Totally drug-resistant TB emerges in India

Discovery of a deadly form of TB highlights crisis of 'mismanagement'.

Physicians in India have identified a form of incurable tuberculosis there, raising further concerns over increasing drug resistance to the disease¹. Although reports call this latest form a “new entity”, researchers suggest that it is instead another development in a long-standing problem.

The discovery makes India the third country in which a completely drug-resistant form of the disease has emerged, following cases documented in Italy in 2007² and Iran in 2009³.

However, data on the disease, dubbed totally drug-resistant tuberculosis (TDR-TB), are sparse, and official accounts may not provide an adequate indication of its prevalence. Giovanni Migliori, director of the World Health Organization (WHO) Collaborating Centre for Tuberculosis and Lung Diseases in Tradate, Italy, suggests that TDR-TB is a deadlier iteration of the highly resistant forms of TB that have been increasingly reported over the past decade. “Totally resistant TB is not new at all,” he says.

Since the 1960s, two drugs — isoniazid and rifampicin — have been the standard TB treatment. Although episodes of resistance cropped up periodically, during the 1990s the incidence of multiple drug resistance grew significantly, leading researchers in 2006 to refer to it as extensively drug-resistant tuberculosis (XDR-TB). Surveillance data from the WHO indicate that XDR-TB is present in at least in 58 countries, with an estimated 25,000 cases occurring each year.

Epidemiologist Carole Mitnick of Harvard Medical School in Boston, Massachusetts, agrees that TDR-TB is not new, and points to the history of XDR-TB. “When XDR-TB was first named, it was a phenomenon that had existed but hadn’t gotten much attention before. TB in general doesn’t receive a lot of attention,” she says.

Inadequate care

Part of the increase in drug resistance is related to complications that arise in treating patients who are also infected with HIV — 13% of TB cases, according to the WHO. However, the greatest part of the problem results from the management of the disease.

Although the WHO describes TB as a “disease of poverty”, drug-resistant varieties might best be understood as resulting from poor treatment. According to a 2011 WHO report, fewer than 5% of newly diagnosed or previously treated patients are tested for drug resistance. And it is estimated that just 16% of patients with drug-resistant TB are receiving appropriate treatment.

“The cases are a story of mismanagement,” says Migliori. “Resistance is man-made, caused by exposure to the wrong treatment, the wrong regimen, the wrong treatment duration.”

In the management of TB, many factors affect whether the disease is cured or becomes resistant to treatment. Drug misuse or mismanagement can result if a patient does not follow a full course of treatment, or if the correct drugs are not available or patients with undiagnosed resistant TB receive inappropriate therapies.

Part of the problem also relates to TB testing. The WHO recommends sputum smear microscopy, a test developed more than one hundred years ago, as the standard diagnosis. Although inexpensive, this method is prone to false negatives, does not provide information on drug susceptibility, and test results can take several weeks — a large window of time for a patient to potentially receive the wrong drugs or transmit the infection. However in 2010, the WHO approved a new rapid and fully automated test, known as Xpert, which assesses resistance to the first-line drug rifampicin. As of July 2011, 26 countries are using Xpert and 145 are eligible to purchase kits at a reduced price.

Drug dearth

The fact that no new first-line TB drugs have been developed for half a century has probably contributed to the emergence of strains that are unresponsive to treatment, says Mitnick. “If you keep using the same drugs for that long, resistance is inevitable.”

Tuberculosis trails behind only HIV as the world’s leading cause of death from infectious disease. But in spite of its impact on human health and economic growth, it has not ranked among the pharmaceutical industry's priorities.

“The pharmaceutical industry had scant interest in TB for decades,” says Richard Chaisson, director of the Center for TB Research at the Johns Hopkins School of Public Health in Baltimore, Maryland. “The industry pretty much concluded it wasn’t an attractive market, there was not enough potential profit.”

But with a growing number of public–private partnerships in research, Chaisson says, industry interest is “an order of magnitude greater than it was a decade ago”.

As of 2011, there were 10 new or repurposed TB drugs in clinical trials that have the potential to either shorten treatment duration or improve therapy for resistant TB. Late-stage studies include a phase III trial by Bayer to assess whether its antibiotic moxifloxacin can help to reduce the duration of standard therapy from 6 months to 2. And both Tibotec and Novartis are in phase II trials for products that may be useful in treating drug-resistant forms.

Nature

 

doi:10.1038/nature.2012.9797

DNA Hackers

DNA Hackers: Synthetic biology weaponized virus, zero-day exploit to infect your brain?

From the let's get futuristically freaky department, future hacking crimes could take a decidedly sinister twist; not hacking to breach systems but brains, bodies and behaviors. This DNA hacking goes way beyond potentially using police bees to bust biohackers, or even storing unhackable data in box of bio-encrypted bacteria. It's not science fiction to hack insulin pumps or to use jamming signals to stop hackers from lethal pacemaker attacks, but now bioengineers and security futurists are warning that the day is coming when criminals and bioterrorists hunt for vulnerabilities that will give a new meaning to zero-day exploits. In the future, a weaponized virus will aim to infect you, your brain and body biology, and not just your computer or mobile device.

While some people resist the idea of needing antivirus or other security software defenses for their smartphones, in the world of synthetic biology, a world where bits, bytes, atoms and biology mix dreams with nightmare realities, it could be lethal to lag behind in patching potential vulnerabilities. Some day, when you hear about something going 'viral,' it will not apply to an idea or video but to a DNA hack going viral to infect the masses. When a computer is infected with malware or a virus, you can reformat a hard drive, but will a future security scenario include needing to worry about BSOD and reformatting your brain?

Just as you can personalize your computer and mobile devices, advances in synthetic biology are allowing DNA hackers to personalize biology so that we will be able to use a DNA printer that will allow us "to print out our own treatments." Think of it as a patch you need to close a vulnerability on a system. In this case, you would download it, print it, and swallow the "cure." You will be able to search for a flu or cold vaccine and then print out the genetic designs or download the "cure" via a smartphone app, reported Genomeweb. Cures for horrific diseases could spread quickly through social media, but with all good so too comes the bad. Just as a tainted app, poisoned link, phishing email, or malicious drive-by-download can target individuals to infect computers for espionage or cybercrime, computer-designed viruses like biologically engineered biotoxins could target groups to try to wipe them out.

Bioengineer Andrew Hessel, co-chair of Biotechnology at Singularity University, has talked extensively about the Internet of Living Things and how synthetic biology will be the next big IT industry. Hessel likes to play with molecules, DNA and computers, and explained "synthetic biology as computer-assisted genetic design will go 'from an idea to printing DNA to ultimately booting DNA'." SmartPlanet reported, "Mobile phones equipped with genome decoders are coming. DIY fabricators that work with cells are already here...The cost barriers around genetic engineering are, in fact, falling, and what are essentially life-form design tools are increasingly accessible."

When Aldith Hunkar interviewed Hessel at TEDx Amsterdam, Hessel said the barriers to engineering bacteria, viruses and much higher forms of life are falling away to create a "parallel biology, one that is moving at about 100 million years of evolutionary time for every calendar year." Synthetic biology "will grow faster than some computer technology" and then almost anyone can play God; the stuff of dreams and nightmares will become real. Hessel looks at cells as computers and viruses as software. To describe his biggest synthetic biology nightmare, he said, "When I look at the world of computing today, I see all of these hacks, all of these little exploits, whether it's spam or whether it's literally hacking into different systems and manipulating them in different ways. And I see the potential for biology to be used in very similar ways."

At Techonomy 2011, Hessel discussed the emerging field of synthetic biology and bioengineering. He said in this video that the engineering of life is like software engineering and computer-assisted genetic design will give us the ability to make viruses and vaccines. He asked, "What happens when we can make a vaccine as easily as we can make a tweet?"

Hessel explained that living systems can be programmed with new functions to do commercially or intellectually useful tasks. That could be great, so long as the people who are creating the bacteria are not out to wreak havoc. At TedXm, Hessel said our bodies have a relationship with bacteria which is constantly sending chemicals into our brains. However an evil bacteria or virus has no borders and hypothetically there might be a bacteria that strikes like a drive-by-download, made to appear like an innocent or helpful cure which we might print out on a DNA printer. But after we "ingest" it into our systems, it might trigger chemicals in the brain that change behavior. The security landscape will change if we have "to learn how to counterattack" such weaponized viruses.

Now consider when we will have the ability to "boot DNA" in the same way as booting up a PC, but the data wirelessly transmits into us to perhaps keep us "healthy." Another scary example from Hessel was if two companies were business competitors and one company infected the other with a virus or bacteria that made the company employees lazy or unhappy. If viruses are like biological spam, we could be infected with bacteria that manipulates our behavior and we might not even know it's happening.

Synthetic biology, when tweaked by bioterrorists, could be used for exploitation and "not only to drive large-scale outbreaks. They will also be able to create targeted attacks against a single individual based on his or her own unique biology," reported The Washington Post. "We will need anti-virus software and defenses just as we have for computer software. But although we can reformat our hard disks to remove a computer virus, we can't reformat our genomes ... yet."

If DNA becomes the next big hacking frontier, it would open a plethora of "Pandora's Box problems." The Washington Post quoted security futurist Marc Goodman, the founder of Future Crimes:

Synthetic biology will lead to new forms of bioterrorism - opportunities for the bad guys to create never-before-seen forms of bio-toxins. These bio-threats might be nearly impossible to detect because they can be customized to the genome of a certain person or groups of people. Goodman, who has long worked on cyber crime and terrorism with organizations such as Interpol and the United Nations, believes the potential bio-threat is greatly underestimated. "Bio-crime today is akin to computer crime in the early 1980s. Few initially recognized the problem, but one need only observe how the threat grew exponentially over time."

The more I read about the topic, and the more synthetic biology videos I watched, the possibilities blew my mind. There would be so many ways to 'save the world' or to destroy it. It's a fictional story waiting to be written. I know people who can't even keep their computers protected, updated and patched . . . I wonder if they will be become more security-minded when the hacking could be literally lethal?

http://blogs.computerworld.com/19409/dna_hackers_synthetic_biology_weaponized_virus_0day_exploit_to_infect_your_brain?source=CTWNLE_nlt_networking_2011-12-14