Utility of C-Reactive Protein Levels for Early Prediction of Dengue Severity in Adults

Chien-Chih Chen, Ing-Kit Lee, Jien-Wei Liu, Shi-Yu Huang, Lin Wang, Chien-Chih Chen, Ing-Kit Lee, Jien-Wei Liu, Shi-Yu Huang, Lin Wang

Abstract

Dengue has broad clinical presentation with unpredictable clinical evolution and outcome. We aimed to evaluate the utility of C-reactive protein (CRP) levels for distinguishing between mild and severe cases in the early phase of the dengue illness. We retrospectively evaluated adults with dengue from 2006 to 2014, according to 1997 and 2009 World Health Organization (WHO) criteria for severity. Of 191 included patients, 32.9% had nonshock dengue hemorrhagic fever (DHF), 3.1% dengue shock syndrome (DSS), and 7.9% severe dengue. The risk of DHF/DSS and severe dengue is significantly related to the increasing levels of CRP. Of 191 patients, 97 had CRP levels measured during the febrile (days 1-3); 85 during the critical (days 4-6); and 9 during the convalescent (days 7-10) illness phases. During the febrile phase, there was significant higher CRP level for DSS versus DF/nonshock DHF and severe dengue versus nonsevere dengue, with CRP cutoff level 30.1 mg/L (area under the receiver operating characteristic curve (AUC), 0.938; 100% sensitivity, 76.3% specificity) and 24.2 mg/L (AUC, 0.717; 70% sensitivity, 71.3% specificity), respectively. Our study highlights the utility of the CRP levels in early prediction of DSS and severe dengue in adult patients.

References

    1. Simmons C. P., Farrar J. J., van Vinh Chau N., Wills B. Dengue. The New England Journal of Medicine. 2012;366(15):1423–1432. doi: 10.1056/nejmra1110265.
    1. World Health Organization. Dengue Hemorrhagic Fever: Diagnosis, Treatment and Control. Geneva, Switzerland: World Health Organization; 1997.
    1. Deen J. L., Harris E., Wills B., et al. The WHO dengue classification and case definitions: time for a reassessment. The Lancet. 2006;368(9530):170–173. doi: 10.1016/s0140-6736(06)69006-5.
    1. Bandyopadhyay S., Lum L. C. S., Kroeger A. Classifying dengue: a review of the difficulties in using the WHO case classification for dengue haemorrhagic fever. Tropical Medicine and International Health. 2006;11(8):1238–1255. doi: 10.1111/j.1365-3156.2006.01678.x.
    1. World Health Organization. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. Geneva, Switzerland: World Health Organization; 2009.
    1. Lee I.-K., Liu J.-W., Yang K. D. Clinical and laboratory characteristics and risk factors for fatality in elderly patients with dengue hemorrhagic fever. American Journal of Tropical Medicine and Hygiene. 2008;79(2):149–153.
    1. Lee I.-K., Liu J.-W., Yang K. D. Fatal dengue hemorrhagic fever in adults: emphasizing the evolutionary pre-fatal clinical and laboratory manifestations. PLoS Neglected Tropical Diseases. 2012;6(2) doi: 10.1371/journal.pntd.0001532.e1532
    1. Thein T.-L., Gan V. C., Lye D. C., Yung C.-F., Leo Y.-S. Utilities and limitations of the World Health Organization 2009 warning signs for adult dengue severity. PLoS Neglected Tropical Diseases. 2013;7(1) doi: 10.1371/journal.pntd.0002023.e2023
    1. Potts J. A., Gibbons R. V., Rothman A. L., et al. Prediction of dengue disease severity among pediatric Thai patients using early clinical laboratory indicators. PLoS Neglected Tropical Diseases. 2010;4(8, article e769) doi: 10.1371/journal.pntd.0000769.
    1. Lee V. J., Lye D. C., Sun Y., Leo Y. S. Decision tree algorithm in deciding hospitalization for adult patients with dengue haemorrhagic fever in Singapore. Tropical Medicine and International Health. 2009;14(9):1154–1159. doi: 10.1111/j.1365-3156.2009.02337.x.
    1. Gewurz H. Biology of C-reactive protein and the acute phase response. Hospital Practice. 1982;17(6):67–81.
    1. Pepys M. B., Hirschfield G. M. C-reactive protein: a critical update. Journal of Clinical Investigation. 2003;111(12):1805–1812. doi: 10.1172/jci200318921.
    1. Clyne B., Olshaker J. S. The C-reactive protein. The Journal of Emergency Medicine. 1999;17(6):1019–1025. doi: 10.1016/s0736-4679(99)00135-3.
    1. Jaye D. L., Waites K. B. Clinical applications of C-reactive protein in pediatrics. The Pediatric Infectious Disease Journal. 1997;16(8):735–747. doi: 10.1097/00006454-199708000-00003.
    1. Epelboin L., Boullé C., Ouar-Epelboin S., et al. Discriminating malaria from dengue fever in endemic areas: clinical and biological criteria, prognostic score and utility of the C-reactive protein: a retrospective matched-pair study in French Guiana. PLoS Neglected Tropical Diseases. 2013;7(9) doi: 10.1371/journal.pntd.0002420.e2420
    1. Villar-Centeno L. Á., Lozano-Parra A., Salgado-García D., Herrán Ó. F. Biochemical alterations as prediction markers for the severity of illness in dengue fever patients. Biomedica. 2013;33(1):63–69. doi: 10.7705/biomedica.v33i0.732.
    1. Shu P.-Y., Chang S.-F., Kuo Y.-C., et al. Development of group- and serotype-specific one-step SYBR Green I-based real-time reverse transcription-PCR assay for dengue virus. Journal of Clinical Microbiology. 2003;41(6):2408–2416. doi: 10.1128/jcm.41.6.2408-2416.2003.
    1. Shu P.-Y., Chen L.-K., Chang S.-F., et al. Comparison of capture immunoglobulin M (IgM) and IgG enzyme-linked immunosorbent assay (ELISA) and nonstructural protein NS1 serotype-specific IgG ELISA for differentiation of primary and secondary dengue virus infections. Clinical and Diagnostic Laboratory Immunology. 2003;10(4):622–630. doi: 10.1128/cdli.10.4.622-630.2003.
    1. Chuansumrit A., Chaiyaratana W., Pongthanapisith V., Tangnararatchakit K., Lertwongrath S., Yoksan S. The use of dengue nonstructural protein 1 antigen for the early diagnosis during the febrile stage in patients with dengue infection. Pediatric Infectious Disease Journal. 2008;27(1):43–48. doi: 10.1097/INF.0b013e318150666d.
    1. Shu P.-Y., Yang C.-F., Kao J.-F., et al. Application of the dengue virus NS1 antigen rapid test for on-site detection of imported dengue cases at airports. Clinical and Vaccine Immunology. 2009;16(4):589–591. doi: 10.1128/cvi.00475-08.
    1. Otsuji S., Shibata H., Umeda M. Turbidimetric immunoassay of serum C-reactive protein. Clinical Chemistry. 1982;28(10):2121–2124.
    1. Price C. P., Trull A. K., Berry D., Gorman E. G. Development and validation of a particle-enhanced turbidimetric immunoassay for C-reactive protein. Journal of Immunological Methods. 1987;99(2):205–211. doi: 10.1016/0022-1759(87)90129-3.
    1. Sanders S., Barnett A., Correa-Velez I., Coulthard M., Doust J. Systematic review of the diagnostic accuracy of C-reactive protein to detect bacterial infection in non-hospitalized infants and children with fever. Journal of Pediatrics. 2008;153(4):570–574.e3. doi: 10.1016/j.jpeds.2008.04.023.
    1. Flood R. G., Badik J., Aronoff S. C. The utility of serum C-reactive protein in differentiating bacterial from non-bacterial pneumonia in children: a meta-analysis of 1230 children. The Pediatric Infectious Disease Journal. 2008;27(2):95–99. doi: 10.1097/inf.0b013e318157aced.
    1. Jupe D. The acute phase response and laboratory testing. Australian Family Physician. 1996;25(3):324–329.
    1. Stuart J., Whicher J. T. Tests for detecting and monitoring the acute phase response. Archives of Disease in Childhood. 1988;63(2):115–117. doi: 10.1136/adc.63.2.115.
    1. Narvaez F., Gutierrez G., Pérez M. A., et al. Evaluation of the traditional and revised WHO classifications of dengue disease severity. PLoS Neglected Tropical Diseases. 2011;5(11) doi: 10.1371/journal.pntd.0001397.e1397
    1. Gabay C., Kushner I. Acute-phase proteins and other systemic responses to inflammation. The New England Journal of Medicine. 1999;340(6):448–454. doi: 10.1056/nejm199902113400607.

Source: PubMed

3
Abonnieren