Visceral leishmaniasis, also called kala-azar, is a parasitic disease that strikes 400,000 people every year and kills around 1 in 10 of its victims. The disease has proven difficult to treat, in part because a large percentage of patients who take the drug of choice, miltefosine, relapse after treatment, coming down with the same disease all over again.
Doctors and scientists have long suspected that drug resistance was behind the failure of miltefosine, but that's not so, according to the researchers. The study reveals that parasites in patients who relapse after leishmaniasis treatment have a greater infectivity than parasites from patients who were treated successfully. They are essentially a worse, more dangerous form of the parasite.
"Parasites from relapsed patients show an increased capacity to infect host cells," says co-author Manu Vanaerschot of the Institute of Tropical Medicine in Antwerp,Belgium. The authors write that it remains to be seen whether miltefosine treatment causes the increased infectivity of the parasite, or if parasites with greater infectivity are capable of escaping treatment.
Miltefosine is at the heart of a vast program aimed at ending visceral leishmaniasis on the Indian subcontinent (India, Bangladesh and Nepal), but 6.8% of Indian patients redevelop symptoms of the disease within 6 months after treatment and 20% of Nepalese patients relapse within 12 months after miltefosine treatment. Parasites collected from patients before and after treatment have been fingerprinted and are very close genetic matches, indicating that these patients are not simply re-infected with new parasites once their treatment ends, they are still carrying the same strain that sickened them before treatment. Other work revealed another surprising fact: parasites from relapsed patients were sensitive to miltefosine, so the failure of treatment was not due to drug resistance, a common suspect in cases where infectious disease treatment fails.
With re-infection and drug resistance now crossed off the list of possible reasons for the high relapse rate, the researchers set out to see what factors might really be at work. They examined the morphology of parasites taken from visceral leishmaniasis patients who were treated successfully and patients who relapsed. They found a significant association between the number of parasites in the metacyclic stage of their life cycle and patient treatment outcome. In other words, patients who relapsed were infected with parasites that have a greater infectivity, meaning they were more capable of infecting human cells.
The precise link between infectivity and treatment failure is not known, write the authors, but they propose that parasites with greater infectivity might cause a greater parasite load in the patient, making the case more difficult to treat, or perhaps they are able to evade the drug by hiding in parts of the body it doesn't easily penetrate, like the skin.
Vanaerschot says he and his colleagues saw a similar correlation between infectivity and treatment failure in patients who had been treated with the types of drugs that used to be favored in the region, pentavalent animonials. "At the time we thought that it was a very special case. But now that we've also seen this in parasites treated with other drugs, this indicates that it might be a more common problem than we originally thought."
Co-author Jean-Claude Dujardin, of the Institute of Tropical Medicine and the University of Antwerp, in Belgium, says regardless of the underlying cause-and-effect relationship, the findings are a wake-up call about the possible effects a therapy might have on pathogens it's supposed to kill.
"When we develop a drug to fight against a pathogen, we need to think about possible collateral damage. Of course we have to use these drugs, but we need surveillance to see if more aggressive parasites start to spread," says Dujardin.
mBio® is an open access online journal published by the American Society for Microbiology to make microbiology research broadly accessible. The focus of the journal is on rapid publication of cutting-edge research spanning the entire spectrum of microbiology and related fields. It can be found online at http://mbio.asm.org.
The American Society for Microbiology is the largest single life science society, composed of over 39,000 scientists and health professionals. ASM's mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.
Jim Sliwa | EurekAlert!
Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
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...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Health and Medicine
30.03.2017 | Health and Medicine
30.03.2017 | Medical Engineering