Multi-Drug Resistant Tuberculosis (TB) treatment a Global threat

The World Health Organisation (WHO) and the Global Fund to Fight AIDS, TB and Malaria says that strains of tuberculosis with resistance to multiple drugs could spread widely and highlight an annual need of at least $1.6 billion in international funding for treatment and prevention of the disease.

Dr. Margaret Chan, director-general of WHO, and Dr. Mark Dybul, executive director of the Global Fund, said that the only way to carry out the urgent work of identifying all new cases of tuberculosis, while simultaneously making progress against the most serious existing cases, will be to mobilize significant funding from domestic sources and international donors.

With the overwhelming majority of international funding for tuberculosis coming through the Global Fund, they said, it is imperative that efforts to raise money be effective this year. Growing alarm about the threat of multi-drug resistant TB, also known as MDR-TB, is making that even more pressing.

“We are treading water at a time when we desperately need to scale up our response to MDR-TB,” says Chan. “We have gained a lot of ground in TB control through international collaboration, but it can easily be lost if we do not act now.”

WHO and the Global Fund have identified an anticipated gap of $1.6 billion in annual international support for the fight against tuberculosis in 118 low- and middle-income countries on top of an estimated $3.2 billion that could be provided by the countries themselves.

Filling this gap could enable full treatment for 17 million TB and multidrug-resistant TB patients and save 6 million lives between 2014-2016.

“It is critical that we raise the funding that is urgently needed to control this disease,” says Dybul. “If we don’t act now, our costs could skyrocket. It is invest now or pay forever.”

Chan and Dybul spoke to the media in Geneva in advance of World TB Day on March 24, which commemorates the day in 1882 when Dr. Robert Koch discovered the mycobacterium that causes tuberculosis.

Read more on TB Research in the European Respiratory Journal

Major Breathrough in TB Research: Questions answered!

After three decades of searching, the random screening of a group of compounds against the bacterium that causes pulmonary tuberculosis has led scientists to a eureka discovery that breaks through the fortress that protects the bacterium and allows it to survive and persist against treatments.

The two findings, which occurred at Colorado State University, are published today in Nature Chemical Biology.

The article describes the discovery of an important cell function in the mycobacterium that causes tuberculosis which allows the mycobacterium to survive. The researchers also discovered a compound that prevents this cell function.

The bacterium that causes tuberculosis is extremely difficult to kill and current tuberculosis drugs on the market don’t do well to treat it. Six months of multiple antibiotics are generally required to treat tuberculosis in most people, and many current drugs no longer work because of resistant strains of the bacterium that causes tuberculosis. Scientists hope that finding new drugs to kill the bacteria in ways different than current drugs will help tackle those strains.

Cell envelopes form a virtually impenetrable bubble around the bacterium cell and protect it. Mycolic acids are key portions of this bacterium’s cell envelope. They are made inside the cell, but have to cross the cell membrane, with the help of a transporter, to reach their final location in the cell envelope.

“Without mycolic acids in the cell envelope, the bacteria die,” said Mary Jackson, one of the leading researchers on the project. Jackson is a professor in the Department of Microbiology, Immunology and Pathology.

“While randomly testing a group of compounds against the bacterium in the lab, we found one class of compounds that powerfully stops the growth of the bacterium, a significant finding on its own.

When we looked closer, we found that the compounds stopped a transporter from moving mycolic acids from inside to outside the cell, which also means this discovery identified a new method of killing the bacterium.

Scientists have been trying to find the transporter of mycolic acids for decades, knowing that understanding how to stop mycolic acids from reaching the surface of the cell could lead to new tuberculosis treatments.

“If mycolic acids cannot be transported, the tuberculosis bacterium cannot grow,” said Mike McNeil, co-researcher on the project with Jackson and also a professor in the Department of Microbiology, Immunology and Pathology at CSU.

“It is like a factory making bricks and no way to get them to the construction site. It is a long, hard road to develop new, badly-needed tuberculosis drugs. Still, we are optimistic that this research will strongly contribute to the worldwide crusade to diminish suffering and death caused by tuberculosis.”

Jackson, McNeil and partner researchers from CSU and St. Jude Children’s Hospital in Memphis also note that there are other potential transporters in the bacterium that resemble the one just found.

“We hope that our work also will pave the way to understanding what those transporters do in the cell and finding how to target them to kill the mycobacteria,” Jackson said.

Tuberculosis causes the death of more than 1.5 million people around the globe each year.

Careless disposal of antibiotics can create aquatic superbugs

A wastewater treatment plant can provide the perfect mating ground for carelessly disposed of antibiotics to form superbugs that are eventually discharged into streams and lakes, says a University of Michigan researcher.

It’s not the fault of the wastewater treatment plants, says Chuanwu Xi, assistant professor at the UM School of Public Health.

His research team sampled water at five sites in and near Ann Arbor’s Waste Water Treatment Plant and found that the water contained the superbug Acinetobacter, a multidrug-resistant bacterium.

The results were first reported by Xi’s group in 2009, and the research is ongoing.

Treatment plants across the country face the same problem due to the overuse of antibiotics and because people improperly flush them down the toilet, whereby the drugs enter the wastewater treatment systems where they can breed, Xi says.

“When we monitored the survival of these bugs in the Huron River, the downstream level dropped quickly to the level of upstream,” Xi said.

“More robust risk-assessment research is needed to assess the exact risk. This study, along with many other studies, alerts us to proper use and handling of antibiotics.”

The Ann Arbor wastewater plant recently installed technology that enhances the removal of bio-solids from the water, which in turn, will help prevent superbugs from forming.

People with unused antibiotics should not flush them down the toilet but should dispose of them properly, Xi says.

New way to treat CDI and other common hospital-acquired infection

The right image shows abundant S-nitrosylation (green) in human colitis compared with much less found in the left image of a normal colon. (Credit: UCLA/University of Texas Medical Branch at Galveston)

Researchers at the David Geffen School of Medicine at UCLA and the University of Texas Medical Branch at Galveston have discovered a molecular process by which the body can defend against the effects of Clostridium difficile infection (CDI), pointing the way to a promising new approach for treating an intestinal disease that has become more common, more severe and harder to cure in recent years.

In the U.S., several million people are infected each year, approximately double the incidence of a decade ago, mainly due to the emergence of a new, highly virulent strain of the bacteria that causes CDI.

As a result of the study findings, published in the Aug. 21 online edition of the journal Nature Medicine, the researchers are preparing to launch clinical trials using their discovery as a new CDI therapeutic approach.

The team also included researchers from Case Western Reserve University, Tufts University and the Commonwealth Medical College.

CDI is a bacterial infection that can cause diarrhea and more serious intestinal conditions, such as colitis, the inflammation of the colon. In the most severe cases, CDI can be fatal. It is most commonly acquired in hospitals by patients, particularly the elderly, who are being treated with antibiotics for another infection.

Currently, one of two potent antibiotics is used to treat the infection, but up to 20 percent of patients experience a relapse and a return of symptoms within a few weeks.

"We are treating a disease caused by antibiotics with yet another antibiotic, which creates the conditions for re-infection from the same bacteria," said study co-author Dr. Charalabos Pothoulakis, director of UCLA's Inflammatory Bowel Disease Center and a professor of medicine in the division of digestive diseases. "Identification of new treatment modalities to treat this infection would be a major advance."

Clostridium difficile causes diarrhea and colitis by releasing two potent toxins into the gut lumen that bind to intestinal epithelial cells, initiating an inflammatory response. These toxins are released only when the Clostridium difficile bacteria are multiplying. When antibiotics are used to treat another infection, it changes the bacterial landscape in the gut and, in the process, may kill bacteria that under normal conditions would compete with Clostridium difficile for energy. Scientists believe this may be what provides the opportunity for Clostridium difficile to grow and release its toxins.

The UCLA and University of Texas researchers found in laboratory studies that upon infection with Clostridium difficile, human cells in the gut are capable of releasing molecules that will neutralize these toxins, rendering them harmless. In animal studies, the researchers showed that using a drug to induce this process, known as protein s-nitrosylation, inhibited Clostridium difficile toxins from destroying intestinal cells. Forthcoming clinical trials will test this approach in humans.

"Our study suggests a novel therapeutic approach for treating Clostridium difficile infection by exploiting a newly discovered defense mechanism that has evolved in humans to inactivate microbial toxins," said Tor C. Savidge, an associate professor in the division of gastroenterology and hepatology at the University of Texas Medical Branch at Galveston and the paper's lead author.

Along with its potential to provide a much-needed new approach to treating CDI, the discovery could be applied to developing new treatments for other forms of diarrhea, as well as non-diarrheal diseases caused by bacteria.

Triclosan and Ubiquitous Antibiotics freely used in Personal Care Products

Earlier this month, the Food and Drug Administration (FDA) issued a press release about triclosan - an ubiquitous antibiotic found in tons of personal care products, including deodorant, toothpaste, hand and facial cleansers, mouthwash, and other household cleaners.

It can't be good for our environment to be flushing lots of antibiotics down the drain. In the press release, the FDA stated that:

For some consumer products, there is clear evidence that triclosan provides a benefit. For other consumer products, FDA has not received evidence that the triclosan provides an extra benefit to health. At this time, the agency does not have evidence that triclosan in antibacterial soaps and body washes provides any benefit over washing with regular soap and water.

After reading the press release, I am sure you are curious what kinds of research have been done on the safety of triclosan, as well as the utility of antibiotics in common household products. Go to the primary literature sources so you can see for yourself what scientists have been researching, and if their research is published in reputable peer-reviewed journals, and first investigate the safety aspects of triclosan.

It isn't hard to find a number of papers that implicated triclosan as problematic in animal studies. One paper (The bactericidal agent triclosan modulates thyroid hormone-associated gene expression and disrupts postembryonic anuran development) found that when bullfrog tadpoles were exposed the levels of triclosan that are typically found in our environment, the tadpoles did not develop normally.

Another paper (Short-term in vivo exposure to the water contaminant triclosan: Evidence for disruption of thyroxine) studying rats found that very low levels of triclosan disrupted thyroid hormone regulation. This has long been a concern about triclosan, as the structure of triclosan is very similar to that of thyroid hormones.

If there is a serious positive influence on our daily lives through the use of triclosan containing products, to some it may be worth the environmental cost. However, this arguement quickly falls apart when looking for evidence to support the claim that triclosan makes our lives better.

In a comprehensive review of the scientific literature published in 2007 (Consumer antibacterial soaps: effective or just risky?). Quoting from their abstract, it says it all:

Soaps containing triclosan within the range of concentrations commonly used in the community setting (0.1%-0.45% wt/vol) were no more effective than plain soap at preventing infectious illness symptoms and reducing bacterial levels on the hands.

So, if you want to avoid contaminating the environment without sacrificing personal hygiene, please check the labels of any household products before you purchase them to see if they contain triclosan (which also is marketed as Microban, Irgasan DP-300, Lexol 300, Ster-Zac, Cloxifenolum, or Biofresh ref).

Not only is this product unnecessary in most circumstances, but it looks like it could have a very negative impact in our environment. So, if it's not really helping you, you might as well find an alternative product that doesn't contain triclosan.

Acne drug prevents HIV breakout

Acne drug prevents HIV breakout

Johns Hopkins scientists have found that a safe and inexpensive antibiotic in use since the 1970s for treating acne effectively targets infected immune cells in which HIV, the virus that causes AIDS, lies dormant and prevents them from reactivating and replicating.

The drug, minocycline, likely will improve on the current treatment regimens of HIV-infected patients if used in combination with a standard drug cocktail known as HAART (Highly Active Antiretroviral Therapy), according to research published now online and appearing in print April 15 in The Journal of Infectious Diseases.

"The powerful advantage to using minocycline is that the virus appears less able to develop drug resistance because minocycline targets cellular pathways not viral proteins," says Janice Clements, Ph.D., Mary Wallace Stanton Professor of Faculty Affairs, vice dean for faculty, and professor of molecular and comparative pathobiology at the Johns Hopkins University School of Medicine.

"The big challenge clinicians deal with now in this country when treating HIV patients is keeping the virus locked in a dormant state," Clements adds. "While HAART is really effective in keeping down active replication, minocycline is another arm of defense against the virus."

Read the full article here

Newly engineered enzyme is a powerful staph antibiotic

Lysins that are effective against drug-resistant staph bacteria bore a hole through their cell walls.

The bacterium's contents ooze out, instantaneously killing it. (Credit: Image courtesy of Rockefeller University)

Newly engineered enzyme is a powerful staph antibiotic

With their best chemical antibiotics slowly failing, scientists are increasingly looking to nature for a way to control deadly staph bacteria -- the culprit behind most hospital infections.

Naturally toxic for bacteria, enzymes called lysins have the promising ability to obliterate staph, but the problem is producing large enough quantities of them to study how they work.

Rockefeller University scientists have now overcome this barrier by engineering a lysin that not only kills multidrug-resistant Staphylococcus aureus (MRSA) in mice, but also works synergistically with traditional antibiotics that have long been shelved due to resistance.

For the past five years, Vincent A. Fischetti, head of the Laboratory of Bacterial Pathogenesis and Immunology, and his colleagues have tried to clone a lysin that specifically targets staph, but they always ran into the same problem.

Although hundreds of thousands of lysins could be expressed in an engineered cell, they all would stick together forming an insoluble clump, rendering them inactive. "They were useless; a real thorn in our side," says Fischetti. "We've come across some problems cloning lysins for other bacteria, such as strep, but nothing to this extent."

Lysins, proteins derived from the viruses that have been infecting bacteria for billions of years, have two basic components. One acts as a recognition system to identify the specific bacteria species it has evolved to target; the other works like a molecular power drill that bores holes through the bacterium's cell wall, killing the organism. Together, these two components work so quickly and so efficiently that bacteria have no time to develop resistance.

Read the full article here

H1N1 Swine Flu: A Serving UK Soldier dies after contracting the virus

A serving UK soldier has been revealed as the latest patient to die after contracting H1N1, swine flu virus.
Bombardier Lee Porter, from Coleraine in Northern Ireland, died last week, two weeks after contracting the bug - it is reported that he had underlying health problems.

The 30-year-old member of the Royal Artillery is thought to be the first UK serviceman to have fallen victim to the bug.

According to the announcement, Bombardier Porter died on Friday at Frimley Park hospital in Surrey, making him the 28th person known to have died after getting swine flu in England.

A spokesman for the Ministry of Defence said: "It is with great sadness that the MoD must confirm the death of Bombardier Lee Porter, who contracted Swine Flu two weeks ago, which complicated existing health problems. Our thoughts go out to his family, who were at his bedside at the time."

110,000 New Cases
The latest figures on swine flu show that cases of the virus "may have plateaued", according to the Government. Their data, released today, showed that there were 110,000 new cases in England last week.

That represents a 10 per cent rise on the 100,000 new cases estimated in the previous weeks. Twenty seven people in England have died from swine flu, while 793 patients are being treated in hospital, that figure is down on the 840 of last week.

UK Schoolgirl on Life-Support
A British schoolgirl being treated in Greece for swine flu is on a life support machine but is showing signs of improvement and is said to be 'a little better.'

Natasha Newman, 16, from Highgate, north London, is in an Athens hospital after falling ill on the island of Cephalonia. Doctors at the intensive care unit of Penteli Children's Hospital described her condition as 'serious but stable.'

Pneumonia
One doctor, who did not wish to be named, said: "She has better lung function than yesterday and the day before. She has pneumonia, which is not something easy, but she has no lasting damage to her lungs and she is not in a dangerous condition."

H1N! Swine Flu: Second man dies of Pneumonic Plague in China

pa.press.net

A second man has died of pneumonic plague in northwest China. The outbreak prompted authorities to seal off an entire town where about a dozen people are infected with the highly contagious deadly lung disease, a state news agency said.

The man who died on Sunday was identified only as 37-year-old Danzin from Ziketan, the stricken town in Qinghai province, the official Xinhua News Agency said.

Relatives Infected
Danzin was a neighbour of the first person who died, a 32-year-old herdsman whose name was not given. Another 10 people, mostly relatives of the first deceased man, are infected and undergoing isolated treatment in hospital, Xinhua said.

Town Quarantined
The town of 10,000 people has been placed under quarantine and a team of experts is being sent to the area, it said.

The local health bureau warned that anyone with a cough or fever who has visited the town since mid-July should seek treatment at a hospital.

Pneumonic Plague
Pneumonic plague is spread through the air and can be passed from person to person through coughing, according to the World Health Organisation (WHO). It is caused by the same bacteria that occurs in bubonic plague - the Black Death that killed an estimated 25 million people in Europe during the Middle Ages.

Bubonic Plague
While bubonic plague - which is usually transmitted by flea bite - can be treated with antibiotics if diagnosed early, pneumonic plague is one of the deadliest infectious diseases. According to the WHO, humans can die within 24 hours of infection.