학술논문

Comparison of Four Serological Methods and Two Reverse Transcription-PCR Assays for Diagnosis and Surveillance of Zika Virus Infection
Document Type
article
Source
Journal of Clinical Microbiology. 56(3)
Subject
Pediatric
Rare Diseases
Infectious Diseases
Vector-Borne Diseases
Prevention
Vaccine Related
Clinical Research
Biodefense
Emerging Infectious Diseases
Infection
Good Health and Well Being
Adolescent
Child
Child
Preschool
Cohort Studies
Cross Reactions
Dengue
Dengue Virus
Enzyme-Linked Immunosorbent Assay
Epidemiological Monitoring
Female
Humans
Nicaragua
Reverse Transcriptase Polymerase Chain Reaction
Sensitivity and Specificity
Serologic Tests
Zika Virus
Zika Virus Infection
ELISA
RT-PCR
Zika virus
dengue virus
diagnosis
serological assay
surveillance
Biological Sciences
Agricultural and Veterinary Sciences
Medical and Health Sciences
Microbiology
Language
Abstract
Zika virus (ZIKV) is a mosquito-borne flavivirus that is responsible for recent explosive epidemics in the Americas. Notably, ZIKV infection during pregnancy has been found to cause congenital birth defects, including microcephaly, and ZIKV has been associated with Guillain-Barré syndrome in adults. Diagnosis and surveillance of Zika in the Americas have been challenging due to similar clinical manifestations and extensive antibody cross-reactivity with endemic flaviviral diseases, such as dengue. We evaluated four serological and two reverse transcription-PCR (RT-PCR) methods in acute-phase (mean day, 1.8), early-convalescent-phase (mean day, 16.7), and late-convalescent-phase (mean, ~7 months) samples from the same individuals in a long-term pediatric cohort study in Nicaragua. Well-characterized samples from 301 cases of Zika, dengue, or non-Zika, nondengue febrile illnesses were tested. Compared to a composite reference, an in-house IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) and the NIAID-Biodefense and Emerging Infections (BEI) MAC-ELISA measuring IgM yielded sensitivities of 94.5% and 70.1% and specificities of 85.6% and 82.8%, respectively. The NS1 blockade-of-binding ELISA measuring anti-ZIKV NS1 antibody levels yielded sensitivities of 85.0% and 96.5% and specificities of 91.4% and 92.6% at early and late convalescence, respectively. An inhibition ELISA detecting total anti-ZIKV antibodies had sensitivity and specificity values of 68.3% and 58.3% for diagnosis and 94.0% and 98.6% for measuring annual infection incidence. Finally, the ZCD and Trioplex real-time RT-PCR assays detecting Zika, chikungunya, and dengue viruses both yielded a sensitivity of 96.1% and specificity of 100%. Together, these assays resolve the urgent need for diagnostic and surveillance tools for countries affected by Zika virus infections.