Studies Examine Effect Of Male Circumcision On Sexual Behavior, Breast-Feeding Interventions For HIV-Positive Women

The following highlights recently released journal articles on HIV/AIDS.

Male Circumcision in Siaya and Bondo Districts, Kenya: Prospective Cohort Study To Assess Behavioral Disinhibition Following Circumcision," Journal of Acquired Immune Deficiency Syndromes: Kawango Agot -- project coordinator of a collaborative research project among the University of Nairobi, University of Illinois and the University of Manitoba -- and colleagues conducted the study among 324 recently circumcised men and 324 uncircumcised men to determine the effect of circumcision on sexual behavior. The researchers compared the two groups' sexual behaviors at one, three, six, nine and 12 months following circumcision or study enrollment. They found that during the first month following circumcision, men were 63% less likely to report having 0 to 0.5 risky sexual acts weekly than uncircumcised men. The researchers also found that during the first month following circumcision, men were 61% less likely to report having more than 0.5 risky sexual acts weekly than uncircumcised men. The differences in sexual behavior disappeared during the remainder of the follow-up period, and similar results were seen for risky unprotected sexual acts, number of at-risk sexual partners and condom use, according to the researchers. The researchers concluded that during the first year following circumcision, men did not report an increased number of risky sexual acts compared with uncircumcised men -- indicating that "any protective effect of male circumcision on HIV acquisition is unlikely to be offset by an adverse behavioral impact" (Kawango et al., Journal of Acquired Immune Deficiency Syndromes, 1/1).

Two-Year Morbidity-Mortality and Alternatives to Prolonged Breast-Feeding Among Children Born to HIV-Infected Mothers in Cote d'Ivoire," PLoS Medicine: Renaud Becquet of the Institut National de la Sante et de la Recherche Medicale Unite in France and colleagues conducted the study from 2001 through 2005 among 557 infants born to HIV-positive women in Abidjan, Cote d'Ivoire. After their infants were born, the women, who underwent prenatal antiretroviral prophylaxis, either received breastmilk substitutes or exclusively breast-fed for four months. Nutritional counseling and clinical management were provided for two years, and breastmilk substitutes were provided at no cost. Thirty-four percent of the 262 infants who were breast-fed for an average of four months during the two-year follow-up period did not experience any adverse health outcomes -- which the researchers defined as diarrhea, acute respiratory infections or malnutrition -- compared with 37% of the infants who received breastmilk substitutes. The two-year probability of presenting with a severe health event -- which the researchers defined as hospitalization or death -- was 14% among the breastmilk substitute group, compared with 15% among the breast-fed infants. The researchers concluded that breastmilk substitutes and short-term breast-feeding can be safe interventions aimed at preventing mother-to-child HIV transmission in urban African settings where adequate nutritional counseling and care, access to clean water and breastmilk substitutes are available (Becquet et al., PLoS Medicine, January 2007). In a related opinion piece, Grace John-Stewart of the University of Washington writes that the researchers "provide good data to suggest that with appropriate provisos, replacement feeding can be a safe option to consider" for HIV-positive women in urban African settings (John-Stewart, PLoS Medicine, January 2007).

"Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Engineered Immune Cells And AIDS

Twenty years after its introduction, gene therapy still holds great promise as a way to harness the insidious power of viruses such as human immunodeficiency syndrome (HIV). But scientists have yet to solve a vexing problem: developing an efficient transport system that is capable of delivering therapeutic payloads to specific cells.

As challenging as the problem has been, researchers in the USC Viterbi School of Engineering may be turning a corner. With support from a $13.9 million grant from the Bill and Melinda Gates Foundation, a multi-institutional team of scientists, including Pin Wang of the USC Mork Family Department of Chemical Engineering and Materials Science, is exploring a completely new way of manipulating the body's natural defense system.

"Rather than focusing on conventional vaccines that boost the immune system, we are experimenting with a way to help the immune system produce antibodies that can neutralize the virus," says Wang. "If we can design a modified virus that will deliver these antibodies to chosen cells, we will be able to insert DNA that will help rather than harm cells."

Viruses are efficient carriers or transport vehicles in the body because they are naturally able to penetrate cells, inserting the genetic material they contain into their new host. By itself, a virus cannot reproduce; it must infect a cell and take control of the host's machinery to make copies.

HIV also possesses an unusual structure and a keen ability to hide from antibodies in a sugar-coated shield. The shield has very few open spaces on its surface, Wang says, which makes it virtually impossible to penetrate. And because the virus also has an uncanny ability to hide, HIV often goes virtually unnoticed by neutralizing antibodies that are roaming the body in search of foreign invaders.

Faced with such a clever adversary, Wang wants to synthetically alter the HIV invaders and use their hollow shells as delivery vehicles to insert DNA that will counteract the infection.

The "Cadillac" of this gene delivery system is an HIV-based "lentiviral vector," a type of retrovirus that uses the backbone of a virus to infect both dividing and nondividing cells. Wang says lentiviral vectors are very efficient delivery vehicles for human cells.

Collaborators on his project are targeting hematopoietic stem cells -- the bone marrow cells that form blood cells - to create B lymphocytes. The researchers want to reprogram these bone marrow cells by adding genes that will instruct the cells to produce rare antibodies such as B12, 4E10, 2G12 and 2F5. Wang says these antibodies are known to neutralize the virus.

"In laboratory tests, we remove harmful genes coding for the HIV virus and engineer the backbone, or spine, of virus so that it is no longer replicable " he says. "Once manufactured recombinantly, this modified virus - the lentiviral vector -- becomes a natural delivery system that can transport useful genes into cells without causing illness."

Although the gene delivery technique looks promising, researchers are still working on ways to manipulate these elusive bone marrow cells and get them to generate "designer immune cells." Another problem seems to be making sure lentiviral vectors target only hematopoietic stem cells, and not other types of cells, to achieve the desired targeted delivery.

With a group of USC biomedical engineering students and Caltech biologists, Wang is experimenting with CD20 as a target antigen for human B cells. His strategy, published in the August 1, 2006 issue of Proceedings of the National Academy of Sciences, targets the human B cells only. After two years of experimentation, the team has been able to demonstrate that they can specifically target human B cells in mice.

"Possibly the most important implication of the work is that gene therapy could now be carried out as an inexpensive procedure, able to be considered even in the less-developed world," Wang and his coauthors wrote.

That's good news for the World Aids Foundation, which announced on World AIDS Day (Dec. 1, 2006) that the disease is on the rise again. More than 39 million people around the world are now infected with HIV, the foundation reported.

"I think we are finally on the right track," Wang says. "If scientists can find a way to genetically engineer immune cells to neutralize HIV, we may be able to develop immunotherapy for HIV-Infected people, as well as find ways to prevent it all together."

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Wang's research is part of the Gates Foundation's Grand Challenges in Global Health initiative, which was launched in 2003 to create "deliverable health tools" that were "not only effective, but also inexpensive to produce, easy to distribute and simple to use in developing countries."

Collaborators on the five-year project, titled "Engineering Immunity Against HIV and Other Dangerous Pathogens," include principal investigator David Baltimore of Caltech, co-principal investigators Pamela Bjorkman of Caltech and Wang of USC. The USC student researchers working on the project are Leslie Bailey, Taehoon Cho, Haiguang Yang and Alex Lei. All four are third-year Viterbi School graduate students majoring in chemical engineering.

Contact: Diane Ainsworth
University of Southern California

China Considering Evidence That Male Circumcision Could Reduce Risk Of HIV Infection, Unlikely To Launch Campaign, Health Official Says

China is considering evidence that routine male circumcision could reduce a man's risk of HIV infection but likely will not implement such a campaign nationwide, Ru Xiaomei, deputy director general of China's National Population and Family Planning Commission, said on Friday, Reuters U.K. reports (Blanchard, Reuters U.K., 1/19). Data from two studies conducted in Kenya and Uganda released last month by NIH indicate that routine male circumcision could reduce a man's HIV infection risk through heterosexual sex by about 50%. According to researchers, male circumcision eliminates the cells most vulnerable to HIV. In addition, a circumcised penis develops thicker skin that is resistant to HIV infection. The results of the Uganda and Kenya studies were similar to the results of a study conducted in South Africa in 2005 (Kaiser Daily HIV/AIDS Report, 12/14/06).

Comments
According to Ru, Chinese officials have seen the results of the studies conducted in Africa, but the "AIDS situation in China has not yet reached such a large scale (as in Africa)." She added, "I'm not yet totally certain about the evidence for circumcision. We should exercise caution." According to Reuters U.K., the number of circumcisions performed in China is low compared with some Asian countries, including South Korea, Japan and Indonesia. In addition, a wide-scale male circumcision campaign might encounter resistance from China's non-Muslim majority, according to Ru. She added that the cost of such a campaign might present an issue because of China's 1.3 billion population. "It would be a big deal," she said, adding, "It's much more reasonable to get people to use condoms" (Reuters U.K., 1/19). <

"Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

A Spoonful Of Sugar Makes The Medicine Work

There will soon be no more bitter pills to swallow, thanks to new research by University of Leeds scientists (UK): a spoonful of sugar will be all we need for our bodies to make their own medicine.

Professor Simon Carding of Leeds' Faculty of Biological Sciences has adapted a bacteria in our own bodies to make it produce a treatment for Inflammatory Bowel Disease (IBD). Bacteria and viruses have been used before to deliver drugs in this way, but Professor Carding has solved the major problem with this kind of treatment: he uses a sugar to 'switch' the bacteria on and off. By eating the sugar, a patient will set the medicine to work and then can end the treatment simply by stopping consumption of the sugar.

"Current bacteria and virus delivery systems produce their drugs non-stop, but for many treatments there is a narrow concentration range at which drugs are beneficial," said Professor Carding. "Outside of this, the treatment can be counterproductive and make the condition worse. It's vitally important to be able to control when and how much of the drug is administered and we believe our discovery will provide that control."

Professor Carding has modified one of the trillions of bacteria in the human gut so that it will produce human growth factors which help repair the layer of cells lining the colon, so reducing inflammation caused by IBD. But he's also adapted the bacteria so it only activates in the presence of a plant sugar called xylan that is found in tree bark. Xylan is naturally present in food in low concentrations, so by taking it in higher quantities, a patient will be able to produce their own medicine as and when they need it.

"The human gut has a huge number of bacteria, and this treatment simply adapts what's there naturally to treat the disease," said Professor Carding. "We're already looking at using the same technique for colorectal cancer, as we believe we could modify the bacteria to produce factors that will reduce tumour growth. Treatment of diseases elsewhere in the body might also be possible as most things present in the gut can get taken into the blood stream."

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The discovery has been patented - and is being developed further with support from the University's technology transfer partner, Techtran Group Ltd - part of the IP Group plc - and the Medical Research Council. The technique has been shown to work in vitro, but the researchers will be testing the treatment over the next twelve months in preparation for clinical trials.

Contact: Jo Kelly
University of Leeds

Cbl-b Resists Pseudomonas Aeruginosa Infection

Infection with Pseudomonas aeruginosa is a major problem for patients in hospital, who are at increased risk of infection because they often have a weakened immune system, as well as individuals with cystic fibrosis. One of the things that makes P. aeruginosa so virulent is the expression of a number of proteins that function as a type III secretion system. In a study that appears online on January 18 in advance of publication in the February print issue of the Journal of Clinical Investigation, researchers from the University of California at San Francisco, have identified Cbl-b as a protein that helps protect mice from infection with P. aeruginosa by targeting one of the components of the type III secretion system, ExoT.

Joanne Engel and colleagues found that in cultured human cells, ExoT was targeted for destruction by the host protein Cbl-b. More importantly, ExoT was shown to be important for bacterial dissemination in mice infected with P. aeruginosa and mice lacking Cbl-b were more susceptible to both intranasal and systemic infection with P. aeruginosa than wild-type mice. This study therefore identifies Cbl-b as a component of early host defense against infection with P. aeruginosa, an observation that could help develop new strategies for the treatment of individuals infected with this major opportunistic pathogen.

TITLE: The ubiquitin ligase Cbl-b limits Pseudomonas aeruginosa exotoxin T-mediated virulence

AUTHOR CONTACT:

Joanne Engel
University of California at San Francisco, San Francisco, California, USA.

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JCI table of contents: Jan. 18, 2007

Contact: Karen Honey
Journal of Clinical Investigation

International Response To Fight HIV/AIDS Among Children 'Tragically Insufficient' But 'Beginning To Change,' U.N. Report Says

The world's response to fighting HIV/AIDS among vulnerable children remains "tragically insufficient," but some countries are making progress in providing treatment for HIV-positive children and preventing transmission of the virus, according to a report released Tuesday by UNAIDS, UNICEF and the World Health Organization, the New York Times reports (Altman, New York Times, 1/17). The report, released on the first anniversary of the "Unite for Children, Unite Against AIDS" program, found 15.2 million children under age 18 have lost one or both parents to AIDS-related complications (AFP/Yahoo! News, 1/16). The campaign -- which is a partnership between UNICEF, UNAIDS, and other organizations and agencies -- aims to reduce the incidence of mother-to-child HIV transmission, curb the spread of the virus among young people, and provide protection as well as emotional and financial support to children who have lost parents to AIDS-related illnesses (Kaiser Daily HIV/AIDS Report, 11/10/05). The report says that 2.3 million children younger than age 15 were living with HIV in 2005 and that 10% of the 780,000 children in need of antiretroviral drugs had access to them during the same time period. About one-third of HIV-positive infants who do not have access to treatment die from AIDS-related complications in their first year, and half of them die from AIDS-related complications by age two, the report found. These statistics indicate that about 380,000 children died from AIDS-related illnesses last year, according to UNICEF. The report identifies seven countries -- Botswana, Cape Verde, the Dominican Republic, Jamaica, Namibia, Rwanda and Thailand -- that provided antiretrovirals to at least 20% of children in need of the drugs. The lack of access to prevention and treatment interventions has left about 15.2 million children orphaned, and the number is expected to increase to 20 million by 2010, according to the report. About 9% of HIV-positive pregnant women living in low- and middle-income countries in 2005 received antiretrovirals that could prevent MTC HIV transmission, up from 3% in 2003, the report found. About 10% of pregnant women living in sub-Saharan African capital cities are HIV-positive, according to the report. The majority of pregnant women in Africa do not have access to drugs aimed at preventing MTC HIV transmission, meaning that about one-third of their infants will become HIV-positive at or shortly after birth, according to UNICEF (New York Times, 1/17). The report also found that the most successful results occurred in countries that instituted a decentralized approach to HIV/AIDS service and training, demonstrated a political commitment to fighting the disease, and incorporated prevention and treatment to entire families (Leopold, Reuters, 1/16).

Recommendations
"Over the past year, there has been a broad, growing recognition of the need to intensify and accelerate action towards universal access to comprehensive prevention, treatment, care and support" for HIV/AIDS, the report says. It calls on governments to provide at least 10% of their HIV/AIDS funding for children and adolescents. According to the report, about $30 billion is required to address the prevention strategy set out by the Unite for Children campaign, which aims to provide services to 80% of HIV-positive mothers by 2010, provide antiretroviral or antibiotic treatment to 80% of children who need it, and reduce the number of HIV-positive young people by 25% within three years (AFP/Yahoo! News, 1/16).

The report is available online. Note: Adobe Acrobat is needed to view the report.

"Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

HIV/AIDS PSA Campaign 'Drawing Attention' Because Of Celebrities Involved, Messages, New York Times Reports

A "provocative" HIV/AIDS public service campaign airing on several media outlets is "drawing attention" nationwide because of the celebrities featured in the announcements and the "frank nature" of their messages, the New York Times reports. The campaign -- called "Look, listen, love, respect" -- has enlisted actresses Whoopi Goldberg, Amanda Peet, Rosie Perez and Susan Sarandon to deliver "candid, no-nonsense" messages linking drug use and risky sexual behavior with the spread of HIV among men who have sex with men, according to the Times. The Internet is a central focus of the campaign, which has launched a Web site, loveandrespect.us. Video clips of the commercials also can be viewed on YouTube and MySpace. The campaign is scheduled to air on two national cable television networks, Here! and Logo, as well as on local cable TV stations owned by companies such as Cablevision, Cox Communications and Time Warner. In addition, there are plans to air the announcements in clubs and bars in cities nationwide and to produce audio versions of the spots for the national Out Q channel of Sirius Satellite Radio, the Times reports. The campaign is a collaboration between the New York City-based organizations HIV Forum NYC and the Callen-Lorde Community Health Center. It is receiving financial backing from Broadway Cares/Equity Fights AIDS and Cable Positive, the Times reports. Dan Carlson, co-founder of HIV Forum NYC, developed the campaign with Jay Laudato, executive director of Callen-Lorde, and Colin Weil, a writer, director and producer. According to Carlson, the campaign features female actors because they "felt these honest, direct, loving messages would be heard best if told by women we can see as our mothers, best friends, sisters." He added, "They can tell us things we may not be ready to hear from each other" (Elliott, New York Times, 1/16).

"Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

WHO's Plan To Monitor HIV Drug Resistance In Botswana Likely To Fail

A World Health Organization (WHO) plan to track transmitted resistance to HIV drugs in Botswana could fail because the threshold the organization has set is too high, according to new UCLA research.

The authors of the study, which will be published Jan. 17 in the peer-reviewed online journal PLoS ONE (), based their research on the WHO's Botswana antiretroviral program, which began in 2002 and now treats some 42,000 patients. The program's goal is to treat 85,000 patients by 2009, roughly 30 percent of all those infected in Botswana.

As greater numbers are treated, the likelihood that a small percentage of patients will develop strains of HIV that are resistant to antiretroviral drugs increases. These patients may then transmit the drug-resistant strains to others, but the rates at which this may happen are unclear. The WHO surveillance system is intended to detect transmitted resistance exceeding a 5 percent threshold by 2009, though officials with the organization have not determined at what point this threshold might be reached, if at all.

According to the UCLA study, the WHO's detection test is based on a sophisticated statistical method, but the 5 percent detection threshold is an arbitrary one. Study co-author Sally Blower, UCLA professor of psychiatry and biobehavioral sciences and a member of the UCLA AIDS Institute, said the WHO threshold was primarily based on guesswork.

"They did not make any mathematical predictions on how long it would take to get to their threshold," Blower said. "Essentially, they've guessed what would happen. They should have done things on a more quantitative basis."

Blower and co-author Raffaele Vardavas, a postdoctoral fellow in Blower's research group, developed a mathematical model that traces the random evolution of drug-resistant strains of HIV in Botswana through 2009. They found that drug resistance would indeed emerge but likely at a much slower rate than the WHO anticipates, and the organization would not be able to detect it.

Though easy to implement, the WHO's statistical test would detect transmitted resistance only after it has reached 5 percent, and that threshold would likely not be reached by 2009 unless the drug-resistant strains of the virus are extremely transmissible, the authors said.

The authors note that while the WHO's monitoring plan requires a small sample size and is relatively inexpensive, it may not be entirely cost-effective at the early stages of the treatment program due to the high threshhold. Instead, they suggest that checking for transmitted resistance early this year and dropping the threshold to about 3 percent would present a better picture of the situation in Botswana. Although a lower threshold requires a larger sample size and is therefore more expensive, it is much more likely to detect transmitted resistance and therefore would be more useful.

"If transmitted resistance is found to be at or above 3 percent, then repeating the WHO's test in the next scheduled occasion using a 5 percent threshold value would provide more information as to how quickly transmitted resistance is increasing in Botswana," Vardavas said. "Although this would be more expensive, it would probably be more cost-effective than the current strategy."

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The National Institute of Allergy and Infectious Diseases funded the study.

About the UCLA AIDS Institute

Established in 1992, the UCLA AIDS Institute is a multidisciplinary think tank drawing on the skills of top-flight researchers in the worldwide fight against HIV and AIDS, the first cases of which were reported in 1981 by UCLA physicians. Institute members include researchers in virology and immunology, genetics, cancer, neurology, ophthalmology, epidemiology, social science, public health, nursing, and disease prevention. Their findings have led to advances in treating HIV as well as other diseases, such as hepatitis B and C, influenza, and cancer.

Contact: Enrique Rivero
University of California - Los Angeles

Washington, D.C., Free Clinic To Close, Staff To Join Whitman-Walker Clinic

The Washington, D.C.-based Washington Free Clinic, which has provided low-cost or no-cost health care services since 1968 to people in the city, is scheduled to close on Friday, and its staff will be joining the Whitman-Walker Clinic, the largest provider of HIV/AIDS services in the region, the Washington Post reports. The Free Clinic serves about 1,800 patients, many of whom are working poor people and immigrants from Central America or Africa without health insurance. The clinic has a staff of about 50 volunteer doctors and nurses. Whitman-Walker -- which was launched by the Washington Free Clinic in 1973 as the Gay Men's VD Clinic and five years later became a separate organization -- is expanding its medical services in the district. Whitman-Walker has 7,000 clients, facilities in the district and Northern Virginia, and a $22 million budget. According to the Post, the alliance between the two clinics also will benefit Whitman-Walker after it experienced financial problems in 2005 that forced its leaders to "reconsider its long-term future," the Post reports. Gardiner Lapham, chair of the Free Clinic board, said, "It does come full circle. [Whitman-Walker is] now taking care of us," adding that closing is "really painful, but it's the right thing for the community." Free Clinic officials said they expect to be treating both Whitman-Walker and former Free Clinic clients by Jan. 29 (Levine, Washington Post, 1/14).

"Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Boston Micromachines' New Deformable Mirror To Enhance Retinal Imaging Systems For Earlier Detection Of Leading Eye Diseases

Boston Micromachines Corporation (BMC), a leading provider of MEMS-based deformable mirror (DM) products for adaptive optics (AO) systems, today announced it has manufactured an enhanced DM capable of meeting the criteria for ultra-high resolution retinal imaging, which is necessary for early detection of ocular diseases. The new mirror will meet the demanding requirements of both OEM retinal imaging systems as well as vision science and microscopy researchers who use AO for biological imaging.

"This new deformable mirror represents a significant scientific advancement in the field of biological imaging, specifically vision science. Until now doctors were limited in their ability to gain a clear view of the human retina due to image distortion caused by tissue-induced wavefront aberration. Our deformable mirror corrects for that wavefront aberration," said Paul Bierden, president of Boston Micromachines. "This marked improvement in retinal imaging will provide doctors the technology necessary to detect the leading diseases of the eye: glaucoma, diabetic retinopathy, and age-related macular degeneration years earlier than previously possible. Earlier detection will result in earlier diagnosis and earlier treatment."

The new mirror, which is an enhanced version of Boston Micromachines' flagship product the Multi-DM, delivers increased stroke while maintaining the high resolution afforded by its 140 independently controlled actuators. The mirror's 3 kilohertz frequency capability allow for high speed real-time imaging with a 6mm aperture perfectly suited for a dilated pupil. In addition, the new Multi-DM also provides the wavefront amplitude correction needed for older eyes by offering 6 microns of stroke. This translates to 12 microns of wavefront correction, the most wavefront correction demonstrated by any MEMS DM on the market today. The development work on this MEMS device was partially funded by the Center for Adaptive Optics, a NSF Science and Technology Center, and by a National Eye Institute Phase I SBIR.

The improved Multi-DM will also enable enhancements in other biological imaging areas. Biological imaging instruments often suffer from resolution limitations, constraining the ability of researchers and clinicians to detect critical detail. This loss in resolution is due to the wavefront aberrations induced by the tissue media through which light passes to reach the object of interest, such as a cell, retina, or tumor. The Multi-DM's ability to actively correct for these aberrations will restore resolution and enable the extracting of vital information from biological specimens.

"The ever increasing strokes in deformable mirrors, such as the 6um achieved with BMC's new Multi-DM, will allow for deeper AO corrected imaging in biological specimens, more effective correction when used at longer wavelengths, and improved performance specifications in systems such as the Adaptive Scanning Optical Microscope (ASOM) and other AO based imaging systems," said Ben Potsaid, Research Scientist at the Center for Automation Technologies and Systems (CATS) located at Rensselaer Polytechnic Institute (RPI).

"Commercial systems require low cost DMs. Never before has there been a compact, affordable DM available with this magnitude of resolution. Ours is the only technology that meets the criteria of resolution, speed, size, stroke," said Bierden. "This will enable adaptive optics to become a reality for commercial instruments."

About the Multi-DM

The Multi-DM is the flagship product in Boston Micromachines' award- winning suite of MEMS deformable mirrors, which are used to improve resolution in microscopes, telescopes, and ophthalmic instruments. The popular and versatile Multi-DM offers sophisticated aberration compensation in an easy-to- use package. Typical applications include advanced retinal imaging systems, laser communication and beam forming.

At Photonics West

Boston Micromachines will be demonstrating the new Multi-DM at Photonics West 2007 (January 20-25) in San Jose, California, at Booth 6180.

Availability

The new Multi-DM is available immediately.

About Boston Micromachines Corporation

Founded in 1999, Boston Micromachines Corporation (BMC) is the leading provider of advanced MEMS-based mirror products for use in commercial AO systems, applying wavefront correction to produce high resolution images of the human retina and enhance images blurred by the Earth's atmosphere. The company's suite of award-winning compact DM products are the most economical high-performance mirrors in the market today. They are widely used in vision science applications such as advanced optic retinal imaging, long range laser communications and astronomy, including NASA's search for planets in other solar systems. Customers include leading manufacturers of optical imaging and communication systems, governmental agencies and contractors and vision science research laboratories worldwide, such as NASA, UCal Berkeley, Lockheed Martin and Boston University. Located in Watertown, Mass., BMC is privately held and also offers custom design-manufacturing services. For more information on BMC, please visit http://www.bostonmicromachines.com.

Boston Micromachines Corporation
http://www.bostonmicromachines.com

Health Department Offers Tips To Avoid Norovirus Infection

With outbreaks of viral gastroenteritis, or "stomach flu," continuing to be reported across the commonwealth and nation, the Pennsylvania Department of Health is reminding the general public about ways they can help to avoid norovirus infection -- a common cause of the illness.

"Norovirus infection is very common this time of year and it's very contagious," said state Health Secretary Dr. Calvin B. Johnson. "If you have symptoms of norovirus, such as vomiting and diarrhea, you should try to stay home and practice good hygiene, like washing your hands frequently and thoroughly to avoid spreading the illness to others."

Norovirus symptoms often begin suddenly and can include nausea, stomach cramping, vomiting and diarrhea. Norovirus illness can be a difficult experience for those affected, but it is normally short-lived and people recover within 12 to 60 hours.

The spread of norovirus can be prevented by following some simple guidelines:

-- Frequently wash your hands, especially after using the bathroom and changing diapers, and before eating or preparing food.

-- Anyone ill with diarrhea should not prepare food for other people. In particular, people with diarrhea should not work in restaurants, day care centers, or medical settings unless they are cleared to do so by their doctor or the local health department.

-- Carefully wash fruits and vegetables, and steam oysters before eating them.

-- Thoroughly clean and disinfect contaminated surfaces immediately after an episode of diarrhea or vomiting by using a bleach-based household cleaner.

-- Immediately remove and wash clothing or linens that may be contaminated with virus after an episode of diarrhea or vomiting (use hot water and soap).

-- Flush or discard any vomit and/or stool in the toilet and make sure that the surrounding area is kept clean.

Because norovirus is very contagious, sudden outbreaks can result when people bring the infection into facilities such as hospitals, residential and nursing homes and schools. No one who has suffered from vomiting and diarrhea should visit or work in crowded places until they have been completely free from symptoms for at least 48 hours.

For most healthy individuals, drinking plenty of fluids and resting at home is sufficient to recover from a norovirus infection and there is no need for hospital treatment. However, the elderly or very young can sometimes get more severe infection and they, or anyone else who is concerned about their medical condition, should talk to their doctor for advice.

For more information about norovirus, visit the Centers for Disease Control and Prevention Web site at http://www.cdc.gov/ncidod/dvrd/revb/gastro/norovirus.htm.

Pennsylvania Department of Health
http://www.state.pa.us/

Study Uncovers A Lethal Secret Of 1918 Influenza Virus

In a study of non-human primates infected with the influenza virus that killed 50 million people in 1918, an international team of scientists has found a critical clue to how the virus killed so quickly and efficiently.

Writing this week (Jan. 18, 2007) in the journal Nature, a team led by University of Wisconsin-Madison virologist Yoshihiro Kawaoka reveals how the 1918 virus - modern history's most savage influenza strain - unleashes an immune response that destroys the lungs in a matter of days, leading to death.

The finding is important because it provides insight into how the virus that swept the world in the closing days of World War I was so efficiently deadly, claiming many of its victims people in the prime of life. The work suggests that it may be possible in future outbreaks of highly pathogenic flu to stem the tide of death through early intervention.

The study "proves the 1918 virus was indeed different from all of the other flu viruses we know of," says Kawaoka, a professor in the UW-Madison School of Veterinary Medicine and at the University of Tokyo.

The new study, conducted at the Public Health Agency of Canada's National Microbiology Laboratory in Winnipeg, Manitoba, utilized the 1918 flu virus, which has been reconstructed by researchers using genes obtained from the tissues of victims of the great pandemic in a reverse genetics process that enables scientists to make fully functioning viruses.

"In 1918, the existence of viruses had barely been recognized. In fact, the influenza virus wasn't identified until 1933. Thanks to recent technological advancements, we are now able to study this virus and how it wreaked havoc around the globe," explains Darwyn Kobasa, research scientist with the Public Health Agency of Canada and lead author of the new study. "This research provides an important piece in the puzzle of the 1918 virus, helping us to better understand influenza viruses and their potential to cause pandemics."

By infecting monkeys with the virus, the team was able to show that the 1918 virus prompted a deadly respiratory infection that echoed historical accounts of how the disease claimed its victims.

Importantly, the new work shows that infection with the virus prompted an immune response that seems to derail the body's typical reaction to viral infection and instead unleashes an attack by the immune system on the lungs. As immune cells attack the respiratory system, the lungs fill with fluid and victims, in essence, drown. The mechanisms that contribute to the lethality of the virus were uncovered by University of Washington researchers using functional genomics, a technique in which researchers analyze the gene functions and interactions. Learning more about the virulence mechanisms of the 1918 flu virus may help researchers understand how to keep the virus from causing such a severe immune response.

"This study in macaques, combined with our earlier research showing the host response in mice infected with the 1918 flu, suggests that the host immune response is out of control in animals infected with the virus," said Michael G. Katze, professor of microbiology at the University of Washington in Seattle, who led the functional genomics portion of the new study and led the previous mouse-based study. "Our analysis revealed potential mechanisms of virulence, which we hope will help us develop novel antiviral strategies to both outwit the virus and moderate the host immune response."

The same excessive immune reaction is characteristic of the deadly complications of H5N1 avian influenza, the strain of bird flu present in Asia and which has claimed nearly 150 human lives but has not yet shown a capacity to spread easily among people.

"What we see with the 1918 virus in infected monkeys is also what we see with H5N1 viruses," Kawaoka says, suggesting that the ability to modulate immune response may be a shared feature of the most virulent influenza viruses.

In the new study, conducted in a high-level biosafety laboratory (BSL 4) at the Public Health Agency of Canada's National Microbiology Laboratory, seven primates were infected with the reconstructed 1918 virus. Clinical signs of disease were apparent within 24 hours of infection and within eight days euthanization was necessary. The rapid course of the disease mirrors how quickly the disease ran its course in its human victims in 1918.

Upon infection, the virus grew rapidly in the infected animals, suggesting the agent somehow sets the stage for virulent infection: "Somehow, early in infection, this virus does something to the host that allows it to grow really well," says Kawaoka. "But we don't know what that is."

Knowing that the virus does something early in infection to trigger such a devastating immune response may provide biomedical researchers with clues about how to intervene and stop or mitigate the virus' potentially lethal effects, Kawaoka says.

"Things may be happening at an early time point (in infection), but we may be able to step in and stop that reaction."

###

In addition to Kawaoka, authors of the new Nature paper include Darwyn Kobasa, Steven M. Jones, Hideki Ebihara, Friederike Feldman, Judie B. Alimonti, Lisa Fernando, Yan Li and Heinz Feldman of Canada's National Microbiology Laboratory; Kyoko Shinya of Japan's Tottori University; John C. Kash and Michael G. Katze of the University of Washington; John Copps of the Canadian Food Inspection Agency's National Centre for Foreign Animal Disease; and Yasuko Hatta, Jin Hyun Kim, Peter Halfmann and Masato Hatta of UW-Madison.

The new study was supported by the Public Health Agency of Canada, the Japanese Ministries of Education, Culture, Sports, Science and Technology, and private grants to Kawaoka. - Terry Devitt.

Contact: Yoshihiro Kawaoka
University of Wisconsin-Madison

Built-in Molecular Brakes Curb The Sniffles

Researchers at Johns Hopkins have discovered how our anti-infection machinery turns itself down and limits the sniffles, congestion and fevers that are a side effect of the campaign against invading viruses. The discovery seems to solve part of the mystery of why the misery of the common cold lasts only so long.

The key to curbing any excess activity by the immune system apparently rests with Carabin, a newly discovered protein made by the specialized white blood cells that march in when a virus attacks.

Results of a study published online this week at Nature show that Carabin "acts like an internal brake to dial down the speed and intensity of an immune response so that it doesn't go too fast or too far, or careen out of control and attack healthy cells," says Jun O. Liu, Ph.D., professor of pharmacology, neuroscience and oncology at Hopkins.

Searching for proteins that control immunity, Liu and his team homed in on those that latch on to parts of cells that are active during an infection. "Carabin popped out," says Liu.

To see what Carabin could do, the research team added it to white blood cells already primed and ready for anti-infection action. The more Carabin in the cells, the less active the cells became.

When people are infected with a cold virus, for example, the virus enters cells and hijacks its works so that the cells become viral factories. The immune system's white blood cells go after these infected cells not only by fielding chemicals that kill them directly, but also by turning on genes that help out. When Liu and his group added Carabin to cells and then studied such genes, they discovered that Carabin disabled the "on" switches, keeping the genes off.

"By now we were pretty convinced that Carabin can turn down the immune system, so the next question was, 'what controls Carabin?'" Liu noted.

Tracking Carabin to its origins, the researchers said they were surprised to learn that viral infection not only turns on the immune system machinery, but also triggers the making of Carabin, which in turn shuts off the immune response.

"It's like having a built-in timer to keep the immune system in check," says Liu.

If Carabin turns out, after further study, to be a keystone natural inhibitor of immune responses, Liu added, it may prove useful in stopping such unwanted immune reactions as the rejection of transplanted organs.

###

The research was funded by the Department of Pharmacology at the Johns Hopkins School of Medicine and the Keck Foundation.

Authors on the paper are Fan Pan, Luo Sun, David Kardian, Katharine Whartenby, Drew Pardoll and Liu, all of Hopkins.

On the Web:

http://www.hopkinsmedicine.org/pharmacology/research/liu.html

http://www.hopkinsmedicine.org/pharmacology/index.html

http://www.nature.com/

Contact: Audrey Huang
Johns Hopkins Medical Institutions

Association Of Tuberculosis With Smoking And Indoor Air Pollution

All works published in PLoS Medicine are open access. Everything is immediately available without cost to anyone, anywhere to read, download, redistribute, include in databases, and otherwise use subject only to the condition that the original authorship is properly attributed. Copyright is retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.

Association of Tuberculosis with smoking and indoor air pollution

Smokers have an increased risk of tuberculosis (TB) infection, TB disease, and of dying from TB compared to people who do not smoke.

A new study from Hsien-Ho Lin and colleagues at Harvard School of Public Health reviewed the published evidence for an association between tobacco smoking, passive smoking, and indoor air pollution from fuels such as wood and charcoal and the risk of infection, disease, and death from TB. Among hundreds of reports from electronic databases, the authors reviewed 33 eligible papers on tobacco smoking and TB, five papers on passive smoking and TB, and five on indoor air pollution and TB.

The researchers separately assessed different aspects of TB risk: TB infection as measured by a positive tuberculin skin test, TB disease, and mortality from TB. They found an approximately 2-fold increase in risk of TB infection among smokers as compared with nonsmokers. The great majority of studies evaluating the link between active smoking and TB disease or TB mortality also showed an association, but these data could not be combined together because of wide potential differences between the studies. In addition, there was some association of TB with passive smoking, and also with indoor air pollution, though the evidence for these associations was more limited, and will need to be confirmed by further work.

The authors conclude that "TB control programs might benefit from a focus on interventions aimed at reducing tobacco and indoor air pollution exposures, especially among those at high risk for exposure to TB".

Citation: Lin H, Ezzati M, Murray M (2007) Tobacco smoke, indoor air pollution and tuberculosis: A systematic review and meta-analysis. PLoS Med 4(1): e20.

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New Proteomic Method To Detect Inflammation In Amniotic Fluid

All works published in PLoS Medicine are open access. Everything is immediately available without cost to anyone, anywhere to read, download, redistribute, include in databases, and otherwise use subject only to the condition that the original authorship is properly attributed. Copyright is retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.

New proteomic method to detect inflammation in amniotic fluid

A score that measures the proteomic profile of amniotic fluid may predict inflammation before delivery. Researchers from Yale University, led by Catalin Buhimschi, have previously identified a set of four protein markers that were closely associated with inflammation in the amniotic fluid, and developed a score based on these proteins В­the "Mass Restricted" (MR) score. This score has been shown to be able to identify women at risk of preterm delivery. In the current study, the researchers assessed whether MR scores were associated with the outcome of pregnancy; the presence of infection in the placenta, and severe infection in the newborn baby.

169 women recruited into the study had a sample of amniotic fluid taken as part of their routine clinical management from which the protein MR score was calculated, and evidence of bacterial infection was sought. These results were then related to length of time until delivery, presence of placental inflammation after birth, and whether there was evidence of infection in the babies. In line with findings from their previous studies, women with a higher MR score gave birth sooner. There was also agreement between the MR score and evidence of inflammation in the placenta, and mothers with a high MR score were more likely to give birth to babies with suspected or confirmed sepsis.

In this group of women, the MR score seemed to be the most accurate in predicting inflammation when compared with other tests for inflammation such as white cell count, and may therefore provide a useful test for recognizing women at risk of preterm delivery and babies at risk of poor outcome. However, although promising, a further evaluation of the test in different populations will be needed before it could become a standard procedure in the clinic.

Citation: Buhimschi CS, Bhandari V, Hamar BD, Bahtiyar MO, Zhao G, et al. (2007) Proteomic profiling of the amniotic fluid to detect inflammation, infection, and neonatal sepsis. PLoS Med 4(1): e18.

About the PUBLIC LIBRARY OF SCIENCE

PLoS is a nonprofit organization of scientists whose aim is to make the world's scientific and medical research literature a public resource. We are funded by a grant from the Gordon and Betty Moore Foundation to develop a publishing program based on the Open Access business model, whereby the costs of publication are paid upfront so that anyone with an internet connection can have access to the content, in a free and unrestricted manner. Our immediate goal is to launch two top-tier journals - PLoS Biology (in October, 2003) and PLoS Medicine (in 2004).

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Billions Of Dollars Saved In U.S. By Polio Vaccination

A new study by researchers at the Harvard School of Public Health (HSPH) finds that polio vaccination in the United States has resulted in a net savings of over $180 billion, even without including the large, intangible benefits associated with avoided fear and suffering. This first study to retrospectively demonstrate the enormous benefits of polio vaccination appears as part of a special issue on polio in the December 2006 issue of Risk Analysis.

The history of polio vaccination in the U.S. spans over 50 years and includes different phases of the disease, multiple vaccines, and a sustained significant commitment of financial resources. Lead author of the study, Kimberly Thompson, associate professor of risk analysis and decision science at HSPH, emphasized that this study "should help people understand and better appreciate the huge economic savings that can come from investments in public health interventions."

The researchers, Professor Thompson and Dr. Radboud Duintjer Tebbens, a research associate at HSPH, estimated the costs and the effectiveness of historical polio vaccination strategies. They found that the U.S. invested over $35 billion between 1955 and 2005 and will continue to invest billions into the future to pay for polio vaccination. They estimated that these historical and future investments translate into over 1.7 billion vaccinations that prevent approximately 1.1 million cases of paralytic polio and over 160,000 deaths, thus saving Americans hundreds of billions of dollars in treatment costs.

Dr. Stephen Cochi, U.S. Centers for Disease Control and Prevention Global Immunization Division Senior Advisor and an expert on polio said, "This study documents the extraordinary power of vaccines not only as highly effective tools to prevent disease, disability, and death, but to provide enormous economic savings to society."

Although the last case of paralytic polio from wild poliovirus occurred in the U.S. in 1979, poliovirus outbreaks currently still occur around the world and American children continue to receive polio vaccinations. Dr. Bruce Aylward, Director of the Global Polio Eradication Initiative at the World Health Organization, stated that, "as we stand on the brink of eliminating wild polioviruses around the world, these results provide a glimpse of the massive economic benefits of global polio eradication." To date, the Global Polio Eradication Initiative has succeeded in reducing the annual cases of paralytic polio from an estimated 350,000 cases in 1988 to less than 2,000 cases in 2006. The only remaining areas of the world that have not yet disrupted transmission include regions in four countries (Afghanistan, India, Nigeria, and Pakistan). Thompson and Duintjer Tebbens also co-authored several other articles in the same issue that characterize the risks and costs of future options for polio risk management, the costs and value of global surveillance, and the trade-offs associated with different choices related to outbreak response.

Support for this study was provided by the Harvard Kids Risk Project. http://www.kidsrisk.harvard.edu/. Support for other studies by the authors in the special issue was provided by the U.S. Centers for Disease Control and Prevention.

Harvard School of Public Health is dedicated to advancing the public's health through learning, discovery, and communication. More than 300 faculty members are engaged in teaching and training the 900-plus student body in a broad spectrum of disciplines crucial to the health and well being of individuals and populations around the world. Programs and projects range from the molecular biology of AIDS vaccines to the epidemiology of cancer; from risk analysis to violence prevention; from maternal and children's health to quality of care measurement; from health care management to international health and human rights. For more information on the school visit: http://www.hsph.harvard.edu/.

Harvard School of Public Health
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Informing Partners Can Help Cut Sexually Transmitted Infections

Doctors should encourage patients with sexually transmitted infections to tell their partners to seek treatment and, in some cases, provide home testing kits or drugs to help reduce infection rates, says a new study on bmj.com.

Partner notification is an important part of managing most curable sexually transmitted infections, but the stigma attached to sexually transmitted infections often makes this difficult.

Researchers analysed 14 studies involving 12,389 women and men diagnosed with a common sexually transmitted infection, including chlamydia, gonorrhoea, and non-specific urethritis.

Three new strategies were used in these studies that made it easier for patients to share responsibility for the care of their sexual partners: patient delivered partner therapy (where a patient is given drugs or a prescription for their partners), home sampling for partners, and providing additional information for partners.

All three strategies were more effective than simple patient referral (where a patient is simply encouraged to tell their partners to seek treatment).

However, the team found that simple patient referral, with extra information about the infection and its treatment that the patient can give to their partners, seemed to be as effective as patient delivered partner therapy.

Involving patients with sexually transmitted infections in shared responsibility for the care of their sexual partners improves outcomes, say the authors. Health professionals should consider these three strategies for the management of individual patients.

Click here to view paper: http://press.psprings.co.uk/bmj/january/partners.pdf.

British Medical Journal
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Bacteria In Staph Infections Can Cause Necrotizing Pneumonia

Researchers at the Texas A&M Health Science Center Institute of Biosciences and Technology at Houston have discovered a toxin present in the bacteria responsible for the current nationwide outbreak of staph infections also has a role in an aggressive pneumonia that is often fatal within 72 hours.

Their study is available online in Science Express and in an upcoming issue of the journal Science.

"The virulence of CA-MRSA (community-associated methicillin-resistant Staphylococcus aureus) strains that produce the PVL (Panton Valentine leukocidin) toxin presents a nightmare scenario," said M. Gabriela Bowden, Ph.D., research assistant professor at HSC-IBT and co-senior author. "If the community-acquired strain establishes itself in the hospital setting, it will be difficult to contain."

The most common cause of staph infections, S. aureus is a bacteria found on the skin or in the nose of about 25-30 percent of people. It also can be the culprit in minor skin infections like pimples and boils, as well as major diseases like meningitis, endocarditis, toxic shock syndrome and pneumonia.

In their study, Dr. Bowden and her colleagues at the HSC-IBT Center for Extracellular Matrix Biology used mice to analyze S. aureus Panton Valentine leukocidin (PVL), a pore-forming toxin secreted by bacterial strains associated with both the current outbreak of CA-MRSA and necrotizing pneumonia.

CA-MRSA causes serious skin and soft tissue infections in healthy persons who have not been recently hospitalized or undergone invasive medical procedures, while necrotizing pneumonia destroys healthy lung tissue and can be fatal within 72 hours. With the PVL toxin, the bacterium also attacks infection-fighting white blood cells (leukocytes).

In the 1940s, the high mortality rate from S. aureus was abated by penicillin, but the bacteria soon developed a resistance. Methicillin provided new treatment options for infections in the late 1950s, but as of the late 1990s, it has become resistant.

In December, the United Kingdom had its first documented report of fatal necrotizing pneumonia cases caused by PVL-positive CA-MRSA. Eight hospitalized patients developed infections from CA-MRSA, and two died. It was previously believed the hospitals were free of these virulent strains of CA-MRSA.

Testing several bacterial strains, the HSC-IBT researchers learned PVL itself has an enhanced ability to disrupt cells in the body, and PVL-positive S. aureus has a greater capacity to attach to and colonize the lung, the latter resulting in necrotizing pneumonia.

"Our research shows in vivo that PVL is sufficient to cause pneumonia," Dr. Bowden said. "PVL-producing S. aureus overexpress other factors that enhance inflammation and bacterial attachment to the lung. These combined effects result in a vicious cycle of tissue destruction and inflammation, explaining the rapid onset and lethal outcome of this type of pneumonia."

Using these findings, the next step is additional studies to identify targets for potential development of therapies to treat S. aureus infections, including the PVL-positive strain.

"The present study underscores the aggressiveness of these strains and the urgent need to develop new strategies to battle these infections," Dr. Bowden said.

Other Science Express study contributors from the Center for Extracellular Matrix Biology were Magnus Höök, Ph.D., director and professor; Eric Brown, Ph.D., assistant professor (now at The University of Texas School of Public Health at Houston); Maria Labanderia-Rey, postdoctoral fellow; Vanessa Vazquez, graduate student; and Elena Barbu, graduate student. Florence Couzon, Sandrine Boisset, Michele Bes, Yvonne Benito, Jerome Etienne and François Vandenesch from the University of Lyon and Hospices Civils de Lyon (France) also contributed.

Grants from the HSC, French Ministry of Research, National Institutes of Health, and Neva and Wesley West and Hamill Foundations supported this research.

The Texas A&M Health Science Center provides the state with health education, outreach and research. Its six components located in communities throughout Texas are Baylor College of Dentistry, the College of Medicine, the Graduate School of Biomedical Sciences, the Institute of Biosciences and Technology, the Irma Lerma Rangel College of Pharmacy, and the School of Rural Public Health.

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Americans In The Dark About Shingles

Thought you were done with the chickenpox as a kid? Think again. Shingles, a disease caused by the same virus as chickenpox, affects roughly one million Americans each year. As people age, their risk of getting shingles increases but despite its incidence many people are completely unaware of the disease.
"People don't really know about shingles unless they know someone who has had shingles, or they develop it themselves," said Stephen Tyring M.D., professor of medicine at the University of Texas Health Science Center in Houston.

The results of a recent national survey by the American Pain Foundation support Trying's position. The survey revealed that many older adults were not aware of their risk for the disease. More than half of the respondents who reported having heard of shingles were not sure of the risk factors. And many respondents were unaware of the relationship between chickenpox and shingles.

After a person gets the chickenpox, most often during childhood, the inactivated virus can live on in certain nerve cells in the body. In healthy people, the body's immune system usually keeps the virus at bay. As people age or their immune system becomes compromised, the virus can reactivate and result in shingles.

The risk of shingles increases with age. "With each decade, a person's immunity weakens, so that by 60 years of age, the likelihood of shingles significantly increases," says Tyring. "In fact, one out of two people who live to the age of 85 will have had shingles." And although seniors are at higher risk, shingles can affect people of all ages.

The first signs of shingles may not be visually noticeable. People often experience tingling, burning, itching or pain. During the first few days of symptoms, fluid-filled blisters will break out in a rash, usually on one side of the body or face. The rash is often painful and will heal in two to four weeks, in most people. However, some people experience post-herpetic neuralgia, or long-term nerve pain which can persist for months or even years after the initial rash. Long-term nerve pain caused by shingles can vary and has been described as burning, throbbing, stabbing or shooting. The older a person gets, the more he or she is at risk for long-term nerve pain.

Men and women are affected equally by shingles. "I have seen, however, in my practice that women come into the doctor's office sooner, while men tend to wait," Tyring said. Shingles patients, both men and women, are often given analgesics along with antiviral medications for treatment. "Antiviral medicines for shingles may help speed up healing and reduce pain in some patients, but if possible, treatment should begin within 72 hours of the onset of symptoms," according to Tyring.

Although the disease affects the sexes equally, its greater impact on older adults should capture the attention of women.

"Women make up more than 60 percent of population 85 years and older, so any condition that is prone to strike older people is of special concern to women," said Phyllis Greenberger, MSW, president and CEO of the Society for Women's Health Research. "Older Americans should talk to their health care providers about their risk for shingles."

To raise awareness about shingles and complications that can arise from the disease, the American Pain Foundation is sponsoring a national education program called "Spotlight on Shingles" that features a Web site and a toll-free number that people can call to receive a free informational brochure about shingles. For more information, visit http://www.spotlightonshingles.com.

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Highly Pathogenic Bird Flu Case Confirmed In South Korea

South Korean authorities have just confirmed that breeding chickens in Chonan, 55 miles south of the capital Seoul, were infected with the highly pathogenic H5N1 bird flu virus strain. This is the fifth outbreak in the country during the last three months.

Preparations are underway to cull over one-quarter of a million birds within half-a-kilometer of the farm, say officials from the Ministry of Agriculture. Measures to stem the spread of the virus also include a total restriction in the movement of birds and eggs within a 10 kilometer radius of the infected area.

Experts were surprised at this latest outbreak. Recently there had been an outbreak at Iksan, to the south of Chonan, where tens of thousands of birds had been culled. Emergency measures at Iksan had been thoroughly carried out. During the last three years over 1.2 million heads of poultry have been culled in South Korea.

Lab tests have revealed a virulent strain of the bird flu virus in bird droppings found at a reservoir about 13 miles from the infected farm in Chonan. Further tests will tell us whether it is the virulent H5N1 strain. If so, we could be looking at migratory birds as the source of the H5N1 bird flu spread.

-- Ministry of Agriculture and Forestry, Rep. of Korea (in English)
-- Ministry of Agriculture and Forestry, Rep. of Korea (in Korean)

Written by: Christian Nordqvist
Editor: Medical News Today

Indonesia Confirms New Human Bird Flu Death

An Indonesian Health Ministry spokesman has confirmed that a woman, aged 19, from the West Java town of Garut, died in hospital last Friday as a result of H5N1 bird flu infection. This brings the total number of human deaths in Indonesia to 62, the highest in the world. This is the fifth human death in the country during the last two weeks - one in Garut, the other four in Jakarta.

It seems Indonesian authorities, long criticized for not doing enough to stem the spread of bird flu, are at last taking serious measures. A massive campaign is underway to eliminate backyard poultry in several provinces. In Jakarta, people have 14 days to get rid of their birds.

Accumulative Total Number of Confirmed Human Cases of Avian Influenza A/(H5N1)
Since the beginning of 2003

Azerbaijan
Cases 8 - Deaths 5

Cambodia
Cases 6 - Deaths 6

China
Cases 22 - Deaths 14

Djibouti
Cases 1 - Deaths 0

Egypt
Cases 18 - Deaths 10

Indonesia
Cases 80 - Deaths 62

Iraq
Cases 3 - Deaths 2

Thailand
Cases 25 - Deaths 17

Turkey
Cases 12 - Deaths 4

Viet Nam
Cases 93 - Deaths 42

Total
Cases 268 - Deaths 162

Written by: Christian Nordqvist
Editor: Medical News Today

Tuberculosis Experts Outline Proposals To Speed Up Drug Development

Proposals to accelerate the development of tuberculosis (TB) drugs were outlined today at the conclusion of a two-day symposium titled "No Time to Wait," convened in New York this week by the international medical humanitarian organization Doctors Without Borders/MГ©decins Sans Frontires (MSF) with the support of Howard P. Milstein and Weill Cornell Medical College's Abby and Howard P. Milstein Program in Chemical Biology. The symposium brought together more than 100 TB specialists, drug developers and regulators, policy makers, donors and activists to outline practical proposals to fill the gaps in TB drug research and development (R&D).

"We are failing people with TB," said Dr. Tido von Schoen-Angerer, Director of MSF's Campaign for Access to Essential Medicines. "Diagnosing and treating TB is one of the greatest challenges facing health care providers around the world. Things are going from bad to worse with multi-drug resistant TB and even extensively drug resistant (XDR) TB, particularly in settings with high HIV prevalence. The urgency for new tools could not be greater - there is no time to wait."

TB kills nearly two million people per year, primarily because of inadequate diagnostic and treatment tools. While roughly one drug for HIV has been developed each year since the start of the epidemic 25 years ago, the latest novel TB drug in today's standard therapy was developed in the 1960s. Basic science is not being translated into new TB drugs needed to improve treatment, according to an MSF analysis of the TB drug pipeline. There are not enough promising drugs in the pipeline and serious funding gaps prevent the development of candidate drug compounds through to clinical trials.

Resistance to TB drugs is growing at a rapid pace, with 450,000 new cases of drug-resistant TB detected each year. The recent detection of hundreds of cases of XDR-TB, which is extremely difficult and sometimes impossible to treat, adds further urgency to the situation. TB remains the main killer of people with HIV, in large part because existing TB drugs and tests are poorly adapted for use in people with HIV/AIDS.

"In TB research, there needs to be a convergence of innovation, incentive, and access," said Dr. Carl Nathan, Rees Pritchett Professor of Microbiology and Chairman of Microbiology and Immunology at Weill Cornell Medical College. "We need to see openness, leadership and collaboration among all TB actors."

Experts attending the symposium emphasized several actions that urgently need to be taken to improve the situation:

1. Drastically increase funding of TB R&D
2. Accelerate drug discovery
3. Expand clinical trial capacity and speed up clinical development
4. Commit to global TB R&D leadership
5. Support new approaches to R&D, such as a global R&D framework

"We need increased clinical trial capacity, fast-tracked clinical trials, and criteria for compassionate use of important candidate drugs," said Dr. von Schoen-Angerer. "To make any real difference, we need to see a dramatic increase in funding and political will."

The symposium emphasized a need to build a global TB R&D movement, as was critical to the advancements in HIV drug development. Strong political leadership is required to improve collaboration between scientists, drug developers, care providers, and affected individuals. Symposium participants agreed on the need for a massive increase in funding by governments for TB R&D, as current TB drug discovery initiatives are insufficient. Participants voiced support for an effort launched by governments at the World Health Assembly in May 2006 to examine alternative ways to prioritize and finance health-needs-driven R&D.

http://www.doctorswithoutborders.org

The New Form Of Trypanosomiasis Discovered In India Stems From A Deficiency In A Particular Immune-system Protein

The two known types of human trypanosomiasis, endemic in two regions of the world, are sleeping sickness in Africa, caused by the parasites Trypanosoma brucei gambiense or T. b. rhodiense, and Chagas' disease in South America induced by T. cruzi. Everywhere else, normally only animals are infected by trypanosomes that, although specific for humans are not pathogenic for them. Yet, in 2004, the first case of human trypanosomiasis was formally identified in India by IRD researcher Philippe Truc, working with the WHO and the Maharashtra State Department of Health (1). The patient was a farmer living in this State who proved to be infected by a trypanosome, T. evansi, usually a parasite of camels and cattle. In South America, North Africa and in a great part of Asia including India, where this parasite is present, many human populations are currently living in contact with infected animals.

Scientists from the UniversitГ© Libre de Bruxelles led by Professor Etienne Pays, in conjunction with Philippe Truc and Indian medical specialists, under an agreement with WHO (2), carried out analyses on blood serum from the infected patient, which led them to identify the cause of this first case of human trypanosomiasis in India.

Humans possess natural resistance to this parasite, as they have towards related African trypanosomes, like T. brucei. In the latter case, the innate immunity results from the trypanolytic activity of a specific human protein, apolipoprotein L-1 (APOL-1). Once absorbed inside the parasite, this protein forms pores in the parasite's organelle membrane, thus inducing the destruction of the trypanosome. However, the two subspecies T. brucei rhodesiense and T. b. gambiense have, with time, overcome human immune defences by acquiring resistance to APOL-1 and thereby causing sleeping sickness in Africa. In T. b. rhodesiense, this resistance mechanism involves a protein that is peculiar to this subspecies, named SRA (Serum Resistance-associated protein), which interacts strongly and specifically with APOL -1, effectively blocking its ability to destroy the trypanosomes.

The major question is whether the first case of T. evansi infection identified in India resulted from the appearance of a mechanism of resistance of this parasite or from a deficiency of the patient's immune system., The gene coding for the SRA protein, specific to the subspecies rhodesiense, was not detected in the trypanosome that had infected the Indian patient, as could be expected considering its specificity (3).

The researchers then assessed in vitro the ability of the infected serum to destroy the parasites. In this way they brought into evidence a complete absence of any trypanolytic activity on two strains of T. evansi, but also on T. b. brucei. Conversely, these same strains were destroyed on contact with normal serum. The APOL-1 protein, responsible for the trypanolytic action against T. b. brucei, was subsequently looked for in the infected serum. This serum appeared to be extremely deficient in this protein, with a concentration in APOL-1 at least 125 times lower than in normal human serum. However, the addition of a normal quantity of purified APOL-1 to the infected serum was sufficient to restore the latter's ability to destroy the different strains tested. This APOL-1 deficiency observed in the patient would clearly therefore be the source of the single case of T. evansi infection identified to date.

Analysis of the apoL-1 gene sequence, perfomred on the patient's DNA, showed that the absence of apolipoprotein results from a double mutation affecting its synthesis (4). In the absence of APOL-1, no other component of the human serum seems capable of forming pores in the parasite membrane and killing the trypanosome.

Furthermore, a serological screening, conducted in 2005 by the Indian authorities in the patient's village, with the IRD researcher and assigned by WHO, brought to light an intense exposure of individuals to T. evansi, probably favoured by transmission of the parasite from infected animals to humans, via an insect vector. In fact, out of 1806 people examined, 60 proved to be strongly positive to the specific serological test for this trypanosome, although no parasite was detected in these subjects, and no case of infection has since been recorded in the village (5). However, only study of the frequency of each of the two mutations within exposed populations will allow assessment of the risk of the appearance of other cases and the emergence of this new form of trypanosomiasis.

(1) See scientific sheet n°230, August-September 2005, accessible at: http://www.ird.fr/fr/actualites/fiches/2005/fiche230.htm

(2) This research was conducted by scientists from the 'Laboratoire de Parasitologie MolГ©culaire (IBMM)' of the UniversitГ© Libre de Bruxelles (Belgium), jointly with a researcher from IRD research unit UR 177, medical specialists from the Department of Medicine of the Government Medical College of Nagpur (India), from the Department of Health at Mumbai (India) and from the WHO (Geneva, Switzerland).

(3) Philippe Truc et al. - Genetic characterization of Trypanosoma evansi isolated from a patient in India, Infection, Genetics and Evolution, 24 August 2006. doi:10.1016/j.meegid.2006.07.004

(4) This occurs in the form of two mutations each of which affects an allele of the same gene apoL-1. The first consists of the absence of two nucleotide bases in position 142, the second is the absence one particular base at position 266. These "frameshift" mutations result in the production of proteins that are cut down in length, and therefore ineffective. And these products are undetectable, as they are probably degraded.

(5) This means that these individuals have been or are still carriers of anti-T. evansi antibodies. They have therefore been carriers of the parasite, no doubt owing to an insufficiency in APOL-1 (mutation of a single allele?). See the reference under "For further information".

About INSTITUT DE RECHERCHE POUR LE DÉVELOPPEMENT, PARIS (IRD)

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Defeating Salmonella Requires An Understanding Of Guerrilla Warfare, UK

New research from scientists at the University of Cambridge has the potential to radically change our understanding of how infection spreads around the body and improve the methods used to control it.

If you are suffering from Salmonella food poisoning or, worse, typhoid fever, you feel like every cell in your body is under attack from an army of invading bacteria. However, rather than the bacteria mounting a mass assault scientists using state-of-the-art microscopy have found that Salmonella bacteria use a guerrilla warfare-like approach to attacking your body's cells. Researchers at the University of Cambridge have found that the majority of cells infected with bacteria in the body contain just one or two bacteria rather than being overrun as might be expected. Working in collaboration with mathematicians they are now proposing a new model to explain infection. The new explanation shows that a single Salmonella bacterium invades a cell, grows and replicates before its progeny is released when the cell bursts. The released bacteria then fan out each independently infiltrating another cell. This forces the host immune system to fight low numbers of bacteria simultaneously at numerous sites of infection rather than having to deal with a small number of well confined "battlefields" each containing large numbers of Salmonella.

Research leader Dr Pietro Mastroeni explains: "When bacteria infiltrate cells one at a time they gain a head start over your body's immune system. When a bacterium infects a cell it triggers an immune response and the inside of the cell becomes an increasingly hostile environment for the invader. By replicating quickly and escaping the bacteria can individually disseminate in the body and attack many more cells where the immune response has to start again from scratch."

By using mathematical models the researchers have been able to show that as an infection develops most bacteria remain isolated in individual infected cells, even as the number of cells infected grows.

Dr Mastroeni commented: "Understanding the hit-and-run tactics used by infectious bacteria has important healthcare implications. It will help us to identify how different drugs might work most effectively in different combinations and to develop new vaccines. In both cases developments would include a dual approach to slow the replication inside the cell and to attack bacteria on the run outside the cell."

The research, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust, not only has public health implications but also demonstrates the importance of animals in research.

Professor Julia Goodfellow, BBSRC Chief Executive, explained: "Salmonella bacteria cause hundreds of thousands of deaths worldwide every year. Without using infected mouse cells we would not understand the behaviour of the bacteria. The combined use of biological data and mathematical models has enabled the researchers to test several and sometimes competing theories about infection, greatly reducing the need for many more animal experiments."

The Biotechnology and Biological Sciences Research Council (BBSRC) is the leading funding agency for academic research and training in the biosciences at universities and institutes throughout the UK.

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http://www.bbsrc.ac.uk

Method Devised For Diagnosis Of Ocular Diseases

GAIKER-IK4 Technological Centre's Area of Biotechnology, together with the Opthtalmological Surgery Clinical Institute of Bilbao (ICQO) are co-operating in a research project the aim of which is to develop a diagnostic system, based on immunochromatographic techniques, for the specific recognition of proteic markers for ocular pathologies in eye teardrop samples.

This system, carried out with a swab (similar to pregnancy testing), will initially detect specific markers for ocular pathologies such as conjunctivochalasis and keratoconus and will enable, with a sample of teardrop liquid, the diagnosis of the patient with these disorders.

The ease of use of the system and both its speed and simplicity (a positive testing sign in the form of a coloured band) enables the system to be employed on a daily basis in the clinic. The markers on which the design of this diagnostic system is based are being analysed throughout the research project and validated by means of their recognition by specific antibodies in samples from the tears of patients affected by these pathologies.

In the future, towards the end of 2008, those responsible for the project hope to develop a multiple system, capable of detecting the presence of other ocular pathologies, besides the two already established in the initial phase, and with the aim of launching the diagnostic tests on the market.

Pathologies studied

Keratoconus or conic cornea condition is a disorder of the human eye which rarely causes blindness but can considerably interfere with vision. This pathology distorts the usual rounded shape of the cornea and forms acone-shaped prominence. It occurs in one in every two thousand persons and generally it coincides with puberty. Keratoconus does not follow any known geographical cultural or social pattern.

Conjunctivochalasis is the relaxation of the bulbar conjunctive capable of creating conjunctive folds over the lower palpebral rim.

Progress of the research

This research project, started in 2004 and due to terminate next year, is based on a comparative study of proteome in samples of teardrops from patients suffering from keratoconus and conjunctivochalasis and, as a control, in samples of healthy patients.

Proteomics is the tool employed in this study to simultaneously analyse all the proteins involved in a pathology and contained in just one sample of teardrops. This set of proteins, known as "proteome", is what enables the determination of which proteins are affected in their expression in ocular pathology conditions, thus indicating to GAIKER-IK4 researchers which are the potential markers to employ as recognition targets within the diagnostic system being developed.

This approximation is important in as far as just one sample enables the analysis not only of one or two proteins, but of all the proteins contained in the teardrop and that are involved in the evolution of a specific ocular pathology, thus enabling finding various markers, suitable for use in developing multiples diagnosis systems. These new systems will have direct benefits on public health and in future can be linked with innovative technologies such as nano- and microtechnologies, capable of incorporating fragments of biomolecules.

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Mozambican Red Cross To Train Hundreds Of Volunteers To Manage Antiretroviral Therapy For HIV-Positive People

The Mozambican Red Cross plans to begin training hundreds of volunteer health workers to manage antiretroviral therapy for HIV-positive people in their care, IRIN News reports. According to the Ministry of Health, the government, with the help of partner organizations, provides antiretroviral treatment to about 34,000 of the estimated 250,000 people living with HIV/AIDS who need treatment. Some nongovernmental organizations in the country have started antiretroviral management training for volunteers, but the NGOs have a limited reach, according to IRIN News. The Red Cross has a nationwide network of 600 volunteers in its home-based care program, which operates in nine of the country's 11 provinces. "This training is extremely important and will improve the work of" Red Cross volunteers, Paula Macava, coordinator of the Red Cross HIV/AIDS program in Mozambique, said, adding that the Red Cross has completed a training course on antiretroviral therapy management that is specifically designed for volunteers. The three-week training course, which is designed for volunteers with at last basic reading and writing skills, includes information on how to judge when an individual is ready to start antiretroviral therapy, and ensuring regimen adherence and good nutrition when taking antiretrovirals. The government aims to provide antiretroviral treatment to about 50,000 people living with HIV/AIDS by the end of 2007, according to the health ministry (IRIN News, 1/16).

"Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Panelists Urge Businesses In Africa To Support HIV-Positive Employees, Women To Get Tested

Businesses in Africa should support HIV-positive employees, and more women on the continent should receive HIV tests and empower themselves with knowledge about HIV/AIDS, panelists at a Pan-African leadership summit in Cape Town, South Africa, said recently, allAfrica.com reports. The conference -- called "Vital Voices of Africa," and organized by the Washington, D.C.-based Vital Voices Global Partnership -- aims to develop an action plan to address HIV/AIDS in Africa. The conference also aims to address other issues, such as trade, economic development, good governance and violence against women. At the opening session of the conference, Joelle Tanguy, managing director of the Global Business Coalition on HIV/AIDS, Tuberculosis and Malaria, said that 90% of HIV-positive people in Africa are unaware of their status. Grietjie Strydom -- former director of Alexander Forbes Health Management Services in South Africa and a panelists at the conference -- said that HIV/AIDS is having a large impact on South Africa's economy. She added that it is financially more beneficial for companies to provide treatment for HIV-positive employees than to not provide treatment. "The private sector thinks that the government is helping" people living with the disease, but this often is not the case and companies should be encouraged to provide support for HIV-positive employees, she said. According to Strydom, HIV-positive people also need psychological therapy and mental and emotional support. According to Miriam Were, chair of the National AIDS Control Council in Kenya and panelist at the conference, there are more women than men living with and affected by HIV/AIDS. She suggested that a fund be created to provide money and support to women living with HIV/AIDS (Hendricks, allAfrica.com, 1/16).

"Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Nigeria Plans To Pass Law Allowing Local Companies To Produce HIV/AIDS, Malaria Drugs

Nigeria is close to passing a law that would allow local pharmaceutical companies to manufacture more drugs to treat HIV/AIDS and malaria, Ahmed Abdulkadir, special adviser to the Nigerian president, said this week, Reuters South Africa reports. There are 14 companies that make antiretroviral drugs and eight companies that make artemisinin-based combination therapies in Nigeria, but they are not producing enough drugs to combat the diseases, according to Reuters South Africa. The country needs 109 million doses of ACTs annually to treat malaria, but local companies only meet 30% of the demand, and the rest is covered by treatments imported from China, Reuters South Africa reports. The new law aims to remove barriers to rapid production of the drugs, Abdulkadir said. He added that the legislation process is in the final stages and that the law will be sent to the National Assembly. Abdulkadir also said that Nigerian companies are preparing to boost drug production once the law is passed. "We are trying to get more machinery to produce more," he said, adding, "We don't want to be an importing nation. We want to be producing en masse and also supplying West and Central Africa." In addition, a program to grow Artemisia annua, the plant from which ACTs are derived, in Nigeria is being developed, according to Abdulkadir. Experts from China, where the plant primarily is grown, are advising Nigeria on how to cultivate the plant (Ee Lyn, Reuters South Africa, 1/17).

"Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.