scholarly journals Reassessment of the risk of birth defects due to Zika virus in Guadeloupe, 2016

2021 ◽  
Vol 15 (3) ◽  
pp. e0009048
Author(s):  
Anna L. Funk ◽  
Bruno Hoen ◽  
Ingrid Vingdassalom ◽  
Catherine Ryan ◽  
Philippe Kadhel ◽  
...  

Background In the French Territories in the Americas (FTA), the risk of birth defects possibly associated with Zika virus (ZIKV) infection was 7.0% (95%CI: 5.0 to 9.5) among foetuses/infants of 546 women with symptomatic RT-PCR confirmed ZIKV infection during pregnancy. Many of these defects were isolated measurement-based microcephaly (i.e. without any detected brain or clinical abnormalities) or mild neurological conditions. We wanted to estimate the proportion of such minor findings among live births of women who were pregnant in the same region during the outbreak period but who were not infected with ZIKV. Methods In Guadeloupe, pregnant women were recruited at the time of delivery and tested for ZIKV infection. The outcomes of live born infants of ZIKV non-infected women were compared to those of ZIKV-exposed live born infants in Guadeloupe, extracted from the FTA prospective cohort. Results Of 490 live born infants without exposure to ZIKV, 42 infants (8.6%, 95%CI: 6.2–11.4) had mild abnormalities that have been described as ‘potentially linked to ZIKV infection’; all but one of these was isolated measurement-based microcephaly. Among the 241 live born infants with ZIKV exposure, the proportion of such abnormalities, using the same definition, was similar (6.6%, 95%CI: 3.8–10.6). Conclusions Isolated anthropometric abnormalities and mild neurological conditions were as prevalent among infants with and without in-utero ZIKV exposure. If such abnormalities had not been considered as ‘potentially linked to ZIKV’ in the original prospective cohort in Guadeloupe, the overall estimate of the risk of birth defects considered due to the virus would have been significantly lower, at approximately 1.6% (95% CI: 0.4–4.1). Trial registration ClinicalTrials.gov (NCT02916732)

2022 ◽  
Author(s):  
Augustina Delaney ◽  
Samantha M. Olson ◽  
Nicole M. Roth ◽  
Janet D. Cragan ◽  
Shana Godfred-Cato ◽  
...  

Abstract During the Centers for Disease Control and Prevention’s Zika Virus Response, birth defects surveillance programs adapted to monitor birth defects potentially related to Zika virus (ZIKV) infection during pregnancy. Pregnancy outcomes occurring during January 2016-June 2017 in 22 U.S. states and territories were used to estimate the prevalence of those brain and eye defects potentially related to ZIKV. Jurisdictions were divided into three groups: areas with widespread ZIKV transmission, areas with limited local ZIKV transmission, and areas without local ZIKV transmission. Prevalence estimates for selected brain and eye defects and microcephaly per 10,000 live births were estimated. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated using Poisson regression for areas with widespread and limited ZIKV transmission compared to areas without local ZIKV transmission. Defects with significantly higher prevalence in areas of widespread transmission were pooled, and PRs were calculated by quarter, comparing subsequent quarters to the first quarter (January – March 2016). Nine defects had significantly higher prevalence in areas of widespread transmission. The highest PRs were seen in intracranial calcifications (PR=12.6, 95% CI [7.4, 21.3]), chorioretinal abnormalities (12.5 [7.1, 22.3]), brainstem abnormalities (9.3, [4.7, 18.4]), and cerebral/cortical atrophy (6.7, [4.2, 10.8]). The PR of the nine pooled defects was significantly higher in three quarters in areas with widespread transmission. The largest difference in prevalence was observed for defects consistently reported in infants with congenital ZIKV infection. Birth defects surveillance programs could consider monitoring a subset of birth defects potentially related to ZIKV in pregnancy.


2017 ◽  
Vol 22 (44) ◽  
Author(s):  
Claude Flamand ◽  
Camille Fritzell ◽  
Séverine Matheus ◽  
Maryvonne Dueymes ◽  
Gabriel Carles ◽  
...  

Zika virus (ZIKV) infection has been associated with complications during pregnancy. Although the presence of symptoms might be a risk factor for complication, the proportion of ZIKV-infected pregnant women with symptoms remains unknown. Following the emergence of ZIKV in French Guiana, all pregnancies in the territory were monitored by RT-PCR and/or detection of ZIKV antibodies. Follow-up data collected during pregnancy monitoring interviews were analysed from 1 February to 1 June 2016. We enrolled 3,050 pregnant women aged 14–48 years and 573 (19%) had laboratory-confirmed ZIKV infection. Rash, arthralgia, myalgia and conjunctival hyperaemia were more frequently observed in ZIKV-positive women; 23% of them (95% confidence interval (CI): 20–27) had at least one symptom compatible with ZIKV infection. Women 30 years and older were significantly more likely to have symptoms than younger women (28% vs 20%). The proportion of symptomatic infections varied from 17% in the remote interior to 35% in the urbanised population near the coast (adjusted risk ratio: 1.6; 95% CI: 1.4–1.9.). These estimates put findings on cohorts of symptomatic ZIKV-positive pregnant women into the wider context of an epidemic with mainly asymptomatic infections. The proportion of symptomatic ZIKV infections appears to vary substantially between populations.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S47-S47
Author(s):  
Margaret (Peggy) Honein ◽  
Marcela Mercado ◽  
Suzanne Gilboa ◽  
Diana Valencia ◽  
Marcela Daza ◽  
...  

Abstract Background Proyecto Vigilancia de Embarazadas con Zika (VEZ) was an intensified surveillance system built upon existing national surveillance of pregnant women with symptoms of Zika virus (ZIKV) disease and conducted in three Colombian cities with a high prevalence of Zika. This analysis of data from VEZ estimates the risk of Zika-associated birth defects among pregnant women with symptoms of ZIKV disease, and among a subset with laboratory evidence of possible ZIKV infection during pregnancy. Methods During April–November 2016, pregnant women were enrolled if they were reported to the surveillance system (Sivigila) or visited participating clinics with symptoms of ZIKV disease. Maternal and pediatric data were abstracted from prenatal care, ultrasound, and delivery records, as well as from pediatric or specialist visit records. Available maternal and infant specimens were tested for the presence of ZIKV RNA and/or anti-ZIKV immunoglobulin (IgM) antibodies. Results Of 1,223 women enrolled, 47.8% and 34.3% reported first or second trimester symptom onset, respectively. Of 381 pregnancies with maternal and/or infant specimens tested, 108 (29%) had laboratory evidence of possible ZIKV infection during pregnancy; half of these (53.3%) were positive for ZIKV RNA only, 37.4% for IgM antibodies only, and 9.3% for both. Of 1,190 of pregnancies with known outcome, 63 (5%) had Zika-associated brain or eye defects; among the subset with any laboratory evidence, 12 (11%) had Zika-associated brain or eye defects. The prevalence of Zika-associated brain or eye defects was 5.9% (35/593) and 4.5% (19/423) among pregnancies with symptom onset in the first and second trimester, respectively. Conclusion Among pregnant women with symptoms of ZIKV disease enrolled during the height of the ZIKV epidemic in Colombia, prevalence of any Zika-associated brain or eye defect was 5%, with a higher prevalence among those with laboratory evidence of possible ZIKV infection. Rapid enhancements to Colombia’s national surveillance enabled the estimation of the risk of birth defects associated with ZIKV disease in pregnancy. Disclosures All Authors: No reported Disclosures.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S47-S47
Author(s):  
Anna Louise Funk ◽  
Bruno Hoen ◽  
Benoit Tressières ◽  
Ingrid Vingadassalom ◽  
Eustase Janky ◽  
...  

Abstract Background In the French Territories in the Americas (FTA), the risk of birth defects possibly associated with Zika virus (ZIKV) infection was estimated at 7% among fetuses/infants in a cohort of 546 women who developed a symptomatic RT-PCR confirmed ZIKV infection during pregnancy (NEJM 2018;378:985–94). There was no concomitant prospective cohort of pregnant women without ZIKV infection to use as a control group. Methods In Guadeloupe, one of the 3 FTAs that participated in the FTA cohort study, pregnant women were recruited at the time of delivery and tested for ZIKV infection. Women who had a confirmed negative IgG serology test for ZIKV at delivery and no other positive ZIKV test during pregnancy were considered to be ZIKV noninfected. Information on the course of the pregnancy was collected retrospectively and outcomes of live born infants of ZIKV noninfected women were analyzed, using the same definition criteria as those used for the FTA cohort study. Pregnancy outcomes were compared with those of the 241 ZIKV-exposed live born infants in Guadeloupe, extracted from the FTA cohort. Results Of the 490 live born infants without in-utero exposure to ZIKV, 42 infants (8.6%) had neurological abnormalities that were described as “potentially linked to ZIKV infection”; all but one of these were microcephaly without any other brain or clinical abnormalities. The proportion of such abnormalities was not statistically different from that observed in the 241 live born infants with ZIKV exposure (6.6%, P = 0.36). When re-considering the combined 8 fetuses and 241 infants of women with confirmed ZIKV infection in Guadeloupe from the FTA cohort, only two (0.8%) live born infants and three (1.2%) medically aborted fetuses had birth defects that could still be linked to ZIKV infection. Conclusion Isolated anthropometric and other mild neurological abnormalities had the same prevalence among live born infants with and without in utero ZIKV exposure. The high prevalence of isolated microcephaly among ZIKV noninfected women in our study population suggests that the sensitive definition for microcephaly, using a −2 SD cut-off with international growth curves, may lead to an overestimate of the rate of neurological complications of ZIKV infection during pregnancy. Disclosures All Authors: No reported Disclosures.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S992-S992
Author(s):  
Sarah Pellerin ◽  
Anna Louise Funk ◽  
Benoit Tressières ◽  
Stéphanie Guyomard ◽  
Fatiha Najioullah ◽  
...  

Abstract Background Adverse fetal outcomes and infant birth defects may develop following Zika virus (ZIKV) infection during pregnancy, especially if this occurs in the first trimester. The aim of this study was to assess the relationship between plasma ZIKV load at the time of acute symptoms and (1) the rate and severity of birth defects in neonates born to mothers who had presented with ZIKV infection during pregnancy, and (2) clinical severity of maternal ZIKV infection. Methods Within a cohort of pregnant women living in the French territories in the Americas and exposed to ZIKV during the 2016 outbreak, we analyzed the data of women who developed a symptomatic infection confirmed by a positive plasma ZIKV RT–PCR, using the RealStar Zika virus RT–PCR Kit (Altona Diagnostics, Hamburg, Germany). Plasma ZIKV load quantification was based on the number of cycle times (CT) at which ZIKV RNA was detected (lower CTs indicating a higher viral load). Variables indicating clinical severity of infection included the number of symptoms experienced and the severity of rash. Birth defects possibly linked to ZIKV infection were defined as microcephaly, brain imaging abnormalities, and central nervous system dysfunction. Multivariable logistic regression was used to examine whether potentially ZIKV-related abnormalities were linked to changes in CT, and multivariable linear regression was used to identify clinical correlates with CT value. Results Of the 277 live-born neonates who were born to mothers who met the selection criteria, 15 (5.4%) had abnormalities possibly linked to ZIKV infection. The median (IQR) ZIKV RT–PCR CT values were similar, with 31.4 (29.3–33.2) and 31.8 (30.0–33.0), in women delivering normal neonates and those delivering neonates with defects, respectively (OR: 1.04, P = 0.685). Plasma ZIKV load was lower with every day since first symptom onset, and higher with each additional symptom experienced, as indicated by changes in CT of 0.3 (95% CI: 0.2 ‒ 0.5, P < .001) and −0.3 (95% CI: −0.5 ‒ −0.1, P = 0.002) for each unit, respectively. Conclusion No relationship was observed between plasma ZIKV load and abnormal pregnancy outcomes but higher plasma ZIKV load was associated with a more recent and severe maternal ZIKV infection. Disclosures All authors: No reported disclosures.


Author(s):  
Elijane de Fátima Redivo ◽  
Camila Helena Bôtto Menezes ◽  
Márcia da Costa Castilho ◽  
Marianna Facchinetti Brock ◽  
Evela da Silva Magno ◽  
...  

The epidemic transmission of Zika virus (ZIKV) in Brazil has been identified as a cause of microcephaly and other neurological malformations in babies of ZIKV-infected women. This study provides a descriptive analysis, since the onset of symptoms to the delivery, of a cohort who were registered as having ZIKV infection in pregnancy, from November 2015 to December 2016. Suspected cases were registered at a referral center for infectious and tropical diseases in Manaus, in the Brazilian Amazonian region. A total of 834 women with suspected ZIKV in pregnancy were included, of whom 91.4% had confirmed pregnancy. Reverse-transcriptase polymerase chain reaction (RT-PCR) confirmed ZIKV infection in 42.2% of the cohort. In 35.2% of the cohort, ZIKV was the sole infection identified. Severe adverse pregnancy outcomes (abortion, stillbirth, or microcephaly) were observed in both RT-PCR ZIKV-positive (4.96%) and ZIKV-negative (2.15%) cases. Women with suspected ZIKV infection were much more likely to have adverse pregnancy outcomes if they were symptomatic during the first trimester of pregnancy (odds ratio 10.5; 95% confidence interval 4.0&ndash;27.0; p&lt;0.001). Among pregnant women with suspected ZIKV infection, the occurrence of symptoms in the first trimester is associated with an especially high risk of severe adverse pregnancy outcomes.


Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 123
Author(s):  
Elizabeth Centeno-Tablante ◽  
Melisa Medina-Rivera ◽  
Julia L. Finkelstein ◽  
Heather S. Herman ◽  
Pura Rayco-Solon ◽  
...  

We systematically searched regional and international databases and screened 1658 non-duplicate records describing women with suspected or confirmed ZIKV infection, intending to breastfeed or give breast milk to an infant to examine the potential of mother-to-child transmission of Zika virus (ZIKV) through breast milk or breastfeeding-related practices. Fourteen studies met our inclusion criteria and inform this analysis. These studies reported on 97 mother–children pairs who provided breast milk for ZIKV assessment. Seventeen breast milk samples from different women were found positive for ZIKV via RT-PCR, and ZIKV replication was found in cell cultures from five out of seven breast milk samples from different women. Only three out of six infants who had ZIKV infection were breastfed, no evidence of clinical complications was found to be associated with ZIKV RNA in breast milk. This review updates our previous report by including 12 new articles, in which we found no evidence of ZIKV mother-to-child transmission through breast milk intake or breastfeeding. As the certainty of the present evidence is low, additional studies are still warranted to determine if ZIKV can be transmitted through breastfeeding.


2018 ◽  
Author(s):  
Anna S. Jaeger ◽  
Reyes A. Murreita ◽  
Lea R. Goren ◽  
Chelsea M. Crooks ◽  
Ryan V. Moriarty ◽  
...  

AbstractCongenital Zika virus (ZIKV) infection was first linked to birth defects during the American outbreak 1–3. It has been proposed that mutations unique to the Asian/American-genotype explain, at least in part, the ability of Asian/American ZIKV to cause congenital Zika syndrome (CZS) 4,5. Recent studies identified mutations in ZIKV infecting humans that arose coincident with the outbreak in French Polynesia and were stably maintained during subsequent spread to the Americas 5. Here we show that African ZIKV can infect and harm fetuses and that the S139N mutation that has been associated with the American outbreak is not essential for fetal harm. Our findings, in a vertical transmission mouse model, suggest that ZIKV will remain a threat to pregnant women for the foreseeable future, including in Africa, southeast Asia, and the Americas. Additional research is needed to better understand the risks associated with ZIKV infection during pregnancy, both in areas where the virus is newly endemic and where it has been circulating for decades.


2019 ◽  
Vol 93 (11) ◽  
Author(s):  
Angelica Cifuentes Kottkamp ◽  
Elfie De Jesus ◽  
Rebecca Grande ◽  
Julia A. Brown ◽  
Adam R. Jacobs ◽  
...  

ABSTRACT Arthropod-borne viruses represent a significant public health threat worldwide, yet there are few antiviral therapies or prophylaxes targeting these pathogens. In particular, the development of novel antivirals for high-risk populations such as pregnant women is essential to prevent devastating disease such as that which was experienced with the recent outbreak of Zika virus (ZIKV) in the Americas. One potential avenue to identify new and pregnancy-acceptable antiviral compounds is to repurpose well-known and widely used FDA-approved drugs. In this study, we addressed the antiviral role of atovaquone, an FDA Pregnancy Category C drug and pyrimidine biosynthesis inhibitor used for the prevention and treatment of parasitic infections. We found that atovaquone was able to inhibit ZIKV and chikungunya virus virion production in human cells and that this antiviral effect occurred early during infection at the initial steps of viral RNA replication. Moreover, we were able to complement viral replication and virion production with the addition of exogenous pyrimidine nucleosides, indicating that atovaquone functions through the inhibition of the pyrimidine biosynthesis pathway to inhibit viral replication. Finally, using an ex vivo human placental tissue model, we found that atovaquone could limit ZIKV infection in a dose-dependent manner, providing evidence that atovaquone may function as an antiviral in humans. Taken together, these studies suggest that atovaquone could be a broad-spectrum antiviral drug and a potential attractive candidate for the prophylaxis or treatment of arbovirus infection in vulnerable populations, such as pregnant women and children. IMPORTANCE The ability to protect vulnerable populations such as pregnant women and children from Zika virus and other arbovirus infections is essential to preventing the devastating complications induced by these viruses. One class of antiviral therapies may lie in known pregnancy-acceptable drugs that have the potential to mitigate arbovirus infections and disease, yet this has not been explored in detail. In this study, we show that the common antiparasitic drug atovaquone inhibits arbovirus replication through intracellular nucleotide depletion and can impair ZIKV infection in an ex vivo human placental explant model. Our study provides a novel function for atovaquone and highlights that the rediscovery of pregnancy-acceptable drugs with potential antiviral effects can be the key to better addressing the immediate need for treating viral infections and preventing potential birth complications and future disease.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S56-S57 ◽  
Author(s):  
Matthew Lozier ◽  
Eli Rosenberg ◽  
Katherine Doyle ◽  
Laura Adams ◽  
Liore Klein ◽  
...  

Abstract Background Identifying factors associated with time-to-loss of Zika virus (ZIKV) RNA in serum and semen is important to inform diagnostic testing and prevention recommendations. CDC currently recommends RT-PCR testing of serum up to two weeks after symptom onset. We evaluated such associations among participants of the Zika virus Persistence (ZiPer) study in Puerto Rico. Methods Patients presenting for care with Zika-like illness and ZIKV RNA detected by RT-PCR in serum or urine (index cases) were offered study participation. Index cases’ household members were offered study participation, and those with detectable ZIKV RNA were eligible for the prospective cohort. Serum and semen were collected weekly for the first month, and biweekly thereafter for participants with detectable ZIKV RNA in any fluid and at 2, 4, and 6 months post-enrollment for all others. We used chi-squared and Fischer’s exact tests to assess if detecting ZIKV RNA in specific specimens at any point was associated with sex, age, Zika-like symptoms (rash, fever, arthralgia, or conjunctivitis), or pregnancy. We performed Weibull regression models to estimate time-to-loss of ZIKV RNA in days post symptom onset (DPO) and evaluated associations between covariates and duration of detection. Results Among 295 participants, 260 (88.1%) had ZIKV RNA detected in serum at any point. Participants aged ≥18 years (n = 244) had a significantly longer median time-to-loss of ZIKV RNA in serum than participants aged &lt; 18 years (n = 50) (13.1 vs. 7.8 DPO, respectively; P = 0.003) (Figure 1). Among women aged 18–39 years (n = 60), pregnant women (n = 9) had a significantly longer median time-to-loss of ZIKV RNA in serum than non-pregnant women (n = 51) (37.4 vs. 15.5 DPO, respectively; P = 0.0005) (Figure 2). The proportion of men who had detectable ZIKV RNA in semen at any point was significantly higher among men with conjunctivitis (47 of 82) than among men without conjunctivitis (3 of 14) (P = 0.01). No other associations were significant. Conclusion Time-to-loss of ZIKV RNA in serum was longer among adults than children, and conjunctivitis was associated with detecting ZIKV RNA in semen. This study provides evidence that time-to-loss of ZIKV RNA is longer among pregnant women than non-pregnant women. Findings may inform the recommended period to test pregnant women for ZIKV using RT-PCR. Disclosures All authors: No reported disclosures.


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