Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria

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Human genetics and immune responses are considered to critically influence the outcome of malaria infections including life-threatening syndromes caused by Plasmodium falciparum. An important role in immune regulation is assigned to the apoptosis-signaling cell surface receptor CD95 (Fas, APO-1), encoded by the gene FAS.

Here, a candidate-gene association study including variant discovery at the FAS gene locus was carried out in a case-control group comprising 1,195 pediatric cases of severe falciparum malaria and 769 unaffected controls from a region highly endemic for malaria in Ghana, West Africa. We found the A allele of c.−436C>A (rs9658676) located in the promoter region of FAS to be significantly associated with protection from severe childhood malaria (odds ratio 0.71, 95% confidence interval 0.58–0.88, pempirical = 0.02) and confirmed this finding in a replication group of 1,412 additional severe malaria cases and 2,659 community controls from the same geographic area.

The combined analysis resulted in an odds ratio of 0.71 (95% confidence interval 0.62–0.80, p = 1.8×10−7, n = 6035). The association applied to c.−436AA homozygotes (odds ratio 0.47, 95% confidence interval 0.36–0.60) and to a lesser extent to c.−436AC heterozygotes (odds ratio 0.73, 95% confidence interval 0.63–0.84), and also to all phenotypic subgroups studied, including severe malaria anemia, cerebral malaria, and other malaria complications. Quantitative FACS analyses assessing CD95 surface expression of peripheral blood mononuclear cells of naïve donors showed a significantly higher proportion of CD69+CD95+ cells among persons homozygous for the protective A allele compared to AC heterozygotes and CC homozygotes, indicating a functional role of the associated CD95 variant, possibly in supporting lymphocyte apoptosis.

Author Summary

Severe malaria caused by infection with the protozoan parasite Plasmodium falciparum is a major health burden, causing approximately one million fatalities annually, predominantly among young children in Sub-Saharan Africa. The occurrence of severe malaria may depend on a complex interplay of transmission dynamics and the development of a protective immune response but also on heritable differences in the susceptibility to the disease.

In two large studies including a total of 2,607 affected children and 3,428 apparently healthy individuals from Ghana, West Africa, we investigated genetic variants of the FAS gene, which encodes CD95, a molecule critically involved in the programmed cell death of lymphocytes. We found that a single nucleotide variant in the FAS promoter was associated with a 29%–reduced risk of developing severe malaria. In individuals carrying two copies of the protective allele, a higher proportion of activated lymphocytes was found to express CD95. These findings indicate that a predisposition to an increased expression of CD95 may help to protect from severe malaria, possibly by rendering activated T-lymphocytes more susceptible to programmed cell death.

Citation: Schuldt K, Kretz CC, Timmann C, Sievertsen J, Ehmen C, et al. (2011) A −436C>A Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria. PLoS Genet 7(5): e1002066. doi:10.1371/journal.pgen.1002066

Editor: Daniel C. Jeffares, University College London, United Kingdom

Received: November 3, 2010; Accepted: March 18, 2011; Published: May 19, 2011

Copyright: © 2011 Schuldt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The work was supported by the German National Genome Research Network (NGFN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Authors: Kathrin Schuldt1,2*, Cosima C. Kretz3, Christian Timmann1,2, Jürgen Sievertsen1, Christa Ehmen1, Claudia Esser1, Wibke Loag4, Daniel Ansong5, Carmen Dering2, Jennifer Evans1, Andreas Ziegler2, Jürgen May4, Peter H. Krammer3, Tsiri Agbenyega5, Rolf D. Horstmann1

1 Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany, 2 Institute of Medical Biometry and Statistics, University at Lübeck, University Hospital Schleswig-Holstein, Lübeck, Germany, 3 Division of Immunogenetics, German Cancer Research Centre, Heidelberg, Germany, 4 Infectious Disease Epidemiology Group, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany, 5 School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

Full text: A −436C>A Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria (PDF)

Wolbachia Bacteria Reduce Parasite Levels and Kill the Mosquitos that Spreads Malaria

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Wolbachia are bacteria that infect many insects, including mosquitoes. However, Wolbachia do not naturally infect Anopheles mosquitoes, which are the type that spreads malaria to humans. Researchers at the Johns Hopkins Bloomberg School of Public Health found that artificial infection with different Wolbachia strains can significantly reduce levels of the human malaria parasite, Plasmodium falciparum, in the mosquito, Anopheles gambiae. The investigators also determined that one of the Wolbachia strains rapidly killed the mosquito after it fed on blood. According to the researchers, Wolbachia could potentially be used as part of a strategy to control malaria if stable infections can be established in Anopheles.

“This is the first time anyone has shown that Wolbachia infections can reduce levels of the human malaria parasite (Plasmodium falciparum) in Anopheles mosquitoes,” said Jason Rasgon, PhD, senior author of the study and associate professor with the Johns Hopkins Malaria Research Institute and the Bloomberg School’s W. Harry Feinstone Department of Molecular Microbiology and Immunology.

For the study, Rasgon and his colleagues infected Anopheles gambiae mosquitoes with two different Wolbachia strains (wMelPop and wAlbB). After infection, Wolbachia disseminated widely in the mosquitoes and infected diverse tissues and organs. Wolbachia also seemed to actively manipulate the mosquito’s immune system to facilitate its own replication. Both Wolbachia strains were able to significantly inhibit malaria parasite levels in the mosquito gut. Although not virulent in sugar-fed mosquitoes, the wMelPop strain killed most mosquitoes within a day after the mosquito was blood-fed.

“These experiments show that Wolbachia could be used in multiple ways to control malaria, perhaps by blocking transmission or by killing infected mosquitoes,” said Rasgon.

Worldwide, malaria afflicts more than 225 million people. Each year, the disease kills nearly 800,000, many of whom are children living in Africa.

In addition to Rasgon, the authors of “Wolbachia infections are virulent and inhabit the human malaria parasite Plasmodium falciparum in Anopheles gambiae” include Grant Hughes and Ping Xue of the Johns Hopkins Malaria Research Institute, and Ryuichi Koga and Takema Fukatsu of the National Institute of Advanced Industrial Science and Technology in Tsukuba, Japan.

Funding was provided by the Johns Hopkins Malaria Research Institute and the National Institute of Allergy and Infectious Diseases. The study is published in the May 19, 2011 edition PLoS Pathogens.

Source: Johns Hopkins Bloomberg School of Public Health

Researchers Find Gene That Fights Severe Malaria in Children

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Scientists have discovered a genetic variant in children that significantly reduces their risk of developing a life-threatening form of malaria.

Children with the unusual, or variant, gene have a 30 percent lower risk of developing cerebral malaria than those without the gene. Cerebral malaria is the most serious form of the parasitic illness that causes very high fever and coma, and leads rapidly to death in the 20 to 50 percent of people whose brains become infected.
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The mosquito-borne illness affects almost 300 million people every year. But most of the one million deaths occur in children under the age of five.

Researchers at Germany’s Bernhard Nocht Institute for Tropical Medicine and Kumasi University in Ghana identified the protective gene in a study involving more than 6,000 children. Called FAS, the gene is responsible for a molecule involved in the programmed cell death of some white blood cells, which are immune system cells that attack and destroy microbes that invade the body.

Researchers think that children who develop a life-threatening form of malaria have a hyper-immune response to the parasite. But youngsters with the FAS variant have increased expression of the molecule, called CD95, which appears to promote a greater number of immune system cell suicides—thus a less intense and ultimately survivable immune reaction to malaria.

At least that’s the theory, according to Kathrin Schuldt, a biologist and co-author of the study. Schuldt says children who are vulnerable to cerebral malaria are constantly bitten by mosquitoes that carry the parasite.

“So the immune response is constantly on a very high level trying to eliminate the pathogen from the body. And so what we found with this naturally occurring variant, these children probably have a regulation in their immune response which down-regulates the immune response to a certain level and therefore is kind of protective,” Schuldt said.

Humans never develop full immunity against malaria, but they can gain a partial immunity to the parasite, which is why the disease is less severe in adults. But children can become quite sick because they have had less exposure to the disease.

Schuldt says her goal now is to figure out the underlying mechanism for the protective effect of the genetic variant. Then, Schuldt says, it may be possible to develop drugs to protect children from this fatal form of malaria.

An article on the protective malaria gene is published in the on-line journal PLoS Genetics.

Source: VOA News

Research Could Lead to Mosquitoes Being Susceptible to Diseases They Transmit

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Mosquitoes are becoming more resistant to current pesticides. That’s troubling to Kansas State University biologist Kristin Michel, as it means malaria and other mosquito-borne diseases will continue spreading. A recent grant from the National Institutes of Health may change all that.

Michel, an assistant professor of biology, is using the nearly $1.5 million grant for the four-year study, “The function(s) of serpin-2 in mosquito immunity and physiology.” Findings from this investigation into the role of the serpin-2 molecule in Anopheles gambiae — the African malaria mosquito — could stop the transmission of malaria and other mosquito-spread diseases by making mosquitoes susceptible to the very diseases they transmit.

As principal investigator, Michel and her laboratory team are focusing on definitively understanding the role of serpin-2 in the mosquito’s body. Serpins are a group of similarly structured proteins that can inhibit a group of enzymes that break down proteins called proteases. Serpin-2 controls certain proteases that create immunity against bacteria and fungi in the mosquito.

“Current insecticides used for controlling vector-borne diseases are chemicals that target an insect’s nervous system,” Michel said. “Because serpin-2 relates to a mosquito’s immunity, it could act as a novel insecticide target.”

Attacking this molecule could avoid or disrupt a response from the mosquito’s immune system that would otherwise protect the insect, she said.

The idea for the research came from a previous project conducted by Michel and fellow Kansas State researchers. By removing serpin-2 from the mosquitoes’ bodies, the researchers noticed melanization is affected. In insects melanin is used to encompass foreign objects that enter their body, like bacteria and parasites. This process prevents the insect’s immune system from constantly fighting the foreign body. It also causes pseudo-tumors in the mosquitoes once serpin-2 is removed.

“We don’t really quite understand yet why this happens, but we do know that the mosquito’s immune response is totally overamplified,” Michel said. “Instead of melanizing parasites or bacteria, the mosquito’s body attacks itself, getting melanotic pseudo-tumors throughout it.”

These pseudo-tumors appear as black dots on the insect’s thorax and abdomen. Afflicted mosquitoes that do not initially die from the tumors steadily lose interest in blood feeding over time.

“So what we’re going to do with this grant is to find out which proteases — since it’s most likely more than one — are being inhibited by serpin-2 for this whole process to occur,” Michel said. “Right now we have very little information about the cloud of proteases that float around in the insect, with regards to what they do and how they interact.”

Finding the proteases will require lots of detective work as more than 50 proteases are potentially being inhibited by serpin-2. However, Michel said, the most time-consuming portion may be collecting enough material from the mosquitoes to sample, as one mosquito yields about 0.1 microliters of bodily material.

Several co-investigators are also lending their expertise to the study. Michael Kanost, university distinguished professor and head of the department of biochemistry, is helping with expression of proteases and in vitro testing. Christopher Culbertson, associate professor of chemistry, is building microfluidics technology that will allow for better plasma analysis from the mosquitoes, potentially helping with the sample sizes. Scott Lovell, director of the protein structure laboratory at the University of Kansas, will use X-ray crystallography to visualize how serpin-2 binds to the proteases it inhibits.

“By the end of the study we really hope to say serpin-2 is a perfect target for an insecticide that prevents the mosquito’s immunity,” Michel said. “The next step will be then to find such chemicals. That’s where we’re hoping to take this research.”

via Newswise.

Researchers Discover Microbe That Could Help Fight Malaria

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Researchers have discovered a bacterium in the gut of the Anopheles mosquito which may someday be used to destroy and, therefore, prevent the spread of the disease-causing parasite.

The World Health Organization estimates 800,000 people die of malaria each year. The parasite that causes the disease is transmitted by the Anopheles mosquito. After the mosquito feeds on the blood of an infected individual, the parasite matures into an infectious stage in the insect’s gut.  From there, the parasite, known as Plasmodium falciparum, takes up residence in the mosquito’s salivary glands so it can infect the next person that’s bitten.

Researchers at Johns Hopkins School of Public Health in Baltimore, Maryland found the bacterium in the gut of the Anopheles mosquito among hundreds of so-called microbial flora that live harmlessly in the stomach of a group of Anopheles mosquitoes collected in an area of southern Zambia where malaria is rampant.

The microbe, which was in the guts of a small percentage of the mosquitoes, protected those insects against infection with the parasite.

Lead researcher George Dimopoulos says the protection seems to be a side-effect of the bacterium’s normal bodily function, adding that scientists would like to figure out a way to use the microbe as a weapon against malaria.

“Our study has shown that this bacterium produces free radicals, molecules that contain oxygen and that can cause damage to cells.  So, we believe that’s how this bacterium is killing the malaria parasite in the mosquito gut.  But we need to understand that mechanism in greater detail.”

To demonstrate the beneficial effect, the researchers used antibiotics to kill the bacterium in mosquitoes that contained it, and were then able to infect those mosquitoes more easily with the Plasmodium parasite.

They also introduced the bacterium into the guts of mosquitoes that didn’t have it. When they fed this group infected blood, the parasite was destroyed in nearly all of the insects.

Dimopoulos says researchers’ goal now is to figure out a way to introduce the microbe into large populations of Anopheles mosquitoes – perhaps through bait laced with their favorite snack.

“Mosquitoes need to feed on sugar every day.  And one can potentially expose mosquitoes in the field to these bacteria through sugar bait.”

The researchers noted that mosquitoes with the bacterium in their guts die sooner than those without it – when both groups are infected with the parasite. Since the malaria parasite lives in mosquitoes for about two weeks before maturing to an infectious stage, Dimopoulos says it’s good news that the stomach bacterium seems to shorten the insect’s lifespan, before it could potentially transmit the parasite to humans.

Source: VOA News

Equatorial Guinea Reduces Malaria in Children by 57% in Four Years

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The Republic of Equatorial Guinea has decreased the prevalence of the malaria parasite in children by 57% in just four years and has increased the number of children protected by bed nets or indoor spraying of insecticides from 4% to 95% in that same period, according to a report by Roll Back Malaria.

Research carried out on the Island of Bioko, funded by the government of Equatorial Guinea and a private consortium led by Marathon Oil Corporation, showed a reduction in infant mortality in nearly one third of the population. The program to control malaria is part of a broader effort by the government, through the Ministry of Health and Social Welfare, to improve public health in the West African nation.

The anti-malaria project is currently focused on the island of Bioko, where more than half the population of Equatorial Guinea lives, and has been extended to 2013 to develop local capacity and enable the campaign to reach the mainland. The project has won numerous high-profile awards for social responsibility and good citizenship.

The sixth report on Business Investing in Malaria Control: Economic Returns and a Healthy Workforce for Africa showcases how malaria control investment has significantly improved in Africa. “Companies in Equatorial Guinea, Ghana, Mozambique, and Zambia have worked to prevent malaria among their workers and workers’ dependents and have seen an excellent return on investment, with significant reductions in malaria-related illnesses and deaths, worker absenteeism, and malaria related spending.”

The Malaria Control Project is a fundamental part of the government-wide effort to meet the goals of the Horizon 2020 development plan set by President Obiang Nguema Mbasogo.

Equatorial Guinea has heavily invested in public health. The government has donated $1.5 million and a headquarters facility to the World Health Organization (WHO) to support research for global health. It has also provided technical assistance to the local United Nations Population Fund (UNFPA) to improve the effectiveness of its Assistance Program as well as the implementation of a host of health programs geared towards improving the health of Equatorial Guineans.

Source: Republic of Equatorial Guinea

Researchers Discover Insect Repellent Thousands of Times More Effective than DEET

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Imagine an insect repellent that not only is thousands of times more effective than DEET – the active ingredient in most commercial mosquito repellents – but also works against all types of insects, including flies, moths and ants.

That possibility has been created by the discovery of a new class of insect repellent made in the laboratory of Vanderbilt Professor of Biological Sciences and Pharmacology Laurence Zwiebel and reported this week in the online Early Edition of the Proceedings of the National Academy of Sciences.

“It wasn’t something we set out to find,” said David Rinker, a graduate student who performed the study in collaboration with graduate student Gregory Pask and post-doctoral fellow Patrick Jones. “It was an anomaly that we noticed in our tests.”

The tests were conducted as part of a major interdisciplinary research project to develop new ways to control the spread of malaria by disrupting a mosquito’s sense of smell supported by the Grand Challenges in Global Health Initiative funded by the Foundation for the NIH through a grant from the Bill & Melinda Gates Foundation.

“It’s too soon to determine whether this specific compound can act as the basis of a commercial product,” Zwiebel cautioned. “But it is the first of its kind and, as such, can be used to develop other similar compounds that have characteristics appropriate for commercialization.”

The discovery of this new class of repellent is based on insights that scientists have gained about the basic nature of the insect’s sense of smell in the last few years. Although the mosquito’s olfactory system is housed in its antennae, 10 years ago biologists thought that it worked in the same way at the molecular level as it does in mammals. A family of special proteins called odorant receptors, or ORs, sits on the surface of nerve cells in the nose of mammals and in the antennae of mosquitoes. When these receptors come into contact with smelly molecules, they trigger the nerves signaling the detection of specific odors.

In the last few years, however, scientists have been surprised to learn that the olfactory system of mosquitoes and other insects is fundamentally different. In the insect system, conventional ORs do not act autonomously. Instead, they form a complex with a unique co-receptor (called Orco) that is also required to detect odorant molecules. ORs are spread all over the antennae and each responds to a different odor. To function, however, each OR must be connected to an Orco.

“Think of an OR as a microphone that can detect a single frequency,” Zwiebel said. “On her antenna the mosquito has dozens of types of these microphones, each tuned to a specific frequency. Orco acts as the switch in each microphone that tells the brain when there is a signal. When a mosquito smells an odor, the microphone tuned to that smell will turn “on” its Orco switch. The other microphones remain off. However, by stimulating Orco directly we can turn them all on at once. This would effectively overload the mosquito’s sense of smell and shut down her ability to find blood.”

Because the researchers couldn’t predict what chemicals might modulate OR-Orco complexes, they decided to “throw the kitchen sink” at the problem. Through their affiliation with Vanderbilt’s Institute of Chemical Biology, they gained access to Vanderbilt’s high throughput screening facility, a technology intended for the drug discovery process, not for the screening of insect ORs.

Jones used genetic engineering techniques to insert mosquito odorant receptors into the human embryonic kidney cells used in the screening process. Rinker tested these cells against a commercial library of 118,000 small molecules normally used in drug development. They expected to find, and did find, a number of compounds that triggered a response in the conventional mosquito ORs they were screening, but they were surprised to find one compound that consistently triggered OR-Orco complexes, leading them to conclude that they had discovered the first molecule that directly stimulates the Orco co-receptor. They have named the compound VUAA1.

Although it is not an odorant molecule, the researchers determined that VUAA1 activates insect OR-Orco complexes in a manner similar to a typical odorant molecule. Jones also verified that mosquitoes respond to exposure to VUAA1, a crucial step in demonstrating that VUAA1 can affect a mosquito’s behavior.

“If a compound like VUAA1 can activate every mosquito OR at once, then it could overwhelm the insect’s sense of smell, creating a repellent effect akin to stepping onto an elevator with someone wearing too much perfume, except this would be far worse for the mosquito,” Jones said.

The researchers have just begun behavioral studies with the compound. In preliminary tests with mosquitoes, they have found that VUAA1 is thousands of times more effective than DEET.

They have also established that the compound stimulates the OR-Orco complexes of flies, moths and ants. As a result, “VUAA1 opens the door for the development of an entirely new class of agents, which could be used not only to disrupt disease vectors, but also the nuisance insects in your backyard or the agricultural pests in your crops,” Jones said.

Many questions must be answered before VUAA1 can be considered for commercial applications. Zwiebel’s team is currently working with researchers in Vanderbilt’s Drug Discovery Program to pare away the parts of VUAA1 that don’t contribute to its activity. Once that is done, they will begin testing its toxicity.

Vanderbilt University has filed for a patent on this class of compounds and is talking with potential corporate licensees interested in incorporating them into commercial products, with special focus on development of products to reduce the spread of malaria in the developing world.

Source: Proceedings of the National Academy of Sciences, Vanderbilt University

 

Malaria-Fighting Plants Under Threat

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Researchers warn that East African plants that could cure malaria could disappear before scientists have a chance to study them.

The World Health Organization estimates 800,000 people die of malaria each year, most of them young children in Africa.

A new book by scientists at the World Agroforestry Centre, “Common Antimalarial Trees and Shrubs of East Africa,” identifies 22 tree and shrub species that traditional healers in East Africa use to fight the disease.

But, the researchers say, they are being cut down for cooking fuel and other uses and could disappear before scientists have a chance to study them.

For example, the threatened African wild olive, Olea africana, has anti-malarial properties that scientists say deserve further study.

Herbal medicine

A person suffering from malaria in East Africa is likely to visit a local herbalist for treatment. Lead author Najma Dharani at the World Agroforestry Center in Kenya says the traditional healer may recommend the patient take a few grams of a plant known locally as knobwood.

Either root or bark may be used, fresh or as powder. “It’s quite bitter,” she says. “Drink it for three or four days, until it cures a person.”

Dharani and her colleagues at the Kenya Medical Research Institute have used modern science to identify promising malaria-fighting compounds in knobwood and 21 other trees and shrubs native to the region.

Traditional cures at risk

She has spent the last 12 years studying medicinal plants in East Africa with the potential to treat a range of diseases. A lot more research is needed to identify how effective they are and how they work, but she notes that they have been used by traditional healers for centuries.

“This is not today’s knowledge,” she says. “This is very old knowledge, indigenous knowledge, which has been disappearing because the youngsters don’t take it (up).”

The knowledge is not all that’s disappearing. Dharani says the some of these anti-malarial trees and shrubs are being cut down at an alarming pace, along with other wood in the area, largely to make charcoal. That’s the cooking fuel of choice for many poor people around the world who can’t afford other options.

Limited options for treatment

She understands the economic motivation to cut down the trees. But, she says, it will be these same poor people who will ultimately suffer.

“They don’t have access to clinics. They don’t have doctors,” she says. “They have to go hundreds of kilometers to reach clinics. So, it’s so very important for local communities to conserve these trees. If [the trees] completely vanish, they will remain with nothing.”

The World Agroforestry Center is working to reduce deforestation by encouraging people to grow their own trees for timber or firewood, rather than harvesting the forest. The center also is helping communities plant medicinal trees and shrubs, and conserving samples of the trees in its genebanks and nurseries.

Knobwood extract would not be the first plant to cure malaria. The first anti-malarial drug, quinine, came from the bark of a South American tree. The latest treatment, artemisinin, comes from a Chinese shrub. The next cure could come from East Africa — but not if the last tree is burned up as charcoal.

Source: VOA News

Principles of Magnetic Levitation and Cell Phone Technology to Be Studied for Malaria Diagnosis Tools

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The Gates Foundation has funded a project at Beth Israel Deaconess Medical Center (BIDMC) that uses the principles of magnetic levitation and cell phone technology to create an inexpensive, portable device to quickly and accurately diagnose malaria outside of the laboratory setting. The GCE received more than 2,500 grant submissions from 100 countries, and selected 88 projects, including that of Ionita Ghiran, MD, an investigator in the Division of Allergy and Inflammation at BIDMC, and Assistant Professor of Medicine at Harvard Medical School. Ghiran has been awarded a $100,000 Grand Challenges Exploration Grant from the Bill & Melinda Gates Foundation. The Grand Challenges Exploration (GCE) program funds scientists and researchers worldwide in the pursuit of novel ideas that can break the mold in solving persistent global health challenges.

“GCE winners are expanding the pipeline of ideas for serious global health and development challenges where creative thinking is most urgently needed,” said Chris Wilson, director of Global Health Discovery at the Bill & Melinda Gates Foundation. “These grants are meant to spur on new discoveries that could ultimately help save millions of lives.”

Malaria causes nearly 1 million deaths per year throughout developing countries (85 percent of which are children under the age of 5) and parasites are becoming increasingly resistant to anti-malarial drugs, in part due to overdiagnosis.

“The lack of suitable methods of malaria diagnosis makes presumptive treatment often the only available option for local health service providers,” notes Ghiran. To address this challenge, Ghiran, in collaboration with Pierre Striehl, PhD, from the Harvard School of Dental Medicine, developed an antibody-free diagnostic screening device which separates malaria-infected red blood cells from uninfected red blood cells by way of magnetic levitation.

“Our screening device is light-weight, disposable and inexpensive to manufacture,” he notes. The prototype system requires less than a drop of finger-prick blood and a small volume of red-blood-cell friendly buffer containing paramagnetic ions. Diagnostic results can be obtained within a few minutes solely by using a set of permanent magnets immobilized in a plastic structure surrounding a glass or plastic capillary containing the blood. Results are visualized, recorded and stored using a standard camera phone. No additional imaging equipment, or staining reagents are required.

“This method helps fill the need for malarial diagnostic technologies capable of promptly and reliably ascertaining true malarial infections in the field,” says Ghiran. “We hope that this will help prevent the overdiagnosis of malaria and subsequent drug resistance.”

Grand Challenges Explorations is a $100 million initiative funded by the Bill & Melinda Gates Foundation. Launched in 2008, Grand Challenge Explorations grants have already been awarded to nearly 500 researchers from over 40 countries. The grant program is open to anyone from any discipline and from any organization. The initiative uses an agile, accelerated grant-making process with short two-page online applications and no preliminary data required. Initial grants of $100,000 are awarded two times a year. Successful projects have the opportunity to receive a follow-up grant of up to $1 million.

Source: Beth Israel Deaconess Medical Center

U.S. Investments to Battle Malaria Show Results

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Progress against Malaria is one area where U.S. investments in global health have made an great impact. Just five years ago, it was estimated that malaria killed nearly one million children annually in sub-Saharan Africa. The economic cost to the continent was estimated to be nearly $30 billion each year in lost productivity.

“Today, the U.S. along with its partners have helped cut malaria cases in half in more than 40 countries and reduced childhood malarial deaths by 200,000, and even seen a reduction in all-cause child mortality in seven initial Presidential Malaria Initiative countries,” said USAID Administrator Raj Shah. He added, “I find that statistic astounding.”

The President’s Malaria Initiative, which is led by the U.S. Agency for International Development and implemented jointly with the Centers for Disease Control and Prevention, has led the fight against this preventable and curable disease which is currently the leading cause of death among children in Africa.

“Today, we have a lot to celebrate, because the rates of death resulting from malaria infection are decreasing,” said Rear Admiral Tim Ziemer, the U.S. Global Malaria Coordinator. “However, we need to be sobered by the job ahead of us.”

That’s because despite lower infection and death rates, and despite the fact that the disease is both preventable and treatable, it is estimated that a child in Africa still dies every 45 seconds from malaria.

The President’s Malaria Initiative, now a central part of the Global Health Initiative, was introduced in 2005 to concentrate on fighting the disease.  Its goal is to reduce malaria-related deaths by 50 percent in 15 focus countries by the year 2016.

[“We] believe we can push the Initiative’s success even further,” said USAID Administrator Raj Shah.  “Over the next five years, . . . .we can save an additional 500,000 lives a year, most of them young children.”

To do so, the U.S will work with partners to train health care workers to quickly identify whether a fever is caused by malaria; develop more effective insecticides that kill the mosquitoes without harming people; and we must find cheaper, more efficient ways to produce artemisinin.

“Finally,” said Dr. Shah, “we need to seek the ultimate answer to malaria: a cheap, effective vaccine. Through the Malaria Vaccine Initiative, USAID will support the development and testing of promising candidates.”

Source: VOA News