Viral and serological kinetics in Zika virus-infected patients in South Korea

Abstract

Zika virus is a mosquito-borne flavivirus that causes clinical symptoms similar to those observed in dengue and chikungunya virus infections. The Korea Centers for Disease Control and Prevention initiated laboratory testing using a real-time reverse transcription-polymerase chain reaction in January 2016. More than 1,000 suspected cases of infection were tested and nine were confirmed as imported cases of Zika virus infection from January to July 2016. The travel destinations of the infected individuals were Brazil, Philippines, Viet Nam, Guatemala, Puerto Rico, and the Dominican Republic. Phylogenetic analysis based on the partial envelope gene indicated that the viruses belonged to the Asian genotype circulating in South America. We further investigated the duration for which the viral RNA and virus-specific antibodies were detectable after the symptom onset. After the day of symptom onset, Zika virus was detectable until 6 days in serum, 14 days in urine and saliva, and 58 days in semen. Immunoglobulin M against Zika virus was detected as early as 2 days after the symptom onset and was maintained at these levels until 41 days, whereas Immunoglobulin G was detectable from 8 days after the symptom onset and was maintained until 52 days. These findings would help diagnostic laboratories improve their testing programs for Zika virus infection.

Keywords: Chikungunya virus; Dengue virus; Enzyme-Linked Immunosorbent Assay; Phylogenetic analysis; Reverse transcription-polymerase chain reaction; Zika virus.

Fig. 1

Phylogenetic analysis of the Zika virus based on the partial envelope gene. The tree was constructed by the neighbor-joining method (substitution model: maximum composite likelihood) using MEGA 6 software. The percentage of bootstrap values is shown at each node (1,000 replications). Sequences of Zika viruses detected in this study are indicated as closed circles and the patient code is marked in the parenthesis. Zika virus genotypes are as defined previously [16]

Fig. 2

Duration of detectability of Zika viral RNA in different specimens. qRT-PCR was performed using a commercial kit (PrimerDesign Ltd., UK) with serum, urine, saliva, and semen samples. A sample with a threshold cycle (C_T) number ≤ 40 was considered to be Zika-positive. In patient 3, the final collection of semen was performed at 86th day after the symptom onset and the result was negative. It was not presented for the sake of brevity

Fig. 3

Profile of IgM and IgG responses to Zika virus infection in human serum. ELISA was performed using Anti-Zika Virus IgM/IgG ELISA kits (Euroimmun, Germany). a IgM ELISA response, b IgG ELISA response; the different symbols represent each patient. Interpretation of the results was based on the ratio of optical density of the patient serum over the value of the calibrator, according to the manufacturer’s instructions. Ratio < 0.8 indicates a negative result, 0.8 ≤ ratio < 1.1 indicates a borderline result, and ratio ≥ 1.1 indicates a positive result