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Zika RNA persists in serum longer than dengue, West Nile

SEATTLE — Preliminary study results showed that Zika RNA may persist in serum longer than other flaviviruses such as dengue and West Nile — a finding that researchers said could impact how the virus at the center of an alarming outbreak in the Americas is diagnosed and prevented.

Approximately 50% of serum samples in a small cohort of patients in Puerto Rico still had detectable Zika virus RNA particles at 14 days after the onset of symptoms, according to a study by Gabriela Paz-Bailey, MD, PhD, of the CDC’s National Center for HIV/AIDS, Viral Hepatitis, Sexually Transmitted Diseases, and Tuberculosis Prevention, and colleagues.

Gabriela Paz-Bailey
Gabriela Paz-Bailey

Paz-Bailey and colleagues said more than 90% of dengue patients clear RNA within 10 days of the onset of symptoms, regardless of serotype, whereas the median RNA clearance for West Nile virus is 13 days.

Their findings on the persistence of Zika in serum came from an evaluation of 150 patients with Zika in Puerto Rico that also tested the persistence of Zika in urine, saliva, semen and vaginal fluids.

Zika RNA remained the longest in semen, with 50% of participants showing detectable particles in their semen 1 month after the start of symptoms. But only about 5% still had detectible Zika virus particles after 3 months — half the length of time that current CDC guidelines say men should wait to have unprotected sex if they have symptoms or have been exposed to the virus.

Results of the study were presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2017 and published simultaneously in The New England Journal of Medicine. The interim analysis provided only early results based on the first 150 participants. Paz-Bailey said they expect to eventually have results from more than 300 patients. The researchers said their findings come amid a poor understanding of how long Zika RNA remains in bodily fluids.

“Most information on the duration of Zika in body fluids comes from individual case reports and observational data, mostly from returning travelers,” Paz-Bailey said during a news conference at CROI 2017.

Zika RNA detected more often in serum than urine

Beginning in May 2016 in Puerto Rico, Paz-Bailey and colleagues collected samples of serum, saliva, urine, semen or vaginal secretions from 66 women and 84 men over a 6-month period.

Although Zika RNA was largely nondetectible in saliva and vaginal fluids after 1 week, it remained detectible at 14 days in serum for half of the participants, and it was still detectible in 5% of serum samples at 8 weeks.

About half of the urine samples had detectable Zika at 8 days, with 5% still detectable at 6 weeks. During the study, Zika RNA was more likely to be found in serum than in urine, a result that Paz-Bailey and colleagues said contrasts other findings showing more frequent detection of Zika RNA in urine than serum.

The CDC currently recommends testing of serum and urine samples from patients with Zika for viral particles less than 14 days after onset of symptoms, they said.

“The data suggest that serum may be a superior diagnostic specimen compared with urine, although some benefit may accrue in testing urine to detect additional Zika virus infection,” Paz-Bailey said.

Findings back CDC guidance

Zika can cause microcephaly and other congenital neurological birth defects, outcomes that have only become evident since the recent outbreak in the Americas centered in Brazil. It is primarily spread through the bite of infected female Aedes aegypti mosquitoes but also can be spread in other ways, including through sexual contact. Zika can be sexually transmitted by both men and women — possibly even without the appearance of symptoms.

The CDC updated its Zika guidance in October to recommend that men, whether they have symptoms or not, use condoms or abstain from sex for at least 6 months since their last possible exposure to the virus before trying to conceive.

The CDC recommends that women who do not live in areas with active Zika transmission wait at least 8 weeks since the onset of their symptoms or last possible exposure to the virus before trying to get pregnant. Women living in areas with active Zika transmission who wish to become pregnant should speak to their physicians.

Paz-Bailey said their study supports the CDC’s current Zika virus guidance.

The revised guidance for men that was published in October was based on reports of Zika RNA being detected in semen for extended periods of time. Paz-Bailey said there have been only two cases where Zika was detected in semen longer than 6 months after the onset of symptoms. In their study, Zika virus was undetectable in semen in 95% of men after about 3 months.

“Based on our findings, such late detection seems unusual,” Paz-Vega said. – by Gerard Gallagher

Reference:

Paz-Bailey G, et al. Abstract 1055LB. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 13-16, 2017; Seattle.

Paz-Bailey G, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1613108.

Disclosure: One researcher reports receiving grant support from the CDC during the study.

Perspective
  • People want to know when they are not contagious anymore. If you get Zika or even just travel to an endemic area, you want to know when you can no longer worry about giving it to your partner. This is especially true for couples trying to have a child due to the obvious consequences. This study not only looked for the virus using PCR but also cultured the virus. Culture is a more reliable way of asking if there is a living virus that can infect another person. Her data suggest the CDC recommendation to wait 6 months is safe.

    • David L. Thomas, MD, MPH
    • Chief, division of infectious diseases
      Professor of medicine
      Johns Hopkins School of Medicine
  • Disclosures: Thomas reports no relevant financial disclosures.

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