title: Diagnosing dengue at the point-of-care: utility of a rapid combined diagnostic kit in Singapore.
abstract: WHO recommendations for dengue diagnosis require laboratory facilities. Antibody-based rapid diagnostic tests (RDTs) have performed poorly, and clinical diagnosis remains the mainstay in dengue-endemic countries. We evaluated a combination antigen-antibody RDT for point-of-care testing in a high-prevalence setting. In this prospective cohort study, adults were enrolled from a tertiary infectious disease centre for evaluation of undifferentiated febrile illness from October 2011 to May 2012. SD Bioline Dengue Duo was evaluated at point-of-care against a WHO-based reference standard of viral isolation, RT-PCR, NS1-, IgM-, and IgG-ELISA. 246 adults were enrolled (median age 34 years, range 18-69), of which 197 could be confirmed definitively as either dengue or non-dengue. DENV-2 was the predominant serotype (79.5%) and the ratio of primary to secondary cases was 1∶1.1. There were no test failures and minimal interobserver variation with a Fleiss' kappa of 0.983 (95% CI 0.827-1.00). Overall sensitivity and specificity were 93.9% (95% CI 88.8-96.8%) and 92.0% (95% CI 81.2-96.9%) respectively. Using WHO clinical criteria alone for diagnosis had similar sensitivities (95.9%, 95% CI 91.4-98.1%) and lower specificities (20.0%, 95% CI 11.2-33.0%). No significant difference in performance was found when testing early versus late presenters, primary versus secondary cases, or DENV-1 versus DENV-2 infections. The use of a combination RDT fulfills WHO ASSURED criteria for point-of-care testing and can enhance dengue diagnosis in an endemic setting. This has the potential to markedly improve clinical management of dengue in the field.
authors.affiliation: Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Gan
authors.affiliation: Environmental Health Institute, National Environment Agency, Singapore, Singapore.
authors.forename: Li-Kiang
authors.initials: LK
authors.lastname: Tan
authors.affiliation: Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: David C
authors.initials: DC
authors.lastname: Lye
authors.affiliation: Environmental Health Institute, National Environment Agency, Singapore, Singapore.
authors.forename: Kwoon-Yong
authors.initials: KY
authors.lastname: Pok
authors.affiliation: Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore.
authors.forename: Shi-Qi
authors.initials: SQ
authors.lastname: Mok
authors.affiliation: Environmental Health Institute, National Environment Agency, Singapore, Singapore.
authors.forename: Rachel Choon-Rong
authors.initials: RC
authors.lastname: Chua
authors.affiliation: Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Yee-Sin
authors.initials: YS
authors.lastname: Leo
authors.affiliation: Environmental Health Institute, National Environment Agency, Singapore, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
authors.forename: Lee-Ching
authors.initials: LC
authors.lastname: Ng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood*; D000956:Antigens, Viral / Q000097:blood*; D003715:Dengue / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D003716:Dengue Virus / Q000276:immunology / Q000302:isolation & purification*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D019095:Point-of-Care Systems; D011446:Prospective Studies; D011933:Reagent Kits, Diagnostic / Q000592:standards / Q000706:statistics & numerical data*; D012680:Sensitivity and Specificity; D012846:Singapore
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011933:Reagent Kits, Diagnostic