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!
Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland
Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy