Malaria mosquitoes putting up resistance

Recent successes have given a glimpse of the possibility of eliminating the pandemic in Africa. But the emergence of Anopheles resistance probably pushes back any hope of eradicating the disease for a long time. This investigation highlights the urgency for developing a vaccine against malaria infection, which still kills about one million people every year, most of them in Africa.

Malaria is the most widespread parasitic disease in the world. Between 300 and 500 million people per year are hit, 90% of them in the African continent where the infection is the premier cause of mortality in children under five. It is brought on by the parasite Plasmodium falciparum, transmitted to humans by mosquitoes called Anopheles gambiae. As a protection measure, insecticide-treated bednets (1) are currently still the best means of control. These nets, distributed on a large scale in Africa over the last few years, in conjunction with artemisinin-based combination therapies (ACTs) administered in all African countries from 2006, have brought a considerable reduction in infections and the number of deaths.

Malaria regaining ground

A new study conducted by IRD researchers and their partners(2) in the village of Dielmo, in Senegal, published in The Lancet Infectious Diseases, casts a shadow over these results. It reveals a resurgence of cases since September 2010, a little over two years after the arrival in the village in August 2008 deltamethrin treated bednets (4). Reduced exposure to the disease made possible by the nets resulted in a weakening of the population's immune protection(3). The persistence of the immunity acquired in early childhood depends on the constancy of exposure to malaria later in life. This immune protection diminishes when exposure is reduced, bringing a rise in malaria attacks some years afterwards in older children and adults.

In parallel, during the first two years of use, the Anopheles have developed resistance to the insecticide adopted for impregnating the bednets. The research team showed that in 2010 37% became deltamethrin-resistant. The genetic mutation kdr, which gives the mosquito this resistance, was observed to have risen from 8% in 2007 to 48% in 2010 in the mosquito population.

The research team has been investigating the long-term relationship between the hosts -humans- and the malaria vector in Dielmo since the 1990s. Daily medical monitoring of fever and monthly collections of mosquitoes enabled them to build up a unique database. This base provided the means to perform historical statistical analyses of the impact of the different health policies implemented for controlling the disease.

Resistance on all fronts

Recent reports in other countries of Africa indicate that the Anopheles mosquito's resistance to pyrethroid insecticides such as deltamethrin is strongly increasing on that continent. Yet to date there are no alternative insecticides that are simultaneously effective, inexpensive and safe for human use.

The emergence of both the vectors' resistance against insecticide and the parasites' resistance against treatments is a major obstacle for pushing back malaria in the world and in particular in Africa. Previously the disease's progress had been checked in many countries by the use of the antimalarial medicine chloroquine, but the appearance of Plasmodium falciparum parasites resistant to it during the 1990s increased mortality, doubling it or even increasing it up to six-fold depending on the region of Africa. To hold back the new advance, therapeutic combinations such as ACTs have been rapidly deployed since 2006. These therapies are now the major arm against the disease in all the endemic countries. Indeed another IRD study, under publication, shows that malaria mortality in Senegal has been cut by about 25% since ACTs were brought in to replace chloroquine. Occurrence of resistance to artemisinin has recently been reported in South America and South-East Asia, but not yet in Africa.

Although ACTs and insecticide-treated bednets currently remain the best antimalarial weapons, in the face of the emergence of resistance -as these new investigations show-combining their use with a vaccine is essential if there is to be any hope of eradicating the disease.

1. The insecticide treated bednet strategy was developed by IRD researchers of the Centre Muraz in Burkina Faso. The World Health Organization (WHO) is promoting these protection measures.
2. These investigations were conducted in partnership with the Dakar Pasteur Institute in Senegal, the Pasteur Institute in Paris, Pasteur Institute of Madagascar and the Senegalese Ministry of Health.
3. Immune protection is the preservation of immunity owing to the pathogen's presence in the organism.
4. Deltamethrin is one of the main insecticides used in malaria control measures in Africa and is recommended by the World Health Organization (WHO) for treating bednets.