Writes Brian B. Tarimo

On April 25, we celebrate World Malaria Day. Malaria prevention, diagnosis and treatment programmes have prevented 1.5 billion cases and saved 7.6 million lives in the past decade. These numbers are undoubtedly impressive; however, we are still far away from a malaria-free world.

The burden of malaria is highest in tropical and subtropical regions. According to the 2020 World Malaria report by WHO, 94% of all malaria cases occurred in Africa. I am from Tanzania and, throughout my life, I have seen members of family and friends fighting the disease several times. I have also had malaria several times.

I have dedicated my career to eradicating malaria and other vector-borne diseases. As a research scientist, I could not stress enough the need for novel tools and methods to fight these diseases. Africa stands to accrue the most benefits from any interventions for malaria control approved for widescale application, including gene drive mosquitoes.

Mosquitoes are one of the deadliest animals on earth!

Mosquitoes and other invertebrates are able to transmit (serve as vectors for) infectious pathogens such as parasites, viruses and bacteria between humans, or from animals to humans. Collectively, the diseases caused by these infectious pathogens are known as vector-borne diseases and include for example malaria, yellow fever, dengue, chikungunya, Zika, schistosomiasis, leishmaniasis, human African trypanosomiasis, Chagas diseases, onchocerciasis to mention a few.

More than half of the world’s population is at risk of contracting vector-borne diseases each year. They are responsible for a great deal of morbidity and mortality accounting for more than 17% of all infectious diseases, causing more than 700,000 deaths annually.

Since 2014, different parts of the world have experienced major outbreaks of malaria, yellow fever, dengue, chikungunya and Zika. These diseases have burdened populations, claimed many lives and overwhelmed health systems in the outbreak countries. One thing in common about these diseases is that they are all transmitted (vectored) by mosquitoes. Female mosquitoes of the genus Anopheles are responsible for the transmission of malaria.

Progress has plateaued, we need to do more

Recent reports from WHO show that the reduction in malaria cases has stalled in many parts of the world, with some countries reporting an increase. It is evident that the current interventions used to control malaria mosquitoes have reached the limit of their efficacy.

Therefore, we cannot proceed with “business as usual” approach by employing the same resources and interventions and expect the targets set to reduce malaria, and eventual elimination and eradication of this disease to be met. The development of novel and complementary interventions is required in order to achieve further gains and not lose any ground.

One such novel intervention is the use of genetically modified mosquitoes with gene drives known as “gene drive mosquitoes”. These are mosquitoes with a genetic modification that either impairs their ability to reproduce and thus overtime aims at eliminating the mosquito from the population (this is known as population suppression) or impairs their ability to transmit malaria parasites and thus overtime aims at the permanent introduction of a new mosquito into the population (this is known as population replacement).

The genetic modification in these mosquitoes is coupled with a super-Mendelian form of inheritance known as gene drive that biases inheritance from one generation to another such that instead of 50/50 chance of the genetic modification to be passed from parents to offspring there is now a near 100% chance of the genetic modification to be passed from parents to offspring. This ensures that the genetic modification is present in each successive generation and not lost over time.

What are the advantages of gene drive?

Gene drive mosquitoes have several advantages over current interventions, such as insecticide-treated bed nets (ITNs) and indoor residual spraying (IRS), used for controlling malaria mosquitoes:

Higher efficiency: there is near 100% guarantee that gene drive mosquitoes will have the genetic modification for suppressing/altering the target population. Current interventions are only efficient if they come into contact with a mosquito, which is not always a guarantee.

Long-lasting: the genetic modification will exist from generation to generation as long as the gene drive mosquitoes are reproducing in the target population. Current interventions such as ITNs lose their efficacy after some time and have to be replaced.

Greater accessibility: mosquitoes can easily spread from one location to another. They do not require any infrastructure to be in place to ensure their spatial spread. This means that gene drive mosquitoes could reach areas that are only served by limited infrastructure. Current interventions require adequate infrastructure such as warehouses for storage, roads and vehicles for transportation from the storage facility to intended users.

Ease of application: the release and spread of gene drive mosquitoes do not require a change in people's behaviour. The gene drive mosquitoes are released into the environment and they do the work for you. Current interventions may require campaigns through various outlets for social and behavioral change of the end-user.

Targeted: the genetic modification will spread in the target population only from parents to offsprings through sexual reproduction. This ensures that the modification only stays in the targeted population and not otherwise. This has the advantage to reduce undesired effects on non-target populations. Current interventions contain insecticides that target all insects indiscriminately, even beneficial ones.

The cost of inaction

The potential of reducing cases and deaths of malaria, especially in children below the age of 5 should not be passed on. Despite all its advantages and potentially high impact, gene drive mosquitoes still raise concerns about ethics, safety and governance which must be addressed. Recent high-level reports from WHO, AU and the Lancet Commission all advocate for a cautious, stepwise approach in research and development of gene drive mosquitoes.

There has never been a technology that is 100% free of any risks. However, if the potential benefits of the technology significantly outweigh its potential risks, then by all means it should be adopted. Fear is often the problem and not the technology itself.

Decisions on whether to proceed with this technology or not should be solely based on science and not otherwise. Only Science would be able to inform if this technology could be useful in the continued fight against Malaria or otherwise. Such research should be conducted in steps and be supported by clear governance mechanisms to evaluate the health, environmental and ecological implications. In order to ensure this, certain issues have to considered and be put in place prior to the onset of any research:

> Guidelines and frameworks for governance & oversight at the institutional, national and global level have  to be developed.
> Risk assessment tools and procedures for biosafety evaluation should be developed.

> Capacity development in terms of appropriate infrastructure and local skilled personnel for handling and carrying out research on this technology.
> Community engagement that is locally driven. Community members must be fully engaged from the beginning. They must be aware of the technology and be engaged in the planning and implementation phase of the technology.

Where are we now?

The research and development of gene drive mosquitoes have been most vigorously pursued to date in Anopheles mosquitoes responsible for transmitting malaria in Africa, since this is arguably where new solutions are most urgently needed. However, research is also undergoing to develop gene drive mosquitoes for other diseases such as dengue, chikungunya and Zika.

It should be emphasized here that the current state of this research is still in its infancy. Everything is still in the laboratory phase and the scientific community does not foresee the release of any gene drive mosquitoes in the field for the next 5-7 years. Furthermore, there are over 3500 different species of mosquitoes. Of these, about 400 are in the genus Anopheles and about 70 have been confirmed by research to transmit Malaria globally.

In Africa, only 4 out of the 70 (Anopheles gambiae s.s., Anopheles colluzzi, Anopheles arabiensis, Anopheles funestus s.s.) are the major transmitters of malaria. Gene drive mosquitoes being discussed here only target one of these 4, the Anopheles gambiae s.s. which is the most effective malaria vector globally.

Current tools have not been enough to eradicate malaria, and that is what makes innovation crucial. Gene drive could be a cost-effective, sustainable, and long-term solution tool, complementing methods already in place. We will only know how efficient and safe it is if we continue to support research and innovation. We cannot have malaria and other vector-borne diseases taking so many lives. #

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Brian Tarimo is a malaria researcher at Ifakara Health Institute. This article was first published on the Outreach Network for Gene Drive Research website.