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

Bioengineered Antibiotic Could Lead to Improved Malaria Therapy

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A natural antibiotic long known for its power to fight bacteria, viruses and tumors has recently shown strength against malaria, but its extreme toxicity has impeded its use in medicine.

However, a bioengineering breakthrough has opened a new avenue in the global battle against malaria.

Scientists at Oregon State University have engineered several new versions of the antibiotic pactamycin that are up to 30 times less toxic than the parent compound. The new compounds, whose genetic structures were modified in the lab, retain their potency against malaria-causing parasites yet pose fewer risks to patients.

“The results could lead to a new direction in the discovery and development of drugs against malaria and other life-threatening infections caused by protozoa,” said OSU researcher Taifo Mahmud, an author of the study reported in the journal Chemistry & Biology.

The natural form of pactamycin occurs in soil bacteria. It attacks not only protozoa such as the mosquito-borne P. falciparum, which causes malaria, but also bacteria, viruses and tumors. Unfortunately, it attacks healthy cells in mammals, as well. In an effort to capture pactamycin’s benefits while eliminating or minimizing its detriments, OSU researchers modified the genetic structure of the microbe that produces the antibiotic by inactivating or “knocking out” certain genes. They tested the new versions – called “analogues” – on human colorectal cancer cells.

“The results revealed that the new analogues are significantly less toxic than pactamycin,” said Mahmud, a medicinal chemist in the OSU College of Pharmacy.

Mahmud said the OSU study is a promising development in the struggle against malaria, which annually infects 250 million people and kills nearly 1 million worldwide, according to the World Health Organization.

“Although pactamycin was first reported in the 1960s and its various biological activities have been extensively investigated, further development of this compound was hampered by its wide-ranging cytotoxicity,” Mahmud said.

“The study resulted in a number of pactamycin analogues that showed potent antimalarial activity but, in contrast to pactamycin, have reduced cytotoxicity against mammalian cells.”

Source: Oregon State University

New Biomarkers Study Could Lead to Improved Malaria Vaccines

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In the first study of its type in the malaria field, Seattle BioMed has been awarded an $8.9 million grant from the Bill & Melinda Gates Foundation to identify biomarkers that will allow malaria vaccine design based on robust predictors of protective immunity.

According to Ruobing Wang, M.D., Ph.D., the goal of the study is to identify and validate biomarkers that correlate with vaccine-induced protective immunity against malaria infection.

“In order to bring the burden of malaria under control – with the ultimate goal of eradicating the pathogens that cause disease – we know we need a highly efficacious anti-infection vaccine,” she explained. “But, without reliable biomarkers of anti-infection immunity, the development and testing of malaria vaccines is a slow and expensive process.” Biomarkers will be used for prediction and monitoring the vaccine efficacy in clinical trials and to select optimal vaccine candidates for development.

To conduct this research, the company will call upon its areas of expertise and knowledge – vaccine and immunology studies in animal models of malaria, the ability to grow human malaria parasites in mosquitoes for research and clinical studies, and its ability to develop genetically attenuated parasite strains for human trials. It will also begin full-scale trials in its Malaria Clinical Trials Center, and employ its newfound expertise in the area of systems biology.

Seattle BioMed scientists have developed genetically attenuated whole parasite vaccine strains that have proven successful in rodent malaria models and have moved into human studies. “In this new study, we will use genetically attenuated parasite strains as probes to determine whether host correlates of immunity can be identified during vaccination in mice,” explained Seattle BioMed’s Stefan Kappe, Ph.D. “These model vaccines provide an opportunity to discriminate biomarkers associated with complete, long-lasting protection from those associated with partial, short-lived or lack of protection.”

Researchers at Seattle BioMed will then apply the knowledge gained in mouse models to human studies. “Through studies conducted at Seattle BioMed’s Malaria Clinical Trials Center, we’ll evaluate whether biomarkers of protection identified in the rodent models will predict protective immunity in humans,” explained Wang.

Seattle BioMed researchers will employ network analysis of transcriptional responses to predict protection in both mice and humans to determine if they can find universal markers that will allow them to optimize vaccine candidates. According to Alan Aderem, Ph.D., the power of systems biology lies in its capacity to predict the behavior of a biological system.  “If we have the ability to predict whether a vaccine candidate for malaria will work before it goes into large scale clinical trials, we could move away from today’s typical ‘trial and error’ method toward a more powerful predictive approach to vaccine discovery and development,” he said.

Through these integrated studies, Seattle BioMed researchers will deliver a set of candidate immune biomarkers associated with protection against malaria infection that can be used for monitoring vaccine efficacy. “This will facilitate future malaria vaccine trials with the ultimate goal of accelerating the development of a highly effective malaria vaccine that has the potential to save millions of lives,” said Wang.

Wang is leading the study – Seattle BioMed’s first to include the integration of its recently announced systems biology approach to infectious disease research – with a team that includes Seattle BioMed’s Stefan Kappe, Ph.D., and Alan Aderem, Ph.D., along with Patrick Duffy, M.D., of the National Institutes of Health, Jonathan Derry, Ph.D., of Sage Bionetworks, and Xiaowu Liang, Ph.D., of Antigen Discovery Inc. (ADi).

Source: PR Newswire

Fighting Malaria with Mobile Phone Technology in Haiti

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Mobile phone technology is being used to bring life saving information to millions of Haitians.The Red Cross has embarked on a nationwide malaria prevention campaign, sending over 3.5 million SMS messages which include information on how malaria is transmitted, how to recognize the symptoms, treatment options, and simple steps for prevention.“There are nearly four million mobile phone subscribers in Haiti” said Sharon Reader, IFRC Beneficiary Communications delegate. “Mobile technology is a fast, easy and cost-effective way to put life-saving information directly in the hands of the population.”

Read more, via IFRC.

Peace Corps Volunteers Join Malaria Fight with Education and Bed Net Distribution Program

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Peace Corps volunteers are collaborating with host country government agencies, nongovernmental organizations (NGOs), the President’s Malaria Initiative (PMI), and local community members to raise awareness of malaria prevention techniques and help control the disease.

Malaria is an infectious disease caused by a parasite (plasmodium) transmitted from human to human by the bite of infected female Anopheles mosquitoes. Young children, pregnant women, and people living with HIV/AIDS have the highest risk for malaria morbidity and mortality. The World Health Organization states that, in 2008, there were 247 million cases of malaria and nearly one million deaths, mostly among children living in Africa.

Peace Corps volunteers are working to mitigate malaria’s devastating impact. Volunteers play a key role in grassroots education and activities that improve community-based knowledge about malaria transmission and promote behavior changes to reduce the spread of the disease.

In addition to their primary service assignments, all Peace Corps volunteers in Benin and Senegal are encouraged to work in malaria-prevention efforts. This year, volunteers have partnered with host-country agencies and NGOs to distribute over 110,000 mosquito nets.

In Senegal, Peace Corps is delivering bed nets to remote villages and conducting malaria lessons with community members before distribution. Volunteers aim to provide a mosquito net for every bed in areas with high malaria rates and are conducting post-distribution evaluations with local health workers to verify that the nets are being properly used.

Peace Corps volunteers in Benin are working closely with PMI cooperating agencies to facilitate the wholesale purchase of mosquito nets from the private sector to sell at a subsidized price to community health centers and individual families. These nets are often distributed during pre-natal consultations and vaccination campaigns.

African nations are not the only ones that have to deal with malaria. In Ecuador, Peace Corps volunteer Kristen Mallory of Cincinnati, Ohio, has taken a hands-on approach with the Ecuadorian Ministry of Public Health to combat malaria and Dengue Fever. Mallory distributed chemicals that kill mosquito larva in water tanks to rural communities and educated locals about malaria prevention and how to destroy mosquito breeding grounds.

April 25th was World Malaria Day, a unified commemoration of the global effort to provide effective control of malaria around the world.

As Peace Corps approaches its 50th anniversary, its service legacy continues to promote peace and friendship around the world with 7,671 volunteers serving in 76 host countries. Historically, nearly 200,000 Americans have served with the Peace Corps to promote a better understanding between Americans and the people of 139 host countries. Peace Corps Volunteers must be U.S. citizens and at least 18 years of age. Peace Corps service is a 27-month commitment.

Read Peace Corps Response volunteer Kris White’s full account.

Mosquitos Make Proteins to Handle Heat Spike of Hot Blood Meals

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Mosquitoes make proteins to help them handle the stressful spike in body temperature that’s prompted by their hot blood meals, a new study has found.

The mosquito’s eating pattern is inherently risky: Taking a blood meal involves finding warm-blooded hosts, avoiding detection, penetrating tough skin and evading any host immune response, not to mention the slap of a human hand.

Until now, the stress of the hot blood meal itself has been overlooked, researchers say.

Scientists have determined in female mosquitoes that the insects protect themselves from the stress of the change in body temperature during and after a meal by producing heat shock proteins. These proteins protect the integrity of other proteins and enzymes, in turn helping the mosquitoes digest the blood meal and maintain their ability to produce eggs.

Tests in two other types of mosquitoes and in bed bugs showed that these insects undergo a similar response after a blood meal.

“These heat shock proteins are really important in a lot of stress responses. Our own bodies make these proteins when we have a fever,” said David Denlinger, professor of evolution, ecology and organismal biology at Ohio State University and senior author of the study. “It’s one of those things that, in retrospect, seems obvious – that blood meals might cause a stress like that. But it hadn’t been pursued before.”

The research appears this week in the online early edition of the Proceedings of the National Academy of Sciences.

Denlinger and colleagues conducted experiments in the Aedes aegypti mosquito, which is a carrier of yellow fever.

The researchers placed sensors on female mosquitoes and observed that upon taking in a blood meal on a chicken, the insects’ body temperatures increased from 22 to 32 degrees Celsius (71.6 to 89.6 Fahrenheit) within one minute – among the most rapid body temperature increases ever recorded in a cold-blooded animal. After the feeding, their body temperatures decreased to room temperature within a few minutes.

In response to that blood feeding, the mosquitoes’ level of Hsp70 – heat shock protein 70 – increased nearly eightfold within one hour and remained at least twice as high as usual for 12 hours. The increase in these proteins was most pronounced in the midgut area.

Denlinger and colleagues tested potential triggers for this protein increase by injecting the mosquitoes with a saline solution at two temperatures: 37 degrees Celsius (98.6 degrees Fahrenheit) and room temperature. Only the warmer saline generated an increase in Hsp70, suggesting that the elevation in temperature associated with the meal, rather than the subsequent increase in body volume, is what causes the generation of those proteins.

Sometimes, mosquitoes feed on cold-blooded amphibians, which should not cause the same amount of stress. To test that theory, the researchers also gave mosquitoes a feeding opportunity on cooler blood, which failed to generate an increase in heat shock proteins.

And what happens if this protein is not produced? The researchers manipulated the mosquitoes’ RNA to figure that out.

When the scientists knocked down expression of the gene that encodes the heat shock protein, the amount of Hsp70 production was reduced by 75 percent. Under those circumstances, mosquitoes still ate a normal blood meal. But blood protein levels remained elevated for a longer period of time, suggesting that digestion of those proteins was impaired. In addition, egg production decreased by 25 percent when the heat shock protein was suppressed.

Heat shock proteins help maintain the three-dimensional integrity of enzymes and proteins when temperatures rise suddenly, and can target damaged proteins and enzymes for elimination, Denlinger said. “We think that in this case, they are important to maintaining the integrity of some critical enzymes and proteins involved in digestive processes. When we knock out those proteins, it impairs digestion a bit and as a result the mosquitoes don’t lay as many eggs,” he said.

The researchers observed similar body temperature increases and elevations in Hsp70 levels in three other insects: Culex pipiens and Anopheles gambiae, mosquitoes that are carriers of West Nile virus and malaria, respectively, and Cimex lectularius, the bed bug. Though new knowledge about the genetics of these insects, especially the mosquitoes, might someday inform attempts to kill them as a method of disease control, Denlinger said the primary contribution of this research is better understanding of how mosquitoes protect themselves in this novel way.

This work was supported by grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases and the National Science Foundation.

Co-authors include Joshua Benoit, a former Ohio State graduate student who is now a postdoctoral researcher at Yale University, and Giancarlo Lopez-Martinez, Kevin Patrick, Zachary Phillips and Tyler Krause of Ohio State’s Departments of Entomology and Evolution, Ecology and Organismal Biology. Lopez-Martinez is now at the University of Florida.

Source: Proceedings of the National Academy of Sciences, Ohio State University

NetGuarantee: Financing Speeds Delivery of Mosquito Nets

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NetGuarantee, a new innovative finance facility, announces its first transaction with Zurich in North America, part of the Zurich Financial Services Group, to celebrate World Malaria Day today, April 25. This collaboration will help accelerate access to and advance the delivery of vital malaria prevention tools in Africa by six to 10 months, and shows how core business competencies and best practices can improve efficiencies in global health and save lives.

[Read more…]

Genetically Modified Mosquito “Selfish Gene” Could Helps Stop Spread of Malaria

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Many scientists have played with the idea of creating a genetically modified mosquito that won’t transmit malaria, which kills about 850,000 people a year, and releasing it into the wild. But in the face of the millions of mosquitoes out there that do ferry malaria around, how would the trait spread fast enough to make a difference?

Now, scientists have developed a way to cause a “selfish” gene to spread to more than half of a mosquito population over just a few generations, suggesting a method to quickly and broadly disrupt genes required for carrying malaria.

Read more, via Discover Magazine.