Scientific papers are now appearing which show mosquitoes with 100 per cent resistance to DDT and pyrethroids. Those are our staple insecticides, on which the whole structure of current malaria control is dependent.
Professor Willem Takken
Over the last decade the global death toll from malaria has been reduced by 25 per cent. While this may seem an unmitigated success for all concerned, there are fears that the dependence of malaria control strategies on insecticide-based tactics could have an undesirable backlash.
Researchers from Wageningen University and Research Centre (Wageningen UR) and colleagues from the United States and United Kingdom suggest that there are significant lessons to be learned from the agricultural sector if the success of malaria prevention efforts is to be maintained and built upon.
The paper, published in the open access journal PLoS Medicine
this month, outlines the outdated nature of an approach relying solely on chemical insecticides and makes the point that malaria mosquito control techniques are at the level of agricultural pest control methods from more than half a century ago.
I spoke to lead author Professor Willem Takken from the Laboratory of Entomology at Wageningen UR in the Netherlands, who began by describing why we need to be worried about the news that the death toll from malaria has fallen by a quarter in ten years.
"We should be worried because we’re not sure whether we can keep it at the current level," he explained. "You would hope that we could get it down by 50 per cent and even further, but the current intervention strategies – which are based on insecticide-treated bed nets, indoor residual sprays and drug treatment – are gravely endangered because of the rapid advances of insecticide resistance on the one hand and drug resistance on the other."
In recent years reports have come in from a number of countries, particularly in Africa, of malaria mosquitoes resistant to the potent insecticides believed to be responsible for the dramatic reduction in fatalities. Insecticide resistance can be an alarmingly rapid process.
"Selection for resistance can happen within three generations," Professor Takken stated. "If you consider that, on average, there are ten generations of mosquitoes in the space of a year, it can happen very quickly. Resistance is never complete in such a short time – complete resistance takes several years – but scientific papers are now appearing which show mosquitoes with 100 per cent resistance to DDT and pyrethroids. Those are our staple insecticides, on which the whole structure of current malaria control is dependent."
This is a situation that echoes the history of agricultural pest control, from which example Professor Takken and his colleagues believe there are many lessons to be learned.
"Until the mid 1960s the agricultural sector was dependent on chemical control, but they were forced against a wall by the very rapid advent of insecticide resistance that was observed in major crop pests," he explained. "They turned things around extremely quickly. In around 20 years they were able to develop a completely novel paradigm for pest control in agriculture in which there was still some room for pesticides.
"The novelty was that for every pest the first consideration was whether there was an environmental system that could be used to make the plants more resilient, through breeding programmes for example, and through looking for natural enemies of plant pests to keep them under control. They started to integrate these control methods with existing insecticides in a method called integrated pest management (IPM). This is a system where a series of different tools is judiciously applied to minimise the need for insecticides."
In the agricultural sector, a threshold level above which a pest becomes economically harmful is routinely established. The IPM system is designed accordingly to keep the levels of all pests below this economic threshold. This is not the case, however, in the health sector where total control – or eradication – is often desirable.
Professor Takken puts the gap between agricultural pest control methods and malaria control methods down to money. While there are huge economic incentives involved in agriculture – from the point of view of large multi-national companies as well as from the perspective of the farming community – the situation in global health and medicine is completely different.
"Health is often considered impossible to express in economic values. Therefore, as far as Western societies are concerned, as soon as an infectious disease appears we start paying for research to find new drugs or vaccines. If you go to the resource poor countries – many of which are in Africa, South America and Asia – the pharmaceutical industry says they won’t pay for research because they will never get their money back."
As similar factors that drive pests which affect cotton or cocoa are at play in malaria mosquitoes, the same integrated pest management techniques can be used to combat the spread of the disease.
"There are usually environmental factors that determine population size and population growth rate. By looking at these various factors you can find ways to intervene in populations to keep them at lower levels. For example, the population of malaria mosquitoes is entirely dependent on the presence of standing water. If there’s no standing water, mosquitoes cannot lay their eggs and they disappear."
There are other potential ways of targeting malaria mosquitoes at the early stages of their development, for example by manipulating populations of predators which are known to devour the larvae during their time in the water. Pathogens have also been developed which are sprayed on the water and kill only the mosquito larvae and nothing else, while others are working on behavioural manipulation tools such as odour-baited traps to draw mosquitoes away from humans.
"Another example of a method being developed here in Wageningen is focused on killing adult mosquitoes with a pathogenic fungus," Professor Takken informed me. "The fungus already exists naturally; we just have to mass produce it under controlled conditions and put it in areas where mosquitoes like to rest. They pick it up on their legs and are killed within three or four days.
"We have various tools at the moment that can be used in integrated vector management strategies which are not entirely or exclusively dependent on insecticides."
This combination of different tactics promotes the use of insecticides as a last resort which, although it cannot be seen as a universal remedy for insecticide resistance, has proven successful in a number of agricultural models around the world. The researchers emphasise that more work is needed to establish effective integrated vector management strategies for malaria.
"We have the tools already, but what we need are a couple of studies to show proof of principle of how this can be operated," Professor Takken said. "There is a lack of confidence at the moment, certainly from the public health authorities. They rely very heavily at the moment on the working mechanisms of insecticides on one hand and drugs on the other, and have never known anything else. If they looked a little further and allowed a couple of programmes to implement integrated pest management for malaria I think we could turn the scene around within five years. It’s not very difficult to demonstrate that it’s working."
As he pointed out, it is necessary to ask what is actually happening with the population in the endemic countries themselves in order to establish whether it is possible to run such a proof of principle experiment when members of said population are suffering from the disease. Professor Takken believes it is possible to have the two different approaches to control running side by side while proof of principle studies are carried out.
"Fortunately at the moment the insecticide treated nets are still working in areas where they are used. Even when the insecticides no longer work, people who sleep under a net get far fewer bites than those who don’t simply because of that physical barrier.
"If we were to develop the proof of principle studies with this in mind – that while they are running we will continue with the current strategy to maintain current levels of malaria control at least – we will have a win-win situation."
Professor Takken described how the least desirable outcome on all sides, following the success of malaria control programmes to date, is a ‘rebound’.
"A rebound could occur because in very well-controlled areas people are beginning to lose their natural immunity. If you were to get an increased number of mosquito bites, the situation could end up worse than it was before control methods were introduced."