WHO Launches Program to Counter Drug-Resistant Malaria

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On World Malaria Day, the World Health Organization has launched an emergency program in Phnom Penh to tackle a worrying regional trend – a strain of malaria that is proving resistant to the most important anti-malarial drug.

Six years ago, health researchers were worried after a strain of malaria in western Cambodia began to show resistance to the world’s key malaria treatment – Artemisinin-based Combination Therapy, known as ACT.

In response, the Cambodian government and its health partners, including the World Health Organization, put in place a program to prevent the resistant strain (falciparum malaria) from spreading within Cambodia and beyond its borders.

That program appears to have contained the resistant strain. But Thailand, Burma and Vietnam have reported pockets of artemisinin-resistant malaria strains.

The WHO malaria specialist in Phnom Penh, Stephen Bjorge, said it is likely the strains in those countries arose independently of Cambodia’s – which means the containment efforts have worked.

But because artemisinin is the standard treatment, it is important the resistant strains in all of these areas are contained and then eradicated. That is the purpose of a three-year, $400-million program the World Health Organization announced Thursday.

“The risks are significant – not only are they significant for the region in terms of having a reversal of the gains that have been made against malaria, but they are actually significant globally,” said Robert Newman, director of the WHO’s Global Malaria Program. “If history is any guide, if we were not to contain this problem then it is very likely to spread elsewhere. Especially risky is to sub-Saharan Africa, where the greatest burden still exists. And, if we were to lose the efficacy of the ACTs today, this really would be a public health catastrophe in Africa.”

The WHO-led program is being funded by the Global Fund, the Bill & Melinda Gates Foundation and by the Australian government’s development arm called AusAID.

It will cover six countries: the four where resistance has already been found, as well as two more considered to be “at risk” from the resistant strain: Laos and an area of southern China.

Newman said some of the lessons learned from Cambodia’s efforts are being used.

“This is not starting from zero,” he explained. “It is building on the experience initially on the Cambodia-Thailand border where those countries gained a lot of experience in how to reach the populations that are actually most difficult to reach – migrant and mobile populations, how to use village health care workers, how to more aggressively remove substandard medicines from the market.”

The program will distribute insecticide-treated bed nets; monitor fake drugs; ensure people have access to reliable testing and treatment; and track the disease. Migrant communities and people living in border regions will be key targets of the program.

AusAID has provided $5 million of funding for the program.

“Well, our initial funding is fixed, but the reality is Australia is part of this region,” said AusAID’s principal health advisor Ben David. “We are part of the Asia-Pacific and we see this as a critical investment to protect the poor in the region from malaria, but also to protect the interests of countries because if this problem gets out of control and we see malaria drug resistance spread in the region and beyond, then we are in to face a big set of problems.”

David says, last year, malaria killed 42,000 people in the Asia-Pacific region and more than half a million worldwide, most of them children in Africa.

Recent years have seen good progress in tackling malaria, but the WHO warns that could be undone should the resistant strains escape the current pockets in the countries of the Greater Mekong sub-region.

David believes governments will do their part to prevent the spread.

“It has actually got significant economic implications, if this problem of resistance continues. So, we really need to make the economic case to governments to continue to invest in this problem,” he added.

The chloroquine-resistant malaria strain has caused millions of deaths globally since it emerged 60 years ago from the forests of western Cambodia.

The World Health Organization warns the world cannot afford a similar repeat outbreak by allowing the new strain or strains of artemisinin-resistant malaria to escape the region.

Source: VOA News

Phase III Trial of RTS,S Malaria Candidate Vaccine Reduces Malaria by One Third

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Results from a pivotal, large-scale Phase III trial, published online today in the New England Journal of Medicine, show that the RTS,S malaria vaccine candidate can help protect African infants against malaria. When compared to immunization with a control vaccine, infants (aged 6-12 weeks at first vaccination) vaccinated with RTS,S had one-third fewer episodes of both clinical and severe malaria and had similar reactions to the injection. In this trial, RTS,S demonstrated an acceptable safety and tolerability profile.

Eleven African research centres in seven African countries1 are conducting this trial, together with GlaxoSmithKline (GSK) and the PATH Malaria Vaccine Initiative (MVI), with grant funding from the Bill & Melinda Gates Foundation to MVI.

Dr. Salim Abdulla, a principal investigator for the trial from the Ifakara Health Institute, Tanzania, said: “We’ve made significant progress in recent years in our battle against malaria, but the disease still kills 655,000 people a year—mainly children under five in sub-Saharan Africa. An effective malaria vaccine would be a welcome addition to our tool kit, and we’ve been working toward this goal with this RTS,S trial. This study indicates that RTS,S can help to protect young babies against malaria. Importantly, we observed that it provided this protection in addition to the widespread use of bed nets by the trial participants.”

Efficacy
When administered along with standard childhood vaccines,2 the efficacy of RTS,S in infants aged 6 to 12 weeks (at first vaccination) against clinical and severe malaria was 31% and 37%,3 respectively, over 12 months of follow-up after the third vaccine dose.4 Insecticide-treated bed nets were used by 86% of the trial participants, which demonstrated that RTS,S provided protection beyond existing malaria control interventions. The efficacy observed with RTS,S last year in children aged 5-17 months of age against clinical and severe malaria was 56% and 47%, respectively. Follow-up in this Phase III trial will continue and is expected to provide more data for analyses to better understand the different findings between the age categories.

Dr. Abdulla added: “The efficacy is lower than what we saw last year with the older 5-17 month age category, which surprised some of us scientists at the African trial sites. It makes us even more eager to gather and analyze more data from the trial to determine what factors might influence efficacy against malaria and to better understand the potential of RTS,S in our battle against this devastating disease. We were also glad to see that the study indicated that RTS,S could be administered to young infants along with standard childhood vaccines and that side effects were similar to what we would see with those vaccines.”

Safety
There was no increase in overall reporting of serious adverse events5 (SAEs) between the infants vaccinated with the RTS,S malaria vaccine candidate and infants in the control group, which received a comparator vaccine. Side effects primarily included local injection site reactions, which were less frequent following RTS,S vaccinations compared to the DTP-HepB/Hib vaccine. Fever was reported more frequently following RTS,S vaccinations than the control vaccine group (30.6% versus 21.1% of vaccine doses, respectively).

Two new cases of meningitis were reported in the 6-12 week-old infant age category in addition to the 9 reported last year; one in the RTS,S group and one in the control vaccine group. Further analysis revealed a bacterial cause of the meningitis in 7 of the 11 cases.

Sir Andrew Witty, CEO, GSK said: “While the efficacy seen is lower than last year, we believe these results confirm that RTS,S can help provide African babies and young children with meaningful protection against malaria. They take us another important step forward on the journey towards having a new intervention available against this disease, which is a huge burden on the health and economic growth of Africa. We remain convinced that RTS,S has a role to play in tackling malaria and we will continue to work with our partners and other stakeholders to better understand the data and to define how the vaccine could best be used to provide public health benefit to children in malaria endemic areas in Africa.”

David Kaslow, Director of the PATH Malaria Vaccine Initiative, said: “Determining the role of RTS,S in Africa will depend on analyses of additional data. We are now an important step closer to that day. Success in developing malaria vaccines depends on many factors: at the top of the list are partnerships and robust evidence, coupled with an understanding that different combinations of tools to fight malaria will be appropriate in different settings in malaria-endemic countries. My congratulations go out to the team at GSK and to the African research centres for their exemplary conduct of this trial.”

“This is an important scientific milestone and needs more study,” said Bill Gates, co-founder of the Bill & Melinda Gates Foundation. “The efficacy came back lower than we had hoped, but developing a vaccine against a parasite is a very hard thing to do. The trial is continuing and we look forward to getting more data to help determine whether and how to deploy this vaccine.”

The vaccine is being developed in partnership by GSK and MVI, together with prominent African research centres1*. The collaborators are represented on the Clinical Trials Partnership Committee, which oversees the conduct of the trial. An extended team of organisations work on RTS,S, including scientists from across Africa, Europe, and North America. Major funding for clinical development of RTS,S comes from a grant by the Bill & Melinda Gates Foundation to MVI.

Looking ahead
Follow-up in this Phase III trial will continue to provide more data for analyses to better understand the different findings between the age categories. These data and analyses should also provide insights into the vaccine candidate’s efficacy in different malaria parasite transmission settings. More data on the longer-term efficacy of the vaccine during 30 months of follow-up after the third dose, and the impact of a booster dose are expected to be publicly available at the end of 2014.

The data and analyses will inform the regulatory submission strategy and, if the required regulatory approvals are obtained and public health information, including safety and efficacy data from the Phase III programme, is deemed satisfactory, the World Health Organization (WHO) has indicated that a policy recommendation for the RTS,S malaria vaccine candidate is possible as early as 2015, paving the way for decisions by African nations regarding large-scale implementation of the vaccine through their national immunisation programmes. An effective vaccine for use alongside other measures such as bed nets and anti-malarial medicines would represent a decisive advance in malaria control.

GSK and MVI are committed to making this vaccine available to those who need it most, should it be approved and recommended for use. In January 2010, GSK announced that the eventual price of RTS,S (also known as MosquirixTM) will cover the cost of manufacturing the vaccine together with a small return of around 5% that will be reinvested in research and development for second-generation malaria vaccines or vaccines against other neglected tropical diseases.

About RTS,S
RTS,S is a scientific name given to this malaria vaccine candidate6 and represents the composition of this vaccine candidate. RTS,S aims to trigger the immune system to defend against Plasmodium falciparum malaria parasite when it first enters the human host’s bloodstream and/or when the parasite infects liver cells. It is designed to prevent the parasite from infecting, maturing, and multiplying in the liver, after which time the parasite would re-enter the bloodstream and infect red blood cells, leading to disease symptoms. In the Phase III efficacy trial, RTS,S is administered in three doses, one month apart. A booster dose administered 18 months after the third dose is also being studied in the trial.

The vaccine, based on a protein first identified in the laboratory of Drs Ruth and Victor Nussenzweig at New York University, was invented, developed, and manufactured in laboratories at GSK Vaccines in Belgium in the late 1980s and initially tested in US volunteers as part of a collaboration with the US Walter Reed Army Institute of Research.

In 2001, the MVI entered into partnership with GSK to study the vaccine candidate’s ability to protect young children in sub-Saharan Africa. Over time, the partnership expanded to include the 11 African research centres and, in some instances, associated scientific institutions from Europe and the United States.

With more than US$200 million in grant monies from the Bill & Melinda Gates Foundation, MVI contributes financial, scientific, managerial, and field expertise to the development of RTS,S. GSK takes the lead in the overall development of RTS,S and has invested more than $300 million to date and expects to invest more than $200 million before the completion of the project.

About the study
The first complete set of results in children aged 5 to 17 months and combined data for severe malaria in the first 250 cases from those aged 6 weeks to 17 months were published in the New England Journal of Medicine in November 2011. The Phase III trial has been designed in consultation with the appropriate regulatory authorities and the WHO. It is conducted in accordance with the highest international standards for safety, ethics, and clinical practices and is overseen by an independent data safety monitoring committee.

About GSK Vaccines
GlaxoSmithKline Vaccines is active in vaccine research and development. Headquartered in Belgium, GSK Vaccines has 14 manufacturing sites strategically positioned around the globe. Of the 1.1 billion doses of our vaccines we distributed in 2011, over 80% went to developing countries, which include the least developed, low- and middle-income countries.

GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information, please visit www.gsk.com.

The PATH Malaria Vaccine Initiative (MVI) is a global program established at PATH through an initial grant from the Bill & Melinda Gates Foundation. MVI’s mission is to accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world. MVI’s vision is a world free from malaria. For more information, please visit www.malariavaccine.org.

PATH is an international nonprofit organization that transforms global health through innovation. PATH takes an entrepreneurial approach to developing and delivering high-impact, low-cost solutions, from lifesaving vaccines and devices to collaborative programs with communities. Through its work in more than 70 countries, PATH and its partners empower people to achieve their full potential. For more information, please visit www.path.org.

1  Burkina Faso – Nanoro, Institut de Recherche en Science de la Santé (IRSS) / Centre Muraz
Gabon – Lambaréné Albert Schweitzer Hospital, Medical Research Unit
Ghana – Agogo/Kumasi: School of Medical Sciences, Kwame Nkrumah University of Science and Technology; Kumasi Centre for Collaborative Research, Agogo Presbyterian Hospital
Ghana – Kintampo: Kintampo Health Research Centre, Ghana Health Service
Kenya – Kilifi, KEMRI-Wellcome Trust Research Program
Kenya – Kombewa (Kisumu), KEMRI-Walter Reed Project Kenya Medical Research Institute
Kenya – Siaya (Kisumu), KEMRI-CDC Research and Public Health Collaboration
Malawi – Lilongwe, University of North Carolina Project at the Tidziwe Centre
Mozambique – Manhica, Centro de Investigação em Saúde de Manhiça
Tanzania – Bagamoyo, Ifakara Health Institute
Tanzania – Korogwe, National Institute for Medical Research, Tanzania, Kilimanjaro Christian Medical Centre
2  Standard childhood vaccines used were the combined diphtheria-tetanus-whole-cell-pertussis, hepatitis B, and Haemophilus influenzae type b vaccine (DTPwHepB/Hib) and the oral polio virus vaccine (OPV).
3  Based on According To Protocol (ATP) statistical methodology.
4 Average risk for malaria in the control group was 0.9 clinical episodes per child per year and 2.3% of the children experienced at least one episode of severe malaria.
5  A serious adverse event refers to any medical event that occurs during the course of a clinical trial and that results in death, is life threatening, requires inpatient hospitalization, or results in a persistent or significant disability or incapacity needs, regardless of whether the event is considered by the investigator to be caused by the study vaccination. All SAEs are reported to regulatory authorities.
6  Contains QS-21 Stimulon® adjuvant licensed from Antigenics Inc, a wholly owned subsidiary of Agenus Inc. (NASDAQ: AGEN), MPL and liposomes

Source: Malaria Vaccine Initiative. Reproduced from the Malaria Vaccine Initiative website at www.malariavaccine.org, Nov. 9, 2012

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

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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

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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

Genetically Engineered Bacteria Prevent Mosquitoes From Transmitting Malaria

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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

Contrasting Patterns of Malaria Drug Resistance Found Between Humans and Mosquitoes

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A recent study has detected contrasting patterns of drug resistance in malaria-causing parasites taken from both humans and mosquitoes in rural Zambia.

Parasites found in human blood samples showed a high prevalence for pyrimethamine-resistance, which was consistent with the class of drugs widely used to treat malaria in the region. However, parasites taken from mosquitoes themselves had very low prevalence of pyrimethamine-resistance and a high prevalence of cycloguanil-resistant mutants indicating resistance to a newer class of antimalaria drug not widely used in Zambia.

The study was conducted by researchers at the Johns Hopkins Malaria Research Institute and their Zambian colleagues and the findings were published November 7, 2011 in the online edition of the journal PNAS.

Surveillance for drug-resistant parasites in human blood is a major effort in malaria control. Malaria in humans is caused by the parasite Plasmodium falciparum, which is spread from person to person through the feeding of the Anopheles mosquito. Over time, through repeated exposure to medications, the parasites can become less susceptible to drugs used to treat malaria infection, limiting their effectiveness.

“This contrast in resistance factors was a big surprise to us,” said Peter Agre, MD, an author of the study and director of the Johns Hopkins Malaria Institute. “The contrast raises many questions, but we suspect that the malaria parasite can bear highly host-specific drug-resistant polymorphisms, most likely reflecting very different selection preferences between humans and mosquitos.”

For the study, Sungano Mharakurwa, PhD, lead author and senior research associate with the Johns Hopkins Malaria Research Institute in Macha, Zambia, conducted a DNA analysis of P. falciparum found in human blood samples to those found in mosquitoes collected inside homes in rural Zambia. In samples taken from human blood, pyrimethamine-resistant mutations were greater than 90 percent and between 30 percent to 80 percent for other polymorphisms. Mutations of cycloguanil-resistance were 13 percent.

For parasites found in the mosquito midgut, cycloguanil-resistant mutants were at 90 percent while pyrimethamine-resistant mutants were detected between 2 percent and 12 percent.

“Our study indicates that mosquitoes exert an independent selection on drug resistant parasites—a finding that has not previously been noticed. If confirmed in other malaria endemic regions, it suggests an explanation for why drug resistance may appear so rapidly,” said Mharakurwa.

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

Authors of “Malaria antifolate resistance with contrasting Plasmodium falciparum dihydrofolate reductase (DHFR) polymorphisms in humans and Anopheles mosquitoes” are Sungano Mharakurwa, Taida Kumwenda, Mtawa A. P. Mkulama, Mulenga Musapa, Sandra Chishimba, Clive J. Shiff, David J. Sullivan, Philip E. Thuma, Kun Liu and Peter Agre.

The Johns Hopkins Malaria Research Institute is a state-of-the-art research facility at the Johns Hopkins Bloomberg School of Public Health. It focuses on a broad program of basic science research to treat and control malaria, develop a vaccine and find new drug targets to prevent and cure this deadly disease.

Funding was provided by the Johns Hopkins Malaria Research Institute, the Bill & Melinda Gates Foundation and the National Institutes of Health.

Source: Johns Hopkins University

Glaxo’s RTS,S Malaria Vaccine Shows Promise

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Preliminary results from the trial of a malaria vaccine show that it protected nearly half of the children who received it from bouts of serious malaria, scientists said Tuesday. The vaccine, known as RTS,S and made by GlaxoSmithKline, has been in development for more than 25 years, initially for the American military and now with most of its support from the Bill and Melinda Gates Foundation. [Read more…]

Study Finds Malaria Vaccine Candidate, RTS,S Significantly Reduces Malaria Risk in African Infants

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First results from a large-scale Phase III trial of RTS,S*, published online today in the New England Journal of Medicine (NEJM), show the malaria vaccine candidate to provide young African children with significant protection against clinical and severe malaria with an acceptable safety and tolerability profile. The results were announced today at the Malaria Forum hosted by the Bill & Melinda Gates Foundation in Seattle, Washington.

Half the world’s population is at risk of malaria. The disease is responsible for close to 800,000 deaths each year, most of whom are children under five in sub-Saharan Africa

5 to 17 month-old children
The trial, conducted at 11 trial sites in seven countries across sub-Saharan Africa showed that three doses of RTS,S reduced the risk of children experiencing clinical malaria and severe malaria by 56 percent and 47 percent, respectively.

This analysis was performed on data from the first 6,000 children aged 5 to 17 months, over a 12-month period following vaccination. Clinical malaria results in high fevers and chills. It can rapidly develop into severe malaria, typified by serious effects on the blood, brain, or kidneys that can prove fatal. These first Phase III results are in line with those from previous Phase II studies.

The widespread coverage of insecticide-treated bed nets (75 percent) in this study indicated that RTS,S can provide protection in addition to that already offered by existing malaria control interventions.

6 to 12 week-old infants
The trial is ongoing and efficacy and safety results in 6 to 12 week-old infants are expected by the end of 2012. These data will provide an understanding of the efficacy profile of the RTS,S malaria vaccine candidate in this age group, for both clinical and severe malaria.

Combined data in 6 to 12 week-old infants and 5 to 17 month-old children
An analysis of severe malaria episodes so far reported in all 15,460 infants and children enrolled in the trial at 6 weeks to 17 months of age has been performed. This analysis showed 35 percent efficacy over a follow-up period ranging between 0 and 22 months (average 11.5 months).

“The publication of the first results in children aged 5 to 17 months marks an important milestone in the development of RTS,S,” said Irving Hoffman, PA, MPH, co-principal investigator at the Lilongwe site. “These results confirm findings from previous Phase II studies and support ongoing efforts to advance the development of this malaria vaccine candidate,” said Hoffman, who is also associate professor of medicine in the UNC School of Medicine.

Long-term efficacy
The RTS,S malaria vaccine candidate is still under development. Further information about the longer-term protective effects of the vaccine, 30 months after the third dose, should be available by the end of 2014. This will provide evidence for national public health and regulatory authorities, as well as international public health organizations, to evaluate the benefits and risks of RTS,S.

Safety
The overall incidence of serious adverse events (SAEs)** in this trial was comparable between the RTS,S candidate vaccine (18 percent) recipients and those receiving a control vaccine (22 percent)

Differences in rates of SAEs were observed between the vaccines groups for specific events, such as seizures and meningitis, and were higher in the malaria vaccine group. Seizures were considered to be related to fever and meningitis was considered unlikely to be vaccine-related. These events will continue to be monitored and additional information about the safety profile of the RTS,S malaria vaccine candidate will become available over the next three years.

“Making progress against this disease has been extremely difficult, and sadly, many have resigned themselves to malaria being a fact of life in Africa. This need not be the case,” said Francis Martinson, MPH, PhD, co-principal investigator in Lilongwe and country director of UNC Project-Malawi. “Renewed interest in malaria by the international community, and scientific evidence such as that we are reporting today, should bring new hope that malaria can be controlled.”

The vaccine is being developed in partnership by GSK and the PATH Malaria Vaccine Initiative (MVI), together with prominent African research centers. The partners are all represented on the Clinical Trials Partnership Committee, which is responsible for the conduct of the trial. Major funding for clinical development comes from a grant by the Bill & Melinda Gates Foundation to MVI.

About UNC Project-Malawi
UNC Project-Malawi, a research, clinical care and training center, was established in 1999 in partnership with the Malawi Ministry of Health. The mission of UNC Project-Malawi is to identify innovative, culturally acceptable, and relatively inexpensive methods of reducing the risk of HIV/STI and infectious disease transmission through research; strengthen the local research capacity through training and technology transfers; and improve patient care for the people of Malawi.

*RTS,S contains QS-21 Stimulon® adjuvant licensed from Antigenics Inc, a wholly owned subsidiary of Agenus Inc. (NASDAQ: AGEN), MPL and liposomes.

**A serious adverse event refers to any medical event that occurs during the course of a clinical trial and that results in death, is life threatening, requires inpatient hospitalization, or results in a persistent or significant disability or incapacity needs, regardless of whether the SAE is considered to be caused by the study vaccination. All SAEs are reported to regulatory authorities.

Source: University of North Carolina at Chapel Hill School of Medicine

RTS,S Malaria Vaccine

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QUESTION:

What information can you provide on this vaccine candidate?

ANSWER:

RTS,S is a vaccine candidate against Plasmodium falciparum malaria which works by encouraging the host’s body to produce antibodies and T cells which diminish the malaria parasite’s ability to survive and reproduce in the liver.

Produced by GlaxoSmithKline, RTS,S is the first vaccine candidate against Plasmodium falciparum that has reached advanced (Phase III) clinical field trials on a large scale. It was developed way back in 1987, and had successive trials in the United States in 1992 and then in Africa in 1998. In 2001, GSK and the Malaria Vaccine Initiative at PATH went into a public-private partnership, with grant money from the Bill and Melinda Gates Foundation, to develop the vaccine for use in children and infants in sub-Saharan Africa.

The Phase III trials are currently underway in a number of African countries; if all goes to plan, the vaccine will be submitted for regulation by drug authorities as early as 2012. This information, and more, can be found courtesy of the Malaria Vaccine Initiative website: http://www.malariavaccine.org/index.php.

Microwaves Against Malaria

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The Bill & Melinda Gates Foundation today announced that twelve grantees have advanced to the next level of Grand Challenges Explorations (GCE), an initiative that enables researchers worldwide to test unorthodox ideas that address persistent health and development challenges. The grantees will receive additional funding to continue Phase II of their research over a two-year period.

“Finding solutions to persistent global health problems is a difficult, lengthy and expensive process. GCE was designed to tap the innovators of the world by providing resources needed to explore bold ideas that are typically too risky to attract funding through other mechanisms,” said Chris Wilson, director of Global Health Discovery at the Bill & Melinda Gates Foundation. “We’re excited to enable further development of novel approaches that can prevent or lessen the burden of diseases that kill or disable millions of the world’s most vulnerable.”

Among projects receiving Phase II funding, Carmenza Spadafora of Panama’s IASI and Jose Stoute of Pennsylvania State University investigate whether malaria can be treated by microwave irradiation.

Grantees who receive Phase II funding will receive up to one million dollars of additional funding over a two-year period.

Fast Company reports: “Malaria drugs are expensive, and the disease is becoming resistant. But nothing can resist microwaves. A new advance might simply explode the parasite inside people’s bodies with a low dose of focused rays. Treatments for malaria, however, have never been a high priority for pharmaceutical companies, and multi-drug resistant malaria is becoming prevalent in Africa, South America, and Southeast Asia, while even the most effective drug combinations are losing their punch. Researchers Carmenza Spadafora and Jose Stoute have now hit upon one treatment that no parasite has ever developed an immunity against, and may never be able to survive: microwaves.”

Read more, via Fast Company.

Sources: Fast Company, Gates Foundation