Archive for the ‘Evolution’ Category

With over half a billion deaths attributed annually, Malaria is one of the world’s worst infectious diseases. The WHO, spurred on by previous success with small pox, has long had the dream of eradicating this disease, but has had to deal with limited success as the mosquitoes have developed resistances to the insecticides traditionally used against this primary vector. Currently, the Global Malaria Action Plan (GMAP) has had ambitious plans “to spray 172 million homes and distribute 730 million insecticide impregnated nets” by 2010, but there is a hidden danger to the plan: natural selection. More and more we are finding that the traditional insecticides (DDT, Pyrethrins, etc) are becoming less able to control populations of Anopheles mosquitoes, because the selective pressure on populations is already powerful even without intervention.

The long term benefits of using ‘quick kill’ insecticides are limited, because they add to the selective pressure already existent in the normal breeding cycle, thus quickly creating populations that are resistant to these traditional methods. The problem is one of diminishing returns. Consider the impracticality of perpetually designing an endless chain of active, weakly human toxic insecticides ad infinitum. Insecticides are toxic chemicals by their nature and very few have been found to date that have the necessarily low human toxicity and insect killing capacity. This paper suggests that using new or old pesticides in new ways might limit or all together remove this selective pressure, while at the same time accomplish the stated objective of controlling malaria.

The Big Idea: How They Work:

Malaria is caused by a eukaryotic protest called Plasmodium falciparum, which is transmitted by the bites of Anopheles mosquitoes. Their life cycle is an important part of the problem. After eating, the females produce and deposit a batch of eggs in water, which in total takes 2-4 days to complete. Even without insecticides exacerbating the problem, the egg mortality rate is around 20-40% per batch. With such a turnover rate, breeding selection will always be a strong factor in mosquito populations. At some point, the mosquitoes encounter and become infected with the malarial parasites. These generally go through an incubation period of 10-14 days before becoming active in mosquito salivary glands. This is ironic considering that most mosquitoes will not live long enough to become infectious and spread the disease. Since they only spread the disease at late stages, there is a window of opportunity to curb not only the selective pressure that encourages resistances, but also dramatically control the malaria transmitting mosquitoes.

Late Life Acting insecticides (LLA) have been proposed that disproportionately kill only the older mosquitoes. A major benefit being that selective resistances would spread much slower, than as with the use of current insecticides, while at the same time cull the infective mosquitoes. Conventional insecticides reduce the mosquito reproductive success by about 85% at first, but the LLA’s, which would allow for a normal reproductive cycle would target only older mosquitoes. Selectively targeting only the older mosquitoes relieves this selective pressure. If only the older insects are killed, it allows the younger ones to proliferate and spread their genes giving little selective benefit for having a resistance to the insecticides. Furthermore, the authors point out that:

The strength of selection declines with age. Beneficial genes that act late in life can fail to spread if they are associated with fitness costs earlier in life.

Though LLA insecticides would leave a large population of mosquitoes, the key point is this is meant to be disease control, rather than insect control.

Several methods have been proposed. First, cumulative exposure to ordinarily sub-lethal doses of pesticides. The idea is that the low doses build up over time killing only the older mosquitoes before they transmit the disease. Second, micro-encapsulation techniques designed to release over a long period of time. (Think about your Imodium 24 hour extended release, except with horrible poison!!) Third, chemicals that negatively affect detoxification pathways in mosquitoes. This exploits the fact that as mosquitoes age they become less able to detoxify chemicals. Fourth, compounds or dosages of pesticides that take advantage of an infected mosquitoes weakened state (malarial parasites negatively affect them as well). By using dosages, which are lower than recommended (especially those which are non-lethal for most healthy mosquitoes), it may be possible to target only those older mosquitoes with a weakened composition. Fifth, fungal bio-pesticides, which are active against mosquitoes, killing them 7-14 days after contact. The final possibility mentioned is using Wolbachia bacteria or a densovirus to control the older populations. Wolbachia are inherited bacteria that infect many kinds of insects, in particular affecting the reproduction system of their hosts and in some species causing parthogenesis (reproducing only one sex). Densovirii are virii that are thought to only infect insects. Both of these could be applied in much the same manner as the above methods, either building up over time or causing a metabolic pitfall as they age, shortening their life spans to die before the malarial parasites become active.


Evolution Proof Insecticides for Malaria Control

Penelope A. Lynch, Andrew F. Read and Matthew B. Thomas


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