By Frank Kamuntu
In the last nine years, Uganda has participated in preliminary activities for prospective field testing of gene-drive mosquitoes, which studies have shown can control malaria mosquito populations.
This year, the country is looking to continue on that path by conducting controlled laboratory test trials of the Friendly mosquito technology developed by the British biotechnology company Oxitec.
In early January, Oxitec was interested in partnering with Uganda’s Health Ministry and the Uganda Virus Research Institute (UVRI) to develop non-biting, self-limiting, and non-persistent male mosquitoes to fight malaria.
It was also reported that Uganda’s President Yoweri Museveni, who has yet to sign the country’s Genetic Engineering Regulatory Bill, supported the partnership.
He expressed his support after the Oxitec team, led by CEO Grey Frandsen, briefed him on the technology at his residence in Rwakitura, Kiruhura District, Western Uganda.
Control the Dengue-carrying Mosquitoes
Professor Pontiano Kaleebu, the Director of the Uganda Virus Research Institute, told the AFS that Oxitec was interested in partnering with the UVRI to produce a Friendly Anopheles funestus mosquito solution for Uganda.
Uganda has the world’s highest malaria incidence rate of 478 cases per 1,000 people per year. The malaria death rate is estimated to be between 70,000 and 100,000 deaths per year, a toll that exceeds that of HIV and AIDS.
“Oxitec has done excellent work in South America to control the dengue-carrying mosquitoes. They wish to collaborate with us to develop an intervention for the Anopheles funestus mosquito, which transmits malaria in primarily arid locations throughout the year. One of the reasons we are interested in collaborating with them is that the Uganda Virus Research Institute, which has a strong entomology department, is focused on developing capacity, particularly in genetic technology, to control vectors for diseases,” Kaleebu said.
Several Ugandan entomologists and molecular geneticists concur that the Anopheles funestus mosquito, which is known to be one of the leading carriers of malaria in sub-Saharan Africa due to its anthropophilic (preferring to feed on humans over other animals) and endophilic (associating with humans and their home environment) characteristics, has emerged as a threat to the success of the country’s insecticide-based malaria vector control programs.
Kaleebu said it mainly rests and bites outdoors and continues to transmit malaria even in the dry seasons. In some parts of the country, like Soroti in eastern Uganda, it is resistant to insecticides.
Delivering Impact Against Mosquitoes
Oxitec is developing a new Friendly Anopheles Stephensi mosquito control solution to combat the growing threat of malaria in the Horn of Africa, where the Anopheles stephensi mosquito, which belongs to the same subgenus as the Anopheles gambiae mosquito, Africa’s primary malaria vector, has contributed to the region’s malaria resurgence since 2012.
While the Anopheles stephensi mosquito is not the predominant malaria vector in Africa, it has been discovered in seven African countries: Ghana, Nigeria, Djibouti, Kenya, Sudan, Ethiopia, and Somalia. Its capacity to breed in urban areas distinguishes it from other malaria-carrying mosquitoes.
It is yet to be detected in Ugandan human settlements, where Anopheles gambiae and funestus are the most common malaria-carrying mosquito species. Still, fears have grown that it could spread to Uganda from Kenya.
Neil Morrison, Oxitec’s Chief Strategy Officer, told the AfS that Oxitec was committed to delivering impact against mosquitoes that spread malaria, killing more than 600,000 people yearly.
“People in Uganda face this threat every year. We’re at a very early stage of developing a collaboration with the Uganda Virus Research Institute, a globally respected public health research institute. We hope to work with them to develop solutions for malaria-transmitting mosquitoes in Uganda,” he said.
Disrupt Mosquito Breeding Cycles
Morrison added that the technology, which has not encountered any resistance anywhere in the world, employs two simple genes to produce safe, non-biting, self-limiting, and non-persistent male mosquitoes.
It is intended to disrupt mosquito breeding cycles and provide a viable alternative to insecticides in mosquito population control.
“The Friendly Aedes, which provides a targeted, safe, and non-toxic method for controlling insect pests that spread diseases such as dengue, Zika, chikungunya, and yellow fever, has proven highly effective and is now fully commercial in Brazil and delivering impact nationwide, Morrison said.
“In the US, we have completed three years of pilots in the Florida Keys (with approvals from the Environment Protection Agency), and we’re expanding our work now to Central America, the Horn of Africa, and the Pacific.”
While the Oxitec/Uganda relationship is still in its early phases, Djibouti, where malaria mortality doubled to 15,900 between 2014 and 2022 and malaria case incidence surged by 55 percent in 2022, according to the WHO’s 2023 World Malaria Report, is advancing fast.
On 14 January 2024, the country announced the importation of Oxitec’s self-limiting and Friendly Anopheles stephensi mosquitoes into dedicated, contained laboratories in Djibouti City, where the invasive Anopheles stephensi mosquitoes have fueled an unprecedented rise in urban malaria cases over the last decade.
The first field trials of the self-limiting and Friendly Anopheles Stephensi mosquitoes, developed over three years and reportedly being imported following regulatory approval, are expected to begin this year.
Oxitec has conducted extensive field surveillance and mosquito biology studies in Djibouti since 2021.
Mosquito Population Is Reduced
According to Morrison, “Friendly” was first applied to the mosquitoes by dengue-affected South American communities, who felt the male mosquitoes were good insects combating ‘bad’ disease-transmitting mosquitoes.
“Friendly mosquitoes carry two introduced genes. The first is a self-limiting gene, which prevents female offspring from surviving to adulthood. This means that we can produce male-only cohorts of Friendly mosquitoes. These males—unlike females, which do not bite—are released into a community where they seek and mate with pest females. As their offspring inherit the self-limiting gene, the female offspring cannot survive. So, with the sustained presence of Friendly males in a community, the target mosquito population is reduced,” said Morrison.
Samatar Kayad Guelleh, head of the Djibouti Malaria National Programme, emphasized that the Friendly Anopheles stephensi mosquitoes would address the country’s malaria problem at its source, attack the vector, and help fight insecticide resistance.
Recent World Health Organisation tests performed on Anopheles Stephensi mosquito populations in Djibouti showed resistance to pyrethroids, organophosphates, carbamates, and DDT.
As with other malaria-endemic African nations, Djibouti is implementing conventional interventions, such as malaria diagnosis, treatment, prevention through mosquito net distribution, and managing larval breeding sites.
Collaborate With African Entomologists
The country aims to return to low or pre-elimination malaria levels before 2030. However, the vector and parasite’s resistance to current vector control methods and antimalarials is hampering progress.
Dr Bouh Abdi Khaireh, the Director of the Djibouti Public Health NGO, Association Mutualis, said the importation of Friendly Anopheles stephensi mosquitoes into dedicated entomology facilities in Djibouti City marked a significant milestone.
“It marks a major milestone in the Government of Djibouti’s efforts to protect its citizens and to serve as a regional and international beacon for leadership in solving climate change-related public health threats with new technologies.”
“We are excited to pioneer this innovative vector control method for this invasive vector species in partnership with Oxitec and Mutualis. We hope that Djibouti’s experience will have a similar impact in other African countries,” said Khaireh.
Morrison responded in the affirmative when asked if the technology provided a sustainable and environmentally friendly strategy for fighting malaria in Djibouti.
He pointed out that the technology, which has been the subject of more than 100 peer-reviewed scientific publications, depended on mating and was highly specific to the target pest species, leaving non-target species like butterflies and bees unharmed.
“The introduced genes produce non-toxic proteins, so predators that feed on Friendly mosquitoes suffer no harm. After releases stop, the self-limiting gene cannot persist in the environment for longer than a few generations. It leaves no footprint. More than 1 billion Friendly mosquitoes have been deployed, with no reports of negative impacts on people and the environment.”
According to Oxitec CEO Grey Frandsen, the Friendly technology platform was ideally equipped to produce a safe, sustainable solution to manage the Anopheles stephensi mosquito vector based on years of experience creating and deploying other Oxitec solutions at scale.
In response to criticism that African scientists are rarely included and consulted in the development stages of new technologies, such as the Friendly mosquito technology, Morrison stated that they strive to collaborate with African entomologists.
“We have partnered with Djiboutian experts and scientists since the program’s launch in 2021. We also hold regular workshops where the region’s most respected malaria and mosquito experts convene to review and guide the program’s progress.”