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Malaria is a global crisis

Malaria is one of the three deadliest infectious diseases on Earth. Over three billion people are at risk of becoming infected with malaria. There are over two hundred million clinical cases of malaria each year, and over one million people are killed by malaria infections every year. The groups of people who are especially vulnerable to malaria infections are children and pregnant women.  Every 30 seconds, another child dies of malaria.

Plasmodium falciparum, the protozoan parasite that causes the most severe form of malaria, kills more people than any other parasite on the planet. Four other species of Plasmodium can also cause malaria infections in people (Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, and Plasmodium knowlesi), but these four species tend to cause a milder form of malaria that is rarely fatal. Plasmodium vivax causes the largest number of malaria infections each year, but Plasmodium falciparum causes about 90% of the deaths that result from malaria infections. Consequently, most of our research on GO Fight Against Malaria will focus on Plasmodium falciparum, but we will also perform some research against the molecular targets from Plasmodium vivax.

Malaria infections are transmitted to humans by certain types of mosquitoes. Female mosquitoes from the genus Anopheles are the specific kinds of mosquitoes that are responsible for hosting and then spreading malaria infections. Since male mosquitoes eat plant nectar instead of blood, only the females transmit malaria infections. Female mosquitoes become infected with the malaria parasite when they drink the blood of a human who has a malaria infection. After being ingested by a mosquito, the parasite progresses through specific stages of its life cycle that can only occur when it is inside a mosquito. When that infected female mosquito then feeds on a different person, its saliva contains the malaria parasite, which gets injected into the person’s skin.  When these parasites replicate themselves in our red blood cells (which the parasites use for food), the symptoms of malaria appear.  Malaria initially causes fevers and headaches, and in severe cases it leads to comas or death.

Detailed descriptions and amazing visualizations of the malaria parasite’s life cycle in both mosquitoes and humans were created by Drew Berry and are available at:  http://youtu.be/zqJIrhLCFgQ?hd=1  (part 1 = human stages) and http://youtu.be/I_qSrFPjtQw?hd=1 (part 2 = mosquito stages). Note: Drew Berry was a 2010 MacArthur Foundation Fellow (that is, he received one of those "genius grants").

The Drew Berry clip on the Plasmodium falciparum parasite's life cycle within humans (listed above):

 

The Drew Berry clip on the malaria parasite's life cycle within the mosquito host (listed above):

 

 

In very rare cases, blood transfusions can also transmit malaria infections, but female mosquitoes are the main culprit.

Malaria thrives in tropical and subtropical regions. Malaria infections are found in at least 106 different countries. It predominantly infects people in Africa, South-East Asia, and South America. However, in this era of globalization, it affects almost all sub-populations of the world, either physically, mentally, or monetarily. Millions of people from developed countries visit or work in malaria-infested regions each year.

After a person has become infected with malaria, "chemotherapeutic approaches" are employed (that is, a drug or a combination of different drugs is used to cure the malaria infection). There are many different drugs that can be used to cure malaria infections; however, the parasites that cause malaria eventually evolve “drug resistance” against the specific chemicals that are used to eliminate the parasites.  Being "resistant" to a drug means that the specific target protein molecule, whose activity the drug blocks, has changed (or "mutated"), and the drug is no longer effective at treating the infection.  But at the same time, the mutation does not prevent the superbug from surviving and reproducing.   Being multi-drug-resistant means that the pathogen has acquired mutations that allow it to escape several different types of drugs simultaneously, while still allowing the pathogen to thrive and spread itself.  Since the ability to escape treatment by the drugs helps the parasite survive and multiply, these drug-resistant strains have a selective advantage that helps them out-compete the regular (“wild type”) strain of the parasite, which allows the superbugs to become persistent and widespread.

The World Health Organization's 2001 report on "Drug Resistance in Malaria" indicates that the parasite Plasmodium falciparum has  already developed resistance to nearly all anti-malaria drugs.  For example, in the past the drug chloroquine was very useful for curing malaria infections, but the Plasmodium parasites eventually evolved drug resistance against chloroquine. Later, the dual drug combination of sulfadoxine plus pyrimethamine was developed. For several years it was very useful for curing malaria infections, and it helped save millions of lives. But then the Plasmodium parasites evolved resistance to this dual drug combination, too. Since resistance to sulfadoxine plus pyrimethamine started becoming very prevalent, the World Health Organization now recommends that artemisinin-based combination therapies (“ACTs”) be used to treat malaria infections. Unfortunately, Plasmodium falciparum parasites that are able to resist treatment with artemisinin, and its derivatives, have recently started to appear at the Thai-Cambodian border. Because new mutant superbugs keep evolving and spreading throughout the world, discovering and developing new types of drugs that can kill the multi-drug-resistant mutants is a significant global health necessity.  The drug resistance phenomenon is the reason why we created the GO Fight Against Malaria project.

 

The GO Fight Against Malaria logo was created by Stefano Forli, Ph.D., a Research Associate in Prof. Art Olson's lab at TSRI.