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Time to give spatial repellency its rightful role in vector control

June 19, 2012 - 19:19 -- Bart G.J. Knols

The following Guest editorial was provided by Richard Tren, Kimberly Hess, and Donald Roberts.

Progress is being made against malaria. As reported by the World Health Organization (WHO), malaria cases have declined by more than 50% between 2000 and 2010, and malaria-specific mortality has declined by 26% [1].  These gains are mainly due to the use of insecticides to control disease-spreading insects (vector control) through insecticide-treated bednets and indoor residual spraying (IRS). Despite the importance of public health insecticides in vector control, there is very little appreciation and understanding of how insecticides actually work in disease prevention.

 
Spatial repellency protects people from insect-borne diseases by reducing contact between disease-spreading insects and humans. This mode of action is not new; in fact, it has been observed since the 1940s with DDT in malaria control. DDT is still one of the most effective chemicals in preventing malaria transmission inside houses. Its powerful spatial repellent action prevents or slows the selection of resistance in mosquitoes [2].  DDT is the only chemical recommended for malaria control that often stops mosquitoes from entering houses and thus transmitting disease. A recent article by Nicole Achee and others, published in Malaria Journal, gives further evidence of the importance of spatial repellency in vector control and the need to develop new active ingredients with characteristics other than toxicity [3].  
 
The modern arsenal of public health insecticides is antiquated and limited to just 12 insecticides, most belonging to one class (pyrethroids). Due to increased reliance on pyrethroids in malaria control and increasing insecticide resistance among mosquito populations, the WHO Global Malaria Programme (GMP) recently released the Global Plan for Insecticide Resistance Management in malaria vectors (GPIRM) [4].  One of the five pillars of the Plan is the development of new and innovative vector control tools. However, there is a dearth of public funding in the search for new public health insecticides. Aside from the Bill and Melinda Gates Foundation’s Innovative Vector Control Consortium (IVCC), no new public investment of any significance has been made in this area.
 
Lack of funding and political emphasis is probably due to two major factors. Influential environmentalist groups, such as the United Nations Environment Programme (UNEP) and Global Environment Facility (GEF), and several non-governmental organizations are waging successful and aggressive advocacy campaigns to eliminate the insecticide DDT and move away from use of all insecticides by making false claims about the effectiveness of non-insecticidal malaria control [5].  Their efforts have translated into almost no popular advocacy, or advocacy targeted at policy-makers, for insecticide development.
 
The more important factor however has been the amazing lack of effective advocacy and leadership for the use of insecticides from the malaria control community and from global public health institutions. While the WHO's GMP does the best it can with available resources, there is a real and urgent need for senior WHO leadership to stand up for evidence-based research and resist pressure to follow the green movement down a deadly insecticide-free path.
 
Despite the knowledge that spatial repellency works, the public health establishment (including private companies) has ignored this vital information. Evidence of this can be seen in the GPIRM. While the GPIRM does acknowledge that, "sustained investment is required to develop new active ingredients with different modes of action," [6]  the only mention of spatial repellents is as one of four new paradigms being developed for vector control. In addition, the GPIRM states: "Like pyrethroids, DDT has been popular because of its rapid knock-down effect, relative longevity (6–12 months when used for IRS) and low cost. Despite chemical structural differences, DDT and pyrethroids have similar modes of action" [7]. This statement is false and misleading as it neglects to mention that DDT acts first as a spatial repellent, second as a contact irritant and third, with prolonged physical contact, as a toxin. Pyrethroids on the other hand have an irritant effect on mosquitoes, with the potential to kill if the mosquitoes rest long enough on the chemical. Pyrethroids are also not long-lasting insecticides and only now are they becoming more efficacious in terms of relative longevity. Furthermore, only in recent years have relative costs of DDT versus pyrethroids attained parity because environmental pressure eliminating DDT production and increasing regulatory controls caused cost of DDT to rise and some pyrethroids have had cost decreases. Also, it remains to be seen if longer-acting pyrethroid formulations will be affordable. Certainly the non-pyrethroid alternatives are considerably more expensive. Carbamates are priced at about four times the cost of pyrethroids or DDT and a new long-lasting organophosphate formulation is priced at around eleven times the cost of pyrethroids or DDT [8].  
 
Perhaps there are vested interests that would stand to lose if spatial repellency were to be accepted as a mainstream form of vector control; or perhaps it is due to intellectual laziness, bureaucratic inertia or public health policy makers wedded to their old ways of doing things. Whatever the reason or reasons, gains against malaria could be lost if the public health and scientific communities do not recognize that modes of action other than toxicity are beneficial to vector control. 
 
While the Malaria Journal article demonstrates that there is growing support for emphasis on active ingredient development other than toxic action, past and present research and development efforts have thus far failed to focus on the multiple modes of chemical actions. Importantly, funding agencies must fully embrace the concept that chemical actions other than toxicity can reduce disease transmission. Although those actions are well documented in both historical and recent literature, until funding agencies get behind the concept, researchers will continue to focus on toxicity as the single approach to disease control. 
 
As documented in the new article in the Malaria Journal and contrary to popular belief, Anopheles mosquitoes do not need to be killed in order for malaria to be controlled. And while killing annoying mosquitoes is certainly satisfying, gone should be the belief that the only good mosquito is a dead mosquito. The Malaria Journal article should act as a call to action for the development of chemicals that function in the same way as DDT and against those who seek to eliminate DDT, the only chemical that has a critically important spatial repellent action.
 
References
 
[1]  World Health Organization: World Malaria Report 2011. [http://www.who.int/malaria/world_malaria_report_2011/en/index.html]
[2]  Grieco J, Achee N, Chareonviriyaphap T, Suwonkerd W, et al: A new classification system for the actions of IRS chemicals traditionally used for malaria control. PLoS ONE. 2007, 2(8):e716. doi:10.1371/journal.pone.0000716.
[3]  Achee N, Bangs M, Farlow R, Killeen G, et al: Spatial repellents: from discovery and development to evidence-based validation. Malar J. 2012, 11:164. doi:10.1186/1475-2875-11-164.
[4]  World Health Organization: Global Plan for Insecticide Resistance Management in Malaria Vectors (GPIRM). [http://www.who.int/malaria/vector_control/ivm/gpirm/en/index.html]
[5]  Roberts D, Tren R: International advocacy against DDT and other public health insecticides for malaria control. Research and Reports in Tropical Medicine. 2011, 2011(2):23-30. DOI: http://dx.doi.org/10.2147/RRTM.S16419.
[6]  World Health Organization: Global Plan for Insecticide Resistance Management in Malaria Vectors (GPIRM). [http://www.who.int/malaria/vector_control/ivm/gpirm/en/index.html]
[7]  World Health Organization: Global Plan for Insecticide Resistance Management in Malaria Vectors (GPIRM). [http://www.who.int/malaria/vector_control/ivm/gpirm/en/index.html]
[8]  Miller M, Tren R: Implications of public-health insecticide resistance and replacement costs for malaria control: challenges and policy options for endemic countries and donors. Research and Reports in Tropical Medicine. 2012, 2012(3):1-19. DOI: http://dx.doi.org/10.2147/RRTM.S30914.
 
 

Comments

Mark Birchmore's picture
Submitted by Mark Birchmore on

Thanks for the challenging editorial. As Head of Syngenta's Vector Control business we take an active interest in finding new chemistry and modes of action as evidenced by our partnership with the IVCC targeted at finding the next generation of insecticides for adult mosquito control. Bayer and Sumitomo have similar initiatives (see www.ivcc.com for an overview).


One of the challenges we have here is of methodology to efficiently screen tens of thousands of candidate molecules for biological activity against adult mosquitoes. Syngenta has developed a unique high throughput screen to test compounds for classical knockdown and killing effects which has enabled us to support our research with very high quality data and select highly interesting new classes of chemistry which have potential for vector control. However, doing the same thing for spatial repellency is extremely difficult. The realities of finding new chemistry means that it really is a numbers game. A general guide is that we need to test 100,000 individual molecules to find an agricultural insecticide for example. You'd spend years and millions trying to do the same for spatial repellents.


So, I think one of the stark realities is that, as a dead mosquito cannot transmit malaria, and our experience means that we are very good at finding new products that do just that, we have to make a short term choice to accelerate activity which finds new killing agents in order to most efficiently find new insecticides, especially when we face of resistance to all the classes of chemistry available today. Its going to be a hard enough job as it is. Our dual R&D strategy for new vector control insecticides includes both the IVCC collaboration and leveraging our agrcultural insecticide pipeline. If we succeed here it will be a massive leap forward.


In addition, its worth noting that any candidate molecules that we do take to the field for evaluation would be evalauted for these additional 'side effects'. Remember, DDT was discovered first as a killing agent and only more recently have people discussed its potential for spatial repellency.


So, despite all the bad news, R&D for new insecticides is well underway and indeed delivering new tools, and Syngenta is actively engaged in this: Our new long lasting Actellic 300CS product is now being actively used to control pyrethroid resistant populations in IRS;  Icon 10CS can indeed last as long as DDT in IRS; and the new insecticide pipeline has never been better for vector control in my view and so there is real cause for optimism.

Mark Birchmore | Head of Vector Control, Syngenta

Bart G.J. Knols's picture
Submitted by Bart G.J. Knols on

Mark,

One small comment: the spatial repellent properties of DDT were described back in the early 1960s, first from Papua New Guinea if I remember correctly. Don Roberts writes a long list of studies from those days in his 2010 book on DDT.

Submitted by Richard Tren on

 

Thanks Mark for the comments,

You raise an important point about the high throughput screening for knockdown and killing agents.  This screening evolved after much energy, effort, brainpower and money went into its development.  What we would like to see is the same sort of effort going into developing a similar system for spatial repellents.  We have seen this done at some level with the work of John Grieco and Nicole Achee, but much more is needed.

Of course none of this is cheap or easy and private companies have their shareholders to answer to.  However unless there is first a recognition of the importance of spatial repellency we will never make progress in really developing chemicals that are unique to public health and embrace the full range of actions that are truly helpful in stopping the spread of vector borne diseases. 

As Bart has already pointed out, the spatial repellent action of DDT was first noted and written up in the scientific literature in the 1940s and there have been countless studies since then confirming this.  It has only been the steadfast refusal of policy makers to truly understand and embrace spatial repellent action as a valid means of disease control that we are stuck in this mode of viewing killing action as the only valuable means of disease control (please note we are talking about disease control, not vector control.)

Donald Roberts & Richard Tren