Comparison of serological and symptomatic diagnosis of Zika virus infection using the reporter virus particle (RVP) neutralization assay on samples from Atlántico, Colombia

Background: Zika virus associated morbidities have prompted a global response to Zika infection detection. Recommended serological tests make diagnostics difficult because of cross-reactivity to other flaviviruses and restriction to laboratory availability. In resource-limited settings where Zika is endemic, it is necessary to assess the utility of clinical symptoms as a standard diagnostic strategy for Zika. This study uses a reporter virus particle (RVP) neutralizing antibody assay to evaluate symptomatic clinical diagnosis of Zika virus. Methods: Serum and plasma samples collected from patients from Atlántico, Colombia who reported clinically defined symptoms of Zika between October 2015 and June 2016 were tested for neutralizing antibodies to Zika virus H/PF/2013 and dengue-II using RVPs. Standard curves against known antibody concentrations were generated to determine specificity of RVPs for analysis. A result was positive if the Zika antibody inhibitory concentration (IC) to 50% of the RVPs was two-fold greater than corresponding dengue IC 50%. Positive predictive value of symptomatic diagnosis was determined. Prevalence odds ratio was used to compare RVP assay determined Zika infection status to patient symptoms, number of symptoms, and time since infection. Regression analysis was used to assess changes in IC titers due to symptoms. Statistical analysis was conducted using SAS (9.4). Results: The RVP analysis was specific for Zika H/PF/2013 and dengue-II virus antibodies. Among the 77 patient specimens analyzed, 53 were Zika positive through RVP analysis, 19 negative, and 4 demonstrated an indeterminate result. The average number of days between symptoms and collection date was 37 days. Patients were on average 44 years old, and more than half were female (69.14%). Half of all patients had 6-8 symptoms. The positive predictive value of symptomatic diagnosis was 69%. Of the eight symptoms assessed symptom type, number of symptoms, collection time, and age had no significant correlation with a positive result compared to negative cases. Neither collection time since symptoms nor age had a significant impact on Zika infection status. Increases in IC 50% for Zika or for dengue-II did not relate to number or type of symptoms. Presence of skin rash was positively associated with a 90% IC antibody titer to dengue-II (p\u3c0.05). Discussion: Symptomatic diagnosis of Zika virus in Colombia may be not useful in the absence of laboratory capacity, and may not be enough to rule out other arboviral diseases. Further study is needed to assess the impact of previous flavivirus history on RVP positivity results