Pentavalent Antimonials Combined with Other Therapeutic Alternatives for the Treatment of Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review

Table 2

Clinic, therapeutic, and epidemiological characteristics of clinical trials included in the study.

Study source	Leishmania species	Treatment	Patients at the end	Previous treatment	Clinically healed	Therapy failed	Relapse or Recurrence
Almeida et al., 2005	L. braziliensis	G1 (MA + GM-CSF)	5	Yes	100% (before 120 days AS); Follow-up: 12 months AH	0% (12 months AH)	0% (12 months AH)
Arevalo et al., 2007	Leishmania spp.	G1 (IM)	6	No	0%; Follow-up: 3 months AS	67% (20 days AS)	33% (3 months AS)
		G2 (MA)	7	No	57% (3 months AS); Follow-up: 3 months AS	43% (3 months AS)	0% (3 months AS)
		G3 (MA + IM)	7	No	100% (3 months AS); Follow-up: 3 months AS	0% (3 months AS)	0% (3 months AS)
Brito et al., 2017	L. braziliensis; (62% of cases)	G1 (MA + PE)	82	NR	45% (6 months AE)	55% (6 months AE)	NR
		G2 (MA + placebo)	82		43% (6 months AE)	57% (6 months AE)	NR
El-Sayed & Anwar, 2010	NR	G1 (il SSG)	10 (12 lesions)	No	50%/58.3% (12 weeks AS; patients/lesions); Follow-up: 6 months AE	50%/41.7% (12 weeks AS; patients/lesions)	NR
		G2 (il SSG + im SSG)	10 (15 lesions)	No	90%/93.3% (12 weeks AS; patients/lesions); Follow-up: 6 months AE	10%/6.7% (12 weeks AS; patients/lesions)	NR
		G3 (il SSG + KE)	10 (13 lesions)	No	90%/92.3% (12 weeks AS; patients/lesions); Follow-up: 6 months AE	10%/7.7% (12 weeks AS; patients/lesions)	NR
Farajzadeh et al., 2015	NR	G1 (Terbinafine + cryotherapy)	40	No (within the past 90 days)	37.5% complete (28 days AS); 10 partial cure^#	15 (28 days AS)	NR
		G2 (MA + cryotherapy)	40	No	52.5% (21 days AS); 7 partial cure^#	12 (21 days AS)	NR
Firooz et al., 2006	L. tropica	G1 (MA + IM)	42	No	18.6% (4 weeks AS); 44.1% (8 weeks AS); 50.8% (20 weeks AS); Follow-up: 16 weeks AE	49.2% (20 weeks AS)	3.1% (16 weeks AS)
		G2 (MA + placebo)	47	No	30.0% (4 weeks AS); 48.3% (8 weeks AS); 53.3% (20 weeks AS); Follow-up: 16 weeks AE	46.7% (20 weeks AS)	8.1% (16 weeks AS)
Khatami et al., 2013	L. major	G1 (il MA)	23 (40 lesions)	No	12.5% (6 weeks AS) lesions; 40.0% (10 weeks AS) lesions; Follow-up: 5 months AE	65.0% (6 weeks AS); 42.5% (10 weeks AS)	0% (5 months AE)
		G2 (il MA + non-silver PD)	21 (46 lesions)	No	6.5% (6 weeks AS) lesions; 42.2% (10 weeks AS) lesions; Follow-up: 5 months AE	80.4% (6 weeks AS); 55.6% (10 weeks AS)	0% (5 months AE)
		G3 (il MA + silver PD)	29 (55 lesions)	No	12.7 (6 weeks AS) lesions; 36.4 (10 weeks AS) lesions; Follow-up: 5 months AE	74.6% (6 weeks AS); 49.1% (10 weeks AS)	3.4% (5 months AE)
Llanos Cuentas et al., 2010	L. braziliensis	G1 (SSG + placebo)	12	No (within the past 30; days); 22.0% had received previously	50% (84 days AS); 100% (336 days AS); Follow-up: 336 days AS	25% (168 days AS); 0% (336 days AS)	8% (336 days AS)
		G2 (SSG + (LEISH-F1 + MPL-SE))	LEISH-F1 5µg = 11		59% (84 days AS); 94% (336 days AS); Follow-up: 336 days AS	13% (168 days AS); 6% (336 days AS)	0% (336 days AS)
			LEISH-F1; 10 µg = 12
			LEISH-F1; 20 µg = 11
Machado et al., 2007	L. braziliensis	G1 (MA + placebo)	12	No	41.6% (90 days AS); Follow-up: 150 days AS	42% (150 days AS)	0% (2 years AE
		G2 (MA + PE)	11	No	82% (90 days AS); Follow-up: 150 days AS	0% (150 days AS)	0% (2 years AE)
Meymandi et al., 2011	L. tropica	G1 (C02 laser)	80	No	56.8% (2 weeks AS); 67.6% (6 weeks AS); 44.4% (12 weeks AS); 93.7% (89/95 lesions); Follow-up: 16 weeks AS	NR	NR
		G2 (il MA + cryotherapy)	80	No	15.8% (2 week AS); 57.5% (6 week AS); 38.2% (12 week AS); 78% (74/95) lesions); Follow-up: 16 weeks AS	NR	NR
Miranda-Verastegui et al., 2005	L. peruviana; L. braziliensis	G1 (MA + IM)	18 (35 lesions)	Yes	6% (20 days AE); 50% (1 month AE); 61% (2 months AE); 72% (3 months AE); 72% (6 months AE); 72% (12 months AE); Follow-up: 12 months AE	27.8% (12 months AE)	NR
		G2 (MA + Vehicle)	20 (40 lesions)	Yes	5% (20 days AE); 15% (1 month AE); 25% (2 months AE); 35% (3 months AE); 50% (6 months AE); 75% (12 months AE); Follow-up: 12 months AE	25% (12 months AE)	NR
Miranda-Verastegui et al., 2009	L. peruviana; L. guyanensis; L. braziliensis	G1 (SSG + vehicle cream)	36	No	17.5% (20 days AS); 33% (1 month AS); 30% (2 months AS); 60% (3 months AS); 63% (6 months AS); 58% (9 months AS); 53% (12 months AS); Follow-up: 12 months AS	41.7% (12 months AS)	NR
		G2 (SSG + IM)	39	No	5% (20 days AS); 43% (1 month AS); 60% (2 months AS); 78% (3 months AS); 75% (6 months AS); 75% (9 months AS); 75% (12 months AS); Follow-up: 12 months AS	23.1% (12 months AS)	NR
Nascimento et al., 2010	Leishmania spp.	G1 (MA + (LEISH-F1 + MPL-SE))	LEISH-F1 5µg = 9	No	80% (84 days AS); Follow-up: 336 days AS	24% (84 days AS)	4% (84 days AS)
			LEISH-F1 10µg = 8
			LEISH-F1 20µg = 8
		G2 (MA +MPL-SE)	8	No	50% (84 days AS); Follow-up: 336 days AS	50% (84 days AS)	NR
		G3 (MA +Saline)	8	No	38% (84 days AS); Follow-up: 336 days AS	62% (84 days AS)	38% (84 days AS)
Nilforoushzadeh et al., 2007	Leishmania spp.	G1 (il MA + topical honey)	33	No	51.1% (6 weeks AS); Follow-up: 4 months AS	48.9% (6 weeks AS)	NR
		G2 (il MA)	35	No	71.1% (6 weeks AS); Follow-up: 4 months AS	28.9% (6 weeks AS)	NR
Nilforoushzadeh et al., 2008	L. tropica; L. major	G1 (MA 60 mg/kg/day + placebo)	43	No	93% (12 weeks AS); Follow-up: 12 weeks AS	7% (12 weeks AS)	NR
		G2 (MA 30 mg/kg/day + OM)	36	No	89% (12 weeks AS); Follow-up: 12 weeks AS	11% (12 weeks AS)	NR
		G3 (MA 30 mg/kg/day + placebo)	45	No	80% (12 weeks AS); Follow-up: 12 weeks AS	20% (12 weeks AS)	NR
Van Thiel et al., 2010	L. major	G1 (il SSG)	118	No	55.1% (6 months AE); Follow-up: 6 months AE	20.3% (6 months AE)	15.3% (6 months AE)
		G2 (il SSG + cryotherapy)	45	No	66.7% (6 months AE); Follow-up: 6 months AE	13.3% (6 months AE)	11.1% (6 months AE)

NR, not reported; G1, Group 1; G2, Group 2; G3, Group 3.
MA, meglumine antimoniate; PE, pentoxifylline; GM-CSF, granulocyte macrophage colony-stimulating factor; IM, imiquimod; il SSG, intralesional sodium stibogluconate; im SSG, intramuscular sodium stibogluconate; KE, ketoconazole; il MA (intralesional meglumine antimoniate); non-silver PD, non-silver containing polyester dressing; silver PD, silver containing polyester dressing; SSG, sodium stibogluconate; LEISH-F1, lyophilized LEISH-F1 protein; MPL-SE, adjuvant; OM, omeprazole.
AS: after the start of treatment, AE: after the end of treatment, and AH: after the healing of the lesion.
No previous treatment of mucosal leishmaniasis. Some patients had previous cutaneous leishmaniasis, but there are no references to previous treatment or not.
Clinical cure rate, therapy failure, and relapse or recurrence given by Firooz et al., 2006, based on the initial number of patients allocated in each group.
^#Partial cure Farajzadeh: decrease in induration size between 25 and 75%.