Children sleep under a long-lasting insecticide-treated nets to prevent malaria.Credit: AusAID / Alamy Stock Photo
Bed nets infused with the insecticide, chlorfenapyr, have consistently been shown to give better protection from malaria-carrying mosquitoes than any other type of net. The use of chlorfenapyr was introduced after 60 countries reported widespread resistance against the pyrethroid insecticides initially used.
The latest World Health Organization Guidelines for Malaria 2023, suggests using chlorfenapyr in combination with a pyrethroid ”to enhance the effect” of insecticide-treated nets (ITNs) and to combat the development of resistance.
A new paper in Scientific Reports says the genetic make-up of some mosquito populations in Africa already show signs of being less susceptible to the impact of chlorfenapyr.
Lead author and medical entomologist, Magellan Tchouakui of the Centre for Research in Infectious Diseases (CRID) Cameroon, says there is practical value in studying the genetic make-up of mosquitoes when monitoring resistance and potential cross-resistance with current insecticides.
Addressing the situation
According to the 2022 Malaria Report, around 90% of the 600 000 malaria-related deaths reported annually occur in Africa, with most fatalities among children.
Cameroon, Uganda, Malawi, Ghana and the Democratic Republic of the Congo (DRC) are among the ten nations most burdened by malaria. As part of the Scientific Reports paper, in 2021, participating scientists from these countries collected Anopheles gambiae and Anopheles funestus mosquitoes — the two major malaria vectors in Africa — in ponds and houses in rural farming areas.
All the Anopheles funestus mosquitoes tested were susceptible to chlorfenapyr.
However, not all samples of Anopheles gambiae obtained from Cameroon, the DRC and Ghana died when exposed to chlorfenapyr in the lab, raising concerns that the insecticide might not be as effective against wild Anopheles gambiae populations in these countries.
“Our results count among the first reports from Africa that some populations of mosquitoes that typically carry the malaria-causing Plasmodium parasite could be developing a tolerance to chlorfenapyr,” explains study co-leader, Charles Wondji, a geneticist associated with CRID and the Liverpool School of Tropical Medicine and a member of the Africa PGI Malaria Working Group.
“Our results do show that it is important to start putting suitable resistance management plans in place to anticipate that chlorfenapyr might not always work everywhere.”
The research team suggests the use of agricultural pesticides could be linked to the development of resistance among some mosquito populations, particularly as the reduced susceptibility was observed in agricultural hotspots.
The Scientific Reports paper contained some good news about the use of chlorfenapyr in communities where mosquito populations are resistant to pyrethroid-derived insecticides.
“We found that mosquitoes, highly resistant to current pyrethroid insecticides through the knockdown resistance (kdr) mechanism, were more likely killed by chlorfenapyr than those harbouring the susceptible allele. This would explain why chlorfenapyr-based nets have been shown to be highly efficient against pyrethroid resistance populations,” says Wondji.
Genomic sequencing is allows for the detection of Plasmodium falciparum's resistance to certain drugs.Credit: piola666/ iStock/ Getty Images Plus
“We need to scale up the genomic surveillance of vectors and Plasmodium parasites to successfully control malaria.”
Wondji believes it is possible to improve continent-wide efforts by creating supportive regional hubs around laboratories with proven expertise, such as is being done at CRID with support from funders such as the Bill and Melinda Gates Foundation and Wellcome Trust.
Developing new approaches
At the end of March, four working groups from across Africa gathered to discuss roadmaps they were drafting on behalf of the Africa CDC Pathogen Genomics Initiative (Africa PGI). The roadmaps proposes steps for genomic surveillance to aid the continent's public health sector further, in tackling malaria, food-borne diseases, vaccine-preventable diseases and antimicrobial resistant (AMR) strains. It will provide a framework for the Africa CDC, individual countries, regions, partners and key stakeholders to incorporate the genomics of multi-pathogen priority diseases and other cases into existing policy and routine disease surveillance systems.
The step follows the successes seen during the COVID-19 pandemic using genomic tools to search for new variants and disease patterns, and so control and manage its spread.
The move from one disease to another is not necessarily seamless. Malaria is a case in point.
“Yes, you can use the same gene sequencers. However, there are different levels of complexity and understanding between the malaria vector and the disease-causing Plasmodium parasite, and SARS-CoV-2. The malaria vector's genome is 10,000 times bigger than that of SARS-CoV-2. And the parasite's genome is around a thousand times bigger,” explains Alfred Amambua-Ngwa, a member of the Africa PGI Malaria Working Group and a researcher from the Medical Research Council Unit in The Gambia, and the London School of Tropical Medicine in Banjul in The Gambia.
Amambua-Ngwa recently co-authored a paper in Human Molecular Genetics that shows people in Cameroon have evolved specific genetic markers that seem to protect them from infections, or from becoming severely ill.
According to Amambua-Ngwa, the use of genomics has already allowed for the detection of the parasite's resistance to certain drugs in Rwanda and Uganda, and such testing would be helpful in high-burden countries such as Nigeria, Cameroon, Sierra Leone and Mozambique.
Earlier this year, the Wellcome Trust released the seventh update of the MalariaGEN Pf7 data resource, a collection of more than 20 000 different genome sequences of Plasmodium falciparum. These have been gathered through the international MalariaGEN network from 82 partner studies in 33 countries.
However, most sequences available were produced by researchers in the UK, US and Asia, and are housed in repositories in the UK and US. Wondji says that it would be valuable to develop similar skills in Africa and to implement robust genomic surveillance in close collaboration with national control programmes.
