American cutaneous and mucocutaneous leishmaniasis, a disfiguring and stigmatising disease affecting Central and South American regions, is caused by a parasite transmitted by sandflies. Pentavalent antimonial drugs (sodium stibogluconate (Pentostam, Stibanate, SSG) and meglumine antimoniate (Glucantime, MA)) have been used since the 1940s as first-line therapeutic agents for cutaneous leishmaniasis worldwide. However, other treatments have been used because these are expensive, toxic and painful, and because resistance is emerging.
We assessed 38 trials involving different interventions.
In L. braziliensis and L. panamensis infections there was good evidence that intramuscular (IM) MA was better than oral allopurinol for 28 days, that 20-day intravenous (IV) MA was better 7-day IVMA and also better than 3 or 7-day IVMA with paromomycin plus 12% methylbenzethonium chloride (PR-MBCL). Oral allopurinol plus intravenous antimonials was better than intravenous antimonials.
There was reasonable randomised controlled trial (RCT) evidence in L. braziliensis infections that oral pentoxifylline plus IVSSG was better than IVSSG alone; IVMA was better than IM aminosidine sulphate and IV pentamidine isethionate; and IMMA was better than the Bacillus Calmette-Guérin vaccine. Regarding L. panamensis infections, oral ketoconazole for 28 days and oral miltefosine and topical PR-MBCL were all better than placebo; oral allopurinol better than IVMA, aminosidine sulphate 12mg/kg/day and 18mg/kg/day for 14 days were better than aminosidine sulphate 12mg/kg/day for 7 days.
There was complete absence of RCT evidence on alternative treatments, surgery, oral itraconazole and fluconazole, oral antibiotics like rifampicin, metronidazole and cotrimoxazole, intravenous or topical amphotericin B, oral dapsone, photodynamic therapy, promoting healing therapies, laser, and cryotherapy treatments. Moreover, none of the studies reported quality of life, "microbiological or histopathological cure of skin lesions", changes in ability to detect the parasite by diagnostic methods (e.g. smear or culture) or mortality.
No general consensus on optimal treatment has been achieved but alternatives to intramuscular or intravenous treatments are under active investigation.
The evidence base for the treatment of American cutaneous and mucocutaneous leishmaniasis has many limitations due to poor design and reporting of clinical trials. Because resources are limited for clinical research into neglected diseases, there is a need for prioritising properly designed clinical trials. Therefore, we suggest the creation of an international strategy to improve the quality and standardization of future trials for a better evidence-based strategic approach in the future.
Most trials have been designed and reported so poorly that they are inconclusive. There is a need for large well conducted studies that evaluate long-term effects of current therapies to improve quality and standardization of methods.
Pentavalent antimonial drugs are the most prescribed treatment for American cutaneous and mucocutaneous leishmaniasis. Other drugs have been used with varying success.
To assess the effects of therapeutic interventions for American cutaneous and mucocutaneous leishmaniasis.
We searched the Cochrane Skin Group Specialised Register (January 2009), the Register of Controlled Clinical Trials in The Cochrane Library (Issue 1,2009), MEDLINE (2003 to January 2009), EMBASE (2005 to January 2009), LILACS (from inception to January 2009), CINAHL (1982-May 2007) and other databases.
Randomised controlled trials (RCTs) assessing treatments for American cutaneous and mucocutaneous leishmaniasis.
Two authors independently assessed trial quality and extracted data.
We included 38 trials involving 2728 participants. Results are based on individual studies or limited pooled analyses. There was good evidence in:
Leishmania braziliensis and L. panamensis infections:
Intramuscular (IM) meglumine antimoniate (MA) was better than oral allopurinol for 28 days (1RCT n=127, RR 0.39; 95% CI 0.26, 0.58). Intravenous (IV)MA for 20-days was better than 3-day and 7-day IVMA plus 15% paromomycin plus 12% methylbenzethonium chloride (PR-MBCL) or 7-day IVMA (1RCT n= 150, RR 0.24; 95% CI 0.11, 0.50; RR 0.69; 95% CI 0.53, 0.90; RR 0.64; 95% CI 0.44, 0.92 respectively). Oral allopurinol plus antimonials was better than IV antimonials (2RCT n= 168, RR 1.90; 95% CI 1.40, 2.59; I2=0%).
L. braziliensis infections:
Oral pentoxifylline plus IV sodium stibogluconate (SSG) was better than IVSSG (1RCT n= 23, RR 1.66; 95% CI 1.03, 2.69); IVMA was better than IM aminosidine sulphate (1RCT n= 38, RR 0.05; 95% CI 0.00, 0.78) and better than IV pentamidine isethionate (1RCT n= 80, RR 0.45; 95% CI 0.29, 0.71). Intramuscular MA was better than Bacillus Calmette-Guérin (1RCT n= 93, RR 0.46; 95% CI 0.32, 0.65).
L .panamensis infections:
Oral allopurinol was better than IVMA (1RCT n= 58, RR 2.20; 95% CI 1.34, 3.60). Aminosidine sulphate at doses of 12mg/kg/day and 18mg/kg/day for 14 days were better than aminosidine sulphate 12mg/kg/day for 7 days (1RCT n= 60, RR 0.23; 95% CI 0.07, 0.73; RR 0.23; 95% CI 0.07, 0.73 respectively). Oral ketoconazole for 28 days, oral miltefosine and topical PR-MBCL were better than placebo.