Accuracy of clinical criteria and an immunochromatographic strip test for dengue diagnosis in a DENV-4 epidemic

BACKGROUND Early diagnosis of dengue infection is important for decision-making and timely implementation of therapeutic measures. Although rapid NS1 assays have been used for dengue diagnosis since 2008, their performance in DENV-4 cases has not yet been fully assessed. METHODS We evaluated the accuracy of NS1 Bioeasy™ immunochromatographic strip test and of three clinical criteria for dengue diagnosis. Patients presenting at an emergency care center within 72 h of an acute febrile illness during the 2013 DENV-4 epidemic in Rio de Janeiro were consecutively enrolled for clinical and laboratory evaluation. We classified patients as suspected dengue or not according to three clinical criteria: WHO 2009, WHO 1997, and INI-FIOCRUZ. Dengue diagnosis was defined by RNA detection using RT-PCR and the negative cases were negative for all dengue serotypes and also Platelia™ NS1 ELISA. We obtained accuracy indices for NS1 Bioeasy™ alone and in combination with the clinical criteria. RESULTS RT-PCR for DENV-4 was positive in 148 out of 325 patients. Positive likelihood ratio, sensitivity, and specificity of NS1 Bioeasy™ with WHO 2009, WHO 1997, and INI-FIOCRUZ criteria were 22.6 (95% CI 7.2-70.6), 40.6% (95% CI 32.3-49.3), and 98.2% (95% CI 94.9-99.6); 18.3 (95% CI 6.8-49.2), 44.2 (95% CI 35.8-52.9), 97.6 (95% CI 94.0-99.3); 26.2 (95% CI 6.5-106.5), 29.7 (95% CI 22.4-37.8), 98.9 (95% CI 96.0-99.9), respectively. WHO 1997 clinical criteria presented high sensitivity to rule out disease, but extremely low specificity. INI-FIOCRUZ had moderate sensitivity and specificity, and could target a group to a more specific test. CONCLUSIONS Although the large rates of false negative results using NS1 Bioeasy™ rapid test advise against its use for triaging (rule out) purposes in DENV-4 epidemics, it could be used as a confirmatory tool in a bedside algorithm.