Q&A on the Global Plan for Insecticide Resistance Management in malaria vectors

May 2012

1. What is insecticide resistance?

Insecticide resistance refers to changes in an insect population that weaken the effect of the given insecticide. Such resistance may be detected through genetic tests performed on the insects, or through assays that measure insect mortality when exposed to a particular compound. In malaria control, the compounds currently being used against the parasite-carrying Anopheles mosquito belong to four classes: carbamates, organochlorines, organophosphates, and pyrethroids. The potential result of mosquito resistance to these insecticides is that they are no longer killed when coming into contact with long-lasting insecticidal nets (LLINs) or a standard dose of insecticide sprayed on wall surfaces as part of indoor residual spraying (IRS) programmes – the two most powerful and widespread malaria control interventions. However, this does not mean that these interventions become less effective immediately, or result in a surge in malaria cases.

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 programmes since insecticides first came into broad use in the 1940s. Endemic countries have been aware of the importance of detecting and preventing the development and spread of insecticide resistance, and many countries have included insecticide resistance monitoring and management practices into their national malaria control strategies. However, in most endemic countries - particularly in sub-Saharan Africa - control strategies in the past decade have focused on scaling up vector control interventions, and only limited resources were available to build capacity for entomological monitoring, insecticide susceptibility testing and to design 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, the pyrethroids. The pyrethroids are not only highly effective, but are the least expensive among the four classes of insecticides available for public health vector control. Pyrethroids are the only class available for use on LLINs. In some areas, the use of pyrethroids and similar insecticides in agriculture also appear to have contributed to the development of resistance in mosquitoes. Currently, existing malaria prevention tools - such as LLINs and IRS spraying - remain highly effective in all countries with malaria transmission. However, urgent action is now required to prevent the further development of resistance in order to maintain the effectiveness of vector control interventions, and the remarkable recent gains in malaria control.

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

According to the Global Plan for Insecticide Resistance Management in malaria vectors (GPIRM), mosquito resistance to at least one class of insecticides has been identified in 64 countries with ongoing malaria transmission. (A map is available on page 29 of the GPIRM showing countries with at least one confirmed report of resistance.) Several countries in sub-Saharan Africa and India have reported widespread resistance. Most affected countries have not yet carried out adequate routine testing, which means that our understanding of the scale of insecticide resistance is incomplete. To tackle this problem, the GPIRM calls for the establishment of a global database on insecticide resistance to help endemic countries and donors take targeted action.

In December 2011, WHO reported that insecticide resistance had been identified in 45 countries to at least one class of insecticides. The numbers presented in the GPIRM are not an indication of further spread. Rather, the difference is due to the fact that WHO has since reviewed and processed data from a range of additional reports from malaria-endemic countries as well as independent studies. As routine monitoring is scaled up, a more detailed picture will emerge about the state of insecticide resistance. The global database - once established - will help to provide timely tracking of changing insecticide resistance patterns, and WHO will issue regular updates about the number of countries affected.

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

The GPIRM is a call to action. Through this document, WHO and the Roll Back Malaria Partnership are calling on governments of malaria-endemic countries, donor organizations, UN agencies, as well as research and industry partners, to implement a five-pillar strategy to tackle the growing threat of insecticide resistance and to facilitate the development of innovative vector control tools and strategies. The GPIRM was called for in 2011 by the World Health Assembly and the Board of the Roll Back Malaria Partnership because of a 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 representing all constituencies of the malaria community, including malaria endemic countries, multilateral agencies, development partners, academia, and industry. The plan contains the latest available evidence on the extent of insecticide resistance around the world, and puts forward a strategy for global and country levels, identifying clear roles and timelines for all stakeholders. The GPIRM also summarizes information about innovative new products being developed and sets out the immediate research and development priorities. The document was launched on 15 May 2012 at WHO headquarters in Geneva.

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

The GPIRM is based on five pillars, addressing 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, as well as partners in the public health insecticide industry. The strategy calls on stakeholders to: 1) plan and implement insecticide resistance management (IRM) strategies in malaria-endemic countries; 2) ensure capacity for proper, timely entomological monitoring and effective data management; 3) develop new, innovative vector control tools; 4) fill knowledge gaps on the mechanisms of insecticide resistance and the impact of current resistance management approaches; and finally 5) ensure that key enabling mechanisms - including advocacy, human and financial resources - are in place.

The most urgent task for malaria-endemic countries will be 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. Countries should strive to have pre-emptive IRM strategies in place and integrate related costs into national malaria control budgets. In parallel, all endemic countries should design a monitoring plan and build capacity to handle and interpret data about resistance. Through IRM, endemic countries can delay the evolution of resistance, preserve the effectiveness of existing insecticides and even reverse resistance in some settings. A successful implementation of the GPIRM will require coordinated action between all partners of the malaria control community as well as other sectors, such as agriculture and finance.

6. What are the implications for the use of long-lasting insecticidal nets?

All types of LLINs currently recommended by WHO are treated with pyrethroids. During the past decade, vector control has relied heavily on the pyrethroids and countries have now reported widespread resistance to this class of insecticide. Despite that, there are very few proven cases where 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 coverage with LLINs, and aim for universal coverage with vector control interventions. This is both because LLINs act as a physical barrier against parasite-carrying mosquitoes, and because even a sub-lethal effect of the insecticide is likely to contribute to malaria control. With continued use of LLINs, the operational impact of their use must be monitored closely and resistance should be tested at sentinel sites at least once a year and - where feasible - every six months. The GPIRM recommends that in areas with high malaria transmission and confirmed levels of resistance, and where LLINs are used together with IRS, only a non-pyrethroid insecticide should be used in IRS programmes.

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

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

One important partner is the Innovative Vector Control Consortium (IVCC), a product development partnership, whose pipeline includes non-pyrethroid-based LLINs and LLINs treated with two classes of insecticides, which may become available within 3-5 years. The pipeline also includes a reformulated, non-pyrethroid, non-DDT compound with a residual efficacy of about 6 months when sprayed on walls. In addition, an active ingredient called chlorfenapyr is currently being tested and evaluated by WHO for IRS programmes. The new compound and active ingredient could be on the market in 2013.

IVCC’s longer-term research pipeline includes longer-lasting IRS compounds and three new active ingredients, including one that could be used on LLINs. These products are about 7-10 years away from reaching the market. In addition to these products, a number of novel approaches are being developed, including spatial repellents, area-wide treatments, traps and targets, and animal treatments. There are also a range of non-insecticide based vector control solutions that are being evaluated for potential public health use.

8. What will be 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 at approximately 200 million USD annually. This calculation takes into account the implementation of IRM strategies in all 99 countries with ongoing malaria transmission. It also includes capacity-building for monitoring at country-level, the costs of operational research into insecticide resistance, increased investment in research and development for new vector control products, and coordination at the global level to support GPIRM implementation.

This investment - while significant - is relatively minor compared to the investment that would be required to protect at-risk populations if resistance to pyrethroids were to result in widespread loss of effectiveness of current vector control tools. It should also be noted that this funding requirement is not an all-or-none proposition. While full funding for the GPIRM would allow for the most robust response to this emerging threat, each extra dollar that is raised to address the problem can be well used to improve monitoring and mount responses in areas of greatest concern, and finance the development of the most promising and urgently needed tools.

Currently, some of the 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.