Battling malaria

"Scientists battling malaria have earned a major victory", according to a Nature Genetics study. "Combating malaria resistance is nothing short of an arms race," says author and pediatrics professor, Dr. Philip Awadalla, from the Universite de Montreal. "As the malaria pathogen evolves, researchers must evolve with it to find ways to counter the disease."

Every year approximately 250 million people contract malaria. "Malaria is transmitted when people are bitten by infected mosquitoes. According to the World Health Organization, malaria symptoms include fever, headaches, vomiting and appear within 10 to 15 days after an infected mosquito bite." If left "untreated, malaria can be life-threatening" and may kill "an estimated five million people yearly." At the current level of malaria treatment one million people die annually, and most of those who die are young children.

The team at Universite de Montreal is deciphering the deadly parasite in an effort to eradicate the disease. This "international group of researchers has used genomics [study of organisms' genomes] to decode the blueprint of Plasmodium falciparum -- a strain of malaria most resistant to drugs that causes the most deaths around the world. The discovery may lead to advanced pharmaceuticals to fight the disease and prevent drug resistance".


"The team decoded 200 malaria samples from Asia, Africa, Central America, South America and Papua New Guinea. Their goal was to identify how Plasmodium falciparum strains were becoming resistant to the eight anti-malaria drugs currently available." The team noted how there is "substantial genetic differences in malaria around the world. What has occurred is a combination of genetic drift, where genes segregated over space and time from differential environments, immune pressures and exposures to drugs."

Research discovered that "Plasmodium falciparum recombined fastest in Africa...New clues garnered by this study...will allow pharmaceutical companies to create treatments that target the evolving malaria genome."

Sources:

Mu et al. Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs. Nature Genetics, 2010; DOI: 10.1038/ng.528

University of Montreal (2010, February 18). Genomic warfare to counter malaria drug resistance. ScienceDaily. Retrieved February 20, 2010, from http://www.sciencedaily.com¬ /releases/2010/02/100216140146.htm

King Tut's Curse

Celebrities draw attention to the diseases that ail them. This is true even if the celebrity is over three-thousand years old. Several media channels released reports pinning the death of King Tutankhamun, a famous pharaoh who died at a young age, on "a severe bout of malaria combined with a degenerative bone condition" (New York Times).

Results from the recent study of Tut's mummy show that he had several genetic bone disorders and that he was "afflicted with avascular bone necrosis, a condition in which diminished blood supply to the bone leads to serious weakening or destruction of tissue." In an already weakened individual, malaria is often fatal. "The finding led to the team's conclusion that it and malaria were the most probable causes of death" (New York Times).

Malaria was nearly impossible to escape during the time of King Tut. Mosquitoes bred in the Nile Valley, fed off whomever they encountered--royalty or not--and carried malaria. In modern times, approximately one million people die from malaria every year. Most of those who die are children, women, and already ill people. Today, a malaria-stricken individual can be treated for malaria. A variety of drugs combat the malaria parasites that cause illness in humans. Malaria can also be prevented through the use of insecticides, mosquito nets, and preventative medicines.


King Tut may not have been so lucky. While the pharaoh may have been able to hide from mosquitoes behind a bed net (a method of malaria prevention still used today), he did not have extensive medical treatments available to him--a fate that still befalls many today.


250 million cases of malaria are reported annually. Many of the humans who fall ill to malaria do not have the medical resources they need to survive. Over three-thousand years after Tut's death, people still suffer and die from malaria. But now, malaria is treatable and preventable. The problem is getting the necessary medical treatment to those in need.

My suggestion: Let the dead do what they do, and worry instead about the people dying today.


Support Roll Back Malaria and Malaria No More. Treating a bout of malaria costs under $5.00. A $10 bednet can save two lives.

Sources:
New York Times. Wilford, John Noble. "Malaria Most Likely Killed King Tut, Scientists Say." 16 February 2010.

Telegraph. Alleyne, Richard. "King Tut died of malaria and bone condition, says new research." 16 February 2010.

Credit: @followthethread deserves recognition for her alert. She's on my Do Not Bite list.

Photo source: Bjørn Christian Tørrissen (via wikimedia creative commons archives)

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

Substandard Medicines

"A high percentage of medicines circulating on national markets", in ten Sub-Saharan African countries, "are of substandard quality and thus may contribute to the growth of drug-resistant strains of Plasmodium falciparum, the most virulent form of malaria." First results of the "large-scale study of key antimalarial medicines" were released for Madagascar, Senegal, and Uganda by the Promoting the Quality of Medicines (PQM) Program, a USAID-funded program.

"Within Madagascar, Senegal and Uganda, the study" focused "on artemisinin-based combination therapy (ACT) products, currently the WHO's recommended form of first-line treatment for uncomplicated malaria, and sulfadoxine-pyrimethamine (SP) products, often used for preventative treatment of malaria during pregnancy." Researchers collected samples from "public and regulated private sectors" and from "informal markets, as many patients obtain their medicines from these sources."

"Substandard and counterfeit versions of antimalarial medicines are highly problematic throughout Africa, Asia and Latin America because of the direct threat they pose to the lives of individual patients as well as their contribution to the development of drug-resistant strains of these diseases." The "study found that approximately 44 percent of sampled medicines from Senegal, 30 percent of samples from Madagascar, and 26 percent of samples from Uganda that underwent full quality control laboratory testing failed such testing and were thus substandard."

"Substandard" medicines are classified as "those that do not meet the quality specifications set for them, primarily because they do not contain the correct amount of the active ingredient(s), do not dissolve properly in the body or include unacceptable levels of potentially harmful impurities." According to the released results, "[n]o samples in the full study completely lacked the active ingredient(s). The results also showed that, as a general rule, when a brand passed or failed in one country, it would also pass or fail in other countries. This indicates that the problem of quality is created at the source, rather than during passage through the distribution chain."

Substandard medicines were not limited to informal markets, and their point of sale varied by country. "In Madagascar, for instance, poor quality medicines appear to be widespread across regions and not limited to any particular type of distributor [public, private, or informal]. In Uganda, samples fared much better in the public sector than in the country's private sector. Despite overall failure rates, this was one of the bright spots the study revealed; in Uganda's public sector, all ACT and SP samples passed quality tests."

The purpose of this study was reveal "the prevalence of substandard antimalarials in Sub-Saharan Africa, which are believed to contribute to antimicrobial resistance of Plasmodium falciparum. Already, Plasmodium falciparum has become resistant to traditional" treatments "such as chloroquine, and more recently to SP products. The sustainability of treatment success depends to a large extent on preventing Plasmodium falciparum's exposure to incomplete doses of these medicines to minimize the possibility of the emergence of drug resistance."

Source:
US Pharmacopeia (2010, February 10). One-third of antimalarial medicines sampled in three African nations found to be substandard. http://vocuspr.vocus.com/vocuspr30/Newsroom/ViewAttachment.aspx?SiteName=USPharm&Entity=PRAsset&AttachmentType=F&EntityID=108111&AttachmentID=f2e22216-44a5-41a2-a9bc-464b7a98e3bf

Malaria vaccine to protect pregant women

"Each year, 25 million pregnant women in sub-Saharan Africa run the risk of contracting malaria." Women who become infected during their first pregnancy are at the most risk for severe anemia and poor fetal growth. "The malaria parasites accumulate in the placenta, resulting in children being born prematurely and underweight." Maternal malaria causes the death of approximately 200,000 infants and 10,000 women each year

"Researchers at the University of Copenhagen have become the first in the world to synthesize the entire protein that is responsible for life-threatening malaria in pregnant women and their unborn children. The protein known as VAR2CSA enables malaria parasites to accumulate in the placenta and can therefore potentially be used as the main component in a vaccine to trigger antibodies that protect pregnant women against malaria. The research team is now planning to test the efficacy of the protein-based vaccine on humans."

"The hope is that within 10 years all African girls could be vaccinated against maternal malaria, thereby preventing more than 200,000 deaths a year." The vaccine "elicits antibodies that stop the [malaria] parasite from binding to the placenta." Laboratory testing is underway, and the vaccine can already be tested in animals.

"These antibodies seem to be effective at preventing the parasite from accumulating in the placental tissue. The next step is to investigate whether we can elicit the same antibodies and so protect against the disease by vaccinating humans. Then the vaccine will be a reality."

Source:
University of Copenhagen (2010, February 5). Vaccine to protect pregnant women from contracting malaria?. ScienceDaily. Retrieved February 12, 2010, from http://www.sciencedaily.com­ /releases/2010/02/100204144433.htm

Pregnant women at risk

Pregnancy, for most women, means planning for a safe and healthy baby, but in malaria-endemic regions, fear of mortality outweighs hope. At "least 125.2 million women" who are at risk of contracting malaria "become pregnant each year".

Malaria during pregnancy creates disaster, causing "miscarriages, preterm births," low-birth-rate, and death. "About 10,000 women and 200,000 babies die annually because of malaria" during pregnancy. "Most malaria deaths are caused by Plasmodium falciparum, which thrives in tropical and sub-tropical regions", but "the most widespread type of malaria is P. vivax malaria, which also occurs in temperate regions." Estimates on the burden of malaria were previously only available for Africa", but now include lesser-realized endemic regions.

"The researchers estimated the sizes of populations at risk of malaria in 2007 by combining maps of the global limits of P. vivax and P. falciparum transmission with data on population densities. They used data from various sources to calculate the annual number of pregnancies (the sum of live births, induced abortions, miscarriages and still births) in each country. They calculated the annual number of pregnancies at risk of malaria in each country by multiplying the number of pregnancies in the entire country by the fraction of the population living within the spatial limits of malaria transmission in that country."

"This study contributes to the global understanding of the risk of malaria in pregnancy. In 2007, 54.7 million pregnancies occurred in areas with stable P. falciparum malaria and a further 70.5 million in areas with exceptionally low malaria transmission or with P. vivax only. This marks the first time species specific risks have been estimated globally for malaria in pregnancy."


Source:
Dellicour S, Tatem AJ, Guerra CA, Snow RW, ter Kuile FO. Quantifying the Number of Pregnancies at Risk of Malaria in 2007: A Demographic Study. PLoS Medicine, 2010; 7 (1): e1000221 DOI: 10.1371/journal.pmed.1000221

Lost Code

Although made of few parts, the complete DNA content or genome of a species is extensive and complicated. Plasmodium falciparum, "the most deadly form of malaria", has about 5,300 genes. "Up until now, scientists [had] a good understanding of the gene functions for only about half" of the genes.


Plasmodium falciparum is a tiny parasite that infects the blood of mammals through mosquito bites and is responsible for approximately 1 million human deaths each year. "Using transcriptional profiling," a process by which "gene expression (activity) patterns" are revealed, the research team lead by Prof Zbynek Bozdech (Nanyang Technological University) "has successfully uncovered the gene functions for almost the entire genome, with more than 90 percent of the gene functions from the previously unknown half now better understood."


"Transcriptional profiling is the measurement of the activity of thousands of genes at once," in order to "create a global picture of cellular function. These profiles can, for example, distinguish between cells that are actively dividing, or show how the cells react to a particular treatment. This outcome in infectious disease pathology could potentially be the decade's big breakthrough as it has yielded critical information about how the malaria parasite...responds to existing compounds with curative potential."


"Preventing malaria infection is important because resistance to anti-malaria drugs is a growing problem worldwide. There is currently no vaccine for malaria, which is widespread in poorer countries where it remains a hindrance to economic development. Also of growing concern to scientists is the confirmation of the first signs of resistance to the only affordable treatment left in the global medicine cabinet for malaria: Artemisinin."


"In successfully using transcriptional profiling to study the behavior of the malaria parasite, ...researchers have ventured into the unknown and paved the way for future breakthroughs in healthcare."

Sources:
Gastin, George. "GenomeGradient.jpg" [Photo hosted by wikimedia, shared under CC license] http://commons.wikimedia.org/wiki/File:Genome_gradient.jpg

Nanyang Technological University (2010, February 6). World's first in-depth study of the malaria parasite genome. ScienceDaily. Retrieved February 7, 2010, from http://www.sciencedaily.com /releases/2010/02/100205102607.htm

Protective immunity

Every year approximately a million people die from malaria, a treatable blood disease, and most of those who die are children under the age of five. "A new vaccine to prevent the deadly malaria infection has shown promise to protect the must vulnerable patients--young children--against the disease."

The results found by the international research team, led by the University of Maryland School of Medicine's Center for Vaccine Development (CVD) and the Malaria Research and Training Center at the University of Bamako in Mali, excites the medical community. "In a new study of the vaccine in young children in Mali, researchers found it stimulated strong and long-lasting immune responses. In fact, the antibody levels the vaccine produced in the children were as high or even higher than the antibody levels found in adults who have naturally developed protective immune responses to the parasite over lifelong exposure to malaria."

"In areas of the world such as Africa, where malaria is particularly rampant, the young are most vulnerable to the disease since they have not built up the same natural immunity as adults. A child dies of malaria every 30 seconds, according to the World Health Organization. There are about 300 million malaria cases worldwide each year, resulting in more than one million deaths, most of them African children."

Malaria is a parasite, "spread to humans through mosquito bites". At this time, "no approved vaccine to protect against the condition" exists, although "using bed nets or killing mosquitoes with insecticides can prevent infection. The parasite is treatable using medications, though drug resistance is a relatively common problem. Eradicating the disease has become a priority for scientists and health officials worldwide. An effective and broadly protective vaccine is a key step toward that goal."

This "vaccine, based on a single strain of the falciparum malaria parasite -- the most common and deadliest form of the parasite found in Africa -- targets malaria in the blood stage. The blood stage is the period after the mosquito bite, when the parasite multiplies in the blood, causing disease and death." Before this discovery, "other blood stage vaccines" existed, but none of them exhibited "the ability to prevent malaria disease."

In addition to preventing malaria, the vaccine (at all three tested doses) "proved to be safe and well tolerated" in each of the 100 Malian children administered with the drug. A new trial is already planned to test more subjects and to examine "whether the vaccine -- though it is based on a single strain of malaria -- can protect against the broad array of malaria parasites that exist."

Sources:
University of Maryland Medical Center (2010, February 6). New malaria vaccine is safe and protective in children, scientists find. ScienceDaily. Retrieved February 6, 2010, from http://www.sciencedaily.com­ /releases/2010/02/100203201425.htm

Lethal Weapon

"Mankind may finally have a weapon to fight two of the world's deadliest diseases." A new vaccine may prove to be a "lethal weapon against malaria" and cholera. Each year approximately a million people die from malaria and cholera sickens hundreds of thousands. Currently, "no FDA approved vaccine to prevent malaria, a mosquito-borne illness" exists. "Only one vaccine to fight cholera, a diarrheal illness that is common in developing countries and can be fatal" is on the market. "The lone vaccine is too expensive to prevent outbreaks in developing countries after floods, and children lose immunity within three years of getting the current vaccine."

Recently, a "University of Central Florida biomedical researcher has developed what promises to be the first low-cost dual vaccine against malaria and cholera."

Led by Henry Daniell, the "team genetically engineered tobacco and lettuce plants to produce the vaccine. Researchers gave mice freeze-dried plant cells (orally or by injection) containing the vaccine. They then challenged the mice with either the cholera toxin or malarial parasite…Untreated rodents contracted diseases quickly, but the mice who received the plant-grown vaccines showed long-lasting immunity for more than 300 days (equivalent to 50 human years)."

In addition to this vaccine, Daniell's lab has "created vaccines against anthrax and black plague that generated a congratulatory call from the top U.S. homeland security official and was featured on the Discovery Channel."

But, why lettuce? "Producing vaccines in plants is less expensive than traditional methods because it requires less labor and technology," Daniell said.

"We're talking about producing mass quantities for pennies on the dollar," he said. "And distribution to mass populations would be easy because it could be made into a simple pill, like a vitamin, which many people routinely take now. There is no need for expensive purification, cold storage, transportation or sterile delivery via injections."

"For Daniell, his research is more than his day job. His passion to find vaccines for the world's top 10 diseases as defined by the World Health Organization comes from growing up in India. He watched many of his childhood friends contract malaria, cholera and other diseases."

"I'm not done yet," he claims. "I still have more diseases to attack."

Source:
University of Central Florida (2010, January 27). New vaccine could be lethal weapon against malaria, cholera. ScienceDaily. Retrieved February 3, 2010, from http://www.sciencedaily.com¬ /releases/2010/01/100126101421.htm