Drug-resistant malaria

"In a dusty village near the Thai-Cambodia border, 24-year-old Oeur Samoeun sits on a dark green hammock recovering from a strain of malaria that has resisted the most powerful drugs available. . . Ravaged by days of fever and chills, he is considered lucky: the parasite has left his body. But for many others, the potentially deadly disease never quite disappears."

Pailin province, where Samoeun lives, is the unwitting nursery of drug-resistant malaria. It "is the epicenter of strains of malaria that have baffled healthcare experts worldwide, raising fears a dangerous new form of malaria could already be spreading across the globe."

Last year, a study published by the New England Journal of Medicine "showed that conventional malaria-fighting treatments derived from artemisinin took almost twice as long to clear the parasites that cause the disease in patients in Pailin and others in northwestern Thailand, suggesting the drugs were losing potency in the area." USAID, a U.S. development agency, agrees that traditional arteminsinin-based therapies are "now taking two to three times longer to kill malaria parasites along the Thai-Cambodian border than elsewhere."

Three drug-resistant malaria parasites have emerged from this province over the past five decades. "Thanks to prolonged civil conflict, dense jungles and movement of mass migrants in the gem mines in the 1980s and 90s, the strains multiplied and dispersed through Myanmar, India and two eventually reached Africa."

"Few can say why it is a hotbed for drug-resistant malaria", but experts point to "a combination of sociological factors and a complicated history spanning the Khmer Rouge era when 1.7 million people, nearly a quarter of Cambodia's population, perished from execution, overwork or torture during their 1975-79 rule."

Insurgents clung to Pailin, and it was "one of their last holdouts" before their defeat in the late 1990s. During the era of the Khmer Rouge, people resided in Pailin illegally. When they contracted malaria, they bought medication through black markets and self-medicated.

Self-medication was the only way to curb the rising number of malaria cases, so Cambodia made the decision to make anti-malarial drugs available over the counter. "The strategy carried risks. Easy access reduced the number of cases but also led to incorrect dosages and substandard or counterfeit medicine". Instead of eradicating the malaria parasites, over-the-counter treatments made the parasitic population stronger against widely used medications.

Without adequate drugs to combat the disease, drug-resistant malaria parasites threaten the world. Preventative measures, such as the use of bed-nets to avoid mosquito bites, may be our best defense against malaria. Donate a bed net through Nothing But Nets.

Source:
Win, Thin Lei. Reuters. "Cambodia drug-resistant malaria stirs health fears." 6 March 2010.

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

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

Who ya gonna call?

Blood-drinkers be warned: Slayers are on the prowl. Taking a note from a cheesy '80s movie, these hunters have equipped themselves with a backpack-carried weapon and are crawling the sewers collecting the flying fiends who annoy the living.

Mosquito hunters from Emory University have developed an efficient way to monitor adult mosquitoes and the deadly diseases they carry, and they have done it cheaply. "Emory has filed a provisional patent on the Prokopack mosquito aspirator, but the inventors have provided simple instructions for how to make it in the Journal of Medical Entomology."

"This device has broad potential, not only for getting more accurate counts of mosquito populations, but for better understanding mosquito ecology," according to Gonzalo Vazquez-Prokopec. "There is a great need for effective and affordable mosquito sampling methods. Use of the Prokopack can increase the coverage area, and the quality of the data received, especially for blood-fed mosquitoes. Ultimately, it can help us develop better health intervention strategies."

This new invention outperformed standards for resting mosquito surveillance in lab and field tests. The Prokopack has a longer reach than the Center For Disease Control and Prevention Backpack Aspirator (CDC-BP), which enables "it to collect more mosquitoes than the CDC-BP". The Prokopack is also "significantly smaller, lighter, cheaper, and easier to build" than its predecessor.

"Anyone with access to a hardware store, and about $45 to $70, can make the Prokopack, which uses a battery-powered motor to suck up live mosquitoes for analysis."

"The CDC-BP can quickly vacuum up samples of live specimens, which can be analyzed in a lab to determine the source of blood they recently consumed. The drawbacks to the CDC-BP, however, include its heavy weight (26 pounds), its bulk and its price -- about $450 to $750 in the United States."

"With a bit of ingenuity and a few trips to the hardware store," the Emory research team "put together a solution: a plastic container, a wire screen, a plumbing pipe coupler, a battery-powered blower motor and painter extension poles. After some experimentation with these components, the Prokopack was born.

"Collecting more mosquitoes in higher locations can give researchers more insights into their behaviors. Upper foliage, for instance, can yield more mosquitoes resting after feeding on birds. And upper walls and ceilings of homes may harbor more mosquitoes resting after a meal on humans."

Source:
Emory University (2010, January 13). Mosquito hunters invent better, cheaper, DIY disease weapon. ScienceDaily. Retrieved January 13, 2010, from http://www.sciencedaily.com¬ /releases/2010/01/100112152402.htm

Meddling with sex

Your mother may have told you that it's not nice to meddle in the business of others (especially when it's 'nasty business'), but when it comes to mosquitoes, meddling may offer very nice results. Imperial College recently released a report, entitled: "Meddling in mosquitoes' sex lives could stop the spread of malaria", revealing how a particular species of Anopheles gambiae has an easily disrupted sexual process, which when interrupted will prevent that mosquito from breeding.

"The new study focuses on the species of mosquito primarily responsible for the transmission of malaria in Africa, known as Anopheles gambiae. These mosquitoes mate only once in their lifetime, which means that disrupting the reproductive process offers a good way of dramatically reducing populations of them in Africa. When they mate, the male transfers sperm to the female and then afterwards transfers a coagulated mass of proteins and seminal fluids known as a mating plug" (Reeves). Prior to the release of this study, the purpose of this mating plug was misunderstood. Unlike similar substances in other species, the "male mating plug is not a simple barrier to insemination from rival males" (Imperial). Instead it is "essential for ensuring that sperm is correctly retained in the female's sperm storage organ, from where she can fertilise eggs over the course of her lifetime. Without the mating plug, sperm is not stored correctly, and fertilisation cannot occur" (Reeves).

"In Imperial's mosquito labs, the scientists showed it was possible to prevent the formation of the plug in males, and that this stopped them successfully reproducing with females" (Imperial). "In the future", researchers may "develop an inhibitor that prevents the coagulating enzyme doing its job inside male An. gambiae mosquitoes in such a way that can be deployed easily in the field -- for example in the form of a spray as it is done with insecticides". In this way, "we could effectively induce sterility in female mosquitoes in the wild. This could provide a new way of limiting the population of this species of mosquito, and could be one more weapon in the arsenal against malaria" (Reeves).

Sources:
Imperial College London. "Meddling in Mosquitoes' Sex Lives Could Help Stop the Spread of Malaria." ScienceDaily 22 December 2009. 27 December 2009 .
Reeves, Danielle. "Meddling in Mosquitoes' Sex Lives Could Help Stop the Spread of Malaria." Imperial College London. http://www.eurekalert.org/pub_releases/2009-12/icl-mim121609.php

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.