XML Feed for RxPG News   Add RxPG News Headlines to My Yahoo!   Javascript Syndication for RxPG News

Research Health World General
 
  Home
 
   Health
 Aging
 Asian Health
 Events
 Fitness
 Food & Nutrition
 Happiness
 Men's Health
 Mental Health
 Occupational Health
 Parenting
 Public Health
 Sleep Hygiene
 Women's Health
 
   Healthcare
 Africa
 Australia
 Canada Healthcare
 China Healthcare
 India Healthcare
 New Zealand
 South Africa
 UK
 USA
 World Healthcare
 
   Latest Research
 Aging
 Alternative Medicine
 Anaethesia
 Biochemistry
 Biotechnology
 Cancer
 Cardiology
 Clinical Trials
 Cytology
 Dental
 Dermatology
 Embryology
 Endocrinology
 ENT
 Environment
 Epidemiology
 Gastroenterology
 Genetics
 Gynaecology
 Haematology
 Immunology
 Infectious Diseases
  AIDS
  Anthrax
  Dengue
  Ebola
  HCV
  Influenza
  Leishmaniasis
  Malaria
  MRSA
  Mumps
  Pertussis
  Prion Diseases
  SARS
  Shigella
  Small Pox
  Tuberculosis
 Medicine
 Metabolism
 Microbiology
 Musculoskeletal
 Nephrology
 Neurosciences
 Obstetrics
 Ophthalmology
 Orthopedics
 Paediatrics
 Pathology
 Pharmacology
 Physiology
 Physiotherapy
 Psychiatry
 Radiology
 Rheumatology
 Sports Medicine
 Surgery
 Toxicology
 Urology
 
   Medical News
 Awards & Prizes
 Epidemics
 Launch
 Opinion
 Professionals
 
   Special Topics
 Ethics
 Euthanasia
 Evolution
 Feature
 Odd Medical News
 Climate
Search

Last Updated: Nov 18, 2006 - 1:55:25 PM

Leishmaniasis Channel
subscribe to Leishmaniasis newsletter

Latest Research : Infectious Diseases : Leishmaniasis

   DISCUSS   |   EMAIL   |   PRINT
Drug-Resistant Leishmania tropica Parasites Detected in Iranian Cutaneous Leishmaniasis
Apr 21, 2006 - 12:41:00 AM, Reviewed by: Dr. Priya Saxena

Overall, these results provide the first evidence that Leishmania parasites can acquire drug resistance that contributes to treatment failure in cutaneous leishmaniasis.

 
Leishmaniases are parasitic diseases that are endemic (constantly present) in many tropical and temperate countries. Every year, 2 million people become infected with one of 20 pathogenic species of Leishmania through the bites of infected female sand flies. These pick up parasites by biting an infected animal (zoonotic transmission) or an infected person (anthroponotic transmission). In their human host, Leishmania parasites reproduce inside macrophages—white blood cells that usually kill microorganisms, clear up cellular debris, and activate other immune cells. When the macrophages are full of parasites, they burst—this destruction causes the symptoms associated with leishmaniases—and the released parasites infect further macrophages.

In cutaneous leishmaniasis—the most common form of the disease—patients develop skin ulcers a few weeks after being bitten by infected sand flies. These usually heal spontaneously but leave ugly, sometimes disabling, scars. Cutaneous Leishmania infections can spread to the nose or mouth to cause mucocutaneous leishmaniasis, which destroys the sensitive linings of these organs. Cutaneous and mucocutaneous leishmaniases are not life-threatening in themselves, but patients can develop fatal secondary infections. Visceral leishmaniasis, which affects the spleen and other internal organs, is often fatal if untreated.

Leishmaniases are usually treated with pentavalent antimony-containing drugs, such as meglumine antimoniate (Glucantime), but patients are becoming increasingly unresponsive to these drugs. In India, for example, more than 60% of cases of visceral leishmaniasis do not respond to treatment. Unresponsiveness can be caused by the parasite developing drug resistance, by changes in the host's immunological status, or by suboptimal treatment regimens. Ramtin Hadighi, Mehdi Mohebali, Marc Ouellette, and colleagues have been investigating whether the increased incidence of Glucantime-unresponsive cutaneous leishmaniasis in Iran correlates with parasite resistance to the drug. They now report that treatment failure for cutaneous leishmaniasis in Iran, like the treatment failure seen for visceral leishmaniasis in India, is due to Glucantime-resistant parasites.

The researchers isolated Leishmania parasites from 185 skin lesions from untreated patients living in Mashhad, a region of Iran where anthroponotic cutaneous leishmania is endemic. Of these patients, 20 did not respond to Glucantime—their skin ulcers failed to heal. To find out if this was due to drug-resistant parasites, the researchers infected mouse macrophages with all 185 isolates and then treated the infected cells with Glucantime. Several days later, the parasites surviving inside the cells were stained with a dye and then counted using a microscope. The researchers report that although initial infection rates were similar, parasites from the unresponsive patients were resistant to intermediate or high levels of Glucantime. On average, parasites from unresponsive patients were 4-fold less susceptible to Glucantime than parasites from responsive patients.

Next, the researchers partly characterized the 20 drug-resistant parasite isolates and 11 drug-susceptible isolates. By sequencing the gene for the metabolic enzyme pteridine reductase 1, the researchers discovered that 28 of the isolates were L. tropica; the remaining three were L. major. Only one unresponsive isolate was L. major; the rest were L. tropica. The researchers also used pulsed-field gel electrophoresis to separate and study Leishmania chromosomes. Because these evolve quickly, the chromosome composition (karyotype) of different isolates indicates their genetic relatedness. The L. major isolates formed one group using this technique but the L. tropica isolates fell into three distinct groups, each of which included drug-susceptible isolates and isolates with intermediate and high Glucantime resistance. In other words, susceptible and resistant isolates were often closely related. Finally, the researchers confirmed the drug sensitivity of several closely related strains by testing their ability to grow in a human monocyte cell line in the presence of Glucantime, and also showed that drug resistance was stable over time in resistant isolates but could be reversed by treatment with an inhibitor of glutathione biosynthesis. This last result indicates that thiols (molecules containing a sulphur atom bonded to a hydrogen atom) may be important for the resistant phenotype, and may suggest a way to reverse drug resistance.

Overall, these results provide the first evidence that Leishmania parasites can acquire drug resistance that contributes to treatment failure in cutaneous leishmaniasis. They also indicate that Glucantime-resistant L. tropica isolates are now frequent in Iran. Additional work is needed to understand the nature of the resistance mechanisms, with the goal to improve diagnosis and treatment of resistant leishmaniasis.
 

- (2006) Drug-Resistant Leishmania tropica Parasites Detected in Iranian Cutaneous Leishmaniasis. PLoS Med 3(5): e230
 

Read Research Article

 
Subscribe to Leishmaniasis Newsletter
E-mail Address:

 

DOI: 10.1371/journal.pmed.0030230

Published: April 18, 2006

Copyright: © 2006 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License


Related Leishmaniasis News
Vaccine developed to fight black fever
Potential vaccine developed for deadly leishmaniasis disease
Drug-Resistant Leishmania tropica Parasites Detected in Iranian Cutaneous Leishmaniasis


For any corrections of factual information, to contact the editors or to send any medical news or health news press releases, use feedback form

Top of Page

 

© Copyright 2004 onwards by RxPG Medical Solutions Private Limited
Contact Us