1873. Pregnancy and Birth Outcomes Among Colombian Women with Zika Virus Disease in 3 Surveillance Sites, Proyecto Vigilancia de Embarazadas con Zika

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.

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

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009048 ◽

2021 ◽

Vol 15 (3) ◽

pp. e0009048

Author(s):

Anna L. Funk ◽

Bruno Hoen ◽

Ingrid Vingdassalom ◽

Catherine Ryan ◽

Philippe Kadhel ◽

...

Keyword(s):

Pregnant Women ◽

Birth Defects ◽

Zika Virus ◽

Prospective Cohort ◽

Trial Registration ◽

Rt Pcr ◽

Zikv Infection ◽

Live Births ◽

Outbreak Period ◽

Neurological Conditions

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)

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1874. Comparison of the Risk of Birth Defects in Live Births From Pregnant Women Infected and Not Infected by Zika Virus in Guadeloupe, 2016–2017

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz359.104 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S47-S47

Author(s):

Anna Louise Funk ◽

Bruno Hoen ◽

Benoit Tressières ◽

Ingrid Vingadassalom ◽

Eustase Janky ◽

...

Keyword(s):

Cohort Study ◽

Pregnant Women ◽

Birth Defects ◽

Zika Virus ◽

Growth Curves ◽

Neurological Complications ◽

In Utero ◽

Control Group ◽

Zikv Infection ◽

Neurological Abnormalities

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.

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Zika viruses of both African and Asian lineages cause fetal harm in a vertical transmission model

10.1101/387118 ◽

2018 ◽

Cited By ~ 1

Author(s):

Anna S. Jaeger ◽

Reyes A. Murreita ◽

Lea R. Goren ◽

Chelsea M. Crooks ◽

Ryan V. Moriarty ◽

...

Keyword(s):

Mouse Model ◽

Vertical Transmission ◽

Birth Defects ◽

Asian American ◽

Zika Virus ◽

French Polynesia ◽

Transmission Model ◽

Foreseeable Future ◽

Zikv Infection ◽

Congenital Zika Syndrome

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.

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Atovaquone Inhibits Arbovirus Replication through the Depletion of Intracellular Nucleotides

Journal of Virology ◽

10.1128/jvi.00389-19 ◽

2019 ◽

Vol 93 (11) ◽

Cited By ~ 12

Author(s):

Angelica Cifuentes Kottkamp ◽

Elfie De Jesus ◽

Rebecca Grande ◽

Julia A. Brown ◽

Adam R. Jacobs ◽

...

Keyword(s):

Viral Replication ◽

Pregnant Women ◽

Vulnerable Populations ◽

Zika Virus ◽

Ex Vivo ◽

Pyrimidine Biosynthesis ◽

Zikv Infection ◽

Antiviral Therapies ◽

Virion Production ◽

Women And Children

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.

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Review of neuroimaging findings in congenital Zika virus syndrome and its relation to the time of infection

The Neuroradiology Journal ◽

10.1177/1971400919896264 ◽

2020 ◽

Vol 33 (2) ◽

pp. 152-157 ◽

Cited By ~ 1

Author(s):

Graciane Radaelli ◽

Magda Lahorgue Nunes ◽

Ricardo Bernardi Soder ◽

Júlia Monteiro de Oliveira ◽

Fernanda Thays Konat Bruzzo ◽

...

Keyword(s):

Zika Virus ◽

Web Of Science ◽

Case Series ◽

Cochrane Library ◽

Second Trimester ◽

Maternal Infection ◽

Zikv Infection ◽

Chi Square ◽

Gestational Period ◽

Time Of Infection

Background Many original articles and case series have been published emphasizing the neuroimaging findings of congenital Zika virus (ZIKV) infection. The majority of these studies do not follow a neuroradiological methodology to describe malformations and brain abnormalities resulting from ZIKV infection. The cause-and-effect correlation between the gestational period of maternal infection and the severity of encephalic changes at birth has rarely been reported. A systematic literature review was conducted on the neuroimaging findings in children affected with microcephaly due to ZIKV. Methods PubMed, Cochrane Library and Web of Science were searched for full-text articles published up to July 2019. Duplicate entries were removed. Two independent reviewers performed a quality assessment of all the studies included. Results A total of 2214 publications were identified. Of these 2170 were excluded by analysis of titles and abstracts, resulting in the inclusion of only eight articles. Chi-square and Fisher’s exact tests were performed with a 95% confidence interval to verify the statistically significant differences in the neuroradiological findings between the cases of ZIKV infection in the first or second trimester of gestation. The studies published so far have described image abnormalities at random, without utilizing any pre-established neuroradiological criteria, and imaging modalities with different sensitivity and accuracy have been used, which jeopardizes a reliable and adequate statistical analysis. Conclusions Neuroimaging abnormalities are much more prevalent and severe when the infection by ZIKV is contracted in the first or second trimester of pregnancy.

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Risk Factors Associated with Persistence of Zika Virus Nucleic Acid in Serum and Semen

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx162.133 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S56-S57 ◽

Cited By ~ 1

Author(s):

Matthew Lozier ◽

Eli Rosenberg ◽

Katherine Doyle ◽

Laura Adams ◽

Liore Klein ◽

...

Keyword(s):

Pregnant Women ◽

Median Time ◽

Symptom Onset ◽

Zika Virus ◽

Diagnostic Testing ◽

Study Participation ◽

Rt Pcr ◽

Weibull Regression ◽

Factors Associated ◽

Index Cases

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 < 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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Seroprevalence of parvovirus B19 IgG and IgM antibodies among pregnant women in Oyo State, Nigeria

The Journal of Infection in Developing Countries ◽

10.3855/jidc.3157 ◽

2013 ◽

Vol 7 (12) ◽

pp. 946-950 ◽

Cited By ~ 3

Author(s):

Iyanda Abiodun ◽

Oluyinka Oladele Opaleye ◽

Olusola Ojurongbe ◽

Ademola Hezekiah Fagbami

Keyword(s):

Pregnant Women ◽

Parvovirus B19 ◽

First Trimester ◽

Intrauterine Fetal Death ◽

Human Parvovirus B19 ◽

Second Trimester ◽

Igg Antibody ◽

Southwestern Nigeria ◽

Igm Antibodies ◽

Wide Range

Introduction: Human parvovirus B19 causes a wide range of complications in pregnant women including abortion, severe fetal anemia, non-immune hydrops fetalis, and even intrauterine fetal death. However, there is a dearth of information on the prevalence of the virus among pregnant women in southwestern Nigeria. Methodology: Blood samples were collected from 231 pregnant women and screened for antibodies to human parvovirus B19 IgM and IgG using an enzyme immunosorbent assay kits. Results: Of the 231 women, 31 were in their first trimester, 146 were in their second trimester, and 54 were in their third trimester. Forty-five (20%) were positive for parvovirus B19 IgG antibodies, 10 (4%) were positive for parvovirus B19 IgM antibodies, and 176 (76%) had no detectable parvovirus B19 antibodies. Twenty-eight (19%) of the 146 pregnant women in their second trimester were positive for parvovirus B19 IgG antibody while three (2%) of the 146 were positive for parvovirus B19 IgM antibody. Conclusions: It is evident that there is a high prevalence of human parvovirus B19 among pregnant women in south-western Nigeria. This suggests that there is an active transmission of the virus in the community; it is therefore necessary to conduct more studies on the virus in pregnant women in Nigeria to ascertain its effect on the fetus.

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Prevalence of individual brain and eye defects potentially related to Zika virus in pregnancy in 22 U.S. states and territories, January 2016 - June 2017

10.21203/rs.3.rs-1189990/v1 ◽

2022 ◽

Author(s):

Augustina Delaney ◽

Samantha M. Olson ◽

Nicole M. Roth ◽

Janet D. Cragan ◽

Shana Godfred-Cato ◽

...

Keyword(s):

Birth Defects ◽

Zika Virus ◽

Cortical Atrophy ◽

Zikv Infection ◽

Live Births ◽

Prevalence Estimates ◽

Surveillance Programs ◽

Prevalence Ratios ◽

Cerebral Cortical Atrophy ◽

In Pregnancy

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.

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Trimester-specific Zika virus infection affects placental responses in women

10.1101/727081 ◽

2019 ◽

Author(s):

Fok-Moon Lum ◽

Vipin Narang ◽

Susan Hue ◽

Jie Chen ◽

Naomi McGovern ◽

...

Keyword(s):

Birth Defects ◽

Zika Virus ◽

Cellular Response ◽

Prenatal Screening ◽

Acute Infection ◽

Transcriptomic Analysis ◽

Placental Development ◽

Zikv Infection ◽

Hofbauer Cells ◽

Screening Procedures

AbstractZika virus (ZIKV) infection during pregnancy is associated with neurologic birth defects, but the effects on placental development are unclear. Full-term placentas from three women, each infected with ZIKV during specific pregnancy trimesters, were harvested for anatomic, immunologic and transcriptomic analysis. In this study, each woman exhibited a unique immune response, but they collectively diverged from healthy controls with raised IL-1RA, IP-10, EGF and RANTES expression, and neutrophil numbers during the acute infection phase. Although ZIKV NS3 antigens co-localized to placental Hofbauer cells, the placentas showed no anatomical defects. Transcriptomic analysis of samples from the placentas revealed that infection during trimester 1 caused a disparate cellular response centered on differential eIF2 signaling, mitochondrial dysfunction and oxidative phosphorylation. These findings should translate to improve clinical prenatal screening procedures for virus-infected pregnant patients.

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Survey on neutralizing antibodies against Zika virus eighteen months post-outbreak in two southern Thailand communities

10.21203/rs.3.rs-34709/v4 ◽

2020 ◽

Author(s):

Theerut Densathaporn ◽

Rassamee Sangthong ◽

Monvaris Sakolnapa ◽

Smonrapat Surasombatpattana ◽

Marisa Kemapunmanus ◽

...

Keyword(s):

General Population ◽

Pregnant Women ◽

Zika Virus ◽

Neutralizing Antibodies ◽

Zikv Infection ◽

Factors Associated ◽

Neutralizing Capacity ◽

Southern Thailand ◽

Outbreak Areas ◽

Index Cases

Abstract Background: In 2016 and 2017, Zika virus (ZIKV) infection outbreaks occurred in two communities in southern Thailand. This re-immerging infection can widely spread by mosquito bites and cause serious complications in a central nervous system among children born to infected mothers. Thus, they should be protected. This study aims to (1) To determine the prevalence of neutralizing ZIKV antibodies in the post-outbreak areas among the general population and pregnancy women residing at various distances from the houses of the nearest index patients; (2) To examine the cross-neutralizing capacity of antibodies against ZIKV on other flaviviruses commonly found in the study areas; (3) To identify factors associated with the presence of neutralizing ZIKV antibodies.Methods: The two post-outbreak communities were visited at 18 months after the outbreaks. We enrolled (1) 18 confirmed ZIKV infected (index) cases, (2) sample of 554 neighbors in the outbreak areas who lived at various distances from the index patients’ houses, (3) 190 residents of non-outbreak areas, and (4) all pregnant women regardless of gestational age residing in the study areas (n = 805). All serum specimens underwent the plaque reduction neutralization test (PRNT). Ten randomly selected ZIKV seropositive and ten randomly selected seronegative specimens were tested for dengue virus serotypes 1-4 (DENV1-4) and Japanese encephalitis virus (JEV) antibodies using PRNT90. Serum titer above 1:10 was considered positive. Multiple logistic regression was used to assess factors associated with seropositivity.Results: Out of all 18 index cases, 9 remained seropositive. The seroprevalence (95% CI) in the two outbreak areas were 43.7% (35.9-51.6%) and 29.7% (23.3-36.0%) in general population, and 24.3% (20.1-28.8%) and 12.8% (9.7-16.5%) in pregnant women. Multivariate analysis showed that seropositivity was independent of the distance gradient from the index’s houses. However, being elderly was associated with seropositivity. DENV1-4 and JEV neutralizing antibodies were present in most ZIKV-positive and negative subsamples.Conclusion: Protective herd immunity for ZIKV infection is inadequate, especially among pregnant women in the two post-outbreak areas in southern Thailand.

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