Zika Virus Transmission Research Articles

Spatiotemporal analysis of Zika virus transmission dynamics incorporating human mobility and seasonal variations using modified homotopy perturbation method

AbstractThis study employed a mathematical model to evaluate how seasonal variations, vector dispersal, and mobility of people affect the spread of the Zika virus. The model's positive solutions, invariant zones, and solution existence and uniqueness were validated through proved theorems. The equilibria points were identified, and the basic reproduction number was calculated. The model was semi-analytically solved using a modified homotopy perturbation approach, and an applied convergence test proved that the solution converges. The simulation results indicated that under optimal breeding conditions, the density of healthy mosquitoes peaked in the fourth month. Two months later, increased mosquito dispersal and human carriers facilitated by favorable weather led to a rise in mosquito infectiousness, peaking between the fourth and eighth months due to significant seasonal effects, resulting in high Zika transmission. To effectively control mosquito populations and reduce Zika transmission, it is recommended that public health interventions focus on the critical periods spanning the third to eighth months.

Analysis of the serum proteome profile of wild stump-tailed macaques (Macaca arctoides) seropositive for Zika virus antibodies in Thailand

Zika virus (ZIKV) is a member of the Flaviviridae virus family and poses a significant global health concern. ZIKV is transmitted by Aedes mosquitoes, and it has been implicated in various neurological conditions associated with fetal brain development. ZIKV has two transmission cycles: a sylvatic cycle in which nonhuman primates are infected via arboreal mosquito bites, and an interhuman (urban) cycle in which the virus is transmitted among primates by Aedes mosquitoes. ZIKV was first discovered in wild macaques, and the danger posed by the virus is increased due to the close proximity between humans and wild animals in modern society. However, data regarding the extent and role of infection in nonhuman primates are limited. Thus, there is an urgent need for improved surveillance, diagnostic methods, and public health interventions to effectively combat ZIKV transmission and its associated health impacts in Southeast Asia. In this study, we used a proteomics and bioinformatics approach to profile serum proteins in wild stump-tailed macaques seropositive for neutralizing antibodies against ZIKV. A total of 9,532 total proteins were identified, and 338 differentially expressed proteins were identified between naïve and seropositive animals. A total of 52 important proteins were used to construct a serum proteomic profile. These 52 important proteins were associated with immune and inflammatory responses (36.54%), neurological damage (23.08%), viral activities (21.15%), the apoptosis signaling pathway (9.61%), and other pathways (9.61%). Our proteomic profile identified proteins that inhibit the apoptosis pathway, intracellular resource competition with the virus, and neurological damage due to ZIKV and the host immune and defense responses.

Modeling Zika Virus Disease Dynamics with Control Strategies

In this research, we formulated a fractional-order model for the transmission dynamics of Zika virus, incorporating three control strategies: health education campaigns, the use of insecticides, and preventive measures. We conducted a theoretical analysis of the model, obtaining the disease-free equilibrium and the basic reproduction number, and analyzing the existence and uniqueness of the model. Additionally, we performed model parameter estimation using real data on Zika virus cases reported in Colombia. We found that the fractional-order model provided a better fit to the real data compared to the classical integer-order model. A sensitivity analysis of the basic reproduction number was conducted using computed partial rank correlation coefficients to assess the impact of each parameter on Zika virus transmission. Furthermore, we performed numerical simulations to determine the effect of memory on the spread of Zika virus. The simulation results showed that the order of derivatives significantly impacts the dynamics of the disease. We also assessed the effect of the control strategies through simulations, concluding that the proposed interventions have the potential to significantly reduce the spread of Zika virus in the population.

Risk of introducing Zika virus in the Canadian cord blood supply: A risk analysis.

In Canada, as many as 24% of mothers are deferred from cord blood (CB) donation due to risk factors for Zika virus (ZIKV). However, the ZIKV epidemic has waned considerably since 2016, and there has not been any report of ZIKV transmission by CB transplantation, which questions this policy. Thus, we performed an analysis of the risk of introducing ZIKV in the CB supply maintained by Héma-Québec (HQ) and Canadian Blood Services (CBS). This simulation considered the following parameters: the risk of travel exposure in a high-risk ZIKV country, the duration of travel, the daily risk of acquiring ZIKV in a high-risk country, the probability of materno-fetal ZIKV transmission, the probability of asymptomatic fetal viremia, and the probability of sexual transmission. A hundred million Monte Carlo simulations were run. In the most-likely scenario (probability of traveling to a high-risk ZIKV country while pregnant = 0.178), the risk was estimated at 0.9 ZIKV-positive donations per million donations (95% confidence interval [CI] = 0.4-1.6)-or one every 868 years at HQ and one every 453 years at CBS. In the pessimistic model (probability of traveling to a high-risk ZIKV country while pregnant = 0.240), the risk was estimated at 1.2 ZIKV-positive donations per million donations (95% CI = 0.6-2.1)-or one every 644 years at HQ and one every 340 years at CBS. We conclude that the risk of introducing ZIKV in the Canadian CB supply is too small to justify maintaining the current policy.

Prenatal Exposure to Herbicide 2,4-Dichlorophenoxyacetic Acid (2,4D) Exacerbates Zika Virus Neurotoxicity In Vitro and In Vivo.

Zika virus (ZIKV) infection during pregnancy can lead to a set of congenital malformations known as Congenital ZIKV syndrome (CZS), whose main feature is microcephaly. The geographic distribution of CZS in Brazil during the 2015-2017 outbreak was asymmetrical, with a higher prevalence in the Northeast and Central-West regions of the country, despite the ubiquitous distribution of the vector Aedes aegypti, indicating that environmental factors could influence ZIKV vertical transmission and/or severity. Here we investigate the involvement of the most used agrochemicals in Brazil with CZS. First, we exposed human neuroblastoma SK-N-AS cells to the 15 frequently used agrochemical molecules or derivative metabolites able to cross the blood-brain barrier. We found that a derived metabolite from a widely used herbicide in the Central-West region, 2,4-dichlorophenoxyacetic acid (2,4D), exacerbates ZIKV neurotoxic effects in vitro. We validate this observation by demonstrating vertical transmission leading to microcephaly in the offspring of immunocompetent C57BL/6J mice exposed to water contaminated with 0.025 mg/L of 2,4D. Newborn mice whose dams were exposed to 2,4D and infected with ZIKV presented a smaller brain area and cortical plate size compared to the control. Also, embryos from animals facing the co-insult of ZIKV and 2,4D exposition presented higher Caspase 3 positive cells in the cortex, fewer CTIP2+ neurons and proliferative cells at the ventricular zone, and a higher viral load. This phenotype is followed by placental alterations, such as vessel congestion, and apoptosis in the labyrinth and decidua. We also observed a mild spatial correlation between CZS prevalence and 2,4D use in Brazil's North and Central-West regions, with R2 = 0.4 and 0.46, respectively. Our results suggest that 2,4D exposition facilitates maternal vertical transmission of ZIKV, exacerbating CZS, possibly contributing to the high prevalence of this syndrome in Brazil's Central-West region compared to other regions.

Seroprevalence of dengue, yellow fever, and related flaviviruses among the rural human population in Nguruman and Kerio Valley, Kenya

BackgroundYellow fever virus (YFV) and dengue virus (DENV) are among the major re-emerging arboviruses that pose a significant threat to public health. Their associated burden and prevalence can be substantially underestimated due to insufficient surveillance and inadequate diagnosis. This study aimed to determine evidence of dengue, yellow and related flaviviruses circulation among the rural human populations residing in Nguruman (Kajiado County) and Kerio Valley (Baringo County), two dryland ecosystems in the Kenyan Rift Valley.MethodsSerum samples obtained from febrile patients between 5 and 85 years through a hospital-based cross-sectional survey from July 2020 – May 2023, were screened for neutralizing antibodies to YFV, DENV-2 and related flaviviruses, West Nile virus (WNV) and Zika virus (ZIKV) via Plaque reduction neutralization test (PRNT). The study sites and important demographic characteristics were obtained using a structural questionnaire and the data analyzed and seroprevalence compared. A multinomial logistic regression model was done to predict risk for each of the most prevalent viruses with covariates; age, gender, and occupation.ResultsOverall, 54.5% (50.1–59.0% 95% confidence interval (CI) of the samples tested positive for at least one of the four Flaviviruses. The percentage was significantly higher in Kerio Valley (64.34%, 184/286) than in Nguruman (40.2%, 78/194) (P<0.0001). YFV had the highest prevalence, followed by WNV (16.25%), ZIKV (5.2%), and DENV-2 (1%). Kerio Valley had a significantly higher YFV seroprevalence (51%) than Nguruman (6%) (P<0.0001), while DENV-2 was observed only in Nguruman with a low seropositivity of 2%. In contrast to Nguruman, where seropositivity rates were higher in males at 47.47% (P=0.049), in Kerio Valley, females showed considerably higher viral seropositivity at 60.82% than males (P<0001).ConclusionThe study suggests that there is significant circulation of Flaviviruses in both regions, posing a public health risk, that could potentially contribute to clinical disease. However, seropositivity rates vary for each specific site. Furthermore, there could be a risk of YFV, WNV, and ZIKV transmission in both sites with DENV transmission specifically noted in Nguruman. The study findings inform direct cost-effective actions (such as YF vaccines) and precise surveillance data of vector populations for improved disease risk prediction.

Modeling the Spatial Dynamics and Human Mobility in Zika Virus Transmission: A Review

Spatial dynamics and human mobility significantly influence the transmission dynamics of vector-borne diseases like Zika virus. This paper reviews advancements in mathematical modeling that integrate spatial factors and human movement to enhance our understanding of disease transmission dynamics. Traditional SEIR (Susceptible-Exposed-Infectious-Recovered) models have been foundational but lack spatial heterogeneity and human mobility considerations. Recent studies have addressed these limitations by developing spatially explicit models that incorporate local interactions, environmental conditions, and human mobility patterns. By synthesizing findings from these studies, we identify strengths, limitations, and future research directions for improving predictive modeling of Zika virus transmission. Key insights include the amplifying effect of local interactions on disease spread and the critical role of human mobility networks in shaping transmission pathways. Addressing remaining challenges, such as refining spatial modeling techniques and integrating real-time data sources, will enhance the accuracy and applicability of spatial disease models in informing public health strategies.

DETERMINISTIC MODEL OF ZIKA-VIRUS WITH CARRIER MOTHER AND RESERVOIRS: A MATHEMATICAL ANALYSIS APPROACH

In this paper, a mathematical model for the Zika virus is suggested to investigate the transmission dynamics of infection based on humans, pregnant carrier mother, infected children and the reservoir (primates) in three connected populations. Vertical and direct transmissions from all people to primates are considered in the proposed model. The Zika virus then spreads from this reservoir of infection via the nonhuman primate population (infected mosquitoes) to other entities. This virus can be passed on to the human population through an infected mosquito. Therefore, the new model with ten compartmental models has been normalized as follows: The normalized model is analyzed in depth to explore linkages between mosquitoes, humans, and primates on the dynamics of Zika-Virus transmission. The mathematical analysis comprises positivity and boundedness of solutions, determination of the basic reproduction number R0 via next-generation matrix approach, existence and stability of all equilibria as well as sensitivity analysis. Local and Global Stability of the Disease-free Equilibrium. Finally, numerical simulations are performed to verify the analytical results obtained and exhibit the contribution of different model parameters on disease transmission dynamics. The results prove that the interaction of forest mosquitoes with primates has a significant effect on human-Zika-Virus transmission dynamics among the susceptible population due to transitions to forested areas. Moreover, the findings suggest that the transmission probabilities and biting rates of mosquitoes on humans and primates are major parameters in transmitting the disease.

Predicting Efficacy of a Purified Inactivated Zika Virus Vaccine in Flavivirus-Naïve Humans Using an Immunological Correlate of Protection in Non-Human Primates.

A traditional phase 3 clinical efficacy study for a Zika vaccine may be unfeasible because of the current low transmission of Zika virus (ZIKV). An alternative clinical development approach to evaluate Zika vaccine efficacy (VE) is therefore required, delineated in the US FDA's Accelerated Approval Program for licensure, which utilizes an anti-Zika neutralizing antibody (Zika NAb) titer correlated with non-human primate (NHP) protection as a surrogate endpoint. In this accelerated approval approach, the estimation of VE would be inferred from the percentage of phase 3 trial participants achieving the established surrogate endpoint. We provide a statistical framework to predict the probability of protection for human participants vaccinated with a purified inactivated ZIKV vaccine (TAK-426), in the absence of VE measurements, using NHP data under a single-correlate model. Based on a logistic regression (LR) with bias-reduction model, a probability of 90% protection in humans is expected with a ZIKV NAb geometric mean titer (GMT) ≥ 3.38 log10 half-maximal effective concentration (EC50). The predicted probability of protection of TAK-426 against ZIKV infection was determined using the two-parameter LR model that fit the calculated VE in rhesus macaques and the flavivirus-naïve phase 1 trial participants' ZIKV NAb GMTs log10 EC50, measured by a ZIKV reporter virus particle assay, at 1 month post dose 2. The TAK-426 10 µg dose predicted a probability of protection from infection of 98% among flavivirus-naïve phase 1 trial participants.

The first confirmed outbreak of chikungunya reported in Timor-Leste, 2024.

Timor-Leste is a mountainous, half-island nation with a population of 1.3 million, which shares a land border with Indonesia and is 550 km from Darwin, Australia. Since independence in 2002, Timor-Leste has achieved significant development; however, high levels of poverty remain. Chikungunya virus (CHIKV) is endemic in over 100 countries in Africa, Asia, Europe and in the Americas. It is transmitted by the bite of infected Aedes aegypti or Ae. albopictus mosquitoes, which are present in Timor-Leste and which contribute to annual rainy-season dengue virus (DENV) outbreaks. Symptomatic people typically suffer from acute onset of fever, usually accompanied by severe arthritis or arthralgia. Joint pain can be debilitating for several days, and may sometimes last for weeks, months or years. Unlike DENV infection which has significant mortality, most people recover completely. Between 2002 and 2023, there were 26 cases of CHIKV notified in Australia who acquired their infection in Timor-Leste; however, laboratory testing capability for CHIKV in Timor-Leste only became available in 2021 using polymerase chain reaction (PCR). The first locally diagnosed case was notified in November 2023. In January 2024, an outbreak of CHIKV was recognised in Timor-Leste for the first time, with 195 outbreak cases reported during 1-31 January 2024; all were PCR positive. There were no cases hospitalised, and no deaths. The median age of cases was 17 years (range 1-76 years); 51% were males. Cases were reported across the country; most (88/195) were from Dili, although the highest incidence was seen in the neighbouring municipality of Ermera (monthly incidence rate of 58.8 cases per 100,000 population). This first reported outbreak of CHIKV in Timor-Leste highlights the need for improved mosquito-borne illness control and response strategies, including minimising breeding sites and promoting early presentation for treatment and differential diagnosis from DENV, and consideration of the deployment of Wolbachia-infected mosquitoes, particularly as they have shown to reduce the transmission of CHIKV, DENV and Zika virus, all of which pose threats in Timor-Leste.

Evidence of Ongoing Transmission of Zika Virus in Mérida, Mexico.

Since the Zika virus (ZIKV) pandemic in 2015-2017, there has been a near absence of reported cases in the Americas outside of Brazil. However, the conditions for Aedes-borne transmission persist in Latin America, and the threat of ZIKV transmission is increasing as population immunity wanes. Mexico has reported only 70 cases of laboratory-confirmed ZIKV infection since 2020, with no cases recorded in the Yucatán peninsula. Here, we provide evidence of active ZIKV transmission, despite the absence of official case reports, in the city of Mérida, Mexico, the capital of the state of Yucatán. Capitalizing on an existing cohort, we detected cases in participants with symptoms consistent with flavivirus infection from 2021 to 2022. Serum samples from suspected cases were tested for ZIKV RNA by polymerase chain reaction or ZIKV-reactive IgM by ELISA. To provide more specific evidence of exposure, focus reduction neutralization tests were performed on ELISA-positive samples. Overall, we observed 25 suspected ZIKV infections for an estimated incidence of 2.8 symptomatic cases per 1,000 persons per year. Our findings emphasize the continuing threat of ZIKV transmission in the setting of decreased surveillance and reporting.

A Pilot Seroprevalence Study Suggests Silent Zika virus Transmission in Bhopal Region of Central India.

Several sporadic cases and outbreaks of Zika virus disease have been reported from different states of India. This paper explored the possibility of any ongoing transmission of Zika virus (ZIKV) in the Bhopal region of Central India, where the last outbreak of this disease was reported in 2018. We screened a group of 75 febrile patients who had already tested negative for the locally endemic causes of fever like dengue, chikungunya, enteric fever, malaria, and scrub typhus and two groups of asymptomatic healthy individuals represented by blood donors (n = 75) and antenatal mothers (n = 75). We tested blood samples of febrile patients for ZIKV RNA using real-time polymerase chain reaction (PCR), and for the healthy individuals, we determined anti-zika immunoglobulin G (IgG) antibodies using enzyme-linked immunosorbent assay. ZIKV RNA was not detected in any of the 75 samples tested by real-time PCR assay. Among the voluntary blood donors and antenatal mothers, a total of 10 (15.38%) and 5 (6.66%) individuals were found to be seropositive for anti-ZIKV IgG antibodies, respectively. The seropositive group was found to have higher age 33.06 (±10.83) years as compared to seronegative individuals 26.60 (±5.12) years (P = 0.037). This study, which is the first survey of seroprevalence of anti-Zika antibodies from India, reports an overall seropositivity rate of 10% for anti-Zika antibodies among the healthy population, suggesting an ongoing, low level, silent transmission of ZIKV in the local community.

Impact of FDA's HCT/P ZIKV Recommendations on Cord Blood Unit Eligibility and Utilization in a Large Public Cord Blood Bank.

Cord blood units (CBUs) that are ineligible for licensure due to incomplete compliance with FDA recommendations may be used for hematopoietic stem cell transplantation under urgent medical need and an Investigational Drug Application. The largest reason for CBU donor ineligibility is Zika virus (ZIKV) risk. The study's objective was to analyze the impact of current FDA recommendations for ZIKA risk on a large public cord blood bank and propose updated recommendations. We performed a retrospective analysis of Carolinas Cord Blood Bank (CCBB), an FDA licensed public CBB, using data from January 1, 2016 to November 21, 2023 and compared FDA recommendations for transfusion transmitted infections (TTI) for blood products and relevant communicable disease agents or diseases for human cell, tissue, or cellular or tissue-based products (HCT/Ps). CCBB: 9057 (84.3% licensed) CBUs were banked. 984/1682 (58.5%) of unlicensed CBUs had ZIKV risk. 22.0% of CBUs with ZIKV risk were from Hispanic parents, compared to 16.1% of all units. 31 of IND CBUs (11 due to ZIKV risk without reported ZIKV transmission) were safely infused. FDA Guidance: HCT/P ZIKV, HIV, and vCJD recommendations have not been updated since 2018 in contrast to FDA removal of ZIKV as a relevant TTI in 2021 and updating HIV and vCJD guidance related to TTI in 2023 and 2022, respectively. The FDA should consider new data to revise the HCT/P donor eligibility recommendations, which will increase the number of eligible HCT/P donors, and potentially improve access to therapies for a more diverse patient population.

Optimal control problem for mathematical modeling of Zika virus transmission using fractional order derivatives

This study delves into the dynamics of Zika virus transmission by employing a mathematical model to explain virus spread with fractional order derivatives. The population is divided into two groups: the human group and the ticks group to accurately explain the transmission routes of the virus. The objective of this research is to protect susceptible individuals from infection and curb the spread of this endemic disease. To achieve this, we have included two control measures: the first is a sensibilization program, and the second is treatment. We investigate the use of optimal control strategies and fractional derivative techniques under the Caputo method to reduce the number of exposed and infected individuals. By employing the Pontryagin maximum principle to analyze and characterize the optimal controls, the proposed method is further validated through numerical simulations. The outcome of this study highlights the importance of containing the rate of dynamic dissemination in preventing the Zika epidemic.

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 effect of demographic stochasticity on Zika virus transmission dynamics: Probability of disease extinction, sensitivity analysis, and mean first passage time.

Viral infections spread by mosquitoes are a growing threat to human health and welfare. Zika virus (ZIKV) is one of them and has become a global worry, particularly for women who are pregnant. To study ZIKV dynamics in the presence of demographic stochasticity, we consider an established ZIKV transmission model that takes into consideration the disease transmission from human to mosquito, mosquito to human, and human to human. In this study, we look at the local stability of the disease-free and endemic equilibriums. By conducting the sensitivity analysis both locally and globally, we assess the effect of the model parameters on the model outcomes. In this work, we use the continuous-time Markov chain (CTMC) process to develop and analyze a stochastic model. The main distinction between deterministic and stochastic models is that, in the absence of any preventive measures such as avoiding travel to infected areas, being careful from mosquito bites, taking precautions to reduce the risk of sexual transmission, and seeking medical care for any acute illness with a rash or fever, the stochastic model shows the possibility of disease extinction in a finite amount of time, unlike the deterministic model shows disease persistence. We found that the numerically estimated disease extinction probability agrees well with the analytical probability obtained from the Galton-Watson branching process approximation. We have discovered that the disease extinction probability is high if the disease emerges from infected mosquitoes rather than infected humans. In the context of the stochastic model, we derive the implicit equation of the mean first passage time, which computes the average amount of time needed for a system to undergo its first state transition.

Attitudinal exposure to mosquito bites in two rural suburb communities of Ado-Ekiti, Nigeria

Presence of infected mosquitoes coupled with poor mosquito avoidance practice of community people have made them predisposed to Mosquito-borne diseases. Attitude and practice that could expose people to mosquito bites were investigated among some volunteer members of two rural suburb communities (Ilokun and Irasa) in Ado-Ekiti, Nigeria. A cross sectional community-based study using questionnaires administration was used to obtain information from respondents and adult mosquitoes were also collected outdoors using light traps in both communities. Data collected were analysed with SPSS version 20 and probability value (p-value) was regarded as significant at p < 0.05 for inferential statistics. Four hundred respondents participated in the study, 219 (54.8%) were males while 181 (45.3%) were females. Only three respondents knew mosquitoes could transmit zika virus. Majority of the respondents, 374 (93.5%) associated mosquito bites with malaria. Majority, 281 (71.2%) claimed to sleep under bed nets, few of their houses, 126 (31.4%) had window screened nets, 88 (22.0%) used mosquito repellent and 154 (38.6%) stayed outdoors at dusk. No significant difference (p > 0.05) existed in the mosquito avoidance practice among respondents from both communities. Five hundred and thirteen (513) mosquitoes were collected from both communities. Culex, 256 (49.9%), Anopheles, 205 (40.0%) and Aedes, 52 (10.1%). Mosquitoes collected at Ilokun, 292 (56.9%) was higher than 221 (43.1.3%) collected at Irasa. No significant difference (P = 0.920) existed in the population distribution of the mosquito genera in both communities. Enlightenment about many diseases transmitted by mosquitoes is needed in the study area.

Case report: Zika surveillance complemented with wastewater and mosquito testing

In June 2023, a local cluster of 15 Zika cases was reported in a neighbourhood in Northeastern Singapore. The last significant local transmission of Zika virus (ZIKV) with more than 450 cases was in 2016-2017. To monitor the situation and mitigate further transmission, case, entomological and wastewater-based surveillance were carried out. Primary healthcare practitioners and the community were alerted to encourage timely case identification. Surveillance was enhanced through testing of Aedes mosquitoes collected from the National Gravitrap surveillance system, and wastewater samples were collected from a network of autosamplers deployed at manholes across the country. ZIKV RNA was detected in mosquito pools (3/43; 7%) and individual mosquitoes (3/82; 3.7%) captured, and in wastewater samples (13/503) collected from the vicinity of the cluster of cases. Respective samples collected from other sites across the country were negative. The peak detection of ZIKV RNA in mosquitoes and wastewater coincided temporally with the peak in the number of cases in the area (15-25 May 2023). The restriction of ZIKV signals from wastewater and mosquitoes within the neighbourhood suggested limited ZIKV transmission. The subsequent waning of signals suggested effectiveness of control measures. We demonstrate the utility of wastewater-based surveillance of ZIKV, which complements existing case- and entomological-based surveillance. The non-intrusive approach is particularly useful to monitor diseases such as Zika, which generally causes silent or mild infections, but may cause severe outcomes such as congenital Zika syndrome. This study was funded by Singapore's Ministry of Finance and the National Environment Agency, Singapore.

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.

Estimating the potential risk of transmission of arboviruses in the Americas and Europe: a modelling study

Estimates of the spatiotemporal distribution of different mosquito vector species and the associated risk of transmission of arboviruses are key to design adequate policies for preventing local outbreaks and reducing the number of human infections in endemic areas. In this study, we quantified the abundance of Aedes albopictus and Aedes aegypti and the local transmission potential for three arboviral infections at an unprecedented spatiotemporal resolution in areas where no entomological surveillance is available. We developed a computational model to quantify the daily abundance of Aedes mosquitoes, leveraging temperature and precipitation records. The model was calibrated on mosquito surveillance data collected in 115 locations in Europe and the Americas between 2007 and 2018. Model estimates were used to quantify the reproduction number of dengue virus, Zika virus, and chikungunya in Europe and the Americas, at a high spatial resolution. In areas colonised by both Aedes species, A aegypti was estimated to be the main vector for the transmission of dengue virus, Zika virus, and chikungunya, being associated with a higher estimate of R0 when compared with A albopictus. Our estimates highlighted that these arboviruses were endemic in tropical and subtropical countries, with the highest risks of transmission found in central America, Venezuela, Colombia, and central-east Brazil. A non-negligible potential risk of transmission was also estimated for Florida, Texas, and Arizona (USA). The broader ecological niche of A albopictus could contribute to the emergence of chikungunya outbreaks and clusters of dengue autochthonous cases in temperate areas of the Americas, as well as in mediterranean Europe (in particular, in Italy, southern France, and Spain). Our results provide a comprehensive overview of the transmission potential of arboviral diseases in Europe and the Americas, highlighting areas where surveillance and mosquito control capacities should be prioritised. EU and Ministero dell'Università e della Ricerca, Italy (Piano Nazionale di Ripresa e Resilienza Extended Partnership initiative on Emerging Infectious Diseases); EU (Horizon 2020); Ministero dell'Università e della Ricerca, Italy (Progetti di ricerca di Rilevante Interesse Nazionale programme); Brazilian National Council of Science, Technology and Innovation; Ministry of Health, Brazil; and Foundation of Research for Minas Gerais, Brazil.