Since the introduction of Zika virus to the Americas in 2015 research has been key to understanding Zika transmission and infection and establishing clinical guidance. Now a new study by investigators at the Florida Department of Health and the US Centers for Disease Control and Prevention (CDC) is adding to the limited data on the duration of detectable Zika virus-specific immunoglobulin M (IgM) in infected persons.
Florida saw more than 350 laboratory-confirmed locally-acquired cases of the virus in 2016. The CDC’s current Zika testing guidance recommends Zika virus and/or dengue virus IgM testing of serum in certain situations and notes that while IgM levels vary in Zika cases, they are generally positive beginning 4 days after onset of symptoms and continuing for up to 12 weeks, though may persist for months to years.
In the new study published in the CDC journal Emerging Infectious Diseases, investigators have found that most study participants with prior Zika infection continued to have detectable Zika virus IgM a year or more beyond onset of illness.
For the study, investigators enrolled 62 participants who were residents of Miami-Dade County, Florida, and who had Zika virus infection confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR). The onset of symptoms for participants ranged from June to October 2016 and participants were enrolled from October 16, 2017, to February 1, 2018. Excluded from the study were Zika cases with asymptomatic infection, pregnant women, and infants with congenital infection. Of those included in the study, 55% acquired their infections locally in Miami-Dade County.
There were 8 (13%) participants who provided follow-up serum specimens 12 months after initial symptom onset: 1 (2%) at 13 months, 13 (21%) at 14 months, 21 (34%) at 15 months, 11 (18%) at 16 months, 3 (5%) at 17 months, 3 (5%) at 18 months, and 2 (3%) at 19 months.
Investigators found that 45 (73%) patients had detectable Zika virus IgM at follow-up, 12 (19%) had an equivocal result, and 5 (8%) were negative. Of the 43 specimens collected at 12 to 15 months following symptom onset, 39 (91%) were IgM positive or equivocal, while 18 (95%) of the 19 specimens collected at 16 to 19 months were positive or equivocal.
In addition, the study team detected Zika virus neutralizing antibodies in all participants at 12 to 19 months following acute illness, and 39 (63%) had dengue virus neutralizing antibody titers at follow-up.
In an interview with Contagion®, study co-author Isabel Griffin, MPH, epidemiologist and biological scientist at the Florida Department of Health explained that the findings on prolonged detection of IgM after Zika virus infection are consistent with previous findings for related flaviviruses such as West Nile virus and dengue virus. “Prior to our study, it was widely accepted that the Zika virus IgM antibody was only detectable up to 12 weeks after Zika virus infection,” said Dr. Griffin. “Our findings demonstrate that 73% of patients still had detectable levels of Zika virus IgM antibodies more than a year after infection.”
The study had several limitations, and the investigators note that the report presents data from a single follow-up specimen, so it remains unknow how long IgM may persist beyond the study’s timeframe although the findings are valuable. “For individuals who were previously diagnosed with Zika, our findings suggest that the body has detectable levels of antibodies over a year after infection,” explained Dr. Griffin. “For public health officials, the results highlight the complexity of using serologic diagnoses, both for determining the specific timing of a recent infection, which is particularly important for pregnant women and complicates the diagnosis of new Zika virus infections in areas with known previous outbreaks, and for determining the specific flavivirus responsible for recent infection.”