Old World cutaneus leishmaniasis (OWCL) is an infection caused by the Leishmania parasite, which is passed onto humans by the bite of sandflies. It is a serious skin disease associated with a broad range of signs, symptoms, and degrees of severity. We wanted to assess the competence and safety of all available treatments for OWCL.
We assessed participants with a healthy immune response who had OWCL diagnosed by laboratory methods. Treatments had to be given alone or in combination with another treatment, and they were compared against no treatment, placebo (an inactive substance) only, or another active treatment. Some of the main outcomes we were interested in included the percentage of wounds cured after the end of treatment, the number of participants completely cured after the end of treatment, speed of healing, side-effects of treatment, and clearance of parasites (i.e. infection).
We reviewed 89 clinical trials, which included 10,583 people, in total, with OWCL. We included participants of both sexes and all ages (mean 24.5 years); most participants were over 18 years of age. Most studies were carried out in single centres in different countries, mainly in the Far or Middle East, and lasted between two to six months. We included a variety of treatments, such as antimonials, antifungals, and antibiotics, which were administered either directly onto the skin or into a wound, taken by mouth, or physically applied (e.g. laser treatment, heat therapy, etc.). Most of the included studies assessed OWCL caused by two species of parasites known as Leishmania major (L. major) and Leishmania tropica (L. tropica).
The evidence is current to November 2016.
Two of the most important treatments that we assessed in this review were itraconazole, an antifungal drug taken by mouth, and paromomycin, an antibiotic applied as an ointment. Trials compared both to a placebo tablet or inactive cream (vehicle).
Participants received 200 mg itraconazole for six to eight weeks or paromomycin ointment at a concentration of 15% plus 10% urea, twice daily for 14 days.
When assessed on average 2.5 months after treatment, more participants were completely cured and cleared of the infection-causing parasites with itraconazole than placebo, but they also had more side effects (mild stomach pain, sickness, and abnormal liver function, as well as headaches and dizziness).
When paromomycin ointment was compared with placebo, there was no difference in the number of completely cured participants or the number who were found to be cleared of parasites when assessed on average 2.5 months after treatment, but those in the paromomycin treatment group had more contained skin reactions (such as swelling, blistering, pain, redness, or itch).
However, as the certainty of the evidence for these outcomes for these particular comparisons was very low, we are not sure of the accuracy of these results.
Neither of our key treatment comparisons assessed the percentage of wounds cured after the end of treatment and speed of healing (i.e. time taken to be cured).
Quality of the evidence
The overall certainty of the evidence for the different outcomes in the two main comparisons was very low. Important reasons for this were that studies were not blinded, or had a small sample size, making the results less precise. Some of the evidence only focused on young people, and the results greatly varied between each study.
We need more research to fill in the following research gaps: 1) trials of OWCL caused by other types of infection such as L. infantum, L. aethiopica, or L. donovani; 2) involving specific subgroups of people such as children; 3) assessing effectiveness and safety of different anti-Leishmania drugs compared with placebo in self-healing forms of leishmaniasis or with traditional first-choice antimonial treatment in complicated form (defined as more than four lesions over 4 cm in size, located close to an opening or small joints, for which previous treatment has failed); and 4) assessing areas such as wound healing and patient-reported outcomes, such as quality of life. In addition, few studies assessed relevant issues such as drug resistance. International collaboration is required to improve the quality and standardisation of future trials in order to develop a better evidence-based approach.