Daily Archives: January 26, 2011

George is OK: Thank the men who stare down microscopes!

The news that actor George Clooney contracted malaria on a recent visit to Sudan focuses fresh attention on the biomedical research that is being done to defeat the disease.

Anopheles funestus, a mosquito which spreads malaria in the Sudan. CDC Public health Image Library

Clooney said that he is “completely over the disease,”  and added  that his second bout with the illness “illustrates how with proper medication, the most lethal condition in Africa can be reduced to a bad 10 days instead of a death sentence.”

 

While the news reports don’t state which drugs Cloony took to beat malaria, It is most likely that he was treated with artemisinin-based combination therapies (ACTs), which became available in the late 1990s and are now in widespread use.  If that is the case, he has benefited from mouse studies done in China the late 1960s and early 1970s when over 100 traditional herbal remedies were screened in a rodent model of malaria for anti-malarial activity (1). Eventually “Project 523” scored a hit when Professor Tu Youyou identified an extract of the plant qinghao, scientific name Artemisia annua, which had good anti-malarial activity, leading to the development of the artemisinin-based anti-malarials which have become the first-line treatment for malaria in the past decade.

Due to the real risk that malaria will evolve resistance to artemisinin – evidence of this have already been observed – the World Health Organization guidelines for the treatment of malaria stress that artemisinins must always be used alongside other anti-malarial drugs in artemisin-based combination therapy (ACT).  Of course the medical community isn’t just going to rely on combination therapies to slow the development of drug resistance in malaria, efforts are underway to develop new antimalarial drugs, such as the drug Arterolane which recently performed well in phase II clinical trials and whose preclinical development relied heavily on assessment in rodent models of malaria.

Nevertheless, the statistics on malaria are horrendous.  Roughly half of the world’s population is at risk for the disease.   Annually, there are an estimated 350 to 500 million cases, and every year one million people die of malaria every year – and 85% of those are children under the age of 5.

Despite the success of ACTs in combating malaria and dramatically reducing the number of deaths in many countries, sustained research is needed to develop new medicines to replace those that are losing effectiveness due to growing resistance in malaria’s parasite hosts. 

Additionally, scientists are working to develop a vaccine.  Two years ago, Speaking of Research took a look at one effective vaccine candidate, RTS,S , which is now in Phase III clinical trials.  RTS,S, a first-generation vaccine with 30- 50% protection in infants and children lasting about one year, is currently planned for release in 2015. Writing about RTS,S in 2009 Paul wrote about the important role basic and applied animal research played in its development:

The clinical development of RTS,S has been a long process that began as a collaboration between the Walter Reed Army Institute of Research (WRAIR)and GlaxoSmithKline in the late 1980s. Two key discoveries guiding the development of RTS,S were the finding in mice (3) that in order to immunize against malaria infection it is necessary to stimulate a cell-mediated immune response in addition to an antibody-mediated response, and the simultaneous discovery by scientists at WRAIR that incorporating a hepatitis B surface antigen into the malaria vaccine construct improved its ability to induce an immune response in mice and rabbits (4). 

Other vaccines are in earlier stages of development and also hold promise.  Some are being combined with RTS,S, which may lead to a highly efficacious vaccine in 8 to 15 years. One of these vaccines that is being developed by Dr. Simon Draper and colleagues at Oxford University was discussed on the Pro-Test blog in 2008 and has the advantage over RTS,S that it induces immunity against all stages of the malaria parasite’s life cycle, not just the liver stage that RTS,S targets. Further refinement of this and other vaccines – a process that, as a review led by vaccine expert Professor Adrian Hill  of the Jenner Institute in Oxford describes,  involved the study of a variety of combinations of viral vectors with malarial genes in rodent models of malaria – has yielded six candidate vaccines that are now being assessed for safety and anti-malarial activity in early clinical trials in humans.

Speaking of Research celebrates George Clooney’s rapid recovery, even as we advocate for the ongoing animal research that will lead to millions of lives being saved through the treatment, control, prevention and eventual eradication of malaria from the planet.

1)       Liwang Cui and Xin-Zhuan Su “Discovery, mechanisms of action and combination therapy of artemisin” Expert Rev Anti Infect Ther. 2009 October ; 7(8): 999–1013. doi:10.1586/eri.09.68.)