Vector Control Advisory Group

Independent evaluation of the public health value of innovative new tools, technologies and approaches for vector control is needed to enable WHO to provide evidence-based advice to Member States on whether their deployment is justified. This is essential to ensure that scarce resources available for disease control are used to maximum impact. In order to assist WHO in developing public health policy on new tools, the Vector Control Advisory Group (VCAG) assesses the public health value of new interventions and provides guidance on developing the evidence base required to inform such assessments.

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Genetic manipulation

Gene drive induces preferential inheritance that allows the frequency of a gene in a targeted population to increase rapidly. It thus increases the likelihood that a trait will be passed on to the next generation. The gene-drive approaches being considered by VCAG use the genome editing tool CRISPR-Cas9 to introduce engineered traits into mosquito genomes to promote the increased frequency of inheritance of the desired traits in subsequent generations. The strategies are designed to lower exposure to infectious mosquitoes and thereby reduce morbidity and mortality in humans.

Population reduction – gene drive approach

How the intervention works: An example of a strategy being evaluated under this intervention class aims to reduce mosquito populations by reducing the number of female mosquitoes. This genetic control strategy, developed by Target Malaria, targets An. gambiae s.l. mosquitoes (the most important vectors of malaria in sub-Saharan Africa). The proposed intervention is a release of male An. gambiae s.l. mosquitoes bearing a gene drive construct that will increase their frequency in populations over successive generations , and as it does so it will disrupt the fertility of female mosquitoes and/or distort the sex ratio (e.g. by decreasing the number of female to male mosquitoes). Both effects are designed to reduce malaria transmission by reducing the numbers of An. gambiae s.l. females.

Population alteration (also known as population replacement or modification) – gene drive approach

How the intervention works: An example of a strategy being evaluated under this intervention class is gene drive approach which aims to make vectors incapable of transmitting pathogens. This gene drive approach is being developed collaboratively by the Tata Institute for Genetics and Society and the University of California, Irvine Malaria Initiative. In this genetic control strategy, Anopheles mosquitoes are genetically engineered so that their offspring cannot transmit the malaria parasites to humans. The idea is that when engineered male mosquitoes are introduced into wild mosquito populations and mate with females, the trait (anti-parasite effector genes) will be replicated by the gene drive and will reduce the females’ ability to transmit malaria parasites to humans. The targets of the technology are major vectors of malaria in Africa (An. gambiae) and India (An. stephensi).

Disease(s) that may be reduced in prevalence or prevented: Malaria

Population(s) intended to be protected: The aim of the population reduction gene drive approach is to reduce the population of Anopheles mosquitoes and consequently reduce the transmission of malaria. The population alteration approach aims to engineer Anopheles mosquitoes genetically to prevent their offspring from transmitting the malaria parasites to humans with a similar effect on reducing exposure to infectious mosquitoes. The intended impact will be to lower or eliminate the burden of malaria disease for hundreds of millions of people living in Africa and Asia.

Status of review: The results of laboratory studies on both interventions have been shared with VCAG.

Last update: 18 June 2020