All Serious Adverse Events (non-related events and related adverse drug reactions) by System Organ Class (bold) and Preferred Term according to MedDRA.

<p>MedDRA, Medical Dictionary of Regulatory Activities; SSG, sodium stibogluconate (20 mg/kg/day for 30 days); PM paromomycin sulphate (20 mg/kg/day for 21 days); SSG & PM (SSG 20 mg/kg/day & PM at 15 mg/kg/day for 17 days); NR, non-related Serious Adverse Events; SADR, Serious Adverse Drug Reaction.</p>a<p>Death due to an unknown cause.</p>b<p>Raised bilirubin/jaundice.</p>c<p>Abdominal sepsis and malaria were considered as unlikely related to the drug by the investigators.</p>d<p>2 PM patients withdrew consent after 4 and 6 days on treatment and 1 SSG & PM patient after 6 days on treatment, no SAE reported prior to withdrawal.</p

Baseline Data.

<p>SSG = sodium stibogluconate (20 mg/kg/day for 30 days); PM = paromomycin sulphate (20 mg/kg/day for 21 days); SSG & PM Combination treatment (SSG at 20 mg/kg/day plus PM at 15 mg/kg/day for 17 days);</p>a<p>Patients 4–17 years old were classified as children and patients 18–60 years old were classified as adults.</p>b<p>These are presented as mean (SD).</p>c<p>Classification based on World Health Organization child growth standards in patients ≤19 years or using body mass index in those ≥20 years.</p>d<p>340 out of 386, 203 out of 205, and 335 out of 381 patients were tested for HIV in the SSG, PM and SSG & PM arms respectively.</p

CONSORT Patient Flowchart – SSG <i>vs.</i> PM.

<p>SSG, sodium stibogluconate; PM, paromomycin sulphate; SAE, serious adverse event; LTFU, loss to follow-up; ITT, intention-to-treat; PP, per protocol. Patients included in the SSG (20 mg/kg/day for 30 days) vs. PM (20 mg/kg/day for 21 days) arms; <b>^a</b> data from these patients were previously reported <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001674#pntd.0001674-Musa1" target="_blank">[14]</a>.</p

Sodium Stibogluconate (SSG) & Paromomycin (PM) versus SSG: Efficacy Data.

<p>CI = confidence interval, ITT = Intention-to-Treat, PP = Per-Protocol.</p>a<p>381patients were originally recruited to the SSG&PM arm, 386 to the SSG arm.</p>b<p>Treatment effect: difference in efficacy between SSG and SSG & PM combination treatment, percent scale with exact binomial 95% CI.</p>c<p>p-value from likelihood ratio test comparing binomial regression models with and without treatment.</p>d<p>p-value from likelihood ratio test comparing binomial regression models with and without factor of interest, after adjustment for treatment allocation.</p>e<p>Complete-case analysis: patients with missing outcome data excluded from analysis.</p>f<p>Worst-case analysis: missing outcomes assumed to be treatment failures.</p

Paromomycin (PM) monotherapy versus Sodium Stibogluconate (SSG): Efficacy Data.

<p>CI = confidence interval, ITT = Intention-to-Treat, PP = Per-Protocol.</p>a<p>205 patients were originally recruited to the PM arm, 386 to the SSG arm.</p>b<p>Treatment effect: difference in efficacy between SSG and PM, percent scale with exact binomial 95% CI. Adjustment for centre was not possible due to only one failure in one centre.</p>c<p>p-value from likelihood ratio test comparing binomial regression models with and without treatment.</p>d<p>Complete-case analysis: patients with missing outcome data excluded from analysis.</p>e<p>Worst-case analysis: missing outcomes assumed to be treatment failures.</p

CONSORT Patient Flowchart – SSG <i>vs.</i> SSG&PM.

<p>SSG, sodium stibogluconate; PM, paromomycin sulphate; SAE, serious adverse event; LTFU, loss to follow-up; ITT, intention-to-treat; PP, per protocol. Patients included in the SSG (SSG at 20 mg/kg/day for 30 days) vs. SSG & PM combination (SSG at 20 mg/kg/day & PM at 15 mg/kg/day for 17 days) arms; <b>^a</b> patient was diagnosed with tuberculosis and was removed from the study before the end of treatment; <b>^b</b> patient died from non-VL causes; <b>^c</b> patient with deviation also had a missing outcome value and was already excluded from the ITT analysis.</p

Serious and non-serious adverse events occurring during the study.

<p>SSG = sodium stibogluconate; PM = paromomycin sulphate; SSG & PM = combination treatment;</p><p>AE, adverse event; SAE, serious adverse event; TEAE, treatment emergent adverse event;</p>a<p>There were two consent withdrawals in the PM arm (after 4 and 6 days on treatment) and 1 withdrawal in the SSG & PM arm (after 6 days on treatment) - data were therefore collected only up to the day of withdrawal for these patients.</p>b<p>Treatment emergent adverse event is defined as onset being between day 1 of treatment and 30 days post end of treatment, inclusive.</p>c<p>No patient experienced more than one SAE.</p>d<p>Adverse drug reaction is defined as any adverse event the investigator recorded as having a probable, possible or unlikely relationship to the study drug.</p>e<p>Cause of deaths were as follows: SSG: unknown (1), Acute Renal Failure (2), cardiotoxicity (1); PM: VL; SSG & PM: Pericarditis tuberculosis (1), malaria (1).</p>f<p>Person-days at risk is defined as the treatment period per study drug regimen plus an additional 30 days post end of treatment.</p