Serodiagnosis of Zika virus infection : implication ofcross‐reactivity between flaviviruses

Abstract

Zika virus is an emerging pathogen and outbreak occurred in many locations since 2007. However, no serosurvey has been done in Hong Kong, which is geographically closed to endemic Southeast Asia and has a large number of travelers returning from endemic area. In addition, result of serological diagnosis is difficult to interpret due to cross reactivity of antibodies against other flaviviruses. A retrospective study was conducted for two groups of subjects. The first group of subjects was patient admitted to Queen Mary Hospital from January 2014 to September 2016. A total of 176 patients with mainly fever and rash were enrolled in this group. The second group of subjects enrolled was healthy blood donor admitted to the Hong Kong Red Cross in 2016. A total of 200 subjects were enrolled in this group. Zika positive sera of 2 confirmed Zika positive cases were tested in this study as reference. From the 176 patients enrolled from January 2014 to September 2016, 3 (1.7%) specimens were believed to be Zika positive. The seroprevalence was found to be 2.5% (1/40) in 2014, 3.2% (2/62) in 2015 and 0% (0/74) in 2016. Among 200 healthy blood donors recruited by the Hong Kong Red Cross, none (0/200) of the specimen was found to be have specific IgG antibody against Zika Virus. No Zika virus RNA was detected by PCR in this study. From the test results in this study, PCR was unable to detect Zika virus in the seropositive sera, including the sera of confirmed positive cases collected on day 6 post symptom onest. Zika‐specific IgM was detected in sera of 2 confirmed positive cases but not in the 3 clinical cases. IgG and IgA antibodies were found low avidity in primary Zika infection but not in secondary Zika infection cases. Zika‐specific IgA was found present in the early phase of Zika virus infection, while Zika‐specific IgM might be absent or in low titer in secondary infection cases. Serological tests showed cross‐reactivity to other flavivirus in secondary Zika infection cases. Detection of IgM and IgG alone cannot differentiate the agent of infection in secondary infection cases. Plaque reduction neutralization showed more specific results in this study. For the five cases investigated in this study, one case was found to be primary Zika virus infection, three cases were believed to be secondary Zika infection with pass exposure to Dengue virus, and one case was believed to be secondary Zika infection with pass exposure to flavivirus which was not included in this study. In conclusion, screening of IgA and PRNT are proposed to include in the panel of tests for diagnosis of Zika infection. Awareness should be raised for those highly suspected patients with Zika PCR and IgM negative, antibody panel for Zika virus and other Flaviviruses should also be further investigated.