Journal of Mosquito Research 2024, Vol.14 http://emtoscipublisher.com/index.php/jmr © 2024 EmtoSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved.
Journal of Mosquito Research 2024, Vol.14 http://emtoscipublisher.com/index.php/jmr © 2024 EmtoSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. Publisher EmtoSci Publisher Editedby Editorial Team of Journal of Mosquito Research Email: edit@jmr.emtoscipublisher.com Website: http://emtoscipublisher.com/index.php/jmr Address: 11388 Stevenston Hwy, PO Box 96016, Richmond, V7A 5J5, British Columbia Canada Journal of Mosquito Research (ISSN 1927-646X) is an open access, peer reviewed journal published online by EmtoSci Publisher. The journal is committed to publishing and disseminating all the latest and outstanding research articles, letters and reviews in all areas of molecular entomology. The range of topics including genome structure of insects, gene expression and their function analysis, molecular evolution, molecular ecology, molecular genetics, insect physiology and biochemistry and other topical advisory subjects. Meanwhile we also publish the articles related to basic research, such as anatomy, morphology and taxonomy, which are fundamental to molecular technique’s innovation and development. All the articles published in Molecular Entomology are Open Access, and are distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. EmtoSci Publisher uses CrossCheck service to identify academic plagiarism through the world’s leading plagiarism prevention tool, iParadigms, and to protect the original authors’ copyrights. EmtoSci Publisher is an international Open Access publisher specializing in insect science, and entomology-related research registered at the publishing platform that is operated by Sophia Publishing Group (SPG), founded in British Columbia of Canada.
Journal of Mosquito Research (online), 2024, Vol.14, No.4 ISSN 1927-646X http://emtoscipublisher.com/index.php/jmr © 2024 EmtoSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. Latest Content Mechanisms of Mosquito-Mediated Pathogen Transmission to Humans Xiaoyun Wang, Hui Lu, Jun Li Journal of Mosquito Research, 2024, Vol. 14, No. 4, 172-183 Global Collaboration in Research and Data Sharing for Mosquito-Borne Diseases Guanli Fu Journal of Mosquito Research, 2024, Vol. 14, No. 4, 184-194 Role of Climate and Environmental Changes in Mosquito Population Dynamics Wenfei Zhang Journal of Mosquito Research, 2024, Vol. 14, No. 4, 195-203 Innovative Physical and Mechanical Methods for Mosquito Control Zhongqi Wu, Xiaojie Liu Journal of Mosquito Research, 2024, Vol. 14, No. 4, 204-214 Future Directions in Vaccine Research for Emerging Mosquito-Borne Pathogens DaweiWang Journal of Mosquito Research, 2024, Vol. 14, No. 4, 215-225
Journal of Mosquito Research 2024, Vol.14, No.4, 172-183 http://emtoscipublisher.com/index.php/jmr 172 Review Article Open Access Mechanisms of Mosquito-Mediated Pathogen Transmission to Humans Xiaoyun Wang, Hui Lu, Jun Li Animal Science Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China Corresponding author: jun.li@cuixi.org Journal of Mosquito Research, 2024, Vol.14, No.4 doi: 10.5376/jmr.2024.14.0017 Received: 01 May, 2024 Accepted: 10 Jun., 2024 Published: 01 Jul., 2024 Copyright © 2024 Wang et al., This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Wang X.Y., Lu H., and Li J., 2024, Applications of geographic information systems in mosquito monitoring, Journal of Mosquito Research, 14(4): 172-183. (doi: 10.5376/jmr.2024.14.0017) Abstract Mosquito-borne diseases pose a significant threat to global health, making it crucial to gain an in-depth understanding of the mechanisms by which mosquitoes transmit pathogens. This study explores the complex biology of mosquitoes, focusing on analyzing their vector competence, anatomical structure, and life cycle, and how these factors contribute to disease transmission. The research examines the processes of pathogen acquisition, development, and persistence within mosquitoes, with particular emphasis on the key barriers that pathogens must overcome, such as the midgut and salivary glands, to ensure successful transmission to humans. Additionally, this study delves into the behavioral and ecological aspects of mosquito biting and pathogen release, as well as the co-evolutionary dynamics between mosquitoes, pathogens, and human hosts. Through detailed case studies of malaria, dengue fever, Zika virus, and West Nile virus, the diverse strategies employed by different pathogens are illustrated. This study also discusses current and emerging control strategies, emphasizing the importance of genetic and biological methods, and proposes future research directions aimed at improving public health outcomes. This study provides critical insights into the mechanisms of mosquito-borne pathogen transmission, which are essential for developing more effective disease control strategies. Keywords Mosquito-borne diseases; Pathogen transmission; Vector competence; Host-pathogen interactions; Control strategies 1 Introduction Mosquito-borne diseases represent a significant public health challenge globally (Weaver and Lecuit, 2015), with a range of viruses such as dengue, Zika, chikungunya, and others causing widespread morbidity and mortality (Roth et al., 2014). These diseases are primarily transmitted by mosquito species like Aedes aegypti and Aedes albopictus, which have adapted to various environmental conditions, facilitating the spread of these pathogens across different regions (Shragai et al., 2017). The reemergence and increasing incidence of these diseases have heightened the need for a comprehensive understanding of the mechanisms underlying mosquito-mediated pathogen transmission to humans (Weaver et al., 2018). Understanding the transmission mechanisms of mosquito-borne pathogens is crucial for several reasons. Firstly, it aids in predicting and preventing outbreaks by identifying key factors that influence transmission dynamics, such as environmental conditions, mosquito behavior, and human activities (Jones et al., 2019). Secondly, it informs the development of targeted vector control strategies and public health interventions, which are essential for mitigating the impact of these diseases (Liu et al., 2020). Lastly, it contributes to the broader field of infectious disease ecology, providing insights into how pathogens evolve and spread in response to changing ecological and climatic conditions (Brugueras et al., 2020). This study synthesizes current knowledge on the mechanisms of mosquito-mediated pathogen transmission to humans, identifies critical gaps in the existing literature, and propose directions for future research. This study covers various aspects of transmission, including the biology and ecology of mosquito vectors, the influence of environmental and climatic factors, and the role of human behavior and socio-economic conditions in shaping transmission patterns. By providing a comprehensive overview of these mechanisms, this study aims to enhance our understanding of mosquito-borne diseases and support the development of more effective control and prevention strategies.
Journal of Mosquito Research 2024, Vol.14, No.4, 172-183 http://emtoscipublisher.com/index.php/jmr 173 2 Mosquito Biology and Vector Competence 2.1 Anatomy and physiology relevant to pathogen transmission Mosquitoes are haematophagous insects, meaning they feed on blood, which is essential for the development of their eggs. The anatomy and physiology of mosquitoes are intricately linked to their role as vectors of pathogens. The process of pathogen transmission begins when a mosquito takes a blood meal from an infected host. The pathogens then propagate within the mosquito's tissues, particularly in the midgut, where they undergo various developmental stages before migrating to the salivary glands. From there, the pathogens can be transmitted to a new host during subsequent blood meals (Wu et al., 2019). The mosquito's immune system plays a crucial role in determining its vector competence, which is the ability to acquire, maintain, and transmit pathogens. The interaction between the mosquito's gut microbiota and its immune system can significantly influence vector competence (Farajollahi, 2011). For instance, certain microorganisms in the mosquito's gut can modulate the immune response, thereby affecting the mosquito's ability to transmit diseases. Additionally, genetic factors and the mosquito's evolutionary history also contribute to its susceptibility to different pathogens (Mitri and Vernick, 2012). 2.2 Lifecycle of mosquitoes: implications for disease spread The lifecycle of mosquitoes consists of four stages: egg, larva, pupa, and adult (Brugueras et al., 2020). The duration of each stage can vary depending on environmental conditions such as temperature and humidity. The adult stage is particularly significant for disease transmission, as only adult female mosquitoes feed on blood. The frequency and preference for blood meals can greatly influence the spread of diseases. For example, species like Anopheles gambiae and Aedes aegypti are known to take multiple blood meals during a single gonotrophic cycle, which increases their potential to transmit pathogens (Wilke et al., 2020). The lifecycle of mosquitoes also includes a process called sporogony, particularly in the case of malaria transmission by Anopheles mosquitoes. During sporogony, the malaria parasite undergoes several developmental stages within the mosquito, including gametocyte ingestion, fertilization in the midgut, and sporozoite formation in the salivary glands (Benelli et al., 2016). This complex lifecycle creates multiple bottlenecks, making it challenging for the parasite to complete its development and be transmitted to a new host (Beier, 1998). 2.3 Key species involved in human pathogen transmission Several mosquito species are key vectors of human pathogens. The Culex pipiens complex, for instance, includes species such as Culex pipiens and Culex quinquefasciatus, which are principal vectors of West Nile virus and St. Louis encephalitis virus. These species are highly adaptable to urban and suburban environments, contributing to their widespread distribution and role in disease transmission. Aedes aegypti and Aedes albopictus are other significant vectors, known for transmitting viruses such as dengue, Zika, and chikungunya. These species are highly invasive and have adapted well to urban environments, increasing their potential to spread diseases (Scott and Takken, 2012). Anopheles gambiae is the primary vector for malaria, and its vector competence is influenced by genetic, ecological, and immunological factors (Kain et al., 2022). Understanding the biology and vector competence of these key mosquito species is essential for developing effective control strategies to reduce the burden of mosquito-borne diseases (Gabrieli et al., 2021). 3 Pathogen Acquisition by Mosquitoes 3.1 Mechanisms of pathogen ingestion during blood feeding Mosquitoes acquire pathogens primarily through the ingestion of blood from an infected host. During blood feeding, mosquitoes ingest various pathogens, including viruses, bacteria, and parasites, which are present in the host's blood. For instance, arboviruses are acquired by naive mosquitoes from infected hosts during blood meals, and these viruses then propagate extensively within the mosquito's tissues. Similarly, malaria parasites are ingested by mosquitoes in the gametocyte stage during blood feeding on an infected host. These parasites undergo fertilization in the mosquito midgut, transforming into ookinetes, oocysts, and eventually sporozoites, which are then transmitted to a new host during subsequent blood meals (Beier, 1998).
Journal of Mosquito Research 2024, Vol.14, No.4, 172-183 http://emtoscipublisher.com/index.php/jmr 174 3.2 Pathogen survival and multiplication within the mosquito host Once ingested, pathogens must survive and multiply within the mosquito host to ensure successful transmission. Arboviruses, for example, exploit the mosquito's physiological processes to enhance their replication. The ingestion of a blood meal activates the GABAergic system in mosquitoes, which suppresses antiviral innate immunity and facilitates arbovirus replication. Malaria parasites, on the other hand, undergo a complex life cycle within the mosquito, involving multiple developmental stages and bottlenecks. Only a small proportion of ingested gametocytes successfully develop into sporozoites, which are capable of infecting new hosts (Dong et al., 2009). The mosquito's immune system plays a crucial role in controlling pathogen propagation, employing mechanisms such as phagocytosis, melanization, and lysis to limit pathogen survival (Kumar et al., 2018). 3.3 Factors influencing pathogen uptake Several factors influence the uptake and subsequent transmission of pathogens by mosquitoes. Host immunity, for instance, can affect the availability and concentration of pathogens in the blood, thereby influencing the likelihood of mosquito infection (Carrington and Simmons, 2014). The gut microbiota of mosquitoes also plays a significant role in modulating pathogen acquisition and survival. The microbiota can inhibit the development of pathogens such as Plasmodium through the activation of the mosquito's immune responses. Additionally, the source of the blood meal can impact pathogen development; for example, the efficiency of malaria parasite development within mosquitoes is influenced by the type of host blood consumed during sporogony (Figure 1) (Emami et al., 2017). Understanding these factors is crucial for developing strategies to control mosquito-borne diseases. In summary, the acquisition of pathogens by mosquitoes involves complex interactions between the mosquito, the pathogen, and various environmental and biological factors. These interactions determine the efficiency of pathogen uptake, survival, and transmission, ultimately influencing the epidemiology of mosquito-borne diseases. Figure 1 Effect of second blood meal from different hosts (cow and human) on oocyst and sporozoite load in mosquitoes (Adapted from Emami et al., 2017) Image caption: Four days after the infectious blood, An. gambiae s.s. (Keele) and An. arabiensis (Ifakara) mosquitoes were offered a second blood meal of human or cow origin, or no second blood meal (control). Number of oocysts per midgut (panels a and d) were measured at day 10 post-infection. The total number of parasites per mosquito was estimated using quantitative PCR within the midgut (oocyst) stages at day 10 post-infection (panels b and e) and within the salivary glands at day 16 post-infection (panels c and f). The top panels (a,b,c) showAn. arabiensis (Ifakara), and the lower panels (c,d,e) showAn. gambiae s.s. (Keele). The infection load values are taken from the negative binomial model estimations. The median is represented as a thick solid line, the box represents the upper and lower quartile range, and the whiskers show the range. Outliers are shown as unfilled circles. Statistically different comparisons are shown by the brackets (***p ≤ 0.001; *p = 0.01) (Adapted from Emami et al., 2017)
Journal of Mosquito Research 2024, Vol.14, No.4, 172-183 http://emtoscipublisher.com/index.php/jmr 175 Emami et al. (2017) found that the type of host from which mosquitoes take a second blood meal significantly influences the parasite load in both the midgut and salivary glands of Anopheles mosquitoes. In their study, Anopheles arabiensis and Anopheles gambiae s.s. that fed on human blood exhibited higher oocyst and sporozoite loads compared to those that fed on cow blood. This effect was particularly pronounced in An. gambiae s.s., where a human blood meal led to significantly higher oocyst numbers and parasite genomes in the salivary glands, suggesting that human blood may enhance the development and transmission potential of malaria parasites. The study highlights the critical role of host selection in malaria transmission dynamics, emphasizing the need for targeted vector control strategies that consider host-mosquito interactions. 4 Pathogen Development and Persistence in Mosquitoes 4.1 Crossing the midgut barrier The midgut of mosquitoes serves as the initial barrier that pathogens must overcome to establish an infection. Upon ingestion of a blood meal containing pathogens, the pathogens encounter the midgut epithelium, which is a critical site for initial infection. The midgut epithelium is composed of various cell types that play roles in digestion, immunity, and maintaining the gut microbiome. Pathogens such as viruses and parasites must navigate through this complex environment to reach the hemocoel. For instance, the Zika virus (ZIKV) must persist in the midgut and then disseminate to secondary tissues, a process facilitated by structural modifications of the midgut basal lamina following blood meal ingestion (Cui et al. 2019). Similarly, the malaria parasite undergoes a series of transformations in the midgut, from gametocytes to ookinetes and then to oocysts, before producing sporozoites that invade the salivary glands. The ability of pathogens to cross the midgut barrier is influenced by their interactions with specific receptors and the mosquito's immune responses, which can limit pathogen propagation (Figure 2) (Hixson et al., 2021). Figure 2 Possible impacts of epithelial dynamics in the mosquito midgut on the hematophagous lifecycle, aging, interactions with gut flora, Plasmodium and arboviral infections (Adopted from Hixson et al., 2021) Image caption: (A) During the post-emergence maturation, JH could stimulate ISCs to proliferate and create new ECs or prompt ECs to endocycle to attain higher ploidy; blood-feeding stimulates the production of 20E, which could stimulate the proliferation of ISCs, the differentiation of new ECs, and transcriptional changes in ECs. (B) Normal microbiota could contribute to aging and basal turnover of EC populations; dying ECs could stimulate ISCs to effect homeostatic replacement; dysbiosis and/or infection with oral bacterial pathogens could accelerate the turnover of epithelial cells; ISC-mediated repair could serve as a disease tolerance mechanism, promoting mosquito survival. Invasion by Plasmodium (C) and/or arboviral pathogens (D) could prompt cell sacrifice mechanisms to limit pathogenic success; ISC proliferation and differentiation could help infected mosquitoes to tolerate epithelial damage (Adopted from Hixson et al., 2021)
Journal of Mosquito Research 2024, Vol.14, No.4, 172-183 http://emtoscipublisher.com/index.php/jmr 176 Hixson et al. (2021) discovered that the dynamics of epithelial cells in the mosquito midgut are integral to the insect’s ability to manage various physiological processes and pathogen infections. Their study revealed that juvenile hormone (JH) and 20-hydroxyecdysone (20E) play crucial roles in stimulating intestinal stem cell (ISC) proliferation and differentiation during different stages of the mosquito lifecycle, such as post-emergence maturation and blood-feeding. Additionally, they found that the normal turnover of epithelial cells, influenced by the gut microbiota, contributes to the aging process and impacts mosquito longevity. In the context of infections, they highlighted how Plasmodium and arboviruses can induce cell loss, prompting epithelial repair mechanisms that enhance disease tolerance and survival of the mosquito. This underscores the significance of epithelial dynamics in the broader context of vector competence and the potential for targeted vector control strategies. 4.2 Pathogen propagation in the hemocoel Once pathogens successfully cross the midgut barrier, they enter the hemocoel, the primary body cavity of the mosquito, where they encounter the mosquito's immune system. The hemocoel provides a route for pathogens to disseminate to various tissues, including the salivary glands. However, this environment is not without challenges. The mosquito's innate immune system, including mechanisms such as phagocytosis, melanization, and lysis, actively works to limit pathogen survival and propagation (Franz et al., 2015). For example, malaria sporozoites face significant immune pressure in the hemocoel, with only a small fraction successfully invading the salivary glands. Sporozoites that fail to invade within a narrow time window are rapidly degraded (Hillyer et al., 2007). The efficiency of pathogen propagation in the hemocoel is thus a critical determinant of transmission success. 4.3 Salivary gland invasion and preparation for transmission The final step in the pathogen's journey within the mosquito is the invasion of the salivary glands, which is crucial for transmission to a new host. Pathogens must overcome the salivary gland barrier, which involves specific receptor-mediated interactions (Kumar et al., 2018). For instance, malaria parasites utilize specific carbohydrate molecules on the salivary gland surface as docking receptors for invasion. The efficiency of salivary gland invasion can be influenced by the mosquito's immune responses and the pathogen's ability to manipulate the host's physiology. Once inside the salivary glands, pathogens prepare for transmission during the mosquito's next blood meal. The salivary glands produce a complex mixture of molecules that facilitate blood feeding and can modulate the host's immune response, thereby enhancing pathogen transmission (Agarwal et al, 2017). Understanding the molecular mechanisms underlying salivary gland invasion and the factors that influence transmission efficiency is essential for developing strategies to interrupt the transmission cycle of mosquito-borne diseases (Mueller et al., 2010). 5 Transmission to Humans 5.1 Mosquito saliva and its role in pathogen transmission Mosquito saliva plays a crucial role in the transmission of pathogens to humans. During blood feeding, mosquitoes inject saliva into the host, which contains a complex mixture of bioactive components that modulate the host's immune response and facilitate pathogen transmission. For instance, mosquito saliva has been shown to contain microRNAs that can regulate gene expression and enhance the infection and establishment of pathogens such as Chikungunya virus (CHIKV). Additionally, specific salivary proteins, such as LTRIN fromAedes aegypti, have been identified to interfere with host immune signaling pathways, thereby facilitating the transmission of viruses like Zika virus (ZIKV). The presence of mosquito saliva at the bite site has been linked to increased virus transmission, host susceptibility, disease progression, and higher viremia levels. These findings underscore the importance of understanding the molecular mechanisms by which mosquito saliva influences pathogen transmission to develop effective control strategies (Figure 3) (Guerrero et al., 2020). Guerrero et al. (2020) found that mosquito saliva plays a significant role in modulating the immune response upon viral inoculation into the skin. The interaction between mosquito saliva and various immune cells, such as Langerhans cells (LCs) and dendritic cells (DCs), is crucial for the subsequent immune activation and viral replication processes. The study highlights how mosquito saliva not only delivers the virus but also influences the recruitment of neutrophils and the production of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α.
Journal of Mosquito Research 2024, Vol.14, No.4, 172-183 http://emtoscipublisher.com/index.php/jmr 177 This immune response is further amplified by the activation of autophagy and the inducible nitric oxide synthase (iNOS) pathway, which contribute to the control of viral replication. The migration of LCs and DCs to the lymph nodes, as influenced by mosquito saliva, is a key step in the spread of the immune response beyond the initial site of infection. Figure 3 Simplified representation of the inoculation of virus and mosquito saliva into the skin (Adopted from Guerrero et al., 2020) Image caption: Recognition of the virus by LCs and DCs, and migration to lymph node. Effect of mosquito saliva on skin immune resident and infiltrating cells (Adopted from Guerrero et al., 2020) 5.2 Behavioral aspects of biting and pathogen release The behavior of mosquitoes during biting significantly impacts the efficiency of pathogen transmission. Mosquitoes exhibit specific feeding patterns that can influence the risk of infection. For example, the Culex pipiens complex, which includes several mosquito species, has adapted to human-altered environments and displays mixed feeding patterns on birds and mammals, including humans. This behavior increases the transmission of avian pathogens to humans (Sangbakembi-Ngounou et al., 2022). Moreover, the timing of mosquito biting can affect the success of vector control measures. In regions where malaria is endemic, a significant proportion of Anopheles mosquitoes bite during the daytime, when people are not protected by insecticidal nets, leading to residual transmission that is difficult to control (Brugueras et al., 2020). Understanding these behavioral aspects is crucial for designing targeted interventions to reduce the risk of pathogen transmission. 5.3 Environmental and ecological factors influencing transmission efficiency Environmental and ecological factors play a pivotal role in the distribution and transmission efficiency of mosquito-borne diseases (Farajollahi et al., 2011). Climate change, temperature, precipitation, and population density are key factors that influence the distribution of mosquito vectors and the risk of disease emergence or re-emergence (Maharaj et al., 2015). For instance, in southern Europe, climatic and environmental variables such as temperature and precipitation have been identified as significant risk factors for the distribution of vectors and the transmission of diseases like dengue, chikungunya, Zika virus, West Nile fever, and malaria1. Additionally, the genetic and ecological variation within mosquito species, such as Anopheles gambiae, can affect their susceptibility to pathogens and, consequently, the efficiency of disease transmission (Mitri and Vernick, 2012). These factors highlight the need for comprehensive studies on the impact of environmental changes on mosquito
Journal of Mosquito Research 2024, Vol.14, No.4, 172-183 http://emtoscipublisher.com/index.php/jmr 178 behavior and pathogen transmission to inform public health strategies and mitigate the spread of mosquito-borne diseases (Jin et al., 2018). 6 Host-Pathogen Interactions 6.1 Immune evasion strategies of pathogens Pathogens transmitted by mosquitoes have developed sophisticated mechanisms to evade the host immune system, ensuring their survival and propagation. For instance, Plasmodium falciparum, the parasite responsible for malaria, employs various strategies to evade both the mosquito and human immune responses. In mosquitoes, the Pfs47 gene inhibits Janus kinase-mediated activation, while in humans, the parasite uses antigenic variation, polymorphism, and sequestration to avoid immune detection (Simões et al., 2018). Similarly, mosquito-borne viruses such as dengue and Zika viruses can antagonize antiviral pathways in their mosquito vectors, engaging in an evolutionary arms race with their hosts (Samuel et al., 2018). These immune evasion strategies are crucial for the pathogens' life cycles and have significant implications for disease control and vaccine development (Bhattacharjee et al., 2023). 6.2 Host immune responses to mosquito bites The interaction between mosquitoes and their hosts triggers a complex immune response. When a mosquito bites, it injects saliva containing various proteins that can modulate the host's immune system. This interaction can lead to both local and systemic immune responses. For example, the mosquito's saliva can induce a proinflammatory response, which is a critical component of the host's defense mechanism (Altinli et al., 2021). Additionally, the gut microbiota of mosquitoes can influence their immune responses, thereby affecting their vector competence. Certain microorganisms in the mosquito microbiota can modulate the immune response of mosquito females, shaping their ability to transmit pathogens (Gabrieli et al., 2021). Understanding these interactions is essential for developing novel strategies to control mosquito-borne diseases. 6.3 Coevolution of mosquitoes, pathogens, and human hosts The coevolution of mosquitoes, pathogens, and human hosts is a dynamic process driven by the continuous adaptation of each party to the others (Benelli et al., 2016). Mosquitoes have evolved various immune mechanisms to defend against pathogens, including phagocytosis, melanization, and lysis8. Pathogens, in turn, have developed strategies to evade these defenses, leading to an ongoing evolutionary arms race. For example, mosquito-borne viruses and Plasmodium parasites have evolved mechanisms to interfere with the mosquito's immune pathways, ensuring their survival and transmission (Martinez et al., 2020). Additionally, the interaction between mosquitoes and their microbiota plays a significant role in this coevolution. The bacteriumWolbachia, for instance, can enhance the mosquito's immune response and reduce its ability to transmit pathogens like dengue and Zika viruses. These intricate interactions highlight the importance of considering the coevolutionary dynamics in the development of effective disease control strategies (Belachew, 2018). 7 Case Studies 7.1 Malaria transmission: Plasmodiumspp. Malaria is primarily transmitted by Anopheles mosquitoes, which are not covered in the provided data (Estrada-Franco et al., 2020). However, the role of Culex species in the transmission of avian malaria parasites in Mediterranean areas has been studied. Culex pipiens, Cx. perexiguus, and Cx. modestus have been identified as vectors for avian malaria, with varying levels of efficiency. Cx. pipiens was found to be the most significant vector for Plasmodiumin wild house sparrows, suggesting that different Culex species contribute differently to pathogen amplification (Turell et al., 2005). 7.2 Dengue and Zika viruses: mechanisms of Aedes spp. transmission Aedes aegypti and Aedes albopictus are the primary vectors for dengue and Zika viruses. Studies have shown that Ae. aegypti is a more competent vector for Zika virus compared to Ae. albopictus, particularly for African strains of the virus (Ferraguti et al., 2020). In Northern Mexico, Ae. aegypti was found to feed on a variety of hosts, including humans, dogs, and cats, which influences the transmission dynamics of mosquito-vectored pathogens
Journal of Mosquito Research 2024, Vol.14, No.4, 172-183 http://emtoscipublisher.com/index.php/jmr 179 (Brugueras et al., 2020). Additionally, Ae. aegypti and Ae. albopictus from Reunion Island showed higher infection rates for the African Zika virus strain compared to Asian strains, indicating that vector competence can vary significantly based on the mosquito and virus strains involved (Rothman et al., 2020). 7.3 West nile virus: Culex spp. as a vector West Nile Virus (WNV) is primarily transmitted by Culex species mosquitoes. Studies have shown that various Culex species, including Cx. tarsalis and Cx. nigripalpus, are competent vectors for WNV under laboratory conditions1. In Mediterranean areas, Cx. perexiguus has been identified as the most important species contributing to the amplification of WNV, with targeted surveillance and control of this species being recommended to reduce WNV spillover into human populations (Gomard et al., 2020). In urban Baltimore, MD, higher WNV infection rates were observed in Culex mosquitoes from lower-income neighborhoods, highlighting the importance of socioeconomic factors in arboviral risk management. Additionally, vertical transmission of WNV by Culex species has been documented, suggesting that these mosquitoes can transmit the virus to their offspring, potentially maintaining the virus in mosquito populations even in the absence of active transmission cycles (Héry et al., 2019). In summary, the transmission of mosquito-borne pathogens such as malaria, dengue, Zika, and West Nile viruses involves complex interactions between different mosquito species, their feeding behaviors, and environmental factors. Understanding these dynamics is crucial for developing effective surveillance and control strategies (Baqar et al., 1993). 8 Control Strategies and Future Directions 8.1 Current strategies for interrupting transmission Current strategies to interrupt mosquito-mediated pathogen transmission primarily involve the use of insecticides and vaccines. Insecticides have been the cornerstone of mosquito control efforts, targeting both adult mosquitoes and larvae to reduce population densities and interrupt disease transmission cycles. However, the widespread use of insecticides has led to the emergence of resistance, diminishing their effectiveness over time (Benelli et al., 2016). Vaccination efforts, particularly for diseases like dengue and yellow fever, have shown promise but are not universally available or effective against all mosquito-borne diseases (Blair et al., 2000). Additionally, new insecticides and insect growth regulators are being researched to overcome resistance issues and provide more sustainable control options (Dahmana et al., 2020). 8.2 Genetic and biological control methods Genetic and biological control methods are emerging as promising alternatives to traditional insecticide-based strategies. One such method involves the genetic manipulation of mosquitoes to render them incapable of transmitting pathogens. This includes the use of gene drives and the introduction of pathogen-blocking bacteria like Wolbachia into mosquito populations (Martinez et al., 2020). These strategies aim to either suppress mosquito populations or replace them with genetically modified individuals that are less capable of disease transmission. Biological control methods also include the use of natural predators, parasites, and pathogens to reduce mosquito populations. For instance, attractive toxic sugar baits and the introduction of symbiotic bacteria such as Asaia are being explored as innovative control measures (Liu et al.,2015). 8.3 Future research directions and emerging technologies Future research directions focus on enhancing the efficacy and sustainability of both existing and novel control strategies. There is a pressing need to understand the mechanisms of insecticide resistance better and develop new compounds that mosquitoes have not yet adapted to (Shragai et al., 2017). Additionally, the integration of genetic and biological control methods with traditional approaches could offer a more comprehensive solution to mosquito-borne diseases. Emerging technologies such as CRISPR-based gene editing and advanced genomic tools are expected to play a significant role in developing next-generation mosquito control strategies8 9. Furthermore, improving our understanding of mosquito behavior, host attraction, and the ecological factors influencing disease transmission will be crucial for designing more effective interventions (Achee et al., 2019). In conclusion, while traditional methods like insecticides and vaccines remain vital, the future of mosquito control lies in the integration of genetic, biological, and ecological approaches. Continued research and innovation are essential to
Journal of Mosquito Research 2024, Vol.14, No.4, 172-183 http://emtoscipublisher.com/index.php/jmr 180 overcome current challenges and develop sustainable solutions for the global burden of mosquito-borne diseases. 9 Concluding Remarks Mosquito-mediated pathogen transmission to humans involves complex interactions between the mosquito vectors, the pathogens they carry, and the environmental factors influencing these dynamics. Key mechanisms include the antiviral immune pathways in mosquitoes, which can be antagonized by viruses such as Zika, West Nile, and dengue, leading to successful transmission cycles. The genetic and ecological diversity within mosquito species, such as the Culex pipiens complex, also plays a significant role in the transmission of various pathogens, including West Nile virus and avian malaria. Additionally, the interplay between mosquito gut microbiota and their immune system significantly affects vector competence and pathogen transmission. Environmental and climatic factors, such as temperature and precipitation, are critical in determining the distribution and emergence of mosquito-borne diseases, particularly in regions like southern Europe. The adaptation of mosquitoes to human-altered environments and their mixed feeding patterns further facilitate the spread of diseases from wildlife to human populations. Understanding the mechanisms of mosquito-mediated pathogen transmission has profound implications for public health and disease control. The insights into mosquito immune pathways and their interactions with pathogens can inform the development of targeted vector control strategies, such as genetic modifications and immune priming to enhance mosquito resistance to pathogens. Additionally, recognizing the role of environmental factors in disease emergence underscores the importance of integrating climate change considerations into public health planning and vector control programs. The complex interactions between mosquito microbiota, immunity, and pathogens suggest that manipulating the mosquito microbiome could be a promising strategy for reducing disease transmission. Approaches such as paratransgenesis and leveraging the relationship between Wolbachia bacteria and mosquito hosts are being explored to disrupt the lifecycle of pathogens within mosquitoes. Combating mosquito-mediated pathogen transmission requires a multifaceted approach that combines advances in molecular biology, ecology, and public health. Continued research into the genetic and ecological factors influencing mosquito vector competence, as well as the development of innovative control strategies, is essential. Addressing the challenges posed by climate change and urbanization will also be crucial in mitigating the spread of mosquito-borne diseases. Ultimately, a concerted effort involving interdisciplinary collaboration and sustained investment in research and public health infrastructure will be necessary to effectively reduce the global burden of mosquito-borne diseases. By leveraging our growing understanding of mosquito-pathogen interactions and environmental influences, we can develop more effective and sustainable strategies to protect human health. Acknowledgments Authors would like to express our gratitude to the two anonymous peer reviewers for their critical assessment and constructive suggestions on our manuscript. Conflict of Interest Disclosure Authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Achee N., Grieco J., Vatandoost H., Seixas G., Pinto J., Ching-Ng L., Martins A., Juntarajumnong W., Corbel V., Gouagna C., David J., Logan J., Orsborne J., Marois E., Devine G., and Vontas J., 2019, Alternative strategies for mosquito-borne arbovirus control, PLoS Neglected Tropical Diseases, 13: 23-26. https://doi.org/10.1371/journal.pntd.0006822 Agarwal A., Parida M., and Dash P., 2017, Impact of transmission cycles and vector competence on global expansion and emergence of arboviruses, Reviews in Medical Virology, 27: 41-47. https://doi.org/10.1002/rmv.1941 Altinli M., Schnettler E., and Sicard M., 2021, Symbiotic interactions between mosquitoes and mosquito viruses, Frontiers in Cellular and Infection Microbiology, 11: 27-29. https://doi.org/10.3389/fcimb.2021.694020 Baqar S., Hayes C., Murphy J., and Watts D., 1993, Vertical transmission of west nile virus by Culex and Aedes species mosquitoes, The American Journal of Tropical Medicine and Hygiene, 48(6): 757-762.
Journal of Mosquito Research 2024, Vol.14, No.4, 172-183 http://emtoscipublisher.com/index.php/jmr 181 Beier J., 1998, Malaria parasite development in mosquitoes, Annual Review of Entomology, 43: 519-543. https://doi.org/10.1146/ANNUREV.ENTO.43.1.519 Belachew E., 2018, Immune response and evasion mechanisms of plasmodium falciparum parasites, Journal of Immunology Research, 10: 55-74. Benelli G., Iacono A., Canale A., and Mehlhorn H., 2016, Mosquito vectors and the spread of cancer: an overlooked connection, Parasitology Research, 115: 2131-2137. https://doi.org/10.1007/s00436-016-5037-y Benelli G., Jeffries C., and Walker T., 2016, Biological control of mosquito vectors: past, present, and future, Insects, 7: 52-59. https://doi.org/10.3390/insects7040052 Bhattacharjee S., Ghosh D., Saha R., Sarkar R., Kumar S., Khokhar M., and Pandey R., 2023, Mechanism of immune evasion in mosquito-borne diseases, Pathogens, 12: 3-18. https://doi.org/10.3390/pathogens12050635 Blair C., Adelman Z., and Olson K., 2000, Molecular strategies for interrupting arthropod-borne virus transmission by mosquitoes, Clinical Microbiology Reviews, 13: 651-661. https://doi.org/10.1128/CMR.13.4.651 Brugueras S., Martínez B., Puente J., Figuerola J., Porro T., Rius C., Larrauri A., and Gómez-Barroso D., 2020, Environmental drivers, climate change and emergent diseases transmitted by mosquitoes and their vectors in southern europe: a systematic review, Environmental Research, 1100: 38. https://doi.org/10.1016/j.envres.2020.110038 Carrington L., and Simmons C., 2014, Human to mosquito transmission of dengue viruses, Frontiers in Immunology, 5: 90-98. https://doi.org/10.3389/fimmu.2014.00290 Cui Y., Grant D., Lin J., Yu X., and Franz A., 2019, Zika virus dissemination from the midgut of Aedes aegypti is facilitated by bloodmeal-mediated structural modification of the midgut basal lamina, Viruses, 11: 58. https://doi.org/10.3390/v11111056 Dahmana H., and Mediannikov O., 2020, Mosquito-borne diseases emergence/resurgence and how to effectively control it biologically, Pathogens, 9: 31-38. https://doi.org/10.3390/pathogens9040310 Dong Y., Manfredini F., and Dimopoulos G., 2009, Implication of the mosquito midgut microbiota in the defense against malaria parasites, PLoS Pathogens, 5: 425. https://doi.org/10.1371/journal.ppat.1000423 Emami S., Ranford-Cartwright L., and Ferguson H., 2017, The transmission potential of malaria-infected mosquitoes (An.gambiae-Keele, An.arabiensis-Ifakara) is altered by the vertebrate blood type they consume during parasite development, Scientific Reports, 7: 52-57. https://doi.org/10.1038/srep40520 Estrada-Franco J., Fernández-Santos N., Adebiyi A., López-López M., Aguilar-Durán J., Hernández-Triana L., Prosser S., Hebert P., Fooks A., Hamer G., Xue L., and Rodríguez-Pérez M., 2020, Vertebrate-Aedes aegypti and Culex quinquefasciatus (Diptera)-arbovirus transmission networks: non-human feeding revealed by meta-barcoding and next-generation sequencing, PLoS Neglected Tropical Diseases, 14: e0008867. https://doi.org/10.1371/journal.pntd.0008867 Farajollahi A., Fonseca D., Kramer L., Kramer L., and Kilpatrick A., 2011, "Bird biting" mosquitoes and human disease: a review of the role of Culex pipiens complex mosquitoes in epidemiology, Infection, Genetics and Evolution: Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases, 11: 1577-1585. https://doi.org/10.1016/j.meegid.2011.08.013 Ferraguti M., Heesterbeek H., Puente J., Jiménez-Clavero M., Vázquez A., Ruíz S., Llorente F., Roiz D., Vernooij H., Soriguer R., and Figuerola J., 2020, The role of different Culex mosquito species in the transmission of west nile virus and avian malaria parasites in mediterranean areas, Transboundary and Emerging Diseases, 11: 76-79. https://doi.org/10.1111/tbed.13760 Franz A., Kantor A., Passarelli A., and Clem R., 2015, Tissue barriers to arbovirus infection in mosquitoes, Viruses, 7: 3741-3767. https://doi.org/10.3390/v7072795 Gabrieli P., Caccia S., Varotto-Boccazzi I., Arnoldi I., Barbieri G., Comandatore F., and Epis S., 2021, Mosquito trilogy: microbiota, immunity and pathogens, and their implications for the control of disease transmission, Frontiers in Microbiology, 12: 36-39. https://doi.org/10.3389/fmicb.2021.630438 Gomard Y., Lebon C., Mavingui P., and Atyame C., 2020, Contrasted transmission efficiency of zika virus strains by mosquito species Aedes aegypti, Aedes albopictus and Culex quinquefasciatus from reunion island, Parasites & Vectors, 13: 67-69. https://doi.org/10.1186/s13071-020-04267-z Guerrero D., Cantaert T., and Missé D., 2020, Aedes mosquito salivary components and their effect on the immune response to arboviruses, Frontiers in Cellular and Infection Microbiology, 10: 40-57. https://doi.org/10.3389/fcimb.2020.00407 Héry L., Boullis A., Delannay C., and Vega-Rúa A., 2019, Transmission potential of african, asian and american zika virus strains by Aedes aegypti and Culex quinquefasciatus from guadeloupe (french west indies), Emerging Microbes & Infections, 8: 699-706. https://doi.org/10.1080/22221751.2019.1615849
Journal of Mosquito Research 2024, Vol.14, No.4, 172-183 http://emtoscipublisher.com/index.php/jmr 182 Hillyer J., Barreau C., and Vernick K., 2007, Efficiency of salivary gland invasion by malaria sporozoites is controlled by rapid sporozoite destruction in the mosquito haemocoel, International Journal for Parasitology, 37: 673-681. https://doi.org/10.1016/J.IJPARA.2006.12.007 Hixson B., Taracena M., and Buchon N., 2021, Midgut epithelial dynamics are central to mosquitoes’ physiology and fitness, and to the transmission of vector-borne disease, Frontiers in Cellular and Infection Microbiology, 11: 15-28. https://doi.org/10.3389/fcimb.2021.653156 Jin L., Guo X., Shen C., Hao X., Sun P., Li P., Xu T., Hu C., Rose O., Zhou H., Yang M., Qin C., Guo J., Peng H., Zhu M., Cheng G., Qi X., and Lai R., 2018, Salivary factor ltrin fromAedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-β receptor, Nature Immunology, 19: 342-353. https://doi.org/10.1038/s41590-018-0063-9 Jones R., Kulkarni M., Davidson T., and Talbot B., 2019, Arbovirus vectors of epidemiological concern in the americas: a scoping review of entomological studies on zika, dengue and chikungunya virus vectors, PLoS ONE, 15: 67-70. https://doi.org/10.1371/journal.pone.0220753 Kain M., Skinner E., Athni T., Ramírez A., Mordecai E., and Hurk A., 2022, Not all mosquitoes are created equal: a synthesis of vector competence experiments reinforces virus associations of australian mosquitoes, PLoS Neglected Tropical Diseases, 16: 71-74. https://doi.org/10.1371/journal.pntd.0010768 Kumar A., Srivastava P., Sirisena P., Dubey S., Kumar R., Shrinet J., and Sunil S., 2018, Mosquito innate immunity, Insects, 9: 95-98. https://doi.org/10.3390/insects9030095 Liu N., 2015, Insecticide resistance in mosquitoes: impact, mechanisms, and research directions, Annual Review of Entomology, 60: 537-559. https://doi.org/10.1146/annurev-ento-010814-020828 Liu Y., Lillepold K., Semenza J., Tozan Y., Quam M., and Rocklöv J., 2020, Reviewing estimates of the basic reproduction number for dengue, zika and chikungunya across global climate zones, Environmental Research, 182: 109114. https://doi.org/10.1016/j.envres.2020.109114 Maharaj P., Widen S., Huang J., Wood T., and Thangamani S., 2015, Discovery of mosquito saliva micrornas during chikv infection, PLoS Neglected Tropical Diseases, 9: 87-90. https://doi.org/10.1371/journal.pntd.0003386 Martinez J., Showering A., Oke C., Jones R., and Logan J., 2020, Differential attraction in mosquitoh-uman interactions and implications for disease control, Philosophical Transactions of the Royal Society B: Biological Sciences, 376: 11-15. https://doi.org/10.1098/rstb.2019.0811 Mitri C., and Vernick K., 2012, Anopheles gambiae pathogen susceptibility: the intersection of genetics, immunity and ecology, Current Opinion in Microbiology, 15(3): 285-291. https://doi.org/10.1016/j.mib.2012.04.001 Mueller A., Kohlhepp F., Hammerschmidt C., and Michel K., 2010, Invasion of mosquito salivary glands by malaria parasites: prerequisites and defense strategies, International Journal for Parasitology, 40(11): 1229-1235. https://doi.org/10.1016/j.ijpara.2010.05.005 Roth A., Mercier A., Lepers C., Hoy D., Duituturaga S., Benyon E., Guillaumot L., and Souarés Y., 2014, Concurrent outbreaks of dengue, chikungunya and zika virus infections - an unprecedented epidemic wave of mosquito-borne viruses in the pacific 2012-2014, Euro Surveillance: Bulletin Europeen sur les Maladies Transmissibles European Communicable Disease Bulletin, 28: 19 41. https://doi.org/10.2807/1560-7917.ES2014.19.41.20929 Rothman S., Jones J., LaDeau S., and Leisnham P., 2020, Higher west nile virus infection in Aedes albopictus (Diptera: Culicidae) and Culex (Diptera: Culicidae) mosquitoes from lower income neighborhoods in urban baltimore, Journal of Medical Entomology, 58: 1424-1428. https://doi.org/10.1093/jme/tjaa262 Samuel G., Adelman Z., and Myles K., 2018, Antiviral immunity and virus-mediated antagonism in disease vector mosquitoes, Trends in Microbiology, 26(5): 447-461. https://doi.org/10.1016/j.tim.2017.12.005 Sangbakembi-Ngounou C., Costantini C., Longo-Pendy N., Ngoagouni C., Akone-Ella O., Rahola N., Cornelie S., Kengne P., Nakouné E., Komas N., and Ayala D., 2022, Diurnal biting of malaria mosquitoes in the central african republic indicates residual transmission may be “out of control”, Proceedings of the National Academy of Sciences of the United States of America, 119: 10-15. https://doi.org/10.1073/pnas.2104282119 Scott T., and Takken W., 2012, Feeding strategies of anthropophilic mosquitoes result in increased risk of pathogen transmission, Trends in Parasitology, 28(3): 114-121. https://doi.org/10.1016/j.pt.2012.01.001 Shragai T., Tesla B., Murdock C., and Harrington L., 2017, Zika and chikungunya: mosquito-borne viruses in a changing world, Annals of the New York Academy of Sciences, 13: 99. Simões M., Caragata E., and Dimopoulos G., 2018, Diverse host and restriction factors regulate mosquito-pathogen interactions, Trends in Parasitology, 34(7): 603-616. https://doi.org/10.1016/j.pt.2018.04.011
RkJQdWJsaXNoZXIy MjQ4ODY0NQ==