Insecticide resistance threatens malaria control in Africa

Abstract

Researchers in west Africa are monitoring a worrying development for malaria-control efforts: the rise of insecticide resistance in mosquitoes in the region. Adele Baleta reports from Burkina Faso.Fields of cotton bolls puffed up like freshly popped corn is a success story for subsistence farmers in Burkina Faso. But bumper crops come with a heavy health cost as insecticide sprays, used to ensure good plant yields, have added to the west African country's malaria burden.Suleyman Kabore, a cotton farmer for more than 30 years in the small, landlocked country, which is ranked the third poorest in the world, does not understand the link between insecticide spray and resistance in malaria vectors. But he is certain that without the “poison” and rain he and his 16-member family will die of starvation.The rains have come, but their short duration (June to October) combined with the intense spraying of crops and high rate of malaria transmission and poverty, has led to the disease becoming endemic in the humid savannah of the southwestern district.Insecticide resistance is one of the biggest threats to sustainable malaria control in Africa. Up to 1 million Africans, mostly children younger than 5 years and pregnant women, die from malaria each year, according to Roll Back Malaria estimates. Meanwhile, 500 million cases of malaria-related illness on the continent have, and will continue to have, a devastating effect on the productivity of African economies.Sodiomon Sirima, interim director of the Centre National de Recherche et de Formation sur le Paludisme (CNRFP) based in the Burkinabe capital Ouagadougou, says that with a long history of crop spraying, malaria vectors, mainly the deadly Anopheles gambiae, have developed increasing resistance to dichlorodiphenyltrichloroethane (DDT) and pyrethroids.Control of Anopheles mosquitoes relies mainly on the use of pyrethroid-impregnated bednets and there are fears that the emergence of insecticide resistance will compromise their efficacy. DDT is used for indoor residual spraying in many countries but not in Burkina Faso, which has not started spraying.“Compared to east and central Africa our rainy season is short and the transmission rates are high. On average there are 300 infective bites per person per year in the rural areas (50 in East Africa) and about 10 per person per year in urban areas”, says Sirima.About 15 000 children younger than 5 years die every year from malaria. Sirima says all children in this age group have a minimum of two episodes a year. Malnutrition compounds the problem. During the rainy season and depending on the area, about 76% of children in this age group have been found to be infected using microscopy and this increases to almost 100% using the more expensive PCR test. For the general population these proportions are 40% and 60%, respectively.The CNRFP research centre is part of a network of the WHO-based Special Programme for Research and Training in Tropical Diseases, studying and doing twice-yearly monitoring of resistance in African malaria vectors in sentinel sites in Burkina Faso, Angola, Benin, Chad, and Sudan. The results and protocols from this work were presented at the 5th Multilateral Initiative on Malaria (MIM) Pan African Malaria conference in Nairobi, Kenya this week.Network coordinator Hilary Ranson, of Liverpool School of Tropical Medicine, said the following five insecticides were tested: DDT; permethrin and deltamethrin (pyrethroids); bendiocarb (carbamate); and fenitrothion (organophosphate). The results are not encouraging. With the exception of Burkina Faso and to a lesser extent Benin, most of the mosquitoes surveyed were susceptible to bendiocarb and fenitrothion. There were marked variations in resistance levels between sites and collection seasons. “Deltamethrin resistance appears to be a bit lower in frequency than permethrin resistance but this would require further investigation. We would expect cross resistance between the two”, says Ranson.Local researchers collect mosquito larvae for analysis from pools of stagnant waterView Large Image Copyright © 2009 Adele BaletaShe told The Lancet that the network is developing standardised protocols for vector population monitoring and for determining the levels of insecticide susceptibility in each study site. Molecular analysis would identify the main mechanisms responsible and improve the detection and management of insecticide resistance in malaria-control programmes.Sagnon N'Falé, head of the Burkinabe research team, says 80% resistance to permethrin and up to 70% resistance to DDT was found in the southwestern cotton growing district of Soumoussa.The pyrethroids are the only WHO-approved class of insecticides for use in insecticide-treated bednets and longlasting insecticide-treated nets. Recent studies have shown a 20% drop in mortality in African settings when insecticide-treated bednets are used. “We have shown that we need to understand the problem of resistance before using certain materials for malaria prevention”, says N'Falé.The CNRFP laboratories are abuzz with 35 scientists and a total of 100 staff working on malaria. In the insectory, larvae collected from the field are reared to adults that are then exposed to insecticide-treated papers using standard WHO methods. Progeny from the bioassays are preserved for molecular analysis. Adult Anopheles are collected indoors and out to test for parasite infection rates.National Malaria Control Programme (NMCP) coordinator Moyenga Laurent says it will be a huge challenge to achieve universal access to bednets by Dec 31, 2010—the deadline set by the Roll Back Malaria Programme.He says the Global Fund to Fight AIDS, Tuberculosis and Malaria has secured 6 million nets (at US$5 per net) but there is a shortfall of $2·5 million that is needed for transporting and distributing the nets. Advocacy and training of staff and volunteers have to be factored in as well. “We are concerned that the arrival of the nets will coincide with the beginning of the rainy season in June and this will make access even more difficult. We are aiming for 100% coverage and a minimum of 80% usage.”N'Falé says monitoring and testing of batches of nets before distribution is another logistical factor that will have to be taken into account. “We will need to test for the concentration of dosage to guard against the development of resistance.”Medical entomologist Guelbeogo Moussa says his greatest wish is for malaria communication, information, and advocacy for the community. “Those that have nets use them to avoid being bitten rather than to avoid malaria.” Myths that malaria is caused by fruits and other means abound. Often nets are accepted but folded away and never used. There is also the danger of access to cheap, inferior nets at markets.Sirima calculates that for “every net an additional $2 is needed to pay for transportation, training, and advocacy costs. There is no point in getting nets if we cannot get them to the people”.He says a major impediment to malaria control is that research findings are not being implemented at grassroots level. “We need resources to implement interventions. In general, those in control want research from multilateral and bilateral funding and the funders come up with ideas that are not based on local needs. We were among the first to implement insecticide-treated nets for research in 2003/4 but look at us now. We still don't have bednets. We don't want money with mandates attached. We need to see results on the ground”, says Sirima.The NMCP's Laurent and Sirima concur that there is not enough communication between researchers and the country's malaria-control programme. “I think there is still a tendency not to go with the research of the Burkinabe scientists but rather to look outside. We should also be informing the programme of our research”, says Sirima.Suleyman and his co-farmers are all using the same insecticide for their crops. It is the only product they use and is likely to result in increased Anopheles mosquito resistance to the chemicals. There is not much communication between the health and agriculture departments to look at ways to ensure different insecticides are used in each sector.In the absence of a malaria vaccine, prevention and control measures will continue to look at the ability of current insecticides to minimise resistance. Sirima believes that “a drama for malaria control will be created if farmers continue to use the same insecticides as those used for bednets…We need to come up with new and different insecticides”.It is getting darker and Suleyman and his co-farmers shake hands with their foreign visitors. Women begin the evening meal as children screech at their faces frozen in pixels on a camera. It is as if nobody has a care in the world. But, the reality is that unless speedy and workable solutions are found to the deepening malaria crisis in Africa, Suleyman's grandchildren may not be around after the next rainy season. Researchers in west Africa are monitoring a worrying development for malaria-control efforts: the rise of insecticide resistance in mosquitoes in the region. Adele Baleta reports from Burkina Faso. Fields of cotton bolls puffed up like freshly popped corn is a success story for subsistence farmers in Burkina Faso. But bumper crops come with a heavy health cost as insecticide sprays, used to ensure good plant yields, have added to the west African country's malaria burden. Suleyman Kabore, a cotton farmer for more than 30 years in the small, landlocked country, which is ranked the third poorest in the world, does not understand the link between insecticide spray and resistance in malaria vectors. But he is certain that without the “poison” and rain he and his 16-member family will die of starvation. The rains have come, but their short duration (June to October) combined with the intense spraying of crops and high rate of malaria transmission and poverty, has led to the disease becoming endemic in the humid savannah of the southwestern district. Insecticide resistance is one of the biggest threats to sustainable malaria control in Africa. Up to 1 million Africans, mostly children younger than 5 years and pregnant women, die from malaria each year, according to Roll Back Malaria estimates. Meanwhile, 500 million cases of malaria-related illness on the continent have, and will continue to have, a devastating effect on the productivity of African economies. Sodiomon Sirima, interim director of the Centre National de Recherche et de Formation sur le Paludisme (CNRFP) based in the Burkinabe capital Ouagadougou, says that with a long history of crop spraying, malaria vectors, mainly the deadly Anopheles gambiae, have developed increasing resistance to dichlorodiphenyltrichloroethane (DDT) and pyrethroids. Control of Anopheles mosquitoes relies mainly on the use of pyrethroid-impregnated bednets and there are fears that the emergence of insecticide resistance will compromise their efficacy. DDT is used for indoor residual spraying in many countries but not in Burkina Faso, which has not started spraying. “Compared to east and central Africa our rainy season is short and the transmission rates are high. On average there are 300 infective bites per person per year in the rural areas (50 in East Africa) and about 10 per person per year in urban areas”, says Sirima. About 15 000 children younger than 5 years die every year from malaria. Sirima says all children in this age group have a minimum of two episodes a year. Malnutrition compounds the problem. During the rainy season and depending on the area, about 76% of children in this age group have been found to be infected using microscopy and this increases to almost 100% using the more expensive PCR test. For the general population these proportions are 40% and 60%, respectively. The CNRFP research centre is part of a network of the WHO-based Special Programme for Research and Training in Tropical Diseases, studying and doing twice-yearly monitoring of resistance in African malaria vectors in sentinel sites in Burkina Faso, Angola, Benin, Chad, and Sudan. The results and protocols from this work were presented at the 5th Multilateral Initiative on Malaria (MIM) Pan African Malaria conference in Nairobi, Kenya this week. Network coordinator Hilary Ranson, of Liverpool School of Tropical Medicine, said the following five insecticides were tested: DDT; permethrin and deltamethrin (pyrethroids); bendiocarb (carbamate); and fenitrothion (organophosphate). The results are not encouraging. With the exception of Burkina Faso and to a lesser extent Benin, most of the mosquitoes surveyed were susceptible to bendiocarb and fenitrothion. There were marked variations in resistance levels between sites and collection seasons. “Deltamethrin resistance appears to be a bit lower in frequency than permethrin resistance but this would require further investigation. We would expect cross resistance between the two”, says Ranson. She told The Lancet that the network is developing standardised protocols for vector population monitoring and for determining the levels of insecticide susceptibility in each study site. Molecular analysis would identify the main mechanisms responsible and improve the detection and management of insecticide resistance in malaria-control programmes. Sagnon N'Falé, head of the Burkinabe research team, says 80% resistance to permethrin and up to 70% resistance to DDT was found in the southwestern cotton growing district of Soumoussa. The pyrethroids are the only WHO-approved class of insecticides for use in insecticide-treated bednets and longlasting insecticide-treated nets. Recent studies have shown a 20% drop in mortality in African settings when insecticide-treated bednets are used. “We have shown that we need to understand the problem of resistance before using certain materials for malaria prevention”, says N'Falé. The CNRFP laboratories are abuzz with 35 scientists and a total of 100 staff working on malaria. In the insectory, larvae collected from the field are reared to adults that are then exposed to insecticide-treated papers using standard WHO methods. Progeny from the bioassays are preserved for molecular analysis. Adult Anopheles are collected indoors and out to test for parasite infection rates. National Malaria Control Programme (NMCP) coordinator Moyenga Laurent says it will be a huge challenge to achieve universal access to bednets by Dec 31, 2010—the deadline set by the Roll Back Malaria Programme. He says the Global Fund to Fight AIDS, Tuberculosis and Malaria has secured 6 million nets (at US$5 per net) but there is a shortfall of $2·5 million that is needed for transporting and distributing the nets. Advocacy and training of staff and volunteers have to be factored in as well. “We are concerned that the arrival of the nets will coincide with the beginning of the rainy season in June and this will make access even more difficult. We are aiming for 100% coverage and a minimum of 80% usage.” N'Falé says monitoring and testing of batches of nets before distribution is another logistical factor that will have to be taken into account. “We will need to test for the concentration of dosage to guard against the development of resistance.” Medical entomologist Guelbeogo Moussa says his greatest wish is for malaria communication, information, and advocacy for the community. “Those that have nets use them to avoid being bitten rather than to avoid malaria.” Myths that malaria is caused by fruits and other means abound. Often nets are accepted but folded away and never used. There is also the danger of access to cheap, inferior nets at markets. Sirima calculates that for “every net an additional $2 is needed to pay for transportation, training, and advocacy costs. There is no point in getting nets if we cannot get them to the people”. He says a major impediment to malaria control is that research findings are not being implemented at grassroots level. “We need resources to implement interventions. In general, those in control want research from multilateral and bilateral funding and the funders come up with ideas that are not based on local needs. We were among the first to implement insecticide-treated nets for research in 2003/4 but look at us now. We still don't have bednets. We don't want money with mandates attached. We need to see results on the ground”, says Sirima. The NMCP's Laurent and Sirima concur that there is not enough communication between researchers and the country's malaria-control programme. “I think there is still a tendency not to go with the research of the Burkinabe scientists but rather to look outside. We should also be informing the programme of our research”, says Sirima. Suleyman and his co-farmers are all using the same insecticide for their crops. It is the only product they use and is likely to result in increased Anopheles mosquito resistance to the chemicals. There is not much communication between the health and agriculture departments to look at ways to ensure different insecticides are used in each sector. In the absence of a malaria vaccine, prevention and control measures will continue to look at the ability of current insecticides to minimise resistance. Sirima believes that “a drama for malaria control will be created if farmers continue to use the same insecticides as those used for bednets…We need to come up with new and different insecticides”. It is getting darker and Suleyman and his co-farmers shake hands with their foreign visitors. Women begin the evening meal as children screech at their faces frozen in pixels on a camera. It is as if nobody has a care in the world. But, the reality is that unless speedy and workable solutions are found to the deepening malaria crisis in Africa, Suleyman's grandchildren may not be around after the next rainy season.