OBJECTIVES:

To determine the efficacy and safety outcomes of different antileishmanial agents used in visceral leishmaniasis.

METHODS:

A systematic literature search in PubMed/MEDLINE, EMBASE, Cochrane, and Google Scholar was done using keywords “randomized controlled trials”, “antileishmanial” and “visceral leishmaniasis”. The outcomes included were cure rate, overall withdrawals, relapse rate, and treatment-emergent adverse events. Effect estimates through the frequentist network meta-analysis approach were presented as OR with 95% CI. Rankogram plots were used for identifying the “best intervention” based on p-scores obtained using the surface under the cumulative ranking. The risk of bias was evaluated by using Pedro Scale.

RESULTS:

Seventeen randomized controlled trials with 5 143 visceral leishmaniasis patients who received different antileishmanial agents (amphotericin B, miltefosine, paromomycin, meglumine antimoniate, sodium stibogluconate, sitamaquine, and pentavalent antimonials) and met the inclusion criteria were included. For efficacy outcomes of the treatments, the rankogram of the network meta-analysis revealed that paromomycin (p-score=0.814 8) has the highest probability of being best in the pool, followed by sodium stibogluconate (OR 0.82, 95% CI 0.24-2.79, p-score=0.758 0), amphotericin B+miltefosine (OR 0.66, 95% CI 0.02-19.04, p-score=0.732 9) as compared to the remaining treatments; however, the most of the treatment-emergent adverse events were reported with sitamaquine.

CONCLUSIONS:

Paromomycin reported the advantage in comparison to other agents in achieving higher cure rates. L-amphotericin B plus Meglumine Antimoniate combination was associated with high relapse rates while L-amphotericin B alone reported the maximum serious treatment-emergent adverse events. Future research with direct head-to-head RCTs and timely update of new findings is warranted to further strengthen these results.