Volume 98 Number 6_Suppl
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Gene drive technology offers the promise for a high-impact, cost-effective, and durable method to control malaria transmission that would make a significant contribution to elimination. Gene drive systems, such as those based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein, have the potential to spread beneficial traits through interbreeding populations of malaria mosquitoes. However, the characteristics of this technology have raised concerns that necessitate careful consideration of the product development pathway. A multidisciplinary working group considered the implications of low-threshold gene drive systems on the development pathway described in the World Health Organization , focusing on reduction of malaria transmission by s.l. mosquitoes in Africa as a case study. The group developed recommendations for the safe and ethical testing of gene drive mosquitoes, drawing on prior experience with other vector control tools, GM organisms, and biocontrol agents. These recommendations are organized according to a testing plan that seeks to maximize safety by incrementally increasing the degree of human and environmental exposure to the investigational product. As with biocontrol agents, emphasis is placed on safety evaluation at the end of physically confined laboratory testing as a major decision point for whether to enter field testing. Progression through the testing pathway is based on fulfillment of safety and efficacy criteria, and is subject to regulatory and ethical approvals, as well as social acceptance. The working group identified several resources that were considered important to support responsible field testing of gene drive mosquitoes.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Article metrics loading...

Loading full text...

Full text loading...



  1. Curtis CF, Graves PM, , 1988. Methods for replacement of malaria vector populations. J Trop Med Hyg 91: 4348.
  2. Beaty BJ, Prager DJ, James AA, Jacobs-Lorena M, Miller LH, Law JH, Collins FH, Kafatos FC, , 2009. From Tucson to genomics and transgenics: the vector biology network and the emergence of modern vector biology. PLoS Negl Trop Dis 3: e343.
  3. Burt A, , 2014. Heritable strategies for controlling insect vectors of disease. Philos Trans R Soc Lond B Biol Sci 369: 20130432.
  4. Adelman ZN, , 2015. Genetic Control of Malaria and Dengue. Academic Press. New York, NY: Elsevier Science Publishing Co.
  5. Sinkins SP, Gould F, , 2006. Gene drive systems for insect disease vectors. Nat Rev Genet 7: 427435.
  6. Macias VM, Ohm JR, Rasgon JL, , 2017. Gene drive for mosquito control: where did it come from and where are we headed? Int J Environ Res Public Health 14: E1006.
  7. Esvelt KM, Smidler AL, Catteruccia F, Church GM, , 2014. Concerning RNA-guided gene drives for the alteration of wild populations. ELife 3: e03401.
  8. Burt A, , 2003. Site-specific selfish genes as tools for the control and genetic engineering of natural populations. Proc Biol Sci 270: 921928.
  9. Marshall JM, , 2009. The effect of gene drive on containment of transgenic mosquitoes. J Theor Biol 258: 250265.
  10. Noble C, Adlam B, Church GM, Esvelt KM, Nowak MA, , 2017. Current CRISPR gene drive systems are likely to be highly invasive in wild populations. bioRxiv, doi: 10.1101/219022.
  11. Gantz VM, Jasinskiene N, Tatarenkova O, Fazekas A, Macias VM, Bier E, James AA, , 2015. Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. Proc Natl Acad Sci USA 112: E6736E6743.
  12. Hammond A, 2016. A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nat Biotechnol 34: 7883.
  13. Eckhoff PA, Wenger EA, Godfray HC, Burt A, , 2017. Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics. Proc Natl Acad Sci USA 114: E255E264.
  14. Deredec A, Godfray HC, Burt A, , 2011. Requirements for effective malaria control with homing endonuclease genes. Proc Natl Acad Sci USA 108: E874E880.
  15. World Health Organization, 2014. Guidance Framework for Testing of Genetically Modified Mosquitoes. Available at: http://apps.who.int/iris/bitstream/10665/127889/1/9789241507486_eng.pdf?ua=1. Accessed January 22, 2018.
  16. Adelman Z, 2017. Rules of the road for insect gene drive research and testing. Nat Biotechnol 35: 716718.
  17. Kaebnick GE, Heitman E, Collins JP, Delborne JA, Landis WG, Sawyer K, Taneyhill LA, Winickoff DE, , 2016. Precaution and governance of emerging technologies. Science 354: 710711.
  18. National Academies of Science, Engineering and Medicine, 2016. Gene Drives on the Horizon Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values. The National Academies Press. Available at: http://nas-sites.org/gene-drives/. Accessed January 22, 2018.
  19. Emerson C, James S, Littler K, Randazzo F, , 2017. Principles for gene drive research. Science 358: 11351136.
  20. VectorBase Bioinformatics Resource for Invertebrate Vectors of Human Pathogens. Anopheles gambiae s.l. Available at: https://www.vectorbase.org/taxonomy/anopheles-gambiae-sl. Accessed January 22, 2018.
  21. Fontaine MC, 2015. Mosquito genomics. Extensive introgression in a malaria vector species complex revealed by phylogenomics. Science 347: 1258524.
  22. Sinka ME, 2012. A global map of dominant malaria vectors. Parasit Vectors 5: 69.
  23. Sinka ME, 2010. The dominant Anopheles vectors of human malaria in Africa, Europe and the Middle East: occurrence data, distribution maps and bionomic precis. Parasit Vectors 3: 117.
  24. Roche JP, , 2015. Anopheles Mosquitoes as Vectors of Malaria in East Africa: Bed Nets and Beyond. Entomology Today: Entomological Society of America. Available at: https://entomologytoday.org/2015/04/24/anopheles-mosquitoes-as-vectors-of-malaria-in-east-africa-bed-nets-and-beyond/. Accessed January 22, 2018.
  25. Bhatt S, 2015. The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. Nature 526: 207211.
  26. WHO, 2017. World Malaria Report 2017. World Health Organization. Available at: http://apps.who.int/iris/bitstream/10665/259492/1/9789241565523-eng.pdf?ua=1. Accessed January 22, 2018.
  27. WHO, 2016. World Malaria Report 2016. World Health Organization. Available at: http://apps.who.int/iris/bitstream/handle/10665/252038/9789241511711-eng.pdf;jsessionid=8F359C7AF7CC0FEB0988D4690942A77F?sequence=1. Accessed May 4, 2018.
  28. Hemingway J, 2016. Averting a malaria disaster: will insecticide resistance derail malaria control? Lancet 387: 17851788.
  29. Nkumama IN, O’Meara WP, Osier FH, , 2017. Changes in malaria epidemiology in Africa and new challenges for elimination. Trends Parasitol 33: 128140.
  30. Patouillard E, Griffin J, Bhatt S, Ghani A, Cibulskis R, , 2017. Global investment targets for malaria control and elimination between 2016 and 2030. BMJ Glob Health 2: e000176.
  31. World Health Organization, 2015. Global Technical Strategy for Malaria 2016–2030. Available at: http://apps.who.int/iris/bitstream/10665/176712/1/9789241564991_eng.pdf. Accessed January 22, 2018.
  32. World Health Organization, 2017. Fifth Meeting of the Vector Control Advisory Group. Geneva, Switzerland, November 2–4, 2016. Available at: http://apps.who.int/iris/bitstream/10665/255824/1/WHO-HTM-NTD-VEM-2017.02-eng.pdf?ua=1. Accessed January 22, 2018.
  33. Champer J, Buchman A, Akbari OS, , 2016. Cheating evolution: engineering gene drives to manipulate the fate of wild populations. Nat Rev Genet 17: 146159.
  34. Tanaka H, Stone HA, Nelson DR, , 2017. Spatial gene drives and pushed genetic waves. Proc Natl Acad Sci USA 114: 84528457.
  35. Noble C, Min M, Olejarz J, Buchthal J, Chavez A, Smidler AL, DeBenedictis EA, Church GM, Nowak MA, Esvelt KM, , 2016. Daisy-chain gene drives for the alteration of local populations. bioRxiv, doi: 10.1101/057307.
  36. Burt A, Deredec A, , 2017. Self-limiting population genetic control with sex-linked genome editors. bioRxiv, doi: 10.1101/236489.
  37. Fischetti M, , 2015. Africa Dwarfs China, Europe and the U.S. The Most Prevalent Flat Maps Make Africa Appear Much Smaller Than It Is. Scientific American: Springer Nature. Available at: https://www.scientificamerican.com/article/africa-dwarfs-china-europe-and-the-u-s/. Accessed January 22, 2018.
  38. Derua YA, Alifrangis M, Magesa SM, Kisinza WN, Simonsen PE, , 2015. Sibling species of the Anopheles funestus group, and their infection with malaria and lymphatic filarial parasites, in archived and newly collected specimens from northeastern Tanzania. Malar J 14: 104.
  39. Djouaka RJ, Atoyebi SM, Tchigossou GM, Riveron JM, Irving H, Akoton R, Kusimo MO, Bakare AA, Wondji CS, , 2016. Evidence of a multiple insecticide resistance in the malaria vector Anopheles funestus in south west Nigeria. Malar J 15: 565.
  40. Beaghton A, Beaghton PJ, Burt A, , 2017. Vector control with driving Y chromosomes: modelling the evolution of resistance. Malar J 16: 286.
  41. Marshall JM, Buchman A, Sanchez CHM, Akbari OS, , 2017. Overcoming evolved resistance to population-suppressing homing-based gene drives. Sci Rep 7: 3776.
  42. Unckless RL, Clark AG, Messer PW, , 2017. Evolution of resistance against CRISPR/Cas9 gene drive. Genetics 205: 827841.
  43. Hammond AM, 2017. The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito. PLoS Genet 13: e1007039.
  44. Drugs for Neglected Diseases Initiative. Target Product Profiles. Available at: https://www.dndi.org/diseases-projects/target-product-profiles/. Accessed March 29, 2018.
  45. U.S. Food and Drug Administration, 2007. Guidance for Industry and Review Staff Target Product Profile—A Strategic Development Process Tool. Available at: https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm080593.pdf. Accessed March 29, 2018.
  46. Global HIV Vaccine Enterprise. Target Product Profile: A Guidance Document. Available at: http://www.vaccineenterprise.org/timely-topics/target-product-profile. Accessed March 29, 2018.
  47. Carballar-Lejarazu R, James AA, , 2017. Population modification of Anopheline species to control malaria transmission. Pathog Glob Health 111: 424435.
  48. Australian Academy of Science, 2017. Synthetic Gene Drives in Australia: Implications of Emerging Technologies. Available at: https://www.science.org.au/files/userfiles/support/documents/gene-drives-discussion-paper-june2017.pdf. Accessed January 22, 2018.
  49. Lunshof JE, Birnbaum A, , 2017. Adaptive risk management of gene drive experiments. Appl Biosaf 22: 97103.
  50. Roberts A, Andrade PP, Okumu F, Quemada H, Savadogo M, Singh JA, James S, , 2017. Results from the workshop “problem formulation for the use of gene drive in mosquitoes”. Am J Trop Med Hyg 96: 530533.
  51. Murray JV, Jansen CC, De Barro P, , 2016. Risk associated with the release of Wolbachia-infected Aedes aegypti mosquitoes into the environment in an effort to control dengue. Front Public Health 4: 43.
  52. Hartley S, Millar KM, , 2014. The challenges of consulting the public on science policy: examining the development of European risk assessment policy for genetically modified animals. Rev Policy Res 31: 481502.
  53. International Association for Impact Assessment and Institute of Environmental Assessment, UK, 1999. Principles of Environmental Impact Assessment Best Practice. Available at: http://www.iaia.org/uploads/pdf/principlesEA_1.pdf. Accessed January 10, 2018.
  54. Vanclay F, , 2003. International principles for social impact assessment. IAPA 21: 511.
  55. Murphy B, Jansen C, Murray J, De Barro P, , 2010. Risk Analysis on the Australian Release of Aedes aegypti (L.) (Diptera: Culicidae) Containing Wolbachia. CSIRO. Available at: http://www.eliminatedengue.com/library/publication/document//riskanalysisfinalreportcsiro.pdf. Accessed January 22, 2018.
  56. Neuhaus CP, Caplan AL, , 2017. Ethical lessons from a tale of two genetically modified insects. Nat Biotechnol 35: 713716.
  57. Wellcome Trust. Sharing Research Data to Improve Public Health: Full Joint Statement by Funders of Health Research. Available at: https://wellcome.ac.uk/what-we-do/our-work/sharing-research-data-improve-public-health-full-joint-statement-funders-health. Accessed January 22, 2018.
  58. Wellcome Trust, 2003. Sharing Data from Large-Scale Biological Research Projects: A System of Tripartite Responsibility. Available at: https://www.genome.gov/pages/research/wellcomereport0303.pdf. Accessed January 22, 2018.
  59. VectorBase. VectorBase Bioinformatics Resource for Invertebrate Vectors of Human Pathogens. Available at: https://www.vectorbase.org/. Accessed January 22, 2018.
  60. Plasmo DB. Plasmodium Genomics Resource. Available at: http://plasmodb.org/plasmo/. Accessed January 22, 2018.
  61. CDISC, 2017. Malaria Therapeutic Area User Guide v1.0. Available at: https://www.cdisc.org/standards/therapeutic-areas/malaria. Accessed January 22, 2018.
  62. Leitner WW, Wali T, Kincaid R, Costero-Saint Denis A, , 2015. Arthropod vectors and disease transmission: translational aspects. PLoS Negl Trop Dis 9: e0004107.
  63. World Health Organization. Ethical Standards and Procedures for Research with Human Beings. Available at: http://www.who.int/ethics/research/en/. Accessed January 22, 2018.
  64. U.S. Department of Health & Human Services, 2009. Code of Federal Regulations Title 45 Public Welfare Department of Health and Human Services Part 46 Protection of Human Subjects. Available at: https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/. Accessed January 22, 2018.
  65. Achee NL, Youngblood L, Bangs MJ, Lavery JV, James S, , 2015. Considerations for the use of human participants in vector biology research: a tool for investigators and regulators. Vector Borne Zoonotic Dis 15: 89102.
  66. Kolopack PA, Lavery JV, , 2017. Gates Open Research. Informed Consent in Field Trials of Gene-Drive Mosquitoes [Version 1; Referees: 4 Approved]. Available at: https://gatesopenresearch.org/articles/1-14/v1. Accessed December 20, 2017.
  67. LAC HSR Health Sector Reform Initiative, 2000. Stakeholder analysis guidelines. Policy Toolkit for Strengthening Health Sector Reform. Washington, D.C.: Pan American Health Organization.
  68. Bandewar SV, Wambugu F, Richardson E, Lavery JV, , 2017. The role of community engagement in the adoption of new agricultural biotechnologies by farmers: the case of the Africa harvest tissue-culture banana in Kenya. BMC Biotechnol 17: 28.
  69. McNaughton D, Duong TT, , 2014. Designing a community engagement framework for a new dengue control method: a case study from central Vietnam. PLoS Negl Trop Dis 8: e2794.
  70. Kolopack PA, Parsons JA, Lavery JV, , 2015. What makes community engagement effective?: lessons from the eliminate dengue program in Queensland Australia. PLoS Negl Trop Dis 9: e0003713.
  71. Lavery JV, Tinadana PO, Scott TW, Harrington LC, Ramsey JM, Ytuarte-Nunez C, James AA, , 2010. Towards a framework for community engagement in global health research. Trends Parasitol 26: 279283.
  72. Nuffield Council on Bioethics, 2012. Emerging Biotechnologies: Technology, Choice and the Public Good. Available at: http://nuffieldbioethics.org/wp-content/uploads/2014/07/Emerging_biotechnologies_full_report_web_0.pdf. Accessed January 22, 2018.
  73. MacQueen KM, Bhan A, Frohlich J, Holzer J, Sugarman J, Ethics Working Group of the HIVPTN; , 2015. Evaluating community engagement in global health research: the need for metrics. BMC Med Ethics 16: 44.
  74. International Finance Corporation, 2007. Stakeholder Engagement: A Good Practice Handbook for Companies Doing Business in Emerging Markets. Available at: http://documents.worldbank.org/curated/en/579261468162552212/pdf/399160IFC1StakeholderEngagement01PUBLIC1.pdf. Accessed January 22, 2018.
  75. International Finance Corporation, 2014. A Strategic Approach to Early Stakeholder Engagement: A Good Practice Handbook for Junior Companies in the Extractive Industries. Available at: https://commdev.org/userfiles/FINAL_IFC_131208_ESSE%20Handbook_web%201013.pdf. Accessed January 22, 2018.
  76. Community Engagement in the NSW planning System, 2003. Crown. Available at: https://www.communityplanningtoolkit.org/sites/default/files/CommunityEngagementHandbookNewSouthWales.pdf. Accessed January 22, 2018.
  77. MESH. MESH Community Engagement Network. Available at: https://mesh.tghn.org/. Accessed January 22, 2018.
  78. Pielke RA, , 2007. The Honest Broker: Making Sense of Science in Policy and Politics. Cambridge, UK: Cambridge University Press.
  79. National Academies of Science, Engineering and Medicine, 2016. Communicating Chemistry A Framework for Sharing Science: A Practical Evidence-Based Guide. The National Academies Press. Available at: http://nap.edu/23444. Accessed January 22, 2018.
  80. Ramsey JM, Bond JG, Macotela ME, Facchinelli L, Valerio L, Brown DM, Scott TW, James AA, , 2014. A regulatory structure for working with genetically modified mosquitoes: lessons from Mexico. PLoS Negl Trop Dis 8: e2623.
  81. World Health Organization. Vector Control Advisory Group (VCAG). Available at: http://www.who.int/neglected_diseases/vector_ecology/VCAG/en/. Accessed January 22, 2018.
  82. Convention on Biological Diversity. The Cartagena Protocol on Biosafety. Available at: https://bch.cbd.int/protocol. Accessed January 22, 2018.
  83. Convention on Biological Diversity. Convention on Biological Diversity Safeguard Life on Earth. Available at: https://www.cbd.int/. Accessed January 22, 2018.
  84. New Partnership for Africa’s Development, 2017. Issue Brief: African Union Model Law for Medical Products Regulation: Increasing Access to and Delivery of New Health Technologies for Patients in Need. Available at: http://www.nepad.org/resource/issue-brief-african-union-model-law-medical-products-regulation-increasing-access-and. Accessed January 22, 2018.
  85. Akbari OS, 2015. Safeguarding gene drive experiments in the laboratory. Science 349: 927929.
  86. Benedict MQ, Burt A, Capurro ML, De Barro P, Handler AM, Hayes KR, Marshall JM, Tabachnick WJ, Adelman ZN, , 2018. Recommendations for laboratory containment and management of gene drive systems in arthropods. Vector Borne Zoonotic Dis 8: 213.
  87. African Biosafety Network of Expertise, 2013. Development of Genetically Modified Crops in Africa. Available at: http://nepad-abne.net/biotechnology/development-of-genetically-modified-crops-in-africa/. Accessed January 22, 2018.
  88. New Partnership for Africa’s Development. ABNE: A Biosafety Resource Network for African Regulators and Policy Makers. Available at: http://nepad-abne.net/. Accessed January 22, 2018.
  89. African Union. Regional Economic Communities (RECs). Available at: https://au.int/en/organs/recs. Accessed January 22, 2018.
  90. Convention on Biological Diversity. The Nagoya—Kuala Lumpur Supplementary Protocol on Liability and Redress to the Cartagena Protocol on Biosafety. Available at: https://bch.cbd.int/protocol/supplementary/. Accessed January 18, 2018.
  91. Wu B, Luo L, Gao XJ, , 2016. Cas9-triggered chain ablation of cas9 as a gene drive brake. Nat Biotechnol 34: 137138.
  92. Gantz VM, Bier E, , 2016. The dawn of active genetics. Bioessays 38: 5063.
  93. Zentner GE, Wade MJ, , 2017. The promise and peril of CRISPR gene drives: genetic variation and inbreeding may impede the propagation of gene drives based on the CRISPR genome editing technology. Bioessays 39: 1700109.
  94. Convention on Biological Diversity. The Nagoya Protocol on Access and Benefit-Sharing. Available at: https://www.cbd.int/abs/. Accessed January 22, 2018.
  95. Benedict M, 2008. Guidance for contained field trials of vector mosquitoes engineered to contain a gene drive system: recommendations of a scientific working group. Vector Borne Zoonotic Dis 8: 127166.
  96. Ferguson HF, Gandon S, Mackinnon MJ, Read AF, , 2006. Malaria parasite virulence in mosquitoes and its implications for the introduction and efficacy of GMM malaria control programmes. Boete C, ed. Genetically Modified Mosquitoes for Malaria Control. Georgetown, TX: Landes Bioscience.
  97. Keese P, , 2008. Risks from GMOs due to horizontal gene transfer. Environ Biosafety Res 7: 123149.
  98. Barratt BIP, Moeed A, Malone LA, , 2006. Biosafety assessment protocols for new organisms in New Zealand: can they apply internationally to emerging technologies? EIA Review 26: 339358.
  99. Popovici J, Moreira LA, Poinsignon A, Iturbe-Ormaetxe I, McNaughton D, O’Neill SL, , 2010. Assessing key safety concerns of a Wolbachia-based strategy to control dengue transmission by Aedes mosquitoes. Mem Inst Oswaldo Cruz 105: 957964.
  100. De Barro PJ, Murphy B, Jansen CC, Murray J, , 2011. The proposed release of the yellow fever mosquito, Aedes aegypti containing a naturally occurring strain of Wolbachia pipientis, a question of regulatory responsibility. J Verbraucherschutz Lebensmsicherh 6: 3340.
  101. Hurst TP, Pittman G, O’Neill SL, Ryan PA, Nguyen HL, Kay BH, , 2012. Impacts of Wolbachia infection on predator prey relationships: evaluating survival and horizontal transfer between wMelPop infected Aedes aegypti and its predators. J Med Entomol 49: 624630.
  102. Endersby NM, Hoffmann AA, , 2013. Effect of Wolbachia on insecticide susceptibility in lines of Aedes aegypti. Bull Entomol Res 103: 269277.
  103. Truong QH, Truong UN, Nguyen VH, Nguyen DC, , 2011. Vietnam Eliminate Dengue Project: Risk Assessment of the Pilot Release of Aedes aegypti Mosquitoes Containing Wolbachia. Vietnam Eliminate Dengue Project. Available at: http://www.eliminatedengue.com/library/publication/document/july_2011_ra_report_eng.pdf. Accessed January 22, 2018.
  104. Beaghton A, Hammond A, Nolan T, Crisanti A, Godfray HC, Burt A, , 2017. Requirements for driving antipathogen effector genes into populations of disease vectors by homing. Genetics 205: 15871596.
  105. James AA, , 2005. Gene drive systems in mosquitoes: rules of the road. Trends Parasitol 21: 6467.
  106. Hammond AM, Galizi R, , 2017. Gene drives to fight malaria: current state and future directions. Pathog Glob Health 111: 412423.
  107. Noble C, Olejarz J, Esvelt KM, Church GM, Nowak MA, , 2017. Evolutionary dynamics of CRISPR gene drives. Sci Adv 3: e1601964.
  108. U.S. Department of Health and Human Services. 2009. Biosafety in Microbiological and Biomedical Laboratories. Section VIII-C: Parasitic Agents. Washington, D.C.: US Department of Health and Human Services, 182194.
  109. American Committee of Medical Entomology ASoTMaH, 2003. Arthropod containment guidelines. A project of the American Committee of Medical Entomology and American Society of Tropical Medicine and Hygiene. Vector Borne Zoonotic Dis 3: 6198.
  110. Adelman ZN, Pledger D, Myles KM, , 2017. Developing standard operating procedures for gene drive research in disease vector mosquitoes. Pathog Glob Health 111: 436447.
  111. U.S. Environmental Protection Agency, 2017. EPA Revised Ecological Risk Assessment for the Section 3 Registration of the Microbial Pesticide End-Use Product ZAP Mosquito Larvae. Available at: https://www.regulations.gov/document?D=EPA-HQ-OPP-2016-0205-0019. Accessed March 30, 2018.
  112. US Department of Health and Human Services, 2018. Facility Inspection Report Response Organization: Florida Keys Mosquito Control District. Available at: https://www.fda.gov/downloads/AnimalVeterinary/DevelopmentApprovalProcess/GeneticEngineering/GeneticallyEngineeredAnimals/UCM514797.pdf. Accessed March 30, 2018.
  113. Convention on Biological Diversity. Country Profiles. Available at: https://www.cbd.int/countries/nfp/default.shtml. Accessed January 22, 2018.
  114. Brown DM, Alphey LS, McKemey A, Beech C, James AA, , 2014. Criteria for identifying and evaluating candidate sites for open-field trials of genetically engineered mosquitoes. Vector Borne Zoonotic Dis 14: 291299.
  115. Ferguson HM, 2008. Establishment of a large semi-field system for experimental study of African malaria vector ecology and control in Tanzania. Malar J 7: 158.
  116. Facchinelli L, Valerio L, Bond JG, Wise de Valdez MR, Harrington LC, Ramsey JM, Casas-Martinez M, Scott TW, , 2011. Development of a semi-field system for contained field trials with Aedes aegypti in southern Mexico. Am J Trop Med Hyg 85: 248256.
  117. Vontas J, Moore S, Kleinschmidt I, Ranson H, Lindsay S, Lengeler C, Hamon N, McLean T, Hemingway J, , 2014. Framework for rapid assessment and adoption of new vector control tools. Trends Parasitol 30: 191204.
  118. Frentiu FD, Zakir T, Walker T, Popovici J, Pyke AT, van den Hurk A, McGraw EA, O’Neill SL, , 2014. Limited dengue virus replication in field-collected Aedes aegypti mosquitoes infected with Wolbachia. PLoS Negl Trop Dis 8: e2688.
  119. Hoffmann AA, Iturbe-Ormaetxe I, Callahan AG, Phillips BL, Billington K, Axford JK, Montgomery B, Turley AP, O’Neill SL, , 2014. Stability of the wMel Wolbachia infection following invasion into Aedes aegypti populations. PLoS Negl Trop Dis 8: e3115.
  120. Smith PG, Ross DA, Morrow RH, ed., 2015. Field Trials of Health Interventions: A Toolbox. Oxford University Press. Available at: http://fdslive.oup.com/www.oup.com/academic/pdf/openaccess/9780198732860.pdf. Accessed January 22, 2018.
  121. Macias VM, James AA, , 2015. Impact of genetic modification of vector populations on the malaria eradication agenda. Adelman ZN, ed. Genetic Control of Malaria and Dengue. Oxford, United Kingdom: Elsevier Academic Press.
  122. Boete C, Koella JC, , 2002. A theoretical approach to predicting the success of genetic manipulation of malaria mosquitoes in malaria control. Malar J 1: 3.
  123. Habicht JP, Victora CG, Vaughan JP, , 1999. Evaluation designs for adequacy, plausibility and probability of public health programme performance and impact. Int J Epidemiol 28: 1018.
  124. Lehmann T, Hawley WA, Grebert H, Danga M, Atieli F, Collins FH, , 1999. The Rift Valley complex as a barrier to gene flow for Anopheles gambiae in Kenya. J Hered 90: 613621.
  125. Dao A, Yaro AS, Diallo M, Timbine S, Huestis DL, Kassogue Y, Traore AI, Sanogo ZL, Samake D, Lehmann T, , 2014. Signatures of aestivation and migration in Sahelian malaria mosquito populations. Nature 516: 387390.
  126. Maliti D, Ranson H, Magesa S, Kisinza W, Mcha J, Haji K, Killeen G, Weetman D, , 2014. Islands and stepping-stones: comparative population structure of Anopheles gambiae sensu stricto and Anopheles arabiensis in Tanzania and implications for the spread of insecticide resistance. PLoS One 9: e110910.
  127. Kayondo JK, Mukwaya LG, Stump A, Michel AP, Coulibaly MB, Besansky NJ, Collins FH, , 2005. Genetic structure of Anopheles gambiae populations on islands in northwestern Lake Victoria, Uganda. Malar J 4: 59.
  128. Miles A, 2016. Natural diversity of the malaria vector Anopheles gambiae. bioRxiv, doi: 10.1101/096289.
  129. World Health Organization. Overview of Malaria Elimination. Available at: http://www.who.int/malaria/areas/elimination/overview/en/. Accessed January 22, 2018.
  130. World Health Organization, 2017. Design of Epidemiological Trials for Vector Control Products: Report of a WHO Expert Advisory Group. Available at: http://apps.who.int/iris/bitstream/10665/255854/1/WHO-HTM-NTD-VEM-2017.04-eng.pdf. Accessed January 22, 2018.
  131. World Health Organization. International Clinical Trials Registry Platform (ICTRP). Available at: http://www.who.int/ictrp/en/. Accessed January 22, 2018.
  132. U.S. National Library of Medicine. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/. Accessed January 22, 2018.
  133. World Health Organization, 2005. Operational Guidelines for the Establishment and Functioning of Data and Safety Monitoring Boards. Available at: http://www.who.int/tdr/publications/documents/operational-guidelines.pdf?ua=1. Accessed January 22, 2018.
  134. Brown CA, Lilford RJ, , 2006. The stepped wedge trial design: a systematic review. BMC Med Res Methodol 6: 54.
  135. World Health Organization, 2017. How to Design Vector Control Efficacy Trials: Guidance on Phase III Vector Control Field Trial Design. Available at: http://apps.who.int/iris/bitstream/10665/259688/1/WHO-HTM-NTD-VEM-2017.03-eng.pdf?ua=1. Accessed January 22, 2018.
  136. Hayes RJ, Moulton LH, , 2017. Cluster Randomised Trials. Boca Raton, Florida: CRC Press.
  137. Wilson AL, Boelaert M, Kleinschmidt I, Pinder M, Scott TW, Tusting LS, Lindsay SW, , 2015. Evidence-based vector control? Improving the quality of vector control trials. Trends Parasitol 31: 380390.
  138. Delrieu I, Leboulleux D, Ivinson K, Gessner BD, Malaria Transmission Blocking Vaccine Technical Consultation Group; , 2015. Design of a phase III cluster randomized trial to assess the efficacy and safety of a malaria transmission blocking vaccine. Vaccine 33: 15181526.
  139. Drame PM, 2015. Specific antibodies to Anopheles gSG6-P1 salivary peptide to assess early childhood exposure to malaria vector bites. Malar J 14: 285.
  140. U.S. National Institutes of Health, 2017. Certificates of Confidentiality: Background Information. Available at: https://humansubjects.nih.gov/coc/background. Accessed January 22, 2018.
  141. Convention on Biological Diversity. The Biosafety Clearing-House. Available at: http://bch.cbd.int/about/. Accessed January 22, 2018.
  142. Alphey N, Alphey L, Bonsall MB, , 2011. A model framework to estimate impact and cost of genetics-based sterile insect methods for dengue vector control. PLoS One 6: e25384.
  143. World Health Organization, 2015. Risks Associated with Scale-Back of Vector Control after Malaria Transmission Has Been Reduced. Available at: http://www.who.int/malaria/publications/atoz/scale-back-vector-control.pdf?ua=1. Accessed January 22, 2018.
  144. Gerardin J, Bever CA, Bridenbecker D, Hamainza B, Silumbe K, Miller JM, Eisele TP, Eckhoff PA, Wenger EA, , 2017. Effectiveness of reactive case detection for malaria elimination in three archetypical transmission settings: a modelling study. Malar J 16: 248.
  145. U.S. Agency for International Development, 2016. Pathways to Scale: A Guide on Business Models and Partnership Approaches to Scale-Up. Available at: https://www.usaid.gov/cii/pathways-scale. Accessed January 22, 2018.
  146. Hoeschle-Zeledon IPN, Kumar L, , 2013. Regulatory Challenges for Biological Control. SP-IPM Secretariat, International Institute of Tropical Agriculture (IITA). Available at: http://www.spipm.cgiar.org/c/document_library/get_file?uuid=3509eb45-64eb-47ac-a933-8ebcd5d5574a&groupId=17812. Accessed January 22, 2018.
  147. New Partnership for Africa’s Development. African Medicines Regulatory Harmonisation (AMRH). Available at: http://www.nepad.org/content/african-medicines-regulatory-harmonisation-armh-programs. Accessed January 22, 2018.
  148. World Health Organization, 2012. Handbook for Integrated Vector Management. Available at: http://apps.who.int/iris/bitstream/10665/44768/1/9789241502801_eng.pdf. Accessed January 22, 2018.
  149. African Leaders Malaria Alliance, 2016. African Heads of State Adopt Roadmap to Eliminate Malaria in Africa by 2030. Available at: http://alma2030.org/content/african-heads-state-adopt-roadmap-eliminate-malaria-africa-2030. Accessed January 22, 2018.
  150. Kabayo JP, Boussaha A, , 2002. Partnerships for Fighting Rural Poverty: Africa Steps up Campaign Against the Tsetse Fly. Vienna, Austria: IAEA Bulletin: International Atomic Energy Agency, 11–16.
  151. World Health Organization, 2017. The Evaluation Process for Vector Control Products. Available at: http://apps.who.int/iris/bitstream/10665/255644/1/WHO-HTM-GMP-2017.13-eng.pdf. Accessed January 22, 2018.
  152. Seck MT, 2015. Quality of sterile male Tsetse after long distance transport as chilled, irradiated pupae. PLoS Negl Trop Dis 9: e0004229.
  153. Gamboa D, 2010. A large proportion of P. falciparum isolates in the Amazon region of Peru lack pfhrp2 and pfhrp3: implications for malaria rapid diagnostic tests. PLoS One 5: e8091.
  154. Maund SJ, Campbell PJ, Giddings JM, Hamer MJ, Henry K, Pilling ED, Warinton JS, Wheeler JR, , 2012. Ecotoxicology of synthetic pyrethroids. Top Curr Chem 314: 137165.
  155. World Health Organization, 2017. A Framework for Malaria Elimination. Available at: http://apps.who.int/iris/bitstream/10665/254761/1/9789241511988-eng.pdf?ua=1. Accessed January 22, 2018.
  156. De Barro PJ, Coombs MT, , 2009. Post-release evaluation of Eretmocerus hayati Zolnerowich and Rose in Australia. Bull Entomol Res 99: 193206.
  157. U.S. Food and Drug Administration, 2017. FDA Issues Final Guidance Clarifying FDA and EPA Jurisdiction over Mosquito-Related Products. Available at: https://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm578420.htm. Accessed January 22, 2018.
  158. Department of Environmental Affairs, Republic of South Africa; and South African National Biodiversity Institute, 2011. Monitoring the Environmental Impacts of GM Maize in South Africa: The Outcomes of the South Africa-Norway Biosafety Cooperation Project (2008–2010). Available at: https://www.sanbi.org/sites/default/files/documents/documents/sanbimaizereportlr.pdf. Accessed January 22, 2018.
  159. South African National Biodiversity Institute, Genetically Modified Organisms Programme. Available at: https://www.sanbi.org/biodiversity/building-knowledge/biodiversity-monitoring-assessment/genetically-modified-organisms-on-the-environment/. Accessed May 23, 2018.
  160. World Health Organization, 2016. A Toolkit for Integrated Vector Management in Sub-Saharan Africa. Available at: http://apps.who.int/iris/bitstream/10665/250267/1/9789241549653-eng.pdf?ua=1. Accessed January 22, 2018.
  161. DHIS 2. In Action. Available at: https://www.dhis2.org/inaction. Accessed January 22, 2018.
  162. ELIMINATION 8, 2016. Available at: https://malariaelimination8.org/. Accessed January 22, 2018.
  163. World Health Organization, 2012. Global Plan for Insecticide Resistance Management in Malaria Vectors. Available at: http://apps.who.int/iris/bitstream/10665/44846/1/9789241564472_eng.pdf?ua=1. Accessed January 22, 2018.
  164. The Worldwide Insecticide Resistance Network (WIN). Available at: https://win-network.ird.fr/. Accessed January 22, 2018.
  165. Worldwide Antimalarial Resistance Network (WWARN). Available at: http://www.wwarn.org/. Accessed January 22, 2018.
  166. IR Mapper. Available at: http://www.irmapper.com/. Accessed January 22, 2018.
  167. National Academies of Science - National Research Council, 1966. Report of the Ad hoc Committee on Principles of Research-Engineering Interaction. Available at: http://www.dtic.mil/dtic/tr/fulltext/u2/636529.pdf. Accessed March 30, 2018.
  168. World Health Organization, 2017. WHO Malaria Terminology. Available at: http://apps.who.int/iris/bitstream/10665/208815/1/WHO_HTM_GMP_2016.6_eng.pdf. Accessed January 22, 2018.

Data & Media loading...

  • Received : 30 Jan 2018
  • Accepted : 04 Apr 2018

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error