ECOWAS Program to Eradicate Malaria

by

QUESTION
Why can I find no mention on your website of the ECOWAS program to eradicate malaria in their countries?

ANSWER
Thanks for bringing up ECOWAS. Since 2011, ECOWAS leaders have signaled a commitment to eradicating malaria in their region by 2015, and pilot programs are already underway in several countries, including Burkina Faso, Nigeria and Ghana. The program has centered on the use of larvicides for control of mosquito populations, thus reducing transmission. In April 2012, ECOWAS signed an agreement with Cuba in order to revitalize joint efforts to eradicate malaria in both West Africa as well as the Caribbean island. Soon after, Venezuela entered the agreement, pledging $20 million to the cause. These funds
will help support the construction of manufacturing facilities for biolarvicides in Nigeria, Cote d’Ivoire and Ghana, among other things.

In August, the Commissioner of ECOWAS emphasized the need for community engagement in the fight against malaria. A road map for measuring future progress was also drawn up by health advisers from the region; the next high-level ministerial meeting to evaluate the program will take place in West Africa, and will likely include Cuban and Venezuealan partners, in December 2012.

WHO recommends that Larviciding is indicated only for vectors which tend to breed in permanent or semi-permanent water bodies that can be identified and treated, and where the density of the human population to be protected is sufficiently high to justify the treatment with relatively short cycles of all breeding places.

Reduction in Child Mortality in Niger

by

Niger has achieved great reductions in child mortality and gains in coverage for interventions in child survival than neighbouring countries in west Africa.
About 59,000 lives were saved in children younger than 5 years in 2009, attributable to the introduction of insecticide-treated bednets (25%); improvements in nutritional status (19%); vitamin A supplementation (9%); treatment of diarrhoea with oral rehydration salts and zinc, and careseeking for fever, malaria, or childhood pneumonia (22%); and vaccinations (11%).

Read more via The Lancet.

Chemists Develop New Synthesis for Antimalarial Drug, Artemisinin

by

Chemists at Indiana University have developed a new synthesis for the world’s most useful antimalarial drug, artemisinin, giving hope that fully synthetic artemisinin might help reduce the cost of the live-saving drug in the future.

Effective deployment of ACT, or artemisinin-based combination therapy, has been slow due to high production costs of artemisinin. The World Health Organization has set a target “per gram” cost for artemisinin of 25 cents or less, but the current cost is about $2.40 per gram, and production of low-cost semi-synthetic artemisinin has yet to materialize.

“In 2005, the WHO claimed that the structure of artemisinin was too complex for cost-effective synthesis,” said IU Bloomington College of Arts and Sciences chemistry professor Silas Cook. “We saw this as a natural challenge to the creativity and tenacity of organic chemists.”

Published recently in the Journal of the American Chemical Society as “A Concise Synthesis of Artemisinin,” Cook and postdoctoral co-author Chunyin Zhu report a succinct five-part process beginning with inexpensive cyclohexenone, an ideal feedstock available on metric-ton scale. Subsequent chemistry highlights several new reactions developed in the Cook group to enable this short, low-cost synthesis.

The result was the production of fully synthetic artemisinin on gram scale, greater than all previous total syntheses combined.

“The key to the ultimate success of synthetic artemisinin will be the large-scale production of the drug,” Cook said. “As such, we had to completely rethink what qualified as suitable starting materials for this synthesis and invent new chemistry.” The result was the use of readily available commodity chemicals in a process that was shorter than any other artemisinin total synthesis ever conducted.

The next challenge will be to move from gram-scale to kilogram-scale production, a process Cook may or may not be involved with.

“There is still work to be done. And we’d love to do it here, but the project has yet to attract outside funding,” he said. “This is still in an experimental phase until you can scale up. We patented it, so the intellectual property rights are in place.”

Source: Indiana University; Journal of the American Chemical Society

Anti Malaria Medication for Dominican Republic

by

QUESTION

I am from the UK and am planning to go to the Dominican Republic (Punta Cana) in October. I have been prescribed Malarone from the nurse at my local GP’s, although my mothers nurse informed her that this drug is not suitable for this area? I would appreciate any help, many thanks.

ANSWER

Malarone is suitable for travel to the Dominican Republic. However, the type of malaria found there is also still considered sensitive to chloroquine, so chloroquine is also an acceptable form of chemoprophylaxis for travel to this country. Mefloquine and doxycycline can also be taken.

Gates Foundation Offers USD$100K Grants for Innovative Global Health and Development Projects

by

The Bill & Melinda Gates Foundation announced today that it is accepting applications for Round 10 of its Grand Challenges Explorations initiative, a USD$100 million grant initiative encouraging innovation in global health and development research.  Anyone with a transformative idea is invited to submit an easy, online, two page application.

Grand Challenges Explorations is pleased to have the opportunity to again partner with Cannes Lions on a topic that will identify new ways to communicate the impact of investments that support global development. It includes four specific submission categories for grant seekers. We hope these will solicit unique proposals from innovators around the world that the foundation can support as part of its overall mission to alleviate global poverty.

Topics for Grand Challenges Explorations Round 10:

  • Aid is Working, Tell the World (Part 2)  (in partnership with Cannes Lions )
  • Labor Saving Innovations for Women Smallholder Farmers (new!)
  • New Approaches in Model Systems, Diagnostics, and Drugs for Specific Neglected Tropical Diseases (new!)
  • New Approaches for the Interrogation of Anti-Malarial Compounds

“Bold thinking from the world’s innovators can address health and development challenges and make a big difference in the lives of those most in need,” said Chris Wilson, Director of Global Health Discovery & Translational Sciences at the Bill & Melinda Gates Foundation.  “We seek pioneering proposals that have the potential to improve the lives of millions.”

The Gates Foundation and an independent group of reviewers will select the most innovative proposals, and grants will be awarded within approximately five months from the proposal submission deadline. Initial grants will be USD$100,000 each. Projects demonstrating potential will have the opportunity to receive additional funding up to USD$1 million.

Proposals are being accepted at the Grand Challenges website through November 7, 2012. Applicants from Africa, Asia, and the developing world are encouraged to apply.

Source: Bill & Melinda Gates Foundation

Malaria Nearly Eliminated in Sri Lanka Despite Decades of Conflict

by

UCSF, Sri Lankan Researchers Credit Adaptability of Malaria Control Program

Despite nearly three decades of conflict, Sri Lanka has succeeded in reducing malaria cases by 99.9% since 1999 and is on track to eliminate the disease entirely by 2014.

According to a paper published today in the online, open-access journal PLOS ONE, researchers from Sri Lanka’s Anti-Malaria Campaign and the UCSF Global Health Group examined national malaria data and interviewed staff of the country’s malaria program to determine the factors behind Sri Lanka’s success in controlling malaria, despite a 26-year civil war that ended in 2009.

Typically, countries with conflict experience a weakening of their malaria control programs and an increased risk of outbreaks and epidemics, the researchers said.

Chief among its keys to success was the program’s ability to be flexible and adapt to changing conditions, the study found. For instance, to protect hard-to-reach, displaced populations, public health workers deployed mobile clinics equipped with malaria diagnostics and antimalarial drugs, whenever it was safe to do so. Likewise, when it was impossible to routinely spray insecticides in homes in conflict zones, the malaria program distributed long-lasting insecticide-treated nets, engaging non-governmental partner organizations familiar with the areas to help with distribution.

The program was able to sustain key prevention and surveillance activities in conflict areas through support from partner organizations and support from the Global Fund to Fight AIDS, Tuberculosis and Malaria.

Otherwise, researchers found that the keys to Sri Lanka’s success were the same as those deployed in non-conflict areas: rigorously and consistently providing interventions to prevent malaria among high-risk populations; proper and prompt diagnosis and treatment of all confirmed malaria cases; and maintenance of an effective surveillance system to quickly detect and respond to spikes in cases. Still, challenges remain.

“Sustaining the gains of elimination efforts and preventing resurgence is even more challenging today, especially in tropical settings such as Sri Lanka,” said Rabindra Abeyasinghe, MD, the paper’s first author, who led the research at the Sri Lankan Anti-Malaria Campaign. “In this era, sustaining the interest of partners and local decision makers, and ensuring continued funding, are becoming increasingly difficult.  To avoid the tragic mistakes of the past, we must resolve to continue to devote the necessary resources and energy to the fight against malaria in Sri Lanka.”

Sri Lanka has an extensive history of battling malaria, and nearly eliminated it once before. In 1963, during the era of global eradication efforts, the country achieved a low of only 17 cases, down from 92,000 cases in 1953. With funding declines and reduced spraying and surveillance, the country saw a massive resurgence to 1.5 million cases in 1967-1968.

Since 1970, Sri Lanka has worked to bring malaria back under control, with compelling success, the authors said. In 2011, the country recorded just 124 locally acquired cases – about six cases per million people. This reduction is particularly noteworthy, the researchers noted, given that much of the progress was made during the civil war.

“It is very exciting to document Sri Lanka’s current progress toward malaria elimination, to add another chapter to our country’s ongoing fight against the disease,” said Gawrie Galappaththy, MD, a study coauthor at the Anti-Malaria Campaign at Sri Lanka’s Ministry of Health. However, she said, achieving zero malaria will require continued investments and hard work.

“There is no silver bullet for malaria elimination,” Galappaththy said. “Instead, it’s a daily commitment to finding the cases, treating the patients and preventing transmission.”

Today, even with the country’s great progress, Sri Lanka continues to face hurdles in its goal of driving malaria transmission to zero. Total malaria cases have dramatically dropped, but the proportion of Plasmodium vivax malaria infections – the more difficult to diagnose and treat form of malaria most common in Sri Lanka – is on the rise.

Another challenge is the shift in the population group at highest risk for malaria.  In most of the world, children and pregnant women are most at risk; however following the success of Sri Lanka’s control program in protecting and treating these populations, the researchers found that the group most at risk today in Sri Lanka is adult men, particularly those exposed to malaria-carrying mosquitoes through their work, such as gem mining, military service and farming. Sri Lanka is developing new strategies to target these groups.

“Sri Lanka is showing the world how to eliminate malaria,” said Sir Richard Feachem, KBE, FREng, DSc(Med), PhD, director of the Global Health Group and senior author of the paper. “The country has made extraordinary progress, reducing malaria by 99.9 percent in the past decade. And all this achieved during a particularly nasty civil war. With continued commitment from the country’s Government and supporters, we are confident that Sri Lanka will finish the fight and become a malaria-free country.”

The paper can be found here: “Malaria control and elimination in Sri Lanka: documenting progress and success factors in a conflict setting,”  The research was funded by the Bill & Melinda Gates Foundation. The authors did not report any disclosures.

The Global Health Group is part of UCSF Global Health Sciences and is dedicated to translating new approaches into large-scale action to improve the lives of millions of people. The group’s Malaria Elimination Initiative provides research and advocacy support to countries moving towards an evidence-based path to malaria elimination.

Source: UCSF

Newly Sequenced Malaria Genomes Show Genetic Variability

by

Genetic variability revealed in malaria genomes newly sequenced by two multi-national research teams points to new challenges in efforts to eradicate the parasite, but also offers a clearer and more detailed picture of its genetic composition, providing an initial roadmap in the development of pharmaceuticals and vaccines to combat malaria.

The research appears in two studies published in the latest issue of the journal Nature Genetics. They focus on Plasmodium vivax (P. vivax), a species of malaria that afflicts humans and the most prevalent human malaria parasite outside Africa, and Plasmodium cynomolgi (P. cynomolgi), a close relative that infects Asian Old World monkeys.

“The bad news is there is significantly more genetic variation in P. vivax than we’d thought, which could make it quite adept at evading whatever arsenal of drugs and vaccines we throw at it,” said Professor Jane Carlton, senior author on both studies and part of New York University’s Center for Genomics and Systems Biology. “However, now that we have a better understanding of the challenges we face, we can move forward with a deeper analysis of its genomic variation in pursuing more effective remedies.”

In one study, the researchers examined P. vivax strains from different geographic locations in West Africa, South America, and Asia, providing the researchers with the first genome-wide perspective of global variability within this species. Their analysis showed that P. vivax has twice as much genetic diversity as the world-wide Plasmodium falciparum (P. falciparum) strains, revealing an unexpected ability to evolve and, therefore, presenting new challenges in the search for treatments.

The second study, performed jointly with Professor Kazuyuki Tanabe at Osaka University, Japan, sequenced three genomes of P. cynomolgi. The researchers compared its genetic make-up to P. vivax and to Plasmodium knowlesi (P. knowlesi), a previously sequenced malaria parasite that affects both monkeys and humans in parts of Southeast Asia.

Their work marked the first time P. cynomolgi genomes have been sequenced, allowing researchers to identify genetic diversity in this parasite. Its similarity to P. vivax means that their results will also benefit future efforts to understand and fight against forms of malaria that afflict humans.

“We have generated a genetic map of P. cynomolgi, the sister species to P. vivax, so we can now push forward in creating a robust model system to study P. vivax,” explained Tanabe. “This is important because we can’t grow P. vivax in the lab, and researchers desperately need a model system to circumvent this.”

Much of the work occurred under a seven-year grant from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The funding has established 10 International Centers of Excellence for Malaria Research (ICEMR). Carlton is heading an ICEMR based in India, where malaria – and P. vivax in particular — is a significant public health burden. A particular aim of this Center of Excellence is to support and help train scientists in India who can then work to combat infectious diseases, such as malaria, where they are most prominent. The P. vivax sequencing was funded by NIAID as part of the NIAID funded Genomic Sequencing Center for Infectious Diseases at the Broad Institute under Contract No. HHSN272200900018C. The Burroughs Wellcome Fund was instrumental in providing pilot funds for the P. cynomolgi sequencing.

Researchers at the following institutions were also part of the P. vivax sequencing: The Broad Institute, the National Institute of Malaria Research in India, Arizona State University, and the Centers for Disease Control and Prevention.

Researchers at the following institutions were also part of the work on P. cynomolgi: Osaka University, Dokkyo Medical University, Japan’s Corporation for Production and Research of Laboratory Primates, Nagasaki University, Juntendo University’s School of Medicine, the University of Tokyo, the National Institute of Biomedical Innovation, the Centers for Disease Control and Prevention, and Arizona State University.

Source: New York University

Researchers ID Key Antibodies in Kenyans with Malaria Immunity

by

Australian scientists say they have made an important discovery in the fight against malaria.   They have found that people in Africa who are immune to malaria have developed powerful natural defenses against the disease.

Researchers at Melbourne’s Burnet Institutewho are searching for ways to develop a vaccine believe that people in east Africa could help unlock some of the secrets of this unremitting disease.

The scientists are investigating why some Kenyans have become immune to malaria.  They have identified antibodies, which are part of the body’s natural defenses, that attack the malaria parasite. The hope is that a vaccine can be developed to recreate this natural immunity. Professor James Beeson, a public health physician at the Burnet Institute, says it is an important breakthrough.

“What we know is that some people who develop malaria and recover, develop an immune response that seems to then protect them against, you know, subsequent infections or attacks,” he said.  “So the big question has been how does the immune system do this?  What specific part of the malaria organism parasite does the immune system attack?  And if we know this, could we use this knowledge to develop a vaccine?”

Malaria causes about one million deaths every year, many of them children under the age of five. The mosquito-born disease is present in 90 countries across Africa, South America and Asia.  It also prevalent in the South Pacific nations of Papua New Guinea, the Solomon Islands and Vanuatu. Australian researchers believe that an effective vaccine could be available within the next decade.

Source: VOA News

New Anti-Malarial Drug Target

by

An international team of scientists have identified the first reported inhibitors of a key enzyme involved in survival of the parasite responsible for malaria. Their findings, which may provide the basis for anti-malarial drug development, are currently published in the online version of the Journal of Medicinal Chemistry.

Tropical malaria is responsible for more than 1.2 million deaths annually. Severe forms of the disease are mainly caused by the parasite Plasmodium falciparum, transmitted to humans by female Anopheles mosquitoes. Malaria eradication has not been possible due to the lack of vaccines and the parasite’s ability to develop resistance to most drugs.

Led by researchers from the Department of Pediatrics at the University of California, San Diego School of Medicine, the team conducted high-throughput screening of nearly 350,000 compounds in the National Institutes of Health’s Molecular Libraries Small Molecule Repository (MLSMR) to identify compounds that inhibit an enzyme which plays an important role in parasite development: Plasmodium falciparum glucose-6-phosphate dehydrogenase (PfG6PD) is essential for proliferating and propagating P. falciparum.

“The enzyme G6PD catalyzes an initial step in a process that protects the malaria parasite from oxidative stress in red blood cells, creating an environment in which the parasite survives,” said senior author Lars Bode, PhD, assistant professor in the UCSD Department of Pediatrics, Division of Neonatology and the Division of Gastroenterology, Hepatology and Nutrition. People with a natural deficiency in this enzyme are protected from malaria and its deadly symptoms, an observation that triggered the reported research.

The parasitic form of the enzyme (PfG6PD) is what contributes the majority of G6PD activity in infected red blood cells. Because the parasite lives in the blood of a malaria-infected person, the scientists aimed at identifying compounds that inhibit the parasitic form but not the human form of the enzyme. “We didn’t want to interfere with the human form of the enzyme and risk potential side effects,” Bode explained.

Scientific testing had previously been limited by a lack of recombinant PfG6PD. Team members in the lab of Katja Becker, PhD, at the Interdisciplinary Research Center at Justus-Liebig-University in Giessen, Germany produced the first complete and functional recombinant PfG6PD, and researchers led by Anthony Pinkerton, PhD, at Sanford-Burnham Medical Research Institute used it to identify the lead compound resulting from their efforts, ML276.

ML276 represents the first reported selective PfG6PD inhibitor, which stops the growth of malaria parasites in cultured red blood cells – even those parasites that developed resistance to currently available drugs. “ML276 is a very promising basis for future drug design of new anti-malarial therapeutics,” said Bode.

Contributors to the study include Janina Preuss, UC San Diego, Justus-Liebig-University and Sanford-Burnham Medical Research Institute; Esther Jortzik, Stefan Rahlfs and Katja Becker, Justus-Liebig-University; Patrick Maloney, Satyamaheshwar Peddibhotla, Paul Hershberger, Eliot Sugarman, Becky Hood, Eigo Suyama, Kevin Nguyen, Stefan Vasile, Arianna Mangravita-Novo, Michael Vicchiarelli, Danielle McAnally, Layton H. Smith. Gregory P. Roth, Michael P. Hedrick, Palak Gosalia, Monika Milewski, Yujie Linda Li, Eduard Sergienko, Jena Diwan, Thomas D.Y. Chung, and Anthony B. Pinkerton, Sanford-Burnham.

The study was supported by the National Institutes of Health (1R21AI082434), the Deutsche Forschungsgemeinschaft, and an NIH Molecular Libraries grant (U54 HG005033) to the Conrad Prebys Center for Chemical Genomics at Sanford Burnham Medical Research Institute, one of the comprehensive centers of the NIH Molecular Libraries Probe Production Centers Network (MLPCN).

Source: University of California, San Diego Health Sciences

Genetically Engineered Bacteria Prevent Mosquitoes From Transmitting Malaria

by

Researchers at the Johns Hopkins Malaria Research Institute have genetically modified a bacterium commonly found in the mosquito’s midgut and found that the parasite that causes malaria in people does not survive in mosquitoes carrying the modified bacterium. The bacterium, Pantoea agglomerans, was modified to secrete proteins toxic to the malaria parasite, but the toxins do not harm the mosquito or humans. According to a study published by PNAS, the modified bacteria were 98 percent effective in reducing the malaria parasite burden in mosquitoes.

“In the past, we worked to genetically modify the mosquito to resist malaria, but genetic modification of bacteria is a simpler approach,” said Marcelo Jacobs-Lorena, PhD, senior author of the study and a professor with Johns Hopkins Bloomberg School of Public Health. “The ultimate goal is to completely prevent the mosquito from spreading the malaria parasite to people.”

With the study, Jacobs-Lorena and his colleagues found that the engineered P. agglomerans strains inhibited development of the deadliest human malaria parasite Plasmodium falciparum and rodent malaria parasite Plasmodium berghei by up to 98 percent within the mosquito. The proportion of mosquitoes carrying parasites (prevalence) decreased by up to 84 percent.

“We demonstrate the use of an engineered symbiotic bacterium to interfere with the development of P. falciparum in the mosquito. These findings provide the foundation for the use of genetically modified symbiotic bacteria as a powerful tool to combat malaria,” said Jacobs-Lorena.

Malaria kills more than 800,000 people worldwide each year. Many are children.

The authors of “Fighting malaria with engineered symbiotic bacteria from vector mosquitoes” are Sibao Wang, Anil K. Ghosh, Nicholas Bongio, Kevin A. Stebbings, David J. Lampe and Marcelo Jacobs-Lorena.

The research was supported by National Institute of Allergy and Infectious Diseases, the Bill & Melinda Gates Foundation, the Johns Hopkins Malaria Research Institute and the Bloomberg Family Foundation.

Source: Johns Hopkins Bloomberg School of Public Health