IACS’s novel compound treats drug-resistant kala-azar infection

Subject : Science and technology

Section: Health

Concept :

Researches at Indian Association for the Cultivation of Science (IACS) has done a experimental work in mice which has shown novel quinoline derivative to be effective in sharply reducing the load of leishmaniasis, also called kalaazar (black fever).

DNA Architecture in parasites

The quinoline derivative is a potent inhibitor of an enzyme called topoisomerase 1 (LdTop1), which is essential for maintenance of DNA architecture in the parasites;
This enzyme is distinct from the one found in humans.
Poisoning of LdTop1 imparts a significant level of cytotoxicity to both the Leishmania parasites found in gut of sandfly vectors (promastigotes) as well as the form found in the infected humans (amastigotes) of both the wild type and the antimony resistant isolates.
It doesn’t induce any lethality to human and mice host cells.

Kala Azar Disease / Leishmaniasis

Leishmaniasis is a disease caused by any species of Leishmania parasite.
It is transmitted by the bite of an infected female sandfly.
In most cases, a person who is infected by the parasite has neither symptoms nor signs of infection and is not considered to have leishmaniasis.
Although there are some 20 different parasites that cause the disease, there are only three different types of leishmaniasis.
Visceral leishmaniasis, which affects multiple organs and is the most serious form of the disease.
Cutaneous leishmaniasis, which causes skin sores and is the most common form.
Mucocutaneous leishmaniasis, which causes skin and mucosal lesions.
Visceral leishmaniasis, which is commonly known as Kala-azar in India, is fatal in over 95% of the cases, if left untreated.
It is one of the most neglected tropical diseases and around 95 % of cases are reported from Bangladesh, Brazil, China, Ethiopia, India, Kenya, Nepal, Somalia, South Sudan, and Sudan.

Drug Resistant

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.
A protein called ‘P4ATPase-CDC50’, is responsible for 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 less accumulation of miltefosine inside the parasite’s body, thus causing it to become resistant to the drug.