Efficacy and safety of a combined treatment of sodium stibogluconate at 20mg/kg/day with upper maximum daily dose limit of 850mg and Paromomycin 15mg/kg/day in HIV negative visceral leishmaniasis patients. A retrospective study, northwest Ethiopia

Background Visceral leishmaniasis (VL) is one of the most neglected tropical infectious diseases. It is fatal if left untreated. The objective of this study was to assess the efficacy and safety of 17-day injections of combined regimen of sodium stibogluconate and paromomycin (SSG/PM) in HIV-negative VL patients. Methods A retrospective analysis of medical records of VL patients treated in the University of Gondar Hospital during period 2012-2019 was carried out. Results A total of 2836 patients were treated for VL from 2012 to 2019. Of these 1233 were treated with SSG-PM, and 1000 of them were included in the study. Initial cure was achieved in 922 (92.2%) patients. The frequency of treatment failure, treatment interruptions, default and deaths respectively were 30 (3%), 20 (2%), 13 (1.3%) and 15 (1.5%). Among 280 patients who completed 6-month follow up, the final cure was 93.9% (263/280), 4 (1.4%) relapsed and 13 (4.6%) developed post-kala-azar dermal leishmaniasis (PKDL). The most common adverse events (AEs) were raised liver transaminases (35.1%; 351 patients), injection site pain (29.1%, 291 patients) and raised serum alpha-amylase (29.1%, 291 patients). Factors associated with poor treatment outcomes were sepsis, pneumonia, and adverse events. Conclusion A combination of SSG at 20mg/kg with upper daily maximum dose of 850mg and PM was effective for achieving initial cure at end of treatment and safe for treatment of HIV negative VL patients in northwestern Ethiopia. Our data are consistent with previous reports and confirms effectiveness of SSG/PM treatment regimen in the Eastern African countries. Efficacy at 6-months (93.9%) was estimated on data derived from patients who completed follow up and needs to be interrogated by future studies. Author summary Visceral leishmaniasis is one of the most neglected tropical diseases caused by the parasite of the genus leishmania. We assessed the efficacy and safety of a 17-day combined regimen of sodium stibogluconate 20mg/kg /day with daily upper maximum dose limit of 850mg and paromomycin 15mg/kg/day injections in HIV negative visceral leishmaniasis patients. We also identified factors associated with poor treatment outcomes in HIV negative VL patients treated with SSG/PM. Seventy two percent of the study participants developed at least one AE during the initial treatment course but most AEs were reversible. The overall initial efficacy was 92.2% which is comparable with previous study results in East Africa. Among patients who completed six-month follow-up, the efficacy was 93.9%, which appears to be biased due to the small proportion of patients (29%) evaluated at 6-month follow-up. The results affirm that the combination of sodium stibogluconate (20mg/kg b.wt) and paromomycin (15mg/kg b.wt) given for 17 days is still effective in Eastern Africa VL endemic countries. This data applies to VL patients who are HIV negative and not presenting with severe signs/symptoms.

Automated summary

The study evaluated the efficacy and safety of a combined regimen of SSG/PM in treating HIV-negative visceral leishmaniasis patients. The results demonstrated good initial cure rates with this regimen, and a high final cure rate after 6 months of follow-up.