Prolonged Detection of Zika Virus RNA in Pregnant Women

Meaney‐Delman, Dana; Oduyebo, Titilope; Polen, Kara; White, Jennifer L.; Bingham, Andrea; Slavinski, Sally; Heberlein-Larson, Lea; George, Kirsten St.; Rakeman, Jennifer L.; Hills, Susan L.; Olson, Christine K.; Adamski, Alys; Barlow, Lauren Culver; Lee, Ellen H.; Likos, Anna; Muñoz, Jorge L.; Petersen, Emily E.; Dufort, Elizabeth; Dean, Amy B.; Cortese, Margaret M.; Santiago, Gilberto A.; Bhatnagar, Julu; Powers, Ann M.; Zaki, Sherif R.; Petersen, Lyle R.; Jamieson, Denise J.; Honein, Margaret A.

doi:10.1097/aog.0000000000001625

Cited by 114 publications

(91 citation statements)

References 21 publications

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“…(38) The longest time that a urine RT-PCR test has been reported as positive in pregnancy was 25 days after symptom onset. (39,40) Viraemia in pregnant women can also be prolonged beyond the estimated time frame, with simultaneously negative urine RT-PCR, (39) which suggests a greater persistence of ZIKV in the circulation. The longest reported case of viraemia was up to 70 days, ending only when the pregnancy was terminated; (25) this suggests that continued propagation could occur within the fetoplacental unit, re-infecting the mother, or that the ability of the maternal immune system to clear the virus may be impaired during pregnancy.…”

Section: Diagnosis Of Zikv Infection During Pregnancymentioning

confidence: 99%

“…(25) However, from the limited number of reported cases, prolonged viraemia does not appear to correlate with poor outcomes for the fetus or the pregnancy. (39) In pregnancy, there also appears to be significant variation in the rates of viral clearance from different fluids. In a prospective case series, among 72 ZIKV-confirmed symptomatic women tested by RT-PCR within five days of symptom onset, only 47% of cases were positive for both serum and urine tests, while 83% were positive for serum only and 64% for urine only, (18) which suggests that serum testing has greater sensitivity than urine testing.…”

Section: Diagnosis Of Zikv Infection During Pregnancymentioning

confidence: 99%

“…The shortest reported interval between maternal ZIKV infection and a positive RT-PCR result on amniotic fluid testing was four weeks in a case where no fetal anomalies were detected by USS. (39) Therefore, the Singapore MOH, ACOG and CDC advise that amniocentesis should only be performed after proper counselling and offered on a case-bycase basis, as with other suspected viral infections in pregnancy.…”

Section: Challenges Of Diagnosing and Managing Czs Antenatallymentioning

confidence: 99%

“…The advantage of testing for ZIKV in urine is due to its prolonged presence, lasting for as long as a month after symptom onset in pregnancy. (38)(39)(40) Thus, the testing of more than one type of body fluid could improve diagnostic sensitivity in pregnancy.…”

Section: Diagnosis Of Zikv Infection During Pregnancymentioning

confidence: 99%

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A review of Zika virus infections in pregnancy and implications for antenatal care in Singapore

Lin

Tambyah

Yong

et al. 2017

smedj

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Given the consensus that there is a causal relationship between Zika virus (ZIKV) infection in pregnancy and congenital Zika syndrome (CZS), clinicians must be prepared to manage affected patients despite the numerous gaps in current knowledge. The clinical course in pregnancy appears similar to that in non-pregnant women, although viraemia may be prolonged. ZIKV infection can be diagnosed by serum and urine reverse transcription-polymerase chain reaction, but commercially available serological tests are currently unreliable in dengue-endemic regions. Although vertical transmission can occur at any time during gestation, first-and second-trimester infections have the highest risk of developing central nervous system anomalies. Aberrant fetal growth and pregnancy loss may also occur. Serial ultrasonography should be conducted for infected cases. Without a vaccine, pregnant women should be advised to minimise mosquito bites and reduce sexual transmission risk. Overall, the absolute risk of CZS arising amid a ZIKV outbreak appears relatively low.

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Section: Diagnosis Of Zikv Infection During Pregnancymentioning

confidence: 99%

Section: Diagnosis Of Zikv Infection During Pregnancymentioning

confidence: 99%

Section: Challenges Of Diagnosing and Managing Czs Antenatallymentioning

confidence: 99%

Section: Diagnosis Of Zikv Infection During Pregnancymentioning

confidence: 99%

See 2 more Smart Citations

A review of Zika virus infections in pregnancy and implications for antenatal care in Singapore

Lin

Tambyah

Yong

et al. 2017

smedj

View full text Add to dashboard Cite

show abstract

“…Serum has been the recommended specimen type for molecular diagnosis although Zika viremia is unlikely to persist beyond several days post-onset of illness (11). A few reports have shown higher viral loads and longer duration of positivity in other sample types (12)(13)(14)(15)(16), and two articles have reported prolonged viremia in pregnant women (17,18).…”

mentioning

confidence: 99%

Zika Virus Testing Considerations: Lessons Learned from the First 80 Real-Time Reverse Transcription-PCR-Positive Cases Diagnosed in New York State

et al. 2017

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The performance and interpretation of laboratory tests for Zika virus (ZKV) continue to be evaluated. Serology is cross-reactive, laborious, and frequently difficult to interpret, and serum was initially solely recommended for molecular diagnosis. ZKV testing was initiated in January 2016 in New York State for symptomatic patients, pregnant women, their infants, and patients with Guillain-Barré syndrome who had traveled to areas with ZKV transmission. Subsequently, eligibility was expanded to pregnant women with sexual partners with similar travel histories. Serum and urine collected within 4 weeks of symptom onset or within 6 weeks of travel were tested with real-time reverse transcription-PCR (RT-PCR) assays targeting the ZKV envelope and NS2B genes. In this review of lessons learned from the first 80 positive cases in NYS, ZKV RNA was detected in urine only in 50 patients, in serum only in 19 patients, and in both samples concurrently in 11 patients, with average viral loads in urine a log higher than those in serum. Among 93 positive samples from the 80 patients, 41 were positive on both gene assays, 52 were positive on the envelope only, and none were positive on the NS2B only. Of the 80 infected patients, test results for 74 (93%) would have defined their infection status as not detected or equivocal if the requirement for positive results from two assay targets (two-target-positive requirement) in the initial federal guidance to public health laboratories was enforced, if urine was not tested, or if the extended eligibility time for molecular testing was not implemented. These changes facilitated more extensive molecular diagnosis of ZKV, reducing reliance on time-consuming and potentially inconclusive serology.

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Birth Defects Among Fetuses and Infants of US Women With Evidence of Possible Zika Virus Infection During Pregnancy

Honein

Dawson

Petersen

et al. 2017

JAMA

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716

435

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; for the US Zika Pregnancy Registry Collaboration IMPORTANCE Understanding the risk of birth defects associated with Zika virus infection during pregnancy may help guide communication, prevention, and planning efforts. In the absence of Zika virus, microcephaly occurs in approximately 7 per 10 000 live births. OBJECTIVE To estimate the preliminary proportion of fetuses or infants with birth defects after maternal Zika virus infection by trimester of infection and maternal symptoms. DESIGN, SETTING, AND PARTICIPANTS Completed pregnancies with maternal, fetal, or infant laboratory evidence of possible recent Zika virus infection and outcomes reported in the continental United States and Hawaii from January 15 to September 22, 2016, in the US Zika Pregnancy Registry, a collaboration between the CDC and state and local health departments. EXPOSURES Laboratory evidence of possible recent Zika virus infection in a maternal, placental, fetal, or infant sample. MAIN OUTCOMES AND MEASURES Birth defects potentially Zika associated: brain abnormalities with or without microcephaly, neural tube defects and other early brain malformations, eye abnormalities, and other central nervous system consequences. RESULTS Among 442 completed pregnancies in women (median age, 28 years; range, 15-50 years) with laboratory evidence of possible recent Zika virus infection, birth defects potentially related to Zika virus were identified in 26 (6%; 95% CI, 4%-8%) fetuses or infants. There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%; 95% CI, 4%-9%) pregnant asymptomatic women and 10 of 167 (6%; 95% CI, 3%-11%) symptomatic pregnant women. Of the 26 affected fetuses or infants, 4 had microcephaly and no reported neuroimaging, 14 had microcephaly and brain abnormalities, and 4 had brain abnormalities without microcephaly; reported brain abnormalities included intracranial calcifications, corpus callosum abnormalities, abnormal cortical formation, cerebral atrophy, ventriculomegaly, hydrocephaly, and cerebellar abnormalities. Infants with microcephaly (18/442) represent 4% of completed pregnancies. Birth defects were reported in 9 of 85 (11%; 95% CI, 6%-19%) completed pregnancies with maternal symptoms or exposure exclusively in the first trimester (or first trimester and periconceptional period), with no reports of birth defects among fetuses or infants with prenatal exposure to Zika virus infection only in the second or third trimesters. CONCLUSIONS AND RELEVANCE Among pregnant women in the United States with completed pregnancies and laboratory evidence of possible recent Zika infection, 6% of fetuses or infants had evidence of Zika-associated birth defects, primarily brain abnormalities and microcephaly, whereas among women with first-trimester Zika infection, 11% of fetuses or infants had evidence of Zika-associated birth defects. These findings support the importance of screening pregnant women for Zika virus exposure.

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Prolonged Detection of Zika Virus RNA in Pregnant Women

Cited by 114 publications

References 21 publications

A review of Zika virus infections in pregnancy and implications for antenatal care in Singapore

A review of Zika virus infections in pregnancy and implications for antenatal care in Singapore

Zika Virus Testing Considerations: Lessons Learned from the First 80 Real-Time Reverse Transcription-PCR-Positive Cases Diagnosed in New York State

Birth Defects Among Fetuses and Infants of US Women With Evidence of Possible Zika Virus Infection During Pregnancy

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