The detection of anti-dengue virus IgM in urine in participants enrolled in an acute febrile illness study in Puerto Rico

• Published in: PLoS neglected tropical diseases 2020-01, Vol.14 (1), p.e0007971-e0007971
• Main Authors: Caraballo, Elba, Poole-Smith, B Katherine, Tomashek, Kay M, Torres-Velasquez, Brenda, Alvarado, Luisa I, Lorenzi, Olga D, Ramos, Carmen, Carrión, Jessica, Hunsperger, Elizabeth
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antibodies, Viral - urine; Biology and Life Sciences; Biomarkers; Child; Chronic illnesses; Dengue; Dengue - diagnosis; Dengue - epidemiology; Dengue - urine; Dengue fever; Dengue Virus - immunology; Detection; Diagnostic systems; Diagnostic Tests, Routine - methods; Disease control; Disease prevention; DNA; ELISA; Enrollments; Evaluation; Female; Fever; Fever - diagnosis; Hospitals; Human diseases; Humans; Illnesses; Immunoassay; Immunoglobulin M; Immunoglobulin M - urine; Infectious diseases; Informed consent; Kidneys; Male; Medical laboratories; Medicine and Health Sciences; Middle Aged; Nucleic acids; Nucleotide sequence; Patients; PCR; Puerto Rico - epidemiology; Ramos, Jessica; Research and Analysis Methods; Ribonucleic acid; RNA; Sensitivity; Sensitivity and Specificity; Serum; Specificity; Supervision; Tropical diseases; Urine; Vector-borne diseases; Vectors (Biology); Viruses; Young Adult
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0007971

Dengue is an important arboviral disease with about 100 million dengue cases per year, of which, ~5% result in severe disease. Clinical differentiation of dengue from other acute febrile illnesses (AFI) is difficult, and diagnostic blood tests are costly. We evaluated the utility of anti-DENV IgM in urine to identify dengue cases among AFI patients enrolled in a clinical study. Between May 2012-March 2013, 1538 study participants with fever for ≤7 days were enrolled, a medical history was obtained, and serum and urine specimens were collected. Serum was tested for DENV RNA and anti-DENV IgM. Urine was tested for anti-DENV IgM, and its sensitivity and specificity to detect sera laboratory-positive dengue cases were calculated. We evaluated if urine anti-DENV IgM positivity early (≤5 days post-illness onset [DPO]) and late (6-14 DPO) in the clinical course was associated with dengue severity. Urine anti-DENV IgM sensitivity and specificity were 47.4% and 98.5%, respectively, when compared with serum anti-DENV IgM ELISA results, and 29.7% and 91.1% when compared with serum rRT-PCR results. There was no correlation between urine anti-DENV IgM positivity and patient sex or pre-existing chronic disease. Early in the clinical course, a significantly higher proportion of those who developed dengue with warning signs had anti-DENV IgM in their urine when compared to those without warning signs (20.4% vs. 4.3%). There was no difference in the proportion with urine anti-DENV IgM positivity between severity groups late in the clinical course. While detection of urine anti-DENV IgM lacked adequate diagnostic sensitivity, it is a highly specific marker for laboratory-positive dengue, and its presence early in the clinical course may distinguish those with more severe disease. Further assessment of urine anti-DENV IgM by DPO is warranted to determine its utility as an early diagnostic (and possibly prognostic) marker for dengue.