Wolbachia Invasion Research Articles

Wolbachia Invasion in Mosquitoes with Incomplete CI, Imperfect Maternal Transmission and Maturation Delay.

The mechanism of cytoplasmic incompatibility (CI) is important in the study of Wolbachia invasion in wild mosquitoes. Su et al. (Bull Math Biol 84(9):95, 2022) proposed a delay differential equation model by relating the CI effect to maturation delay. In this paper, we investigate the dynamics of this model by allowing the same density-dependent death rate and distinct density-independent death rates. Through analyzing the existence and stability of equilibria, we obtain the parameter conditions for Wolbachia successful invasion if the maternal transmission is perfect. While if the maternal transmission is imperfect, we give the ranges of parameters to ensure failure invasion, successful invasion and partially suppressing, respectively. Meanwhile, numerical simulations indicate that the system may exhibit monostable and bistable dynamics when parameters vary. Particularly, in the bistable situation an unstable separatrix, like a line, exists when choosing constant functions as initial values; and the maturation delay affects this separatrix in an interesting way.

Gene Drive and Symbiont Technologies for Control of Mosquito-Borne Diseases.

Mosquito-borne diseases, such as dengue and malaria, pose a significant burden to global health. Current control strategies with insecticides are only moderately effective. Scalable solutions are needed to reduce the transmission risk of these diseases. Symbionts and genome engineering-based mosquito control strategies have been proposed to address these problems. Bacterial, fungal, and viral symbionts affect mosquito reproduction, reduce mosquito lifespan, and block pathogen transmission. Field tests of endosymbiont Wolbachia-based methods have yielded promising results, but there are hurdles to overcome due to the large-scale rearing and accurate sex sorting required for Wolbachia-based suppression approaches and the ecological impediments to Wolbachia invasion in replacement approaches. Genome engineering-based methods, in which mosquitoes are genetically altered for the modification or suppression of wild populations, offer an additional approach for control of mosquito-borne diseases. In particular, the use of gene drive alleles that bias inheritance in their favor is a potentially powerful approach. Several drives are frequency dependent, potentially giving them broadly similar population dynamics to Wolbachia. However, public acceptance and the behavior of released drives in natural mosquito populations remain challenges. We summarize the latest developments and discuss the knowledge gaps in both symbiont- and gene drive-based methods.

Population genetic structure of Culex tritaeniorhynchus in different types of climatic zones in China

BackgroundCulex tritaeniorhynchus is widely distributed in China, from Hainan Island in the south to Heilongjiang in the north, covering tropical, subtropical, and temperate climate zones. Culex tritaeniorhynchus carries 19 types of arboviruses. It is the main vector of the Japanese encephalitis virus (JEV), posing a serious threat to human health. Understanding the effects of environmental factors on Culex tritaeniorhynchus can provide important insights into its population structure or isolation patterns, which is currently unclear.ResultsIn total, 138 COI haplotypes were detected in the 552 amplified sequences, and the haplotype diversity (Hd) value increased from temperate (0.534) to tropical (0.979) regions. The haplotype phylogeny analysis revealed that the haplotypes were divided into two high-support evolutionary branches. Temperate populations were predominantly distributed in evolutionary branch II, showing some genetic isolation from tropical/subtropical populations and less gene flow between groups. The neutral test results of HNQH (Qionghai) and HNHK(Haikou) populations were negative (P < 0.05), indicating many low-frequency mutations in the populations and that the populations might be in the process of expansion. Moreover, Wolbachia infection was detected only in SDJN (Jining) (2.24%), and all Wolbachia genotypes belonged to supergroup B. To understand the influence of environmental factors on mosquito-borne viruses, we examined the prevalence of Culex tritaeniorhynchus infection in three ecological environments in Shandong Province. We discovered that the incidence of JEV infection was notably greater in Culex tritaeniorhynchus from lotus ponds compared to those from irrigation canal regions. In this study, the overall JEV infection rate was 15.27 per 1000, suggesting the current risk of Japanese encephalitis outbreaks in Shandong Province.ConclusionsTropical and subtropical populations of Culex tritaeniorhynchus showed higher genetic diversity and those climatic conditions provide great advantages for the establishment and expansion of Culex tritaeniorhynchus. There are differences in JEV infection rates in wild populations of Culex tritaeniorhynchus under different ecological conditions. Our results suggest a complex interplay of genetic differentiation, population structure, and environmental factors in shaping the dynamics of Culex tritaeniorhynchus. The low prevalence of Wolbachia in wild populations may reflect the recent presence of Wolbachia invasion in Culex tritaeniorhynchus.

Wolbachia invasion dynamics of a random mosquito population model with imperfect maternal transmission and incomplete CI.

In this work, we formulate a random Wolbachia invasion model incorporating the effects of imperfect maternal transmission and incomplete cytoplasmic incompatibility (CI). Under constant environments, we obtain the following results: Firstly, the complete invasion equilibrium of Wolbachia does not exist, and thus the population replacement is not achievable in the case of imperfect maternal transmission; Secondly, imperfect maternal transmission or incomplete CI may obliterate bistability and backward bifurcation, which leads to the failure of Wolbachia invasion, no matter how many infected mosquitoes would be released; Thirdly, the threshold number of the infected mosquitoes to be released would increase with the decrease of the maternal transmission rate or the intensity of CI effect. In random environments, we investigate in detail the Wolbachia invasion dynamics of the random mosquito population model and establish the initial release threshold of infected mosquitoes for successful invasion of Wolbachia into the wild mosquito population. In particular, the existence and stability of invariant probability measures for the establishment and extinction of Wolbachia are determined.

Comparing the long-term persistence of different Wolbachia strains after the release of bacteria-carrying mosquitoes

This paper proposes a bidimensional modeling framework for Wolbachia invasion, assuming imperfect maternal transmission, incomplete cytoplasmic incompatibility, and direct infection loss due to thermal stress. Our model adapts to various Wolbachia strains and retains all properties of higher-dimensional models. The conditions for the durable coexistence of Wolbachia-carrying and wild mosquitoes are expressed using the model’s parameters in a compact closed form. When the Wolbachia bacterium is locally established, the size of the remanent wild population can be assessed by a direct formula derived from the model. The model was tested for four Wolbachia strains undergoing laboratory and field trials to control mosquito-borne diseases: wMel, wMelPop, wAlbB, and wAu. As all these bacterial strains affect the individual fitness of mosquito hosts differently and exhibit different levels of resistance to temperature variations, the model helped to conclude that: (1) the wMel strain spreads faster in wild mosquito populations; (2) the wMelPop exhibits lower resilience but also guarantees the smallest size of the remanent wild population; (3) the wAlbB strain performs better at higher ambient temperatures than others; (4) the wAu strain is not sustainable and cannot persist in the wild mosquito population despite its resistance to high temperatures.

Insect population dynamics under Wolbachia-induced cytoplasmic incompatibility: Puzzle more than buzz in Drosophila suzukii.

In theory, the introduction of individuals infected with an incompatible strain of Wolbachia pipientis into a recipient host population should result in the symbiont invasion and reproductive failures caused by cytoplasmic incompatibility (CI). Modelling studies combining Wolbachia invasion and host population dynamics show that these two processes could interact to cause a transient population decline and, in some conditions, extinction. However, these effects could be sensitive to density dependence, with the Allee effect increasing the probability of extinction, and competition reducing the demographic impact of CI. We tested these predictions with laboratory experiments in the fruit fly Drosophila suzukii and the transinfected Wolbachia strain wTei. Surprisingly, the introduction of wTei into D. suzukii populations at carrying capacity did not result in the expected wTei invasion and transient population decline. In parallel, we found no Allee effect but strong negative density dependence. From these results, we propose that competition interacts in an antagonistic way with Wolbachia-induced cytoplasmic incompatibility on insect population dynamics. If future models and data support this hypothesis, pest management strategies using Wolbachia-induced CI should target populations with negligible competition but a potential Allee effect, for instance at the beginning of the reproductive season.

Wolbachia invasion to wild mosquito population in stochastic environment

Releasing Wolbachia-infected mosquitoes to invade the wild mosquito population is a method of mosquito control. In this paper, a stochastic mosquito population model with Wolbachia invasion perturbed by environmental fluctuation is studied. Firstly, the well-posedness, positivity, and Markov-Feller property of the solution for this model are proved. Then a group of sharp threshold-type conditions is provided to characterize the long-term behavior of the model, which pinpoints the almost necessary and sufficient conditions for the persistence and extinction of Wolbachia-infected and uninfected mosquito populations. Our results indicate that even for a low initial Wolbachia infection frequency, a successful Wolbachia invasion into the wild mosquito population can be driven by stochastic environmental fluctuations. Finally, some numerical experiments are carried out to support our theoretical results.

Sex-structured model of Wolbachia invasion and design of sex-biased release strategies in Aedes spp mosquitoes populations

Laboratory experiments as well as some field essays have revealed that the intracellular bacterium Wolbachia, deliberately introduced in Aedes spp female mosquitoes, drastically reduces their vector competence for dengue virus and, also, other mosquito-borne viral diseases. However, female mosquitoes infected with Wolbachia still need to ingest human blood while male mosquitoes, either wild or Wolbachia-carrying, do not bite people. As such, Wolbachia-carrying females may transmit the virus to people during blood-feeding, even though with far less probability than the wild ones. Therefore, massive releases of Wolbachia-carrying females may increase both the nuisance and the epidemiological risk among human residents. With the goal of exploring in depth the practical aspects of sex-biased releases, we introduce in this paper a simple sex-structured model of Wolbachia invasion that brings forward the possibility of developing male-biased release strategies of Wolbachia-carriers leading to Wolbachia invasion. Thanks to this model, we study at length the minimal amount of mosquitoes necessary to complete this task, according to the relative sex-ratio of the released mosquitoes and the release schedule. We also pay attention to the estimate of the time needed to achieve the ultimate population replacement.

Developing Wolbachia-based disease interventions for an extreme environment.

Aedes aegypti mosquitoes carrying self-spreading, virus-blocking Wolbachia bacteria are being deployed to suppress dengue transmission. However, there are challenges in applying this technology in extreme environments. We introduced two Wolbachia strains into Ae. aegypti from Saudi Arabia for a release program in the hot coastal city of Jeddah. Wolbachia reduced infection and dissemination of dengue virus (DENV2) in Saudi Arabian mosquitoes and showed complete maternal transmission and cytoplasmic incompatibility. Wolbachia reduced egg hatch under a range of environmental conditions, with the Wolbachia strains showing differential thermal stability. Wolbachia effects were similar across mosquito genetic backgrounds but we found evidence of local adaptation, with Saudi Arabian mosquitoes having lower egg viability but higher adult desiccation tolerance than Australian mosquitoes. Genetic background effects will influence Wolbachia invasion dynamics, reinforcing the need to use local genotypes for mosquito release programs, particularly in extreme environments like Jeddah. Our comprehensive characterization of Wolbachia strains provides a foundation for Wolbachia-based disease interventions in harsh climates.

Wolbachia Invasion Dynamics by Integrodifference Equations

Releasing mosquitoes infected with the endosymbiotic bacterium Wolbachia to invade and replace the wild populations can effectively interrupt dengue transmission. Recently, a reasonable discrete competitive non-spatial model was developed and the conditions for the successful invasion of Wolbachia were given. However, Wolbachia propagation is a matter of spatial dynamics. In this paper, we introduce a dispersal kernel and establish integrodifference equations, a class of discrete-time spatial diffusion systems that have recently gained much attention as an important tool for spatial ecology. We analyzed the spatial model by average dispersal success approximation to find the criteria for the successful spread of Wolbachia, and then compared it with the non-spatial model to discuss the effect of spatial parameters.

Monotonicity properties arising in a simple model of Wolbachia invasion for wild mosquito populations.

In this paper, we propose a simplified bidimensional Wolbachia infestation model in a population of Aedes aegypti mosquitoes, preserving the main features associated with the biology of this species that can be found in higher-dimensional models. Namely, our model represents the maternal transmission of the Wolbachia symbiont, expresses the reproductive phenotype of cytoplasmic incompatibility, accounts for different fecundities and mortalities of infected and wild insects, and exhibits the bistable nature leading to the so-called principle of competitive exclusion. Using tools borrowed from monotone dynamical system theory, in the proposed model, we prove the existence of an invariant threshold manifold that allows us to provide practical recommendations for performing single and periodic releases of Wolbachia-carrying mosquitoes, seeking the eventual elimination of wild insects that are capable of transmitting infections to humans. We illustrate these findings with numerical simulations using parameter values corresponding to the wMelPop strain of Wolbachia that is considered the best virus blocker but induces fitness loss in its carriers. In these tests, we considered multiple scenarios contrasting a periodic release strategy against a strategy with a single inundative release, comparing their effectiveness. Our study is presented as an expository and mathematically accessible tool to study the use of Wolbachia-based biocontrol versus more complex models.

Reduced competence to arboviruses following the sustainable invasion of Wolbachia into native Aedes aegypti from Southeastern Brazil

Field release of Wolbachia-infected Aedes aegypti has emerged as a promising solution to manage the transmission of dengue, Zika and chikungunya in endemic areas across the globe. Through an efficient self-dispersing mechanism, and the ability to induce virus-blocking properties, Wolbachia offers an unmatched potential to gradually modify wild Ae. aegypti populations turning them unsuitable disease vectors. Here we describe a proof-of-concept field trial carried out in a small community of Niterói, greater Rio de Janeiro, Brazil. Following the release of Wolbachia-infected eggs, we report here a successful invasion and long-term establishment of the bacterium across the territory, as denoted by stable high-infection indexes (> 80%). We have also demonstrated that refractoriness to dengue and Zika viruses, either thorough oral-feeding or intra-thoracic saliva challenging assays, was maintained over the adaptation to the natural environment of Southeastern Brazil. These findings further support Wolbachia’s ability to invade local Ae. aegypti populations and impair disease transmission, and will pave the way for future epidemiological and economic impact assessments.

Controlling Wolbachia Transmission and Invasion Dynamics among Aedes Aegypti Population via Impulsive Control Strategy

This work is devoted to analyzing an impulsive control synthesis to maintain the self-sustainability of Wolbachia among Aedes Aegypti mosquitoes. The present paper provides a fractional order Wolbachia invasive model. Through fixed point theory, this work derives the existence and uniqueness results for the proposed model. Also, we performed a global Mittag-Leffler stability analysis via Linear Matrix Inequality theory and Lyapunov theory. As a result of this controller synthesis, the sustainability of Wolbachia is preserved and non-Wolbachia mosquitoes are eradicated. Finally, a numerical simulation is established for the published data to analyze the nature of the proposed Wolbachia invasive model.

A simplified monotone model of Wolbachia invasion encompassing Aedes aegypti mosquitoes

AbstractWolbachia‐based biocontrol has recently emerged as a potential method for the prevention and control of dengue and other vector‐borne diseases. Major vector species, such as Aedes aegypti females, when deliberately infected with Wolbachia become far less capable of getting infected and transmitting the virus to human individuals. In this paper, we propose and qualitatively analyze a simplified model of Wolbachia invasion that describes an interaction and competition between Wolbachia‐infected and wild Aedes aegypti mosquitoes. This model not only facilitates better visualization of the Wolbachia invasion dynamics thanks to its bidimensionality, but it also possesses the noticeable property of monotonicity and exhibits the saddle‐point behavior. The latter helps to identify a threshold manifold consisting of points in that couple the minimum viable population sizes of wild and Wolbachia‐carrying insects and also regulate the survival and extinction of each population of mosquitoes.

Wolbachia-Mitochondrial DNA Associations in Transitional Populations of Rhagoletis cerasi.

Simple SummaryWolbachia is an endosymbiotic bacterium that infects numerous insects and crustaceans. Its ability to alter the reproduction of hosts results in incompatibilities of differentially infected individuals. Therefore, Wolbachia has been applied to suppress agricultural and medical insect pests. The European cherry fruit fly, Rhagoletis cerasi, is mainly distributed throughout Europe and Western Asia, and is infected with at least five different Wolbachia strains. The strain wCer2 causes incompatibilities between infected males and uninfected females, making it a potential candidate to control R. cerasi. Thus, the prediction of its spread is of practical importance. Like mitochondria, Wolbachia is inherited from mother to offspring, causing associations between mitochondrial DNA and endosymbiont infection. Misassociations, however, can be the result of imperfect maternal transmission, the loss of Wolbachia, or its horizontal transmission from infected to uninfected individuals. These are important parameters influencing the spread of infection. Here, we studied Wolbachia-mitochondrial haplotype associations in R. cerasi in two transition zones in the Czech Republic and Hungary, where wCer2 is currently spreading. Our results suggest imperfect maternal transmission only in the early phases of wCer2 invasion and no evidence of horizontal transmission of wCer2 in R. cerasi.The endosymbiont Wolbachia can manipulate arthropod host reproduction by inducing cytoplasmic incompatibility (CI), which results in embryonic mortality when infected males mate with uninfected females. A CI-driven invasion of Wolbachia can result in a selective sweep of associated mitochondrial haplotype. The co-inheritance of Wolbachia and host mitochondrial DNA can therefore provide significant information on the dynamics of an ongoing Wolbachia invasion. Therefore, transition zones (i.e., regions where a Wolbachia strain is currently spreading from infected to uninfected populations) represent an ideal area to investigate the relationship between Wolbachia and host mitochondrial haplotype. Here, we studied Wolbachia-mitochondrial haplotype associations in the European cherry fruit fly, Rhagoletis cerasi, in two transition zones in the Czech Republic and Hungary, where the CI-inducing strain wCer2 is currently spreading. The wCer2-infection status of 881 individuals was compared with the two known R. cerasi mitochondrial haplotypes, HT1 and HT2. In accordance with previous studies, wCer2-uninfected individuals were associated with HT1, and wCer2-infected individuals were mainly associated with HT2. We found misassociations only within the transition zones, where HT2 flies were wCer2-uninfected, suggesting the occurrence of imperfect maternal transmission. We did not find any HT1 flies that were wCer2-infected, suggesting that Wolbachia was not acquired horizontally. Our study provides new insights into the dynamics of the early phase of a Wolbachia invasion.

ModelingWolbachiaDiffusion in Mosquito Populations by Discrete Competition Model

Dengue fever is caused by dengue virus and transmitted byAedesmosquitoes. A promising avenue to control this disease is to infect the wildAedespopulation with the bacteriumWolbachiadriven by cytoplasmic incompatibility (CI). To study the invasion ofWolbachiainto wild mosquito population, we formulate a discrete competition model and analyze the competition between released mosquitoes and wild mosquitoes. We show the global asymptotic properties of the trivial equilibrium, boundary equilibrium, and positive equilibrium and give the conditions for the successful invasion ofWolbachia. Finally, we verify our findings by numerical simulations.

Matching the genetics of released and local Aedes aegypti populations is critical to assure Wolbachia invasion.

BackgroundTraditional vector control approaches such as source reduction and insecticide spraying have limited effect on reducing Aedes aegypti population. The endosymbiont Wolbachia is pointed as a promising tool to mitigate arbovirus transmission and has been deployed worldwide. Models predict a rapid increase on the frequency of Wolbachia-positive Ae. aegypti mosquitoes in local settings, supported by cytoplasmic incompatibility (CI) and high maternal transmission rate associated with the wMelBr strain.Methodology/principle findingsWolbachia wMelBr strain was released for 20 consecutive weeks after receiving >87% approval of householders of the isolated community of Tubiacanga, Rio de Janeiro. wMelBr frequency plateued~40% during weeks 7–19, peaked 65% but dropped as releases stopped. A high (97.56%) maternal transmission was observed. Doubling releases and deploying mosquitoes with large wing length and low laboratory mortality produced no detectable effects on invasion trend. By investigating the lab colony maintenance procedures backwardly, pyrethroid resistant genotypes in wMelBr decreased from 68% to 3.5% after 17 generations. Therefore, we initially released susceptible mosquitoes in a local population highly resistant to pyrethroids which, associated with the over use of insecticides by householders, ended jeopardizing Wolbachia invasion. A new strain (wMelRio) was produced after backcrossing wMelBr females with males from field to introduce mostly pyrethroid resistance alleles. The new strain increased mosquito survival but produced relevant negative effects on Ae. aegypti fecundity traits, reducing egg clutche size and egg hatch. Despite the cost on fitness, wMelRio successful established where wMelBr failed, revealing that matching the local population genetics, especially insecticide resistance background, is critical to achieve invasion.Conclusions/significanceLocal householders support was constantly high, reaching 90% backing on the second release (wMelRio strain). Notwithstanding the drought summer, the harsh temperature recorded (daily average above 30°C) did not seem to affect the expression of maternal transmission of wMel on a Brazilian background. Wolbachia deployment should match the insecticide resistance profile of the wild population to achieve invasion. Considering pyrethroid-resistance is a widely distributed phenotype in natural Ae. aegypti populations, future Wolbachia deployments must pay special attention in maintaining insecticide resistance in lab colonies for releases.

The threshold infection level for Wolbachia invasion in random environments

Dengue fever and Zika are mosquito-borne diseases threatening human health. A novel strategy for mosquito-borne disease control uses the bacterium Wolbachia to block virus transmission. It requires releasing Wolbachia infected mosquitoes to exceed a threshold level. Since an accurate forecast for temperature and rainfall, the major environmental conditions regulating the mosquito dynamics, is often not available over a long time period, it is important to explore how the threshold releasing level changes in random environments. In this work, we estimate the threshold level in a stochastic system of differential equations where the reproduction rates of mosquitoes change randomly. We prove that the threshold level is, surprisingly, defined by a deterministic curve that does not fluctuate with environmental conditions. The major difficulty in the proof is to construct various auxiliary curves to limit the dynamic behaviors of the whole family of innumerable solutions satisfying a given initial condition.

The Effect of Nonrandom Mating on Wolbachia Dynamics: Implications for Population Replacement and Sterile Releases in Aedes Mosquitoes.

Wolbachia bacteria are known to cause deviations from random mating and affect sperm competition (SC) in some of their arthropod hosts. Because these effects could influence the effectiveness of Wolbachia in mosquito population replacement and suppression programs, we developed a theoretical framework to investigate them and we collected relevant data for the wMel infection in Aedes aegypti. Using incompatibility patterns as a measure of mating success of infected versus uninfected mosquitoes, we found some evidence that uninfected males sire more offspring than infected males. However, our theoretical framework suggests that this effect is unlikely to hamper Wolbachia invasion and has only minor effects on population suppression programs. Nevertheless, we suggest that mating effects and SC need to be monitored in an ongoing manner in release programs, given the possibility of ongoing selection for altered mating patterns.

Molecular evidence for new sympatric cryptic species of Aedes albopictus (Diptera: Culicidae) in China: A new threat from Aedes albopictus subgroup?

BackgroundAedes (Stegomyia) albopictus (Skuse) is an indigenous species and the predominant vector of dengue fever in China. Understanding of genetic diversity and structure of the mosquito would facilitate dengue prevention and vector control. Sympatric cryptic species have been identified in the Ae. albopictus subgroup in Southeast Asia; however, little is known about the presence and distribution of cryptic species in China. This study aimed to examine the genetic diversity, evaluate potential new cryptic sibling species, and assess the prevalence of Wolbachia infections in field populations.MethodsAedes adult female specimens were collected from five provinces in southern and central China during 2015–2016. Morphological identification was performed under dissection microscope. The mitochondrial DNA cytochrome c oxidase subunit 1 (cox1, DNA barcoding) locus and the ribosomal DNA internal transcribed spacer region 2 (ITS2) marker were used to examine the genetic variation, evaluate cryptic sibling species, and population structure in the field populations. Screening for the presence of Wolbachia was performed using multiplex PCR.ResultsA total of 140 individual specimens with morphological characteristics similar to Ae. albopictus were sequenced for DNA barcoding. Among these, 129 specimens (92.1%) were confirmed and identified as Ae. albopictus. The remaining 11 specimens, from 2 provinces, were identified as 2 distinct sequence groups, which were confirmed by ITS2 marker sequencing, suggesting the existence of potential cryptic species of Ae. albopictus. In Ae. albopictus, we found significant genetic differentiation and population structure between populations collected from different climate zones. Medium to high frequencies of Wolbachia infections were observed in natural Ae. albopictus populations, whereas Wolbachia was infrequent or absent in cryptic species populations.ConclusionsOur findings highlight the population differentiation by climate zone and the presence of novel, cryptic Aedes species in China. The low prevalence of Wolbachia infections in cryptic species populations could reflect either a recent invasion of Wolbachia in Ae. albopictus or different host immune responses to this symbiont in the cryptic species. The study provides useful information for vector control and host-symbiont coevolution. Further study is needed to investigate the potential for arbovirus infection and disease transmission in the emerged cryptic species.