Leishmaniasis drug resistance mechanism exposed

Leishmaniasis parasites Copyright: WHO/TDR/Pasteur Inst.

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Indian researchers have identified a mechanism of drug resistance in the parasites that cause visceral leishmaniasis, and suggest an effective way to reverse it.

The study was published in the April issue of the American Journal of Tropical Medicine and Hygiene.

Shyam Sundar, an author on the study from the Institute of Medical Sciences of Banaras Hindu University, told SciDev.Net that the resistance of the leishmaniasis parasite, Leishmania donovani, to sodium stibogluconate ― a common drug used to treat the disease ― is widespread in India.   

The researchers studied leishmaniasis parasites and found that those resistant to sodium stibogluconate had an increased concentration of thiols ― sulphur-containing compounds ― in their cells.

The researchers also identified an enzyme, trypanothione reductase, and a gene, MRPA (multidrug resistance protein A) in the resistant parasites.

Sundar told SciDev.Net that these three factors increased the removal of the drug from the parasite’s cell, thus resulting in drug resistance

According to the World Health Organization, India accounts for 50 per cent of global leishmaniasis burden, and rural parts of the region of Bihar account for 90 per cent of Indian cases. Bangladesh, Nepal and Sudan are also affected.

"In the most severely affected villages in Bihar, resistance is so high that stibogluconate can effectively treat only one third of the cases even when its dose is 6−8 times higher," said Sundar.

However, the researchers suggested that resistance can be reversed.

The enzyme glutathione reductase is essential in increasing the concentration of thiols in cells.

"An inhibitor of this enzyme may be used to decrease the thiol level and thus revert the drug resistance," Sundar explained.

Testing these inhibitors on the leishmaniasis parasite is the next step in future research.

Swapan Jana, secretary of the Society for Social Pharmacology ― an Indian nongovernmental organisation ― said, "Leishmaniasis predominantly affects poor people and hence despite the advent of various new drugs, stibogluconate, for its low cost, has importance in this disease."

"This study is impressive, because drug resistance is a big problem with stibogluconate, and this shows a way to revert it," he added.

Reference: American Journal Of Tropical Medicine 76, 681 (2007)