Chemical paths

Frequent use and misuse of antimalarials [drugs that fight malaria] can lead to malaria parasites that are resistant to existing treatments. For this reason, there "is an urgent need for new drugs to combat malaria". "Researchers report that they have discovered -- and now know how to exploit -- an unusual chemical reaction mechanism that allows malaria parasites and many disease-causing bacteria to survive."

The same research team from the University of Illinois, led by Eric Oldfield, developed an inhibitor of a pivotal chemical reaction. This inhibitor may fight malaria [and other bacterial and parasitic diseases] in a manner that is different from the traditional medicines. The situation is dire, according to Oldfield. "The parasites that cause malaria also have become resistant to quinine, chloroquine and now, artemisinin, three common treatments for the disease."

"The new study focuses on an essential chemical pathway that occurs in malaria parasites and in most bacteria but not in humans or other animals, making it an ideal drug target." An enzyme, known as IspH, promotes the assembly of a "class of compounds, called isoprenoids, which are essential to life" and prove to be necessary to the bacteria and parasites that cause disease.

"Isoprenoids are the largest class of compounds on the planet," Oldfield said. "There are over 60,000 of them. Cholesterol is an isoprenoid. The orange beta-carotene in carrots is an isoprenoid. And bacterial cell walls are made using isoprenoids." After a decade of research, scientists believe that they understand the structure and function of IspH and hope that it will "allow them to find a way to... shut down production of isoprenoids in the disease-causing bugs," thereby reducing their numbers.

"We're really at the initial, key stage, which is understanding structure and function and getting clues for inhibitors -- drug leads," he said. "But there are a finite number of proteins unique to bacteria and malaria parasites that can be targeted for the development of new drugs. And everyone agrees that this enzyme, IspH, is a tremendous target."

Further research:
Eric Oldfield et al. Bioorganometallic mechanism of action, and inhibition, of IspH. Proceedings of the National Academy of Sciences, Feb 15, 2010. http://www.news.illinois.edu/WebsandThumbs/Oldfield,Eric/0215pnas.200911087.pdf
The National Institute of General Medical Sciences at the National Institutes of Health funded this research.


Source:
University of Illinois at Urbana-Champaign (2010, February 16). New weapon to fight disease-causing bacteria, malaria developed. ScienceDaily. Retrieved February 16, 2010, from http://www.sciencedaily.com¬ /releases/2010/02/100215173944.htm

Photo source:
http://insciences.org/article_album_file.php?article_id=8350&articlemedia_id=1069

Genetically-engineered malaria vaccine

Scientists have created a "weakened strain of the malaria parasite" that "will be used as a live vaccine against the disease." This type of vaccine "has proven successful in eradicating smallpox and controlling diseases such as flu and polio" (Walter). It has already been advantageous in animal studies, and it is hoped that it will prove successful when it enters human trials (slated for early next year).

Professor Alan Cowman, head of the Walter and Eliza Hall Institute's Infection and Immunity division, said that "in developing the vaccine the research team...deleted two key genes in the Plasmodium falciparum parasite - which causes the form of malaria most deadly to humans" (Walter). "The deletions did not affect the parasites throughout most of the life cycle," but "by removing the genes the malaria parasite is halted during its liver infection phase, preventing it from spreading to the blood stream where it can cause severe disease and death" (Cowman; Walter). The photo to the left shows the parasitic cells during the liver stage (WT is normal).

The fact that the deletion of the genes "did not result in any observable defect during blood-stage replication...indicated that gene deletions did not affect the sexual stages of the parasite" (Cowman). "Although two genes have been deleted the parasite is still alive and able to stimulate the body's protective immune system to recognize and destroy incoming mosquito-transmitted deadly parasites" (Walter).

"Similar vaccines" have "been tested in mice and offered 100 per cent protection against malaria infection." Cowman "said it was hoped the vaccine would produce similar results in humans" (Walter). Whenever working with an attenuated [definition: weakened] strain of a disease, mutation is always a concern. Some people fear that the parasite will mutate to a viable form, thereby infecting individuals through the vaccine. "Professor Cowman said it was unlikely the weakened parasites used in the vaccine would regain their potency as the genes had been deleted from the genome and could not be recreated by the parasite" (Walter).

The fact that two essential genes have been deleted "make it extremely unlikely that the attenuated parasite vaccine could restore its capacity to multiply and lead to disease." The scientists believe that their "genetically attenuated parasite approach provides a safe and reproducible way of developing a whole organism malaria vaccine," which has the unique ability of being nearly 100% effective (Walter).


Sources:
Cowman, Alan F. et al. "Preerythrocytic, live-attenuated Plasmodium falciparum vaccine candidates by design." 10 June 2009.

Walter and Eliza Hall Institute (2009, August 24). First Genetically-engineered Malaria Vaccine To Enter Human Trials. ScienceDaily.

Microchip detects malaria in Glasgow

"Scientists from Glasgow University claim they have created a device which can detect malaria within minutes." A microchip has been created to detect the malaria parasites in a blood sample. After the "blood samples are placed in the microchip" the device detects "the strain of disease. This means the best drug can be used to treat it." This method of detection is much better than previous methods because it is more accurate and faster (BBC).

"The current way of diagnosing is using a blood smear on a slide and examining it on a microscope," said project-leader Dr Ranford-Cartwright. "That will take a good microscopist a good hour to reach a diagnosis, it's extremely difficult to make that diagnosis accurately." This microchip "can give us a result in as little as half an hour."

Although malaria is less prevalent in the UK than in tropical regions of the world, it is not absent. "Last year a study revealed more cases of the most dangerous type of malaria than ever before are being brought back to the UK from trips abroad." Most malaria infections are imported, but the number of detected cases is rising. "The Health Protection Agency study identified 6,753 cases of falciparum malaria diagnosed between 2002 and 2006" (BBC).

Correct diagnosis is only one step toward malaria eradication. Another involves the development and use of effective drugs in the fight against the parasite. Ranford-Cartwright leads several research programs at the University of Glasgow including studies that examine the genetic markers for drug resistance. She says, "For this work we maintain different species of Anopheles mosquitoes in insectaries, and we infect them with P. falciparum sexual stages grown in culture. We use genetic techniques to study complex traits such as the interaction between the malaria parasite and its mosquito vector. We are also involved in work to identify factors important in the spread of anti-malarial resistance" (Ranford-Cartwright). "There is" further "need for a specific, sensitive, robust, and large-scale method for diagnosis of drug resistance genes in natural Plasmodium falciparum infections" (Abdel-Muhsin).

Sources:
Abdel-Muhsin, AM. LC Ranford-Cartwright, et al. "Detection of mutations in the Plasmodium falciparum dihydrofolate reductase (dhfr) gene by dot-blot hybridization." Am. J. Trop. Med. Hyg., 67(1), 2002, pp. 24-27

BBC News. "Doctors welcome Malaria Microchip." 24 April 2009.

Ranford-Cartwright, Lisa. "Research Interests." University of Glasgow. 7 August 2009.