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      Gene-drive mosquitoes: a prospect for future malaria control

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          Abstract

          Despite major developments in malaria control over the past two decades, the disease continues to scourge the human population across the globe. Rising concerns such as insecticide resistance amongst vector mosquitoes are a cause of huge fear amongst healthcare providers and policymakers. Amidst such dire circumstances, a recent development may form the blueprint for future malaria control as for the first time ever researchers were able to decimate an entire mosquito population using gene-drive technology within a span of one year in a multi-generation, ecologically challenging study. Despite some concerns, the technology displayed a high potential of becoming a powerful tool in malaria control.

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          The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito

          Andrew Hammond, Kyros Kyrou, Marco Bruttini … (2017)
          Gene drives have enormous potential for the control of insect populations of medical and agricultural relevance. By preferentially biasing their own inheritance, gene drives can rapidly introduce genetic traits even if these confer a negative fitness effect on the population. We have recently developed gene drives based on CRISPR nuclease constructs that are designed to disrupt key genes essential for female fertility in the malaria mosquito. The construct copies itself and the associated genetic disruption from one homologous chromosome to another during gamete formation, a process called homing that ensures the majority of offspring inherit the drive. Such drives have the potential to cause long-lasting, sustainable population suppression, though they are also expected to impose a large selection pressure for resistance in the mosquito. One of these population suppression gene drives showed rapid invasion of a caged population over 4 generations, establishing proof of principle for this technology. In order to assess the potential for the emergence of resistance to the gene drive in this population we allowed it to run for 25 generations and monitored the frequency of the gene drive over time. Following the initial increase of the gene drive we observed a gradual decrease in its frequency that was accompanied by the spread of small, nuclease-induced mutations at the target gene that are resistant to further cleavage and restore its functionality. Such mutations showed rates of increase consistent with positive selection in the face of the gene drive. Our findings represent the first documented example of selection for resistance to a synthetic gene drive and lead to important design recommendations and considerations in order to mitigate for resistance in future gene drive applications.
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            Prevention Efforts for Malaria

            Tinashe Tizifa, Alinune N. Kabaghe, Robert S McCann … (2018)
            Purpose of Review Malaria remains a global burden contributing to morbidity and mortality especially in children under 5 years of age. Despite the progress achieved towards malaria burden reduction, achieving elimination in more countries remains a challenge. This article aims to review the prevention and control strategies for malaria, to assess their impact towards reducing the disease burden and to highlight the best practices observed. Recent Findings Use of long-lasting insecticide-treated nets and indoor residual spraying has resulted a decline in the incidence and prevalence of malaria in Sub-Saharan Africa. Other strategies such as larval source management have been shown to reduce mosquito density but require further evaluation. New methods under development such as house improvement have demonstrated to minimize disease burden but require further evidence on efficacy. Development of the RTS,S/AS01 malaria vaccine that provides protection in under-five children has provided further progress in efforts of malaria control. Summary There has been a tremendous reduction in malaria burden in the past decade; however, more work is required to fill the necessary gaps to eliminate malaria.
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              Gene-drive suppression of mosquito populations in large cages as a bridge between lab and field

              Andrew Marc Hammond, Paola Pollegioni, Tania Persampieri … (2021)
              CRISPR-based gene-drives targeting the gene doublesex in the malaria vector Anopheles gambiae effectively suppressed the reproductive capability of mosquito populations reared in small laboratory cages. To bridge the gap between laboratory and the field, this gene-drive technology must be challenged with vector ecology. Here we report the suppressive activity of the gene-drive in age-structured An. gambiae populations in large indoor cages that permit complex feeding and reproductive behaviours. The gene-drive element spreads rapidly through the populations, fully supresses the population within one year and without selecting for resistance to the gene drive. Approximate Bayesian computation allowed retrospective inference of life-history parameters from the large cages and a more accurate prediction of gene-drive behaviour under more ecologically-relevant settings. Generating data to bridge laboratory and field studies for invasive technologies is challenging. Our study represents a paradigm for the stepwise and sound development of vector control tools based on gene-drive. Experimental analysis of gene drive population dynamics has mostly been limited to small cage trials. Here the authors, to fill the gap between lab based studies and field studies, use large indoor cages and see population suppression without the emergence of resistant alleles
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Pan Afr Med J
                Journal ID (iso-abbrev): Pan Afr Med J
                Journal ID (publisher-id): PAMJ
                Title: The Pan African Medical Journal
                Publisher: The African Field Epidemiology Network
                ISSN (Electronic): 1937-8688
                Publication date (Electronic): 08 February 2022
                Publication date Collection: 2022
                Volume: 41
                Electronic Location Identifier: 109
                Affiliations
                [1 ]Department of Internal Medicine, Ziauddin Medical University, Karachi, Sindh, Pakistan,
                [2 ]Jordan University Hospital, Amman, Jordan,
                [3 ]Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan,
                [4 ]Kabir Medical College, Gandhara University, Peshawar, Pakistan
                Author notes
                [& ] Corresponding author: Syed Abdullah Monawwer, Department of Internal Medicine, Ziauddin Medical University, Karachi, Sindh, Pakistan. abdullah.munawwer@ 123456gmail.com
                Article
                Publisher ID: PAMJ-41-109
                DOI: 10.11604/pamj.2022.41.109.31687
                PMC ID: 8977354
                PubMed ID: 35432707
                SO-VID: 4b1df65d-03bb-4154-b373-833a2e3188df
                Copyright © Copyright: Syed Abdullah Monawwer et al.
                License:

                The Pan African Medical Journal (ISSN: 1937-8688). This is an Open Access article distributed under the terms of the Creative Commons Attribution International 4.0 License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 20 September 2021
                Date accepted : 23 December 2021
                Categories
                Subject: Commentary

                ScienceOpen disciplines: Medicine
                Keywords: malaria,malaria control,gene-drive
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: malaria, malaria control, gene-drive

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