The first reported case of insecticide resistance was in 1914, when A. L. Melander described observing scale insects still alive under a “crust of dried spray” of sulphur-lime.

As of February 2022, 14,388 cases of field-evolved insecticide resistance have been recorded in the Michigan State University Arthropod Pesticide Resistance Database. This includes insect and mite pests of agricultural as well as public health importance.

In the 1950s and 60s, dieldrin and DDT were being used to combat malaria mosquitoes. However, resistance to dieldrin rapidly developed in the Anopheles malaria mosquitoes, as it did to a lesser extent to DDT.

As a 1969 report from the WHO states: “Again, dieldrin-resistance usually leads to this insecticide being abandoned while a simultaneous DDT-resistance (which is less intense) renders the final stages [of the malaria eradication programme] excessively difficult.” The report goes on to state, “The widespread dieldrin-resistance in West Africa renders HCH [an insecticide from the same mode of action class as dieldrin] useless there.”

Fourteen years earlier in 1955, the WHO had introduced the Global Malaria Eradication Program (GMEP). The GMEP had great success, permanently eradicating malaria from many regions. However, the initiative was discontinued in 1969 when it was realised that global elimination was not possible with the tools available at the time. In some areas, the great gains made in malaria control were rapidly lost, with a huge human cost. Whilst there were a number of reasons that the goal of elimination was not achievable then, the development of resistance to the insecticides available at the time was a key factor.

A definition

There are several definitions of Insecticide Resistance. The one given by the Insecticide Resistance Action Committee (IRAC) is: “a heritable change in the sensitivity of a pest population that is reflected in the repeated failure of a [insecticidal] product to achieve the expected level of control when used according to the label recommendation for that pest species”.

The situation in the 1960s clearly fits the IRAC definition of resistance; there was repeated failure of the insecticides to achieve the expected level of mosquito control. This in turn was reflected in an inability to reduce malaria transmission.

However, it is not always easy to directly correlate insecticide resistance development in a mosquito population with epidemiological outcomes. Mosquito populations can be relatively easily evaluated for their susceptibility to a given insecticide. However, the impact of resistance on epidemiological outcomes can be complex. More than one mosquito species may be involved in transmission. Improvements to healthcare systems and access to drug therapies and diagnostics will also influence the epidemiology of malaria. In the case of insecticide-treated nets, even if the mosquitoes are resistant to the insecticide, the net may still offer a physical barrier.

An example of this complex situation can be found in the case of the South African malaria epidemic of the late 1990s. Resistance to the pyrethroid insecticides developed in one of the main vector species, Anopheles funestus, in northern KwaZulu-Natal and Mpumalanga provinces. As the main intervention was pyrethroid-based indoor residual spraying (IRS), resistance development led to a failure in mosquito control.

Changing to a programme with insecticides to which the mosquitoes were susceptible led to a restoration of mosquito control, with a concurrent fall in malaria cases. However, this coincided with a change in the drug therapies used, this time as a result of reported drug resistance in the malaria parasite. It is therefore difficult to assign the impact that management of insecticide resistance alone had on the epidemiology.

The modern context

Very high levels of pyrethroid insecticide resistance can be found in many species and populations of Anopheles mosquitoes in malaria-endemic regions today. As the vast majority of long-lasting insecticide-treated bed nets (LLINs) currently in use contain pyrethroid insecticides, this is a very worrying situation. However, a large study coordinated by the WHO across a number of malaria-endemic countries found no convincing evidence of an association between insecticide resistance and malaria infection or incidence. In all cases, users of LLINs were better protected from malaria than non-users, although they were still exposed to a high malaria infection risk.

It is encouraging that the pyrethroid resistance hasn’t led to a major failure of vector control. However, this is no reason to be complacent. It has been seen that in regions where non-pyrethroid insecticides, to which the mosquitoes are not resistant, are used (in addition to LLINs or in their place), malaria cases have further fallen.

This suggests that epidemiological outcomes would be improved with the use of insecticides to which the mosquitoes are susceptible. If we wait for unambiguous evidence of an association between insecticide resistance to the current insecticides and malaria incidence before acting, we may already be too late.

Author: Mark Hoppé

References

Insecticide Resistance Action Committee (IRAC)

Michigan State University Arthropod Pesticide Resistance Database

WHO Report 1969. Busvine, J R, Pal, R. Bull. World Health Organization. 1969. 40:731-744. Cited in: Pal, R. The Present Status of Insecticide Resistance in Anopheline Mosquitos. 1973. WHO MAL 73.815, 8.