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Mosquitoes on birth control

- Beth Amato

Eradicating malaria in SA is a national policy goal, but is easier said than done. But sterile insect technique could take the bite out of mosquitoes.

In a north eastern corner of KwaZulu-Natal, the community of Jozini is at the centre of a groundbreaking trial to eradicate malaria. The innovation, known as the sterile insect technique (SIT), is essentially male mosquito birth control.

These exclusively lab-reared male mosquitoes are sterilised before being released in infested areas. Male mosquitoes (referred to as “non-biters”) do not carry malaria and so when they mate with native female mosquitoes in malaria-infested areas, only “non-diseased” offspring are produced. This drastically reduces the resident mosquito population size.

When a human contracts malaria, the body takes a hard knock. Usually, about 10-15 days after being bitten by an infected mosquito, a person will experience symptoms such as fever, nausea, vomiting and severe headaches which can result in seizures, susceptibility to bacterial infection, cognitive impairment and even death. If not treated, people can experience recurrences of the disease or act as carriers of the deadly malaria parasite.

A recent study notes that despite exposure to malaria assisting in the build-up of immunity against the disease, not seeking treatment is dangerous. “The resultant chronic yet silent infection not only helps perpetuate malaria transmission but, over time, also contributes to serious?health and developmental impairments,” the study reports.

Mosquitoes and malaria | Curiosity 16: #Drugs ? /curiosity/

Introducing the SIT

The SIT is a biological vector control technique based on the release of many laboratory-reared sterile insects in significantly higher numbers compared to the natural population. The technology has been applied successfully in agriculture, such as in the control of the screwworm.

SIT for mosquitoes was conceived in 2010 to supplement existing malaria prevention techniques which include oral prophylaxis and indoor residual spraying (IRS). The former is only helpful once the diseased mosquito has bitten (and some of the pills have concerning side effects, including psychological). Malaria parasites may develop resistance to these drugs. Meanwhile, other mosquitoes have built resistance to the IRS insecticides.

While IRA targets indoor feeding and resting mosquitoes, in South Africa, it has been less efficient in controlling Anopheles arabiensis, a mosquito species that sometimes feeds and rests outside, contributing to outdoor transmission. This is the most significant challenge in malaria-affected provinces.

Dr Givemore Munhenga, Principal Medical Scientist at the National Institute for Communicable Diseases (NICD) and a Senior Researcher at the Wits Research Institute for Malaria (WRIM), says that the SIT might be a game changer in addressing these challenges. SIT is highly effective in suppressing and eventually eliminating mosquito populations regardless of their biting and resting behaviour, or insecticide resistance status.

The technique requires community buy-in in order for people to understand the process and its implications. In some cases, locals believed that the treated male mosquitoes represented a threat to their health, but as Muhenga explains, “As only female mosquitoes bite their host, the release of non-biting sterilised males will have no negative effects on people in the area.”

In order to dispel concerns about this potentially controversial public health intervention, intensive community dialogue and public engagement processes were undertaken in Jozini before the technology was piloted.

Finally, in 2022, sterile male mosquitoes were released into the field site, the first time in such a large area targeting an African malaria vector. Already, there are positive signs of a mosquito population reduction.

“The ultimate goal of the SIT project is to establish mass-rearing capabilities so that a good number of sterile male mosquitoes can support the efforts to eliminate malaria,” explains Munhenga. The next phase of the SIT project, funding permitting, is to test its suitability and affordability as a public health initiative.

A changing climate portends treatment and prevention complications

As mosquitoes thrive in warmer environments, hotter temperatures generate more breeding grounds. Floods and droughts work in the mosquitoes’ favour as they breed in temporary pools when it rains and in permanent bodies of water in dryer periods.

Malaria elimination: a social justice issue

Professor Lizette Koekemoer, the Co-Director at Wits Research Institute for Malaria, explains that 90% of the global annual malaria mortality cases emanate from Africa. Children under the age of five account for at least half a million deaths.

“There are major repercussions when someone is infected with malaria. If a breadwinner, for example, becomes ill, then the family suffers. Often this is in a context where there is already widespread poverty. Yes, there have been gains on the treatment front, but it is expensive and follow up treatments are often not completed,” says Koekemoer.

She notes that malaria reduction and elimination research takes between five and 10 years. “We see that once we have identified drugs and screened the compounds, the parasites develop resistance very quickly.” This challenging task has been made easier by the combined expertise of multiple units from the University of Cape Town, the University of Pretoria, the NICD and Wits.

Koekemoer says that elimination is an ambitious goal. This is because transmission is complex, involving 40 parasitic mosquito species behaving very differently.

Global Health Priority Boxes to determine which vector-control drugs would work

COVID-19 highlighted the critical importance of pandemic preparedness and a robust response to current and emerging public health threats. As crises breed innovation, new tools can rapidly be developed, particularly when barriers to collaboration are removed.

One such tool, the Medicines for Malaria Venture Global Health Priority Box, has a collection of compounds acting against pathogens and vectors. Scientists can access this at no cost and build on each other’s work. The box provides scientists with confirmed starting points to further advance the development of treatments and insecticides to tackle drug resistance and communicable diseases.

The WRIM’s Dr Ashley Burke, Ayesha Aswat, Nelius Venter and Erica Erlank are screening the Global Health Priority Box as part of a collaboration with the University of Pretoria.

The components of the box include 80 compounds with confirmed activity against drug-resistant malaria, 80 compounds donated by the Bristol-Myers Squibb compound library for screening against neglected and zoonotic diseases, and 80 compounds tested for activity against various vector species from the Innovative Vector Control Consortium. The plate can be used to screen and develop compounds for vector control and transmission blocking medicines.

The World Health Organization has certified 38 countries malaria-free.

In southern Africa, South Africa and eight other countries have made malaria elimination a policy goal.

While scientists have many hurdles to jump over, the WRIM is committed to developing new and innovative methods which can be implemented in the field.

Malaria – a history

The World Health Organization describes malaria as an ancient disease. Indeed, there are inscriptions on bones, tortoise shells and bronzeware in China, dating back more than 3500 years.

“The circular nature of transmission of the parasite, from human to mosquito and back to human, the ability of the parasites to form resistance to treatments and of the mosquitoes to form resistance to insecticides, and the complex lifecycle of the parasites makes malaria a tough disease to eliminate.”

South Africa has a long history (about 120 years) of malaria control activities. This has led to a drastic reduction in malaria cases. Nevertheless, the country is still prone to epidemics: the 1999/2000 outbreak resulted in about 65?000 cases in malaria season. Before this, the cases were totalling around 11?000.

More on this research

Known as the Sterile Insect Technique for Malaria Mosquitoes in a South African Setting, the initiative is a multiple and global stakeholder initiative coordinated and operated under the auspices of the Nuclear Technologies in Medicine and the Biosciences Initiative.??

  • Beth Amato is a freelance writer.
  • This article first appeared in?Curiosity,?a research magazine produced by?Wits Communications?and the?Research Office
  • Read more in the 16th issue, themed: #Drugs, where we highlight the diversity, scope, and multi-dimensional nature of drug-related research at Wits University.
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