Pregnancy May Be Independently Associated With Prolonged Detection of Zika Virus RNA

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Age and days post-symptom onset at enrollment were not different between pregnant and nonpregnant women.
Age and days post-symptom onset at enrollment were not different between pregnant and nonpregnant women.

Zika virus RNA may stay in serum longer in pregnant women than in nonpregnant women of similar ages, according to a study published in Clinical Infectious Diseases.

Several cases have reported longer-than-expected window for detection of Zika virus RNA in pregnant women. Because existing evidence is limited to case reports without nonpregnant controls, it is unknown whether pregnancy is independently associated with prolonged detection of Zika virus RNA. This cohort study used data from the Zika Virus Persistence Study (ZiPer) to test whether symptomatic pregnant women have longer detection of Zika virus RNA than symptomatic, nonpregnant women of similar ages.

Puerto Rican women (n=58) aged 18 to 39 years who reported a recent Zika-like illness were included in this analysis; 9 were pregnant. Serum, urine, saliva, and vaginal secretions were collected weekly for the first month and at 2, 4, and 6 months postenrollment. For participants in whom Zika virus RNA was detected at week 4, biweekly collection continued until all specimens tested negative via RT-PCR. "Time-to-loss" of Zika virus RNA was defined as the number of days between onset of Zika virus symptoms and the first nonpositive result.

There were no reported differences in symptom frequency, except nonpregnant women were more likely to report fever than pregnant women (78% vs 22%; P =.003). The last serum specimen collected from pregnant women was an average of 169 days after illness onset; nonpregnant women provided serum until 152 days after illness onset (P =.26). All birth outcomes were normal, other than 1 that resulted in fetal death at 24 weeks' gestation.

Throughout the study, Zika virus RNA was detected in the serum of all 9 pregnant women and almost all nonpregnant women (96%). Zika virus RNA detection in urine was more common among nonpregnant women than pregnant women (49% vs 11%; P =.06). The median interval between the last positive specimen collected and the first subsequent specimen that tested nonpositive for Zika virus RNA was not significantly different between pregnant and nonpregnant women (14 days vs 17 days; P =.85).

Three different statistical models consistently demonstrated a significantly longer median duration among pregnant women. The Turnbull model-derived median time to loss of detectable Zika virus RNA in serum was about 3 times longer among pregnant women than nonpregnant women (40 vs 14 days; P <.001). In addition, a sensitivity analysis using the last-positive RT polymerase chain reaction result to estimate duration showed that pregnant women had significantly longer duration of detectable Zika virus RNA than nonpregnant women. When correcting for women who were intermittent shedders, a statistically significant difference in duration between pregnant and nonpregnant women remained (P =.01).

Because this study only included symptomatic women, results may not be generalized to women with asymptomatic infections.

Findings continue to support the Centers for Disease Control and Prevention's current recommendations, and the study authors conclude that "further research to identify definitively the mechanism of prolonged ZIKA RNA detection could assist in development of interventions to reduce risk of fetal infection."

Reference

Lozier MJ, Rosenberg ES, Doyle K, et al. Prolonged detection of Zika virus nucleic acid among symptomatic pregnant women: a cohort study [published online March 9, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy209

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