David Smith, associate director of disease ecology at UF's Emerging Pathogens Institute, said the study will guide scientists and policy makers in extending the longevity of current artemisinin-based malaria drugs combined with partner drugs. Smith is a co-author of a report on the study, scheduled to publish online this week in the Proceedings of the National Academy of Sciences and in print on Sept. 16.
Smith collaborated with lead author Maciej Boni of Resources for the Future and Princeton University, and Ramanan Laxminarayan, also with RFF, to create mathematical models assessing the strategic effectiveness and clinical outcomes of using one, two and three first-line drug therapies to treat malaria within a population over a 20-year period. Their results show that using two or three drugs simultaneously reduced the total clinical cases and number of failed treatments , and slowed the rate at which drug-resistant genes spread within the parasites that cause malaria: Plasmodium falciparum, P. vivax, P. malariae and P. ovale.
"The models indicate that we can slow the evolution of resistance to current artemisinin-based therapies if nations use them in combination with two or more partner drugs," Smith said. "Currently, most nations don't do this. They use one therapy at a time, wait for it to fail, and then switch to a different therapy."
Artemisinin-combined therapies, or ACTs, are currently not widely implemented due to operational challenges and expense, Smith said. But he said the study offers compelling evidence for global leaders to collaborate and overcome these issues.
"This is not to say that implementing multiple first-line therapies solves all of our malaria problems," Boni said. "Anti-malarial drug development needs to continue so that we have novel and highly effective anti-malarials that can be plugged into the recommended strategy of deploying multiple therapies."
In the past century, chloroquine and sulfadoxine-pyrimethamine were widely used to combat malaria, but the parasites eventually evolved resistance leading to the drugs' failure. Artemesinin drugs, derived from the herb Artemisia annua, are relatively new and the malaria parasite does not yet appear to have a resistance to it. They work by triggering chemical reactions which damage the Plasmodium parasite.
"We don't have anything in the pipeline after ACTs, and it's basically just a matter of time until drug resistance evolves and artemisinin also fails," Smith said. "So the question becomes how do we keep ACTs in our arsenal for as long as effectively possible?"
The researchers' models also show that cycling through single drugs accelerated the rate at which malaria parasites evolved drug resistance. Smith said this occurred because cycling a single drug degraded the parasite's average fitness, which made it easier for drug-resistant genes to spread throughout the parasite population.
The cycling models predicted a declining therapeutic value of a single drug within 3.54 years, versus a longer effective therapeutic value of 9.95 years when three drugs were used in equal proportions within a population. The research was funded in part by grants from the Bill and Melinda Gates Foundation, and the National Institutes of Health.
"Using multiple first-line drugs reduces the selection pressure for resistance to a single drug," Smith said. "This is one way to make the ACTs last longer and benefit more people."
Co-author Laxminarayan, a senior research fellow at RFF, said ACTs are the best treatment option for malaria, now as well as in the foreseeable future.
"Novel treatment strategies improve our ability to delay the emergence of drug resistance without the need to deny treatment," Laxminarayan said.
Wil Milhous, associate dean for research at the University of South Florida's College of Public Health, said the research is "clearly a superb breakthrough in mathematical modeling applied to malaria drug deployment." Milhous has worked to develop new drugs for malaria for more than 25 years and is unaffiliated with the study.
"We have done the math in drug development, but only in terms of the cost of goods for drug combinations to include advanced preclinical and clinical testing. These are extremely time-consuming and costly but critical to regulatory approval," Milhous said. "Now we have a highly quantitative reality check that poor implementation strategies doom drugs to failure."
DeLene Beeland | EurekAlert!
Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University
New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
21.03.2018 | Physics and Astronomy
21.03.2018 | Materials Sciences
21.03.2018 | Life Sciences