Table 1. Main methodological characteristics of the Old World leishmaniasis studies.
| Year, Author | Country (cases) | Study arms (patients) | Prospective/ Comparative | Randomized | Inclusion criteria | Exclusion criteria | Cure criteria | Follow-up (months) |
|---|---|---|---|---|---|---|---|---|
| 1987, Zahaf | Tunisia (10) | Ketoconazole (10) | Yes/No | No | Clinical diagnosis or parasitologically confirmed CL | NR | Complete re-epithelialization and negative direct skin smear | 1,5 |
| 1990, Dogra | India (20) | Itraconazole (15) | Yes/ Yes | Yes | Parasitologically confirmed CL | NR | Complete re-epithelialization and negative direct skin smear | 3 |
| No treatment (5) | ||||||||
| 1991, Al-Fouzan | Kuwait (24) | Itraconazole (15) | Yes/ Yes | Yes | Parasitologically confirmed CL | NR | NR | 3 |
| Placebo (9) | ||||||||
| 1992, Norton | Egypt/ Israel (23) | Ketoconazole (23) | No/No | No | Clinical diagnosis or parasitologically confirmed CL | NR | Reduction in the size of lesion by 80% up to complete clearance | 8 |
| 1993, Singh | India (30) | Ketoconazole (30) | Yes/ Yes | No | Parasitologically confirmed CL due to Leishmania donovani | Pregnancy, children below 2 years | Negative direct skin smear | 1,5 |
| No treatment (10) | ||||||||
| 1994, Dogra | India (20) | Itraconazole (10) | Yes/ Yes | Yes | Parasitologically confirmed CL | Pregnancy, children, previous antileishmanial therapy | Complete re-epithelialization and negative direct skin smear | 6 |
| No treatment (10) | ||||||||
| 1994, Enden | Belgium (22) | Itraconazole (22) | Yes/No | No | Parasitologically confirmed CL, absence/failure of previous other specific antileishmanial treatment, absence of spontaneous healing tendency, informed consent obtained. | Pregnancy | Complete re-epithelialization | 6 |
| 1995, Alsaleh | Kuwait (33) | Ketoconazole (18)a | Yes/ Yes | No | Parasitologically confirmed CL | Pregnancy, age younger than 14 years, nursing women | More than 90% re-epithelization and negative direct skin smear | 6 |
| Ketoconazole (15)b | ||||||||
| 1995, Singh | India (16) | Ketoconazole (16) | Yes/No | No | Parasitologically confirmed CL due to Leishmania tropica. | Previous antileishmanial therapy | Complete re-epithelialization and, no evidence of inflammation, negative direct skin smear | 2 |
| 1996, Dogra | India (20) | Itraconazole (10) | Yes/ Yes | Yes | Parasitologically confirmed CL | Chronic disease, abnormality in liver function tests, children below 18 years immunocompromised, previous antileishmanial therapy, lactating females | Complete re-epithelialization accompanied by 3 consecutive and negative direct skin smear | 3 |
| Placebo (10) | ||||||||
| 1996, Momemi | Iran (140) | Itraconazole (65) | Yes/ Yes | Yes | Parasitologically confirmed CL | Pregnancy, age younger than 12 years, duration of disease of more than 4 months. | Complete re-epithelialization and negative direct skin smear | 1 |
| Placebo (66) | ||||||||
| 1997, Ozgoztasi | Turkey (72) | Ketoconazole (32) | Yes/ Yes | Yes | NR | Pregnancy, nursing, serious concomitant diseases | Complete re-epithelialization | 2 |
| P-ointment by El-On (40) | ||||||||
| 1997, Viriyavejakul | Thailand (11) | Ketoconazole (11) | No/No | No | NR | NR | Complete re-epithelialization and/or scar formation | 6 |
| 1998, Siddiqui | Saudi Arabia (55) | Itraconazole (37) | Yes/No | No | Ability to attend King Fahad Hospital at fortnightly intervals, absence of systemic diseases, no previous antileishmanial treatment | Pregnancy, systemic disease, inability to attend at regular intervals | Complete re-epithelialization and negative direct skin smear | 1 |
| SSG (18) | ||||||||
| 2001, Salmanpour | Iran (96) | Ketoconazole (64) | Yes/ Yes | Yes | NR | Pregnancy, lactating females, children below 3 years, systemic disease | Complete re-epithelialization at 6 weeks post-treatment. | 6 |
| MA (32) | ||||||||
| 2002, Alrajhi | Saudi Arabia (209) | Fluconazole (106) | Yes/ Yes | Yes | NR | Lesions that were not parasitologically confirmed by smear, culture, or both. | Complete re-epithelialization | 12 |
| Placebo (103) | ||||||||
| 2005, Nassiri-Kashani | Iran (200) | Itraconazole (100) | Yes/ Yes | Yes | Parasitologically confirmed CL | Pregnancy, lactating females, females in child-bearing age without contraception, receipt of antileishmanial treatment previous, allergy to itraconazole, Duration of lesions > 45 days, lesions on face or near the mucous membranes, more than 5 lesions, lesion with a diameter > 3 cm | Complete re-epithelialization | 3 |
| Placebo (100) | ||||||||
| 2005, Willard | Iraq (237) | Fluconazole (15) | No/ Yes | No | Parasitologically confirmed CL | NR | NR | 6 |
| Itraconazole (2) | ||||||||
| SSG (62) | ||||||||
| Thermotherapy (26) | ||||||||
| Cryotherapy (4) | ||||||||
| 2007, Morizot | France/Swiss (45) | Fluconazole (45) | Yes/ No | No | Parasitologically confirmed CL, if clinical follow-up over the telephone was performed later than day 90 | Pregnancy, systemic disease, acquired immunodeficiency syndrome, disease of the oronasal mucosa | Complete re-epithelialization | 3 |
| 2007, Rafaa | France (14) | Fluconazole (14) | Yes/No | No | NR | NR | Complete re-epithelialization | 3 |
| 2007, Saleem | Pakistan (200) | Itraconazole (100) | Yes/ Yes | No | ||||
| MA (100) | ||||||||
| 2009, Al-Mutairi | Kuwait (78) | Itraconazole (12) | No/ Yes | No | NR | NR | Complete re-epithelialization, no relapse during 6 months after completion of therapy, negative direct skin smear | 6 |
| Cryotherapy (44) | ||||||||
| Dapsone (16) | ||||||||
| Imiquimod (6) | ||||||||
| 2011, Emad | Iran (120) | Fluconazole (60)c | Yes/ Yes | Yes | NR | NR | NR | 1,5 |
| Fluconazole (60)d | ||||||||
| 2014, Khan | Saudi Arabia (20) | Fluconazole (10) | Yes/Yes | No | NR | NR | NR | 8 |
| Itraconazole (10) |
NR: not reported; CL: cutaneous leishmaniasis; SSG: Sodium stibogluconate; MA: Meglumine antimoniate
a: 600 mg/once
b: 800 mg/once
c: 100 mg/twice
d: 200 mg/twice