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.