Why Hair Turns Gray Is No Longer A Gray Area: Our Hair Bleaches Itself As We Grow Older

Going gray is caused by a massive build up of hydrogen peroxide due to wear and tear of our hair follicles. The peroxide winds up blocking the normal synthesis of melanin, our hair's natural pigment.

"Not only blondes change their hair color with hydrogen peroxide," said Gerald Weissmann, MD, Editor-in-Chief of The FASEB Journal. "All of our hair cells make a tiny bit of hydrogen peroxide, but as we get older, this little bit becomes a lot. We bleach our hair pigment from within, and our hair turns gray and then white. This research, however, is an important first step to get at the root of the problem, so to speak."

The researchers made this discovery by examining cell cultures of human hair follicles. They found that the build up of hydrogen peroxide was caused by a reduction of an enzyme that breaks up hydrogen peroxide into water and oxygen (catalase). They also discovered that hair follicles could not repair the damage caused by the hydrogen peroxide because of low levels of enzymes that normally serve this function (MSR A and B). Further complicating matters, the high levels of hydrogen peroxide and low levels of MSR A and B, disrupt the formation of an enzyme (tyrosinase) that leads to the production of melanin in hair follicles. Melanin is the pigment responsible for hair color, skin color, and eye color. The researchers speculate that a similar breakdown in the skin could be the root cause of vitiligo.

"As any blue-haired lady will attest, sometimes hair dyes don't quite work as anticipated," Weissmann added. "This study is a prime example of how basic research in biology can benefit us in ways never imagined."

New Test May Help To Ensure That Dengue Vaccines Do No Harm

As vaccines against a virus that infects 100 million people annually reach late-stage clinical trials this year, researchers have developed a test to better predict whether a given vaccine candidate should protect patients from the infection, or in some cases, make it more dangerous, according to an article just published in the journal Clinical and Vaccine Immunology.

Cases of tropical, mosquito-borne dengue fever have expanding globally for more than 50 years, with nearly a third of the human population in 100 countries now at risk of infection with the four types of dengue virus. Infection with the dengue flavivirus, which is related to West Nile Virus and Yellow Fever, results in an estimated 500,000 hospitalizations and 22,000 deaths, mostly among infants, each year, according to the World Health Organization. After decades of absence in the United States, experts say the disease is causing illness again along the Texas-Mexico border, and that widespread dengue infection in the continental United States is a real possibility.

A typical dengue infection confines a patient to bed for more than a week with fever and severe limb pains, but most recover. In less than five percent of cases, however, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), often deadly complications, develop just as the fever breaks. Mostly affecting babies between five and eight months of age, DHF causes victims to vomit and pass blood in their feces and urine. If diagnosed quickly, patients respond to intensive hospital treatment and fluids, but mortality can reach 15 percent when undiagnosed. DSS comes when the infection has caused so much fluid to leak out of capillaries that there is not enough blood to supply organs. As of 2008, there were no antiviral drugs designed to treat dengue and no drug candidates in late-stage development.

"Aggressive health education and mosquito abatement programs have saved lives, but hopes for a true solution lie with vaccine design," said Xia Jin, M.D., Ph.D., associate professor in the Department of Medicine, Division of Infectious Diseases, at the University of Rochester Medical Center. "Our study shows that the new test is likely superior to the standard test in its ability to tell whether a patient's response to a vaccine is safe," said Jin, an author for the CVI paper.

Second Time Deadly

Most people, upon first exposure to any dengue virus, develop an immune response that protects them against that version of the virus for life. Unfortunately, the dengue virus, in its ancient relationship with humans, has evolved into four related but independent classes of virus called serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). The frightening aspect of the disease comes with a person's second dengue infection with one of the other three dengue serotypes, which may place them at much greater risk for bleeding and shock.

In cases where simple dengue fever progresses to DHS, patients have about 100 times as much virus in their blood as seen in a mild infection. What makes the virus so much better at penetrating human cells and reproducing the second time around? Decades of research are just now providing the answer, which lies within the intricacies of the immune system designed to recognize and destroy invading organisms.

As patients attempt to fight off a dengue infection, their immune systems activate antibodies, immune proteins that lock onto certain identifying pieces of the virus to form antibody-virus complexes that flag the virus for destruction. Humans produce a vast variety of antibodies, each with a unique "business end" shaped to recognize one specific viral protein, which enables the system to react to most invaders encountered. Ideally, an infected patient produces a large amount of the type of antibody that binds most strongly to the virus and that covers the greatest amount of the viral surface area to "neutralize" the virus (takes away its ability to reproduce).

Complicating matters is a second feature of antibodies, one which is the same across all antibodies: the crystalizable fragment (Fc). The Fc is designed to bind to proteins called the Fc receptors on the surfaces of macrophages, immune cells that roam the bloodstream seeking to engulf and "dissolve" viruses and bacteria. Coated with Fc receptors, macrophages constantly stick to the Fc end of antibodies, which brings whatever the antibody has locked onto into close contact with the cells capable of destroying it. In most people infected with their first dengue serotype, antibodies bind tightly to the viral surface and escort the virus via the Fc/Fc receptor link to macrophages where the virus is destroyed. The immune system then stores away a few of the successful antibodies in case that same virus is ever encountered again. When the system encounters a second dengue serotype, however, the antibodies from the first infection do not attach as securely to the new version in many cases, enabling the virus to break away from its antibody partner and begin copying itself. In this scenario, the antibody's Fc/Fc receptor interaction has served only to deliver the virus into cells that it could not otherwise penetrate.

The latter phenomenon, called antibody-dependent enhancement (ADE), has delayed the development of dengue vaccines for decades. The threat of enhancement dictates that any dengue vaccine must raise protective immunity against all four dengue serotypes simultaneously and equally, and several vaccine candidates have generated unequal responses across serotypes. That creates the possibility that some of the antibodies created by such vaccines could raise the risk for hemorrhagic fever and shock, and calls for the development of tests that can precisely measure enhancement risk.

Different versions of dengue move around the globe, sometimes displacing each other. Asian serotype DENV-2 strains, for example, have been taking the place of relatively more benign American DENV-2. One important example of this was seen in 1981, when Asian DENV-2 struck Cuba with nearly 900 people hospitalized following an uneventful DENV-1 outbreak four years earlier. While the Cuba outbreak followed the standard pattern, with a spike in serious cases accompanying a second infection, another outbreak, in Iquitos, Peru, in 1995, was unusual. In an area infected with DENV-1 four years previously, the second infection in 1995 with DENV-2 outbreak did not cause fatal complications. The reasons why one DENV 2 strain caused fatal second infections, and another did not, remained a mystery for years.

The current study may have helped solve the mystery, while pointing out a weakness of the standard test of antibody responses. The assay used originally to analyze the blood of patients in Iquitos was the plaque-reduction neutralization test (PRNT), the recognized gold standard for determining how effectively the human immune system responds to dengue infection. PRNT starts with a sheet of cells chosen because they can be invaded by the virus, and because they share some qualities with the kind of cell targeted by the virus in the body, the macrophage.

When the viral strain being studied is introduced to this cell culture, it begins invading and killing the cells, and making copies of itself. By diluting these mixtures, scientists can identify and count "islands" (or plaques) in the culture where the virus has destroyed cells.

When serum (which contains antibodies) from an infected patient's blood is added to this mix, the number of spots over time reveals the degree to which the patient's antibodies can effectively neutralize the virus. In the case of dengue research, PRNT tests are used to measure how efficiently the antibodies from a natural infection protect the cultured cells from the experimental infection with a second dengue serotype.

According to past experiments on the standard PRNT test, it took on average about seven times as many antibodies created by DENV-1 infection to neutralize Asian DENV-2 vs. American DENV-2. Jin and colleagues added an important element to the PRNT test, and then retested the Iquitos samples. The new, more sensitive test found that it took up to 100 times as many DENV-1 antibodies to neutralize the Asian DENV-2 virus as it did to the American DENV-2 infection. The results suggest that, in the harmless Iquitos outbreak, the second dengue serotype to hit the region was the American version of DENV-2, was cross-neutralized with relative ease by antibodies created by the first infection. In Cuba, however, the people were unfortunate to be hit by the Asian DENV-2 upon second infection, which their antibodies from DENV-1 infection could not shut it down, and only helped to deliver the virus into their cells. By magnifying the differences in the ability of an antibody for a given dengue serotype to neutralize other serotypes, researchers believe the new test will capture enhancement that the older test misses.

To construct the new test of cross-neutralization, researchers took CV-1 fibroblast cells, which share some traits with macrophages, and genetically engineered them to include a gene that directs for the building of an FC receptor on their surfaces. They also constructed a CV-1 cell line for culture without Fc receptors for use as a control group that resembles standard PRNT cultures used in the past. Both sets of cultures were then subjected the blood taken from patients in the 1995 Peru outbreak, and the new test captured for the first time the contribution of antibodies to more severe disease via fc/fc receptor delivery of virus to target cells.

Along with Jin, the work in Rochester was led by corresponding author Jacob Schlesinger, M.D., and Robert Rose, Ph.D., as well as by graduate student W. W. Shanaka I. Rodrigo, who conducted the genetic engineering experiments on CV-1 cells. Also contributing in Rochester were Danielle Alcena and Zhihua Kou. Tadeusz Kochel contributed from at the Naval Medical Research Center Detachment, Lima, Peru, as did Kevin Porter at the US Naval Medical Research Center, Silver Spring, Maryland. Guillermo Comach led a team as well at the Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales in Maracay Estado Aragua, Venezuela.

"Beyond the Peruvian case, our test promises to have a profound effect on the design of vaccines because we can take the antibodies generated by two different candidate vaccines, and better compare which strongly neutralizes virus without threat of enhancement across all four serotypes," Jin said. "With experimental vaccines from companies like GlaxoSmithKline and Sanofi Aventis entering Phase II and Phase III clinical trials this year, we hope the new test will be adopted widely and soon because it is more likely to catch enhancement."

Stem Cells From Skin Cells Can Make Beating Heart Muscle Cells

In a study published online Feb. 12 in Circulation Research, UW-Madison School of Medicine and Public Health professor of medicine Tim Kamp and his research team showed that they were able to grow working heart-muscle cells (cardiomyocytes) from induced pluripotent stem cells, known as iPS cells.

The heart cells were originally reprogrammed from human skin cells by James Thomson and Junying Yu, two of Kamp's co-authors on the study.

"It's an encouraging result because it shows that those cells will be useful for research and may someday be useful in therapy,'' said Kamp, who is also a cardiologist with UW Health. "If you have a heart failure patient who is in dire straits — and there are never enough donor hearts for transplantation — we may be able to make heart cells from the patient's skin cells, and use them to repair heart muscle. That's pretty exciting."

It's also a few more discoveries away. The researchers used a virus to insert four transcription factors into the genes of the skin cell, reprogramming it back to an embryo-like state. Because the virus is taken up by the new cell, there is a possibility it eventually could cause cancer, so therapies from reprogrammed skin cells will likely have to wait until new methods are perfected.
Still, the iPS cardiomyocytes should prove immediately useful for research. And Kamp said the speed at which knowledge is progressing is very encouraging.

Jianhua Zhang, lead author on the study, noted that it took 17 years, from when a mouse embryonic stem cells were first created in 1981, to 1998, when Thomson created the first human embryonic stem cells. In contrast, the first mouse iPS stem cells were created in 2006, and Thomson and Yu published their paper in November 2007, announcing the creation of human iPS stem cells that began as a skin cells.

While research on embryonic stem cells is controversial, because it destroys a human embryo, lessons learned through such research apply to current work with iPS cells made from adult cells.

"That's one of the important things that have come out of the research with embryonic stem cells, it taught us how human pluripotent stem cells behave and how to work with them,'' Kamp says. "Things are able to progress much more quickly thanks to all the research already done with embryonic stem cells."

Many types of heart disease have known genetic causes, so creating cardiomyocytes grown from patients who have those diseases will likely be some of the next steps in the research. One of Kamp's colleagues, Clive Svendsen, a UW-Madison School of Medicine and Public Health professor of neurology and anatomy, has grown the iPS cells into disease-specific neural cells. Kamp and Svendsen are also on the faculty of the Waisman Center and the Stem Cell and Regenerative Medicine Center.

Kamp's latest research, proving that iPS cells can become functional heart cells, is just one step along the way to better understanding and treatment of disease.
"We're excited about it, because it's the some of the first research to show it can be done, but in the future, we'll probably say, 'Well, of course it can be done,'" he says. "But you don't know until you do it. It's a very mysterious and complicated dance to get these cells to go from skin cells to stem cells to heart cells."

Wrinkles Removed With Protein RHAMM

Hollywood stars of a certain age take note: Research at Berkeley Lab suggests that a protein linked to the spread of several major human cancers may also hold great potential for the elimination of wrinkles and the rejuvenation of the skin. If this promise bears fruit, controlling concentrations of the RHAMM protein could one day replace surgical procedures or injections with neurotoxins that carry such unpleasant side-effects as muscle paralysis and loss of facial expressions.

RHAMM stands for Receptor for Hyaluronan Mediated Motility. Mina Bissell, a cell biologist with Berkeley Lab’s Life Sciences Division and a leading authority on breast cancer, was collaborating with Eva Turley, an oncology professor at the University of Western Ontario and leading authority on tissue polysaccharides, on a study of the role that RHAMM plays in regulating the signaling of adipocytes (fat cells) during the repairing of tissue wounds from injuries such as skin cuts, heart attacks and stroke. Earlier research by Turley, who discovered RHAMM, had shown that over-expression of this protein points to a poor patient outcome for such human cancers as breast, colon, rectal and stomach.

In the course of their collaborative study, Bissell and Turley, working with mice, discovered that blocking the expression of the RHAMM protein - either by deleting its gene, or through the introduction of a blocking reagent - can be used to selectively induce the generation of fat cells to replace those lost in the aging process. At the same time blocking RHAMM expression also reduces deposits of unhealthy visceral fat.

“This technique could be developed as a means of providing a non-surgical approach for normalizing skin appearance after reconstructive surgery, for wrinkle reduction, and for face lifts and figure enhancement,” said Bissell.

Said Turley, “Unlike neurotoxin agents, which have to be injected periodically, a localized injection of a RHAMM inhibitor should produce long-lasting skin volumizing effects and would not involve muscle paralysis, which means there would be no loss of expression if it were to be injected into the face.”

There are compounds now on the market that promote the production of adipocyte cells and result in increased subcutaneous fat, however, these adipocyte-promoting factors also increase the production of visceral fat. The mouse studies led by Bissell and Turley have shown that blocking RHAMM expression significantly increases subcutaneous fat while decreasing visceral fat. This suggests that blocking RHAMM should also have a beneficial effect on patients with obesity-related diseases, cardiovascular disease or diabetes. Another unique advantage of RHAMM is that its expression in normal adult human tissues is restricted.

“Therefore, anti-RHAMM agents should have low toxicity and according to preliminary animal studies, could be beneficial to patients with a tumor or inflammation-related disease,” said Turley.

Potential applications of RHAMM modulation in addition to wrinkle reduction include normalizing skin appearance after reconstructive or cosmetic surgery, e.g., grafted tissue on burn victims. It has also been shown to have a beneficial effect on tumors and inflammatory diseases in mice.

Alzheimer's Prevented And Reversed With Natural Protein In Animal Models

Memory loss, cognitive impairment, brain cell degeneration and cell death were prevented or reversed in several animal models after treatment with a naturally occurring protein called brain-derived neurotrophic factor (BDNF). The study by a University of California, San Diego-led team – published in the February 8, 2009 issue of Nature Medicine – shows that BDNF treatment can potentially provide long-lasting protection by slowing, or even stopping the progression of Alzheimer's disease in animal models.

"The effects of BDNF were potent," said Mark Tuszynski, MD, PhD, professor of neurosciences at the UC San Diego School of Medicine and neurologist at the Veterans Affairs San Diego Health System. "When we administered BDNF to memory circuits in the brain, we directly stimulated their activity and prevented cell death from the underlying disease."

BDNF is normally produced throughout life in the entorhinal cortex, a portion of the brain that supports memory. Its production decreases in the presence of Alzheimer's disease. For these experiments, the researchers injected the BDNF gene or protein in a series of cell culture and animal models, including transgenic mouse models of Alzheimer's disease; aged rats; rats with induced damage to the entorhinal cortex; aged rhesus monkeys, and monkeys with entorhinal cortex damage.

In each case, when compared with control groups not treated with BDNF, the treated animals demonstrated significant improvement in the performance of a variety of learning and memory tests. Notably, the brains of the treated animals also exhibited restored BDNF gene expression, enhanced cell size, improved cell signaling, and activation of function in neurons that would otherwise have degenerated, compared to untreated animals. These benefits extended to the degenerating hippocampus where short-term memory is processed, one of the first regions of the brain to suffer damage in Alzheimer's disease.

The demonstration of the effectiveness and safety of BDNF administration in animals provides "a rationale for exploring clinical translation" to humans, the team concludes, suggesting that the protective and restorative effects of BDNF on damaged neurons and neuronal signaling may offer a new approach to treating Alzheimer's disease.

This work builds on previous studies by Tuszynski and others, demonstrating the therapeutic affects of nerve growth factor (NGF) administered to patients with Alzheimer's disease. In 2001, Tuszynski and his team at UC San Diego Medical Center performed the first surgical implants of NGF genes into the brains of Alzheimer's patients, with follow-up results showing these patients experienced a possible slowing in cognitive decline and increased metabolic function in the brain. The NGF studies continue today, with Phase 2, multi-center studies currently underway.

"NGF therapy aims to stimulate the function of specific cholinergic neurons, which are like the air traffic controllers of the brain, helping to direct the activities of cells in broad regions of the brain," Tuszynski explained. However, he added that the benefits of NGF therapy, if validated in ongoing trials, will not be curative. Eventually, the effect of the NGF "boost" will be countered by the widespread death of neurons in the cerebral cortex as a result of advancing Alzheimer's disease.

"In contrast, BDNF acts directly on dying cells in specific memory circuits of the brain," Tuszynski said. "In this series of studies, we have shown that BDNF targets the cortical cells themselves, preventing their death, stimulating their function, and improving learning and memory. Thus, BDNF treatment can potentially provide long-lasting protection by slowing, or even stopping disease progression in the cortical regions that receive treatment."

The protective and restorative effects of BDNF occurred independently of the build-up of amyloid, a protein that accumulates in the brain to form plaques in Alzheimer's disease. Many current experimental treatments for Alzheimer's disease target amyloid production, so the potential role of BDNF as an alternative protective intervention is of great potential interest, said Tuszynski. Because BDNF targets a different set of disease mechanisms than amyloid modulation, there is also potential to combine BDNF and amyloid-based treatments, theoretically providing a two-pronged attack on the disease.

The study was supported by the National Institutes of Health, the California Regional Primate Research Center, the Veterans Administration, the Alzheimer's Association, the State of California, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and the Shiley Family Foundation. Tuszynski is scientific founder of Trophin Therapeutics, a company that may potentially benefit from the research results.

Study co-authors are Alan H. Nagahura, David A. Merrill, Shingo Tsukada, Brock E. Schroeder, Gideon M. Shaked, Ling Want, Armin Blesch, James M. Conner, Edward Rockenstein, Edward H. Koo, and Eliezer Masliah of the UC San Diego Department of Neurosciences, and Andrea A. Chiba of the UC San Diego Departments of Neurosciences and Cognitive Science. Giovanni Coppola and Daniel Geschwind of the Program in Neurogenetics, Department of Neurology at UCLA, and Albert Kim and Moses V. Chao, Skirball Institute of Biomolecular Medicine at New York University School of Medicine.

Breakthrough To Treat Malaria: Scientists Deactivate Malaria Parasite's Digestive Machinery

The research, performed in collaboration with Professor John Dalton at the University of Technology, Sydney, provides a new approach to treating and controlling the disease that is contracted by half a billion people and causes around 1 million deaths a year.

The team, based at the Monash University ARC Centre of Excellence in Structural and Functional Microbial Genomics, has been able to deactivate the final stage of the malaria parasite's digestive machinery, effectively starving the parasite of nutrients and disabling its survival mechanism. This process of starvation leads to the death of the parasite.

Professor Whisstock said the results had laid the scientific groundwork to further develop a specific class of drugs to treat the disease.
"About forty percent of the world's population are at risk of contracting malaria. It is only early days but this discovery could one day provide treatment for some of those 2.5 billion people across the globe," Professor Whisstock said.

"Drug-resistant malaria is an ever increasing problem, meaning that there is an urgent requirement to develop new therapeutic strategies."
Researchers used the Australian Synchrotron, located adjacent to Monash University's Clayton campus. The results are published today in the prestigious Proceedings of the National Academy of Sciences U.S.A.

Lead author of the research paper, Dr Sheena McGowan, from the Monash University NHMRC program on protease systems biology said their findings prove their concept.
"We had an idea as to how malaria could be starved and we have shown this, chemically, can be done," Dr McGowan said.

"A single bite from an infected mosquito can transfer the malaria parasite into a human's blood stream. The malaria parasite must then break down blood proteins in order to obtain nutrients. Malaria carries out the first stages of digestion inside a specialised compartment called the digestive vacuole – this can be considered to be like a stomach. However, the enzyme we have studied (known as PfA-M1), which is essential for parasite viability, is located outside the digestive vacuole meaning that it is easier to target from a drug perspective."

This breakthrough is in addition to existing malaria drug discovery research advances at Monash University. A new drug candidate which aims to provide a single dose cure, discovered by a major international project involving the Monash Institute of Pharmaceutical Sciences, is currently progressing to first human studies with support from the Medicines for Malaria

Venture, Geneva, Switzerland.

World faces threat from deadly diseases as scientists struggle to keep up

The world is facing deadly threat on the scale of Aids, Sars and Ebola within a decade, the world's leading authority on health said , as it warned that diseases were spreading more quickly than at any time in history.

(An electron micrograph showing the bird influenza virus strain H5N1)

New diseases are emerging at an unprecedented rate, of one a year, and are becoming more difficult to treat, says the World Health

Organisation's annual report. It paints a bleak picture of future health threats, with science struggling to keep up as diseases increasingly become drug resistant.

The authors point to passenger flights, now numbering more than 2bn a year, as being a chillingly efficient mechanism for spreading diseases rapidly across continents. New diseases that pose a sudden threat in one part of the world are only "a few hours away" from becoming a threat somewhere else, the WHO says.

"Profound changes have occurred in the way humanity inhabits the planet," said Margaret Chan, the director general of the WHO. "The disease situation is anything but stable. Population growth, incursion into previously uninhabited areas, rapid urbanisation, intensive farming practices, environmental degradation, and the misuse of anti-microbials, have disrupted the equilibrium of the microbial world. The rate of emergence of new diseases, at one year, was "historically unprecedented".

The report, A Safer Future, identifies 40 diseases unknown a generation ago, and reveals that during the past five years the WHO has verified more than 1,100 epidemic events worldwide. It says:

· Cholera, yellow fever and epidemic meningococcal diseases made a comeback in the last quarter of the 20th century.

· Severe acute respiratory syndrome and avian influenza in humans still have the potential to wreak havoc globally.

· Viral diseases such as Ebola, Marburg haemorrhagic fever and Nipah virus, pose threats to global public health security.

· The use of smallpox in bioterrorism is a particularly worrying threat. Authorities around the world should work together to combat the kind of bioterrorism that occurred with the letters warning of anthrax after September 11 2001.

· A flu pandemic would affect more than 1.5 billion people, or 25% of the world's population. Even if the disease were mild in itself the economic and social disruption would be "enormous".

The WHO report adds: "It would be extremely naive and complacent to assume that there will not be another disease like Aids, another Ebola, or another Sars, sooner or later."

To prepare for these events will take unprecedented global and political collaboration, it advises. "No single country, however capable, wealthy or technologically advanced, can alone prevent, detect and respond to all public health threats." The organisation is calling for renewed international efforts to share information.

The UK's Department of Health said it strongly supported "the approach of managing these risks through cooperation".

Worries about the effects of international travel were underscored in June when an American national, Andrew Speaker, 31, who had a contagious and deadly strain of tuberculosis, took an international flight. US authorities tracked every passenger who had shared one of two transatlantic flights with Mr Speaker, who had fallen ill with the drug-resistant XDR form of TB while on honeymoon in Europe. He went back home via Montreal to avoid the US authorities, who had ordered him into quarantine, and would not have allowed him to fly, he believed.

In South Africa, the courts have considered forcibly detaining people who have the same form of TB to prevent its spread, amid fears that many more than those officially diagnosed are suffering and have not informed the authorities. The XDR strain of TB is a highly infectious disease spread by airborne droplets and kills 98% of those infected within about two weeks. Experts believe it emerged after inappropriate and overuse of antibiotics to treat TB.