Improving dengue diagnosis and case confirmation in children by combining rapid diagnostic tests, clinical, and laboratory variables

Abstract

BackgroundDengue is the most widely distributed arboviral disease in tropical and subtropical countries. Most suspected cases are diagnosed according to the clinical criteria, and early diagnosis is difficult. Moreover, in underdeveloped countries, several factors continue to challenge the diagnosis and surveillance of dengue cases. This study aimed to design a diagnostic algorithm using rapid diagnostic tests (RDTs), ELISA tests, and clinical and hematological variables to confirm dengue cases in febrile patients in Colombia.MethodsAltogether, 505 samples were collected. Serum samples were evaluated by RDTs (IgM and IgG antibodies and NS1 antigen), capture IgM and IgG ELISAs, and endpoint hemi-nested RT-PCR assay (qualitative). We statistically analyzed the performance of individual tests to determine the most useful ones to confirm dengue cases accurately.ResultsIndividual results for IgM, IgG, and NS1 RDTs yielded lower sensitivity and specificity values than the reference standard. High sensitivity and specificity were obtained after combining IgM and NS1 ELISA results (96.3% and 96.4%) and NS1 RDT plus IgM ELISA results (90.3% and 96.2%), respectively. Adjusted odds ratios (aORs) were calculated for clinical variables and laboratory tests to differentiate dengue from other febrile illnesses (OFI). This approach showed that myalgia, abdominal tenderness, and platelet count were identified with higher sensitivity to confirm dengue cases. IgM RDT and NS1 RDT differentiated dengue cases from OFI. A positive IgM RDT or a positive NS1 RDT combined with specific signs or symptoms confirmed 81.6% of dengue cases. A combination of clinical findings and a positive NS1 RDT or positive ELISA IgM confirmed 90.6% of the cases.ConclusionOur findings showed that clinical diagnoses in pediatric population alone cannot confirm true dengue cases and needs to be complemented by laboratory diagnostic tests. We also demonstrate the usefulness of combining clinical criteria with RDTs, suggesting that their implementation with the IgM ELISA test improves dengue case confirmation.