One of the central pillars of malaria control efforts in Africa is the use of bed nets that contain an insecticide; pyrethroids have become the backbone of mosquito net programs worldwide. However, the heavy reliance on the compound has led to the growing issue of pyrethroid resistance.
Now, a team has identified that the E205D amino acid change in the metabolic resistance cytochrome P450 CYP6P3 that drives pyrethroid resistance in the Anopheles gambiae mosquito—one of the main vectors of malaria in Africa. The team also developed a DNA test that could track the spread of this mutation across West and Central Africa.
This new research is the first to identify a DNA marker for metabolic pyrethroid resistance in West and Central African populations of Anopheles gambiae.
This new finding is published in Science Translational Medicine in the paper, “The E205D mutation in CYP6P3 drives metabolic pyrethroid resistance in the African malaria mosquito vector Anopheles gambiae.”
“Our study designed field-applicable tools to easily track the spread of metabolic resistance in the major malaria mosquito species and assess its impact on control interventions,” notes Charles Wondji, PhD, professor of genetics and vector biology at Liverpool School of Tropical Medicine. “These important findings can help to maintain the effectiveness of insecticide-based tools such as bed nets which remain a cornerstone of malaria prevention.”
Building on previous research, the team interbred insecticide-resistant and susceptible colonies of A. gambiae mosquitoes and performed genetic analysis. Using whole-genome DNA sequencing, they isolated a single point mutation (E205D) in the gene CYP6P3 that drives pyrethroid resistance. Further work showed that this mutation boosted the ability of some enzymes to detoxify permethrin, a pyrethroid insecticide, by more than three-fold.
A malaria transmitting mosquito resting on insecticide-treated net because of its ability to breakdown insecticides. [C. Wondji]
Based on this marker, the researchers developed a DNA-based diagnostic to track the spread of E205D in the field and enable the detection and monitoring of pyrethroid resistance. This test revealed that the mutation was present in mosquitoes in Sierra Leone, Ghana, Cameroon, and Uganda, but seemed to be spreading more slowly in East and South Africa.
The authors write that their assay, “will enable the detection and monitoring of P450-based pyrethroid resistance, the assessment of potential cross-resistance to new insecticides, and, ultimately, the implementation of effective malaria vector control strategies.”
This work may help to better implement insecticide resistance management strategies and contribute to reducing the burden of malaria in sub-Saharan Africa, home to 90% of cases globally. Bed nets and indoor residual spraying have been critical to controlling the spread of malaria, but progress has slowed over the last decade because of increased insecticide resistance, notably through metabolic resistance processes in mosquitoes through the production of detoxification enzymes.
This growing global threat must be addressed to improve the effectiveness of current and future vector control strategies and further reduce the malaria burden, with 200 million cases and 600,000 deaths annually worldwide.