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draadje Malaria

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Public release date: 19-Jun-2006

Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Study points to genes responsible for malaria parasite's survival in attempts to eradicate it
Findings Could Lead to New drug and vaccine targets
The study is being published online June 16 in PloS Pathogens, a peer-reviewed, open access journal published by the Public Library of Science.
"While millions of dollars have been spent to develop a malaria vaccine, we still don't have a licensed product," says Associate Professor Elizabeth Winzeler of Scripps Research, who led the study. "Our findings may help in the vaccine-development effort, because they point to novel immunogens that could be targeted."
Winzeler adds the study also identified novel genes involved in the parasite's development of drug resistance-another critical issue in the fight against malaria.
Malaria is a nasty and often fatal disease, which may lead to kidney failure, seizures, permanent neurological damage, coma, and death. There are four types of Plasmodium parasites that cause the disease, of which falciparum, the subject of the recent study, is the most deadly.
Despite a century of effort to globally control malaria, the disease remains endemic in many parts of the world. With some 40 percent of the world's population living in these areas, the need for more effective vaccines and treatments is profound. The spread of drug-resistance adds to the urgency.
In the study, the scientists used gene-chip technology to compare the genomes of 14 different field and laboratory strains of Plasmodium falciparum collected from four continents. Of the parasite's roughly 5,000 genes, about 500 were found to be highly variable across the different strains, indicating that these genes are evolving at a faster-than-neutral rate.
"These genes exhibit variability far above and beyond basic housekeeping genes," notes Winzeler. "Most genes in the malaria parasite are highly conserved, but these appear to be evolving rapidly."
Why? According to the study, "guilt by association" would indicate that the genes that are rapidly evolving are the very genes responding to our best attempts to eradicate the parasite. "The two largest forces exerting selection pressures on the parasite are our immune system and anti-malarial drugs, particularly chloroquine," says Winzeler.
Previous to this study, no systematic overview of these potential targets in the parasite's genome existed. The study's results include known drug and vaccine targets and intriguingly, areas of the genome not currently under investigation.
One example of a promising potential target highlighted by the research is the P. falciparum GTP cyclohydrolase gene, the first enzyme in the folate biosynthesis pathway. Downstream members of this pathway are targeted by several widely used antimalarials, and authors speculate that an amplification of the GTP cyclohydrolase enzyme facilitates parasite resistance to antifolate drugs.
"I'm super excited about the paper," says Winzeler. "It's going to have an impact on the research community."

The article, "A Systematic Map of Genetic Variation in Plasmodium falciparum," was authored by Claire Kidgell, Sarah K. Volkman, Johanna Daily, Justin O. Borevitz, David Plouffe, Yingyao Zhou, Jeffrey R. Johnson, Karine G. Le Roch, Ousmane Sarr, Omar Ndir, Soulyemane Mboup, Serge Batalov, Dyann F. Wirth, and Elizabeth A. Winzeler. It can be viewed at: dx.doi.org/10.1371/journal.ppat.0020057. This work was supported by the National Institutes of Health; the Ellison Medical Foundation; and the W. M. Keck Foundation.
www.eurekalert.org/
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Novartis seeks next generation of malaria drugs

By Gregory Roumeliotis




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02/06/2006 - Determined to eradicate a disease that takes the lives of more than one million people worldwide each year, Novartis has announced it will participate in a new public-private partnership which aims to discover more potent drugs to combat malaria.

The Novartis Institute for Tropical Diseases (NITD) will focus on the development of a one-dose cure for Plasmodium falciparum, the most dangerous form of malaria, and a curative modality for Plasmodium vivax, the most frequent and widely distributed cause of malaria.
According to estimates, between 300m and 500m new cases of malaria occur each year, 90 per cent of which occur in children in Africa.

Malaria morbidity and mortality rates are rising in developing countries, largely due to the emergence of drug resistant parasites rendering traditional antimalarial drugs, such as chloroquine and sulfadoxine-pyrimethamine (SP) ineffective.

This new partnership will investigate the potential for development of existing compounds that have already shown antimalarial activity, and explore novel compounds.

Resarchers will perform basic and applied drug discovery research, including target identification, development of screening assays, synthesis and the testing of drug candidates.

“NITD brings together the best of industry and academic knowledge along with technology and strong scientific networks,” Daniel Vasella, Chairman and CEO of Novartis, said.

“This funding will allow us to utilize these capabilities in the fight against malaria.”

Resources will be allocated by the partnership, which includes the Singapore-based NITD, the Wellcome Trust, the Singapore Economic Development Board (EDB) and Medicines for Malaria Venture (MMV).

The NITD, which is expanding its focus on tropical diseases to include malaria as well as dengue fever and tuberculosis, was established in 2003 as a public-private initiative between Novartis and the Singapore Economic Development Board.

“The NITD is an important member of Singapore's rapidly growing biomedical sciences research community,” said Philip Yeo, chairman of Singapore's Agency for Science, Technology and Research (A*STAR).

“Singapore is pleased to support this important endeavor to develop better treatments for malaria and advance human healthcare around the world.”

In 2005, Novartis delivered nine million treatment courses of the anti-malarial medicine Coartem at cost for public-sector use by patients in malaria-endemic countries.

To meet demand, Novartis and partners on three continents have scaled up manufacturing capacity to make it possible to produce around 70 million treatment courses of Coartem by the end of 2006.

www.drugresearcher.com/news/ng.asp?n=...
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GAVI Alliance
Vaccine-preventable childhood diseases
Berna Biotech (a Crucell Company), GSK Biologicals, Merck & Co.,
Novartis Vaccines & Diagnostics (formerly Chiron), sanofi pasteur,
Wyeth & IFPMA
Since 2000
Access: global strategy, distribution of new & under-used vaccines,
vaccine donations & training
Low-income countries
www.gavialliance.org

The GAVI Alliance was created to reduce childhood morbidity and mortality from vaccine preventable diseases by increasing immunization rates and improving vaccine access for children in developing
countries, in response to stagnating global immunization rates and a widening gap in vaccine access among children in developing countries.

The Alliance’s partners include Berna Biotech (a Crucell company), GSK Biologicals, Merck & Co., Novartis Vaccines and Diagnostics(formerly Chiron Vaccines), sanofi pasteur, Wyeth and the IFPMA,
plus industrialized and developing country governments, UNICEF, the WHO, the World Bank, charitable foundations and NGOs.

www.ifpma.org/pdf/IFPMA_Partnerships_...

pagina 50

===============

www.gavialliance.org/

Leuke GAVI partners ;-)

GAVI Partners:
The Bill & Melinda Gates Foundation
WHO
UNICEF
The World Bank Group
Developing Country Governments
Nongovernmental Organization
Industrialized Country Governments
Research Institutes
Vaccine Industry-Industrialized Country
Technical Health Institutes
Vaccine Industry-Developing Country
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Scientific American
CHANNELS: TECHNOLOGY AND BUSINESS
July 2006 issue

Dangling a Carrot for Vaccines

Drug companies do not see much of a market in treating diseases of developing nations. Michael Kremer hopes to change that--with a plan that taps the profit motive By JR Minkel

It's a gray, drizzly March day at Harvard University. Economist Michael Kremer is recalling his postcollegiate year, 1985, spent teaching high school in Kenya, contracting malaria, recovering and watching sick Kenyans fare worse than he. Melancholy enters his voice. "The burden of disease is just very clear," he nearly sighs. "This is a terrible crisis. It seems vital to put the same sorts of entrepreneurial spirit and effort, and creativity, unleashed by the market sector"--he laughs dryly, as if in disbelief--"to work on these diseases as is being done for the diseases in rich countries."
Poor nations labor under the weight of malaria, AIDS, tuberculosis and a score of diseases lesser known in rich countries, but they cannot afford to pay the prices companies want for drugs. Whereas some might denounce the pharmaceutical industry's profit seeking, Kremer wants to harness it. He has championed the idea that governments and other donors should try to make a malaria or tuberculosis vaccine as attractive to industry as the average drug market is. "I want them to do the same thing for malaria they would do for breast cancer," he says.

Right now research and development for neglected vaccines occurs primarily through public-private partnerships, which have invigorated the field in the past half a decade. Nonprofit groups such as the International AIDS Vaccine Initiative channel money from donors into deals with biotech and pharma companies. Industry involvement is growing, says Michel Zaffran, deputy executive secretary of the Global Alliance for Vaccines and Immunization, "but it's still not at the level one would like to see." Aid groups negotiate with drugmakers to procure vaccines for poor nations, but industry remains wary it will be haggled down to an unwelcome price.
Kremer advocates constructing a kind of artificial market for a vaccine. A donor would commit to paying a certain sum, a few hundred million dollars up to perhaps $5 billion, on delivery of a viable vaccine. Once a vaccine is manufactured, the donor would purchase it at a high price per dose until the sum is exhausted; thereafter, the company would be obligated to supply the vaccine to poor countries at a low price. "The idea is quite simple, and it really gets at the heart of the problem--that there are insufficient markets in the developing world to attract industry," remarks Wendy Taylor, founder of BIO Ventures for Global Health.
The recipient of a MacArthur fellowship in 1997, the 41-year-old Kremer is adept at sketching out institutional fixes for problems in developing countries. To ease these nations' debt, he has argued that the international community should regard loans to odious regimes as loans to the ruling despots themselves, perhaps dissuading banks and other private lenders. To break up black markets surrounding the antiquities of poor countries, he proposes leasing the artifacts to museums.
His first foray into financial incentives for disease treatment was in 1998, when he studied the idea that the public sector could buy out the patents of working vaccines. A year later Kremer had an inspirational conversation with Jeffrey D. Sachs, a development economist at Columbia University. The concept evolved into a vaccine purchase fund, in which a donor would commit to buying doses of an already manufactured vaccine--something the World Bank had also recommended. "We were both quite enthusiastic about the idea of buying out the product," Kremer says. At a colloquium, Sachs and Kremer outlined the idea in front of attendees from international aid groups and industry, who were not immediately persuaded.

"The details of how this is done will make a big difference," Kremer acknowledges. One trade-off hinges on the commitment's payment structure, which could range from a competition that awards a sum to the first company that develops a vaccine to a more marketlike approach, in which any product meeting the clinical requirements is eligible for purchase. By judiciously selecting the price and quantity of doses that they commit to, donors can choose to reward the fast development of an initial vaccine or the intro-duction of subsequent, possibly superior products, Kremer says.
One criticism leveled at advanced market commitments (AMCs), as the purchase commitments are now called, is that they would encourage industry to dust off abandoned, mediocre vaccine candidates. To Kremer, that is the whole point: "If they have something they think has a 10 percent chance, I want them to take that off the shelf."

To succeed, the commitment has to minimize industry's risk of supplying vaccines to a single buyer, the donor, who might decide to pay the lowest price possible once a vaccine was developed. The U.S. government's Project BioShield illustrates the danger. Enacted in 2004, it allocated $5.6 billion over 10 years to stimulate development of vaccines and drugs for potential terrorist threats. The government has purchased drugs from a few biotech firms. But BioShield's original rules, now modified, gave administrators discretion in whether, how much and at what price to buy, and some companies that sunk millions into drug development were left without a customer.
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The Center for Global Development, where Kremer is a nonresident fellow, convened a working group in 2003 to study the feasibility of purchase commitments. Made up of economists, lawyers, public health experts and representatives from industry, the group published its recommendations last year, including sample contracts. It advocated allowing multiple companies to share in an AMC, in part to attract more industry participation, and letting poor countries refuse a vaccine, in case circumstances changed. These efforts caught the attention of the Group of Seven nations. In its December meeting last year, the G7 called for a pilot proposal from the World Bank for one of six diseases: malaria, HIV, tuberculosis, rotavirus, pneumococcus or human papillomavirus.
The concern persists that AMCs might compete with public-private partnerships. A commitment would have to be designed to tie up funds only on completion of a vaccine, Kremer emphasizes. "There was a tendency earlier on to present this as an alternative to up-front funding," he admits. "We're not trying to take the public sector out of this."
Indeed, getting industry, donors and the public sector working together seems key to making an AMC work. Industry still faces uncertainty about how much vaccine poor countries would want to buy and how to set a long-term price in advance. The G7 has asked the World Bank and the Global Alliance for Vaccines and Immunizations to help improve demand forecasting and other implementation issues. Robert Hecht of the International AIDS Vaccine Initiative notes that the international vaccine procurement system and laws governing liability and intellectual property also need further development. "There are many people who doubt it will actually work, and there are many who hope it will," Zaffran says.
If Kremer errs on the side of overexuberance, it stems partly from his desire to help those sharing the lot of the Kenyans he knew and partly from his belief as an economist in the power of institutions to shape incentives. "There's a tendency for this whole debate over pricing of drugs in the developing world to be framed in terms of access versus incentives," he says--poverty versus profit. "Both sides in that debate are taking the existing institutions as given. I'm trying to think about ways to make the market work to the advantage of people."

www.sciam.com/article.cfm?chanID=sa00...
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Public release date: 27-Jun-2006

Contact: Steve Baragona
sbaragona@idsociety.org
703-299-0412
Infectious Diseases Society of America

Preventive treatment reduces risk of malaria in infants
A new study shows that giving 3, 4, and 9-month-old infants a single dose of a common anti-malarial drug significantly lowers their risk of contracting malaria. The research appears in the August 1 issue of The Journal of Infectious Diseases, now available online.

Malaria is one of the leading causes of death worldwide, causing an estimated 3,000 deaths each day and at least 300 million cases of severe illness each year, particularly among infants in sub-Saharan Africa. Prior attempts at prevention that relied on frequent administration of antimalarial drugs were unaffordable in the long run and might promote drug resistance. But intermittent preventive treatment, a more focused use of antimalarials at a few specific intervals, has proved promising in earlier studies.

Clara Menendez, MD, and her colleagues in Mozambique and Spain explored the intermittent administration of the antimalarial sulfadoxine-pyrimethamine (SP) to infants in their first year. Infants given SP at 3, 4, and 9 months of age were compared with those given a placebo at the same intervals.

Dr. Menendez and colleagues found that giving infants SP was safe and well tolerated, and reduced the incidence of hospital admissions by one fifth.

According to editorialists Feiko O. ter Kuile, MD, PhD, of the Liverpool School of Tropical Medicine and the U.S. Centers for Disease Control and Prevention, and Richard W. Steketee, MD, MPH, of the Malaria Control and Evaluation Partnership in Africa, "SP has a combination of features that may make it highly suitable for use as intermittent preventive treatment; it has relatively long half-lives, is very well tolerated in young infants, and it can be given as a single dose."

Intermittent preventive treatment with sulfadoxine-pyrimethamine is seen by Drs. ter Kuile and Steketee to provide a satisfactory balance of safety and efficacy. There is "substantial protective efficacy of this approach," they said.

www.eurekalert.org
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Antihistamine could fight malaria: study 35 minutes ago

WASHINGTON (Reuters) - An allergy drug pulled off the market in 1999 could work to treat malaria, U.S. researchers reported on Sunday.

The drug is called astemizole and marketed under the brand name Hismanal by Janssen Pharmaceutica, a unit of Johnson & Johnson, and can kill the Plasmodium falciparum parasite that causes malaria.

Researchers from the Johns Hopkins University Schools of Medicine and Public Health tested astemizole in test tubes and in mice. Moderate doses reduced the numbers of Plasmodium parasites by 80 percent in mice whose infection also could be affected by the malaria drug chloroquine.

In mice resistant to chloroquine, the antihistamine reduced parasite numbers by 40 percent, the researchers report in this week's issue of Nature Chemical Biology.

"Time and money are major roadblocks when it comes to developing new drugs for the treatment of neglected diseases like malaria," said Dr. David Sullivan, who oversaw the study.

"Astemizole is promising as an antimalarial, but still needs to be evaluated for effectiveness as an antimalarial in humans."

Malaria, caused by a single-cell parasite called Plasmodium that is carried by mosquitoes, kills at least a million people every year and makes 300 million people seriously ill.

The best treatment is with compounds known as artemisinins. They have been shown to reduce deaths from malaria by up to 30 percent if used properly and can cure falciparum malaria in seven days. In combination with other drugs they can do the job in three days.

Yet many countries still use older, much less effective drugs because the newer drugs are not available and are expensive.

For their study, Sullivan's team screened 2,687 known drugs for potential effectiveness in killing Plasmodium and found that astemizole was one of the more promising.

Janssen withdrew astemizole from the U.S. and European markets in 1999 after warnings about the drug's safety. It could cause rare, but life-threatening heart arrhythmias when patients took an overdose or with drugs that affected its metabolism.

But similar arrhythmias are reported with existing malaria drugs and other antihistamines now sold over the counter. Astemizole is still used in 30 countries, including Cambodia, Thailand and Vietnam where malaria is endemic, the researchers said.
news.yahoo.com/s/nm/20060703/hl_nm/
antihistamine_malaria_dc;_ylt=AtW1T3T0AMvfmBVxEOQSDlKs0NUE;_ylu=X3oDMTA3czJjNGZoBHNlYwM3NTE-
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Gates Foundation helps drive revolution in global health care

"This will allow Africa to make a generational leap"

The Associated Press (apwire)

Published 2006-07-04 10:01 (KST)

At field offices in the African bush, at medical schools and research laboratories in Europe and America, doctors and scientists funded by Bill Gates' Internet millions are starting to make a difference on this continent all to familiar with poverty, disease and early death.

There is a revolution taking place in global health care, new well-financed initiatives that have saved millions of lives and promise to save millions more, said Dr. Melinda Moree, the head of the Malaria Vaccine Initiative.

One of the driving forces in this revolution, said Moree, is the Bill and Melinda Gates Foundation. It was already the best-endowed private charitable foundationwhen its endowment doubled to about US$60 billion (euro47.2 billion) when billionaire Warren Buffett announced June 26 that he was giving it 80 percent of his fortune.

''We can't be very specific at the moment about where the (new) funds will go,'' Gates Foundation spokeswoman Jacquelline Fuller said from Seattle. ''What is clear is that the foundation will have more resources available.'' Buffet made sure the money will be available soon, stipulating his donations were to be spent in the same year they are received.

Since it was founded in 2000, the foundation has donated about US$6 billion (euro4.7 billion) to finance programs and research projects to improve access to health care and the quality of that care in developing countries all over the world. Africa has been a prime beneficiary.

In Botswana, for example, the National HIV/AIDS treatment and prevention initiative increased the number of HIV-postive patients getting life-prolonging anti-retroviral treatment from 3,000at the end of 2002 to more than 48,000 today. It did so partly with the help of a US$50 million (euro39.3 million) grant from the Gates Foundation.

''Botswana was the first country in the world to meet the World Health Organization goal of having half of the identified and eligible patients in the country on anti-retroviral treatment. We could have never have done this without the help of the Gates and the Merck Foundations,'' said program spokesman Pierre Pelletier in Gaborone.

The Gates Foundation is also funding a special project in Zambia that aims to gauge the success of a national anti-malaria program attacking the disease with drugs and with insecticide treated nets and spraying to control mosquitos. The goal of the program that began last year is to reach 80 percent of the population, reduce malaria infections by 75 percent and use the program as a model for other countries. No target date has been set.

Malaria infects between 350 million and 500 million people a yearandkills about a million, the vast majority African children.

Julian Lob-Levyt, head of the Geneva-based Gavi Alliance, a Gates-funded, disease-fighting initiative, said the Zambian project shows how the Gates Foundation tries to think creatively and to use its enormous intellectual capacity to solve problems.

''They have developed their own staff that is hard to match. They have the best global health organization outside of the World Health Organization or perhaps the World Bank and it could even be better than the World Bank,'' Lob-Levyt said.

Gavi spokesman Jean Pierre Le Calvez said its program to provide vaccines for such diseases as hepatitis B, yellow fever, tetanus and diphtheria has saved an estimated 1.7 million lives, about two-thirds of them in sub-Saharan Africa, since it began in 2000.

Gates has already given the vaccine initiative US$1.7 billion (euro1.3 billion) and has just guaranteed its funding for the next 10 years, Lob-Levyt said in a telephone interviewfrom Geneva.

Lob-Levyt and others involved in global health projects believe that the foundation, bolstered with Buffet's massive donation, will broaden and deepen its commitment to improving health care in the developing world and improving its already astonishing success.

''What this will allow is Africa to make a generational leap. In the next 20 years it will make health gains it took Europe 150 years to achieve,'' said Lob-Levyt.

In awarding grants, the foundation looks for programs that deal with the cause of widespread illness and death in developing countries and that would otherwise be underfunded.

It has spent billions on HIV/AIDS and malaria, the two biggest killers in Africa, but also millions on acute diarrheal illnesses, tuberculosis, child health, poor nutrition, vaccine preventable diseases and other infectious diseases.

Besides funding hands-on projects, the foundation spends millions to develop knowledge and strategies. Its researchers study success stories inglobal health to learn what made them succeed, develop new technologies that will enable scientists to prevent and treat serious disease, and have targeted studies to apply advances in genetics and microbiology to global health problems.

Moree, the head of the malaria vaccine program, said the Gates Foundation is very involved in every aspect of the programs it funds. The malaria vaccine initiative is working on a vaccine for children with help from the Gates Foundation.

''When there is a problem, they have access to some of the smartest people in the world,'' Moree said.
english.ohmynews.com/ArticleView/arti...
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One example is malaria, which the Gateses mentioned repeatedly at the New York news conference announcing Buffett's gift.

The World Health Organization estimates that the mosquito-borne parasite, virtually eradicated in the industrialized world, strikes 300 million people each year and kills about a million of its victims. Ninety percent of those deaths are in Africa, and most are of children.

Economist Jeffrey D. Sachs of Columbia University notes that malaria also cripples economies. Besides keeping millions home from school or work, it causes long-term learning disabilities and discourages trade and tourism.

Vaccines are among the most effective tools for promoting health. Yet, by the late 1990s, only a few scientists were working on one for malaria. The world's pharmaceutical giants weren't interested. Development costs were steep and the risk of failure high. Even if they succeeded, drug makers knew, a malaria vaccine could not turn a profit.
"How does a company put the millions or billions that are required to develop an effective malaria vaccine when the people in the countries you're marketing it to don't have any money?" asks Dr. Michael Klag, dean of Hopkins' Bloomberg School of Public Health.
Lees verder via:
www.baltimoresun.com/news/opinion/ide...,0,680888.story?coll=bal-home-headlines
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Am J Trop Med Hyg. 2006 Jul;75(1):166-70.

Phase 1 safety and immunogenicity trial of malaria vaccine rts,s/as02a in adults in a hyperendemic region of Western kenya.

Stoute JA, Heppner DG Jr, Mason CJ, Siangla J, Opollo MO, Kester KE, Vigneron L, Voss G, Walter MJ, Tornieporth N, Cohen JD, Ballou WR.

U.S. Army Medical Research Unit, Nairobi, Kenya; Kenya Medical Research Institute, Nairobi, Kenya; GlaxoSmithKline Biologicals, Rixensart, Belgium; Malaria Vaccine Program, Walter Reed Army Institute of Research, Silver Spring, Maryland.

We conducted a phase 1 trial of candidate malaria vaccine RTS,S/AS02A in western Kenya to determine its safety and immunogenicity in healthy adults in an area hyperendemic for malaria. Twenty adults were enrolled and received RTS,S/AS02A (50 mug of RTS,S in 0.5 mL of AS02A) by intramuscular injection on a 0-, 28-, and 178-day schedule. All 60 scheduled immunizations were given, and 18 of 20 volunteers completed the last study visit on day 210. The vaccine was safe and well-tolerated. There were no vaccine-related severe adverse events. The most common solicited adverse events associated with immunization were injection site pain and headache. The geometric mean concentration of antibodies to circumsporozoite protein was 1.9 mug/mL at baseline and it increased 2-4 weeks after each dose to 16, 17.8, and 36.6 mug/mL, respectively. These safety and immunogenicity data from adults in hyperendemic Kenya are comparable to data reported earlier from two trials in west African adults in hypo-endemic and meso-endemic areas of The Gambia. We conclude that in this small study, RTS,S/AS02A is safe and similarly immunogenic in malaria-exposed African adults of different ethnicity in different transmission settings.

PMID: 16837726 [PubMed - in process]
www.ncbi.nlm.nih.gov/entrez/query.fcg...
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Disputes Stall Efforts to Finance Medicine for Poor Countries
By ELISABETH ROSENTHAL
Published: July 16, 2006

Hopes that world leaders meeting in Russia this weekend will agree to a much-anticipated program to help finance vaccines and drugs for the developing world are fading, with competing proposals stalled by political differences and rivalries, advocacy groups and international health experts familiar with the negotiations say.

Aid programs have recently focused on vaccines because preventing disease is cheaper than treating it. But most recently released vaccines, against viral diarrhea, for example, are too expensive for the poor countries where they would help most.
“The market doesn’t work to get vaccines where they are needed,” said Amie Batson, a health specialist at the World Bank. “For manufacturers, the big risk is that these developing countries can’t pay high enough prices to cover their investments.”

The Advanced Market Commitment seeks to address this flaw more directly, Ms. Batson said, by guaranteeing specific financial rewards to manufacturers that develop vaccines for diseases that primarily afflict the developing world, like malaria. The Group of 8 would essentially promise to pay manufacturers in advance for purchases by poor nations that wanted to use a new vaccine.
www.nytimes.com/2006/07/16/world/euro...
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*DJ GlaxoSmithKline: Phase III Studies Begin For New Antimalarial In Sub-Saharan Africa>GSK

07/24/2006
Dow Jones News Services
(Copyright © 2006 Dow Jones & Company, Inc.)


(MORE TO FOLLOW) Dow Jones Newswires

07-24-06 0801ET

Copyright (c) 2006 Dow Jones & Company, Inc.

*DJ GlaxoSmithKline, WHO, MMV Are Developing Antimalarial CDA


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Waar blijft Crucell en/of Crucell/Merck???

'Quote R. Brus, jaarcijfers 2004 (jan.2005)
"Dit jaar (2005) zullen we het meest horen over Malaria"
Nu, 1 1/2 jaar later nog niets.
Het wordt tijd dat Brus c.s. zich een stuk bescheidener gaan opstellen.

Dirk

PR Newswire - July 24, 2006 08:02

LONDON and GENEVA, Switzerland, July 24, 2006 /PRNewswire-FirstCall via COMTEX/ -- Phase III studies have begun for a potential new antimalarial treatment, chlorproguanil hydrochloride-dapsone-artesunate (CDA). The studies will take place in a number of sites across sub-Saharan Africa to further examine the safety and efficacy of treating acute, uncomplicated Plasmodium falciparum malaria with CDA.

CDA is being developed as a fixed-dose combination to meet the urgent need for new malaria treatments in the developing world where multi-drug resistance is contributing to an escalating health crisis. More than 90 percent of the malaria cases and the great majority of deaths occur in sub-Saharan Africa, where P. falciparum malaria is the most common form.(1) Currently, the Global Malaria Programme of the World Health Organisation (WHO) recommends that National Malaria Control Programmes use artemisinin-based combination therapies (ACT) for the treatment of uncomplicated malaria in the public sector.

Phase III Clinical Trial Programmes

Two Phase III trials for CDA will involve almost 2,300 children, adolescents and adults. One study will evaluate CDA relative to artemether/lumefantrine (Coartem(R)), currently the most widely registered and used fixed-dose ACT for the treatment of P. falciparum malaria. This study will measure the parasitological cure rate at 28 days, as well as safety and parasite and fever clearance times.

The second study will compare CDA's efficacy at 28 days to that of Lapdap(TM). Lapdap is a fixed-dose combination pill containing two well-established antimalarial agents, chlorproguanil and dapsone, which act synergistically. The study will also determine the advantage of CDA over Lapdap in terms of parasite clearance at 24 hours following the first dose.

Commenting on the beginning of the Phase III trials, Dr. Chris Hentschel, CEO of Medicines for Malaria Venture (MMV) said, "Moving into Phase III trials marks a key step in the development of this promising antimalarial. If proven safe and effective, CDA could become a major weapon in the fight against drug-resistant malaria."

CDA is being developed in collaboration between GlaxoSmithKline (GSK), UNICEF/UNDP/World Bank, WHO Special Programme for Research and Training in Tropical Diseases (WHO/TDR), and MMV. Academic partners in its development are the University of Liverpool, Liverpool School of Tropical Medicine and the London School of Hygiene & Tropical Medicine, as well as clinical investigators across sub-Saharan Africa.

Dr. Robert Ridley, Director of WHO/TDR, stated, "The collaboration between WHO, MMV and GSK has been crucial in the development of CDA, enabling resources and expertise to be shared and ultimately speeding the development of this new antimalarial treatment." Dr. Lynn Marks, Senior Vice President, Infectious Diseases Medicine Development Centre for GSK added, "Working together in public-private partnerships, such as with CDA, helps ensure that urgently needed new medicines are made available as quickly and safely as possible."

CDA will be studied using once-daily administration for three days. Completing a full course of therapy is important to achieve parasite clearance and minimize the potential for resistance development. If its development is successful, CDA will be supplied at affordable, preferential prices to the public sector in malaria-endemic developing countries to maximise access for those in need.

Approximately 40 percent of the world's population - mostly those living in the poorest countries - are at risk of malaria.(2) The WHO estimates that there are over 300 million new clinical cases of malaria annually, directly causing over one million deaths.(2) Malaria kills one child every 30 seconds, and many children who survive an episode of cerebral malaria suffer from learning impairments or brain damage.(2) Beyond the human toll, malaria has a significant economic impact in endemic countries - costing Africa US$12 billion in lost GDP every year and consuming 40 percent of all public health spending.(3)

Dirk
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quote:

Dirk R. Wijnen schreef:

Waar blijft Crucell en/of Crucell/Merck???

'Quote R. Brus, jaarcijfers 2004 (jan.2005)
"Dit jaar (2005) zullen we het meest horen over Malaria"
Nu, 1 1/2 jaar later nog niets.
Het wordt tijd dat Brus c.s. zich een stuk bescheidener gaan opstellen.

Dirk

PR Newswire - July 24, 2006 08:02

LONDON and GENEVA, Switzerland, July 24, 2006 /PRNewswire-FirstCall via COMTEX/ -- Phase III studies have begun for a potential new antimalarial treatment, chlorproguanil hydrochloride-dapsone-artesunate (CDA). The studies will take place in a number of sites across sub-Saharan Africa to further examine the safety and efficacy of treating acute, uncomplicated Plasmodium falciparum malaria with CDA.
...
Dirk
Dit (CDA) is overigens geen vaccin, maar een geneesmiddel, en heeft dus geen connectie met enig vaccin development van GSK of GSK/Crucell.

En met Crucell/Merck bedoel je Crucell/GSK?

Ben het overigens heel erg met je eens over het 1 1/2 jaar uitblijven van aangekondigd nieuws. Zeg dan niets. Het lijkt er inderdaad op (zoals later door Brus aangegeven), dat Crucell zich tijdens onderhandelingen met GSK zodanig heeft opgesteld (50% winstdeling) dat er geen deal is/komt, en dat Crucell het alleen probeert. Met een veelbelovend vaccin, dat wel.
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IFFIm plans bond to fund vaccine programmes

27 Jul 2006 17:11:14 GMT
Source: Reuters
By Richard Barley and Kristina Cooke

LONDON, July 27 (Reuters) - A plan by European countries to provide $4 billion in life-saving vaccines to millions of poor children took a step forward on Thursday as the institution running the scheme announced plans for its first bond issue.

The International Finance Facility for Immunisation (IFFIm), a new development institution aimed at boosting funding for health and immunisation in poor countries, said it would raise $500 million to $1 billion from its first issue.

The funding raised will be used by the GAVI Alliance to reduce the nymber of vaccine-preventable deaths among children under five in 70 of the world's poorest countries and to scale up health systems, IFFIm said in a statement.

In the first year funding is expected to go to measles and tetanus campaigns and fund a stockpile of polio vaccines.

"An anticipated IFFIm investment of $4 billion over 10 years will support efforts to immunise millions of children and is expected to prevent an additional 5 million child deaths between 2006 and 2015, and more than 5 million future adult deaths," the institution said.

IFFIm will receive payments from sovereign donors including the UK, which is making the biggest commitment, France, Italy, Spain, Sweden and Norway.

British finance minister Gordon Brown announced the scheme in September last year as a pilot for a broader International Finance Facility, aimed at raising larger amounts of money for development aid. Some critics said then, however, that the scheme was flawed without the participation of the United States.

TRIPLE-A RATING EXPECTED

Deutsche Bank and Goldman Sachs will manage the sale of the bond. The World Bank will manage IFFIm's financial activities. Goldman Sachs has served as financial advisor on a pro bono basis.

Thanks to the backing of the sovereigns and conservative financial policies, IFFIm said it expects to gain the highest triple-A credit ratings for its debt issues.

"The investor base we expect will be similar to other supranationals," said Heike Reichelt, head of investor relations at the World Bank Treasury.

She said that some preliminary discussions had been held with key investors, and the response was good.

"They were actually quite enthusiastic: a new issuer in the sovereign and supranational space doesn't come along that often ... but also because of the aim. Everyone can relate to immunisation," Reichelt said.

"It could also be an extremely appealing issuer for socially responsible investors," said Doris Herrera-Pol, head of capital markets at the World Bank Treasury. She said that work was under way with ratings agencies and on documentation, with the first issue expected in the autumn.

The IFFIm issue will follow a 550-million-pound bond issue from UK charity the Wellcome Trust in mid-July, which will use the cash to boost investment in research spanning the human genome, bird flu and malaria.

That bond issue saw strong demand, with over 1.1 billion pounds of orders placed by more than 40 investors.
www.alertnet.org/thenews/newsdesk/L27...
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GSK's thirst for adjuvants grows

By Gregory Roumeliotis

17/07/2006 - GlaxoSmithKline (GSK) has asked vaccine developing firm Antigenics to supply it with more of its QS-21 adjuvant as its vaccines progress in the pipeline, while at the same the British drug giant is pushing ahead with its own adjuvant, MPL, seeking not just clinical but also manufacturing benefits.

As more of GSK's vaccine candidates reach Phase III stage and require more clinical-grade material, the second largest drugmaker in the world has now decided to expand its licence and supply agreement with Antigenics for QS-21 until 2014 but also obtain the manufacturing technologies for the adjuvant.
In-PharmaTechnologist.com has learned that the vaccine candidate furthest ahead in GSK's pipeline formulated with QS-21 is a malaria vaccine expected to be in the market by 2010.
P. falciparum, the bacterium which causes more than 2m malaria deaths annually, has frustrated the efforts of many researchers who have been working for years to develop a vaccine against it.
However, GSK has had success in the malaria vaccine using QS-21 in combination with two other adjuvants, one of which is MPL, a derivative of the lipid A molecule found in Gram-negative bacteria.
MPL was developed by US firm Corixa which GSK acquired last year for €233m, relieving itself from the burden of royalties.
www.in-pharmatechnologist.com/news/ng...
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Kom op met dat vaccin!!!
************

Real risks -- and irrelevant risks

By Fiona Kobusingye-Boynes
web posted July 31, 2006

Few parents want themselves or their children on drugs that cause anemia, nausea, diarrhea, increased infection risks, fertility problems, fetal defects and hair loss. But when those chemotherapy drugs prevent death from cancer, it's an easy choice.
That's the situation facing Africa -- only for us it's not cancer. (Most Africans simply don't live long enough to get cancer.) Our concern is malaria, which infects nearly 400 million of us, and kills 1 million of our precious children, every single year.
We desperately need the African equivalent of chemo drugs -- DDT and other insecticides -- to prevent this terrible disease. Thankfully, the USAID, World Health Organization and other agencies are helping us launch spraying programs. Just spraying tiny amounts of DDT on the walls keeps 90% of mosquitoes from even entering homes, irritates those that do come in so they don't bite, and kills any that land -- for six months or more. No other chemical, at any price, can do that.
But chemical-hating activists continue to oppose these life-saving programs and raise constantly changing "concerns" like: "Some researchers think DDT could be inhibiting lactation and might be related to premature births, low birth weights and slow reflexes in babies."
The latest "concerns" come from the University of California-Berkeley and LA Times. They claim "very high exposure" to DDT causes mental test scores in two-year-olds to drop slightly. They say the problem may disappear by the time the children enter school -- but still argue that Africa should consider "alternative anti-malarial controls," and "balance" risks carefully against benefits.
However, the study isn't even relevant to Africa. No one is talking about massive DDT spraying for agriculture, or even insect control. We're talking about limited, controlled spraying on walls of houses.
There are no viable "alternatives" for DDT. Nothing repels mosquitoes as well or as long as DDT does, or costs so little. However, larvacides, bednets, drugs, sanitation and other insecticides are also vital weapons in our war on malaria.
Moreover, every chemical has risks. In fact, DDT is 100 times less toxic to humans than nicotine in cigarettes, just as safe as pyrethroids used in agriculture and mosquito control, and far less toxic than chemotherapy drugs, say experts like Dr. Donald Roberts, professor of tropical disease at the Uniformed Services University of the Health Sciences.
Anti-malaria drugs are also powerful chemicals. Fansidar can cause severe vomiting and lung and liver damage; Chloroquine (which no longer even works well) has harmful physical effects; and even Artemisia-based drugs have neurological side effects. People aren't just exposed to them. Babies, little children, pregnant women and old people alike must ingest them, every time they get malaria.
Bed nets are impregnated with pyrethroids, to make them kill mosquitoes -- and people have to sleep under them, breathing in the vapors and rubbing their skin up against the nets.
Researchers and activists have never studied or compared these side effects, or evaluated their risks and benefits. Nor have they recommended taking these products (or chemotherapy drugs) off the market -- which would be shortsighted and tragic.
A half-billion people worldwide get acute malaria every year. Hundreds of thousands are left with permanent brain damage. Up to two million die.
School children age 6-14 who had more than five malaria attacks scored 15% lower than those who had fewer than three attacks, researchers from Sri Lanka and the WHO found. The DDT effects claimed by the Berkeley study were trivial by comparison.
I have had malaria over a dozen times. I lost my son, two sisters and three nephews to it. My nephew Noel got malaria at age two, and he is still four years behind high school boys of his age in reading and writing skills, because it affected his mental powers so horribly. My nephew Joseph used to help in an office and with complex farming tasks, but his mind no longer works well because of malaria.
Many mothers have anemia, premature births and tiny babies because of malaria, and many people die from other diseases they would survive if they weren't so weakened by malaria. These tragedies are repeated all over Africa, Asia and Latin America.
How can these impacts from malaria possibly be compared to minor effects of DDT on babies, two-year-olds or nursing mothers?
Africans must use every available weapon to combat malaria. We cannot afford to let a million of our children die every year, while we wait decades for a vaccine, better drugs, alternatives to DDT or genetically modified mosquitoes that can't carry malaria parasites.
What we need are risk-benefit studies comparing mothers and children in communities where DDT is used, versus where it is not used -- assessing days absent from work or school, days severely ill, mental impairment, financial well-being, amounts spent on anti-malaria medicines, and death rates.
We need to calculate the value of lives affected by being sick with malaria for weeks every year … of mental capacity lost due to malaria … of 1.5 million African lives lost every year. Even at $1,000 to $10,000 per life, the impact of malaria -- and the value of DDT -- is monumental.
This month, another malaria outbreak hit the Kabale district in southern Uganda. Over 6,000 people were admitted to clinics in one week. Spraying with Icon resulted in the deaths of two students. That is terrible, but last year 70,000 Ugandans died from malaria. In 65 years, DDT never killed anyone.
Should we stop spraying, to prevent more deaths from Icon or possible learning delays from using DDT -- and sacrifice another 70,000 Ugandans again this year, and next year, and the year after that?
Yes, there are risks in using DDT -- or other anti-malaria weapons. But the risk of not using them is infinitely greater. Irresponsible, one-sided "studies" and "news" stories frighten people into not using the most effective weapons in our arsenal -- and millions pay the ultimate price. That is unethical and unconscionable.

www.enterstageright.com/archive/artic...
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August 03, 2006
Movie Spies on Malaria Parasite's Sneaky Behavior

Malaria has been outsmarting the human immune system for centuries. Now, using real-time imaging to track malaria infections in live mice, researchers have discovered one of the parasite's sneakiest tricks—using dead liver cells to cloak and transport itself back into the bloodstream after leaving the liver.
Robert Ménard, a Howard Hughes Medical Institute (HHMI) international research scholar, and his postdoctoral fellow, Rogerio Amino, at the Institut Pasteur in Paris, filmed the malaria parasite as it transitioned from infecting liver cells to infecting red blood cells. During this stage of the parasite's life cycle, the classic symptoms of malaria—high fevers and chills—are triggered in people who are infected.
Ménard and Amino collaborated with Volker Heussler at the Bernhard-Nocht Institute for Tropical Medicine in Hamburg, Germany. Their images of the parasite sneaking back into the host's bloodstream—published in advance online in Science Express on August 3, 2006 and scheduled for September 2006 publication in Science—clear up a long-standing puzzle about the malaria parasite's life cycle. The discovery could lead to new ways of treating malaria, a disease that infects 300 million people per year and kills 1 million.
The parasite has evolved this complex structure. The best image to describe it is the Trojan horse, because it both transports the parasites and camouflages them,” said Ménard. Like the ancient Greek warriors who hid inside a giant hollow horse to gain entry to Troy, the malaria parasites wrap themselves in a structure made of liver cell membrane. This membrane cloak enables them to sneak past immune cell sentinels and return to the bloodstream.
The malaria parasite, Plasmodium falciparum, has a complex life cycle. It passes from a mosquito's saliva to a human's blood, and then travels to the liver, where it infects and kills liver cells. After it leaves the liver, the parasite moves back into the bloodstream to infect and kill red blood cells. The rupturing of blood cells causes the worst symptoms of the infection, which can be deadly to children, pregnant women, and others with weak immune systems.
After leaving this trail of cellular death and destruction in its wake, the parasite is finally taken up again from the blood when another mosquito bites. Then it reproduces and waits for the mosquito to bite again to infect another person.
Researchers have long assumed that the form of the parasite that infects red blood cells, called a merozoite, was released from a ruptured liver cell and moved on its own back to the bloodstream. But studies in the laboratory have shown that the liver's resident macrophage immune cells happily gobble up free-moving merozoites.
“This was a paradox,” said Ménard. "We could not understand how the rate of infection could be so successful.”
Heussler's research team noticed irregular protrusions on the surface of liver cells that had been grown in a culture dish and infected with malaria. So they asked Ménard and Amino for help finding out whether liver cells in an infected animal developed the same protrusions.
Amino captured a series of images inside living mice at one-second intervals to track the parasites' journey. By using parasites labeled with a green fluorescent marker and staining the mouse's blood vessels with a red fluorescent marker, Amino was able to record microscopic images inside the animal's liver. He found that not only did the structures Heussler's group saw on the liver cells in the culture dish, called merosomes, protrude from the animal's liver cells as well, but the scientists watched as they pinched off and carried the parasite safely into the blood vessels.
Amino recalls watching the first data "movie" with Heussler. They could clearly see the merosome forming, pinching off the parasite, and traveling away with it along the blood vessel. “That is the beauty of this technique. You can really see what happens in real time—there are no gaps,” said Amino, now a professor of biochemistry at Federal University of Sao Paulo, Brazil.
The scientists also found that while the parasites are physically hidden inside the merosome, they further protect themselves with a biochemical cloaking device. They prevent the dying liver cell from broadcasting a chemical "death signal" that would normally tell a macrophage to ingest it.
“The parasite did not evolve this complex system for nothing,” Ménard commented. “It is probably very important that the parasite not travel free in the liver.”
If researchers could interfere with the formation of the merosome or restore the death signal, then immune system cells could stop most of the parasites before they reach the bloodstream—the place where they are most destructive.
How the parasites direct the dead liver cell to form the merosome structure and how that bag eventually bursts open in the blood are questions that remain to be answered.
But the power of using imaging to follow parasite movements inside live, infected animal hosts is clear. “It is now possible to follow in real time and quantitative terms the parasite in its host, and that is something we were only dreaming of a few years ago,” said Ménard.

The Making of Merosomes
3.5MB QuickTime Movie (requires Quicktime Player)
Movie will automatically play when loaded.
The parasites, which express green fluorescent protein, are shown in green; the sinusoids, or cavities through which blood flows in the liver, are shown in red after injection of red-fluorescent bovine serum albumin. The movie shows the formation of one or more merosome(s), which bud from the infected liver cell, reach a liver sinusoid, and finally detach from the mother cell inside the sinusoid. The merosomes usually remain intact for some time while slowly drifting through the blood in the liver.
Movie: R. Amino & R. Ménard

watch movie
www.hhmi.org/news/menard20060804.html
Bijlage:
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Bill Gates Foundation schenkt 500 miljoen dollar aan Aids Fonds
De Bill en Melinda Gates Foundation schenkt 500 miljoen dollar (388 miljoen euro) aan het Global Fund, het Aids Fonds dat zich wereldwijd inzet voor de strijd tegen aids, tuberculose en malaria.

(belga) - Dat heeft de Stichting van het miljardairskoppel woensdag in Genève aangekondigd. Zondag gaat in Toronto de jaarlijkse Wereldaidsconferentie van start.

De bijdrage van Bill Gates en zijn echtgenote is de grootste som geld die het Global Fund ooit heeft ontvangen. De oprichter van softwaregigant Microsoft is van plan om vanaf dit jaar gedurende vijf jaar telkens 100 miljoen dollar (77,5 miljoen euro) aan het fonds te schenken.

VN-secretaris-generaal Kofi Annan richtte het Global Fund in januari 2002 op om extra financiële middelen aan te boren om de drie meest dodelijke ziektes in arme landen te bestrijden.

Het Global Fund financiert momenteel voor 5,4 miljard dollar (4,2 miljard euro) hulpprogramma's in 132 landen. Daardoor krijgen 544.000 hiv-patiënten aidsremmers, worden 1,4 miljoen tuberculosepatiënten verzorgd en zijn al meer dan 11 miljoen muskietennetten uitgedeeld om vrouwen en kinderen tegen malaria-infecties te beschermen.

Foto: Belga

19:39 - 09/08/2006
Copyright © Tijd.be

MVG
Eagle
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