Microcephaly Outcomes among Zika Virus–Infected Pregnant Women in Honduras

The impact of Zika virus (ZIKV) infection on pregnancies shows regional variation emphasizing the importance of studies in different geographical areas. We conducted a prospective study in Tegucigalpa, Honduras, recruiting 668 pregnant women between July 20, 2016, and December 31, 2016. We performed Trioplex real-time reverse transcriptase–PCR (rRT-PCR) in 357 serum samples taken at the first prenatal visit. The presence of ZIKV was confirmed in seven pregnancies (7/357, 2.0%). Nine babies (1.6%) had microcephaly (head circumference more than two SDs below the mean), including two (0.3%) with severe microcephaly (head circumference [HC] more than three SDs below the mean). The mothers of both babies with severe microcephaly had evidence of ZIKV infection. A positive ZIKV Trioplex rRT-PCR was associated with a 33.3% (95% CI: 4.3–77.7%) risk of HC more than three SDs below the mean.

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2801. Post-Natal Zika Virus Infection and Impact on Neurodevelopment Among a Cohort of Children in Rural Guatemala

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2478 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S990-S991

Author(s):

Daniel Olson ◽

Molly Lamb ◽

Amy Connery ◽

Kathryn Colborn ◽

Muktha S Natrajan ◽

...

Keyword(s):

Zika Virus ◽

Receptive Language ◽

Fine Motor ◽

Serum Samples ◽

Zikv Infection ◽

Related Factors ◽

Material Support ◽

And Gender ◽

The Impact ◽

Research Grant

Abstract Background The impact of early post-natal Zika virus (ZIKV) infection on neurodevelopment (ND) is unknown. A prospective study of post-natal ZIKV infection in rural Guatemala (ZIKV study) enrolled a cohort of children ages 1–5 years, including children previously enrolled in a dengue virus (DENV) study during the 2015–2016 ZIKV epidemic. We evaluated ND outcomes by age and ZIKV infection status. Methods Subjects enrolled in the ZIKV study June 2017–April 2018 underwent ND testing using the Mullen Scales of Early Learning (MSEL) at baseline and 12 months later. ZIKV/DENV-1/2 FRNT50 was performed on enrollment and on banked serum samples from the 2015 to 2016 subset. ZIKV serostatus and MSEL scores were correlated using multiple linear mixed models, adjusted for age and gender when appropriate, to evaluate their association. Geolocation was used to explore clustering of ZIKV serostatus and MSEL score. Results We enrolled 183 children (43% female, mean age 3.2 years). Of these, 38 (21%) were classified as ZIKV-positive (+), 111 (61%) ZIKV-negative (-), 31 (17%) ZIKV-possible, and 3 (2%) ZIKV-indeterminate. ZIKV(+) cases and higher composite MSEL scores clustered in more densely populated areas (Figure 1). ZIKV(+) serostatus was associated with higher MSEL composite (increase in log score 0.09, P = 0.003) and subdomain scores: fine motor (0.13, P = 0.011), visual reception (0.15, P = 0.002), receptive language (0.09, P = 0.041), gross motor (0.14, P = 0.09), and expressive language (0.09, P = 0.058) (Figure 2). Of the 78 children (43%) with 2015–2016 samples, 46 (59%) remained ZIKV(−), 16 (21%) seroconverted from ZIKV(−) or possible/indeterminate to ZIKV(+), and 16 (21%) were indeterminate when enrolled in the ZIKV study. ZIKV seroconversion was associated with higher composite (0.13, P = 0.02) MSEL scores compared with ZIKV(−). Conclusion In this exploratory analysis, post-natal ZIKV infection was not associated with adverse ND outcomes in children age 1–5 years. Overall, ZIKV(+) status was associated with higher average ND scores than ZIKV(−), and scores decreased with age for most children, independent of ZIKV status. The correlation of ZIKV(+) status and higher MSEL scores may be confounded by geographic-related factors or other confounders. NIAID Contract HHSN272201300015I Task Order HHSN27200013 (Co-PIs: FMM & EJA). Disclosures Flor M. Munoz, M.D, Biocryst: Grant/Research Support; CDC: Research Grant; Moderna: Other Financial or Material Support, Safety Monitoring Board Member/Chair; NIH: Research Grant; Novavax: Research Grant; UP to Date: Author and Editor - Royalties, Other Financial or Material Support.

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Pregnant Women Infected with Zika Virus Show Higher Viral Load and Immunoregulatory Cytokines Profile with CXCL10 Increase

Viruses ◽

10.3390/v13010080 ◽

2021 ◽

Vol 13 (1) ◽

pp. 80

Author(s):

Elizabeth Camacho-Zavala ◽

Clara Santacruz-Tinoco ◽

Esteban Muñoz ◽

Rommel Chacón-Salinas ◽

Ma Isabel Salazar-Sanchez ◽

...

Keyword(s):

Viral Load ◽

Inflammatory Response ◽

Pregnant Women ◽

Inflammatory Cytokines ◽

Zika Virus ◽

Epidemiological Surveillance ◽

Congenital Defects ◽

Serum Samples ◽

Zikv Infection ◽

Anti Inflammatory

Background: Zika virus (ZIKV) infection during pregnancy usually shows only mild symptoms and is frequently subclinical. However, it can be vertically transmitted to the fetus, causing microcephaly and other congenital defects. During pregnancy, the immune environment modifications can alter the response to viruses in general and ZIKV in particular. Objective: To describe the role of pregnancy in the systemic pro- and anti-inflammatory response during symptomatic ZIKV infection. Materials and Methods: A multiplex assay was used to measure 25 cytokines, chemokines, and receptors in 110 serum samples from pregnant and nonpregnant women with and without ZIKV infection with and without symptoms. Samples were collected through an epidemiological surveillance system. Results: Samples from pregnant women with ZIKV infection showed a higher viral load but had similar profiles of inflammatory markers as compared with nonpregnant infected women, except for CXCL10 that was higher in infected pregnant women. Notably, the presence of ZIKV in pregnancy favored a regulatory profile by significantly increasing anti-inflammatory cytokines such as interleukin (IL)-10, receptors IL-1RA, and IL-2R, but only those pro-inflammatory cytokines such as IL-6, interferon (IFN)-α, IFN-γ and IL-17 that are essential for the antiviral response. Interestingly, there were no differences between symptomatic and weakly symptomatic ZIKV-infected groups. Conclusion: Our results revealed a systemic anti-inflammatory cytokine and chemokine profile that could participate in the control of the virus. The anti-inflammatory response in pregnant women infected with ZIKA was characterized by high CXCL10, a cytokine that has been correlated with congenital malformations.

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Social determinants associated with Zika virus infection in pregnant women

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009612 ◽

2021 ◽

Vol 15 (7) ◽

pp. e0009612

Author(s):

Nivison Nery ◽

Juan P. Aguilar Ticona ◽

Claudia Gambrah ◽

Simon Doss-Gollin ◽

Adeolu Aromolaran ◽

...

Keyword(s):

Pregnant Women ◽

Social Determinants ◽

Zika Virus ◽

Maternity Hospital ◽

Cross Sectional Study ◽

Zikv Infection ◽

Cross Sectional ◽

Sociodemographic Determinants ◽

The Impact ◽

The Relationship

This study aims to describe the sociodemographic determinants associated with exposure to Zika Virus (ZIKV) in pregnant women during the 2015–2016 epidemic in Salvador, Brazil. Methods We recruited women who gave birth between October 2015 and January 2016 to a cross-sectional study at a referral maternity hospital in Salvador, Brazil. We collected information on their demographic, socioeconomic, and clinical characteristics, and evaluated their ZIKV exposure using a plaque reduction neutralization test. Logistic regression was then used to assess the relationship between these social determinants and ZIKV exposure status. Results We included 469 pregnant women, of whom 61% had a positive ZIKV result. Multivariate analysis found that lower education (adjusted Prevalence Rate [aPR] 1.21; 95%CI 1.04–1.35) and food insecurity (aPR 1.17; 95%CI 1.01–1.30) were positively associated with ZIKV exposure. Additionally, age was negatively associated with the infection risk (aPR 0.99; 95%CI 0.97–0.998). Conclusion Eve after controlling for age, differences in key social determinants, as education and food security, were associated with the risk of ZIKV infection among pregnant women in Brazil. Our findings elucidate risk factors that can be targeted by future interventions to reduce the impact of ZIKV infection in this vulnerable population.

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Neurodevelopment in Children Exposed to Zika Virus: What Are the Consequences for Children Who Do Not Present with Microcephaly at Birth?

Viruses ◽

10.3390/v13081427 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1427

Author(s):

Paula Sobral da Silva ◽

Sophie Eickmann ◽

Ricardo Ximenes ◽

Celina Martelli ◽

Elizabeth Brickley ◽

...

Keyword(s):

Neurological Examination ◽

Zika Virus ◽

Control Group ◽

P Value ◽

Zikv Infection ◽

Clinical Neurological Examination ◽

Cognitive Delay ◽

Increased Risk ◽

Neurodevelopmental Impairment ◽

The Impact

The relation of Zika virus (ZIKV) with microcephaly is well established. However, knowledge is lacking on later developmental outcomes in children with evidence of maternal ZIKV infection during pregnancy born without microcephaly. The objective of this analysis is to investigate the impact of prenatal exposure to ZIKV on neuropsychomotor development in children without microcephaly. We evaluated 274 children including 235 ZIKV exposed and 39 controls using the Bayley-III Scales of Infant and Toddler Development (BSIDIII) and neurological examination. We observed a difference in cognition with a borderline p-value (p = 0.052): 9.4% of exposed children and none of the unexposed control group had mild to moderate delays. The prevalence of delays in the language and motor domains did not differ significantly between ZIKV-exposed and unexposed children (language: 12.3% versus 12.8%; motor: 4.7% versus 2.6%). Notably, neurological examination results were predictive of neurodevelopmental delays in the BSIDIII assessments for exposed children: 46.7% of children with abnormalities on clinical neurological examination presented with delay in contrast to 17.8% among exposed children without apparent neurological abnormalities (p = 0.001). Overall, our findings suggest that relative to their unexposed peers, ZIKV-exposed children without microcephaly are not at considerably increased risk of neurodevelopmental impairment in the first 42 months of life, although a small group of children demonstrated higher frequencies of cognitive delay. It is important to highlight that in the group of exposed children, an abnormal neuroclinical examination may be a predictor of developmental delay. The article contributes to practical guidance and advances our knowledge about congenital Zika.

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From Mosquito Bites to Sexual Transmission: Evaluating Mouse Models of Zika Virus Infection

Viruses ◽

10.3390/v13112244 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2244

Author(s):

Elizabeth Balint ◽

Amelia Montemarano ◽

Emily Feng ◽

Ali A. Ashkar

Keyword(s):

Mouse Models ◽

Zika Virus ◽

Reproductive Tract ◽

Sexual Transmission ◽

Zikv Infection ◽

Sexually Transmitted ◽

Advantages And Disadvantages ◽

Effective Use ◽

The Impact ◽

Male To Female

Following the recent outbreak of Zika virus (ZIKV) infections in Latin America, ZIKV has emerged as a global health threat due to its ability to induce neurological disease in both adults and the developing fetus. ZIKV is largely mosquito-borne and is now endemic in many parts of Africa, Asia, and South America. However, several reports have demonstrated persistent ZIKV infection of the male reproductive tract and evidence of male-to-female sexual transmission of ZIKV. Sexual transmission may broaden the reach of ZIKV infections beyond its current geographical limits, presenting a significant threat worldwide. Several mouse models of ZIKV infection have been developed to investigate ZIKV pathogenesis and develop effective vaccines and therapeutics. However, the majority of these models focus on mosquito-borne infection, while few have considered the impact of sexual transmission on immunity and pathogenesis. This review will examine the advantages and disadvantages of current models of mosquito-borne and sexually transmitted ZIKV and provide recommendations for the effective use of ZIKV mouse models.

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Zika Virus Serologic Diagnosis by NS1 ELISA in Curacao

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.698 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S302-S303 ◽

Cited By ~ 1

Author(s):

Samantha Manuel ◽

Liane Virginia-Cova ◽

Loubiela Joseph ◽

Chris Roggeveen ◽

Radjin Steingrover

Keyword(s):

Zika Virus ◽

Cross Reactivity ◽

Pregnant Female ◽

Serum Samples ◽

Zikv Infection ◽

Igm Elisa ◽

Pcr Diagnosis ◽

Two Samples ◽

Negative Controls

Abstract Background Zika virus (ZIKV) was introduced in the Caribbean island of Curacao in January 2016. A commercially available ZIKV IgM and IgG ELISA was evaluated on patients that were PCR-positive for ZIKV. Methods ZIKV infection was established by PCR in urine samples. Samples from PCR-positive patients were selected for validation of a ZIKV NS1 IgG and IgM ELISA. Patients with a follow-up sample ≥ 2 weeks after initial presentation were used to assess the sensitivity of the assay. Samples of 15 historical controls with serological evidence of Dengue, Chikungunya or an unrelated viral infection were included to establish specificity and cross-reactivity. Results Fourteen patients with positive ZIKV PCR diagnosis had repeated serum samples drawn ≥ 2 weeks after the initial sample. The combined results of these repeated IgM and IgG tests resulted in a sensitivity of 92%. One pregnant female showed no presence of IgG or IgM in any of the two samples. Testing of the panel of historical ZIKV-negative controls resulted in a specificity of 100% in both the quantitative and semi-quantitative setting of the ELISA. One patient with known high-titers of antibodies against Chikungunya virus in the respective panel displayed borderline reactive results for ZIKV IgG in both quantitative and semi-quantitative setting of the assay. Conclusion In this PCR-positive ZIKV cohort of patients, the newly available ZIKV NS1 ELISA displayed excellent performance characteristics. Cross-reactivity was indicated for Chikungunya in one case. No cross-reactivity was found for Dengue virus infection. One pregnant female showed no signs of developing anti-ZIKV IgM or IgG in this study. In the light of intrauterine pathogenesis, the lack of development of maternal IgG during ZIKV infection is a concern. Disclosures All authors: No reported disclosures.

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Zika Virus Pathogenesis: From Early Case Reports to Epidemics

Viruses ◽

10.3390/v11100886 ◽

2019 ◽

Vol 11 (10) ◽

pp. 886 ◽

Cited By ~ 5

Author(s):

Ryan D. Pardy ◽

Martin J. Richer

Keyword(s):

Risk Factors ◽

Zika Virus ◽

Case Reports ◽

Viral Persistence ◽

The Body ◽

Therapeutic Approaches ◽

Zikv Infection ◽

Congenital Zika Syndrome ◽

Early Case ◽

The Impact

For the first 60 years following its isolation, Zika virus (ZIKV) remained a relatively poorly described member of the Flaviviridae family. However, since 2007, it has caused a series of increasingly severe outbreaks and is now associated with neurological symptoms such as Guillain-Barré syndrome and congenital Zika syndrome (CZS). A number of reports have improved our understanding of rare complications that may be associated with ZIKV infection in adults, the areas of the body to which it spreads, and viral persistence in various tissues. Likewise, studies on the effect of ZIKV infection during pregnancy have identified risk factors for CZS and the impact this syndrome has on early childhood. Understanding these outcomes and the factors that drive ZIKV pathogenesis are key to developing vaccination and therapeutic approaches to avoid these severe and potentially debilitating symptoms.

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Clinical manifestations and perinatal outcomes of pregnant women with COVID-19: a systematic review and meta-analysis

Scientific Reports ◽

10.1038/s41598-020-75096-4 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Jeong Yee ◽

Woorim Kim ◽

Ji Min Han ◽

Ha Young Yoon ◽

Nari Lee ◽

...

Keyword(s):

Systematic Review ◽

Pregnant Women ◽

Fetal Death ◽

Web Of Science ◽

Meta Analysis ◽

Clinical Manifestations ◽

Perinatal Outcomes ◽

Current Review ◽

The Mean ◽

The Impact

Abstract This systematic review and meta-analysis aimed to evaluate the impact of COVID-19 on pregnant women. We searched for qualified studies in PubMed, Embase, and Web of Science. The clinical characteristics of pregnant women with COVID-19 and their infants were reported as means and proportions with 95% confidence interval. Eleven studies involving with 9032 pregnant women with COVID-19 and 338 infants were included in the meta-analysis. Pregnant women with COVID-19 have relatively mild symptoms. However, abnormal proportions of laboratory parameters were similar or even increased, compared to general population. Around 30% of pregnant women with COVID-19 experienced preterm delivery, whereas the mean birth weight was 2855.9 g. Fetal death and detection of SARS-CoV-2 were observed in about 2%, whereas neonatal death was found to be 0.4%. In conclusion, the current review will serve as an ideal basis for future considerations in the treatment and management of COVID-19 in pregnant women.

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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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Embryotoxic impact of Zika virus in a rhesus macaque in vitro implantation model†

Biology of Reproduction ◽

10.1093/biolre/ioz236 ◽

2020 ◽

Vol 102 (4) ◽

pp. 806-816 ◽

Cited By ~ 4

Author(s):

Lindsey N Block ◽

Matthew T Aliota ◽

Thomas C Friedrich ◽

Michele L Schotzko ◽

Katherine D Mean ◽

...

Keyword(s):

Rhesus Macaque ◽

Pregnancy Outcomes ◽

Zika Virus ◽

Negative Impact ◽

Culture Media ◽

Blastocyst Formation ◽

Placental Development ◽

Zikv Infection ◽

The Impact

Abstract Zika virus (ZIKV) infection is associated with adverse pregnancy outcomes in humans, and infection in the first trimester can lead to miscarriage and stillbirth. Vertical and sexual transmissions of ZIKV have been demonstrated, yet the impact of infection during the initial stages of pregnancy remains unexplored. Here we defined the impact of ZIKV on early embryonic and placental development with a rhesus macaque model. During in vitro fertilization (IVF), macaque gametes were inoculated with a physiologically relevant dose of 5.48log10 plaque-forming units (PFU) of Zika virus/H.sapiens-tc/PUR/2015/PRVABC59_v3c2. Exposure at fertilization did not alter blastocyst formation rates compared to controls. To determine the impact of ZIKV exposure at implantation, hatched blastocysts were incubated with 3.26log10, 4.26log10, or 5.26log10 PFU, or not exposed to ZIKV, followed by extended embryo culture for 10 days. ZIKV exposure negatively impacted attachment, growth, and survival in comparison to controls, with exposure to 5.26log10 PFU ZIKV resulting in embryonic degeneration by day 2. Embryonic secretion of pregnancy hormones was lower in ZIKV-exposed embryos. Increasing levels of infectious virus were detected in the culture media post-exposure, suggesting that the trophectoderm is susceptible to productive ZIKV infection. These results demonstrate that ZIKV exposure severely impacts the zona-free blastocyst, whereas exposure at the time of fertilization does not hinder blastocyst formation. Overall, early stages of pregnancy may be profoundly sensitive to infection and pregnancy loss, and the negative impact of ZIKV infection on pregnancy outcomes may be underestimated.

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