. et al. The global distribution and burden of dengue. Nature 2013; 496 (7446): 504-507
    CrossrefPubMedGoogle Scholar
  • 4 Karyanti MR, Uiterwaal CS, Kusriastuti R. et al. The changing incidence of dengue haemorrhagic fever in Indonesia: a 45-year registry-based analysis. BMC Infect Dis 2014; 14: 412
    CrossrefPubMedGoogle Scholar
  • 5 Kliks SC, Nisalak A, Brandt WE, Wahl L, Burke DS. Antibody-dependent enhancement of dengue virus growth in human monocytes as a risk factor for dengue hemorrhagic fever. Am J Trop Med Hyg 1989; 40 (04) 444-451
    CrossrefPubMedGoogle Scholar
  • 6 Waggoner JJ, Gresh L, Vargas MJ. et al. Viremia and clinical presentation in nicaraguan patients infected with zika virus, chikungunya virus, and dengue virus. Clin Infect Dis 2016; 63 (12) 1584-1590
    CrossrefPubMedGoogle Scholar
  • 7 Douglas KO, Dutta SK, Martina B, Anfasa F, Samuels TA, Hilaire MG. Dengue fever and severe dengue in Barbados, 2008–2016. Trop Med Infect Dis 2020; 5 (02) 2008-2016
    PubMedGoogle Scholar
  • 8 Wong PF, Wong LP, AbuBakar S. Diagnosis of severe dengue: Challenges, needs and opportunities. J Infect Public Health 2020; 13 (02) 193-198
    CrossrefPubMedGoogle Scholar
  • 9 Gubler DJ. Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century. Trends Microbiol 2002; 10 (02) 100-103
    CrossrefPubMedGoogle Scholar
  • 10 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 (01) 120
    CrossrefPubMedGoogle Scholar
  • 11 Sangkaew S, Ming D, Boonyasiri A. et al. Risk predictors of progression to severe disease during the febrile phase of dengue: a systematic review and meta-analysis. Lancet Infect Dis 2021; 21 (07) 1014-1026
    CrossrefPubMedGoogle Scholar
  • 12 Brasier AR, Ju H, Garcia J. et al; Venezuelan Dengue Fever Working Group. A three-component biomarker panel for prediction of dengue hemorrhagic fever. Am J Trop Med Hyg 2012; 86 (02) 341-348
    CrossrefPubMedGoogle Scholar
  • 13 Ahmad MH, Ibrahim MI, Mohamed Z. et al. The sensitivity, specificity and accuracy of warning signs in predicting severe dengue, the severe dengue prevalence and its associated factors. Int J Environ Res Public Health 2018; 15 (09) E2018
    CrossrefPubMedGoogle Scholar
  • 14 Wichmann O, Gascon J, Schunk M. et al; European Network on Surveillance of Imported Infectious Diseases. Severe dengue virus infection in travelers: risk factors and laboratory indicators. J Infect Dis 2007; 195 (08) 1089-1096
    CrossrefPubMedGoogle Scholar
  • 15 The Asia Pacific perspective: redefining obesity and its treatment. February 2000. Available at: 0957708211_eng.pdf (who.int). Accessed March 9, 2022
    PubMedGoogle Scholar
  • 16 Narvaez F, Gutierrez G, Pérez MA. et al. Evaluation of the traditional and revised WHO classifications of dengue disease severity. PLoS Negl Trop Dis 2011; 5 (11) e1397
    CrossrefPubMedGoogle Scholar
  • 17 Steyerberg EW, Vickers AJ, Cook NR. et al. Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology 2010; 21 (01) 128-138
    CrossrefPubMedGoogle Scholar
  • 18 Ruopp MD, Perkins NJ, Whitcomb BW, Schisterman EF. Youden Index and optimal cut-point estimated from observations affected by a lower limit of detection. Biom J 2008; 50 (03) 419-430
    CrossrefPubMedGoogle Scholar
  • 19 Clemens SL, Lincoln DJ. Where children play most: physical activity levels of school children across four settings and policy implications. Aust N Z J Public Health 2018; 42 (06) 575-581
    CrossrefPubMedGoogle Scholar
  • 20 Maneerattanasak S, Suwanbamrung C. Impact of nutritional status on the severity of dengue infection among pediatric patients in Southern Thailand. Pediatr Infect Dis J 2020; 39 (12) e410-e416
    CrossrefPubMedGoogle Scholar
  • 21 Junia J, Garna H, Setiabudi D. Clinical risk factors for dengue shock syndrome in children. Paediatr Indones 2007; 47 (01) 7
    CrossrefPubMedGoogle Scholar
  • 22 Srikiatkhachorn A. Plasma leakage in dengue haemorrhagic fever. Thromb Haemost 2009; 102 (06) 1042-1049
    PubMedGoogle Scholar
  • 23 de Azeredo EL, Monteiro RQ, de-Oliveira Pinto LM. Thrombocytopenia in dengue: interrelationship between virus and the imbalance between coagulation and fibrinolysis and inflammatory mediators. Mediators Inflamm 2015; 2015: 313842
    PubMedGoogle Scholar
  • 24 Leo Y-S, Gan VC, Ng E-L. et al. Utility of warning signs in guiding admission and predicting severe disease in adult dengue. BMC Infect Dis 2013; 13 (01) 498
    CrossrefPubMedGoogle Scholar
  • 25 Rosenberger KD, Alexander N, Martinez E. et al; DENCO Clinical Study Group. Severe dengue categories as research endpoints-Results from a prospective observational study in hospitalised dengue patients. PLoS Negl Trop Dis 2020; 14 (03) e0008076
    CrossrefPubMedGoogle Scholar
  • 26 Rathore APS, Senanayake M, Athapathu AS. et al. Serum chymase levels correlate with severe dengue warning signs and clinical fluid accumulation in hospitalized pediatric patients. Sci Rep 2020; 10 (01) 11856
    CrossrefPubMedGoogle Scholar
  • 27 Madanayake P, Jayawardena A, Wijekoon SL, Perera N, Wanigasuriya J. Fluid requirement in adult dengue haemorrhagic fever patients during the critical phase of the illness: an observational study. BMC Infect Dis 2021; 21 (01) 286
    CrossrefPubMedGoogle Scholar
  • 28 Centers for Disease Control and Prevention. Dengue: clinical presentation. Accessed September 19, 2021 at: https://www.cdc.gov/dengue/healthcare-providers/clinical-presentation.html
    PubMed
  • 29 Jagadishkumar K, Jain P, Manjunath VG, Umesh L. Hepatic involvement in dengue fever in children. Iran J Pediatr 2012; 22 (02) 231-236
    PubMedGoogle Scholar
  • 30 Fernando S, Wijewickrama A, Gomes L. et al. Patterns and causes of liver involvement in acute dengue infection. BMC Infect Dis 2016; 16 (01) 319
    CrossrefPubMedGoogle Scholar
  • 31 Samanta J, Sharma V. Dengue and its effects on liver. World J Clin Cases 2015; 3 (02) 125-131
    CrossrefPubMedGoogle Scholar
  • 32 Gupta B, Nehara HR, Parmar S, Meena SL, Gajraj S, Gupta J. Acute abdomen presentation in dengue fever during recent outbreak. J Acute Dis 2017; 6 (05) 198-204
    CrossrefPubMedGoogle Scholar
  • 33 Shabbir B, Qadir H, Shafi F, Mahboob F. Acute abdominal pain in dengue fever. WHO International 2009; 33: 70-79
    PubMedGoogle Scholar
  • 34 Weerakoon KGAD, Chandrasekaram S, Jayabahu JPSNK, Gunasena S, Kularatne SAM. Acute abdominal pain in dengue haemorrhagic fever: a study in Sri Lanka, 2009. Dengue Bull 2009; 33: 70-74
    PubMedGoogle Scholar
  • 35 Thein T-L, Gan VC, Lye DC, Yung C-F, Leo Y-S. Utilities and limitations of the World Health Organization 2009 warning signs for adult dengue severity. PLoS Negl Trop Dis 2013; 7 (01) e2023
    CrossrefPubMedGoogle Scholar
  • 36 Giraldo D, Sant'Anna C, Périssé ARS. et al. Characteristics of children hospitalized with dengue fever in an outbreak in Rio de Janeiro, Brazil. Trans R Soc Trop Med Hyg 2011; 105 (10) 601-603
    CrossrefPubMedGoogle Scholar
  • 37 Alexander N, Balmaseda A, Coelho ICB. et al; European Union, World Health Organization (WHO-TDR) supported DENCO Study Group. Multicentre prospective study on dengue classification in four South-east Asian and three Latin American countries. Trop Med Int Health 2011; 16 (08) 936-948
    CrossrefPubMedGoogle Scholar
  • 38 Adam AS, Pasaribu S, Wijaya H, Pasaribu AP. Warning sign as a predictor of dengue infection severity in children. Med J Indones 2018; 27 (02) 101-107
    PubMedGoogle Scholar
  • 39 Martina BEE, Koraka P, Osterhaus ADME. Dengue virus pathogenesis: an integrated view. Clin Microbiol Rev 2009; 22 (04) 564-581
    CrossrefPubMedGoogle Scholar
  • 40 Abualamah WA, Banni HS, Almasmoum HA, Allohibi YA, Samarin HM, Bafail MA. Determining risk factors for dengue fever severity in jeddah city, a case-control study (2017). Pol J Microbiol 2020; 69 (03) 331-337
    CrossrefPubMedGoogle Scholar