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(Health) Malaria: Epidemiology of Malaria in the Philippines
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PostPosted: Tue Dec 20, 2005 10:19 am    Post subject: (Health) Malaria: Epidemiology of Malaria in the Philippines Reply with quote






Epidemiology of malaria in RP
STAR SCIENCE By Vicente Y. Belizario Jr., M.D.
The Philippine STAR 12/15/2005

Malaria, caused by a parasite belonging to the genus Plasmodium, has long been a significant health problem in the Philippines, and the recent unfortunate demise of the son of a known TV journalist and his companions after doing a story in the hinterlands of Palawan has put into the public limelight once again this deadly but preventable and curable disease.

Malaria is the world’s most important tropical parasitic disease. It kills more people than any other communicable diseases, except tuberculosis. In many developing countries, especially in Africa, malaria has an enormous toll on lives, medical costs, and days of labor lost. The geographical areas affected by malaria have shrunk considerably over the past 50 years, but control is becoming more difficult due to activities like road-building, mining, logging, and new agricultural and irrigation projects, particularly in "frontier" areas like the Amazon. Disintegration of health services, armed conflicts and mass movements of refugees has also worsened the malaria situation.

Malaria is a public health problem today in more than 100 countries inhabited by a total of some 3.2 billion people. High-risk groups in endemic countries include pregnant women, non-immune travelers, refugees, displaced persons, and laborers entering endemic areas.

Malaria causes 1.5 million to 2.7 million deaths each year, and the majority of mortalities occur among young children in Africa, especially in remote rural areas with poor access to health services. Its worldwide prevalence is estimated at 350 million to 500 million clinical cases each year. Around 60 percent of clinical malaria cases and 80 percent of all deaths due to malaria are in sub-Saharan Africa. In the Western Pacific Region, the World Health Organization lists 10 countries as being endemic to malaria, namely Cambodia, China, Lao People’s Democratic Republic, Malaysia, Papua New Guinea, the Philippines, Republic of Korea, Solomon Islands, Vanuatu, and Vietnam.

In the Philippines, malaria still ranks as one of the 10 leading causes of morbidity with 65 out of 79 endemic provinces reported. The profile of malaria varies throughout the country. There is relatively high endemicity in the provinces of Palawan, Kalinga, Apayao and Ifugao. Other provinces have been reported to have generally low endemicity and sporadic malaria. It appears that in areas of low malaria endemicity, there is clustering of cases, resulting in pockets of high endemicity.

A total of 11.3 million Filipinos or 14.8 percent of the population, consisting mostly of farmers, indigenous people, miners, forest product gatherers and soldiers, are at risk for the disease. In 2003, the incidence in the Philippines was reported at 0.5 per 1,000 population. Standardized rates of reported malaria cases in the Philippines have been stable with a gradual decreasing trend, from a high of 1.4 cases per 1,000 in 1990 to 0.5 cases per 1,000 in 2003, but still above the regional average. The Department of Health reported 286 deaths due to malaria in 2000.

More than 70 percent of malaria cases in the Philippines are caused by Plasmodium falciparum, while less than 30 percent are caused by P. vivax. P. malariae occurs in less than one percent of cases.

In the Philippines, the principal malaria vector is Anopheles minimus var. flavirostris, a night biter, which breeds in slow flowing, partly shaded streams that abound in the foothill areas. Occasionally, it has the ability to adapt to or utilize new habitats such as irrigation ditches, ricefields, pools and wells. Its horizontal flight range has been reported to be about one to two kilometers.

Malaria can also be transmitted through blood transfusion from infected donors, and by contaminated needles and syringes. Blood from semi-immune donors without clinical symptoms may also contain malaria parasites. In congenital malaria, infected mothers transmit parasites to their child before or during birth.

Malaria is initially suspected in patients based on clinical symptomatology. Signs and symptoms include fever, chills, headaches and muscle pains, all of which are non-specific and can also be found in other diseases like common viral infections such as the "flu." Hence, early clinical findings are not reliable, thus necessitating the use of laboratory tests to confirm malaria. Microscopic diagnosis for malaria remains the "gold standard" for laboratory confirmation, where malarial parasites are identified in a drop of a patient’s blood smeared on a slide. Other tests available include the more expensive antigen detection or rapid diagnostic tests, which provide immediate test results but may have variable sensitivity.

In the Philippines, the treatment of choice for malaria has been chloroquine, until reports of the emergence of drug-resistant strains of P. falciparum were made. According to the 2005 World Malaria Report, the efficacy of chloroquine in the country, as expressed in percentage of treatment failure, was reported to be 42 percent, which is above the acceptable value of less than 25 percent. On the other hand, with the use of chloroquine combined with sulfadoxine-pyrimethamine, the current first-line drug regimen for falciparum malaria, higher efficacy has been shown with a lower treatment failure rate of 18 percent. This regimen appears to be more expensive, thus illustrating the importance of optimizing present treatment protocols for malaria.

Although the challenge for more effective malaria control in the country remains, there are efforts that show considerable promise in the fight against this disease. The Agusan del Sur Malaria Control and Prevention Project, a collaborative work among the Department of Health, Research Institute of Tropical Medicine, University of the Philippines-College of Public Health, and the local government units in Agusan del Sur, with support from the Australian Agency for International Development, has shown what can be described as a success story in the battle against malaria. The project combined strategies such as early case detection and treatment, surveillance with the use of a Malaria Information System, health education and promotion, use of insecticide-treated nets (ITNs), social mobilization and institutional strengthening. More importantly, the project was able to develop and test a malaria control program that is self-sustaining, community-based and currently managed by the local government units of the province. The project has demonstrated a reduction of malaria cases by 85 percent compared to baseline levels.

The challenges for malarial control in the coming decade include ensuring the quality of available antimalarial drugs in both the public and private sectors, increasing the coverage of quality microscopic diagnosis and rapid diagnostic tests, and increasing distribution and utilization of ITNs. In all these, evidence must be derived as basis for policy and practice. Moreover, national and empowered local government agencies and units should then make possible access to quality and community-based health services that will be crucial for early diagnosis and prompt treatment, thereby ensuring reductions in morbidity and prevention of mortality. And the lives of the young journalist, his companions and thousands more won’t have to be taken.
* * *

Dr. Vicente Y. Belizario Jr. is a practicing tropical medicine specialist in the Philippines. He has a medical degree from the University of the Philippines and a postgraduate degree from the Uniformed Services University of the Health Sciences in Bethesda, Maryland, USA. He is currently the deputy director of the National Institute of Health (UP, Manila), and a professor of parasitology and public health in the College of Public Health, University of the Philippines Manila.


*************************************************************

Questions to explore further this topic:

What is epidemiology?

http://www.cdc.gov/excite/classroom/intro_epi.htm
http://www.collegeboard.com/yes/ae/we0.html

Who is John Snow?

http://www.cdc.gov/ncidod/dbmd/snowinfo.htm

What is malaria?

http://www.nlm.nih.gov/medline.....lesson.htm
http://www.cdc.gov/malaria/disease.htm
http://www.cdc.gov/malaria/history/
http://www.brown.edu/Courses/B...../ldpg.html

What is the malarial parasite?

http://www.wellcome.ac.uk/en/m...../peatb.htm

What is the life cycle of this parasite?

http://www.sirinet.net/~jgjohnso/plasmodium.html

What carries the parasite?

http://www.wellcome.ac.uk/en/m.....quito.html
http://www.malariasite.com/mal.....ontrol.htm

Are mosquitoes attracted to people infected with malaria?

http://faculty.washington.edu/chudler/malaria.html

What is the life cycle of mosquitoes?

http://www.co.hernando.fl.us/mosquito/biology.htm

What are antimalarial drugs?

http://www.malariasite.com/mal....._drugs.htm

What other diseases are carried by mosquitoes?

http://www.co.hernando.fl.us/mosquito/diseases.htm

GAMES

http://www.lostjungle.com/play.php?id=105
http://www.co.hernando.fl.us/mosquito/kids.htm
http://www.ababasoft.com/kids/mosquito_killer.html
http://www.bam.gov/site_games.html


Last edited by adedios on Sat Jan 27, 2007 4:47 pm; edited 3 times in total
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PostPosted: Mon Dec 26, 2005 7:12 am    Post subject: A key that opens cells to the deadly malaria parasite Reply with quote

Grenoble, December 21, 2005

A key that opens cells to the deadly malaria parasite

Researchers at the International Centre for Genetic Engineering and Biotechnology (ICGEB) in India and a unit of the European Molecular Biology Laboratory (EMBL) in France have made a key discovery about a molecule that helps the malaria parasite infect human cells. India is one of the countries most affected by this disease, which has infected 300 million people across the world and leads to over one million fatalities per year. The breakthrough, which was achieved at the European Synchrotron Radiation Facility (ESRF) in Grenoble, may represent an important step towards finding new therapies. The study appears in this week’s online edition of Nature (December 21).
Malaria is caused by a one-celled organism called Plasmodium, which is passed to humans through the bite of Anopheles mosquitoes. The parasite replicates inside red blood cells, which eventually burst. In order to enter these cells, it first has to bind to the cell through interactions of proteins on the surfaces of red blood cells and the parasite.

The new study reveals key features of a protein on the surface of Plasmodium that permits it to bind. The researchers obtained crystals of a module of this protein, called the Duffy-Binding Like (DBL) domain, which directly interacts with a "receptor" protein on red blood cells. Then they examined the crystals using very powerful X-rays of the UK-Medical Research Council Beamline BM14 at the European Synchrotron Radiation Facility (ESRF) in Grenoble. X-ray crystallography is one of the only methods available to create atom-by-atom maps of proteins, which are too small to be seen by microscopes.

"Until now we have not had a close-up view of the precise surface where the two proteins interact," explains Amit Sharma, the corresponding author of the paper. "That surface is absolutely crucial in permitting the parasite to enter the cell. If we can determine its features in atomic detail, we may be able to find weak points that could make good targets for drugs."

In addition to interfering with the binding process, such drugs would also have to be specific: in other words, they shouldn't interfere with normal processes in red blood cells. The receptor protein that allows Plasmodium to enter undoubtedly has other important functions. "What we've found is that the DBL has an absolutely unique architecture, which means that there should be a way to inhibit its activity without affecting healthy blood cells," says Hassan Belrhali, an EMBL researcher who participated in the project.

Evolution has produced many different species of Plasmodium. This work was carried out using a form of the parasite that doesn't normally infect humans, but DBL modules are similar in different forms of the organism. This makes it likely that the findings can be extended to other types of Plasmodium. “Our results provide a structural framework by which to understand the DBLs of most malaria parasites, and could have an impact in the design of drugs to fight against this illness,” explains Amit Sharma.

The researchers are also investigating molecules important at an earlier phase of malaria infections, when parasites invade the liver.


Source article
S.K. Singh, R. Hora, H. Belrhali, C.E. Chitnis & A. Sharma. Structural basis for Duffy recognition by malaria parasite Duffy-binding-like domain. Nature, online publication December 21, 2005.
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PostPosted: Wed Jan 18, 2006 12:57 pm    Post subject: Inventor develops anti-malaria wristwatch Reply with quote

Inventor develops anti-malaria wristwatch
By Rebecca Harrison
Wed Jan 18, 2:00 AM ET

A South African inventor has developed an anti-malaria wristwatch to help combat one of Africa's biggest killers by monitoring the blood of those who wear it and sounding an alarm when the parasite is detected.

Gervan Lubbe said his "Malaria Monitor" wristwatch, due to launch next month, could save lives and keep millions out of hospital by heading off the disease before patients even feel ill.

"It picks up the parasite and destroys it so early that the possibility of dying is absolutely zero and you don't even feel the early cold symptoms," Lubbe told Reuters in a telephone interview this week.

Malaria, caused by a parasite carried by mosquitoes, kills more than a million people every year and makes 300 million seriously ill, according to the World Health Organization. Ninety percent of deaths are in sub-Saharan Africa.

The sturdy digital timepiece pricks the wrist with a tiny needle four times a day and tests the blood for malaria parasites.

If the parasite count tops 50 an alarm sounds and a brightly-colored picture of a mosquito flashes on the watch face. The wearer must take three tablets that kill all traces of the disease within 48 hours.

Lubbe was approached by a major mining company to develop the device after it found high levels of malaria among workers in Africa was hurting productivity.

"If you wait until you get symptoms and a malaria diagnosis you can be in bed for six months and have to take huge quantities of quinine which can be dangerous," Lubbe said.

His company Gervans Trading has already received 1.5 million orders for the wristwatch from companies, governments and aid organization working in Africa, he said.

The watch will cost around 1,700 rand ($280), which Lubbe says is cheaper than treating a patient with severe malaria.

It also means people working or traveling in malarial areas can avoid taking expensive anti-malaria tablets which can come with nasty side effects.

Mining companies can monitor miners by making them walk through a scanner each day. The watch's radio frequency will transmit the wearer's information to a central computer so health departments can ensure people at risk take tablets.

Lubbe said several African governments and the World Health Organization had expressed interest in distributing the watch in rural Africa where access to treatment is scarce.

Lubbe, 38, won a gold medal for the world's best medical invention at the International Inventions Show in Geneva in 1998 for a pain relief device.
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PostPosted: Wed Feb 01, 2006 3:09 pm    Post subject: Malaria and weather come under same umbrella Reply with quote

Published online: 1 February 2006; | doi:10.1038/news060130-8
Malaria and weather come under same umbrella

Weather forecasting models could provide early warnings of malaria epidemics.
Jacqueline Ruttimann


Today's forecast predicts heavy showers and ... a chance of mosquitoes? That's the hope of scientists who have unveiled a weather forecasting computer model that can provide up to five months warning of malaria epidemics in the most vulnerable countries.

Malaria kills more than 1 million people each year, and infects a staggering 500 million people worldwide. Africa is home to about 90% of people affected by malaria, most of whom are part of a constant level of endemic cases. However, malaria epidemics can trigger a significant rise in cases and deaths at the local level, even though they account for only a small percentage of the world's total.

Because climate drives both the development of the malaria parasite, and the behaviour of the mosquitoes that carry it, weather forecasting can help to predict the likelihood of an outbreak.

In theory, an early warning of such epidemics should help governments and aid agencies to deploy anti-malarial drugs and bed nets to the regions most likely to be hit, along with strategic pesticide spraying.

"We can make better use of very limited resources to prevent outbreaks of these epidemics," said Tim Palmer, a climate modeller at the European Centre for Medium-Range Weather Forecasts in Reading, UK, and part of the research team that presents its forecasting system in this week's Nature1.

Degree of uncertainty

Previous climate models have been able to predict malaria epidemics up to one month in advance by analysing rainfall and sea surface temperatures2. In general, higher than average rainfall will lead to increased cases of malaria.

The new malaria forecast model relies on a technique known as ensemble forecasting, which combines several different climate models into one system to provide a more accurate prediction.

The team successfully used the model, developed as part of the EU-funded DEMETER project, to retrospectively predict malaria outbreaks in Botswana between 1982 and 2002.

The advantage of using ensemble forecasting is that it also delivers the uncertainty of that prediction, explains Palmer. That means that in years when strong predictions cannot be made, resources can be spread around a region more uniformly.

Catherine Dibble of the University of Maryland, College Park, who develops computer models of epidemics, agrees that this new system would allow healthcare workers to "hedge their bets" and to "get good information a lot sooner".

But Andrew Spielman, an expert in tropical diseases from Harvard University in Cambridge, Massachusetts, cautions that this model's predictive power still needs to be tested on current epidemiological data.

Palmer now hopes that this modelling system could be used to predict outbreaks of other diseases that have climactic links, such as dengue fever, cholera and meningitis. It could also have an impact on agriculture, helping farmers to decide what types of crops to grow in the rainy season.
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PostPosted: Wed Apr 12, 2006 12:58 pm    Post subject: Research milestone brings goal closer of cheap antimalarial Reply with quote

University of California - Berkeley
12 April 2006

Research milestone brings goal closer of cheap antimalarial drug for developing world

Berkeley -- Researchers striving to create a less expensive version of a life-saving antimalarial drug, artemisinin, have cleared a major hurdle, according to a new report in the journal Nature.
Two and a half years ago, a University of California, Berkeley, team led by Jay D. Keasling, UC Berkeley professor of chemical engineering and bioengineering, succeeded in engineering bacteria to make a chemical precursor of artemisinin - the best drug available today to cure malaria.

The team's ultimate goal was to retool the microbe's metabolism to perform as much of the drug synthesis as possible in order to sidestep the expensive laboratory synthesis needed to make artemisinin. That synthesis would have increased the drug's cost beyond the researchers' ambitious target of 25 cents per dose.

They now have nearly achieved that goal by engineering the production of artemisinic acid, one chemical alteration away from artemisinin. The fact that the researchers have not yet been able to produce artemisinin itself is not a disadvantage, they said, since drugs currently on the market - all made from extracts of the wormwood plant, Artemisia annua - are synthetic derivatives of both artemisinic acid and artemisinin.

"This is probably as close to artemisinin as we are going to get in microbes. The rest is going to be done by chemistry," said Keasling, His lab partnered with the San Francisco-based Institute for OneWorld Health, a nonprofit pharmaceutical company, and Emeryville, Calif.,-based Amyris Biotechnologies in late 2004 on a $43 million grant from the Bill and Melinda Gates Foundation to develop low-cost artemisinin drugs using Keasling's genetically engineered microbes.

A detailed description of the researchers' work appears in the April 13 issue of Nature.

Keasling noted that his team achieved its recent feat in yeast, not E. coli bacteria. Bacteria breed faster and are often the microbes of choice, but the ability to get the drug out of both bacteria and yeast provides flexibility in achieving the goal of complete synthesis of artemisinin within another four years, he said.

Despite its achievement, the team cautioned that a microbe-produced version of artemisinin will not be on the market soon. It added that the current method of production - extraction from the wormwood plant grown by farmers in Asia - will be essential in the next five to 10 years until production and widespread distribution of the less costly alternative becomes possible.

"While we have made a lot of progress in the past two years, there still are a lot of unknowns," Keasling said. Keasling is director of the UC Berkeley Synthetic Biology Center and of the Lawrence Berkeley National Laboratory's Synthetic Biology Department, and a UC Berkeley member of the California Institute of Quantitative Biomedical Research (QB3).

Artemisinin derivatives, in combination with other drugs, have proven nearly 100 percent effective against malaria, and thus represent a major hope for the 300-500 million people each year who become infected with malaria, and the more than 1.5 million people - largely children in Africa and Asia - who die. Even at $2.40 per person for a cure, however, the cost is too great for most developing countries.

In 2003, Keasling and his team pieced together bacterial genes, yeast genes and genes from the wormwood plant to create a chemical pathway - essentially a miniature factory - in bacteria to make amorphadiene, an artemisinin precursor that can be converted chemically into artemisinin.

Supported by funding from the Gates Foundation, Keasling and his team will work with Amyris to push the research towards a final goal: a microbe that can make sufficient amounts of artemisinic acid to allow scientists to produce the antimalarial drug inexpensively enough for widespread use in Africa and Asia, where malaria is endemic.

To ensure affordability, UC Berkeley has issued a royalty-free license to both OneWorld Health and Amyris to develop the technology to treat malaria. Amyris will transform the Keasling lab's research into a robust fermentation process and perform the chemistry and scale-up necessary to bring the drug to market. OneWorld Health will conduct pre-clinical studies and implement a global access strategy for the drug.

"The work coming out of the Keasling lab is world-class. We are very confident that the UC Berkeley-Amyris collaboration team will be able to build on this work to finish the development of an artemisinin production process," said Kinkead Reiling, president of Amyris.

"The team at UC Berkeley has done a great job moving this important project forward," said Victoria Hale, founder and CEO of OneWorld Health. "We still have a long way to go, but this puts us one step closer to a low-cost treatment for malaria."

The team's work accelerated after first author Dae-Kyun Ro, the UC Berkeley artemisinin project manager, identified last July the enzyme in wormwood that chemically changes amorphadiene into artemisinic acid. He plucked the gene out of wormwood after searching for candidate genes in the published genomes of A. annua's relatives - lettuce and the sunflower.

The enzyme, a member of a large family of cytochrome P450 enzymes, attaches itself to internal cell structures not present in bacteria, so Keasling's team tried first to make it work in yeast, which has the required internal membranes.

Led by UC Berkeley graduate student Eric Paradise, co-first author of the Nature article, a large team of plant biologists, chemical engineers, organic chemists, biochemists, bacteriologists, bioengineers, bioinformatics and fermentation specialists worked together to construct in yeast a mirror of the pathway engineered earlier in bacteria. The researchers used some of the yeast's own genes, plus bacterial genes and wormwood genes inserted into the yeast genome. With the added wormwood gene for the P450 enzyme, the yeast manufactured the desired chemical, artemisinic acid.

"We reached our goal early, thanks to a number of miracles: The first gene Dae-Kyun isolated was the right one, the gene was functional in yeast, the gene's enzyme did in one step what we thought took three enzymes, and the artemisinic acid it produced didn't interfere much with the cell," Keasling said.

The yeast produces perhaps one-tenth the amount of amorphadiene as the current version of the engineered bacteria, he noted, so its output of artemisinic acid is still relatively low. But Keasling is optimistic.

"This was our highest hurdle, what kept me up at night," he said. "Now that we've got all the parts, I feel it's just a matter of time before we have a microbe ready for scale-up to production."

The team's next goal, he said, is to try for the same result in bacteria, which grow faster and thus are preferable if the goal is to produce lots of the drug quickly and inexpensively. Ro admitted, however, that large scale production of the drug by yeast could turn out to be a superior strategy.

"Yeast is an easier host in which to express the P450 enzyme that transforms amorphadiene to artemisinic acid," he said. "However, we plan to push forward with engineering the P450 and expressing it in the amorphadiene-producing E. coli strain. For now, we are delighted to have one attractive host strain for artemisinic acid production in our hands, and we now are considering yeast as an alternative fermentation organism for the production of artemisinic acid."

UC Berkeley coauthors with Ro, Paradise and Keasling are co-project manager Karyn L. Newman and post-doc Michelle C. Y. Chang and research assistants Mario Ouellet, Rachel A. Eachus and Kimberly A. Ho of QB3; post-docs James Kirby and Sydnor T. Withers and visiting scholar Yoichiro Shiba of the Department of Chemical Engineering; post-doc John M. Ndungu and assistant professor Richmond Sarpong of the Department of Chemistry; and graduate student Timothy S. Ham of the Department of Bioengineering. Karl J. Fisher of Amyris also coauthored the paper.


###
The work was supported by the Gates Foundation as well as by the Akibene Foundation, U.S. Department of Agriculture, UC Discovery Grant Program, National Science Foundation and Diversa Corp.

More information on the collaboration between the Institute for OneWorld Health, UC Berkeley and Amyris Biotechnologies to develop a low-cost malaria drug, can be found at http://www.artemisininproject.org
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PostPosted: Mon Jul 24, 2006 4:32 pm    Post subject: Back to the future malaria control spelled D-D-T Reply with quote

Back to the future malaria control spelled D-D-T
Chemical & Engineering News
24 July 2006

With the U. S. Agency for International Development (AID) embracing DDT to battle malaria in Africa, a classic debate is reemerging over the benefits and risks of a pesticide hailed as a lifesaver by some and condemned as an environmental menace by others, according to an article scheduled for the July 24 issue of Chemical & Engineering News.

USAID announced last year that it was funding the use of DDT for spraying the inside walls of houses if a country requests it and if an environmental assessment indicates the insecticide will be safe and effective, C&EN senior editor Bette Hileman explains in the article. The decision comes at a time when new studies suggest that prenatal exposure to DDT may retard child development and lead to preterm birth. In addition, there is concern that DDT may end up on crops, endangering wildlife and beneficial insects.

DDT, however, may be the cheapest and most effective way to reduce malaria’s toll in Africa, Hileman writes, noting that malaria kills one child every 30 seconds. The U. S. National Academy of Sciences estimated that DDT’s use in the past, before a 1970s-era ban in the developed world, saved 500 million lives. The article describes the trade-offs involve in resumption of DDT in malaria-control programs, and the new research reports about DDT’s adverse health effects.

"Malaria control with DDT: Resurgent use to prevent malaria poses a dilemma"

FOR FULL ARTICLE CONTACT:
Michael Woods
ACS News Service
Phone: 202-872-6293
Fax: 202-872-4370
Email: m_woods@acs.org
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PostPosted: Fri Aug 04, 2006 12:39 pm    Post subject: Movie Spies on Malaria Parasite's Sneaky Behavior Reply with quote

August 03, 2006
Movie Spies on Malaria Parasite's Sneaky Behavior
HHMI

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.

For the full article and the movie:

http://www.hhmi.org/news/menard20060804.html
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PostPosted: Fri Sep 29, 2006 9:51 am    Post subject: New treatment for severe malaria Reply with quote

Karolinska Institutet
29 September 2006

New treatment for severe malaria

The most dangerous form of malaria is difficult to treat and claims two million lives a year. Now, researchers at Karolinska Institutet in Sweden have developed a powerful new weapon against the disease.

Severe anaemia, respiratory problems and encephalopathy are common and life-threatening consequences of serious malaria infection. The diseases are caused when the malaria bacteria P.falciparium infects the red blood cells, which then accumulate in large amounts, blocking the flow of blood in the capillaries of the brain and other organs.

The reason that the blood cells conglomerate and lodge in the blood vessels is that once in the blood cell the parasite produces proteins that project from the surface of the cell and bind with receptors on other blood cells and on the vessel wall, and thus act like a glue. The challenge facing scientists has been to break these bonds so that the infected blood cells can be transported by the blood stream into the spleen and destroyed.

The research group, which is headed by Professor Mats Wahlgren, has now developed a substance that prevents infected blood cells from binding in this way. The substance also releases blood cells already bound. Using this method, scientists have been able to treat severe malaria in rats and primates effectively; it now remains to be seen whether these results can be replicated in people.

"There's often a lack of ability to treat people suffering from severe malaria," says Professor Wahlgren. "We've developed a substance that might be able to help these patients."

Previously, an anti-coagulant called heparin was used in the treatment of severe malaria. Heparin was able to release the blood cells, but it was soon withdrawn when it was shown that the substance caused internal bleeding. The new substance is a development of heparin, and has the important difference of having no effect on normal blood coagulation.

###
The study, which is jointly financed by Swedish International Development Cooperation Agency and Dilafor AB, is to be presented on 29 September in PLoS Pathogens.

Publication:
"Release of sequestered malaria parasites upon injection of a glycosaminoglycan," Anna M. Vogt, Fredrik Pettersson, Kirsten Moll, Cathrine Jonsson, Johan Normark, Ulf Ribacke, Thomas G. Egwang, Hans-Peter Ekre, Dorothe Spillmann, Qijun Chen and Mats Wahlgren, PLoS Pathogens, September 2006, Vol. 2, Issue 9, e100.
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PostPosted: Fri Nov 10, 2006 8:24 pm    Post subject: Malaria Reversal: Drug regains potency in African nation Reply with quote

Malaria Reversal: Drug regains potency in African nation
Nathan Seppa

An inexpensive drug that has lost much of its punch against malaria over the past 20 years is showing signs of regaining its strength in the African nation of Malawi. But researchers warn that the entire continent would have to coordinate its fight against the disease in order for the drug to regain a prominent place among malaria fighters.

For the full article:

http://sciencenews.org/articles/20061111/fob1.asp
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PostPosted: Mon Nov 20, 2006 5:45 pm    Post subject: Safer Method for Large-Scale Malaria Screening Developed Reply with quote

November 20, 2006
Johns Hopkins - Bloomberg School of Public Health

Safer Method for Large-Scale Malaria Screening Developed

New PCR Test Detects Malaria Parasite in Urine or Saliva Rather than Blood

Researchers at the Johns Hopkins Bloomberg School of Public Health’s Malaria Research Institute have developed a new test for detecting the malaria parasite in human urine and saliva. Although not a diagnostic test for determining treatment, the method could potentially reduce the need for blood sampling in epidemiological studies where large-scale malaria screening is required. Drawing blood increases the risk of spreading HIV and other diseases, particularly in those developing countries where both HIV and malaria are prevalent. Blood drawing must also be performed by trained personnel, whereas urine and salvia sampling does not. The study was published online in the November 8, 2006, edition of Malaria Journal.

“Testing urine or saliva could be an easier and safer way to collect the information needed for studying malaria in communities. For instance, it could be used in studies to determine if a population is growing resistant to malaria drugs, which is a very serious problem,” said David J. Sullivan, MD, senior author of the study and a professor in the Bloomberg School’s Malaria Research Institute.

The test uses polymerase chain reaction (PCR), a technique for duplicating and then examining unique bits of DNA from a sample, thereby allowing DNA to be multiplied in the laboratory. The same PCR technique is used for examining malaria in blood, but has never been applied to urine and saliva samples.

The study was conducted in collaboration with colleagues at the Malaria Research Institute’s research hospital in Macha, Zambia. Urine and salvia samples were obtained from 47 volunteers with malaria and 4 without, and were then examined with the PCR method. DNA from the Plasmodium falciparum, the parasite that causes malaria, was replicated at higher levels from the saliva compared to the urine samples. However, neither method was as sensitive as that using blood samples.

“Programs for monitoring antimalarial drug and vaccine efficacy could therefore adopt such a bloodless method, while maintaining high sensitivity for clinically significant infections,” said Sungano Mharakurwa, PhD, lead author of the study and a researcher with the Malaria Research Institute in Macha.

“PCR detection of Plasmodium in human urine and saliva samples” was written by Sungano Mharakurwa, Christopher Simoloka, Philip E. Thuma, Clive Shiff and David J. Sullivan.

Funding for the research was provided by the Johns Hopkins Malaria Research Institute.
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PostPosted: Thu Dec 07, 2006 3:26 pm    Post subject: Malaria may fuel spread of HIV in sub-Saharan Africa Reply with quote

Fred Hutchinson Cancer Research Center
7 December 2006

Malaria may fuel spread of HIV in sub-Saharan Africa

SEATTLE – Malaria may be fueling the spread of HIV in areas of sub-Saharan Africa where there is a substantial overlap between the two diseases, while HIV may be playing a role in boosting adult malaria-infection rates in some parts of the region, according to a new study by researchers at Fred Hutchinson Cancer Research Center and the University of Washington.

The findings, published in the Dec. 8 issue of Science, found that because malaria increases the viral load of an HIV-infected person on the order of 10 times, it makes HIV more transmissible to a sex partner. Conversely, HIV may play a role in the geographic expansion of malaria in Africa because HIV-infected persons are more susceptible to malaria infections due to their already-compromised immune systems, according to study co-authored by Laith J. Abu-Raddad, Ph.D., Padmaja Patnaik, Ph.D. and James G. Kublin M.D., M.P.H.

"While HIV/AIDS is predominantly spreading through sexual intercourse, this biological co-factor induced by malaria has contributed considerably to the spread of HIV by increasing HIV transmission probability per sexual act," said Abu-Raddad, an HIV/AIDS research scientist in the Hutchinson Center's Statistical Center for HIV/AIDS Research and Prevention and the Center for Studies in Demography and Ecology at the University of Washington.

"In turn, the weakening of the immune system by HIV infection has fueled a rise in adult malaria-infection rates and may have facilitated the expansion of malaria in Africa," said Kublin, an HIV/AIDS scientist in the Hutchinson Center's Clinical Research Division.

Using a mathematical model designed by Abu-Raddad that was based on HIV and malaria co-infection data in Malawi measured and collected by Kublin, the scientists for the first time were able to assess quantitatively the impact of malaria on HIV and vice versa, as well as provide the first assessment of the role of "blips" in HIV viral load seen during HIV co-infection with some other diseases. They estimate that tens of thousands of HIV infections and millions of malaria cases are likely the result of this co-infection.

Using the town of Kisumu, Kenya on the shore of Lake Victoria as an example, Abu-Raddad estimates that 5 percent of all HIV infections are attributed to the heightened HIV viral load induced by malaria. "In Kisumu, we estimate that 10 percent of adult malaria episodes are attributed to HIV," he said.

That translates into 8,500 excess HIV infections and 980,000 excess malaria episodes since 1980 in a town with an adult population of about 200,000, the researchers said.

Kublin said that these findings suggest that other co-infections such as genital herpes or tuberculosis may have also contributed to the rapid expansion of HIV in Africa.

The study's findings have implications for public health, Kublin said. "We can reduce HIV/AIDS transmission by concomitantly treating HIV/AIDS co-infections with malaria as well as other diseases," he said.

"The global public-health system's failure to deal with the challenge of HIV/AIDS contributes directly to its failure to tackle other public-health challenges such as malaria and tuberculosis," Abu-Raddad said. "As long as HIV/AIDS continues to spread, it will aggravate the difficulties we face with these other diseases and may contribute to the emergence of more lethal or drug-resistant strains of these infections," Kublin added.


###
The study was funded by the Center for AIDS Research (CFAR) at the University of Washington through the Mathematical Modeling Program for HIV/STD Research. The HIV Vaccine Trials Network at Fred Hutchinson Cancer Research Center provided partial support for this work.

Note for media only: To arrange an interview with one of the authors, please contact Dean Forbes in Hutchinson Center media relations, (206) 667-2896 or dforbes@fhcrc.org. To obtain a copy of the paper "Dual infection with HIV and malaria fuels the spread of both diseases in sub-Saharan Africa," please contact the AAAS Office of Public Programs at 202-326-6440 or scipak@aaas.org.

About Fred Hutchinson Cancer Research Center – The Hutchinson Center's interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Center researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit fhcrc.org.
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PostPosted: Tue Dec 26, 2006 8:28 am    Post subject: New compound isolated from Madagascan plant shows activity a Reply with quote

Public Library of Science
26 December 2006

New compound isolated from Madagascan plant shows activity against malaria

Two papers in this week's PLoS Medicine suggest possible new avenues of treatment against malaria. In the first paper, researchers led by Dominique Mazier from the Laboratory INSERM/ University Pierre et Marie Curie, Pitié-Salpêtrière Hospital, Paris, isolated a novel compound, tazopsine, from a plant traditionally used against malaria in Madagascar and showed it to be active against the liver stages of human and mouse malaria. One of its semisynthetic derivatives, NCP-tazopsine, completely protected mice from a challenge with malarial parasites, and was specifically active against the liver stage, but inactive against the blood forms of the malaria parasite. This unique specificity in an antimalarial drug makes the development of drug resistance much less likely, and suggests that this compound is a promising new candidate for anti-malarial prophylaxis.


###
Citation: Carraz M, Jossang A, Franetich JF, Siau A, Ciceron L, et al. (2006) A plant-derived mor phinan as a novel lead compound active against malaria liver stages. PLoS Med 3(12): e513.

PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSION S OF YOUR REPORT:
http://medicine.plosjournals.o.....ed.0030513

PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-03-12-mazier.pdf
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PostPosted: Thu Mar 08, 2007 9:37 am    Post subject: NT researchers discover breakthrough in malaria treatment Reply with quote

Research Australia
8 March 2008

NT researchers discover breakthrough in malaria treatment

An article published in the prestigious international journal 'The Lancet' by researchers from the Menzies School of Health Research (MSHR) in Darwin has revealed a breakthrough in the battle to treat Malaria – a disease which effects 40 per cent of the worlds population.

There are two major strains of malaria effecting humans, P. vivax and P. falciparum. Although attention focuses on the more virulent P. falciparum, vivax malaria causes a huge amount of illness in the tropical countries of our region and puts many Australian travelers at risk of disease. Vivax malaria is becoming increasingly resistant to standard treatments, but few studies have determined the best way of treating it.

In collaboration with partners at the Indonesian Ministry of Health, the MSHR team conducted a study in Papua, where they compared, head to head, two new treatments for malaria. Both contained a combination of drug based on a Chinese herbal extract (artemisinin) with a longer acting antimalarial drug.

The researchers found that both treatments provided initial cure from disease. However those receiving a treatment which stayed in the blood stream for longer were three times less likely to have another episode of malaria within 42 days and were less likely to be anaemic.

MSHR scientist, Dr Ric Price, said that the findings have important implications for the treatment of malaria in our region and relevance to areas of Africa where the risk of malaria is greatest.

"Scientists and doctors wage a constant battle to develop and implement effective treatments for malaria. This study is one of the first to highlight the best treatment of drug resistant strains of vivax malaria found in the Asia pacific region." said Dr Price.

"It also provides evidence that longer acting drugs can prevent patients, who remain at risk of further infections, from getting sick again within 6 weeks. This "post treatment prophylaxis" is similar to the approach of giving travelers regular medication to protect them from infection, but can be applied opportunistically to people at high risk of infection in poor tropical communities." he added.

A concern with such a policy is that the resistance will emerge quickly to the long acting drug. However the team believes that by combining the two drugs will help to prevent this from happening.
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PostPosted: Tue Mar 20, 2007 6:57 am    Post subject: Malaria-Resistant Mosquito Developed Reply with quote

Malaria-Resistant Mosquito Developed

By Randolph E. Schmid
Associated Press
posted: 19 March 2007
06:00 pm ET

WASHINGTON (AP) — Researchers have developed a malaria-resistant mosquito, a step that might one day help block the spread of an illness that has claimed millions of lives around the world.

When they fed on malaria-infected mice, the resistant mosquitoes had a higher survival rate than nonresistant ones, meaning they could eventually replace the ones that can carry the disease, according to a report in Tuesday's issue of Proceedings of the National Academy of Sciences.

Jason Rasgon of the department of molecular microbiology and immunology at Johns Hopkins University cautioned that the research so far is only a proof of principle and any field tests remain far away.

For the full article:

http://www.livescience.com/hum.....quito.html
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PostPosted: Tue Apr 17, 2007 5:29 pm    Post subject: Malaria-infected mice cured by 1 dose of new drug Reply with quote

Johns Hopkins University
17 April 2007

Malaria-infected mice cured by 1 dose of new drug

Compound based on plant-derived, ancient Chinese folk remedy

Johns Hopkins University researchers have cured malaria-infected mice with single shots of a new series of potent, long lasting synthetic drugs modeled on an ancient Chinese herbal folk remedy.

The team also has developed several other compounds which defeated the febrile disease in rodents after three oral doses.

These peroxide compounds, containing a crucial oxygen-oxygen unit, promise not only to be more effective than today's best malaria remedies, but also potentially safer and more efficient, said research team leader Gary Posner, Scowe Professor of Chemistry in the Krieger School of Arts and Sciences at Johns Hopkins.

An article about the team's work is slated to appear on the Web on April 17 in the ASAP section of The Journal of Medicinal Chemistry. Go here: http://tinyurl.com/3cwg3a

"We are disclosing, for the first time, the curative activity of a new generation of compounds that are long-lasting and therapeutic, even when used by themselves," Posner said. "Older drugs in this family of peroxide antimalarials also are known to be fast-acting, but they are unfortunately short-lived and not curative when used by themselves."

Though they say their results are very promising, the researchers caution that the new compounds must be thoroughly tested for safety and for how they are absorbed, distributed and metabolized in, and eliminated from, rodents' bodies before human tests begin.

Malaria afflicts between 300 million and 500 million people a year, killing between 1.5 million and 3 million, mostly children and mostly in developing nations. The parasite that causes the disease is spread by female mosquitoes feeding on human blood. The most commonly fatal species of the malaria parasite now shows strong resistance to most current treatments, making the development of effective new drugs a worldwide priority.

Since 1992, Posner and his team, which includes collaborator Theresa Shapiro, professor and chair of clinical pharmacology at the Johns Hopkins School of Medicine, have been tackling that challenge by designing a series of peroxide compounds, called trioxanes.

"As a class, these compounds have proven to be unusually valuable in several ways, from their brisk and potent antimalarial activity to their lack of resistance and cross-resistance with other antimalarial agents," Shapiro said.

The Johns Hopkins trioxanes mimic artemisinin, the active agent in a Chinese herbal drug used to treat malaria and other fevers for thousands of years. Artemisinin comes from the Artemisia annua plant, an herb also known by a variety of names including sweet wormwood.

The oxygen-oxygen unit in the peroxides causes malaria parasites essentially to self-destruct. The parasites digest hemoglobin, the oxygen-carrying pigment of red blood cells, and, in the process, release a substance called heme, a deep-red iron-containing blood pigment. When the heme encounters peroxides, a powerful chemical reaction occurs, releasing carbon-free radicals and oxidizing agents that eventually kill the parasites.

But the first generation of trioxane drugs also had a number of shortcomings, including a half-life of less than one hour. (A drug's half-life is the amount of time it takes for half of it to be metabolized.) Posner and team believe that their new compounds address those disadvantages.

"Our semi-synthetic artemisinin-derived compounds successfully overcome the disadvantages of their first-generation predecessors," he said. "Most important is their curative activity after a single, low dose, which is distinctly unusual. But based on our intentional design, they may also have a longer half-life in animals. We also designed them to be more lipophilic, meaning they have an enhanced ability to dissolve in fats and thus to arrive inside malaria-infected red blood cells."

In addition, the new compounds are far less likely to break down into toxic substances when they are metabolized in the test animals' bodies, making them potentially safer than their predecessors.

Although the substance is inexpensive by Western standards, the widespread use of artemisinins in the developing world remains limited, in part by availability and the cost of separating the active ingredient from the Artemisia annua plant. Posner and his team contend that the potency and curative activity of their compounds provide "a substantially more efficient and economical use of the price-setting natural product."


###
The team's research was supported by the National Institutes of Health and the Johns Hopkins University Malaria Research Institute.
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PostPosted: Thu May 03, 2007 10:57 am    Post subject: Cerebral malaria: Approaching a diagnostic test Reply with quote

CNRS
3 May 2007

Cerebral malaria: Approaching a diagnostic test

Scientists at CNRS and the Pasteur Institute, collaborating with physicians in Gabon, have just undertaken a study on cerebral malaria in children living in an endemic region. This study, which was published in PLoS ONE, should allow us to better understand this severe form of malaria which affects 20 to 40 percent of people infected by the Plasmodium falciparum parasite, and is fatal in 30 to 50 percent of cases. The study also provides a lead on how to perfect a diagnostic test, which should allow for better patient care.

Cerebral malaria presents with a high fever and convulsions followed by coma. The high mortality rate from this form of malaria is also linked to a problem of patient care because, despite the availability of effective treatment, patients often arrive at hospital too late. The availability of predictive tests would therefore be useful in improving patient care. It is this hope that has been raised by the study undertaken by Sylviane Pied and her team. Pied, a scientist at CNRS, leads the malaria immunophysiology group* at the Pasteur Institute, which collaborated on the study with Maryvonne Kombila of the Science and Health University of Libreville, the Libreville Hospital Center, and with the Owendo Pediatric Hospital (Gabon).

The study concentrated on the particular immunological phenomenon observed in people infected by Plasmodium falciparum. The B-lymphocytes, the main antibody - producing cells, increase their secretion of a range of antibodies, notably those directed against various components of the organism (DNA, red blood cells, etc.). Today we still don't know if these "auto-antibodies" are the result of pathological mechanisms associated with the infection or if they contribute to the events leading to the severe forms of the illness.

The French and Gabonese teams sought to understand if some of these auto-antibodies were directed against the molecules in the brain. In order to do this, they worked on the blood samples of some 350 children aged between 6 months and 5 years who had been treated in Gabonese hospitals. The cohort was divided into 5 groups: control patients (without parasites in the blood), asymptomatic patients, patients developing simple malaria, patients suffering from serious, non-cerebral malaria (notably severe anaemia), and finally patients suffering from neurological infection. The results of the study show that, in 90% of children suffering from cerebral malaria, the antibodies specifically recognize a protein in the brain, cerebral alpha-spectrin.

"Our hope today is that this discovery will allow for the development of a diagnostic test for cerebral malaria," explains Pied. "Our hypothesis is that the production of auto-antibodies against alpha-spectrin is a predisposition to the development of cerebral malaria, and our current research aims to verify this. If, in the field, we had a test which allowed us to tell whether or not a person is susceptible to developing cerebral malaria it would enable us to considerably improve their treatment".

This study also opens a new sector of malaria research; understanding the role of auto-antibodies directed against cerebral antigens in the development of the illness.


###
* Study undertaken in the Infectious Immunophysiopathology Unit (CNRS URA 1961) directed by Pierre-André Cazenave

This project received the support of the PAL+ program of the French Ministry of Research and the Genopole of the Pasteur Institute.

Sources:

Self-reactivities to the non-erythroid alpha spectrin correlate with cerebral malaria in Gabonese children: PLoS ONE, 25 avril 2007
Guiyedi Vincent1-2, Chanseaud Youri1-3, Fesel Constantin3, Snounou Georges4, Rousselle Jean- Claude5, Lim Pharat1, Koko Jean6, Namane Abdelkader5, Cazenave Pierre-André1, Kombila Maryvonne2, et Pied Sylviane1-3

1. Infectious Immunopathology Unit, Pasteur Institute - URA CNRS 1961, Pierre et Marie Curie University, Paris

2. Department of Tropical Parasitology-Mycology-Medecine, Department of Medicine, Science and Health University, Libreville, Gabon

3. Gulbenkian de Ciëncia Institute, Oeiras, Portugal

4. Comparative Parasitology and Experimental Models, Department of Ecology et Biodiversity Management, Natural History Museum, Paris

5. Proteomics Platform, Pasteur Génopole, Pasteur Institute, Paris

6. Owendo Pediatric Hospital, Libreville, Gabon
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PostPosted: Wed May 23, 2007 10:53 am    Post subject: Vaccine hope for malaria Reply with quote

Vaccine hope for malaria
PA92/07 — May 22 2007
University of Nottingham

One person dies of it every 30 seconds, it rivals HIV and tuberculosis as the world's most deadly infection and the vast majority of its victims are under five years old. Now, just over 100 years since Britain's Sir Ronald Ross was awarded the Nobel Prize for finally proving that malaria is transmitted by mosquitoes, researchers at The University of Nottingham believe they have made a significant breakthrough in the search for an effective vaccine.



Malaria infects around 400 million people every year and kills between one and three million, mostly children.



Dr Richard Pleass, from the Institute of Genetics, said: “Our results are very, very significant. We have made the best possible animal model you can get in the absence of working on humans or higher primates, as well as developing a novel therapeutic entity.”



Using blood from a group of people with natural immunity to the disease, a team from the School of Biology refined and strengthened the antibodies using a new animal testing system which, for the first time, mimics in mice the way malaria infects humans. When injected into mice, these antibodies protected them against the disease.



The World Health Organisation (WHO) says malaria is a public health problem in more than 90 countries and describes it as by far the world's most important tropical parasitic disease. It kills more people than any other communicable disease except tuberculosis and more than 90 per cent of all malaria cases are in sub-Saharan Africa. According to WHO, the dream of the global eradication of malaria is beginning to fade with the growing number of cases, rapid spread of drug resistance in people and increasing insecticide resistance in mosquitoes.



Until now there has been no reliable animal model for human malaria. Mice do not get sick when infected with the blood-borne parasite that causes malaria in people. And the immune system of mice shows a different response to humans when it comes into contact with the parasite.



This meant that despite making a promising antibody vaccine that worked against the parasite in a lab dish, the team could not test it in a living animal.



In a new study published in the journal PLoS Pathogens an open access journal published by the Public Library of Science — Dr Pleass and his collaborators in London, Australia and The Netherlands describe how they got around the problem by creating a mouse model of the human malaria infection. They took a closely related mouse parasite and genetically modified it to produce an antigen that the human immune system recognises.



Next, they genetically altered the mouse's immune system to produce a “human molecule” on its white blood cells that recognises the parasite and, together with antibodies, destroys it. In trials the team showed that human antibodies given to the mice protected them from the parasite.



The team, who were funded by the Medical Research Council and the European Union, are now hoping to refine the model with a view to starting the first phase of clinical trials in humans.




— Ends —



Notes to editors: The University of Nottingham is Britain's University of the Year (The Times Higher Awards 2006). It undertakes world-changing research, provides innovative teaching and a student experience of the highest quality. Ranked by Newsweek in the world's Top 75 universities, its academics have won two Nobel Prizes since 2003. The University is an international institution with campuses in the United Kingdom, Malaysia and China.



The research can be viewed at PLoS pathogens

http://pathogens.plosjournals......=1553-7374
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PostPosted: Fri May 25, 2007 8:40 am    Post subject: MIT-led team ID's cell mechanics of hallmark malaria protein Reply with quote

MIT-led team ID's cell mechanics of hallmark malaria protein
GEM4's multidisciplinary, multinational research targets public health crises like malaria
Anne Trafton, News Office
May 21, 2007


During the first 24 hours of invasion by the malaria-inducing parasite Plasmodium falciparum, red blood cells start to lose their ability to deform and squeeze through tiny blood vessels--one of the hallmarks of the deadly disease that infects nearly 400 million people each year. Now, an international team of researchers led by an MIT professor has demonstrated just why that happens.

By knocking out the gene for a parasite protein called RESA (ring-infected erythrocyte surface antigen), the researchers found that the protein, transferred from the parasite to the cell's interior molecular network, causes red blood cells to become less deformable.

"This is the first time a particular protein has been shown to have such a large effect on red blood cell deformability," said Subra Suresh, Ford Professor of Engineering and senior author of a paper on the work appearing in the online edition of the Proceedings of the National Academy of Sciences the week of May 21.

The work, a collaboration between researchers at MIT, the Institut Pasteur in Paris, France and the National University of Singapore, could ultimately lead to the development of treatments that target the parasite protein.

Suresh, who holds appointments in materials science and engineering, biological engineering, mechanical engineering and the Harvard-MIT Division of Health Sciences and Technology, has been studying the mechanics of red blood cells and the effects of malaria on those cells for several years.

When the malaria parasite, Plasmodium falciparum, infects red blood cells, the blood cells lose their ability to deform and eventually clump together and get stuck in tiny blood vessels, or capillaries.

The RESA protein has long been suspected to be involved in the early stages of that process. The parasite produces RESA during the first stage of malaria (known as the ring stage) and then transports it to the cell surface.

In this experiment, the researchers cloned the parasite and then knocked out the gene that produces RESA and then measured the red blood cells' deformability with "optical tweezers," which use lasers to stretch cell membranes.

They found that in red blood cells infected by parasites without RESA, deformability remained normal during the first 24 hours of infection. In other parasites where RESA was turned back on after being knocked out, deformability was affected just as it was by (wild type) parasites in which RESA was never knocked out.

"That the deformability changed several-fold was a big surprise," said Suresh.

Because malaria patients usually experience high fever episodes, the researchers also performed their experiments at fever temperatures (about 41 degrees Celsius), as well as normal body temperature (37 degrees Celsius). They found that RESA has a much greater impact on deformability at fever temperatures.

The research team believes that when RESA travels to the cell membrane, it binds to the cell's cytoskeleton--a scaffolding of proteins that lies just inside the cell membrane. In a paper published earlier this year, Suresh and colleagues demonstrated that healthy red blood cells' ability to deform depends on the structure of this network. (See web.mit.edu/newsoffice/2007/blood.html)

When the bonds in the protein network are broken, holes open up in the cytoskeleton, allowing the cell to become more fluidic and squeeze through narrow passages. But when RESA binds to the network, it likely interferes with the proteins' ability to break and form bonds with each other, decreasing deformability, according to Suresh. In an unrelated parallel study, researchers at the New York Blood Center and their collaborators have recently identified specific sites in the red cell cytoskeleton to which RESA binds.

In future studies, the researchers plan to study the effects of proteins produced by the malaria parasite during later stages of infection. They also plan to look at whether the RESA protein plays any role in why another strain of the malaria parasite, Plasmodium vivax, is less lethal than P. falciparum.

The collaboration between MIT and the Institut Pasteur began with a serendipitous encounter: In a crowded cafeteria at the École des Mines in Paris, where Suresh was visiting a few years ago, he met a colleague from Institut Pasteur. She introduced him to the researchers studying malaria at Pasteur, who included microbiologist Monica Diez-Silva, now an MIT and GEM4 postdoctoral fellow and a lead author of the PNAS paper.

Shortly after this meeting, Suresh started a formal collaboration known as GEM4 (Global Enterprise for MicroMechanics and Molecular Medicine), which brings together researchers from MIT, Institut Pasteur, the National University of Singapore and other universities around the world. This year, GEM4 will holds its second summer school, where scientists learn about one another's work and form research partnerships. This GEM4 activity is supported by a number of institutions, including the National Science Foundation.

Multidisciplinary, multinational research at the intersections of engineering, life sciences and medicine, with major implications for public health is "exactly what GEM4 was designed to facilitate and accomplish," Suresh said.

Lead authors of the PNAS paper are Diez-Silva and John P. Mills, both postdoctoral associates in materials science and engineering. Other MIT authors are David J. Quinn, graduate student in mechanical engineering; Ming Dao, research scientist in materials science and engineering; and Matthew Lang, assistant professor of biological engineering and mechanical engineering. Authors from Institut Pasteur are Genevieve Milon, Peter H. David, Odile Mercereau-Puijalon and Serge Bonnefoy. Authors from the National University of Singapore are Kevin S.W. Tan and Chwee Teck Lim.

The research was funded by an interuniversity grant received by GEM4, a Pasteur Institut research grant, Agence Nationale de Recherche sur le Sida, the National University of Singapore and the Computational Systems Biology Program of the Singapore-MIT Alliance.

http://web.mit.edu/newsoffice/.....k51-28.pdf
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PostPosted: Wed Jun 06, 2007 1:51 pm    Post subject: Largest synthetic gene ever built offers insights into anti- Reply with quote

Largest synthetic gene ever built offers insights into anti-malarial drug resistance

Georgetown University Medical Center
6 June 2007

Washington, DC-- Researchers at Georgetown University Medical Center say they are moving closer to understanding why the most lethal form of human malaria has become resistant to drug treatment in the past three decades. They have been able to artificially construct, and then express in yeast, a protozoan gene that contributes to such resistance. And it was no small feat. The gene they laboriously constructed over a two-year period is believed to be the largest “synthetic” one ever built, and it successfully produces large quantities of the encoded protein, whose function can now be easily studied.




In research published in the May 22 issue of the journal Biochemistry, the researchers say that with the addition of the recreated gene, PfMDR1 and its protein, they have all the biomolecular tools necessary to molecularly understand how the malarial parasite Plasmodium falciparum (P. falciparum), has become resistant to most of the drugs that could once destroy it. They have already described and expressed two other genes known to confer drug resistance.




“Now that we have these genes expressed in a convenient yeast system, we can work to understand the molecular basis of anti-malarial drug resistance, providing insight into how future drugs might be designed to effectively kill the parasite,” said Paul Roepe, PhD, a professor in the Department of Biochemistry and Cellular & Molecular Biology and the Department of Chemistry.




Any animal with red blood cells can develop malaria, which is caused by a single-cell protozoan parasite transmitted by the bite of the female Anopheles mosquito. There are about 160 different species of malaria parasites, according to Roepe. Five infect humans, but P. falciparum is responsible for about 1 million deaths out of 300 million acute cases of infection each year. Most of these deaths occur in young children living in sub-Saharan Africa.




Roepe and his collaborators at Georgetown University, in collaboration with investigators at the National Institutes of Health, described in 2000 that the PfCRT gene is primarily responsible for the vast majority of drug resistance that leads to human death from malaria. Earlier this year, they also helped describe how the gene PfNHE likely contributes, and this turns out not to be as vital as PfCRT. Now, based in part on this study, they know that PfMDR1 is dependent on mutated PfCRT, and probably doesn’t act independently.




“The contribution of PfMDR1 to anti-malarial drug resistance is important, but much smaller than what many researchers thought it would be,” said Roepe. “Before the discovery of PfCRT, many thought PfMDR1 would be the primary culprit.”




Roepe, and his two other co-authors, Georgetown researchers Linda Amoah, PhD, and Jacqueline Lekostaj, an MD/PhD student at Lombardi Comprehensive Cancer Center, employed an unusual method to construct the PfMDR1 gene. They first obtained the PfMDR1 protein sequence from the NIH PubMed data base. They then “back translated” the protein sequence using a computer program to change the parasite gene sequence -- which combines nucleotide base pairs in a way that is found in no other life form -- into one that could be “read” by yeast. The yeast are then able to produce the PfMDR1 protein, in its proper sequence, from this synthetic gene. They previously used this same technique to create and express a synthetic version of the much smaller PfCRT gene. PfMDR1 is made up of about 4,000 base pairs and its protein is particularly large, Roepe said, making the recent work much more challenging.




Already, analysis of these three anti-malarial drug resistance genes is painting a picture of how the parasite escapes destruction by most of the agents now used against it, he said.




When a malaria parasite is transmitted through a mosquito bite, the mosquito injects the parasite into skin or blood, which then travels to the liver within minutes, grows and divides there, and then ruptures liver cells, spewing many new parasites into the blood. A fever results from the infection, and this is followed by repeated cycles of mounting parasitic reproduction within red blood cells and accompanying fever. During red blood cell infection, P. falciparum degrades the hemoglobin in the red cell, producing a toxic byproduct known as heme, which the parasite then crystallizes so that it won’t be poisoned by it. Eventually, however, an infected person can die from cerebral hemorrhages or anemia that are consequences of red cell infection.




Natural products such as quinine, extracted from the cinchona tree, and leaves from the artemisinin shrub were the only options available to treat the infection until World War II, when both Germany and the United States started massive drug discovery programs based on the toll the parasite was having on soldiers -- more U.S. soldiers died from malaria in the Pacific than from all enemy fire, Roepe said. The Germans first invented chloroquine (CQ), a synthetic version of quinine, which quickly became the treatment of choice because it was inexpensive -- now seven cents a dose ? and needs no refrigeration. The drug works by preventing heme crystallization, which destroys the parasite by building up toxic levels of non crystalline heme.




But because of the overuse of chloroquine, isolates of P. falciparum from around the globe have developed genetic mutations that make them resistant to that drug as well as other similar agents. Not all mutations found in all resistant isolates are the same, however. Parasites in different geographic regions have developed unique patterns of mutations in the three genes mentioned above. Now, researchers can tell where a drug resistant parasite comes from depending on the varied mutations in the three different resistance genes, Roepe said. “There are patterns of mutations in these genes that can tell you if the parasite came from Africa, or Asia, or South America, and what drugs it is most likely to be resistant to,” he said.




The goal now is to understand molecularly how these mutations lead to drug resistance. So far, the researchers have found that two of the three resistance genes act to change the pH (acid/alkaline balance) within the parasite when it is growing inside the red cell. These changes affect how drugs like chloroquine enter the parasite, and how efficiently they bind to pre – crystalline heme. If these drugs can’t enter blood cells as efficiently, and if the efficiency of heme binding is pushed in the wrong direction, they can’t prevent heme from crystallizing.




“We know these mutant proteins are controlling pH across two different membranes, but we don’t yet know exactly how they are doing it,” Roepe says. “Still, knowing the pH values can help pharmacologists and chemists redesign a molecule to take advantage of these changes.”




The study was funded by grants from the National Institutes of Health.




About Georgetown University Medical Center
Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through our partnership with MedStar Health). Our mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, the world-renowned Lombardi Comprehensive Cancer Center and the Biomedical Graduate Research Organization (BGRO).
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PostPosted: Tue Jul 03, 2007 9:19 am    Post subject: Bed nets for tackling malaria Reply with quote

Public Library of Science
2 July 2007

Bed nets for tackling malaria
In this week’s press release:

- Bed nets for adults and older children key to tackling malaria

Please mention PLoS Medicine in your report and use the links below to take your readers straight to the online articles:

Based on malaria transmission models, Gerry Killeen and colleagues suggest that, while coverage of pregnant women and children should still be prioritized, wide-scale communal use of insecticide-treated bed nets would provide considerable benefit to vulnerable groups and should be promoted and evaluated in the field.

Citation: Killeen GF, Smith TA, Ferguson HM, Mshinda H, Abdulla S, et al. (2007) Preventing childhood malaria in Africa by protecting adults from mosquitoes with insecticide treated nets. PLoS Med 4(7): e229.

###
EMBARGO: MONDAY, 2 July, 5 P.M. PDT

Everything published by PLoS Medicine is Open Access: freely available for anyone to read, download, redistribute and otherwise use, as long as the authorship is properly attributed.

IN YOUR ARTICLE, PLEASE LINK TO THIS URL, WHICH WILL PROVIDE ACCESS TO THE PUBLISHED PAPER:: http://medicine.plosjournals.o.....ed.0040229

PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-04-07-killeen.pdf

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PostPosted: Fri Jul 06, 2007 9:33 am    Post subject: Malaria-resistant mosquitoes battle disease with 'molecular Reply with quote

UT Southwestern Medical Center

Malaria-resistant mosquitoes battle disease with 'molecular warhead'

DALLAS – July 5, 2007 -- A team led by UT Southwestern Medical Center researchers has discovered why some mosquitoes are resistant to malaria, a finding that may one day help fight a disease that afflicts and kills millions of people.

A team led by UT Southwestern Medical Center researchers has discovered why some mosquitoes are resistant to malaria, a finding that may one day help fight a disease that afflicts and kills millions of people.

The researchers focused on TEP1, a protein in the mosquito’s immune system. When a mosquito is infected with a parasite that causes malaria, a biochemical reaction is triggered that physically transforms TEP1 into an active state capable of grabbing on to the parasite’s surface and targeting it for termination.

In a study appearing online this week in the Proceedings of the National Academy of Sciences, the UT Southwestern group used a method called X-ray crystallography to uncover TEP1’s three-dimensional structure. They found that the genetic differences between mosquitoes that are resistant and those that are susceptible to the parasite mostly manifest in a region of the TEP1 protein dubbed “the warhead,” the portion that grabs the malarial parasite.

“TEP1 is a scout that finds the enemy, in this case malarial parasites, then plants a homing signal on the enemy and calls in the air strike,” said Dr. Richard Baxter, a postdoctoral researcher in biochemistry at UT Southwestern and lead author of the study.

Understanding how some mosquitoes can fend off malaria might someday lead to reducing or even eliminating the mosquito’s capacity to transmit the devastating disease, Dr. Baxter said.

“We have been trying to cure people of malaria for over a century,” said Dr. Baxter, who also is a research associate with the Howard Hughes Medical Institute at UT Southwestern. “Only recently have people started to think about curing mosquitoes of malaria.”

Nobel laureate Dr. Johann Deisenhofer, who is senior author of the study, said, “This finding opened my eyes to the fact that mosquitoes are almost as unhappy about malaria as we are. “They try to get rid of it.” Dr. Johann Deisenhofer is a professor of biochemistry, an HHMI investigator and holder of the Virginia and Edward Linthicum Distinguished Chair in Biomolecular Science. He was awarded the 1988 Nobel Prize in chemistry for using X-ray crystallography to describe the structure of a protein involved in photosynthesis.

Malaria is one of the leading causes of disease and death in the world. About 350 million to 500 million worldwide are infected with malaria, according to the Bill and Melinda Gates Foundation. Each year more than one million die, primarily children in Africa.

About 40 percent of the world’s population lives in areas with mosquitoes that carry malaria. Prevention and treatment have been hampered by cost, the rise of drug-resistant malarial parasites, and the lack of a vaccine.

Malaria is caused by parasites of the genus Plasmodium, which are spread to humans through mosquito bites. A mosquito picks up the parasite via infected human blood. The parasite then embeds itself in the mosquito’s gut wall and reproduces, eventually passing to the salivary glands. The mosquito then infects new people during subsequent bites.

The research group’s French collaborators, using a Plasmodium species that infects rodents, previously determined that the gene for TEP1 occurs in two forms, or alleles. One, called TEP1r, occurs in mosquitoes that are resistant to malarial infection. Another, TEP1s, is found in mosquitoes that are vulnerable to infection.

The TEP1r and TEP1s proteins are 93 percent genetically identical, and the new study, in which TEP1r was structurally analyzed, shows that the differences cluster around the warhead area, Dr. Baxter said. This finding reinforces the theory that the warhead is a key element of the overall immune response to malaria in mosquitoes.

In future studies, the researchers will genetically manipulate the warhead to study its binding properties, Dr. Baxter said. In addition, further research is needed to determine what other elements of the mosquito’s immune system are activated once TEP1 binds to an invader.

###
Other UT Southwestern researchers involved in the study were Dr. Chung-I Chang, a former postdoctoral researcher, and Yogarany Chelliah, an HHMI research specialist. Researchers from the Institut de Biologie Moléculaire et Cellulaire in Strasbourg, France, also participated.

The work was supported by The Welch Foundation.

This news release is available on our World Wide Web home page at http://www.utsouthwestern.edu/.....92511.html

To automatically receive news releases from UT Southwestern via e-mail, subscribe at www.utsouthwestern.edu/receivenews

Dr. Johann Deisenhofer - http://www.utsouthwestern.edu/.....43,00.html
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PostPosted: Thu Aug 16, 2007 9:27 pm    Post subject: Free distribution of insecticide-treated mosquito nets can s Reply with quote

Public Library of Science
16 August 2007

Free distribution of insecticide-treated mosquito nets can save lives

Malaria is still responsible for over a million deaths every year, even though it has been known for some years that sleeping under an insecticide-treated net (ITN) greatly reduces the chance of being bitten by the mosquitoes which carry the disease. There have been heated arguments as to how best to increase the use of such nets, particularly for children and pregnant women. Now research in Kenya, published in the latest issue of PLoS Medicine, has shown that a free mass distribution programme has raised the rate of ITN use to an impressive 66%. Further good news from this research is that this high rate is more or less the same whatever the family income level.

Back in 2004 almost all ITNs available in Kenya were sold commercially and only 7% of children slept under nets, according to a survey conducted by Abdisalan Noor and colleagues at the Kenya Medical Research Institute (KEMRI). Their survey, involving 3,700 children in four parts of Kenya, also found that, in the poorest families, who are most at risk of malaria, only 3% slept under nets.

During 2005 ITNs became increasingly available, heavily subsidised in clinics, and the researchers found an increase in the overall level of use to 24%. Free mass distribution began in 2006 and by the end of that year two-thirds of children were sleeping under nets. Rates of use need to be improved still further so that every child sleeps under a net, but the result is still impressive after just one year of free distribution.

The researchers argue that their findings show that ITNs must be available free if high levels of use are to be achieved. This will cost money but will save many lives. There will also be savings to the health services; if there are fewer cases of malaria, less will be spent on treatment. The findings of the study will be used by the Government of Kenya as a powerful argument for more international support for its ITN distribution programme. The study has also identified other factors which will be important in the continuing efforts to increase ITN use


###
Note: The insecticide used in ITNs is of extremely low toxicity to humans. It must be reapplied at intervals but long-lasting nets are now available which remain effective for 3-5 years.

Citation: Noor AM, Amin AA, Akhwale WS, Snow RW (2007) Increasing coverage and decreasing inequity in insecticide-treated bed net use among rural Kenyan children. PLoS Med 4(Cool: e255.

IN YOUR ARTICLE, PLEASE LINK TO THIS URL, WHICH WILL PROVIDE ACCESS TO THE PUBLISHED PAPER: http://medicine.plosjournals.o.....ed.0040255

PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-04-08-noor.pdf

Related image for press use: http://www.plos.org/press/plme-04-08-bates.jpg
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PostPosted: Wed Aug 29, 2007 1:29 pm    Post subject: Discovery could help stop malaria at its source -- the mosqu Reply with quote

Rensselaer Polytechnic Institute
29 August 2007

Discovery could help stop malaria at its source -- the mosquito

Troy, N.Y. – As summer temperatures cool in the United States, fewer mosquitoes whir around our tiki torches. But mosquitoes swarming around nearly 40 percent of the world’s population will continue to spread a deadly parasitic disease — malaria. Now an interdisciplinary team led by researchers from Rensselaer Polytechnic Institute has found a key link that causes malarial infection in both humans and mosquitoes.

If this link in the chain of infection can be broken at its source — the mosquito — then the spread of malaria could be stopped without any man, woman, or child needing to a take a drug. The researchers’ discovery will be published in the Aug. 31 edition of the Journal of Biological Chemistry.

The team found that humans and the mosquitoes that carry the malaria parasite share the same complex carbohydrate, heparan sulfate. In both humans and mosquitoes, heparan sulfate is a receptor for the malaria parasite, binding to the parasite and giving it quick and easy transport through the body. The team was led by Robert J. Linhardt, the Ann and John H. Broadbent Jr. ’59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer.

“The discovery allows us to think differently about preventing the disease,” Linhardt said. “If we can stop heparan sulfate from binding to the parasite in mosquitoes, we will not just be treating the disease, we will be stopping its spread completely.”

Malaria parasites are extremely finicky about their hosts, Linhardt explained. Birds, rodents, humans, and primates all can be infected with malaria, but each species is infected by a different species of mosquito — and each of those mosquitoes is infected by a different malaria parasite. In other words, there needs to be a perfect match at the molecular basis for malaria to spread from one species to another, Linhardt said. Researchers have long understood this deadly partnership, but the molecular basis for the match had never been determined.

“The discovery marks a paradigm shift in stopping malaria,” Linhardt said “Now, we can work to develop an environmentally safe, inexpensive way to block infection in mosquitoes and not have to worry about drug side effects in humans.”

Malaria kills over one million people around the world, mostly young children. And the problem is growing, Linhardt noted. As the Earth heats up due to global warming, outbreaks of malaria are being reported higher up the coast of South America and Mexico each year, he said.

“Unfortunately, there is little direct funding on malaria in this country outside of the Bill and Melinda Gates Foundation, because it is not considered a major threat in this country,” Linhardt noted. “We do our research on a shoestring. Malaria research funding needs to move higher up on the scientific priority list.”

Linhardt and his collaborators were the first to discover the link between the spread of malaria in humans and heparan sulfate in 2003. Those findings were also published in the Journal of Biological Chemistry. In this earlier study, Linhardt compared the receptors in the liver of humans to those of rodents. The liver is the first organ to be infected by the malaria parasite in mammals. The researchers found that heparan sulfate in the human liver was the unwitting transporter of the disease to the human bloodstream. The receptor found in rodents was a different heparan sulfate.

The next step for Linhardt, outlined in the current research, was to determine if heparan sulfate was also present in the species of mosquito known to spread malaria to humans, Anopheles stephensi. To make this key link, Linhardt and his current research team, which includes Rensselaer doctoral students Melissa Kemp and Jin Xie, enlisted the help of New York University physician and entomologist Photini Sinnis. Sinnis and her team at NYU provided their entomological expertise and the ill-fated mosquitoes needed for the experiments.

After finding heparan sulfate in mashed mosquitoes, the researchers needed to determine if heparan sulfate was in the mosquito organs known to host the malaria parasite. If so, it was likely that heparan sulfate was the reason malaria spreads from mosquito to human and human to mosquito.

In mosquitoes, the malaria parasite infects the digestive tract. A mosquito bites a human who carries the malaria parasite in his or her bloodstream. The parasites move into the bug’s gut and then to their salivary glands, allowing the mosquito to infect another human during its next blood meal. To isolate a two-microgram salivary gland and the four-microgram digestive tract from each mosquito required the extreme skill of Sinnis and her team, which included Alida Coppi. Once isolated, the guts and glands were analyzed by internationally renowned microanalysts Toshihiko Toida, Hidenao Toyoda, and Akiko Kinoshita-Toyoda at Chiba University in Japan. Heparan sulfate was found in both mosquito organs.

As a final step, the Rensselaer team proved that the heparan sulfate in the mosquito bound to the same malaria parasite that heparan sulfate found in the human liver did. It was an unfortunate perfect match.
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PostPosted: Tue Sep 25, 2007 5:31 pm    Post subject: How adhesive protein causes malaria Reply with quote

Karolinska Institutet
25 September 2007

How adhesive protein causes malaria

Researchers at the Swedish medical university Karolinska Institutet (KI) and the Swedish Institute for Infectious Disease Control (SMI) have identified the biochemical mechanism behind the adhesive protein that give rise to particularly serious malaria in children. The knowledge of how the malaria parasite makes blood vessels become sticky paves the way for a future vaccine for the disease, which currently kills some 2 million people every year.

Severe anaemia, respiratory problems and cardiac dysfunction are common and life-threatening symptoms of serious malaria infection. The diseases are caused when the malaria bacteria Plasmodium falciparium infects the red blood cells, which then accumulate in large amounts, blocking the flow of blood in the capillaries of the brain and other organs.

The reason that the blood cells conglomerate and lodge in the blood vessels is that once in the blood cell the parasite produces proteins that project from the surface of the cell and bind with receptor molecules on other blood cells and on the vessel wall, and thus act like a glue. The challenge facing scientists has been to understand why certain proteins produce a stronger adhesive and thus cause more severe malaria.

The research group, which is headed by Professor Mats Wahlgren at the Department of Microbiology, Tumour and Cell Biology, KI, has studied the adhesive protein PfEMP1 in children with severe malaria. The group has identified specific parts of PfEMP1 that are likely to bond more strongly to the receptors in the blood vessels, therefore producing a stronger adhesive effect. What the scientists show in their newly published study is that these protein parts are much more common in parasites that cause particularly severe malaria. If they can identify enough adhesive proteins causing severe malaria, it will be possible to design a vaccine that prepares the body’s own immune defence.

“There are no vaccines yet that can prevent the development of malaria and cure a seriously infected person,” says Professor Wahlgren. “We’ve now discovered a structure that can be used in a vaccine that might be able to help these people.”


###
The study is a collaboration between Karolinska Institutet, the Swedish Institute for Infectious Disease Control, Makerere University and Medical Biotech Laboratories in Uganda, and has been financed by the Swedish International development cooperation Agency (Sida), the Swedish Research Council and the EU.

Publication:

“PfEMP1-DBL1a amino acid motifs in severe disease states of Plasmodium falciparum malaria”, Johan Normark, Daniel Nilsson, Ulf Ribacke, Gerhard Winter, Kirsten Moll, Craig E. Wheelock, Justus Bayarugaba, Fred Kironde, Thomas G. Egwang, Qijun Chen, Björn Andersson and Mats Wahlgren PNAS Online Early Edition, 24-28 September 2007
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PostPosted: Thu Oct 04, 2007 1:25 pm    Post subject: Malaria product portfolio would benefit from greater cohesio Reply with quote

Research Australia
4 October 2007

Malaria product portfolio would benefit from greater cohesion amongst stakeholders

Malaria drug and vaccine research is booming. According to a report launched today in the UK by Australian researchers at The George Institute for International Health, 16 new malaria vaccine candidates are now in clinical trials; six new malaria drugs are about to reach the market; and by 2011 we will have up to 12 new anti-malarial drug product registered.

However, this unprecedented level of malaria R&D activity is not necessarily all good news. The report’s authors found that the high number of malaria vaccine candidates was the result of scientific and technical gaps and lacking policy coordination rather than a reflection of cohesive global activity. Lack of coordination and planning mean that invested funding and efforts are not delivering as much as they should, and may be costing donors tens of millions of dollars.

According to Dr Mary Moran, the report’s lead author, improved vaccine research co-ordination and investment decisions could save more than USD20 million over 5 years and prevent up to 3,000 unnecessary test vaccinations in African children. “The most tantalizing finding was that these high-impact policy interventions – and the resulting savings - are well within reach if donors and developers can work together”, said Dr Moran. “We need a system to ensure that fewer and better vaccine candidates enter clinical trials in Africa”.

On the drug front, the report welcomed the arrival of new anti-malarials after a dearth of many decades, but noted that this meant donors, purchasers and developing countries are now faced with the challenge of working out which of the many competing products offer the best cost-benefit for African populations, and the funding of very large and expensive studies which are needed to determine this. Post-registration trials of tens to hundreds of thousands of patients will be needed to ensure that these new drugs are appropriately absorbed by already strained health systems and appropriately delivered to malaria patients.

Over the past year, Dr Mary Moran and her team from The George Institute, supported by the Global Forum for Health Research through World Bank funding, engaged with main stakeholders in the malaria field to provide donors with a 5-year map of the future, including what malaria products are in the pipeline, how much donors will need to spend to move them towards success, and where this spending should focus. Key findings were:

The additional cost for clinical development of the global malaria vaccine and drug portfolio over the next 5 years is likely to be around $US 600 million
A substantial proportion of this (e.g. up to 60% in the case of vaccine trials) will go to Africa. This represents a very large injection of business funding into Africa
Up to US $250 million may go to small Western drug companies and Contract Research Organizations and to developing country manufacturers: again, a substantial injection of funds into desired growth areas.

The report also debunks some common beliefs about African capacity (or lack thereof). In particular, the notion that Africa needs investment to build new malaria trial sites, and that existing African trial sites could be sustainable if they were only more business-like. “Sustainability is a myth”, said Dr Moran, “at least under current conditions. Currently, many donors and developers strangle a site’s ability to stay afloat because they routinely pay project overheads that are well below costs, and are resistant to providing core funding. No Western institution could survive under those conditions.”

More encouragingly, the report noted that well-planned and sustained donor investment since 2000 means that, if well managed, we now have enough malaria trial sites in Africa to meet all likely future demand out to 2012 and probably well beyond. “Funders and trial sites can justly congratulate themselves on their site capacity-building efforts in Africa in the last 10 years”, said Dr Moran. “However, this also means the time has come to move on from building new product trial sites in Africa to supporting current sites in a sustainable way.”

“The key to success in the next five years will be providing the right amount of funding in the right places supported by the right policies,” said Professor Stephen Matlin, Executive Director of the Global Forum for Health Research. “We hope this report helps donors and product developers reach that goal.”

WHO estimates that 300 - 500 million new malaria infections occur per year, resulting in more than 1.2 million deaths annually. The overwhelming majority of these deaths are in children under five years of age and in pregnant women.


###
The George Institute for International Health seeks to improve global health through high quality research, and applying this research to health policy and practice. For further information, please visit www.thegeorgeinstitute.org

The Global Forum for Health Research believes that more health research needs to be devoted to improving the health of people in developing countries. For further information, please visit www.globalforumhealth.org
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