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

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

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

Digestive enzymes

"Malaria causes more than two million deaths each year, but an expert multinational team battling the global spread of drug-resistant parasites has made a breakthrough in the search for better treatment" (McGill). Examining the way malaria parasites reproduce, a team led by John Dalton, has identified "a plan of attack" to develop new and urgently needed treatments, which combat malaria.

The secret lies in how the parasites propagate. "Malaria parasites live inside our red blood cells and feed on proteins". They break down the proteins to "use the proceeds (amino acids) as building blocks for their own proteins". Once they "a sufficient size they divide and burst out of the red cell, entering another and repeating the process until severe disease or death occurs."

Specialized digestive enzymes of the parasites "enable them to undertake this process." Researchers have now developed three-dimensional structures of these two enzymes and "demonstrated how drugs can be designed to disable the enzymes."

"By blocking the action of these critical parasite enzymes, we have shown that the parasites can no longer survive within the human red blood cell," Dalton explains. "The team is putting their findings into action immediately and is already pursuing anti-malarial drug development."

Publications: The discovery will be published in the Proceedings of the National Academy of Sciences, and is the result of collaboration including Australia’s Queensland Institute of Medical Research, Monash University and the University of Western Sydney, Wroclaw University of Technology in Poland and the University of Virginia in the U.S.

Read more about digestive enzymes and malaria

Source:
McGill University (2010, January 29). Breakthrough could lead to new treatment for malaria. ScienceDaily. Retrieved January 31, 2010, from http://www.sciencedaily.com¬ /releases/2010/01/100128165850.htm

Alarm amid medicine shortage

Kenya's rainy season is the most dangerous for contracting malaria, a deadly disease carried by mosquitoes, and children are the most susceptible. "A shortage of malaria drugs for children has hit hospitals as fears of an outbreak of the disease loom following heavy rains in various parts of the country."

"The Kenya Medical Supplies Agency said stocks of the drugs were running low, but were in the process of being procured and could be delivered by the beginning of February." The Chief executive, John Munyu, is hopeful that the crisis will be avoided because deliveries are continuing. He indicated that "adult malarial drugs are already being supplied after a reported shortage in parts of the country."

The minister of medical services, Anyang' Nyong'o, claims that "the shortage of drugs was caused by inadequate funding by the Treasury." The "budget for Health ministries was laughable when compared to that for the Ministry of Education", he says. This is not the first shortage that Kenya has suffered in recent years. Antibiotics used to treat cholera "were nearly exhausted due to last year's outbreak".

Still, Nyong'o is confident that disaster will be avoided. He says, "I do not envisage any crisis because the government is already adding stocks to what is already there in the health facilities. That is mere replenishment."

Ogo, Kenneth. "Children's malaria drugs run out." Daily Nation. 7 January 2010.

Critically weakened

What happens when a vampire does not feed on human blood?

If you believe the tales spun in Vampire Diaries, then the once-deadly creature becomes significantly weakened, looses the ability to affect the human brain, and is generally much less threatening than his human blood consuming counterpart. The same is true for the variety of parasite that Dr Andrea Crisanti is studying in an attempt to find a malaria vaccine.

Malaria, a mosquito-borne disease that affects 300-500 million people each year, is caused by infection with Plasmodium parasites. The deadly disease kills approximately one million people every year, most of whom are children and pregnant women, is treatable and preventable. The search for a malaria vaccine is well under way, but the "number of life cycle changes" that the parasites undergo increase "the challenges of malarial vaccine development." In other words, because the malaria parasites change and adapt rapidly, a workable vaccine is difficult to develop.

However, recent research by Crisanti and her colleagues "have found that weakened Plasmodium elicits a protective immune response." This means that clinically and genetically weakened parasites may be used for vaccine development. Crisanti's team targeted Plasmepsin 4, "a digestive enzyme that is critical for Plasmodium growth and survival within the host red blood cells." Research showed that parasites without the critical digestive enzyme "were significantly less virulent than their wild-type [define: normal] counterparts."

Furthermore, "infection with plasmepsin 4-deficient parasites, in contrast to infection with wild-type Plasmodium, did not induce cerebral complications", which means that infection with the weaker parasite produces a less severe illness than an ordinary malaria infection. Also, parasites without the digestive enzyme "induced strong protective immune responses against secondary immunization with wild-type Plasmodium." This weakened parasite may provide a model for comparing genetically-weakened malarial vaccines.

Dr. Crisanti and colleagues conclude that "it is possible, by engineered inactivation of parasite proteins, to generate attenuated blood stage parasites that are capable of inducing protective immunity against blood-stage infection. Such parasites should be powerful tools in elucidating parasite-derived factors that cause severe disease and should provide additional insight into factors that are required to induce protective immunity."

Source:
American Journal of Pathology (2009, December 31). Weakened Plasmodium generates protective immunity. ScienceDaily. Retrieved January 3, 2010, from http://www.sciencedaily.com¬ /releases/2009/12/091230193211.htm

Antimalarial side effects

In early October, a study comparing the side effects of commonly prescribed malaria medication was conducted by a team led by Dr. Frederique Jacquerioz at Tulane University. "The review looked at eight clinical trials" of commonly prescribed anti-malarials. Both "atovaquone-proguanil -- sold under the brand-name Malarone -- and doxycycline appear to have fewer side effects" than the other drugs tested. "With these two drugs, there is lower risk of nausea, stomach pain and other gastrointestinal side effects, and also neurological and psychiatric side effects, such as dizziness, sleep disturbances, anxiety and depression."

No drugs produced side effects that were considered life-threatening or required hospitalization; however, the investigators did discover a disturbing link between mefloquine and patient death. They uncovered "published case reports linking mefloquine to 22 deaths, including five suicides." It is important to note that "no other anti-malaria drugs have been linked to deaths when taken at prescribed doses".

Mefloquine is still an effective anti-malarial and may be safely prescribed to patients who have previously taken it without adverse effects. Doctors believe that risk of death is higher for patients who fail to take mefloquine when they should than the risk of serious side effects.

"[S]evere reactions to mefloquine are rare, noted Dr. Andrea Boggild of Toronto General Hospital in Canada, who was not involved in the study. In a written statement, Boggild said that severe neurological and psychiatric symptoms develop in just one out of every 6,000 to 10,000 people who take the drug."

In regard to antimalarial side effects, the Jacquerioz says this: "The main message is that you have to take some malaria chemoprophylaxis (preventive treatment) if you go to an endemic area". Malaria kills approximately one-million people each year, and an estimated ten-thousand to thirty-thousand travelers develop malaria annually.

"Boggild advised people who are planning a trip to a malaria-endemic area to talk with a healthcare provider who specializes in travel medicine about how to best protect themselves."

Source:
Reuters Health. " Two anti-malaria drugs have fewer side effects". Wednesday, October 7, 2009.

Genetic Diversity

"Scientists and health officials worldwide have made eradication of" malaria "a priority, with an effective and broadly protective vaccine a critical step toward that goal. Malaria -- a parasite spread to humans through mosquito bites -- is prevented by avoiding mosquito bites using bed nets or by killing mosquitoes with insecticides. The parasite is treatable using medications, although drug resistance is a relatively common problem. According to the World Health Organization, a child dies of malaria every 30 seconds" (University). Currently, "no approved vaccine for malaria" exists, but "various experimental vaccines are in development" (University). As of now, "vaccines directed against the blood stages of Plasmodium falciparum malaria [a deadly strain] are intended to prevent the parasite from invading and replicating within host cells. No blood-stage malaria vaccine has shown clinical efficacy in humans" (Takala).

"Researchers at the University of Maryland School of Medicine Center for Vaccine Development (CVD) have charted the extreme genetic differences that occur over time in the most dangerous malaria parasite in the world" (University). They "examined the extent and within-host dynamics of genetic diversity in the blood-stage malaria vaccine" and concluded that this "extreme diversity may pose a serious obstacle" to the creation of an effective vaccine.

"The CVD study suggests that developing a broadly protective vaccine for malaria may be challenging because the parasite's genetic makeup is so variable, constantly changing" (University).

Sources:
Takala, Shannon L. et al. "Extreme Polymorphism in a Vaccine Antigen and Risk of Clinical Malaria: Implications for Vaccine Development." Sci Transl Med 14 October 2009:
Vol. 1, Issue 2, p. 2ra5.

University of Maryland Medical Center. "Extreme Genetic Variability In Malaria Parasite Found." ScienceDaily 15 October 2009. 21 October 2009 .

Fungus reduces malaria transmission

"Biopesticides containing a fungus that is pathogenic to mosquitoes may be an effective means of reducing malaria transmission, particularly if used in combination with insecticide-treated bednets" (Public). Mosquito adaptation and resistance to insecticides is a major hindrance to malaria eradication. "In developing strategies to control malaria...there is increased interest in biological methods that do not cause instant" mosquito or parasite death. Instead, scientists are searching for preventative measures, which "have sublethal and lethal effects at different ages and stages in the mosquito life cycle", with the hope that these more mild approaches will be more effective in the long run than the aggressive techniques used in the past. (Hancock).

"[A]ccording to a modelling study conducted by Dr. Penelope Hancock from Imperial College London," incorporating fungal biopesticides "may substantially reduce malaria transmission rates and help manage insecticide resistance...Efficient combinations of interventions may allow each to be used at lower levels, and slow the development of resistance in the mosquito population" (Public).


Sources:
Hancock, Penelope A. "Combining Fungal Biopesticides and Insecticide-Treated Bednets to Enhance Malaria Control".

Public Library of Science. "Control Of Mosquito Vectors Of Malaria May Be Enhanced By A New Method Of Biocontrol." ScienceDaily 1 October 2009. 7 October 2009 .

Herbal medicine

"An ancient Chinese folk medicine that's effective against malaria also might be a potent cancer-fighting candidate, scientists at the University of Washington say" (Hill). "A derivative of the sweet wormwood plant used since ancient times to fight malaria and shown to precisely target and kill cancer cells may someday aid in stopping breast cancer before it gets a toehold" (Harril). "Artemisia annua...has shown favorable...results" against "breast cancer and prostate cancer" (Artemisinin).

"The substance, artemisinin, appeared to prevent the onset of breast cancer in rats that had been given a cancer-causing agent." Artemisinin is "selectively toxic to cancer cells" (Harril). "The compound appears to be extremely" harmful "to cancer cells but had little impact on normal cells," according to the researchers (Hill).

"The properties that make artemisinin an effective antimalarial agent also appear responsible for its anti-cancer clout. When artemisinin comes into contact with iron, a chemical reaction ensues that spawns free radicals -- highly reactive chemicals that, when formed inside a cell, attack the cell membrane and other structures, killing the cell...The malaria parasite can't eliminate iron in the blood cells it eats, and stores it. Artemisinin makes that stored iron toxic to the parasite...The same appears to be true for cancer. Because they multiply so rapidly, most cancer cells have a high rate of iron uptake. Their surfaces have large numbers of receptors, which transport iron into the cells. That appears to allow the artemisinin to selectively target and kill the cancer cells, based on their higher iron content" (Harril). "In addition," artemisinin has already "been shown to be safe" in humans, as is evident in malaria patients who have taken the drug (Hill). Artemisnin may provide an alternative for harsh chemotherapy in some cancer cases.


Sources:
“Artemisinin Herbal Extract Cures Malaria, Breast Cancer and Leukemia”. Associated Content. 29 March 2009.

Harril, Rob. “Malaria drug may help prevent breast cancer, study shows”. University Week. Jan. 12, 2006

Hill, Richard. The Oregonian, 28 Nov 2001 p C12.

Koresby Online. Artemisinin Annua. (Photo)

Malaria and antibiotics

Malaria is a parasite that is transmitted by mosquitoes and infects a million people a year. Since this disease is not caused by a bacterium, how is it that antibiotics affect malaria and improve the health of sickened individuals?

From 1920 to 1950, antibiotics were a widely used treatment for malaria, although medical practitioners were not entirely sure why this treatment was so effective (Butcher). In the early 1980s, it was "discovered that antibiotics ... are active as antimalarial agents" (Oronsky). More recently, azithromycin [also called Zithromax] has been used to treat malaria in Ethiopia after it was shown "to have efficacy in the prevention and treatment of malaria due to both Plasmodium falciparum and Plasmodium vivax," (Travis).

After research, scientists have hypothesized that antibiotics treat malaria because they attack the plasmodia (a protozoa) within the parasites; therefore the antibiotics diminish the malaria" (Flam). Furthermore, antibiotics alleviate the immune system of other infections that may coexist with malaria.

"The treatment may also have unintended consequences...including the inducement of antibiotic resistance" (Travis). However, the situation is further complicated by the development of drug-resistant bacteria in malaria-infested areas that have had no exposure to antibiotics.

As mysterious as the seemingly unfounded effectiveness of antibiotics on malaria in the 20th century, the unexplained drug-resistant bacteria in "remote rainforest communities in Guyana" confounded scientists (Juncosa). New studies revealed "that overuse of a drug used to prevent and treat malaria may be contributing to growing antibiotic resistance...Drug-resistant bacteria are known to arise from the overuse of antibiotics, which is why researchers were surprised to discover that they can develop in areas that do not have access to" that particular antibiotic [ciprofloxacin]. Michael Silverman, "an infectious disease specialist at Lakeridge Health Network in Ontario" says that antibiotic-resistant E. coli were more widespread in these remote Guyanese villages than in U.S. hospitals "where every second person is on antibiotics." Silverman's study showed that the patients infected with drug-resistant E.coli had been "given the drug chloroquine to prevent and treat malaria" (Juncosa).

According to Silverman, "It is very possible that the antimalarial drugs may be inducing a large amount of the antibiotic resistance that occurs in the tropics." Unfortunately, "plasmodia, the causative organisms of malaria, have developed resistance to antibiotics" as well and "at the same time, the mosquitoes that carry plasmodia have become resistant to the insecticides that were once used to control them. Consequently, although malaria had been almost entirely eliminated, it is now again rampant in Africa, the Middle East, Southeast Asia, and parts of Latin America" (MSN).

The increasing number of drug-resistant strains of malaria parasite, plasmodia, and other bacteria is another reason why an effective malaria vaccine is so important. We cannot continue treating malaria in the ways that we have in the past, for very soon, these old methods will be rendered ineffective.

Sources:
Butcher, Geoff. “Million Murdering Death.” History Today April 1998: 24-28.

Flam, Fray. “Scientists Find Weak Spot in Defense of Tenacious Malaria Parasite.” Tribune News Service November 1997: 26-28.

Juncosa, Barbara. "Antibiotic Resistance: Blame it on Lifesaving Malaria Drug?" Scientific American 21 July 2008.

MSN Encarta."Antibiotics"

Oronsky, Arnold L. Treatment of malaria with antibiotics. "United States Patent 4496549" 29 Jan 1985.

Science News. "Distribution Of Antibiotic For Eye Disease Linked To Low Death Risk Among Ethiopian Children." 1 Sept 2009.

Travis C. Porco; Teshome Gebre; Berhan Ayele; Jenafir House; Jeremy Keenan; Zhaoxia Zhou; Kevin Cyrus Hong; Nicole Stoller; Kathryn J. Ray; Paul Emerson; Bruce D. Gaynor; Thomas M. Lietman. Effect of Mass Distribution of Azithromycin for Trachoma Control on Overall Mortality in Ethiopian Children: A Randomized Trial. JAMA, 2009; 302 (9): 962-968

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.

The solution with a crystalline heart

A team at McGill University (and RI-MUHC) in Montreal is scrambling to create a malaria vaccine. The researchers, lead by Dr. Martin Oliver, "may have blazed a trail towards the development of vaccine-like treatments to limit the severity of the devastating parasitic ailment" (Science).



The team's new discovery may lead to the development of a medication that stops malaria from creating the debilitating inflammation that is associated with malaria. "Inside the human body, the malaria parasite infects red blood cells where it survives and reproduces by feeding on the cells' contents. Eventually the cells burst, releasing the parasites and also a waste byproduct of their reproductive process: hemozoin" (Tiemi). Hemozoin is the "chemically inert crystalline substance produced in the digestive food vacuole of blood-stage malaria parasites" (Parasitology).

Although chemically inert, it is still a foreign substance in the body. The Hemozoin is "one way by which the immune system is alerted to malarial infection." It "activates the immune system, resulting in the production of inflammation mediators and in the high fever." The researchers believe that hemozoin "may be the missing link that explains why malaria leads to devastating inflammation and fever...The researchers believe it will be possible to familiarize the immune system to small quantities of hemozoin and diminish the inflammatory response in the event of infection, according to a principle similar to that of vaccines" (Science). Dr. Olivier explains that "Now our picture of the process that goes from infection to fever is more or less complete."

However, a final solution is not yet apparent. "Malaria is too complex to be narrowed down to one single mechanism" (Tiemi). Although the relationship between hemozoin and inflammation is important, there are most like many other mechanisms at work.

Will a malaria vaccine ever be available? It is certainly possible, but more research and development is needed before we will know for sure.

Sources:

Parasitology Encyclopedia. Hemozoin.

Tiemi Shio M, Eisenbarth SC, Savaria M, Vinet AF, Bellemare M-J, et al. Malarial Hemozoin Activates the NLRP3 Inflammasome through Lyn and Syk Kinases. PLoS Pathogens, 2009; 5 (8): e1000559 DOI: 10.1371/journal.ppat.1000559

Hempelmann, Birefringent Plasmodium falciparum hemozoin. [Photo]

Science Daily. "Towards Malaria 'Vaccine': Discovery Opens The Door To Malaria-prevention Therapies." 23 Aug 2009.

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.

The Threat of Drug Resistant Malaria

Recent tests indicate that the most common malaria strains are becoming resistant to combination treatments in vulnerable areas. "Selected trials" showed "high failure rates for some combinations" of medicines. Anti-malarial treatments must be questioned, particularly in susceptible regions (Wiley).

The most common type of malaria parasite causes uncomplicated malaria, which is a mild form of the disease. However, if this strain remains untreated, it can develop into a life-threatening condition. "Resistance" of this strain "to the older antimalarials has led the WHO to recommend treatments combining" a fast-acting drug with a "longer-lasting drug to combat resistance."

Malaria can be a difficult disease to cure and is most often treated with a combination of medicines. During the recent tests, "there were examples of treatment failure rates above 10% for all evaluated combinations." According to the WHO, this exceeds the "maximum allowable failure rate for a first line antimalarial" treatment.

A recently introduced drug, dihydroartemisinin-piperaquine, performed well when compared to the standard treatment of artemisinin-based combination therapies (ACTs). This new treatment "offers another potential first-line therapy for the disease".

"Patterns of resistance change from place to place and over time," so continued testing of infected individuals and monitoring of progress is necessary to ensure successful treatment. These research and medical programs are costly, and severely underfunded. If you would like to contribute money to malaria research, please visit the following sites.

Anti-malaria agencies:

• Roll Back Malaria Partnership: Index of non-profit organizations that fight malaria (and need donations)
• United Nations Foundation: With your donation you are helping us expand the worldwide fight against disease, poverty, climate change, and conflict

(Infectious bite is not currently accepting donations. Please see the appropriate agencies for information on donations)

Source:
Wiley-Blackwell. "Continued Vigilance Against Drug-resistance Malaria Is Needed." ScienceDaily 7 July 2009. 9 July 2009 < http://www.sciencedaily.com­ /releases/2009/07/090707201209.htm >.

Advances Against Malaria | Combination Treatment

New studies conducted with children in Burkino Faso have shown that "in combination with newer malaria drugs, methylene blue prevents the malaria pathogen in infected persons from being re-ingested by mosquitoes and then transmitted to others and is thus twice as effective as the standard therapy" (University).

Methylene blue is one of the oldest synthetic treatments of malaria. In 1891, Paul Ehrlich identified its success at treating the disease (Schirmer). The chemical fell out of favor because of its cosmetic side-effects: whites of the eyes acquire a blue tint (image) and urine turns green.

Methylene blue is relatively cheap to produce and may see a resurgence in use since "combination therapies are twice as effective against gametocytes as the standard therapy" (University).

Sources:
Schirmer H, Coulibaly B, Stich A, et al. (2003). "Methylene blue as an antimalarial agent--past and future". Redox Rep 8: 272–276. doi:10.1179/135100003225002899

University Hospital Heidelberg. "Spread Of Malaria Parasites Curbed With Combination Of Methylene Blue And New Malaria Drugs." ScienceDaily 26 May 2009. 24 June 2009

Malaria Symptoms

Malaria "can lead to impaired function of the brain or spinal cord, seizures, or loss of consciousness." Infection with certain parasites cause severe symptoms and can be fatal.

Common symptoms of malaria:

• Fever
• Chills
• Headaches
• Fatigue
• Sweating
• Nausea
• Vomiting

Symptoms of malaria often cycle or fluctuate. "The cyclic pattern of malaria symptoms is due to the life cycle of malaria parasites as they develop, reproduce, and are released from the red blood cells and liver cells in the human body. This cycle of symptoms is also one of the major indicators that you are infected with malaria."

Malaria has a variable incubation time (the period of time between initial infection and the illness). Symptoms can appear as early as 7 days after infection. "Occasionally, the time between exposure and signs of illness may be as long as 8 to 10 months".

Source:
WebMD. "Malaria." Retrieved on 24 June 2009.

Malaria Statistics

Sobering statistics:

• 300-500 million malaria infections each year
• More than 1 million deaths each year related to malaria
• Nearly 40% of the world's population lives in affected regions.
• Malaria causes 1 in 5 of all childhood deaths in Africa
• African children have between 1.6 and 5.4 episodes of malarial fever each year.

Malaria Cases
2006 Estimates

Sources:
Global Health Facts. "Malaria Cases". Retreived 24 June 2009.

Seattle Biomedical Research Institute (SBRI). "Diseases: Malaria". Retreatived 24 June 2009.