New study examines pyriproxyfen resistance in dual treated bednets

News article 21 Sep 2016
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Photograph © M. Hallahan/Sumitomo Chemical

Researchers from LSTM have examined the mechanisms of resistance to the insect growth regulator pyriproxyfen (PPF) in a paper published in Insect Biochemistry and Molecular Biology, and assessed the likelihood of cross resistance occurring between this chemical and other insecticide classes used in malaria control.

The dramatic reductions in malaria cases in Africa over the last 15 years are largely attributed to targeting the adult mosquito through vector control mechanisms, primarily long lasting insecticidal nets (LLINs) treated with the pyrethroid class of insecticide. Due to the growing problem of resistance to pyrethroids in the major malaria vectors in Africa there is an urgent need both for new insecticides to maintain the efficacy of these proven tools, and for new tools to reduce malaria transmission by the mosquito.

Pyriproxyfen (PPF) is an insect growth regulator that inhibits metamorphosis, sterilises the female mosquito and reduces longevity in adults. It has been used for several decades to protect against other insects and has extremely low toxicity to humans. Sumitomo Chemicals Ltd has developed a LLIN incorporating both permethrin and PPF. This Olyset Duo®, net has been shown to be effective in laboratory and experimental huts and is currently being evaluated in a randomised control trial in Burkina Faso to determine whether this combination net is more effective at reducing malaria transmission than conventional pyrethroid only LLINs in an area with very high levels of insecticide  resistance.

However, concerns have been raised about the performance of Olyset Duo against pyrethroid resistant populations, and an experimental hut study of Olyset Duo carried out in an area where the Anopheles gambiae population has high levels of both target site and metabolic resistance to pyrethroids found no significant difference in the number of sterile mosquitoes in huts with Olyset Duo compared to control huts.

Resistance to PPF has been reported in other insects and while the mechanisms of resistance have not been fully described, cytochrome P450 enzymes, which metabolise insecticides appear to be involved.  Certain P450s are produced at high levels in pyrethroid resistant mosquitoes, leading to a faster detoxification of insecticides. These enzymes could cause cross-resistance to other insecticides. In this study researchers have expressed these P450s in bacteria andfound they can also metabolize PPF. They also assessed the likelihood of cross resistance between PPF and other insecticide classes by comparing the efficacy of PPF in inhibiting metamorphosis and inducing female sterility in an insecticide susceptible strain of An. gambiae and a multiple resistant strain from Cote d’Ivoire. 

LSTM’s Dr Mark Paine was lead author on the study. He said: “Given that pyrethroid resistant populations of malaria vectors are now ubiquitous in Africa, it is important to evaluate the possible impact of this resistance on the performance of any new vector control tools. Our study finds that the same enzymes responsible for elevated pyrethroid metabolism in insecticide resistant mosquitoes can also metabolize PPF, potentially indicating that PPF resistance may already be present in field populations of Anopheles mosquitoes. We recommend continual monitoring for resistance be undertaken in any area employing PPF as a larvicide or considering PPF use for adult mosquito control.”

You can read the paper here.