Leishmaniasis (Kala-azar)

Recently a team of researchers at the Department of Biotechnology’s National Centre for Cell Science (DBT-NCCS) in Pune has been exploring ways to tackle miltefosine (a drug used to treat Leishmaniasis/Kala-azar) resistance. Visceral leishmaniasis, which is commonly known as Kala-azar in India, is fatal in over 95% of the cases if left untreated.

Mechanism of Resistance for Kala-azar

• Specific types of protein molecules, called transporter proteins, play a major role in carrying miltefosine into and out of the parasite’s body, which comprises a single cell.
• A protein called ‘P4ATPase-CDC50’ is responsible for the intake of the drug by the parasite, and another protein, called ‘P-glycoprotein’, is responsible for throwing this drug out from within the parasite’s body.
• A decrease in the activity of the former protein, and an increase in the activity of the latter results in fewer amounts of miltefosine being accumulated inside the parasite’s body, thus causing it to become resistant to the drug. The researchers worked with one of the species of Leishmania that causes infection, called Leishmania major.
• They tried to manipulate these transporter proteins in the species in a manner that would result in increased uptake of the drug and decrease in its being thrown out of the parasite’s body.
• The only drug available against leishmaniasis, miltefosine, is rapidly losing its effectiveness because of emerging resistance to this drug due to a decrease in its accumulation inside the parasite, which is necessary for the drug to kill the parasite.

About Leishmaniasis

• It is a neglected tropical disease affecting almost 100 countries, including India.
• It is caused by a parasite called Leishmania, which is transmitted through the bite of sandflies.
• There are three primary forms of leishmaniasis
• Visceral which affects multiple organs and is the most severe form of the disease
• Cutaneous, which causes skin sores and is the most common form.
• Mucocutaneous, which causes skin and mucosal lesion.

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