BACKGROUND: The U.S. Virgin Islands (USVI) is currently experiencing a territory-wide outbreak of Zika virus (ZIKV). CSTE developed a case definition for ZIKV that considers the possibility of cross-reactivity with dengue virus (DENV). Due to the endemic nature of DENV in the USVI population, the Virgin Islands Department of Health (VIDOH) has employed a case definition that takes past infection with DENV into account. The purpose of this study is to compare the utilization of the CSTE and VIDOH case definitions.
METHODS: The VIDOH and CSTE case definition criteria were applied to current ZIKV cases in USVI. For VIDOH, a case of ZIKV disease is defined as having clinically compatible symptoms and being 1) positive by serum or urine PCR for ZIKV and/or 2) positive for ZIKV IgM in serum and having a positive ZIKV plaque reduction neutralization test (PRNT) titer, regardless of dengue IgM and PRNT titers. A case is defined as probable when PCR results are negative and/or ZIKV IgM results are positive and ZIKV PRNT titer results are pending or not performed. CSTE defines a case of ZIKV as confirmed with a positive PCR result, or by having a positive ZIKV PRNT titer with a negative DENV PRNT titer. Cases with positive ZIKV and DENV PRNT titers are classified as having possible ZIKV.
RESULTS: When 548 cases were compared, 419 (76%) were classified as confirmed by both CSTE and VIDOH with positive PCR results by urine and/or serum. Thirty-four (6%) cases had positive ZIKV PRNT titer results and negative dengue PRNT titer results, and were classified as confirmed by both CSTE and VIDOH. Ninety-five (17%) had positive ZIKV PRNT titer results and positive dengue PRNT titer results, and were classified as possible ZIKV by CSTE definition, and confirmed ZIKV by VIDOH definition.
CONCLUSIONS: Current CDC DENV PRNT testing includes IgM and IgG antibodies and detects long-term immunity in addition to a short-term immune response. DENV is endemic in the USVI and using DENV PRNT titers to confirm a recent infection with DENV is not conclusive and should not be used to classify a case as possible ZIKV. The current CSTE ZIKV disease case definition underestimates the true burden of ZIKV in the territory. This suggests a need for tailoring the ZIKV case definition to fit the geographic area to which it is being applied. Additionally, future PRNT testing excluding IgG antibodies should be considered.