Malaria, Resistance, and Paying Attention in Class
There is still no vaccine for malaria1. And despite efforts to prevent the mosquito bites that transmit the disease, it kills one child every 30 seconds and a total of one million people each year (for perspective, this is a full half of the number of people who die from AIDS each year).
Nations in areas where malaria is endemic use several tactics to control mosquito populations and some, like insecticide-treated bed nets (ITNs), have been very helpful in preventing deaths2. However, these methods mainly focus on killing the mosquitoes with insecticides and, while the tactics certainly do lower the number of bites and infections, they become less effective over time.
Because of genetic variation, some mosquitoes are naturally resistant to the insecticides used in anti-malaria campaigns. When insecticide is used, the mosquitoes with susceptible genes are killed and the resistant mosquitoes survive to pass the resistance on to future generations. Mosquitoes reproduce relatively rapidly, and, in some instances, populations have become resistant to insecticides within only a few years. In fact, resistance was a major impediment for the failed Global Malaria Eradication Campaign in the '50s and '60s. The situation could have been a case study in evolution and resistance in any introductory biology textbook. (Wait, that evolution lesson in high school bio was this important?)
All kidding aside, resistance to insecticides is a big problem in the war against malaria. It's not that people don't understand the concept, of course, it's just that there hasn't yet been a better alternative.
An effective and affordable vaccine would certainly be one of those alternatives. In the meantime, however, regions with endemic malaria will continue fighting the disease by controlling the mosquitoes that transmit it. Fortunately, a recent study3 by Dr. Andrew Read and his team at Pennsylvania State University might lead to another alternative. The researchers believe they have developed an approach to disease control that works around the problem of evolutionary resistance. When refined, they think the method could reduce the number of infectious bites by 95% and significantly prolong the useful life of an insecticide.
According to an article published in The Economist:
Dr Read started from the observation that it is old, rather than young, mosquitoes that are infectious. Only females can transmit malaria (males suck plant juices, not blood) but they are not born with the parasites inside their bodies. They have instead to acquire them from humans already carrying the disease, and that takes time. Once a female does feed on infected blood, the parasites she ingests require a further 10 to 14 days to mature and migrate to her salivary glands, whence they can be transmitted to another host when she next feeds. In theory, then, killing only the oldest female mosquitoes—those at significant risk of being infectious—could stop the transmission of the disease. Since these females would have had plenty of time to reproduce before they died, the evolutionary pressure imposed by killing them would be much lower.
So the question is: how do we kill only the old mosquitoes? More diluted insecticide solutions may work because older mosquitoes are more vulnerable than younger ones. Alternatively, experiments are underway with a fungus that becomes lethal to mosquitoes in 10 to 12 days, a short enough time period to kill them before they are at highest risk to transmit the parasite, but long enough that they can reproduce and pass the susceptible genes on. Other insecticide compounds might also have the desired effect. The authors of the study label insecticides that act in this manner "late-life-acting," or LLA, insecticides.
Unfortunately, current policies are structured to select insecticides for their ability to deliver rapid mortality in exactly the population that leads to the highest pressure for development of resistance. According to the study, the World Health Organization (WHO) requires, for laboratory testing approval, that insecticides target greater than 80% mortality within 24 hours post-exposure for young female mosquitoes.
The authors concede that insecticides that work in this way have greater initial effectiveness in reducing mortality, but point out that they provide "very poor medium- to long-term disease control" because of the effects of resistance. With the Global Malaria Action Plan (GMAP) aiming to spray 172 million houses with insecticide annually and to distribute 730 million ITNs by 2010, they write, the threat of widespread resistance would be unprecedented if the program is implemented with existing insecticides.
Hopefully, this study will begin a conversation that leads to further research into LLA insecticides. And, hopefully, it will help high school students bridge the gap between the (sometimes sleepy) theory in the classroom and its real, life-or-death implications out in the world. Thankfully, Dr. Read must have paid attention on the day he was given this lesson.
1 Fortunately, a major clinical trial by GlaxoSmithKline and Gates Foundation-funded Path Malaria Vaccine Initiative is underway and, if successful, would mean vaccines could be available by 2013.
2 According to the U.S. Center for Disease Control, insecticide-treated bed nets, or ITNs, have been shown to reduce mortality by 20% in field trials. For an interesting account of local production of ITNs (vs. traditional production in Asia), see Jacqueline Novogratz's presentation upon accepting the CASE Leadership Award (roughly 17 minutes in).
3 I recommend reading the study, entitled "How to Make Evolution-Proof Insecticides for Malaria Control," as it explains some interesting facets to the fight against malaria, including the implications of current methods of insecticide use, the process by which proposed insecticide compounds are approved by the WHO, and practical recommendations for next steps.
