Malaria

Q&A on the Global plan for insecticide resistance management in malaria vectors

November 2015

1. What is insecticide resistance?

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 four classes: carbamates, organochlorines, organophosphates and pyrethroids. These insecticides are commonly deployed through the core malaria interventions of long-lasting insecticidal nets (LLINs) 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 LLINs 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, LLINs may still be effective by providing physical protection for the people using them.

2. When was insecticide resistance first identified?

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 have been aware of the importance of detecting and preventing the development and spread of insecticide resistance, and 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. Also, they are the least expensive of the four classes of insecticides used in malaria control, and are the only class available for use on LLINs. In some areas, the use of pyrethroids and similar insecticides in agriculture appears to have contributed to the development of resistance in mosquitoes.

Currently, LLINs appear to remain effective in all 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.

3. How many countries currently have evidence of insecticide resistance?

Since 2010, a total of 60 countries have reported resistance to at least one class of insecticide, with a total of 49 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 and India.

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 database will assist endemic countries and their partners to take targeted action. WHO will issue regular updates about the number of countries monitoring and detecting insecticide resistance.

4. What is the GPIRM and how has it been developed?

The 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.

WHO and the Roll Back Malaria Partnership through the GPIRM 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.

5. What are the solutions put forward by the GPIRM?

The GPIRM is based on five 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.

The most urgent task for malaria-endemic countries is 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, in 2014, WHO produced a draft Framework for development of national insecticide resistance monitoring and management plans, which is currently being field tested. Countries should strive to have pre-emptive IRM strategies in place, and integrate related costs into national budgets for malaria control.

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.

6. What are the implications of insecticide resistance for LLIN and IRS effectiveness?

All types of LLINs currently recommended by the WHO Pesticide Evaluation Scheme (WHOPES) 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 LLINs or increases in malaria cases.

Even in areas where resistance has been identified, countries should continue to scale up or maintain universal coverage with LLINs, because:

  • 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, as part of an IRM strategy. 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.

7. What kind of innovative new products are being developed?

A number of private sector companies and research institutions are actively working to discover and develop new vector-control formulations, tools and technologies. The current pipeline for reformulations of existing insecticides and new active ingredients is promising. However, more investment will be required to speed up the research and development process.

One important partner is the Innovative Vector Control Consortium (IVCC). The IVCC is a product-development partnership whose pipeline includes non-pyrethroid LLINs and LLINs treated with two classes of insecticides, which may become available within 2–5 years. The IVCC has already supported the development of a reformulated non-pyrethroid compound with a residual efficacy of up to 6 months. The longer term research pipeline includes longer lasting IRS compounds and three new active ingredients, one of which could be appropriate for use on LLINs. These products are about 5–8 years away from reaching the market.

Various other novel approaches are being developed, including spatial repellents, attract-and-kill trapping systems, new larvicides, and microbial and genetic manipulation of mosquitoes. Also, a range of non-insecticidal vector-control solutions are being evaluated for potential public health use.

In 2013, WHO established a Vector Control Advisory Group (VCAG) on new tools. VCAG serves as an advisory body on new forms of vector control for malaria and other vector-borne diseases, to provide a clearer pathway for novel forms of vector control. The first four meetings of VCAG reviewed 22 dossiers from innovators of potential tools and technologies of public health importance.

The group is currently developing guidelines on evaluating products based on new paradigms, including LLINs with a claim of improved efficacy against pyrethroid-resistant malaria vectors. Operational conditions governing the deployment of such products also require definition.

8. What are the financial implications of implementing the GPIRM?

WHO and the Roll Back Malaria Partnership urge funding agencies and bilateral donors to commit funding to support the implementation of the GPIRM. The overall cost of implementing the five pillars at the global level is estimated to be about US$ 200 million per year. The calculation takes into account:

  • the implementation of IRM strategies in all countries with ongoing malaria transmission;
  • capacity-building for monitoring at country level;
  • the costs of operational research on insecticide resistance;
  • increased investment in research and development of new vector-control products; and
  • coordination at the global level to support GPIRM implementation.

Although this investment is significant, it is minor in comparison to the cost of protecting at-risk populations, should resistance to pyrethroids increase to the extent that the current core tools for vector control become ineffective.

Also, this funding requirement is not an all-or-nothing proposition. Full funding for the GPIRM would allow for the most robust response to this emerging threat; however, each extra dollar can be well used to improve monitoring and mount responses in the areas of greatest concern, and to finance the development and deployment of the most promising and urgently needed tools.

Currently, most non-pyrethroid insecticides are more expensive than pyrethroids, which accounts for some of the costs of implementing the GPIRM. With a continued scale-up of vector-control interventions, and increasing demand for non-pyrethroid insecticides, it is expected that prices will decrease, easing some of the financial pressures on countries and development partners.

9. What progress has been made in implementing the GPIRM since its release in 2012?

In September 2014, an update on implementation of GPIRM was provided to the Malaria Policy Advisory Committee. A situation analysis of available insecticide-resistance data and additional information provided by national malaria control programmes found that reported resistance (particularly to pyrethroids) has increased. Some progress has been made in implementing GPIRM technical recommendations. However, adoption of policies and operational implementation at country level have generally been poor because of a lack of political will, coupled with major deficiencies in financing, human resources and infrastructure.

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.

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