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

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

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

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

Vaccine trials

Raise your hand if you took note of the press release regarding the malaria vaccine to jump at the chance to announce it before me. I see you there, sitting alone, sheepishly raising your hand. Actually, I'm quite proud of you. You're paying attention, spreading the word, and enlightening the world. Raise your hand higher, be proud! Oh wait. You in the public library: Put your hand down. People can see you.

So why is Ana so late to the party? No one told me the media gods were releasing the news today. I'm not psychic, you know. Also, I was preoccupied with public transit issues. Don't ask...

Of the emails and messages I received from avid followers, these are my favorites:
Can this really be true? Yaa!
Vampire fans -- this could be a breakthough.
Look [link] Why haven't you written yet? Did you get staked?

Calm yourselves, people. I'm not hindered by the strike of a little stake. The picketing version may be a different story, however.

Now that I'm back online, let me abbreviate the news:

"A pivotal efficacy trial of RTS,S, the world's most clinically advanced malaria vaccine candidate, is now underway in seven African countries: Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique and Tanzania" (PATH). This vaccine is the first to be designed specifically for malaria in Africa. Trials are being conducted in seven countries and different regions "across Sub-Saharan Africa" in order "to evaluate the vaccine candidate's efficacy in a variety of settings, with diverse patterns of malaria transmission. For example, some trial sites are located in areas where there is a year-round threat of malaria, while others experience only seasonal transmission". "The vaccine profile is intended primarily for infants, as they and children under the age of five are the most vulnerable to malaria" (PATH).

Previous research "studies showed that RTS,S reduced clinical episodes of malaria by 53 percent over an eight-month follow-up period" (PATH). Phase III trials are being conducted in what is now "the largest trial ever conducted in Africa of a vaccine specifically designed for use with African children."

Sources:
PATH Malaria Vaccine Initiative (2009, November 3). World's Largest Malaria Vaccine Trial Now Underway In Seven African Countries. ScienceDaily. Retrieved November 3, 2009, from http://www.sciencedaily.com¬ /releases/2009/11/091103102248.htm

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 .

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.

Halting Malaria Transmission

Brought to my attention by @sarahsearle

"Researchers at the Johns Hopkins Malaria Research Institute have for the first time produced a malarial protein" that can "generate a significant immune response" and be used to create "a potential transmission-blocking vaccine" (Parsons). Antibodies produced in response to the protein, inhibit the "sexual development of the malaria-causing parasite, Plasmodium, as it grows within the mosquito".

"According to the study, a single-dose vaccine provided a 93 percent transmission-blocking immune response, reaching greater than 98 percent after a booster was given several months later" (Parsons).

Humans are on the verge of successfully creating a vaccine that may inhibit the spread of malaria. In the late 1980s, scientists understood the possibility of transmission-blocking immunity. They discovered that individuals can "develop immunity that suppresses the infectivity of the sexual stages of the parasite." This "immunity is antibody mediated and is directed against the parasites in the mosquito midgut shortly after ingestion of blood by a mosquito." In 1987, scientists declared that "This immunity could be expected to have significant effects on the natural transmission of P. vivax malaria" (Mendis).

"Development of a successful transmission-blocking vaccine is an essential step in efforts to control the global spread of malaria" (Kumar). This study indicates that "it is possible to gradually reduce malaria transmission to a point of almost eradication" (Parsons).

Sources:
Kumar, Nirbhay.

Mendis, K N. Y D Munesinghe, Y N de Silva, I Keragalla, and R Carter. Malaria transmission-blocking immunity induced by natural infections of Plasmodium vivax in humans. 1987 February.

Parsons, Tim. Vaccine Blocks Malaria Transmission in Lab Experiments. 22 July 2009.