Zika Virus Outbreak Research Articles

Oropouche Virus Infection: Differential Clinical Outcomes and Emerging Global Concerns of Vertical Transmission and Fatal Cases

Oropouche virus (OROV), a member of the Peribunyaviridae family, has emerged as a significant arboviral threat, particularly in South and Central America. Traditionally causing mild febrile illness, recent outbreaks have revealed severe clinical outcomes, including aseptic meningitis, encephalitis, and, more recently, vertical transmission leading to congenital anomalies and fatalities. Environmental changes, including deforestation and climate shifts, have expanded the virus's geographic range, as seen in Brazil, where over 8,000 cases were reported by August 2024, compared to fewer than 831in 2023. For the first time, vertical transmission has been confirmed, with cases of fetal deaths and congenital anomalies such as microcephaly and agenesis of the corpus callosum, drawing parallels to the Zika virus outbreak in 2015–2016. Despite these alarming trends, key mechanisms of placental transmission, maternal immunity, and fetal susceptibility remain poorly understood. This perspective highlights the urgent need for a coordinated global response, focusing on enhanced surveillance in newly affected regions, vector control strategies, and research into the factors driving severe clinical outcomes. Strengthening global efforts will be crucial in mitigating the public health threat posed by OROV, particularly in light of its potential for further geographic expansion and severe clinical manifestations.

Computational investigation of stochastic Zika virus optimal control model using Legendre spectral method

This study presents a computational investigation of a stochastic Zika virus along with optimal control model using the Legendre spectral collocation method (LSCM). By accumulation of stochasticity into the model through the proposed stochastic differential equations, we appropriating the random fluctuations essential in the progression and disease transmission. The stability, convergence and accuracy properties of the LSCM are conscientiously analyzed and also demonstrating its strength for solving the complex epidemiological models. Moreover, the study evaluates the various control strategies, such as treatment, prevention and treatment pesticide control, and identifies optimal combinations that the intervention costs and also minimize the proposed infection rates. The basic properties of the given model, such as the reproduction number, were determined with and without the presence of the control strategies. For R0<0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$R_0<0$$\\end{document}, the model satisfies the disease-free equilibrium, in this case the disease die out after some time, while for R0>1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$R_0>1$$\\end{document}, then endemic equilibrium is satisfied, in this case the disease spread in the population at higher scale. The fundamental findings acknowledge the significant impact of stochastic phonemes on the robustness and effectiveness of control strategies that accelerating the need for cost-effective and multi-faceted approaches. In last the results provide the valuable insights for public health department to enabling more impressive mitigation of Zika virus outbreaks and management in real-world scenarios.

Geographic Distribution and Temporal Trends of Zika Virus Outbreaks in India (2016-2023): Insights From the Integrated Disease Surveillance Programme Data.

Introduction This study examines the geographic distribution and temporal trends of Zika virus (ZIKV) outbreaks in India from 2016 to 2023 using data from the Integrated Disease Surveillance Programme (IDSP). The burden of ZIKV in India has risen due to its rapid spread and significant health impacts. Existing literature highlights seasonal and geographic patterns but lacks a comprehensive, long-term analysis specific to India. This study addresses this gap by analyzing trends over seven years to inform better public health responses. Methods A secondary data analysis was conducted using publicly available data from the IDSPon reported Zika cases from January 2016 to December 2023. Descriptive statistical methods and geographic information system(GIS) mapping techniques were employed to analyze the geographic distribution and temporal trends of ZIKVoutbreaks in India. The data were analyzed and visualized using R software version 4.3.2 (R Foundation for Statistical Computing, Vienna, Austria), with heat maps and choropleth maps to identify hotspots, and line diagrams to identify temporal trends. Results Zika outbreaks predominantly occurred during the post-monsoon season, accounting for 47.62% (n= 10) of the total 21 outbreaks, followed by the monsoon season with 33.33% (n = 7), and summer with 19.05% (n = 4). Two deaths were reported during a significant outbreak in Madhya Pradesh in 2018. Temporal trends indicated notable spikes in cases in 2018 (131 cases) and 2021 (234 cases), with no cases reported in 2019 and 2020. The geographic distribution maps highlighted significant concentrations of ZIKV outbreaks in specific districts within Uttar Pradesh, Madhya Pradesh, and Kerala. Discussion The study identified seasonal patterns, with most cases occurring in the post-monsoon season. The geographic spread of the ZIKV was observed in eight states from 2016 to 2023. GIS identified three hotspots in Uttar Pradesh, Madhya Pradesh, and Kerala. Conclusion The study highlights the need for heightened surveillance and targeted intervention preparedness during high-risk seasons. Enhancing testing facilities and data reporting systems could improve outbreak identification, management, and response.

Recent advances in the study of zika virus structure, drug targets, and inhibitors.

Zika Virus (ZIKV) is a positive-strand RNA virus that can lead to Guillain-Barré syndrome or encephalitis in some individuals and hence presents a serious public health risk. Since the first outbreak of ZIKV in Brazil in 2015, no effective clinical inhibitors have been developed, making the development of effective ZIKV drugs an urgent issue that needs to be addressed. ZIKV belongs to the Flaviviridae family, and its structure includes three structural proteins, namely, capsular (C), premembrane (prM), and envelope (E) proteins, as well as seven nonstructural proteins, namely, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. To provide a reference for the development of future ZIKV drugs, this paper reviews the structure of the ZIKV based on recent literature reports, analyzes the potential therapeutic targets of various proteins, and proposes feasible drug design strategies. Additionally, this paper reviews and classifies the latest research progress on several protease inhibitors, such as E protein inhibitors, NS2B-NS3 inhibitors, and NS5 inhibitors, so that researchers can quickly understand the current status of development and the interconnections among these inhibitors.

Targeting glucose metabolism with dichloroacetate (DCA) reduces zika virus replication in brain cortical progenitors at different stages of maturation

The underlying threat of new Zika virus (ZIKV) outbreaks remains, as no vaccines or therapies have yet been developed. In vitro research has shown that glycolysis is a key factor to enable sustained ZIKV replication in neuroprogenitors. However, neither in vivo nor clinical investigation of glycolytic modulators as potential therapeutics for ZIKV-related fetal abnormalities has been conducted. Accordingly, we tested the therapeutic potential of metabolic modulators in relevant in vitro systems comprising two pools of neuroprogenitors (NPCs), which resemble early and late stages of pregnancy. Effective doses of metabolic modulators [3.0 μM] dimethyl fumarate (DMF), [3.2 mM] dichloroacetate (DCA), and [6.3 μM] VER-246608 were determined for these cells by their effect on lactate release, pyruvate dehydrogenase (PDH) activity and cell survival. The drugs were used in a 24h pre-treatment and kept throughout ZIKV infection of NPCs. Drug effects and ZIKV replication were assessed at 24- and 56-h post-infection. In early NPCs treated with DMF, DCA and VER-246608, there was a significant reduction in the extracellular release of ZIKV potentially by PDH-mediated increased mitochondrial oxidation of glucose. Out of the three drugs, only DCA was observed to reduce viral replication in late NPCs treated with DCA. Altogether, our findings suggest that reduction of anaerobic glycolysis could be of therapeutic potential against ZIKV-related fetal abnormalities and that clinical translation should consider the use of specific glycolytic modulators over different trimesters.

Zika Virus Infection Knowledge and Communication Preferences Among Women of Reproductive Age in Central Brooklyn, New York: A Thematic Analysis.

The 2016 outbreak of Zika virus (ZIKV) infected millions and resulted in thousands of infants born with malformations. Though the clusters of severe birth defects resulting from this outbreak have subsided, ZIKV continues to be a concern throughout much of Latin America and the Caribbean. Travel and sexual intercourse remain the dominant transmission risk factors for women of reproductive age and their partners. This is particularly true for communities in Brooklyn, New York, that comprise large immigrant and foreign-born populations. Practitioners of public health understand little about how women at risk for ZIKV are most likely to receive information about the virus or who they trust most to provide that information. In the context of five focus group discussions, this study explored the knowledge and communication preferences of 20 women of reproductive age in Central Brooklyn. Results derived from a thematic analysis suggest that while most women are familiar with mosquitos as ZIKV vectors, knowledge of sexual transmission is considerably lower. Many respondents believe that only women who are pregnant or trying to become pregnant are at risk, and public health agencies, such as the U.S. Centers for Disease Control and Prevention, remain the most trusted sources of information. These findings can support more effective communication about the risks of ZIKV infection and other vector-borne diseases to women in New York City and similar urban communities.

Characteristics, risk factors, and outcomes related to Zika virus infection during pregnancy in Northeastern Thailand: A prospective pregnancy cohort study, 2018-2020.

In response to the 2015-2016 Zika virus (ZIKV) outbreak and the causal relationship established between maternal ZIKV infection and adverse infant outcomes, we conducted a cohort study to estimate the incidence of ZIKV infection in pregnancy and assess its impacts in women and infants. From May 2018-January 2020, we prospectively followed pregnant women recruited from 134 participating hospitals in two non-adjacent provinces in northeastern Thailand. We collected demographic, clinical, and epidemiologic data and blood and urine at routine antenatal care visits until delivery. ZIKV infections were confirmed by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Specimens with confirmed ZIKV underwent whole genome sequencing. Among 3,312 women enrolled, 12 (0.36%) had ZIKV infections, of which two (17%) were detected at enrollment. Ten (83%, 3 in 2nd and 7 in 3rd trimester) ZIKV infections were detected during study follow-up, resulting in an infection rate of 0.15 per 1,000 person-weeks (95% CI: 0.07-0.28). The majority (11/12, 91.7%) of infections occurred in one province. Persistent ZIKV viremia (42 days) was found in only one woman. Six women with confirmed ZIKV infections were asymptomatic until delivery. Sequencing of 8 ZIKV isolates revealed all were of Asian lineage. All 12 ZIKV infected women gave birth to live, full-term infants; the only observed adverse birth outcome was low birth weight in one (8%) infant. Pregnancies in 3,300 ZIKV-rRT-PCR-negative women were complicated by 101 (3%) fetal deaths, of which 67 (66%) had miscarriages and 34 (34%) had stillbirths. There were no differences between adverse fetal or birth outcomes of live infants born to ZIKV-rRT-PCR-positive mothers compared to live infants born to ZIKV-rRT-PCR-negative mothers. Confirmed ZIKV infections occurred infrequently in this large pregnancy cohort and observed adverse maternal and birth outcomes did not differ between mothers with and without confirmed infections.

Zika infection among international students after five months in Thailand.

Zika virus outbreak was traced among international students in Thailand. Testing was prompted by a single symptomatic case, which revealed seropositivity in two students. These results highlight the potential risk of Zika and emphasize the importance of implementing preventive measures for those travelling to endemic regions such as Thailand.

In vitro enhancement of Zika virus infection by preexisting West Nile virus antibodies in human plasma-derived immunoglobulins revealed after P2 binding site-specific enrichment.

Human immunoglobulin preparations contain a diverse range of polyclonal antibodies that reflect past immune responses against pathogens encountered by the blood donor population. In this study, we examined a panel of intravenous immunoglobulins (IGIVs) manufactured over the past two decades (1998-2020) for their capacity to neutralize or enhance Zika virus (ZIKV) infection in vitro. These IGIVs were selected specifically based on their production dates in relation to the occurrences of two flavivirus outbreaks in the U.S.: the West Nile virus (WNV) outbreak in 1999 and the ZIKV outbreak in 2015. As demonstrated by enzyme-linked immunosorbent assay (ELISA) experiments, IGIVs made before the ZIKV outbreak already harbored antibodies that bind to various peptides across the envelope protein of ZIKV because of the WNV outbreak. Using phage display, the most dominant binding site was mapped precisely to the P2 peptide between residues 211 and 230 within domain II, where BF1176-56, an anti-ZIKV monoclonal antibody, also binds. When tested in permissive Vero E6 cells for ZIKV neutralization, the IGIVs, even after undergoing rigorous enrichment for P2 binding specificity, failed, as did BF1176-56. Meanwhile, BF1176-56 enhanced ZIKV infection in both FcγRII-expressing K562 cells and human peripheral blood mononuclear cells. However, for enhancement by the IGIVs to be detected in these cells, a substantial increase in their P2 binding specificity was required, thus linking the P2 site with ZIKV enhancement in vitro. Our findings warrant further study of the significance of elevated levels of anti-WNV antibodies in IGIVs, considering that various mechanisms operating in vivo may modulate ZIKV infection outcomes.IMPORTANCEWe investigated the capacity of intravenous immunoglobulins manufactured previously over two decades (1998-2020) to neutralize or enhance Zika virus infection in vitro. West Nile virus antibodies in IGIVs could not neutralize Zika virus initially; however, once the IGIVs were concentrated further, they enhanced its infection. These findings lay the groundwork for exploring how preexisting WNV antibodies in IGIVs could impact Zika infection, both in vitro and in vivo. Our observations are historically significant, since we tested a panel of IGIV lots that were carefully selected based on their production dates which covered two major flavivirus outbreaks in the U.S.: the WNV outbreak in 1999 and the ZIKV outbreak in 2015. These findings will facilitate our understanding of the interplay among closely related viral pathogens, particularly from a historical perspective regarding large blood donor populations. They should remain relevant for future outbreaks of emerging flaviviruses that may potentially affect vulnerable populations.

An Update on Zika Virus Vaccine Development and New Research Approaches

Zika virus (ZIKV) is an emerging flavivirus that represents significant public health challenges, particularly in the Americas, and is a substantial risk to other parts of the world due to its rapid expansion and its established association with neurological disorders, including Guillain–Barré syndrome and an intrauterine fetal infection that can cause microcephaly, blindness, and other congenital neurological complications. To date, no vaccine to prevent ZIKV infections has been approved. Therefore, developing a safe and effective vaccine against this virus is a global health priority. This review analyzes the ZIKV outbreaks, as well as associated neurological complications, its genome, and immunological responses. The current vaccines in development have reported results from preclinical and clinical trials about novel approaches to obtain safer and more effective vaccines and the challenges faced by ZIKV vaccine development.

Continuation of Reversible Contraception Following Enrollment in the Zika Contraception Access Network (Z-CAN) in Puerto Rico, 2016-2020.

The Zika Contraception Access Network (Z-CAN) provided access to high-quality client-centered contraceptive services across Puerto Rico during the 2016-2017 Zika virus outbreak. We sent online surveys during May 2017-August 2020 to a subset of Z-CAN patients at 6, 24, and 36 months after program enrollment (response rates: 55-60 percent). We described contraceptive method continuation, method satisfaction, and method switching, and we identified characteristics associated with discontinuation using multivariable logistic regression. Across all contraceptive methods, continuation was 82.5 percent, 64.2 percent, and 49.9 percent at 6, 24, and 36 months, respectively. Among continuing users, method satisfaction was approximately ≥90 percent. Characteristics associated with decreased likelihood of discontinuation included: using an intrauterine device or implant compared with a nonlong-acting reversible contraceptive method (shot, pills, ring, patch, or condoms alone); wanting to prevent pregnancy at follow-up; and receiving as their baseline method the same method primarily used before Z-CAN. Other associated characteristics included: receiving the method they were most interested in postcounseling (6 and 24 months) and being very satisfied with Z-CAN services at the initial visit (6 months). Among those wanting to prevent pregnancy at follow-up, about half reported switching to another method. Ongoing access to contraceptive services is essential for promoting reproductive autonomy, including supporting patients with continued use, method switching, or discontinuation.

Wastewater surveillance and Wolbachia-aedes method to combat Zika virus outbreaks in tropical countries.

Wastewater surveillance and Wolbachia-aedes method to combat Zika virus outbreaks in tropical countries.

Single proxy control.

Negative control variables are sometimes used in nonexperimental studies to detect the presence of confounding by hidden factors. A negative control outcome (NCO) is an outcome that is influenced by unobserved confounders of the exposure effects on the outcome in view, but is not causally impacted by the exposure. Tchetgen Tchetgen (2013) introduced the Control Outcome Calibration Approach (COCA) as a formal NCO counterfactual method to detect and correct for residual confounding bias. For identification, COCA treats the NCO as an error-prone proxy of the treatment-free counterfactual outcome of interest, and involves regressing the NCO on the treatment-free counterfactual, together with a rank-preserving structural model, which assumes a constant individual-level causal effect. In this work, we establish nonparametric COCA identification for the average causal effect for the treated, without requiring rank-preservation, therefore accommodating unrestricted effect heterogeneity across units. This nonparametric identification result has important practical implications, as it provides single-proxy confounding control, in contrast to recently proposed proximal causal inference, which relies for identification on a pair of confounding proxies. For COCA estimation we propose 3 separate strategies: (i) an extended propensity score approach, (ii) an outcome bridge function approach, and (iii) a doubly-robust approach. Finally, we illustrate the proposed methods in an application evaluating the causal impact of a Zika virus outbreak on birth rate in Brazil.

Assessing vulnerability for future Zika virus outbreaks using seroprevalence data and environmental suitability maps.

The 2015-17 Zika virus (ZIKV) epidemic in the Americas subsided faster than expected and evolving population immunity was postulated to be the main reason. Herd immunization is suggested to occur around 60-70% seroprevalence, depending on demographic density and climate suitability. However, herd immunity was only documented for a few cities in South America, meaning a substantial portion of the population might still be vulnerable to a future Zika virus outbreak. The aim of our study was to determine the vulnerability of populations to ZIKV by comparing the environmental suitability of ZIKV transmission to the observed seroprevalence, based on published studies. Using a systematic search, we collected seroprevalence and geospatial data for 119 unique locations from 37 studies. Extracting the environmental suitability at each location and converting to a hypothetical expected seroprevalence, we were able to determine the discrepancy between observed and expected. This discrepancy is an indicator of vulnerability and divided into three categories: high risk, low risk, and very low risk. The vulnerability was used to evaluate the level of risk that each location still has for a ZIKV outbreak to occur. Of the 119 unique locations, 69 locations (58%) fell within the high risk category, 47 locations (39%) fell within the low risk category, and 3 locations (3%) fell within the very low risk category. The considerable heterogeneity between environmental suitability and seroprevalence potentially leaves a large population vulnerable to future infection. Vulnerability seems to be especially pronounced at the fringes of the environmental suitability for ZIKV (e.g. Sao Paulo, Brazil). The discrepancies between observed and expected seroprevalence raise the question: "why did the ZIKV epidemic stop with large populations unaffected?". This lack of understanding also highlights that future ZIKV outbreaks currently cannot be predicted with confidence.

The impact of ZIKV infection on gene expression in neural cells over time.

Zika virus (ZIKV) outbreak caused one of the most significant medical emergencies in the Americas due to associated microcephaly in newborns. To evaluate the impact of ZIKV infection on neuronal cells over time, we retrieved gene expression data from several ZIKV-infected samples obtained at different time point post-infection (pi). Differential gene expression analysis was applied at each time point, with more differentially expressed genes (DEG) identified at 72h pi. There were 5 DEGs (PLA2G2F, TMEM71, PKD1L2, UBD, and TNFAIP3 genes) across all timepoints, which clearly distinguished between infected and healthy samples. The highest expression levels of all five genes were identified at 72h pi. Taken together, our results indicate that ZIKV infection greatly impacts human neural cells at early times of infection, with peak perturbation observed at 72h pi. Our analysis revealed that all five DEGs, in samples of ZIKV-infected human neural stem cells, remained highly upregulated across the timepoints evaluated. Moreover, despite the pronounced inflammatory host response observed throughout infection, the impact of ZIKV is variable over time. Finally, the five DEGs identified herein play prominent roles in infection, and could serve to guide future investigations into virus-host interaction, as well as constitute targets for therapeutic drug development.

Investigation of Yellow Fever Virus at the Human-Animal Interface after a Zika Virus Outbreak in Midwest Brazil.

Following the first report of zika virus in March 2015, Brazil experienced its largest sylvatic yellow fever outbreak between 2016 and 2019. This study aimed to investigate the circulation of yellow fever virus (YFV) in non-human primates (NHPs) and mosquitoes collected in urban parks and other metropolitan areas of midwest Brazil between 2017 and 2018. Whole blood samples from 80 NHPs, including 48 black-tailed marmosets (Mico melanurus) and 2332 mosquitoes from six different genera, were collected in the states of Mato Grosso (MT) and Mato Grosso do Sul (MS) and then tested for YFV by RT-qPCR. Additionally, 23 plasma samples of NHPs were tested for neutralizing antibodies for YFV by a plaque reduction neutralization test (PRNT). No YFV RNA or neutralizing antibodies for YFV were detected in NHPs and mosquitoes from MT and MS. The continuous monitoring of YFV circulation in different species of NHPs and vectors in urban areas is instrumental to quickly assess potentially unknown maintenance cycles of yellow fever at the human-animal interface in Brazil.

Population-based surveillance for birth defects potentially related to Zika virus infection including 3-year mortality and developmental outcomes, and Early Intervention Program service use-New York City, 2016 birth cohort.

In response to the 2015-2017 Zika virus outbreak, New York City (NYC) identified and monitored infants with birth defects potentially related to congenital Zika virus. Administrative data matches were used to describe the birth characteristics of children born in 2016 meeting screening criteria for birth defects potentially related to congenital Zika virus infection relative to other NYC births and to monitor mortality and Early Intervention Program use through age 2. Among 120,367 children born in NYC in 2016, 463 met screening criteria and 155 met the Centers for Disease Control and Prevention's case definition for birth defects potentially related to congenital Zika virus infection (1.3 per 1000; 95% confidence interval [CI], 1.1-1.5). Post-neonatal deaths occurred among 7.7% of cases (12) and 5.2% of non-cases (8). Odds of referral to the Early intervention Program among children who met screening criteria were lower among children of mothers who were married (OR, 0.60; 95% CI, 0.37-0.97) and among children not classified as cases whose mothers were born in Latin America and the Caribbean (OR, 0.59; 95% CI, 0.37-1.09). Prevalence of birth defects potentially related to congenital Zika virus infection was similar to that seen in other jurisdictions without local transmission. Birth defects attributable to congenital Zika virus infection may also have been present among screened children who did not meet the case definition.

Analysis of congenital Zika syndrome clinicopathologic findings reported in the 8 years since the Brazilian outbreak

Aim: A Zika virus outbreak that began in Brazil, developed into an international public health emergency that extended from February 2015 until November 2016. Zika-infected pregnant women gave birth to a cohort of infants with congenital Zika syndrome (CZS) originally defined by severe microcephaly, retinal scarring, joint deformities, and hypertonia. This study examines the nature, extent, and severity of all CZS clinicopathologic findings described to date, compiled and analyzed by system. It reviews studies monitoring disease progression and proposing classification schemes for CZS stages. The teratogenic cellular and molecular mechanisms implicated in CZS pathogenesis are also discussed. Methods: A systematic review was conducted by literature search through WorldCat.org and ProQuest Central databases to identify studies on case series from the 2015–2016 CZS outbreak. Results: Twenty-six reports were included describing radiologic, ophthalmologic, audiologic, orthopedic, and laboratory test results in CZS cases including stillborns between 2016 and 2023. CZS neuropathology included prenatal and postnatal microcephaly, cerebral calcifications, quadriparesis, epilepsy, ventriculomegaly, reduced cerebral parenchyma, malformation of cortical development, and sleep electroencephalogram disturbances. Visual deficits were due to retinal and optic nerve lesions. Conductive and sensorineural hearing deficits were stable. Hypertonia, hypotonia, and spasticity with foot, hip, knee, and shoulder deformities resulted in arthrogryposis and restricted joint mobility. There was enlargement of immune organs, increased leukocyte counts, and cytokine dysregulation. Oro-craniofacial deformities affected the midface and caused dental eruption delay. Additional studies proposed that these systemic teratogenic effects could be attributable to transplacental Zika virus infection of multiple fetal progenitor cell lineages. Conclusions: The CZS-associated impairments in brain, eye, musculoskeletal, and immunologic functions caused disabilities that varied from moderate to severe, and significantly increased age-specific mortality rates. Further research is warranted to assess progression, classify stages, elucidate the precise molecular mechanisms mediating Zika teratogenicity, develop suitable therapeutic strategies, and design supportive social policies.

Protective efficacy of a Zika purified inactivated virus vaccine candidate during pregnancy in marmosets

Zika virus (ZIKV) infection during pregnancy poses significant threats to maternal and fetal health, leading to intrauterine fetal demise and severe developmental malformations that constitute congenital Zika syndrome (CZS). As such, the development of a safe and effective ZIKV vaccine is a critical public health priority. However, the safety and efficacy of such a vaccine during pregnancy remain uncertain. Historically, the conduct of clinical trials in pregnant women has been challenging. Therefore, clinically relevant animal pregnancy models are in high demand for testing vaccine efficacy. We previously reported that a marmoset pregnancy model of ZIKV infection consistently demonstrated vertical transmission from mother to fetus during pregnancy. Using this marmoset model, we also showed that vertical transmission could be prevented by pre-pregnancy vaccination with Zika purified inactivated virus (ZPIV) vaccine. Here, we further examined the efficacy of ZPIV vaccination during pregnancy. Vaccination during pregnancy elicited virus neutralizing antibody responses that were comparable to those elicited by pre-pregnancy vaccination. Vaccination also reduced placental pathology, viral burden and vertical transmission of ZIKV during pregnancy, without causing adverse effects. These results provide key insights into the safety and efficacy of ZPIV vaccination during pregnancy and demonstrate positive effects of vaccination on the reduction of ZIKV infection, an important advance in preparedness for future ZIKV outbreaks.

Arboviruses and pregnancy: are the threats visible or hidden?

Mosquito-borne arboviral diseases are a global concern and can have severe consequences on maternal, neonatal, and child health. Their impact on pregnancy tends to be neglected in developing countries. Despite hundreds of millions of infections, 90% pregnancies being exposed, scientific data on pregnant women is poor and sometimes non-existent. Recently and since the 2016 Zika virus outbreak, there has been a newfound interest in these diseases. Through various neuropathogenic, visceral, placental, and teratogenic mechanisms, these arbovirus infections can lead to fetal losses, obstetrical complications, and a wide range of congenital abnormalities, resulting in long-term neurological and sensory impairments. Climate change, growing urbanization, worldwide interconnectivity, and ease of mobility allow arboviruses to spread to other territories and impact populations that had never been in contact with these emerging agents before. Pregnant travelers are also at risk of infection with potential subsequent complications. Beyond that, these pathologies show the inequalities of access to care on a global scale in a context of demographic growth and increasing urbanization. It is essential to promote research, diagnostic tools, treatments, and vaccine development to address this emerging threat.Background The vulnerability of pregnant women and fetuses to emergent and re-emergent pathogens has been notably illustrated by the outbreaks of Zika virus. Our comprehension of the complete scope and consequences of these infections during pregnancy remains limited, particularly among those involved in perinatal healthcare, such as obstetricians and midwives. This review aims to provide the latest information and recommendations regarding the various risks, management, and prevention for pregnant women exposed to arboviral infections.