A review of measures taken to address a 2004 outbreak of the highly infectious Norwalk virus at The Johns Hopkins Hospital has provided the first solid documentation of expenses and efforts in the United States to stop the infection from spreading among patients, staff and visitors. Total hospital costs for the three-month outbreak – including extra cleaning supplies, staff sick leave, diagnostic tests, replacement staff, and salaries and lost revenue from closed beds – were estimated at more than $650,000.

The outbreak at The Johns Hopkins Hospital (JHH) was one of at least 24 at Maryland hospitals during the first half of 2004. Norwalk virus is highly contagious because only small amounts, as few as 10 to 100 viral particles, can lead to infection. It is spread or passed from person to person through fecal matter when people fail to wash their hands properly after using the bathroom and when people touch or share handling of the same objects, such as doorknobs.

“We hope our approach will help other hospitals prepare for or manage an outbreak,” says Cecilia Johnston, M.D., an instructor at Hopkins in infectious diseases who led the investigation.

“Outbreaks need to be identified quickly and dealt with immediately, and relying on standard infection control procedures is not adequate,” she adds. “It may be necessary to close the infected units, isolate the infection source, get strict on hand hygiene, conduct a thorough washing down of units, and keep repeating these steps until the outbreak is stopped. Health care workers especially need to be vigilant about these steps because they are the group primarily affected by outbreaks.”

Reporting in the Sept. 1 edition of the journal Clinical Infectious Disease, Johnston and her team of Hopkins patient safety experts describe how an outbreak spread among 265 health care workers and 90 patients between February and May 2004.

No one at Hopkins died from their infection, but 13 afflicted hospital staff either visited the emergency room for treatment or required hospitalization after becoming severely dehydrated. Norwalk-like viruses, formally known as noroviruses, cause serious gastrointestinal illness for which no treatment currently exists except for keeping the patient well hydrated. Symptoms include nausea, vomiting, diarrhea and severe stomach cramps. Those infected generally recover on their own within two to three days after symptoms appear.

“Health care workers really do need to be on the lookout for norovirus infections, and if there is an outbreak, hospitals need to address it very aggressively,” says senior hospital epidemiologist Trish Perl, M.D., a professor of medicine and pathology at The Johns Hopkins University School of Medicine. “Our experience shows that people can get very sick and that it costs a lot to fix the problem and address disruptions to staffing.”

First reported in the hospital’s coronary care unit, or CCU, the JHH outbreak quickly spread over a two-week period but remained clustered in the CCU, a nearby echocardiography laboratory and a floor housing psychiatric services where patients and staff frequently interact, especially during group therapy sessions.

The outbreak was detected soon after it began when two staff members who worked closely together became ill with diarrhea. Their illnesses were immediately reported to Hopkins’ infection control team, which monitors hospital operations daily for potential hazards to patient safety.

A norovirus outbreak was immediately suspected because there had been numerous reports of illness throughout the Baltimore region.

As part of their investigation, nurse managers began screening all staff and patients for any signs of gastrointestinal illness. Patient stool samples confirmed that the culprit was a norovirus, and genetic testing later verified that it was the same viral strain, genogroup II.4, that caused a series of widely publicized outbreaks in nursing homes and on cruise ships traveling from Europe and the United States in 2002.

As the investigation proceeded, staff implemented strict precautions to control the outbreak and prevent it from spreading. Patients with symptoms were placed in isolation, by being moved to either private rooms or into the same room with other sick patients. Group therapy sessions in psychiatry were temporarily halted, and no new patients were admitted to the units primarily affected. Sick staff were sent home for as long as they had symptoms plus an additional 72 hours, sufficient time for the illness to pass and no longer be contagious.

The investigation showed that many of the initial health care workers in the CCU who became ill had attended a social event outside of the hospital, where one of the non-staff guests was already experiencing symptoms. Others likely became ill after touching a patient chart that had been handled by another ill colleague.

Standard precautions to guard against infection were also followed, including a mandatory, hospital-wide staff review of basic infection control procedures with an emphasis on more frequent hand washing, accompanied by a thorough washing down of all affected hospital facilities. Even the CCU was closed for 24 hours to allow for a thorough cleaning, with all exposed surfaces getting washed down with bleach solution.

The easiest known way to kill noroviruses is through repeat washing of surfaces using bleach solutions containing at least 10 percent sodium hypochlorite. However, researchers say that even after intense cleaning efforts, norovirus particles have been found to cling to carpet surfaces, elevator buttons, bed rails and dining room tabletops.

To address any virus remaining, all disposable supplies in infected areas were thrown out and replaced with fresh ones, an effort that cost more than $53,000.

Because the norovirus outbreak was citywide, staff from outside of JHH were not allowed to work on site, while Hopkins staff, in turn, were banned from working at other facilities. Even visitors to the Hospital were asked screening questions to identify stomach problems and, if present, were told not to see patients for 72 hours. Staff working on units hit by the outbreak wore gowns and gloves to guard against unwittingly picking up or spreading the disease. All group meals or shared-food events were banned inside the Hospital.

After three months of intense efforts to prevent the spread of infection, new infections stopped by early May 2004. The outbreak was deemed to be over, and affected units returned to normal activity.

The researchers’ review showed that the number of patients infected, or so-called attack rate of the virus, in the CCU was low, at 5 percent (seven patients out of 133), but was notably higher for health care workers, at 30 percent (29 out of 97). The attack rate numbers were higher for psychiatry services, at 17 percent for patients (39 out of 233) and 38 percent for staff (76 out of 200).

Everyone infected experienced diarrhea or vomiting, while some others experienced such symptoms as chills and muscle aches.

Calculations of costs associated with the cleanup included expenses for cleaning supplies ($96,000), staff sick leave and overtime ($89,000), plus lost revenue from closing the units and echocardiogram laboratory to new patients ($418,000). Indeed, nearly 460 hours of sick leave were used by staff on the CCU, 138 hours in the echocardiogram lab, and more than 2,000 hours in psychiatry services.

Expenses not taken into account were those associated with other areas of the hospital where few cases were reported and no restrictions were placed on the unit. Costs incurred outside of main units were not included in this estimate because researchers were not certain that the infection had indeed resulted from contact within the hospital and not from exposure in the community. In addition, costs associated with lengthier stays in the hospital and more intensive patient care were also not factored into the estimates because researchers would have had to guess at what the patients’ length of stay would have been in the absence of a norovirus outbreak.

Researchers say their next step is to evaluate which specific infection control strategies and procedures are most effective at preventing noroviruses from spreading.

The U.S. Centers for Disease Control and Prevention estimate that each year more than 23 million people become infected with Norwalk or Norwalk-like viruses, and the disease is considered a leading cause of foodborne illness, after people have contaminated food with dirty hands.

Funding for the study was provided by The Johns Hopkins Hospital. Testing services were provided by the state of Maryland’s Department of Health and Mental Hygiene, with additional confirmations provided by the National Institutes of Health.

Besides Perl and Johnston, other members of the Hopkins team involved in this investigation and study were Haoming Qiu; John Ticehurst, M.D.; Conan Dickson, Ph.D.; Patricia Rosenbaum; Patricia Lawson; Amy Stokes; Charles Lowenstein, M.D.; Michael Kaminsky, M.D.; Sara Cosgrove, M.D., M.S.; and Kim Green, Ph.D.

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Scientists have discovered a new way to attack dangerous pathogens, marking a hopeful next step in the ever-escalating battle between man and microbe.

In a paper published online Feb. 10 in the journal PLoS Pathogens, scientists demonstrate that by stopping bacteria’s ability to degrade RNA – a “housekeeping” process crucial to their ability to thrive – scientists were able to stop methicillin-resistant Staphylococcus aureus or MRSA both in the laboratory and in infected mice.

The team, headed by a microbiologist at the University of Rochester Medical Center, is now developing closely related compounds designed to be much more potent than the one discussed in the paper.

The new approach shows promise against the most severe strains of MRSA as well as the toughest type of MRSA infection for antibiotics to infiltrate – bacteria enmeshed in biofilms.

“This offers a whole new way to go on the offensive against some of the world’s most dangerous bugs,” said the leader of the group, Paul Dunman, Ph.D., associate professor of Microbiology and Immunology at the University of Rochester Medical Center and formerly of the University of Nebraska. “We’re hoping our research opens the door to an entirely new class of antibiotics.”

The team also includes scientists from the University of Nebraska, the University of Arkansas, Vanderbilt University, and the University of North Texas Health Science Center.

MRSA infections are among the most virulent infections known. The superbug causes nearly 500,000 hospitalizations and 19,000 deaths in the United States each year – more deaths than caused by AIDS. The bug can be acquired in the community or in hospitals.

MRSA and other dangerous microbes are so deadly largely because of their ability to adapt quickly to changing conditions. Bacteria’s knack for adaptation hinges on their ability to constantly churn out new molecules of RNA, which carry crucial messages that tell a cell what proteins to make and in what quantities.

The new research focuses on a critical cellular step that is part of the process, known as RNA degradation. Once an RNA molecule is no longer needed, the molecule is sliced and diced up, and its components are returned to the pool of available raw material that the cell taps again and again to construct other RNA molecules as needed.

“In bacteria, RNA degradation is crucial. The cells are replicating very quickly and responding to environmental changes very rapidly. In less than three minutes, a new RNA transcript is made, the protein is made, and then the RNA is degraded, and that material is made available to make other RNA molecules,” Dunman said.

Dunman’s team discovered that a molecule known as RnpA is central to the degradation process. After nailing down the activity of RnpA, the team tested more than 29,000 compounds in its search for one that inhibits its activity. The team found one, a small molecule called RNPA1000, that brings MRSA nearly to a standstill.

Throwing a monkey wrench into bacteria’s RNA recycling system might harm MRSA in a number of ways. One possibility is that since messenger RNA molecules are not destroyed like they should be, the bacteria are overcome by an array of confusing instructions that should have been turned off. Another possibility is that bacteria are unable to make essential new RNA molecules, since the supply of raw material is not available.

“We believe this basically makes the bacterial cell go haywire. The cell is producing proteins it no longer needs, and it can’t produce proteins that it does need,” said Dunman.

The team found that RNPA1000 is active against the predominant MRSA types circulating in the United States, vancomycin intermediate susceptible S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA). The compound also showed significant antimicrobial activity against a host of other bugs tested, including Staphylococcus epidermidis, antibiotic-resistant Streptococcus pneumoniae, Streptococcus pyogenes, and vancomycin-resistant Enterococcus faecium.

Especially promising was its activity against MRSA biofilms, whose formation is central to the bacterium’s virulence in medical settings. Today’s antibiotics have a tough time breaking through MRSA biofilms on equipment like catheters, but RNPA1000 brought the bacteria to a halt even when they were ensconced within biofilms.

The agent does not affect other drugs used to treat MRSA infections, including vancomycin, daptomycin, or rifampicin; it does affect oxacillin, making it more potent. That find might make it possible to eventually combine an agent like RNPA1000 with other drugs that also target the infection.

The compound was also moderately effective in mice. In an experiment with infected mice, all of the untreated mice died from their infection, but half the mice survived when treated with a large dose of RNPA1000. The compound is also somewhat toxic to human cells at the largest doses. Those findings make it unlikely that RNPA1000 itself will end up as an antibiotic and spurred Dunman and colleagues to design safer, more potent alternatives.

“This is a great starting point,” said Dunman. “We’ve identified a compound that is very active against RnpA, and now we can use chemistry to try to increase its potency by hundreds of times, as well as make it less toxic to human cells. We’ve gotten a lead from the drug screen, and now we’re building a better molecule.”

Dunman is a leader in the development and use of array technology to study microbes and explore fresh approaches to the development of antibiotics. While microarrays are widely used by scientists to take what amounts to a snapshot of the activity of thousands of genes in a cell, Dunman adds a twist. His team employs the technology constantly to watch what happens to RNA molecules after they’ve been made, typically taking dozens of snapshots in the span of hours to get an ongoing, intimate look at RNA degradation.

The paper caps a six-year effort that began when the first author, Patrick Olson, was a high school student working as an intern in Dunman’s laboratory in Nebraska. Olson is now in graduate school at Washington University in St. Louis, working toward both his medical and doctoral degrees.

Notes:

In addition to Dunman and Olson, other authors of the paper include post-doctoral associate Christelle Roux of the University of Rochester; Lisa Kuechenmeister, Kelsi Anderson, Tami Lewis, Oluwatoyin Asojo, and Khalid Sayood of the University of Nebraska; graduate student John Morrison of the University of Nebraska Medical Center, currently a visiting scientist in Dunman’s Rochester laboratory; Sonja Daily, Karen Beenken, and Mark Smeltzer of the University of Arkansas; Michelle Reniere and Eric Skaar of Vanderbilt University; and William Weiss, Mark Pulse, Phung Nguyen, and Jerry Simecka of the University of North Texas Health Science Center.

These researchers are among scientists at two dozen laboratories around the world with which Dunman works. He is also a founder and owner of Caddis Research LLC, which is developing antimicrobial agents that target bacteria that pose a threat to public health, and he is a consultant for Pfizer Research.

The project was funded by the National Institute of Allergy and Infectious Diseases, the American Heart Assn., and the Nebraska Research Initiative.

Source:
Tom Rickey
University of Rochester Medical Center Continue reading →

Scientists at Johnson & Johnson Pharmaceutical Research and Development (J&JPRD) have identified a novel
anti-tuberculosis (TB) compound that works better and faster than the current standard of care in mouse models of TB
infection. Also, preliminary studies in healthy human volunteers show that the drug is safe. The findings are published in
the December 9 issue of Science Express, the online version of the journal Science, and will be published in the January 14
print edition. The studies are reported by scientists at J&JPRD and colleagues at the Swedish Institute for Infectious
Disease Control in Solna, Sweden, and Piti?-Salp?tri?re School of Medicine in Paris, France.

The compound, called R207910, belongs to a new family of anti-TB agents called diarylquinolines (DARQ) and appears to have
better, and more differentiated antibiotic properties than currently used drugs for TB, individually and in combination.
R207910 was better at clearing infection from the lungs of mice than the triple cocktail regimen currently recommended by the
World Health Organization (WHO). Also, cocktail regimens containing R207910 cleared infection in mice in half the time than
the currently used regimen.

“The drug acts through a novel mechanism of action, and is therefore active against all multi-drug resistant (MDR) strains of
TB tested so far,” says Dr. Koen Andries, D.V.M., Ph.D., Distinguished Research Fellow, Antimicrobial Research at J&JPRD. “A
combination including R207910 but excluding rifampin, one of the current TB drugs, looks especially promising. A combination
excluding rifampin would be compatible with anti-HIV drugs, making it suitable for treating patients co-infected with HIV and
TB.”

The World Health Organization (WHO) has declared TB a global health crisis. TB now infects one-third of the world’s
population and causes close to nine million new cases of active TB and 2 million deaths each year. Unfortunately, many TB
strains have become resistant to several antibiotics used today to treat the disease. More than 300,000 new cases of
multi-drug-resistant TB per year are detected, mainly in Eastern Europe and Central Asia.

“For a long time, there has been a move to find a drug that is safe and effective and completely cures the patient in a
shorter time,” Andries says. “A new drug that could shorten or simplify effective treatment of TB would dramatically improve
TB control programs.”

No new anti-TB drugs have been brought into the clinic in the past 40 years, and although doctors have effective first-line
TB drugs that work, there have been difficulties getting these medicines to the patients who need them as well as effectively
treating patients with drug resistant disease.

One out of three people in the world are infected with latent TB. Even in the developed world, one out of twenty carry the TB
bacillus. In some developing countries, one in two people are infected. A carrier of latent TB has a 10 percent life-long
risk to develop TB. However, in HIV patients, that risk is 10 percent per year.

“That is the main reason why there is now such a resurgence of tuberculosis in countries that were previously hit by HIV,”
Andries says. “The HIV epidemic has worsened the TB epidemic substantially.”

TB is currently treated with a cocktail of antibiotics, including rifampin, isoniazid, and pyrazinamide, which must be taken
for six to nine months. The TB symptoms disappear after several weeks, and patients begin to feel healthy. However, to
completely clear the infection, they must continue therapy at least four more months. This is often difficult, especially for
people living in remote areas in developing countries, and discontinuing treatment prematurely increases the risk of
developing resistant bacteria.

To ensure compliance, TB patients are monitored under the DOT (Directly Observed Treatment) program, with patients taking
their cocktail of medicines each day under the supervision of a healthcare worker.

R207910 Study Findings

“Our findings suggest that at least in mice, R207910 seems to have the desired properties of simplifying and shortening the
treatment duration, and perhaps, more,” says Andries. In bacterial cell cultures, R207910 was effective against many
different strains of mycobacteria, including strains that are resistant to other drugs. The drug is bactericidal, meaning
that it kills the TB bacilli.

In mouse models, the studies showed that a cocktail regimen containing this compound reduced bacterial load after one month
to the same level as the currently used regimen after two months of treatment, shortening normal treatment time by 50
percent. After two months treatment with the R207910 containing cocktail, no TB bacilli could be isolated from the lungs
anymore, a finding that the French group that did those studies called “unprecedented”.

The mouse studies also show that this new compound quickly enters the bloodstream and is actually concentrated in lung
cells-which harbour the TB bacilli-killing the bacilli soon after they enter the body. Also, R207910 lingers in the body for
days continuing to kill bacilli even when administered only once a week in mice.

R207910 is unique in the way it works. The compound attacks an enzyme called ATP synthase, the energy source for the
bacterium. Given its new mechanism of action and apparent impact on drug resistant strains of TB, according to Andries,
R207910 could lead to a shift in the current treatment paradigm for tuberculosis. “Preliminary data show R207910 has the
desired properties we need and holds a great deal of promise,” he said.

However, Koen added, considerable work needs to be done to fully determine this compound’s clinical potential. Since the
compound seems to be safe and well tolerated in Phase I studies with healthy human volunteers, R207910 will now be tested in
humans with active pulmonary TB.

Dr. Andries’ coauthors are Peter Verhasselt, Hinrich G?hlmann, Jean-Marc Neefs, Hans Winkler, Jef Van Gestel, Philip
Timmerman, and Didier de Chaffoy at Johnson & Johnson Pharmaceutical Research and Development, LLC in Beerse, Belgium; Jerome
Guillemont at Johnson & Johnson Pharmaceutical Research and Development in Val de Reuil, France; Min Zhu at Johnson & Johnson
Pharmaceutical Research and Development, LLC in Raritan, NJ; Ennis Lee, and Peter Williams at Johnson & Johnson
Pharmaceutical Research and Development, LLC in High Wycome, UK; Emma Huitric and Sven Hoffner at Swedish Institute for
Infectious Disease Control in Solna, Sweden; Emmanuelle Cambau, Chantal Truffot-Pernot, Nacer Lounis, and Vincent Jarlier at
Piti?-Salp?tri?re School of Medicine in Paris, France. Nacer Lounis is currently at Johns Hopkins University School of
Medicine in Baltimore, MD.

The study was supported by Johnson & Johnson Pharmaceutical Research and Development, and animal work in Paris was also
supported by annual grants from Association Fran?aise Raoul Follereau, INSERM and, Minist?re de l’Education Nationale et de
la Recherche.

About R207910

A French chemist from the Johnson & Johnson pharmaceutical group synthesised the substance; and the team in Beerse, Belgium
discovered its anti-TB action. The compound has been transferred to its sister company, Tibotec, whose lead compounds are for
HIV/AIDS, for clinical development.

About Johnson & Johnson Pharmaceutical Research & Development

Johnson & Johnson Pharmaceutical Research & Development, (J&JPRD) is part of Johnson & Johnson, the world’s most broad-based
producer of healthcare products. J&JPRD, with its headquarters in Raritan, New Jersey (USA), has sites throughout Europe and
the United States. J&JPRD leverages drug discovery, drug evaluation, and drug development in a variety of therapeutic areas
to address unmet medical needs worldwide. The company’s major therapeutic areas of focus include hematology, oncology,
infectious disease, obesity and metabolic disorders, neurology and psychiatry, pain and women’s health.

About Tibotec

Tibotec is a pharmaceutical research and development company with headquarters in Belgium and operating subsidiaries in the
United States and Ireland. The company, like J&JPRD, is a subsidiary of Johnson & Johnson. Tibotec’s lead development
compounds are for the treatment of HIV/AIDS and the pandemics of TB and HIV/AIDS are closely intertwined. Drug interactions
between HIV/AIDS drugs and TB drugs are particularly problematic.

(This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995.
These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown
risks or uncertainties materialize, actual results could vary materially from the Company’s expectations and projections.
Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and
currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new
product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws
and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties
and other factors can be found in Exhibit 99(b) of the Company’s Annual Report on Form 10-K for the fiscal year ended
December 28, 2003. Copies of this Form 10-K are available online at sec or on request from the Company. The Company assumes no obligation to update any
forward-looking statements as a result of new information or future events or developments.)

For more information on Johnson & Johnson, please visit the Company’s website at
jnj.

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Mark Krajnak (U.S.)
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Leaders of the Group of Eight industrialized nations in the final communique issued at the close of their summit in Heiligendamm, Germany, agreed to provide more than $60 billion to fight HIV/AIDS and address other issues in Africa, Germany’s Development Minister Heidemarie Wieczorek-Zeul announced Friday before G8 leaders met with African and international officials, the AP/International Herald Tribune reports (AP/International Herald Tribune, 6/8). According to the Financial Times, about half of the $60 billion will come from President Bush’s recent request for a five-year, $30 billion extension of the President’s Emergency Plan for AIDS Relief (Williamson, Financial Times, 6/8). Germany will contribute $5.4 billion between 2007 and 2015, according to Wieczorek-Zeul (AP/International Herald Tribune, 6/8).

Package Details
The communique indicated the $60 billion would be disbursed “over the the coming years” but did not lay out a specific time frame, Reuters UK reports (Chambers/Heller, Reuters UK, 6/8). Part of the funding includes $6 billion to $8 billion for the Global Fund To Fight AIDS, Tuberculosis and Malaria, according to AFP/Yahoo! News (Cole, AFP/Yahoo! News, 6/8). The communique also “recommits” to the aid pledges made during the 2005 G8 summit in Gleneagles, Scotland, to increase aid to $50 billion annually by 2010 (Financial Times, 6/8). Leaders in the communique also pledged to support local production of drugs, including antiretrovirals, to ensure lower prices for treatments. The document also includes three “significant dollar commitments” to support actions on mother-to-child HIV transmission, pediatric treatments, and maternal and child health totaling $4.8 billion, AFP/Yahoo! News reports. Leaders in the communique also pledged to help reduce malaria prevalence and deaths in 30 African countries (AFP/Yahoo! News, 6/8). According to the Times, the communique includes more than $1 billion for such efforts (Financial Times, 6/8). In addition, the communique pledges support for national health strategies and peacekeeping efforts in Africa, as well as $500 million for education programs in 2007 and support for long-term funding (AFP/Yahoo! News, 6/8).

The $60 billion will not be a “firm pledge” because “some countries are cautious about increased spending,” according to some diplomats, the Times reports. The final communique also includes the goal of providing five million HIV-positive people with drug access by 2010 — the treatment target included in a draft of the communique dated June 1 — according to an unnamed source close to the German delegation. Leaders announced a target of providing 10 million people with drug access by 2010 in the Gleneagles communique, according to the Times (Financial Times, 6/8).

Reaction
British Prime Minister Tony Blair praised the communique, the PA/Guardian reports. “The important thing about what we have agreed is that we have recommitted ourselves to all the commitments we made … at Gleneagles,” Blair said, adding, “It’s a deal between Africa and the developed world, and just as we have recommitted ourselves to substantial increases in support and help, so Africa has recommitted itself to its responsibilities as part of a partnership — proper governance against corruption, proper democracy and so on” (PA/Guardian, 6/8). Michel Kazatchkine, executive director of the Global Fund, said the G8 agreement “makes it possible to defeat” HIV/AIDS, TB and malaria (Global Fund release, 6/8). German Chancellor Angela Merkel said, “We are aware of our obligations and would like to fulfill our promises” (AFP/Yahoo! News, 6/8).

“We will have to watch the G8 carefully to see they keep their promises,” Paul Zeitz, executive director of the Global AIDS Alliance, said, adding, “But even if they do keep them, the funding falls far short of what is needed” (GAA release, 6/8). “We must not be distracted by big numbers,” an unnamed Oxfam policy adviser said, adding, “What the $60 billion headline means at best is just three billion extra in aid by 2010. Before this summit, Oxfam showed the G8 were set to miss their 2010 target by a massive $30 billion. Today’s announcement may only close that gap to $27 billion.” Irish HIV/AIDS advocate Bono said of the communique, “I think it is deliberately the language of obfuscation. It is deliberately misleading” (Reuters UK, 6/8).

NPR’s “All Things Considered” on Thursday reported on the summit, including the HIV/AIDS agreement. The segment includes comments on HIV/AIDS from Jurgen Wilhelm, director general of the German Development Service; Eve Odete of Oxfam; and a representative from South Africa (Harris, “All things Considered,” NPR, 6/7). Audio of the segment and expanded NPR coverage are available online.

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To develop new strategies to control tuberculosis (TB), a contagious disease that infects one-third of the world’s population and kills almost two million people every year, the University of Pittsburgh Center for Vaccine Research has received an $11.4 million grant from the Bill & Melinda Gates Foundation. The grant will enable Pitt researchers to use new imaging technologies to study TB to shorten and simplify its course of treatment, potentially improving survival and curtailing the global TB epidemic.

“One of the most challenging issues in treating TB and stopping its spread is the length of time it takes to adequately stem the infection,” said JoAnne Flynn, Ph.D., principal investigator of the grant and professor of microbiology and molecular genetics, University of Pittsburgh School of Medicine. “Current drugs are available, but we don’t fully understand how or why they work. TB treatment must be continued for at least six months to be effective, placing an undue burden on those who are infected – often from the poorest and most disadvantaged countries.”

According to Dr. Flynn, TB is difficult to control because the germs that cause the infection hide from the immune system in small tissue nodules called granulomas, enabling the infection to reactivate years, and even decades, later. Although for the most part TB is a curable disease, patients must adhere to treatment long after symptoms have faded. This proves challenging in many regions of the world where medication is not readily accessible. Indeed, an inadequate or incomplete course of treatment is the major factor that causes drug-resistant TB strains to develop. These strains are alarmingly high in many countries around the world.

“Current medications for TB were developed more than three decades ago,” said Dr. Flynn. “To create significantly shorter and simplified approaches to treatment, we must improve our understanding of this disease and how current drugs are localized at the site of infection.”

To understand more about the basic biology of TB, Dr. Flynn and colleagues are using the grant to develop positron emission tomography (PET) and computed tomography (CT) imaging studies in non-human primates. By using combined PET/CT, the researchers will be able to follow the progression of the disease in animals over time and analyze changes in tissue and responses to particular drugs. They will be using three imaging technologies – radionuclides, fluorescence and mass spectrometry – in combination to develop imaging probes and techniques to precisely locate bacteria associated with TB and to explore the underlying factors responsible for slow drug metabolism.

“By applying the tools of modern medicine to TB, we hope to lay the groundwork for real-time measurements of TB drug efficacy in clinical trials and develop new targeted therapies that will considerably shorten the length of treatment,” said Dr. Flynn.

Tuberculosis is a bacterial disease usually affecting the lungs. Called pulmonary TB, the disease is characterized by a persistent cough, shortness of breath, weight loss and chest pain. Left untreated, one person with active pulmonary TB will infect on average between 10 and 15 other people every year. The bacteria associated with the disease also can infect nearly any part of the body, such as the lymph nodes, the spine or bones. TB is deadly if left untreated.

###

Co-investigators on the grant include Clifton Barry III, Ph.D., National Institute of Allergy and Infectious Diseases; Richard Caprioli, Ph.D., and Michelle Reyzer, Ph.D., Vanderbilt University; David Russell, Ph.D., and Warren Zipfel, Ph.D., Cornell University; Kim Janda, Ph.D., and Tobin Dickerson, Ph.D., The Scripps Research Institute; Benjamin Davis, Ph.D., Oxford University; Chet Mathis, Ph.D., Jonathan P. Carney, Ph.D., and Brian J. Lopresti, B.S., University of Pittsburgh; and Veronique Dartois, Ph.D., Novartis Institute of Tropical Disease.

The Center for Vaccine Research (CVR) at the University of Pittsburgh houses both the Regional Biocontainment Laboratory and the Vaccine Research Laboratory. Researchers at the CVR, directed by Donald S. Burke, M.D., dean of the University of Pittsburgh Graduate School of Public Health and UPMC Jonas Salk Professor of Global Health, develop new methods and strategies to prevent and treat infectious diseases, potentially improving and protecting global health.

Source: Clare Collins

University of Pittsburgh Schools of the Health Sciences Continue reading →

South Carolina lawmakers have approved $2.4 million for the state’s AIDS Drug Assistance Program, the Columbia State reports (Reid, Columbia State, 5/8). ADAPs are federal- and state-funded programs that provide HIV/AIDS-related medications to low-income, uninsured and underinsured HIV-positive individuals (Kaiser Daily HIV/AIDS Report, 4/9).

The Legislature approved $4 million for the state’s ADAP last year, according to the State. South Carolina’s contribution has increased from 5% of the program’s budget in 2007 to 19% this year. South Carolina ADAP Director Sonya Bayone said that about 100 people in the state apply for ADAP monthly.

“We have finally, as a state, come to grips with HIV/AIDS and are willing to put resources to stem the spread of this disease,” Rep. Joe Neal (D), who has led efforts in the state House to allocate money for HIV/AIDS services, said.

According to the State, the new money will help prevent waiting lists, such as the one that increased to 567 people after federal funding for the program was reduced last year. However, the program is expected to face federal funding cuts and increased costs again in the future, the State reports. Higher drug prices, new recommendations that HIV-positive people start treatment earlier and concerted efforts to increase HIV testing have contributed to rising ADAP costs, according to the State.

Helmut Albrecht, chief of Infectious Diseases at the University of South Carolina School of Medicine, said, “This is just bringing us up to where we should be,” adding, “In all honesty, we had a lot of catching up to do.” Bambi Gaddist, executive director of the South Carolina HIV/AIDS Council, said, “A health agenda is important for economic stability. In the past, we have left HIV off. It’s important that we place HIV on that health agenda.” About 800 people in South Carolina are diagnosed with HIV/AIDS annually (Columbia State, 5/8).

Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation.

© 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved. Continue reading →

Researchers have identified what they believe is the original source of malignant malaria: a parasite found in chimpanzees in equatorial Africa.

UC Irvine biologist Francisco Ayala and colleagues think the deadly parasite was transmitted to humans from chimpanzees perhaps as recently as 5,000 years ago – and possibly through a single mosquito, genetic analyses indicate. Previously, malaria’s origin had been unclear.

This discovery could aid the development of a vaccine for malaria, which sickens about 500 million people and kills about 1.5 million each year. It also furthers understanding of how infectious diseases such as HIV, SARS, and avian and swine flu can be transmitted to humans from animals.

“When malaria transferred to humans, it became very severe very quickly,” said Ayala, co-author of the study that reports these findings. “The disease in humans has become resistant to many drugs. It’s my hope that our discovery will bring us closer to making a vaccine.”

The study appears online the week of Aug. 3 in the Proceedings of the National Academy of Sciences.

Human malignant malaria is caused by a parasite called Plasmodium falciparum, which is responsible for 85 percent of all infections and nearly all malaria deaths. Chimpanzees were known to carry a closely related parasite called Plasmodium reichenowi, but most scientists assumed the two had existed separately in humans and chimpanzees for the last 5 million years.

Scientists in the current study examined several new strains of the parasite found in blood taken from wild and wild-born chimpanzees in Cameroon and Ivory Coast sanctuaries during routine health exams.

A gene analysis linked one chimpanzee strain to all worldwide strains of the human malaria parasite. This connection suggests that one mosquito may have transferred malaria to humans. Because there is little genetic variance among strains of the human parasite, scientists believe the transmission occurred in the recent past – maybe 5,000 to 2 million years ago – though an exact time could not be determined.

The results support an earlier hypothesis by Dr. Ajit Varki of UC San Diego and colleagues that genetic mutations made humans first resistant to sickness from the chimpanzee parasite, then extremely susceptible to illness from the human form.

They also corroborate an earlier finding by Ayala and former UCI graduate student Stephen Rich that malignant malaria started spreading throughout the tropics and world about 5,000 years ago, when agriculture began in Africa. Rich, now a professor at the University of Massachusetts Amherst, also is the lead author of the current PNAS study.

In addition to Ayala and Rich, Nathan Wolfe of Stanford University worked on the study, along with collaborators from the Robert Koch Institute and the Max Planck Institute for Evolutionary Anthropology in Germany; the Global Viral Forecasting Initiative in San Francisco; the Biotechnology Centre in Cameroon; the U.S. Department of Agriculture; and the Ebola Tai Forest Project in the Ivory Coast.

The study was funded by the National Institutes of Health, with additional support from the Cummings School of Veterinary Medicine at Tufts University and the National Geographic Society Committee for Research & Exploration.

Source:
Jennifer Fitzenberger
University of California – Irvine Continue reading →

Bacteria that infect chronic wounds can be deadly to maggot ‘biosurgeons’ used to treat the lesions, show researchers writing in the journal Microbiology. The findings could lead to more effective treatment of wounds and the development of novel antibiotics.

Scientists from the Copenhagen Wound Healing Centre, Statens Serum Institut and the University of Copenhagen in Denmark showed that maggots applied to simulated wounds heavily infected with the bacterium Pseudomonas aeruginosa, were unable to treat the wound and were left dead after 20 hours.

Chronic wounds, such as leg ulcers, affect 1% of the Western population and are painful and difficult to treat. Use of maggots to disinfect wounds is an ancient practice that regained popularity in the early 1990s. Maggot Debridement Therapy (MDT) is now a standard procedure at wound care centres all over the world, in which sterile larvae from the green bottle fly Lucilia sericata are applied to the wound either directly or contained within a sealed nylon bag. The maggots gently ingest necrotic (dead) tissue and kill ingested bacteria in the gut. In addition, the maggots secrete antimicrobial compounds into the wound, help reduce inflammation and promote wound healing. The actual biological mechanisms responsible for the process are still largely a mystery.

P. aeruginosa is an opportunistic bacterium responsible for many hospital-acquired infections. It is often associated with chronic wounds in which the bacteria clump together to form biofilms. By effectively talking to each other via a well-studied communication system called quorum sensing (QS), bacteria in biofilms are known to be more successful at avoiding destruction by the host immune system as well as antibiotics.

Dr Anders Schou Andersen, who led the research, explained that QS was also the key to P. aeruginosa’s toxicity to maggots. “When we blocked the QS signalling pathways in the bacteria, the maggots were much better at surviving and potentially cleansing the wounds. Signalling between bacteria growing in biofilms is known to lead to the production of lethal toxins, without which the bacteria are more vulnerable to eradication.”

Dr Andersen believes the research could benefit patients with persistent wounds. “MDT is generally very effective. It has been said that in a few cases MDT had failed, leaving the maggots dead in the lesion. We now think that this was probably due to the presence of P. aeruginosa in the wound,” he said. “If we can find the specific bacterial mechanism that kills the maggots, we could target this when developing new treatments. For example, wounds infected with P. aeruginosa could be treated with an agent that interrupts bacterial signalling to ensure the success of maggot therapy and thereby wound healing.”

Source:
Laura Udakis
Society for General Microbiology Continue reading →

New guidelines outline steps to eliminate catheter-related bloodstream
infections (CRBSI), one of the most deadly and costly threats to patient
safety. Released by the Centers for Disease Control and Prevention and
the Healthcare Infection Control Practices Advisory Committee (HICPAC),
the guidelines were developed by a working group led by clinical
scientists from the National Institutes of Health Clinical Center
Critical Care Medicine Department (CCMD) along with 14 other
professional organizations.

“The publication of these guidelines is a great contribution to the
continued improvement of quality patient care and is illustrative of the
power of collaboration across government agencies and with academic
institutions,” said NIH Director Dr. Francis S. Collins.

Major areas of emphasis in the guidelines include educating and training
health care personnel, using maximal sterile barrier precautions during
catheter insertion, cleaning skin with chlorhexidine (an antibacterial
scrub), and avoiding routine replacement of certain catheters.

“Preventing these infections is an excellent example of how hospitals
and other health care facilities can improve patient care and save
lives, all while reducing excess medical costs,” said Thomas R. Frieden,
M.D., M.P.H., CDC director.

Replacing a 2002 edition, the new guidelines are titled “Guidelines for
the Prevention of Intravascular Catheter-Related Infections” and were
published April 1, 2011, in Clinical Infectious Diseases and are
available on CDC’s HICPAC website. They will also be included in a
special supplement to the American Journal of Infection Control. HICPAC
advises CDC on infection prevention in healthcare facilities.

“Catheter-related bloodstream infections – like many infections in
health care – are now seen as largely preventable,” said lead author
Naomi O’Grady, M.D., medical director of procedures, vascular access,
and conscious sedation services at the NIH Clinical Center CCMD.
“Implementation of these critical infection control guidelines is an
important benchmark of health care quality and patient safety.”

Efforts to track, report, and prevent bloodstream infections have
improved in recent years. As part of its Action Plan to Prevent HAIs,
the U.S. Department of Health and Human Services has a national goal of
reducing one type of CRBSI, central line-associated bloodstream
infections (CLABSI), by 50 percent by 2013.

Starting in 2011, hospitals throughout the country must track and report
CLABSIs in intensive care units in order to get an annual 2 percent
Medicare payment increase. Hospitals will report their infection rates
to CDC’s National Healthcare Safety Network, and the data will be shared
with the Centers for Medicare and Medicaid Services. These data will be
made available to the public later this year on the Hospital Compare
website.

In addition to local efforts, a prevention effort called On the CUSP:
Stop BSI has been expanded nationally through funding from the Agency
for Healthcare Research and Quality (AHRQ). Also, CDC has provided
funding in recent years to state health departments to allow for better
tracking and prevention efforts at the state level.

The combination of national and local focus on preventing CRBSIs, and
specifically CLABSIs, has proven to be effective in improving patient
safety. A recent CDC report showed a 58 percent decrease in CLABSIs
among hospital ICU patients in 2009, compared to 2001. In 2009 alone,
reducing these infections saved about 3,000 to 6,000 lives and about
$414 million in extra medical costs, compared with 2001. However,
infections still occur in healthcare settings, and diligent prevention
efforts must continue.

“Education and reinforcement of care and maintenance protocols among
staff is key. We all have a role to play in protecting patients from
these infections,” O’Grady said.

Source:

U.S. Department of Health and Human Services Continue reading →

The Global Fund To Fight AIDS, Tuberculosis and Malaria needs to improve its oversight of programs in developing countries and find ways to ensure that programs it funds are effective, according to a report released on Wednesday by the Center for Global Development, the Boston Globe reports. Although the Global Fund has “[s]everal success stories” in countries like Rwanda and China, “trouble persists” in many African countries that have histories of corruption or with “little expertise in managing vast amounts of donor funds,” according to the Globe. There are three countries where Global Fund programs have had “particularly rocky starts” — Kenya, Nigeria and Uganda, the Globe reports. Kenya has disbursed 38% of its $235 million in grants, and one malaria program in the country receiving Global Fund support is running six months behind schedule, according to the Globe. Nigeria pledged to use its Global Fund grant to provide 14,000 people with access antiretroviral drugs in one year, but no one received the drugs, the Globe reports. The Global Fund in April suspended its HIV/AIDS grant to Nigeria, retracting $81 million, according to the Globe. Uganda’s five Global Fund grants were suspended in 2005 because of mismanagement by the Health Ministry, and although the funds later were reinstated, programs in the country are running an average of six months behind schedule, the Globe reports.

Other Issues
The report also says that the Global Fund’s Geneva headquarters “feels chaotic” because staff are “constantly making a new rule for a new situation,” Celina Schocken, who has worked at the Global Fund and contributed to the report, said. She added that health ministries receiving grants from both the Global Fund and the President’s Emergency Plan for AIDS Relief often respond faster to requests from U.S. officials who live in the country. The Global Fund “is not breathing down anyone’s neck asking for a meeting to get things going, but others are,” Schocken said. Bernard Rivers — editor of the Global Fund Observer and one of 22 health specialists who produced the report — said whoever is selected next week to replace Richard Feachem as executive director of the Global Fund “must be really focusing on grants that are in trouble or could be in trouble.” Steve Radelet, chair of the report, and some U.S. officials think that rather than hiring hundreds of technical experts to oversee its grants, the Global Fund should coordinate its programs more closely with U.S. and European donors, as well as U.N. agencies, the Globe reports. British and German aid organizations have started assisting the Global Fund’s programs in a few countries, and the U.S. has set aside $12.5 million in technical assistance (Donnelly, Boston Globe, 10/26). According to sources familiar with the Global Fund executive director selection process, Rep. Jim Kolbe (R-Ariz.) and Vice Chair of MTV Networks Bill Roedy, who also is president of MTV Networks International, are on the list. Michel Kazatchkine, a former Global Fund vice chair and France’s global ambassador for HIV/AIDS and communicable diseases, also is a finalist. The two other candidates on the list are Michel Sidibe, director of UNAIDS’ country and regional support department, and Hilde Johnson, Norway’s former minister of international development (Kaiser Daily HIV/AIDS Report, 10/10).

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