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Malaria eradication: Doing it better the second time round

May 22, 2014 - 20:40 -- Bart G.J. Knols
This guest editorial was contributed by Dr. Carlos Chaccour - he and his team are currently running an Indiegogo fundraising campaign to further develop ivemectin as an anti-malaria strategy. Visit the campaign's website by clicking here.
 
The eighth World Health Assembly took action to “help put an eventual end to an ancient problem. Malaria, the single most serious worldwide communicable disease…” [1]. The meeting took place in Mexico in May 1955. In exactly a year we will mark the 50th anniversary of the launching of the Global Malaria Eradication Programme (1955-1969). Several reasons have been given for the failure of this multinational endeavour to achieve its primary goal. Vertical structures, a lack of community integration and the (almost) exclusive use of indoor-residual spraying are some of them. The resulting program was not particularly flexible nor quick enough to spot and correct some of these failures before international support was withdrawn [2]...

Almost seven years ago we witnessed a new call for malaria eradication [3]. The result of Bill and Melinda Gates’ commitment has increased private funding and renewed political interest. It is clear that this second time we will do our best to avoid the mistakes of the past and a thorough research agenda has been proposed [4]. It seems clear that in the lack of an effective vaccine that could also block transmission, vector control will once more play a key role in stopping the disease.
 
The eradication idea is particularly threatened today by the appearance of artemisinin-resistant strains of Plasmodium falciparum in the Thai-Cambodian border region. A containment strategy has been proposed, fearing that once more, resistant parasites from South-East Asia will spread to Africa and increase mortality. Some even advocate the elimination of malaria in the whole region. Here again, vector control will be of capital importance.
 
A stumbling point for vector control today is insecticide resistance. Resistant Anopheles force us into a race of coming up with different mechanisms of actions for residual insecticides, just to lose them again to resistance. This costs money and effort which is not invested into new tools or other equally pressing issues.
 
Another problem is evolution. Selective pressure on indoor-biting and resting vectors causes behavioural adaptation. Transmission is then shifted to places and times were current mainstay measures lose strength, namely outdoors or around sunset/sunrise [5,6].
 
Endectocides have recently been proposed as a possible solution to circumvent both of these challenges.  Ivermectin is the one endectocide we have most experience with. Its story is one of enormous success, commitment and generosity. It involves a serendipitous discovery, a prompt approval by authorities and an unprecedented commitment to donate it for as long as needed for the control of onchocerciasis. In this context, over 2.000 million doses have been used safely over the last 27 years.
 
For some time now, we have had the evidence that ivermectin can kill Anopheles mosquitoes and disrupt malaria transmission. It seems, however, that this line of research has gotten relatively little attention so far.
 
As much as I believe that it is important to drive more attention into this field of research, the obvious temptation here is to treat endectocides as the new silver bullet that will, this time around (this time for sure), bring malaria to a definitive end. That is pretty much the way we treated DDT 60 years ago. If something has been learned in the last half-century is that malaria is a smart foe. Both the parasite and the mosquito evolve and respond quickly to new drugs, new control methods, new environments. So if we are to see the end of this disease in our lifetime, innovation and traditional tools must go hand in hand to make malaria history, everywhere and forever this time around. 

Carlos Chaccour MD MSc DTMH is the research coordinator at the Malaria MISSION project at the Universidad de Navarra. They are currently trying to crowdfund resources for the second phase of their trials of a slow release ivermectin formulation.

 
1.- Mayo CW, Brady FJ. The Eighth World Health Assembly. Public Health Rep. Nov 1955; 70(11): 1057–1060.
2.- Nájera JA, González-Silva M, Alonso PL. Some lessons for the future from the Global Malaria Eradication Programme (1955-1969).  PLoS Med. 2011 Jan 25;8(1):e1000412. 
3.- Gates B. Malaria Forum Keynote Address (October 17, 2007). Retrieved from: http://www.gatesfoundation.org/media-center/speeches/2007/10/bill-gates-...
4.- Alonso PL, Brown G, Arevalo-Herrera M, Binka F, Chitnis C, Collins F et al. A research agenda to underpin malaria eradication.  PLoS Med. 2011 Jan 25;8(1):e1000406. 
5.- Sougoufara S, Diédhiou SM, Doucouré S, Diagne N, Sembène PM, Harry M et al. Biting by Anopheles funestus in broad daylight after use of long-lasting insecticidal nets: a new challenge to malaria elimination. Malar J. 2014 Mar 28;13:125. 
6.- Gatton ML, Chitnis N, Churcher T, Donnelly MJ, Ghani AC, Godfray HC et al. The importance of mosquito behavioural adaptations to malaria control in Africa. Evolution. 2013 Apr;67(4):1218-30.