Transmission Dynamics Of Zika Virus Research Articles

Transmission dynamics of Zika virus with multiple infection routes and a case study in Brazil

The Zika virus (ZIKV) is a serious global public health crisis. A major control challenge is its multiple transmission modes. This paper aims to simulate the transmission patterns of ZIKV using a dynamic process-based epidemiological model written in ordinary differential equations, which incorporates the human-to-mosquito infection by bites and sewage, mosquito-to-human infection by bites, and human-to-human infection by sex. Mathematical analyses are carried out to calculate the basic reproduction number and backward bifurcation, and prove the existence and stability of the equilibria. The model is validated with infection data by applying it to the 2015–2016 ZIKV epidemic in Brazil. The results indicate that the reproduction number is estimated to be 2.13, in which the contributions by mosquito bite, sex and sewage account for 85.7%, 3.5% and 10.8%, respectively. This number and the morbidity rate are most sensitive to parameters related to mosquito ecology, rather than asymptomatic or human-to-human transmission. Multiple transmission routes and suitable temperature exacerbate ZIKV infection in Brazil, and the vast majority of human infection cases were prevented by the intervention implemented. These findings may provide new insights to improve the risk assessment of ZIKV infection.

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.

Optimal control applied to Zika virus epidemics in Colombia and Puerto Rico

Zika virus (ZIKV) is a mostly non-lethal disease in humans transmitted by mosquitoes or humans that can produce severe brain defects such as microcephaly in babies and Guillain-Barré syndrome in elderly adults. The use of optimal control strategies involving information campaigns about insect repellents and condoms alongside an available safe and effective vaccine can prevent the number of infected humans with ZIKV. A system of nonlinear ordinary differential equations is formulated for the transmission dynamics of ZIKV in the presence of three control strategies to evaluate the impact of various scenarios during a ZIKV epidemic. In addition, we estimate parameters using weekly incidence data from previous ZIKV outbreaks in Colombia and Puerto Rico to capture the dynamics of an epidemic in each country when control measures are available. The basic reproduction number, R0, of each country is calculated using estimated parameters (without the controls). The vector-borne transmission threshold (Rv) is dominant in both countries, but the sexual transmission threshold (Rd) in Colombia is considerably higher than in Puerto Rico. Numerical simulations for Colombia show that the most effective strategies are to use three controls since the start of the outbreak. However, for Puerto Rico only information campaigns about mosquito repellents and vaccination are the most effective ways to mitigate the epidemic.

Modeling and transmission dynamics of Zika virus through efficient numerical method

Zika virus infection is a vastly transmitted disease among humans. It was carried worldwide by international travelers. In 2016, Zika virus infection was present in more than 20 countries and territories in America. Thousands of cases were diagnosed in Cabo Verde, western Africa. Fifty-seven regions suffered from Zika virus in 2020, and the World Health Organization reported more than one hundred thousand cases worldwide. In this work, the modeling and transmission dynamics of Zika virus are studied dynamically and numerically. Positivity, boundedness, reproduction number, equilibria, and local stability are part of the numerical analysis. New nonstandard numerical techniques are examined for the said model. The primary purpose is to maintain the continuous model’s behavior and dynamical properties. The proposed nonstandard finite approximation is studied according to the consistency and local stability of the solutions. Some numerical examples clearly show the improvement of the new schemes compared to other well-known methods.

Experimental infection of Artibeus lituratus bats and no detection of Zika virus in neotropical bats from French Guiana, Peru, and Costa Rica suggests a limited role of bats in Zika transmission.

Bats are important natural reservoir hosts of a diverse range of viruses that can be transmitted to humans and have been suggested to play an important role in the Zika virus (ZIKV) transmission cycle. However, the exact role of these animals as reservoirs for flaviviruses is still controversial. To further expand our understanding of the role of bats in the ZIKV transmission cycle in Latin America, we carried out an experimental infection in wild-caught Artibeus lituratus bats and sampled several free-living neotropical bats across three countries of the region. Experimental ZIKV infection was performed in wild-caught adult bats (4 females and 5 males). The most relevant findings were hemorrhages in the bladder, stomach and patagium. Significant histological findings included inflammatory infiltrate consisting of a predominance of neutrophils and lymphocytes, in addition to degeneration in the reproductive tract of males and females. This suggests that bat reproduction might be at some level affected by ZIKV. Leukopenia was also observed in some inoculated animals. Hemorrhages, genital alterations, and leukopenia are suggested to be caused by ZIKV; however, since these were wild-caught bats, we cannot exclude other agents. Detection of ZIKV by qPCR was observed at low concentrations in only two urine samples in two inoculated animals. All other animals and tissues tested were negative. Finally, no virus-neutralizing antibodies were found in any animal. To determine ZIKV infection in nature, the blood of a total of 2056 bats was sampled for ZIKV detection by qPCR. Most of the sampled individuals belonged to the genus Pteronotus sp. (23%), followed by the species Carollia sp. (17%), Anoura sp. (14%), and Molossus sp. (13.7%). No sample of any tested species was positive for ZIKV by qPCR. These results together suggest that bats are not efficient amplifiers or reservoirs of ZIKV and may not have an important role in ZIKV transmission dynamics.

Mathematical modeling on co-infection: transmission dynamics of Zika virus and Dengue fever

Mathematical modeling on co-infection: transmission dynamics of Zika virus and Dengue fever

Caputo fractional order derivative model of Zika virus transmission dynamics

The Zika Virus (ZIKV) is a highly contagious disease, and several outbreaks have occurred since it emerged. It is transmitted from one to another human via a mosquito Aedes aegypti. There is no vaccine or established medicine available for ZIKV to date. There is an urgent need to enhance an understanding of the progression mechanism of the disease when drugs or vaccines are not available. Mathematical modeling is a tool that might be helpful to understand the progression dynamics of ZIKV which can enable us to make control strategies for invading the progression dynamics of disease. SEIR-SEI is a famous compartmental deterministic modeling based on integer-order derivative calculus. Nowadays, conversion from integer to fractional order-based derivative modeling is in trend, and it is a very effective and high degree of accuracy. In this paper, we proposed a Caputo fractional-order based susceptible-exposed-infected-recovered (SEIR) structure for hosts and a susceptible-exposed-infected (SEI) structure for mosquitoes for transmission dynamics of ZIKV. For this purpose, we modified the classical compartmental model used in the study of progression dynamics of the Zika fever outbreak in El-Salvador during 2015-16. The modified model involves nonlinear differential equations of fractional (non-integer) order which has an advantage over the classical model due to its memory effect property. Our study includes eight regions across the globe where the Zika outbreak has occurred during the year 2013-2016 including six major archipelagos of French Polynesia, i.e., Tahiti, Sous-le-vent, Moorea, Tuamotu, Marquises, and Australes. The other two regions included Costa Rica and Colombia. The outbreak in selected regions was studied first using a classical model and then compared by a fractional-order model. The data of outbreaks are best fitted with the fractional-order model which enables us to estimate the best parameters values for the outbreaks. Using this modeling, the epidemic threshold parameter $R_0$ was computed which is more accurate than the classical one. Hence, the fractional-order model for ZIKV transmission dynamics is much better prediction, analysis, and disease parameters estimation than the classical model. This modeling enhances the knowledge in the field of fractional order and understanding the ZIKV transmission accurately.

Transmission dynamics of zika virus in presence of vertical transmission and some preventive measures

Zika virus (ZIKV) infection is a vector-born human disease which enhances the chance of various types of neurological complications in affected individual. In this work we have studied a mathematical model of ZIKV by incorporating vector, direct (sexual) and vertical transmission paths of the virus. In our model also we have considered different kind of preventive measures like as: protection of susceptible individuals from mosquito bites, isolation of infected individuals from mosquito, protection of susceptible individuals from sexual interaction with infected individuals, and mosquitoes control effort. We have found the analytical expression of basic reproduction number and studied the stability of the disease free equilibrium point. Existence of endemic equilibrium point and its stability are also studied. The proposed model exhibits a backward bifurcation when the virus transmission probability from infected human to mosquito crosses the crucial value. We have fitted the model to real data and estimated the key model parameters and their 95% confidence interval which depict the ZIKV outbreak in French Polynesia in 2013-14. We also have estimated the basic reproduction number using first nine epidemic weeks (EW) data and the estimated value is 2.87 with lower and upper values are 2.47 and 3.32 respectively. The effective reproduction number of the outbreak also has been studied and which decreases gradually from 5.404 to 0.2499 during the period 11th October, 2013 and 28th March, 2014. According to our sensitivity analysis, the basic reproduction number is the most sensitive with controllable parameters, biting rate, mosquito recruitment rate, mosquito death rate and recovery rate from infection. Finally, numerically we have studied the impact of different parameters on the basic reproduction number and on the number of infected human population.

A mathematical analysis of Zika virus transmission with optimal control strategies

This paper presents a mathematical model for transmission dynamics of Zika virus by considering standard incidence type interaction for the human to human transmission. The model involves the transmission through the bite of infected Aedes mosquitoes and human to human sexual transmission. The equilibria of the proposed model are found and the basic reproduction number R0 is computed. If R0 1. The sensitivity analysis is performed to identify the key parameters that affect the basic reproduction number, which can be regulated to control the transmission dynamics of the Zika. Further, this model is extended to the optimal control model and to reveals the optimal control strategies we used the Pontryagin’s Maximum Principle. It has been noticed that the optimal control gives better result than without the optimal control model. Numerical simulation is presented to support our mathematical findings.

Transmission dynamics of zika virus in presence of vertical transmission and some preventive measures

Transmission dynamics of zika virus in presence of vertical transmission and some preventive measures

Low Aedes aegypti Vector Competence for Zika Virus from Viremic Rhesus Macaques.

Despite worldwide efforts to understand the transmission dynamics of Zika virus (ZIKV), scanty evaluation has been made on the vector competence of Aedes aegypti fed directly on viremic human and non-human primates (NHPs). We blood-fed Ae. aegypti from two districts in Rio de Janeiro on six ZIKV infected pregnant rhesus macaques at several time points, half of which were treated with Sofosbuvir (SOF). Mosquitoes were analyzed for vector competence after 3, 7 and 14 days of incubation. Although viremia extended up to eight days post monkey inoculation, only mosquitoes fed on the day of the peak of viremia, recorded on day two, became infected. The influence of SOF treatment could not be assessed because the drug was administered just after mosquito feeding on day two. The global infection, dissemination and transmission rates were quite low (4.09%, 1.91% and 0.54%, respectively); no mosquito was infected when viremia was below 1.26 × 105 RNA copies/mL. In conclusion, Ae. aegypti vector competence for ZIKV from macaques is low, likely to be due to low viral load and the short duration of ZIKV viremia in primates suitable for infecting susceptible mosquitoes. If ZIKV infection in human and macaques behaves similarly, transmission of the Zika virus in nature is most strongly affected by vector density.

Releasing Wolbachia-infected mosquitos to mitigate the transmission of Zika virus

Although many people infected with Zika virus do not get sick or only have mild symptoms, pregnant women infected with Zika virus may have babies with severe birth defects. To understand the transmission dynamics of Zika virus, we develop deterministic and stochastic models, taking into account mosquito-human transmission, sexual transmission, and the release of Wolbachia-infected male mosquitoes. For the deterministic model, we analyze the stability of the disease-free equilibrium and evaluate the impact of the parameters on the basic reproduction number by sensitivity analysis. We found the upper and lower bounds for the release rate of Wolbachia-infected male mosquitoes to be cost effective. Since the transmission of infectious diseases is affected by many stochastic factors, we incorporate the impact of environmental white noise on death rates of adult mosquitoes, mosquitoes at aquatic stages, and humans to develop a stochastic model for Zika. We proved that the stochastic model has a unique and bounded global solution and derived the sufficient conditions for the extinction of Zika. We also proved the existence of a unique ergodic stationary distribution of the solutions. Numerical simulations show that the stochasticity may drive the disease to extinction when the intensity of the white noise is large enough, and the release of Wolbachia-infected mosquitoes shortens the time it takes for the wild mosquitoes to become extinct.

MODELING ZIKA TRANSMISSION DYNAMICS: PREVENTION AND CONTROL

The Zika virus (ZIKV) epidemic is depicted to have high spatial diversity and slow growth, attributable to the dynamics of the mosquito vector and mobility of the human populations. In an effort to understand the transmission dynamics of Zika virus, we formulate a new compartmental epidemic model with a system of seven differential equations and 11 parameters incorporating the decaying transmission rate and study the impact of protection measure on basic public health. We do not fit the model to the observed pattern of spread, rather we use parameter values estimated in the past and examine the extent to which the designed model prediction agrees with the pattern of spread seen in Brazil, via reaction–diffusion modeling. Our work includes estimation of key epidemiological parameters such as basic reproduction number ([Formula: see text], and gives a rough estimate of how many individuals can be typically infected during an outbreak if it occurs in India. We used partial rank correlation coefficient method for global sensitivity analysis to identify the most influential model parameters. Using optimal control theory and Pontryagin’s maximum principle, a control model has been proposed and conditions for the optimal control are determined for the deterministic model of Zika virus. The control functions for the strategies (i) vector-to-human contact reduction and (ii) vector elimination are introduced into the system. Numerical simulations are also performed. This work aimed at understanding the potential extent and timing of the ZIKV epidemic can be used as a template for the analysis of future mosquito-borne epidemics.

Impact of temperature on the extrinsic incubation period of Zika virus in Aedes aegypti.

Since Zika virus (ZIKV) emerged as a global human health threat, numerous studies have pointed to Aedes aegypti as the primary vector due to its high competence and propensity to feed on humans. The majority of vector competence studies have been conducted between 26–28°C, but arboviral extrinsic incubation periods (EIPs), and therefore transmission efficiency, are known to be affected strongly by temperature. To better understand the relationship between ZIKV EIPs and temperature, we evaluated the effect of adult mosquito exposure temperature on ZIKV infection, dissemination, and transmission in Ae. aegypti at four temperatures: 18°C, 21°C, 26°C, and 30°C. Mosquitoes were exposed to viremic mice infected with a 2015 Puerto Rican ZIKV strain, and engorged mosquitoes were sorted into the four temperatures with 80% RH and constant access to 10% sucrose. ZIKV infection, dissemination, and transmission rates were assessed via RT-qPCR from individual mosquito bodies, legs and wings, and saliva, respectively, at three to five time points per temperature from three to 31 days, based on expectations from other flavivirus EIPs. The median time from ZIKV ingestion to transmission (median EIP, EIP50) at each temperature was estimated by fitting a generalized linear mixed model for each temperature. EIP50 ranged from 5.1 days at 30°C to 24.2 days at 21°C. At 26°C, EIP50 was 9.6 days. At 18°C, only 15% transmitted by day 31 so EIP50 could not be estimated. This is among the first studies to characterize the effects of temperature on ZIKV EIP in Ae. aegypti, and the first to do so based on feeding of mosquitoes on a live, viremic host. This information is critical for modeling ZIKV transmission dynamics to understand geographic and seasonal limits of ZIKV risk; it is especially relevant for determining risk in subtropical regions with established Ae. aegypti populations and relatively high rates of return travel from the tropics (e.g. California or Florida), as these regions typically experience cooler temperature ranges than tropical regions.

Arbovirus vectors of epidemiological concern in the Americas: A scoping review of entomological studies on Zika, dengue and chikungunya virus vectors

Three arthropod-borne viruses (arboviruses) causing human disease have been the focus of a large number of studies in the Americas since 2013 due to their global spread and epidemiological impacts: Zika, dengue, and chikungunya viruses. A large proportion of infections by these viruses are asymptomatic. However, all three viruses are associated with moderate to severe health consequences in a small proportion of cases. Two mosquito species, Aedes aegypti and Aedes albopictus, are among the world's most prominent arboviral vectors, and are known vectors for all three viruses in the Americas. This review summarizes the state of the entomological literature surrounding the mosquito vectors of Zika, dengue and chikungunya viruses and factors affecting virus transmission. The rationale of the review was to identify and characterize entomological studies that have been conducted in the Americas since the introduction of chikungunya virus in 2013, encompassing a period of arbovirus co-circulation, and guide future research based on identified knowledge gaps. The preliminary search for this review was conducted on PubMed (National Library of Health, Bethesda, MD, United States). The search included the terms 'zika' OR 'dengue' OR 'chikungunya' AND 'vector' OR 'Aedes aegypti' OR 'Aedes albopictus'. The search was conducted on March 1st of 2018, and included all studies since January 1st of 2013. A total of 96 studies were included in the scoping review after initial screening and subsequent exclusion of out-of-scope studies, secondary data publications, and studies unavailable in English language. We observed a steady increase in number of publications, from 2013 to 2018, with half of all studies published from January 2017 to March 2018. Interestingly, information on Zika virus vector species composition was abundant, but sparse on Zika virus transmission dynamics. Few studies examined natural infection rates of Zika virus, vertical transmission, or co-infection with other viruses. This is in contrast to the wealth of research available on natural infection and co-infection for dengue and chikungunya viruses, although vertical transmission research was sparse for all three viruses.

Transmission dynamics of Zika virus incorporating harvesting.

In this paper, we establish a ZIKV model and investigate the transmission dynamics of ZIKV with two types of harvesting: proportional harvesting and constant harvesting, and give the stability of the steady states of both disease-free and endemic equilibrium, analyze the effect of harvesting on ZIKV transmission dynamics via numerical simulation. We find that proportional harvesting strategy can eliminate the virus when the basic reproduction number $R_0$ is less than 1, but the constant harvesting strategy may control the virus whether the basic reproduction number is less than 1 or not. Epidemiologically, we find that increasing harvesting may stimulate an increase in the number of virus infections at some point, and harvesting can postpone the peak of disease transmission with the mortality of mosquito increasing. The results can provide us with some useful control strategies to regulate ZIKV dynamics.

A33 Using serological and surveillance data to infer the introduction date and unobserved transmission dynamics of Zika virus in Fiji 2013–7

Zika virus (ZIKV) has been circulating in the South Pacific since 2007, and transmission in Fiji was first confirmed in 2015. To better understand the history and transmission dynamics of ZIKV in Fiji, we combined a transmission dynamic model with serological and surveillance data from Central Division, Fiji. A longitudinal population representative of seroepidemiological data were available from participants sampled in 2013, 2015, and 2017. In addition, ZIKV case reports were available from 2015 and 2016. Using a Bayesian approach, we fitted a transmission dynamic model with a seasonally varying transmission to these data. We also estimated the virus introduction date, given the effect this has on transmission dynamics as it interacts with the observed seasonal pattern of transmission. We found evidence that the virus was introduced in October 2013 (95% credible interval: April 2013–April 2014) and that the strong seasonal transmission pattern meant the virus persisted for several years with multiple waves of infection in consecutive years. It is important to corroborate this evidence against other work done in the same area. A phylogenetic analysis was performed on 5 ZIKV strains obtained from Fiji in 2015 and 2016, which were aligned with 33 E gene sequences from the Pacific, Americas, and Africa. This analysis showed evidence of virus persistence over multiple years in Central Division, Fiji. The estimated most recent common ancestor of the group isolated from Central Division was November 2013 (95% credible interval: March 2013–July 2015). Our modeling estimate is consistent with these results despite the very different methods being used. The availability of detailed case and serology data in an island outbreak setting, combined with mathematical models, presented a unique opportunity to gain crucial insights into these infections. Our analysis provides evidence that seasonal variation in transmission, combined with other co-circulating flaviviruses, means the timing of ZIKV introduction can have a major impact on outbreak transmission dynamics.

Modeling Zika Virus Transmission Dynamics: Parameter Estimates, Disease Characteristics, and Prevention

Because of limited data, much remains uncertain about parameters related to transmission dynamics of Zika virus (ZIKV). Estimating a large number of parameters from the limited information in data may not provide useful knowledge about the ZIKV. Here, we developed a method that utilizes a mathematical model of ZIKV dynamics and the complex-step derivative approximation technique to identify parameters that can be estimated from the available data. Applying our method to epidemic data from the ZIKV outbreaks in French Polynesia and Yap Island, we identified the parameters that can be estimated from these island data. Our results suggest that the parameters that can be estimated from a given data set, as well as the estimated values of those parameters, vary from Island to Island. Our method allowed us to estimate some ZIKV-related parameters with reasonable confidence intervals. We also computed the basic reproduction number to be from 2.03 to 3.20 across islands. Furthermore, using our model, we evaluated potential prevention strategies and found that peak prevalence can be reduced to nearly 10% by reducing mosquito-to-human contact by at least 60% or increasing mosquito death by at least a factor of three of the base case. With these preventions, the final outbreak-size is predicted to be negligible, thereby successfully controlling ZIKV epidemics.

Exosomes mediate Zika virus transmission through SMPD3 neutral Sphingomyelinase in cortical neurons

ABSTRACT The harmful effects of ZIKA virus (ZIKV) infection are reflected by severe neurological manifestations such as microcephaly in neonates and other complications associated with Guillain-Barré syndrome in adults. The transmission dynamics of ZIKV in or between neurons, or within the developing brains of the foetuses are not fully understood. Using primary cultures of murine cortical neurons, we show that ZIKV uses exosomes as mediators of viral transmission between neurons. Cryo-electron microscopy showed heterogeneous population of neuronal exosomes with a size range of 30–200 nm. Increased production of exosomes from neuronal cells was noted upon ZIKV infection. Neuronal exosomes contained both ZIKV viral RNA and protein(s) that were highly infectious to naïve cells. RNaseA and neutralizing antibodies treatment studies suggest the presence of viral RNA/proteins inside exosomes. Exosomes derived from time- and dose-dependent incubations showed increasing viral loads suggesting higher packaging and delivery of ZIKV RNA and proteins. Furthermore, we noted that ZIKV induced both activity and gene expression of neutral Sphingomyelinase (nSMase)-2/SMPD3, an important molecule that regulates production and release of exosomes. Silencing of SMPD3 in neurons resulted in reduced viral burden and transmission through exosomes. Treatment with SMPD3 specific inhibitor GW4869, significantly reduced ZIKV loads in both cortical neurons and in exosomes derived from these neuronal cells. Taken together, our results suggest that ZIKV modulates SMPD3 activity in cortical neurons for its infection and transmission through exosomes perhaps leading to severe neuronal death that may result in neurological manifestations such as microcephaly in the developing embryonic brains.

Transmission dynamics of Zika virus with spatial structure—A case study in Rio de Janeiro, Brazil

In this paper, we investigate the effect of the spatial heterogeneity on the extinction and persistence of the Zika virus (ZIKV) further. We define the basic reproduction number R0 and prove that R0 can be used to govern the threshold dynamics of the ZIKV: if R0<1, the unique disease-free equilibrium is globally asymptotic stable and the ZIKV will die out, while if R0>1, there is at least one endemic equilibrium and the ZIKV will persist uniformly. Via numerical simulations, we show the evolution of the spatial distribution of infected people and find that the final size of the infected people is 25,717, which agrees nearly with the real weekly reported case data 25,400 from November 1, 2015 to April 10, 2016 in Rio de Janeiro, Brazil.