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(Health) Malaria: Epidemiology of Malaria in the Philippines
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adedios
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PostPosted: Wed Oct 24, 2007 2:12 pm    Post subject: Johns Hopkins Malaria Research Institute Releases Special Re Reply with quote

October 24, 2007
JHMRI

Johns Hopkins Malaria Research Institute Releases Special Report

“Breaking the Cycle” chronicles five years of scientific discovery conducted by researchers at the Johns Hopkins Malaria Research Institute (JHMRI). Founded at the Johns Hopkins Bloomberg School of Public Health in 2001, JHMRI is a state-of-the-art malaria research facility with 19 full-time faculty dedicated to the search for medical and scientific breakthroughs in malaria prevention and treatment by advancing basic science along every stage of the malaria parasite lifecycle.

For the full article:

http://malaria.jhsph.edu/breakingthecycle

The Report:

http://malaria.jhsph.edu/breakingthecycle.pdf
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PostPosted: Thu Nov 08, 2007 5:02 pm    Post subject: Bug-Zapper: A dose of radiation may help knock out malaria Reply with quote

National Institute of Standards and Technology (NIST)
8 November 2007

Bug-Zapper: A dose of radiation may help knock out malaria

How are physicists helping an effort to eradicate malaria, the mosquito-borne disease that kills more than one million people every year" Researchers at the National Institute of Standards and Technology (NIST) used their expertise in radiation science to help a young company create weakened, harmless versions of the malaria-causing parasite. These parasites, in turn, are being used to create a new type of vaccine that shows promise of being more effective than current malaria vaccines.

The new vaccine is a departure from previous approaches, which have usually depended on proteins derived from only part of the parasite Plasmodium falciparum, the most dangerous species of parasite that causes malaria. Using vaccines based on whole living parasites had been on scientists’ minds for several decades, after they discovered that volunteers built up high levels of protection to malaria after being exposed to mosquitoes containing live, radiation-weakened parasites. But manufacturing technology only recently has been developed to the point where it is possible to efficiently extract weakened parasites from their mosquito carriers in order to make a vaccine.

With their knowledge of measuring radiation doses for industrial processes such as medical equipment sterilization, NIST researchers have been lending their expertise for several years to Maryland-based biotech firm Sanaria Inc., which is creating the new vaccine. In the manufacturing process, live mosquitoes containing the parasite are exposed to gamma rays. To ensure that the parasites are sufficiently weakened for the vaccine, yet remain alive, they must be exposed to a radiation dose of at least 150 gray, but not much more. Coincidentally, this is also the dose used to delay sprouting in potatoes and onions.

One critical design issue is ensuring a relatively uniform radiation dose regardless of where the mosquito is in the chamber. Using radiation-sensitive test materials inside the chamber as well as sophisticated measuring equipment, NIST researchers mapped out the radiation dose at different parts of the chamber. They initially found there was a variation in dose within the chamber, but by suggesting that the manufacturer change the position of the chamber relative to the radiation source they were able to significantly reduce this variation in dose. This not only increases the speed of the process, but more importantly improves the quality of the process. To be safe for human trials all mosquitoes in the chamber must get their minimum dose of 150 gray.

The vaccine is currently being manufactured for the anticipated human clinical trials. NIST researchers will continue to be active in the manufacturing process by doing regularly scheduled quality-assurance tests that ensure the desired dose is being delivered to the mosquitoes.


###
Stephen Hoffman, Sanaria’s CEO and Chief Scientific Officer, will describe the development of the malaria vaccine at a colloquium on Nov. 16 at NIST’s Gaithersburg, Md., campus. For information on attending, see www.nist.gov/public_affairs/colloquia/20071116.htm
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PostPosted: Wed Nov 28, 2007 1:21 pm    Post subject: Study of malaria parasite in patient blood finds distinct ph Reply with quote

Broad Institute of MIT and Harvard
28 November 2007

Study of malaria parasite in patient blood finds distinct physiological states

Novel states, not seen in lab cell cultures, may be linked to variable course of disease; Insight flows from unique approaches to analyzing genomic data
The malaria parasite has been studied for decades, but surprisingly, little is known about how it behaves in humans to cause disease. In a groundbreaking study published November 28 in the advance online edition of Nature, an international research team has for the first time measured which of the parasite's genes are turned on or off during actual infection in humans, not in cell cultures, unearthing surprising behaviors and opening a window on the most critical aspects of parasite biology.

That insight springs from the genomic analysis of parasites in their natural state, derived directly from patients residing in Senegal, and also from the researchers' use of innovative computational approaches to interpret their results. These computational methods helped to identify three distinct biological states of the malaria parasite: an active growth-based state, a starvation response and an environmental stress response, presumably related to the body's inflammatory response to the parasite. This physiological diversity was previously unknown and may help explain the widely varying course of the disease in different patients, from mild, flu-like illness to coma and even death.

"For the first time, we have glimpsed the biology of the malaria parasite in one of its most important environments -- humans," said co-senior author Aviv Regev, a core member of the Broad Institute of MIT and Harvard and an assistant professor of biology at MIT. "Our unique computational approach holds promise not only for understanding the malaria pathogen, but likely other important microbes as well."

"This work illustrates the true power that comes from developing the right computational methods and applying them to important biomedical problems," said co-senior author Jill Mesirov, director of Computational Biology and Bioinformatics at the Broad Institute of MIT and Harvard. "Even more importantly, it reflects scientific research at its best -- a global effort that brings together clinicians and researchers with diverse expertise, working directly with patients in areas hardest hit by disease."

In its natural state, the malaria parasite, Plasmodium falciparum, leads a complicated life. It proceeds through a series of distinct developmental stages both in humans and in mosquitoes, the main vector for disease transmission. Malaria researchers typically circumvent this complexity by studying the parasite in cultured cells. Yet in this artificial setting, few differences have been found in the genes that are turned on or off in various strains of P. falciparum. That uniformity is surprising, because it fails to explain the drastically different courses experienced by malaria patients.

To explore the basis for these differences, first author Johanna Daily, an infectious disease physician at Brigham and Women's Hospital, assistant professor of medicine at Harvard Medical School, and a researcher at both the Harvard School of Public Health and the Broad Institute, set out to observe P. falciparum in its natural environment: the human circulation. Using small samples of blood collected from more than 40 malaria patients in Senegal, Daily and her colleagues worked meticulously to devise a method for isolating genetic material from parasites, allowing them to determine which of the nearly 6,000 P. falciparum genes are switched on or off during infection in humans. Importantly, all of the patients involved in the study harbored similar-looking parasites, yet their symptoms varied widely.

These clinical research efforts were led by Professor Souleymane Mboup and Dr. Daouda Ndiaye at Cheikh Anta Diop University. "This project would not have been possible without the dedicated work of our collaborators in Senegal," said co-author Dyann Wirth, a professor and chairman of the department of immunology and infectious diseases at the Harvard School of Public Health and the co-director of the Broad Institute's Infectious Disease Initiative. "We are grateful to them and to the many malaria patients who generously volunteered to participate in this study."

From the parasites in patients' blood, the researchers simultaneously measured the activity level, or "expression", of every P. falciparum gene. Co-author Elizabeth Winzeler, an associate professor at The Scripps Research Institute, led this aspect of the study. "The ability to look across the parasite's entire genome was essential," said Winzeler. "We uncovered extraordinary things about parasite biology -- things we could not have even imagined."

Winzeler, who is also head of malaria research at the Genomics Institute of the Novartis Research Foundation (GNF), where much of the genomic work was performed, is grateful that organizations like GNF choose to encourage these types of high-risk studies. "We are especially excited about using these observations to guide our drug discovery efforts," she said.

The key to interpreting these results lay in two computational tools, first developed by Mesirov and her colleagues to study the genomics of human cancer cells. By adapting these tools for malaria, the researchers were able to identify distinct groups of parasites, each marked by characteristic sets of active and inactive genes. The biological underpinnings of these groups were made clearer through a second innovative approach: systematically comparing P. falciparum -- whose genes and genome are poorly understood -- to the baker's yeast, an organism that has been extensively characterized at the genetic level. Since the malaria parasite and the baker's yeast are both single-celled eukaryotes, it is possible they may share some of the same cellular machinery and could also respond in some similar ways to their surroundings.

With this unusual approach, co-senior author Regev and her colleagues were able to describe three different classes of parasites, one of which displayed features associated with a well-known form of parasite metabolism. The other groups, however, were very unusual, reflecting modes of parasite behavior that had never before been described.

One of these novel groups seems to signal parasites that are under extreme environmental stress. Importantly, this group shows a clear correlation with patient symptoms, including high fevers and elevated levels of inflammatory markers in the blood. "This is a remarkable result -- it suggests the malaria parasite can sense what is happening within its host and adjust its biology accordingly," said Daily. "That interaction signals a fundamental shift in the way we think about malaria, one which will hopefully lead to more effective treatments -- particularly for the most severe cases of the disease."

The other parasite group is associated with an alternative form of parasite metabolism, which relies on two specialized cellular compartments called the mitochondria and the apicoplast. That result is particularly surprising since mitochondria in P. falciparum were previously thought to be non-functional.

"For decades, our knowledge of the parasite has been driven solely by studies in cultured cells, not in humans," said Wirth. "Our work underscores the importance of studying the malaria parasite in its natural environment and will hopefully spark novel approaches to malaria drug discovery."


###
Paper cited:

Daily JP et al. Distinct physiological states of Plasmodium falciparum in malaria-infected patients. Nature DOI: 10.1038/nature06311
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PostPosted: Sat Dec 15, 2007 1:23 pm    Post subject: The Modern Fight Against an Ancient Killing Machine Reply with quote

The Modern Fight Against an Ancient Killing Machine
By Meredith F. Small, LiveScience's Human Nature Columnist

posted: 14 December 2007 09:34 am ET

They come at night, just when the family is settling down for dinner or sleep. The only warning is an irritating whine, but sometimes there's no sound at all, just a pinch and later an itch. And much later the fevers, shivering, and perhaps death.

Malaria, the disease caused by a parasite delivered in a mosquito bite, is one of the greatest killers of our time, which is why scientists are working very hard, and with various methods, to develop a vaccine against this disease.

For the full article:

http://www.livescience.com/his.....laria.html
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PostPosted: Thu Dec 20, 2007 9:45 pm    Post subject: Sea cucumber protein used to inhibit development of malaria Reply with quote

Imperial College London
20 December 2007

Sea cucumber protein used to inhibit development of malaria parasite
Scientists have genetically engineered a mosquito to release a sea-cucumber protein into its gut which impairs the development of malaria parasites, according to research out today (21 December) in PLoS Pathogens. Researchers say this development is a step towards developing future methods of preventing the transmission of malaria.

Malaria is caused by parasites whose lives begin in the bodies of mosquitoes. When mosquitoes feed on the blood of an infected human, the malaria parasites undergo complex development in the insect’s gut. The new study has focused on disrupting this growth and development with a lethal protein, CEL-III, found in sea cucumbers, to prevent the mosquito from passing on the parasite.

Human blood infected with malaria contains parasitic gametocytes – cells which can create parasite sperm and eggs in the gut of the insect. These then fertilise, kick-starting the parasite reproductive process and life cycle by producing invasive offspring called ookinetes.

These ookinetes then migrate through the mosquito’s stomach wall and produce thousands of ‘daughter’ cells known as sporozoites. After 10-20 days these are ready in the salivary glands to infect another human when the mosquito takes a subsequent blood meal.

The international team fused part of the sea cucumber lectin gene with part of a mosquito gene so that the mosquito would release lectin into its gut during feeding. The released lectin is toxic to the ookinete and therefore kills the parasite in the mosquito’s stomach.

In laboratory tests the research team showed that introducing lectin to the mosquito’s gut in this way significantly impaired the development of malaria parasites inside the mosquito, potentially preventing transmission to other people. Early indications suggest that this sea cucumber protein could be effective on more than one of the four different parasites that can cause malaria in humans.

Professor Bob Sinden from Imperial College London’s Department of Life Sciences, one of the authors on the paper said: “These results are very promising and show that genetically engineering mosquitoes in this way has a clear impact on the parasites’ ability to multiply inside the mosquito host.”

However, Professor Sinden explains that there is still a lot of work to do before such techniques can be used to combat the spread of malaria in real-world scenario. This is because although the sea cucumber protein significantly reduces the number of parasites in mosquitoes, it does not totally remove all parasites from all mosquitoes and as such, at this stage of development, would not be effective enough to prevent transmission of malaria to humans.

Professor Sinden says he hopes studies such as this one, which improve scientists’ understanding of the complex process by which malaria parasites are transmitted, will lead to new advances in the quest to prevent malaria.

“Ultimately, one aim of our field is to find a way of genetically engineering mosquitoes so that the malaria parasite cannot develop inside them. This study is one more step along the road towards achieving that goal, not least because it has been shown that more than one species of malaria can be killed in this way.”

About 40% of the world’s population are at risk of malaria. Of these 2.5 billion people at risk, more than 500 million become severely ill with malaria every year and more than 1 million die from the effects of the disease. Malaria is especially a serious problem in Africa, where one in every five childhood deaths is due to the effects of the disease. An African child has on average between 1.6 and 5.4 episodes of malaria fever each year.
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PostPosted: Sat Jan 05, 2008 6:10 am    Post subject: New Task: Malaria drug might inhibit some cancers Reply with quote

Week of Jan. 5, 2008; Vol. 173, No. 1 , p. 3

New Task: Malaria drug might inhibit some cancers
Nathan Seppa

In the 1970s and 1980s, researchers in Tanzania distributed millions of doses of chloroquine to children as part of a 5-year malaria-prevention project. While the study yielded only mixed results against that disease, the researchers noticed a striking drop in cases of Burkitt's lymphoma, a blood cancer.

New studies in mice show that chloroquine may indeed prevent Burkitt's lymphoma and also a rare disease called ataxia telangiectasia that can lead to leukemia.

For the full article:

http://sciencenews.org/articles/20080105/fob3.asp
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PostPosted: Tue Jan 15, 2008 3:32 pm    Post subject: Monkey malaria widespread in humans and potentially fatal Reply with quote

Wellcome Trust
15 January 2008

Monkey malaria widespread in humans and potentially fatal
A potentially fatal species of malaria is being commonly misdiagnosed as a more benign form of the disease, thereby putting lives at risk, according to research funded by the Wellcome Trust and the University Malaysia Sarawak.

Researchers in Malaysia studied more than 1,000 samples from malaria patients across the country. Using DNA-based technology they found that more than one in four patients in Sarawak, Malaysian Borneo, were infected with Plasmodium knowlesi, a malaria parasite of macaque monkeys, and that the disease was more widespread in Malaysia than previously thought. Infections were most often misdiagnosed as the normally uncomplicated human malaria caused by P. malariae.

Malaria, which kills more than one million people each year, is caused when Plasmodium parasites are passed into the bloodstream from the salivary glands of mosquitoes. Some types, such as P. falciparum, found most commonly in Africa, are more deadly than others. P. malariae, found in tropical and sub-tropical regions across the globe, is often known as "benign malaria" as its symptoms are usually less serious than other types of malaria.

Until recently, P. knowlesi, was thought to infect only monkeys, in particular long-tailed macaques found in the rainforests of South East Asia. Natural infections of man were thought to be rare until human infections were described in one area in Sarawak, Malaysian Borneo. However, in a study published today in the journal Clinical Infectious Diseases, Professors Janet Cox-Singh and Balbir Singh with colleagues at the University Malaysia Sarawak and three State Departments of Health in Malaysia have shown that knowlesi malaria is widespread in Malaysia.

Under the microscope, the early parasite stages of P. knowlesi look very similar to P. falciparum, the most severe form of human malaria, while the later parasite stages are indistinguishable from the more benign P. malariae. Misdiagnosis as P. falciparum is clinically less important as P. falciparum infections are treated with a degree of urgency and P. knowlesi responds to the same treatment. However, misdiagnosis as the more benign slower growing parasite P. malariae is a problem.

P. knowlesi is unprecedented among the malaria parasites of humans and non-human primates as it reproduces every 24 hours, and one of the features of fatal P. knowlesi infections is the high number of infected red blood cells in these patients. Therefore, even a short delay in accurate diagnosis and treatment could lead to the rapid onset of complications, including liver and kidney failure, and death.

Using DNA detection methods, Professor Cox-Singh and colleagues found malaria infection with P. knowlesi to be widely distributed in Malaysian Borneo and mainland Malaysia, sometimes proving fatal. In addition, single human infections have been reported in Thailand and Myanmar.

"I believe that if we look at malaria infections in South East Asia more carefully, we will find that this potentially fatal type of the disease is more widespread than is currently thought," says Professor Cox-Singh. "Given the evident severity of the illness that it causes, I would recommend that doctors treating patients with a laboratory diagnosis of P. malariae remain alert to the possibility that they may be dealing with the potentially more aggressive P. knowlesi. This would be particularly important in patients who have spent time in the forest fringe areas of South East Asia where the non-human primate host exists."
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