Doses when given in combination: paromomycin sulfate (20 mg/kg [equivalent to 15 mg/kg/day paromomycin base] per day IM once a day for 14 days) plus miltefosine (allometric doses, orally BID for 14 days). Doses when given in combination: SSG (20 mg/kg per day IV or IM once a day for 17 days) plus paromomycin sulfate (15 mg/kg [equivalent to 11 mg/kg/day paromomycin base] per day IM once a day for 17 days).

• 1.The following are the exclusion criteria in the paromomycin plus miltefosine trial and other excluded conditions. ⸋ patient’s age<4 years and>50 years; pregnant or lactating women; female patients of childbearing potential who do not agree to a pregnancy test at screening for VL and/or to use contraception from the treatment period until 5 months after treatment; VL relapse; severe malnutrition; VL concurrent with PKDL; haemoglobin<5 g/dL; severe VL according to the physician’s judgement based on clinical manifestations (e.g. jaundice, bleeding, oedema) and significant abnormalities in laboratory parameters (e.g. haemoglobin, white blood cells, platelets, liver enzymes [alanine and aspartate transaminases], total bilirubin and creatinine); history of hypersensitivity to drugs or known drug class allergies; pre-existing hearing loss; underlying comorbid conditions (e.g. cardiac, renal or hepatic); concomitant infections such as pneumonia, tuberculosis, schistosomiasis, HIV infection or any other immunosuppressive condition; and ⸋ unable to comply with the planned study visits and regimen (e.g. unable to swallow miltefosine capsules, severe side-effects or drug intolerance).
• 2.Miltefosine is to be provided in allometric doses, particularly for patients weighing<30 kg (see Annex 2).
• 3.Miltefosine is potentially teratogenic. Its use in pregnancy is contraindicated. It should not be used in women of childbearing potential for whom pregnancy cannot be ruled out and adequate contraception cannot be assured for the duration of treatment and 2 months (for shorter miltefosine regimens, e.g. 5, 7 or 10 days) or 5 months (for 28-day or longer miltefosine regimens) post-treatment.
• 4.The availability and acceptability of contraception (oral versus injectable) should be taken into account before prescription.
• 5.Supportive treatment is important; patients should be properly hydrated and given nutritional supplements. Severe anaemia should be corrected with blood transfusions, and concomitant infections should be treated with appropriate anti-infective agents.