The results seem to challenge the current approach endorsed by the World Health Organization. Under that method, directly observed therapy-short-course strategy (DOTS), TB that responds to medication is treated with a cocktail of drugs under the supervision of health care workers, who in many countries must travel to isolated villages – a costly and time-consuming process.
“Every TB patient is supposed to be watched as they swallow their pills in order to increase adherence and decrease emergence of drug resistance. This is the most expensive part of the program, but has been felt to be cost-effective since it improves compliance,” said Dr. Gumbo, administrative director of research programs for the Office of Global Health at UT Southwestern.
In this study, UT Southwestern researchers created a sophisticated system of high-tech test tubes, which they called a “glass mouse,” that mimicked standard therapy being given daily for 28 to 56 days, with dosing adherence varying between 0 percent and 100 percent. The threshold for defined non-adherence (failure to take a required dose of medication) was reached at 60 percent of the time or more.
“The first main finding in our laboratory model was that in fact non-adherence did not lead to multidrug resistance or emergence of any drug resistance in repeated studies, even when therapy failed. In fact, even when we started with a bacterial population that had been spiked with drug-resistant bacteria, non-adherence still did not lead to drug resistance,” he said.
In fact, using computer simulations based on 10,000 TB patients in Cape Town, South Africa, the researchers discovered that approximately 1 percent of all TB patients with perfect adherence still developed drug resistance because they cleared the drugs from their bodies more quickly.
The body sees drugs as foreign chemicals and tries to rid itself of them, Dr. Gumbo said. A population of individuals with a genetic trait that speeds the process has been found in one area of South Africa that has a high rate of multidrug-resistant TB. In that population, patients who receive standard doses of drugs end up with concentrations in their bodies that are too low to kill the TB bacillus and drug resistance develops, he said.
A Journal of Infectious Diseases editorial that accompanies the study suggests that monitoring the levels of TB drugs in a patient’s blood could be as important as monitoring compliance with therapy – in contrast to current WHO guidelines.
“These data, based on our preclinical model, show that non-adherence alone is insufficient for the emergence of multidrug-resistant TB,” Dr. Gumbo said. “It might be more cost-effective to measure patients’ drug concentrations during treatment and intervene with dosage increases in those who quickly clear the drugs from their systems.”
The work was supported by a grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
Other UT Southwestern investigators involved in the study are lead author Dr. Shashikant Srivastava, former postdoctoral researcher, and Dr. Jotam G. Pasipanodya, research scientist in internal medicine. Researchers from the School of Pharmacy at Texas Tech University Health Science Center, Dallas, also participated.
Deborah Wormser | EurekAlert!
Inselspital: Fewer CT scans needed after cerebral bleeding
20.03.2019 | Universitätsspital Bern
Building blocks for new medications: the University of Graz is seeking a technology partner
19.03.2019 | Karl-Franzens-Universität Graz
DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.
The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...
Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.
The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...
Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.
Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...
The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.
A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...
Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.
"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...
11.03.2019 | Event News
01.03.2019 | Event News
28.02.2019 | Event News
22.03.2019 | Life Sciences
22.03.2019 | Life Sciences
22.03.2019 | Information Technology