Global plan for insecticide resistance management in malaria vectors

Insecticide resistance refers to changes in an insect that increase its ability to withstand or overcome the effects of one or more insecticides. When the frequency of resistant insects in a population increases (e.g. through resistance traits being passed on from one generation to another), the efficacy of an insecticidal intervention can be compromised. Increased frequency of resistant insects may be detected through assays that measure insect mortality in response to a particular insecticide, or through genetic tests that detect resistance mechanisms in individual insects.

In malaria control, the insecticides currently recommended for use against the potential parasite-carrying adult Anopheles mosquitoes belong to five classes: carbamates, organochlorines, organophosphates, pyrethroids and neonicotinoids. These insecticides are commonly deployed through the core malaria interventions of insecticide-treated nets (ITNs) and indoor residual spraying (IRS).

The potential result of mosquito resistance to insecticides is that the insects are not killed when they come into contact with a standard dose of an insecticide deployed through ITNs or IRS. However, this does not mean that these interventions will be ineffective immediately, or that there will be a surge in malaria cases. For example, when mosquitoes are resistant to pyrethroids, ITNs still provide protection for the people using them.

Insecticide resistance is not a new phenomenon; it has been an undesired side-effect of malaria vector control since insecticides first came into broad use in the 1940s. Malaria-endemic countries should be aware of the importance of detecting and preventing the development and spread of insecticide resistance. Increasingly, countries are including insecticide-resistance monitoring and management practices in their national malaria control strategies.

However, in most endemic countries – particularly in sub-Saharan Africa – control strategies focus on scaling up vector-control interventions. Only limited resources are made available to build capacity for entomological monitoring and insecticide susceptibility testing, and to design and implement strategies to manage insecticide resistance.

The main factor driving the emergence and spread of resistance during the past decade has been the heavy reliance on a single class of insecticides – pyrethroids – for both public health and agriculture purposes. Pyrethroids are highly effective and safe. They are the least expensive of the 5 classes of insecticides used in malaria vector control, and are the only class available for use on ITNs. In some areas, the use of pyrethroids and similar insecticides in agriculture appears to have contributed to the development of resistance in mosquitoes.

Currently, ITNs appear to remain effective in countries with malaria transmission although there is evidence emerging from some areas that resistance can reduce the impact of pyrethroid IRS. To sustain the remarkable gains in malaria control and move towards malaria elimination, urgent action is required to prevent the further development of resistance and maintain the effectiveness of vector-control interventions.

Since 2010, a total of 68 countries have reported resistance to at least one class of insecticide, with 57 of those countries reporting resistance to two or more classes. Widespread resistance to pyrethroids has been reported for malaria vectors from numerous countries in sub-Saharan Africa as well as central and south-east Asia.

Recent data are considered the most relevant because insecticide resistance can vary over time in response to a range of factors, and can also differ greatly over short distances. However, not all countries with ongoing malaria transmission undertake routine resistance monitoring, and when monitoring is done, it often fails to include all insecticide classes, main malaria vectors or eco-epidemiological zones. In addition, there are critical issues with the national management and timely sharing of resistance data. Our understanding of the scale of insecticide resistance is therefore incomplete. As routine monitoring is scaled up, a more detailed picture will emerge about the state of insecticide resistance.

A global database on insecticide resistance was established in 2014 to provide timely tracking of changing insecticide-resistance patterns and to identify where data are lacking. The data have also been made available through the online Malaria Threats Map. Such databases can assist endemic countries and their partners to take targeted action. WHO provides updates on the number of countries monitoring and detecting insecticide resistance in the annual World malaria report.

• Guidelines for malaria vector control
• Global report on insecticide resistance in malaria vectors: 2010–2016

he WHO Global plan for insecticide resistance management in malaria vectors (GPIRM) was released in May 2012 as a call to action to tackle the threat of insecticide resistance. It was developed in response to a request in 2011 by the World Health Assembly and the Board of the Roll Back Malaria Partnership which reflected the collective belief that a global strategy was needed to serve as the foundation of a coordinated multi-stakeholder response.

The GPIRM was developed through a broad-based consultation with over 130 stakeholders. These stakeholders represented all constituencies of the malaria community, including malaria-endemic countries, multilateral agencies, development partners, academia and industry. The plan included the latest available evidence on the extent of insecticide resistance around the world, and put forward a strategy for global and country levels, identifying clear roles and timelines for all stakeholders.

Through the GPIRM, WHO and the Roll Back Malaria Partnership urge governments of malaria-endemic countries and their partners to implement a five-pillar strategy to tackle the growing threat of insecticide resistance, including to facilitate the development of innovative tools and strategies for vector control.

• Global plan for insecticide resistance management in malaria vectors

The GPIRM is based on 5 pillars that address actions spanning the short, medium and long term. It requires coordinated action from all stakeholders, including national malaria control programmes and national regulatory authorities, WHO, donors and other multilateral organizations, research institutions and partners in the public health insecticide industry. The strategy calls on stakeholders to:

• plan and implement insecticide-resistance management (IRM) strategies in malaria-endemic countries;
• ensure capacity for proper, timely entomological monitoring and effective data management;
• develop new, innovative vector-control tools;
• fill knowledge gaps on the mechanisms of insecticide resistance and the impact of current approaches to IRM; and
• ensure that key enabling mechanisms – including advocacy, and human and financial resources – are in place.

Malaria-endemic countries are encouraged to modify their vector-control programmes to address insecticide resistance. The starting point is to analyse the state of insecticide resistance and to design a comprehensive IRM strategy. To support this, WHO produced a Framework for national plan for monitoring and management of insecticide resistance in malaria vectors. Countries should strive to have pre-emptive IRM strategies in place and integrate related costs into national budgets for malaria control.

• Framework for a national plan for monitoring and management of insecticide resistance in malaria vectors

In parallel, all endemic countries should build capacity to collect, handle and interpret data on resistance, and leverage that information for making decisions about vector control. Through IRM, endemic countries can delay the evolution of resistance, preserve the effectiveness of existing insecticides, and even reverse resistance in some settings. Successful implementation of the GPIRM will require coordinated action between all partners in the malaria control community as well as other sectors, such as agriculture and finance.

All types of ITNs currently recommended by WHO are treated with pyrethroids. During the past decade, vector control has relied heavily on pyrethroids, and countries have now reported widespread resistance to insecticides of this class. Nevertheless, there are few proven cases in which insecticide resistance has been linked to decreased effectiveness of ITNs or increases in malaria cases.

In 2016, WHO reported on the findings of a large, multi-country evaluation to assess the impact of insecticide resistance on malaria vector control interventions – primarily long-lasting insecticidal nets (LLINs). The 5-year evaluation found that people who slept under LLINs in the evaluation areas had significantly lower rates of malaria infection than those who did not use a net, even though mosquitoes showed resistance to pyrethroids in all of these areas.

This study reaffirms the WHO recommendation of universal LLIN coverage for all populations at risk of malaria. Even in areas where resistance has been identified, countries should continue to scale up or maintain universal coverage with LLINs as:

• LLINs act as a physical barrier against parasite-carrying mosquitoes; and
• even a sublethal effect of the insecticide on mosquitoes is likely to contribute to malaria control.

IRS using non-pyrethroid insecticides may also be implemented in areas with LLINs, for resistance management purposes. Larval source management may provide an opportunity for IRM, because there is greater diversity in larvicides including biological formulations, and habitat modification or manipulation can reduce overall dependence on insecticides.

However, interventions targeting the larval and pupal stages of mosquitoes are appropriate only in certain settings, where mosquito aquatic habitats are few, fixed and findable. With continued reliance on LLINs and IRS, the operational impact of their use must be monitored closely, and resistance should be tested at sentinel sites at least once a year and more often if feasible.

According to the World malaria report 2018, 40 countries have completed their insecticide resistance monitoring and management plans, in line with the GPIRM. WHO continues to work with governments of endemic countries, donor organizations, United Nations agencies, and research and industry partners to implement the 5-pillar strategy contained in the GPIRM; this includes ongoing support for the development of new and innovative vector-control tools and strategies.

Urgent efforts are required to ensure the correct use of existing interventions and the availability of new tools to maintain the effectiveness of malaria vector control.

• Guidelines for malaria vector control
• Global plan for insecticide resistance management in malaria vectors
• Indoor residual spraying: An operational manual for IRS for malaria transmission, control and elimination. Second edition
• Test procedures for insecticide resistance monitoring in malaria vector mosquitoes (Second edition)
• The use of DDT in malaria vector control. WHO position statement

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