Control Of Mosquito-borne Diseases Research Articles

Requirements for market entry of gene drive-modified mosquitoes for control of vector-borne diseases: analogies to other biologic and biotechnology products.

Gene drive-modified mosquitoes (GDMMs) are proposed as new tools for control and elimination of malaria and other mosquito-borne diseases, and promising results have been observed from testing conducted in containment. Although still at an early stage of development, it is important to begin now to consider approval procedures and market entry strategies for the eventual implementation of GDMMs in the context of disease control programs, as these could impact future research plans. It is expected that, as for other types of new products, those seeking to bring GDMMs to market will be required to provide sufficient information to allow the regulator(s) to determine whether the product is safe and effective for its proposed use. There already has been much emphasis on developing requirements for the biosafety components of the "safe and effective" benchmark, largely concerned with their regulation as genetically modified organisms. Other potential approval requirements have received little attention, however. Although GDMMs are expected to be implemented primarily in the context of public health programs, any regulatory analogies to other public health products, such as pharmaceuticals, vaccines, or chemical pesticides, must take into account the characteristics of live mosquito products. Typical manufacturing standards related to product identity, potency or quality will need to be adapted to GDMMs. Valuable lessons can be drawn from the regulatory approval processes for other whole organism and genetically modified (GM) organism products. Supply chain requirements, such as scale of production, location and design of production facilities, and methods of distribution and delivery, will be dependent upon the characteristics of the particular GDMM product, the conditions of use, and the region to be served. Plans for fulfilling supply chain needs can build upon experience in the development of other live insect products for use in public health and agriculture. Implementation of GDMMs would benefit from additional research on enabling technologies for long-term storage of mosquito life stages, efficient mass production, and area-wide delivery of GDMMs. Early consideration of these practical requirements for market entry will help to mitigate downstream delays in the development of these promising new technologies.

Isolation and identification of microbiota of Culex quinquefasciatus for their application as paratransgenic tools in vector control.

Although the study on the bacteria residing in the mid-gut, salivary gland, and reproductive organs of insect vectors have drawn appeal to the host-pathogen interactions, we know comparatively less about microbiota that naturally exist in different mosquito organs within Iran. In the current investigation, PCR assay by using 16S rRNA gene amplification and DNA sequencing, in addition to the traditional culture-based approach utilized for the detection of cultivable bacterial assemblages in mid-gut and reproductive tracts of Culex quinquefasciatus. The identified bacteria isolated from different tissues of 45 individuals were consisted of Achromobacter, Aeromonas, Arthrobacter, Asaia, Enterobacter, Gluconobacter, Klebsiella, Lysinibacillus, Micrococcus, Psuedomonas and Serratia. The results showed that Proteobacteria was the most prevalent phylum in both genders' mid-gut and reproductive tracts, and Asaia was the most common bacteria that originated in adult females and males' tissues. These outcomes recommend that the discovered microbiome may span through Cx. quinquefasciatus populations. This data can be utilized to interfere with the transmission of pathogens and design new strategies for the control of mosquito-borne diseases.

A cryopreservation method to recover laboratory- and field-derived bacterial communities from mosquito larval habitats.

Mosquitoes develop in a wide range of aquatic habitats containing highly diverse and variable bacterial communities that shape both larval and adult traits, including the capacity of adult females of some mosquito species to transmit disease-causing organisms to humans. However, while most mosquito studies control for host genotype and environmental conditions, the impact of microbiota variation on phenotypic outcomes of mosquitoes is often unaccounted for. The inability to conduct reproducible intra- and inter-laboratory studies of mosquito-microbiota interactions has also greatly limited our ability to identify microbial targets for mosquito-borne disease control. Here, we developed an approach to isolate and cryopreserve bacterial communities derived from lab and field-based larval rearing environments of the yellow fever mosquito Aedes aegypti-a primary vector of dengue, Zika, and chikungunya viruses. We then validated the use of our approach to generate experimental microcosms colonized by standardized lab- and field-derived bacterial communities. Our results overall reveal minimal effects of cryopreservation on the recovery of both lab- and field-derived bacteria when directly compared with isolation from non-cryopreserved fresh material. Our results also reveal improved reproducibility of bacterial communities in replicate microcosms generated using cryopreserved stocks over fresh material. Communities in replicate microcosms further captured the majority of total bacterial diversity present in both lab- and field-based larval environments, although the relative richness of recovered taxa as compared to non-recovered taxa was substantially lower in microcosms containing field-derived bacteria. Altogether, these results provide a critical next step toward the standardization of mosquito studies to include larval rearing environments colonized by defined microbial communities. They also lay the foundation for long-term studies of mosquito-microbe interactions and the identification and manipulation of taxa with potential to reduce mosquito vectorial capacity.

Spatiotemporal overlapping of dengue, chikungunya, and malaria infections in children in Kenya

Malaria, chikungunya virus (CHIKV), and dengue virus (DENV) are endemic causes of fever among children in Kenya. The risks of infection are multifactorial and may be influenced by built and social environments. The high resolution overlapping of these diseases and factors affecting their spatial heterogeneity has not been investigated in Kenya. From 2014-2018, we prospectively followed a cohort of children from four communities in both coastal and western Kenya. Overall, 9.8% were CHIKV seropositive, 5.5% were DENV seropositive, and 39.1% were malaria positive (3521 children tested). The spatial analysis identified hot-spots for all three diseases in each site and in multiple years. The results of the model showed that the risk of exposure was linked to demographics with common factors for the three diseases including the presence of litter, crowded households, and higher wealth in these communities. These insights are of high importance to improve surveillance and targeted control of mosquito-borne diseases in Kenya.

Is the presence of mosquitoes an indicator of poor environmental sanitation?

The World Health Organization has designated mosquitoes as the most lethal animal since they are known to spread pathogen-transmitting organisms. Understanding the many environmental elements that contribute to the spread of these vectors is one of the many strategies used to stop them. If there are mosquitoes around people, it may indicate that there is not an appropriate environmental sanitation program in place in the community or region. Environmental sanitation involves improving any elements of the physical environment that could have a negative impact on a person's survival, health, or physical environment. Keywords containing 'Aedes,' 'Culex,' 'Anopheles,' 'dengue,' 'malaria,' 'yellow fever,' 'Zika,' 'West Nile,' 'chikungunya,' 'resident,' 'environment,' 'sanitation,' 'mosquito control,' and 'breeding sites' of published articles on PubMed, Google Scholar, and ResearchGate were reviewed. It was discovered that the general population should be involved in mosquito and mosquito-borne disease control. Collaboration between health professionals and the general population is essential. The purpose of this paper is to increase public awareness of environmental health issues related to diseases carried by mosquitoes.

Survey of mosquito species and mosquito-borne viruses in residential areas along the Sino-Vietnam border in Yunnan Province in China.

Mosquitoes are capable of carrying complex pathogens, and their feeding habits on the mammalian blood can easily mediate the spread of viruses. Surveillance of mosquito-based arbovirus enables the early prevention and control of mosquito-borne arboviral diseases. The climate and geography of Yunnan Province in China are ideal for mosquitoes. Yunnan shares borders with several other countries; therefore, there exists a high risk of international transmission of mosquito-mediated infectious diseases. Previous studies have focused more on the Sino-Laos and Sino-Myanmar borders. Therefore, we focused on the neighborhoods of Malipo and Funing counties in Wenshan Prefecture, Yunnan Province, China, which are located along the Sino-Vietnam border, to investigate the species of mosquitoes and mosquito-borne viruses in the residential areas of this region. This study collected 10,800 mosquitoes from 29 species of 8 genera and grouped to isolate mosquito-borne viruses. In total, 62 isolates were isolated and classified into 11 viral categories. We demonstrated a new distribution of mosquito-borne viruses among mosquitoes in border areas, including Tembusu and Getah viruses, which can cause animal outbreaks. In addition, Dak Nong and Sarawak viruses originating from Vietnam and Malaysia, respectively, were identified for the first time in China, highlighting the complexity of mosquito-borne viruses in the Sino-Vietnam border region. The awareness of the importance of viral surveillance and prevention measures in border areas should be further encouraged to prevent future outbreaks of potentially infectious diseases.

Novel paradigm of mosquito-borne disease control based on self-powered strategy.

Novel paradigm of mosquito-borne disease control based on self-powered strategy.

Molecular characterization of anopheline mosquitoes from the goat malaria-endemic areas of Thailand.

Despite the fact that over a 100 anopheline mosquito species have been identified as human malaria vectors, little is known about ungulate malaria vectors. Consequently, we focused on investigating the bionomics and genetic characterizations of anopheline mosquitoes in goat malaria-endemic regions. We also attempted to screen for ungulate malaria potential vectors. A total of 1019 female anopheline mosquitoes were collected from six goat farms in four provinces of Thailand from 2020 to 2021. Mosquitoes were morphologically identified and subsequently confirmed using the mitochondrial DNA barcoding region-cytochrome oxidase c subunit I (MtDNA-COI), mitochondrial DNA-cytochrome c oxidase subunit II (MtDNA-COII), and ribosomal DNA internal transcribed spacer 2 (rDNA-ITS2) sequences. The current study reveals the genetic characteristics and distribution of nine mosquito species within the Anopheles and Cellia subgenera. Four dominant species, including Anopheles peditaeniatus, Anopheles subpictus, Anopheles vagus, and Anopheles aconitus exhibited significant intraspecific gene flow within their corresponding species. Although malaria parasites were not found in 126 mosquito pools, meaning more investigation is necessary, the current study adds to the existing DNA barcoding data collection and improves the current understanding of the genetic structure and distribution of anopheline mosquito species, which could be useful for effective control of mosquito-borne diseases.

A Review of Pathogens Transmitted by the Container-Inhabiting Mosquitoes, Aedes Albopictus, A Global Public Health Threat.

Dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV) are highly pathogenic human arboviruses transmitted by the Aedes (Stegomyia) albopictus (Skuse) (Diptera: Culicidae) or Ae. Albopictus mosquito. These arboviruses are responsible for causing fever, hemorrhagic conditions, and neurological diseases in humans post-bite from an infected Aedes mosquito. Over the past 80 years, the Ae. albopictus has infested every habitable continent, bar Antarctica, thereby escalating the probability of global insect-borne infectious disease outbreaks. This research follows the global transmission pattern of Ae. albopictus and provides a summary of disease prevention and control strategies for mosquito-borne infections, as implemented by the World Health Organization (WHO) and both Asian and European countries. Consequently, this study can aid in the prevention and control of mosquito-borne diseases while acting as a basis for international collaboration on effectively managing arbovirus infection issues in public health.

Knowledge, attitudes, and practices on mosquito control in urban informal settlements of Lagos, southwest Nigeria

Abstract The knowledge, attitudes, and practices (KAP) on the control of mosquitoes and mosquito-borne diseases were investigated in urban informal settlements of Lagos State, Nigeria, during the coronavirus disease 2019 (COVID-19) period. The survey was conducted between December 2021 and March 2022 using a cross-sectional approach in the informal settlements of Bariga, Makoko, and Ajegunle, and in the formal settlement of Ikeja, all in Lagos State. A total of 400 semistructured questionnaires, 100 per community, were administered to consenting adult participants, and the data collected were analyzed using descriptive and inferential statistics. The results showed that of the total respondents, 262 (65.5%) claimed to have previously seen mosquito larvae, while 54.2% of the total were aware that larvae usually develop into adult mosquitoes. Only 167 (41.8%) of the respondents owned insecticide-treated bed nets, out of which 126 (75.4%) slept under such bed nets. The rate of bed net ownership and reasons for not using them were significant in relation to the study communities. The majority of respondents (81.2%) reported using aerosol insecticides almost daily, potentially contributing to the challenge of insecticide resistance in mosquito vectors. Of the mosquito-borne diseases endemic in Nigeria, malaria was the most well-known by respondents (62.7%), followed by yellow fever (13.6%), and lymphatic filariasis (1.5%). These findings highlight the need for both public education on mosquito control and government interventions in urban informal settlements.

Larvicidal Activities of Allium sativum L. and Zingiber officinale Rosc. Extracts against Filariasis Vectors in Hadiya Zone, Ethiopia.

Mosquitoes present an immense threat to millions of people worldwide and act as vectors for filariasis disease. The objective of the study was to determine the effect of Allium sativum and Zingiber officinale extracts against filariasis vectors. The larvae were collected from the breeding site by using standard procedures for identification and larvicidal activities. Twenty grams (20 g) from each (Allium sativum and Zingiber officinale) were extracted separately by aqueous, ethanol, and methanol solvents. The phytochemical analysis was determined in the crude sample by using standard methods. Then, larvicidal effects were determined by introducing 10 larvae of the vectors to the concentrations of 250 ppm, 500 ppm, and 750 ppm of the crude sample, and data were subjected to probit analysis to determine the LC50 and Chi-squared test to check the significance of the mortality by R software. Anopheles funestus, Anopheles gambiae s.l., Anopheles pharoensis, Culex antennatus, and Culex quinquefasciatus were the filariasis vectors identified during the study period. The presence of phytochemical tests such as anthraquinones, flavonoids, glycosides, phenol, saponin, steroids, tannin, and terpenes was obtained. The larvicidal effects of the selected plant extracts ranged from 0%-100%. The lowest LC50 (53 ppm) was observed for A. sativum methanol test extract against Cx. quinquefasciatus. Ethanol extracts of A. sativum have a significant effect on An. funestus (X2 = 7.5, p = 0.02352) and Cx. quinquefasciatus (X2 = 10.833, p = 0.0.0044), whereas aqueous extracts have a significant effect only on An. gambiae s.l. (X2 = 7.0807, p = 0.029. Ethanol extracts of Z. officinale have a significant effect only on the mortality of An. pharoensis (X2 = 7.0807, p = 0.029), but methanol and aqueous extracts have no significant effect against filariasis vectors. In conclusion, A. sativum have a high toxic effect than Z. officinale extract against filariasis vectors in all type of solvents. So using those plant extracts is the best to reduce the risk of the synthetic chemical on nontarget organisms and the environment, in addition to the control of mosquito-borne diseases, but further studies will be conducted to evaluate the toxicity at different stages of the vectors.

Molecular and metabolic resistance mechanisms in insecticides resistant Culex quinquefasciatus population from Lagos, Nigeria

Background: The control and management of mosquito-borne diseases heavily rely on the use of insecticide-based measures, but the emergence and spread of insecticide resistance have been a challenge and led to a significant setback in recent gains against the control of mosquito-borne diseases. Here, we as-sessed the susceptibility of Cx. quinquefasciatus to different classes of neurotoxic insecticides and deter-mined the possible resistance mechanisms. Methodology: Culex mosquitoes were collected from Kosofe, Alimosho, Ibeju-Lekki, and Badagry Lo-cal Government Areas (LGAs) of Lagos State. Adult females were exposed to permethrin, Bendiocarb, and piperonyl butoxide (PBO) synergized assays using WHO protocols. Resistance mechanisms were assessed using molecular and biochemical techniques. Results: Resistance to permethrin in Cx. quinquefasciatus was recorded in all the study locations, with 24-hour mortality ranging from 5% to 89%. Resistance to bendiocarb was also recorded in Alimosho (7%) and Kosofe (19%) LGAs, while possible resistance (96%) in Ibeju-Lekki LGA. PBO synergists significantly reduced the KDT50 and KDT95 of the synergized bioassays compared to the non-synergized bioassay. Heterozygote-resistant Ace1R gene was detected in Cx. quinquefasciatus popula-tion from Kosofe and Alimosho, kdr L1014S and L1014F were not detected in this study. Conclusion: The activities of Cytochrome P450 monooxygenase and glutathione S-transferase detoxify-ing enzymes negatively correlate with 24-hour percentage mortality of Cx. quinquefasciatus. Resistance reported in Cx. quinquefasciatus to multiple classes of insecticides may result in difficulty controlling lymphatic filariasis in these areas.

Effectiveness of structured Behavior Change Communication methods in control of mosquito-borne diseases: A quasi-experimental study

BackgroundBehavior Change Communication (BCC) is evidence-based, theoretically supported and utilizes all opportunities for communication. Evidence reports BCC as a relevant tool for averting and controlling many forms of public health challenges. Through schools, many countries have shown health improvements via students and the community's exposure to behavior change messages. The study was planned with an aim of evaluating the effectiveness of mosquito-borne disease control measures implementation through BCC to adolescent school students in a Cantonment area, in North India. MethodsThe present study was undertaken as a quasi-experimental study from April 2019 to March 2020. Of the 334 students enrolled in the school as per eligibility criteria, 315 were available during the initial assessment, and 288 were available throughout the study. For the evaluation of effectiveness of the BCC at household level, 200 households (100 intervention and 100 control) were selected. Students' knowledge about mosquito-borne diseases was the primary outcome measure. The difference in proportions was tested using the chi-square test. The difference in proportions for paired samples was tested using Mc Nemar's test. ResultsProportion of students who gave correct responses significantly increased after intervention in post-test as compared to pre-test for most of the knowledge-related questions. The proportion of households with the availability of mosquito nets and self-reported use of mosquito nets was significantly high in intervention group as compared to control group post-intervention. ConclusionBCC in the form of different intervention programs to adolescent school children was effective in improving the knowledge and attitude toward mosquito-borne diseases and also ensured less mosquito-genic environment in households.

Mosquito microbiome and its application in mosquito-bornediseases control

<p indent="0mm">Mosquitoes are physically colonized by a complex population of microbes, which constitute a diverse and dynamic microbiome. Mosquito microbiome plays an important role in mosquito physiological functions including nutrition, metabolism, and immunity, and is indispensable for mosquito development and propagation. Meanwhile, the mosquito microbiome significantly affects the infection and transmission of mosquito-borne pathogens, thus has important application potential in the prevention and control of mosquito-borne diseases. Therefore, a comprehensive understanding of mosquito physiology and mosquito-borne diseases transmission cannot ignore the critical role of the microbiome. This review summarizes the advances of mosquito microbiome and its influencing factors, the influence of gut microbiome on host physiology and mechanisms underlying gut microbiota-host-pathogen interactions in mosquitoes. We also provide an overview on the use of microbiome in the prevention and control of mosquito-borne diseases. Finally, directions for future work are discussed.

Insecticide resistance in malaria and arbovirus vectors in Papua New Guinea, 2017–2022

BackgroundInsecticide resistance (IR) monitoring is essential for evidence-based control of mosquito-borne diseases. While widespread pyrethroid resistance in Anopheles and Aedes species has been described in many countries, data for Papua New Guinea (PNG) are limited. Available data indicate that the local Anopheles populations in PNG remain pyrethroid-susceptible, making regular IR monitoring even more important. In addition, Aedes aegypti pyrethroid resistance has been described in PNG. Here, Anopheles and Aedes IR monitoring data generated from across PNG between 2017 and 2022 are presented.MethodsMosquito larvae were collected in larval habitat surveys and through ovitraps. Mosquitoes were reared to adults and tested using standard WHO susceptibility bioassays. DNA from a subset of Aedes mosquitoes was sequenced to analyse the voltage-sensitive sodium channel (Vssc) region for any resistance-related mutations.ResultsApproximately 20,000 adult female mosquitoes from nine PNG provinces were tested. Anopheles punctulatus sensu lato mosquitoes were susceptible to pyrethroids but there were signs of reduced mortality in some areas. Some Anopheles populations were also resistant to DDT. Tests also showed that Aedes. aegypti in PNG are resistant to pyrethroids and DDT and that there was also likelihood of bendiocarb resistance. A range of Vssc resistance mutations were identified. Aedesalbopictus were DDT resistant and were likely developing pyrethroid resistance, given a low frequency of Vssc mutations was observed.ConclusionsAedes aegypti is highly pyrethroid resistant and also shows signs of resistance against carbamates in PNG. Anopheles punctulatus s.l. and Ae. albopictus populations exhibit low levels of resistance against pyrethroids and DDT in some areas. Pyrethroid-only bed nets are currently the only programmatic vector control tool used in PNG. It is important to continue to monitor IR in PNG and develop proactive insecticide resistance management strategies in primary disease vectors to retain pyrethroid susceptibility especially in the malaria vectors for as long as possible.Graphic abstract

A Swin Transformer-based model for mosquito species identification

Mosquito transmit numbers of parasites and pathogens resulting in fatal diseases. Species identification is a prerequisite for effective mosquito control. Existing morphological and molecular classification methods have evitable disadvantages. Here we introduced Deep learning techniques for mosquito species identification. A balanced, high-definition mosquito dataset with 9900 original images covering 17 species was constructed. After three rounds of screening and adjustment-testing (first round among 3 convolutional neural networks and 3 Transformer models, second round among 3 Swin Transformer variants, and third round between 2 images sizes), we proposed the first Swin Transformer-based mosquito species identification model (Swin MSI) with 99.04% accuracy and 99.16% F1-score. By visualizing the identification process, the morphological keys used in Swin MSI were similar but not the same as those used by humans. Swin MSI realized 100% subspecies-level identification in Culex pipiens Complex and 96.26% accuracy for novel species categorization. It presents a promising approach for mosquito identification and mosquito borne diseases control.

Integrating city resilience and mosquito-borne diseases – a multi-site case study from the Resilient Cities Network

ABSTRACT Urbanisation is increasing the risk of mosquito-borne diseases such as dengue and malaria in cities, with resulting impacts on health and development. At the same time, cities worldwide are building and investing in urban resilience. It is not known to what extent and how cities are considering mosquito-borne diseases in their resilience strategies. This research uses a multi-site case study methodology, focused on Resilient Cities Network member cities Chennai (India), Paynesville (Liberia) and Medellín (Colombia), to understand the intersection between mosquito-borne diseases and city resilience. Data collection involved in-depth interviews with resilience representatives of each city and document review to explore perceptions of mosquito-borne diseases, their prioritisation in resilience planning and what resilience activities are implemented and how. Analysis showed that while mosquito-borne diseases are not considered explicitly as a resilience challenge, many resilience activities implemented by cities have co-benefits for mosquito-borne disease control or could be enhanced to realise this potential. For Resilient Cities Network member cities looking to integrate mosquito-borne disease control into their resilience approach, we recommend increasing awareness of interlinkages between city resilience and mosquito-borne diseases, leveraging multi-sectoral collaborations with co-benefits for mosquito-borne disease control, and engaging communities in urban planning and mosquito-borne diseases control efforts.

The impact of transgenesis on mosquito fitness: A review.

Transgenic mosquitoes developed by genetic manipulation, offer a promising strategy for the sustainable and effective control of mosquito-borne diseases. This strategy relies on the mass release of transgenic mosquitoes into the wild, where their transgene is expected to persist in the natural environment, either permanently or transiently, within the mosquito population. In such circumstances, the fitness of transgenic mosquitoes is an important factor in determining their survival in the wild. The impact of transgene expression, insertional mutagenesis, inbreeding depression related to laboratory adaptation, and the hitchhiking effect involved in developing homozygous mosquito lines can all have an effect on the fitness of transgenic mosquitoes. Therefore, real-time estimation of transgene-associated fitness cost is imperative for modeling and planning transgenic mosquito release programs. This can be achieved by directly comparing fitness parameters in individuals homozygous or hemizygous for the transgene and their wild-type counterparts, or by cage invasion experiments to monitor the frequency of the transgenic allele over multiple generations. Recent advancements such as site-specific integration systems and gene drives, provide platforms to address fitness issues in transgenic mosquitoes. More research on the fitness of transgenic individuals is required to develop transgenic mosquitoes with a low fitness cost.

Bio-products from Serratia marcescens isolated from Ghanaian Anopheles gambiae reduce Plasmodium falciparum burden in vector mosquitoes.

Novel ideas for control of mosquito-borne disease include the use of bacterial symbionts to reduce transmission. Bacteria belonging to the family Enterobacteriaceae isolated from mosquito midgut have shown promise in limiting Plasmodium intensity in the Anopheles vector. However, the mechanism of interaction between bacteria and parasite remains unclear. This study aimed at screening bio-products of two bacteria candidates for their anti-Plasmodial effects on mosquito stages of P. falciparum. Enterobacter cloacae and Serratia marcescens were isolated from field-caught Anopheles gambiae s.l. Spent media from liquid cultures of these bacteria were filtered, lyophilized and dissolved in sterile phosphate buffered saline (PBS). The re-dissolved bacterial products were added to gametocytaemic blood meals and fed to An. gambiae mosquitoes via membrane feeders. Control groups were fed on infected blood with or without lyophilized LB medium. The effect of the products on the infection prevalence and intensity of P. falciparum in mosquitoes was assessed by dissecting mosquito midguts and counting oocysts 10-11 days post-infection. S. marcescens bio-products elicited significant reduction in the number of mosquitoes infected (P=4.02 x10-5) with P. falciparum and the oocyst intensity (P<2 x 10-16) than E. cloacae products (P>0.05 for both prevalence and intensity) compared to the control (lyophilized LB medium). These data support the use of bioproducts released by S. marcescens for malaria control based on transmission blocking in the vector.

Constrained control of gene-flow models

In ecology and population dynamics, gene-flow refers to the transfer of a trait (e.g. genetic material) from one population to another. This phenomenon is of great relevance in studying the spread of diseases or the evolution of social features, such as languages. From the mathematical point of view, gene-flow is modelled using bistable reaction-diffusion equations. The unknown is the proportion $p$ of the population that possesses a certain trait, within an overall population $N$. In such models, gene-flow is taken into account by assuming that the population density $N$ depends either on $p$ (if the trait corresponds to fitter individuals) or on the location $x$ (if some zones in the domain can carry more individuals). Recent applications stemming from mosquito-borne disease control problems or from the study of bilingualism have called for the investigation of the controllability properties of these models. At the mathematical level, this corresponds to boundary control problems and, since we are working with proportions, the control $u$ has to satisfy the constraints $0\leq u \leq 1$. In this article, we provide a thorough analysis of the influence of the gene-flow effect on boundary controllability properties. We prove that, when the population density $N$ only depends on the trait proportion $p$, the geometry of the domain is the only criterion that has to be considered. We then tackle the case of population densities $N$ varying in $x$. We first prove that, when $N$ varies slowly in $x$ and when the domain is narrow enough, controllability always holds. This result is proved using a robust domain perturbation method. We then consider the case of sharp fluctuations in $N$: we first give examples that prove that controllability may fail. Conversely, we give examples of heterogeneities $N$ such that controllability will always be guaranteed: in other words the controllability properties of the equation are very strongly influenced by the variations of $N$. All negative controllability results are proved by showing the existence of non-trivial stationary states, which act as barriers. The existence of such solutions and the methods of proof are of independent interest. Our article is completed by several numerical experiments that confirm our analysis.