Featured Research

from universities, journals, and other organizations

How the parasite responsible for severe forms of malaria can resist a major antimalarial agent

Date:
May 5, 2010
Source:
CNRS (Délégation Paris Michel-Ange)
Summary:
Researchers have demonstrated how the parasite Plasmodium falciparum, which causes severe forms of malaria, is able to circumvent the action of artemisinin and its derivatives, which are today the first-line drugs used to treat this disease. This study supplies some important findings that will enable a clearer understanding of the mechanisms of resistance to antimalarial drugs and the testing of novel therapeutic strategies in a context where the drug resistance of parasites is of increasing concern.

Different stages of Plasmodium falciparum inside red blood cells.
Credit: Copyright LCC

Researchers from CNRS, INSERM and Toulouse University Hospital have demonstrated how the parasite Plasmodium falciparum, which causes severe forms of malaria, is able to circumvent the action of artemisinin and its derivatives, which are today the first-line drugs used to treat this disease. This study supplies some important findings that will enable a clearer understanding of the mechanisms of resistance to antimalarial drugs and the testing of novel therapeutic strategies in a context where the drug resistance of parasites is of increasing concern.

Published in the May 2010 issue of Antimicrobial Agents and Chemotherapy, this work was carried out in collaboration with the US National Institutes for Health (NIH).

Malaria still continues to kill nearly a million people each year throughout the world. There is no vaccine against this infectious disease caused by a parasite of the Plasmodium genus and propagated via the bites of certain mosquitoes. Plasmodium falciparum is the most pathogenic species, causing a high death rate. It accounts for more than 80% of cases of human malaria and is present in the tropical regions of Africa, Latin America and Asia.

For the past ten years, artemisinin (ART), a substance extracted from a Chinese plant, has become the first-line drug for malaria, particularly since other compounds have lost their efficacy. Its action against all strains of Plasmodium falciparum, including those resistant to other antimalarials, is the principal advantage of ART. Furthermore, its antimalarial activity is very rapid, and it has few adverse effects. Combining artemisinin with another antimalarial agents considerably reduces the risk of onset of resistance. For this reason, the WHO has for several years been recommending the systematic use of this compound and its derivatives in combination with other antimalarial agents. Artermisinin-based Combination Therapies (ACT) now constitute the most effective treatment for malaria (1), achieving a 95% cure rate.

However, in July 2009, the first cases of resistance to artesunate, the ART derivative most widely used in ACT, were observed among patients in South-East Asia. It has therefore become essential to determine how Plasmodium falciparum is able to circumvent the action of ART and its derivatives.

Thus the team led by Françoise Benoit-Vical, senior INSERM researcher in the CNRS Laboratoire de Chimie de Coordination (2), sought to isolate ART-resistant strains in an experimental manner. This feat was achieved at the end of 2009 when the scientists managed to obtain a strain of Plasmodium falciparum that was resistant to this compound and some of its derivatives, and the first to be adapted to in vitro culture. By furthering their investigations, the team was able to demonstrate that this ART-resistant strain was able to survive in the presence of ART at a dose that was 7000 times higher than the IC50 on susceptible strains. In addition, this experimental strain shared certain traits with the resistant strains found in the field.

The researchers also identified and characterized a new mode of parasite resistance. To evade the action of ART, Plasmodium falciparum arrested its development and entered a so-called state of quiescence. It thus functioned at a slow metabolic rate until the drug was eliminated. This quiescence phenomenon was only observed in parasites at the ring stage (3). In parallel, an analysis performed with a National Institutes of Health team suggested that the expression of some proteins involved in the cell cycle of Plasmodium falciparum might be modified in resistant strains. Further studies are planned to identify the genes responsible for the acquisition of ART resistance.

The scientists were thus able to demonstrate a novel resistance mechanism and now benefit from an important tool that will allow a clearer understanding of the mechanisms of resistance to antimalarial drugs; this will also enable the testing of different therapeutic options (new compounds, new therapeutic combinations, new targets, etc.).

Notes:

  1. 160 million doses of ACT were administered to treat malaria in 2009.
  2. Attached to this CNRS research unit, the team is based in the Parasitology-Mycology Department at Toulouse University Hospital.
  3. First stage of the parasitic cycle in red blood cells

Story Source:

The above story is based on materials provided by CNRS (Délégation Paris Michel-Ange). Note: Materials may be edited for content and length.


Journal Reference:

  1. B. Witkowski, J. Lelievre, M. J. Lopez Barragan, V. Laurent, X. z. Su, A. Berry, F. Benoit-Vical. Increased Tolerance to Artemisinin in Plasmodium falciparum Is Mediated by a Quiescence Mechanism. Antimicrobial Agents and Chemotherapy, 2010; 54 (5): 1872 DOI: 10.1128/AAC.01636-09

Cite This Page:

CNRS (Délégation Paris Michel-Ange). "How the parasite responsible for severe forms of malaria can resist a major antimalarial agent." ScienceDaily. ScienceDaily, 5 May 2010. <www.sciencedaily.com/releases/2010/05/100505092519.htm>.
CNRS (Délégation Paris Michel-Ange). (2010, May 5). How the parasite responsible for severe forms of malaria can resist a major antimalarial agent. ScienceDaily. Retrieved August 2, 2014 from www.sciencedaily.com/releases/2010/05/100505092519.htm
CNRS (Délégation Paris Michel-Ange). "How the parasite responsible for severe forms of malaria can resist a major antimalarial agent." ScienceDaily. www.sciencedaily.com/releases/2010/05/100505092519.htm (accessed August 2, 2014).

Share This




More Health & Medicine News

Saturday, August 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Quintuplets Head Home

Texas Quintuplets Head Home

Reuters - US Online Video (Aug. 1, 2014) — After four months in the hospital, the first quintuplets to be born at Baylor University Medical Center head home. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Ebola Patient Coming to U.S. for Treatment

Ebola Patient Coming to U.S. for Treatment

Reuters - US Online Video (Aug. 1, 2014) — A U.S. aid worker infected with Ebola while working in West Africa will be treated in a high security ward at Emory University in Atlanta. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Ebola Vaccine Might Be Coming, But Where's It Been?

Ebola Vaccine Might Be Coming, But Where's It Been?

Newsy (Aug. 1, 2014) — Health officials are working to fast-track a vaccine — the West-African Ebola outbreak has killed more than 700. But why didn't we already have one? Video provided by Newsy
Powered by NewsLook.com
Study Links Certain Birth Control Pills To Breast Cancer

Study Links Certain Birth Control Pills To Breast Cancer

Newsy (Aug. 1, 2014) — Previous studies have made the link between birth control and breast cancer, but the latest makes the link to high-estrogen oral contraceptives. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins