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  • New handle on drug-resistant leishmaniasis

[NEW DELHI] Scientists have found that the parasite that causes leishmaniasis, a neglected tropical disease, deploys ‘glycan’, a sugary substance, to outwit the human immune system and resist current treatments with antimony-based drugs.  

Spread through the bites of sandflies, the Leishmania parasite affects the skin, mucous linings of the mouth, throat or abdomen. The abdominal form, 'visceral leishmaniasis', is characterised by high fever, weight loss, anaemia and swelling of the spleen and liver.

Visceral leishmaniasis, known as 'kala azar' in India and caused by Leishmania donovani, is reported to be re-emerging and spreading worldwide due to a mix of reasons that includes resistance to the widely used antimony-based drugs.

The discovery by researchers from Belgium and India, that glycan found on the surface of the parasite makes human host cells expel antimony-based drugs, holds out the promise of better management of leishmaniasis. 

SPEED READ

  • Leishmania parasites deploy sugar-based substances called 'glycans' to expel drugs
  • The finding could help devise better disease management
  • Effective drugs needed to tackle leishmaniasis

This particular glycan was identified for the first time by our group in leishmania parasites and found to have some critical role in conferring antimony resistance to the parasites," Syamal Roy, scientist at the Indian Institute of Chemical Biology, Kolkata, told SciDev.Net.

Roy said the discovery explains "how leishmania parasites outwit the immune system and evade antimonial drugs."

Insights into how antimony-resistant parasites influence human cell functions, will help design new drugs, the scientists say. Research on drug-resistant leishmaniasis, so far focussed on the parasite itself, now looks at how the organism genetically manipulates the host cell's immune system.

On the Indian sub-continent where the infection is endemic, treatment failure is now at a high 65 per cent. In India's Bihar state antimony drugs are now obsolete, says a report published last month (22 January) in Proceedings of the National Academy of Sciences.

Some 500,000 individuals in 61 countries around the Mediterranean basin, East Africa and India are afflicted each year by leishmaniasis which, if left untreated, can turn fatal. Areas where drug resistance has escalated up to 70 per cent include Brazil and Sudan.

Jean-Claude Dujardin, head of the department of biomedical sciences at the Institute of Tropical Medicine, Antwerp, and member of the research team, says control of leishmaniasis suffers from a "dramatic lack of effective drugs." 

"Anitmonials are lost, the efficacy of miltefosine (a new drug) when used in monotherapy (single drug treatment) is declining in the whole Indian sub-continent, and there are only a few other drugs available," Dujardin said.

Link to article in Proceedings of the National Academy of Sciences:

 

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