Researchers examine efficacy of kala-azar therapy regimens in India

NEW DELHI: Researchers have evaluated the efficacy of current therapy regimens for the neglected tropical disease, Visceral Leishmaniasis (VL), and published their findings in The Lancet Regional Health-Southeast Asia journal. The researchers conducted a meta-analysis of 131 studies aimed at quantifying the proportion of relapses observed at and beyond 6-months using the University of Oxford's (UK) Infectious Diseases Data Observatory (IDDO) systematic review database.

Overall, 27,687 patients were included in the analysis, of which 1193 were found to have relapsed. The analysis included 101 studies from the Indian sub-continent (India, Nepal and Bangladesh), 14 from East Africa, along with studies from the Mediterranean region, Latin America and Central Asia.

The team of researchers, including those from India's Banaras Hindu University, Varanasi, estimated that the proportion of VL patients relapsing after following the currently recommended drug regimen ranged from 0.5 to 4.5 per cent in the Indian sub-continent.

Further, they found that over one-quarter of relapses would be missed with 6-months follow-up suggesting a longer follow-up may be warranted.

Visceral Leishmaniasis, also known as kala-azar, is a protozoan parasitic disease spread by sandflies and manifests as sores, untreated cases of which can be highly fatal in most of the cases. Therapeutic interventions can, however, reduce mortality significantly.

In the Indian sub-continent (ISC), relapse estimates at 6-months was 4.5 per cent following single dose of liposomal amphotericin B (L-AmB) and 1.5 per cent for L-AmB in a combination therapy. Currently, 10 milligrams per kilogram (mg/kg) dosage of the single dose L-AmB is the first line regimen and had the estimated average relapse of 3.5 per cent, the researchers said in their study.

In the Indian sub-continent, the overall relapse rate at 6-months for single dose L-AmB was 8.4 per cent for 5 mg/kg dosage and 1.8 per cent for 15 mg/kg dosage, indicating that higher doses of L-AmB may be more effective in preventing relapse, they said.

The lower relapse rates observed at higher doses of L-AmB may be due to the increased drug exposure and higher tissue concentrations achieved with higher dosages, the researchers wrote in the study.

Along with dosage, they found that other factors such as patient characteristics, parasite susceptibility, and drug action in the body, could influence the efficacy of the L-AmB regimen.

With every 1 mg/kg increase in dosage, the chances of a relapse decreased by 19 per cent, they found.

Further, the researchers also found fewer relapses to occur in patients following a combination regimen compared to a monotherapy.

Combination therapy was found to largely reduce the treatment duration leading to an overall lower burden to the health systems and thus, the researchers strongly advocated for its use for the treatment of VL.

This may also potentially delay the emergence of drug resistance in VL patients, they said.

Overall, the decreased rates of relapse in the Indian sub-continent over time likely demonstrates the effect of prompt changes in treatment recommendation and the importance of regularly conducting drug efficacy surveillance, the researchers said in their study.