New online tool to predict genetic resistance to tuberculosis drugs

Faster process to find appropriate drugs for TB patients may improve likelihood of cure

2015-05-27

(Press-News.org) Finding out what drugs can be used to treat a patient with tuberculosis (TB) can be can sped up by days or weeks, thanks to a new free online tool.

The new TB-Profiler tool, developed by a team of scientists led by Dr Taane Clark at the London School of Hygiene & Tropical Medicine, analyses and interprets genome sequence data to predict resistance to 11 drugs used for the treatment of TB. This rapid tool only takes a few minutes and means that sequence data can now be used without delay. Importantly, it also removes dependence on specialised bioinformatics skills that are not readily available in clinical settings. Data on how the tool works is published in open access journal Genome Medicine.

Speeding up the process to find appropriate drugs when treating a patient with drug-resistant TB improves the likelihood of cure. By enabling the optimum course of treatment to be selected without delay, toxic drugs found to be ineffective because of resistance can be disregarded, relieving patients of damaging, unpleasant, and often long-lasting side effects.

Researchers say the TB-Profiler tool - available at tbdr.lshtm.ac.uk - will aid control of drug resistant TB, the emergence of which currently threatens to derail global efforts to control the disease. The World Health Organisation estimates that 5% of the world's 11 million TB cases have multi drug-resistance disease (MDR-TB), with approximately 480,000 new MDR-TB cases arising in 2013 and 210,000 deaths.

The TB-Profiler was developed using global data and refers to a library of 1,325 mutations to M. tuberculosis (the bacteria that causes TB), making the tool the most comprehensive and accurate data source to date.

Dr Taane Clark, Reader in Genetic Epidemiology and Statistical Genomics, said: "Sequencing already assists patient management for a number of conditions such as HIV, but now that it is possible to sequence M. tuberculosis from sputum from suspected multi-drug resistance patients means it has a role in the management of tuberculosis. We have developed a prototype to guide treatment of patients with drug resistant disease, where personalised medicine and treatment offers improved rates of cure."

Traditional lab-based methods of determining resistance involve growing the bacteria to see if it survives the drug, a process that can take weeks and sometimes months, and requires stringent safety measures to protect the laboratory personnel.

The researchers highlight that their research demonstrates the potential of whole genome sequencing to increase the accuracy of molecular tests for resistance, with improved sensitivity and specificity. The tool also provides data on the genotype of the bacteria which can be used in epidemiological studies and by public health experts to track chains of disease transmission.

Co-author Dr Ruth McNerney of TB Alert added: "This is a welcome step forward in our battle against drug resistance. It is now time to take sequencing out of the research lab and into the clinic. Patients with drug resistant disease have to endure many months of treatment with toxic drugs with no guarantee of success. Personalised treatment will increase their chances of survival while minimising the horrible side effects."

INFORMATION:

For more information or to request interviews with Dr Taane Clarke please contact the press office at the London School of Hygiene & Tropical Medicine: press@lshtm.ac.uk or +44 (0)20 7927 2802. For interview with Dr Ruth McNerney: Ruth.Mcnerney@gmail.com or +44 (0)7557020305 or +27 (0)78358815 (South Africa)

Notes to Editors Francesc Coll, Ruth McNerney, Mark D Preston, José Afonso Guerra-Assunção, Andrew Warry, Grant Hill-Cawthorne, Kim Mallard, Mridul Nair, Anabela Miranda, Adriana Alves, João Perdigão, Miguel Viveiros, Isabel Portugal, Zahra Hasan, Rumina Hasan, Judith R Glynn, Nigel Martin, Arnab Pain, Taane G Clark. Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences. Genome Medicine. DOI: 10.1186/s13073-015-0164-0 http://genomemedicine.com/content/7/1/51

The emergence of TB that cannot be cured using the standard cocktail of four antibiotics is threatening to disrupt control of the disease on a global scale. The World Health Organisation estimates that 5% of the world's 11 million TB cases have multi drug-resistance disease (MDR-TB) and that 480,000 new cases arose during 2013 alone. Of those approximately 9% have extensively resistant tuberculosis (XDR-TB) where, in addition to resistance to at least both of the major first line drugs (isoniazid and rifampicin), they also have resistance to two classes of second line drugs used to treat MDR-TB (the fluoroquinolones and the injectable drugs, amikacin, kanamycin, or capreomycin). Further details: http://www.who.int/tb/publications/global_report/en/

It is a global problem as XDR-TB has been reported in at least 100 countries but the problem is most acute in Eastern Europe, the Russian Federation, South Africa and parts of India and China. Incurable TB, resistant to all the available drugs tested has been reported in several countries (including India, South Africa, Iran and Italy).

TB is an aerosol borne disease that spreads through the air. If not treated with effective drugs patients can remain infectious, coughing out the drug resistant bacteria until they die.

Treatment for patients with drug resistant tuberculosis is prolonged (years), expensive and outcomes are poor. The drugs used are toxic and poorly tolerated, adverse events are common and may be severe and irreversible. Common side effects include nausea, depression, liver damage, nerve damage and hearing loss.

Resistance is mainly caused by mutations in the genome of the bacteria that cause the disease, Mycobacterium tuberculosis. Mutations occur naturally in genes but are rare and usually of no significance but if patients have been exposed to sub-standard treatment instead of effective therapy with multiple drugs the mutated bacteria can survive and multiply and drug resistance emerges. Once resistant the bacteria can spread to other people and cause drug resistant disease.

The large number of drugs used to treat TB means that detecting the mutations that cause resistance is a complex business as there are many genes involved and hundreds of sites in the genome that need to be examined. Whole genome sequencing offers the most effective way of detecting resistance mutations but although the sequencing technologies have advanced rapidly and desk top analysers are now available for use in hospitals the vast amounts of data generated has previously needed analysis by expert bioinformaticians, a process that often delays results by weeks.

Whole genome sequencing of TB is used for managing patients with drug resistant TB in London. Further details: http://jcm.asm.org/content/early/2015/02/06/JCM.02993-14

About the London School of Hygiene & Tropical Medicine

The London School of Hygiene & Tropical Medicine is a world-leading centre for research and postgraduate education in public and global health, with 3,900 students and more than 1,000 staff working in over 100 countries. The School is one of the highest-rated research institutions in the UK, and among the world's leading schools in public and global health. Our mission is to improve health and health equity in the UK and worldwide; working in partnership to achieve excellence in public and global health research, education and translation of knowledge into policy and practice. http://www.lshtm.ac.uk

ELSE PRESS RELEASES FROM THIS DATE:

Zebrafish model gives new insight on autism spectrum disorder

2015-05-27

CORAL GABLES, Fla. (May 27, 2015) - Autism Spectrum Disorder (ASD) is a neurological condition that affects approximately two percent of people around the world. Although several genes have been linked to multiple concurring conditions of ASD, the process that explains how specific genetic variants lead to behaviors characteristic of the disorder remains elusive. Now, researchers are utilizing animal models to understand how dysfunction of either of two genes associated with ASD, SYNGAP1 and SHANK 3, contributes to risk in ASD. The new findings pinpoint the actual place ...

New electronic stent could provide feedback and therapy -- then dissolve

2015-05-27

Every year, an estimated half-million Americans undergo surgery to have a stent prop open a coronary artery narrowed by plaque. But sometimes the mesh tubes get clogged. Scientists report in the journal ACS Nano a new kind of multi-tasking stent that could minimize the risks associated with the procedure. It can sense blood flow and temperature, store and transmit the information for analysis and can be absorbed by the body after it finishes its job. Doctors have been implanting stents to unblock coronary arteries for 30 years. During that time, the devices have evolved ...

Tablets can help elderly cross the 'digital divide'

2015-05-27

One way to help the elderly cross what's known as the "digital divide" is the use of tablets, those smaller, lighter, easy-to-use computers that seem to be taking the place of laptops. New Michigan State University research has found that the use of tablets does make it easier, breaking down some of the barriers that keep seniors from getting connected. In addition to being smaller, lighter and more portable, tablets allow people to maneuver online without having to move and click a mouse. "The dexterity required to control a mouse is really hard for some older adults," ...

Discovery shows what the solar system looked like as a 'toddler'

2015-05-27

An international team of astronomers, including researchers from the University of Cambridge, has identified a young planetary system which may aid in understanding how our own solar system formed and developed billions of years ago. Using the Gemini Planet Imager (GPI) at the Gemini South telescope in Chile, the researchers identified a disc-shaped bright ring of dust around a star only slightly more massive than the sun, located 360 light years away in the Centaurus constellation. The disc is located between about 37 and 55 Astronomical Units (3.4 - 5.1 billion miles) ...

Expanding the code of life with new 'letters'

2015-05-27

The DNA encoding all life on Earth is made of four building blocks called nucleotides, commonly known as "letters," that line up in pairs and twist into a double helix. Now, two groups of scientists are reporting for the first time that two new nucleotides can do the same thing -- raising the possibility that entirely new proteins could be created for medical uses. Their two studies appear in ACS' Journal of the American Chemical Society. Synthetic biologists have been attempting for years to expand on nature's genetic "alphabet," consisting of the nucleotide bases cytosine, ...

Why Americans can't buy some of the best sunscreens

2015-05-27

With summer nearly here, U.S. consumers might think they have an abundance of sunscreen products to choose from. But across the Atlantic, Europeans will be slathering on formulations that manufacturers say provide better protection against the sun's damaging rays -- and skin cancer -- than what's available stateside, according to an article in Chemical & Engineering News (C&EN), the weekly newsmagazine of the American Chemical Society. Marc S. Reisch, a senior correspondent at C&EN, reports that sunscreens on the U.S. market do protect users from some ultraviolet-A and ...

Telemedicine exams result in antibiotics as often as regular exams, study finds

2015-05-27

Patients treated for an acute respiratory infection by a doctor on a telephone or live video are as likely to be prescribed an antibiotic as patients who are treated by a physician face-to-face for the same illness, according to a new RAND Corporation study. However, the patients treated virtually were more likely to be prescribed a broad-spectrum antibiotic -- concerning since overuse of the drugs increases costs and contributes to antibiotic resistance, according to the study. Researchers say both treatment settings had high rates of inappropriate prescribing for ...

Autism and rare childhood speech disorder often coincide

2015-05-27

Some children with autism should undergo ongoing screenings for apraxia, a rare neurological speech disorder, because the two conditions often go hand-in-hand, according to Penn State College of Medicine researchers. Over the course of a three-year study, 64 percent of children initially diagnosed with autism were found to also have apraxia. The study also showed that the commonly used Checklist for Autism Spectrum Disorder (CASD) accurately diagnoses autism in children with apraxia. "Children with apraxia have difficulty coordinating the use of their tongue, lips, ...

Experiment confirms quantum theory weirdness: ANU media release

2015-05-27

The bizarre nature of reality as laid out by quantum theory has survived another test, with scientists performing a famous experiment and proving that reality does not exist until it is measured. Physicists at The Australian National University (ANU) have conducted John Wheeler's delayed-choice thought experiment, which involves a moving object that is given the choice to act like a particle or a wave. Wheeler's experiment then asks - at which point does the object decide? Common sense says the object is either wave-like or particle-like, independent of how we measure ...

Physicists solve quantum tunneling mystery: ANU media release

2015-05-27

An international team of scientists studying ultrafast physics have solved a mystery of quantum mechanics, and found that quantum tunneling is an instantaneous process. The new theory could lead to faster and smaller electronic components, for which quantum tunneling is a significant factor. It will also lead to a better understanding of diverse areas such as electron microscopy, nuclear fusion and DNA mutations. "Timescales this short have never been explored before. It's an entirely new world," said one of the international team, Professor Anatoli Kheifets, from The ...

LAST 30 PRESS RELEASES:

Proactively screening diabetics for heart disease does not improve long-term mortality rates or reduce future cardiac events, new study finds

Innovative risk score accurately calculates which kidney transplant candidates are also at risk for heart attack or stroke, new study finds

Amid record year for dengue infections, new study finds climate change responsible for 19% of today’s rising dengue burden

New study finds air pollution increases inflammation primarily in patients with heart disease

AI finds undiagnosed liver disease in early stages

The American Society of Tropical Medicine and Hygiene and the Bill & Melinda Gates Foundation announce new research fellowship in malaria genomics in honor of professor Dominic Kwiatkowski