Interventions for Old World cutaneous leishmaniasis
Abstract
Background
Cutaneous leishmaniasis is caused by a parasitic infection and is considered one of the most serious skin diseases in many developing countries. Antimonials are the most commonly prescribed treatment but other drugs have been used with varying success.
Objectives
To assess the effects of treatments for Old World cutaneous leishmaniasis (OWCL).
Search methods
We searched the Cochrane Skin Group Specialised Register (April 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2008), MEDLINE (2003‐April 2008), EMBASE (2005‐April 2008), CINAHL (1982‐August 2007), LILACS (from inception to April 2008) and ongoing trials databases (August 2007).
Selection criteria
Randomised controlled trials assessing treatments in immuno‐competent people with OWCL confirmed by smear, histology, culture or polymerase chain reaction.
Data collection and analysis
Two authors independently assessed trial quality and extracted data.
Main results
We included 49 trials involving 5559 participants. Reporting quality was generally poor and only two studies contained sufficiently similar data to pool.
InLeishmania major infections, there was good RCT evidence of benefit of cure around 3 months after treatment when compared to placebo for 200 mg oral fluconazole (1 RCT n = 200, RR 2.78; 95% CI 1.86, 4.16), topical 15% paromomycin + 12% methylbenzethonium chloride (PR‐MBCL) (1 RCT n = 60, RR 3.09; 95% CI 1.14, 8.37) and photodynamic therapy (1 RCT n = 60, RR 7.02; 95% CI 3.80, 17.55). Topical PR‐MBCL was less efficacious than photodynamic therapy (1 RCT n = 65, RR 0.44; 95% CI 0.29, 0.66). Oral pentoxifylline was a good adjuvant therapy to intramuscular meglumine antimoniate (IMMA) when compared to IMMA plus placebo (1 RCT n = 64, RR 1.63; 95% CI 1.11, 2.39)
InLeishmania tropica infections, there was good evidence of benefit for the use of 200 mg oral itraconazole for 6 weeks compared with placebo (1 RCT n = 20, RR 7.00; 95% CI 1.04, 46.95), for intralesional sodium stibogluconate (1 RCT n = 292, RR 2.62; 95% CI 1.78, 3.86), and for thermotherapy compared with intramuscular sodium stibogluconate (1 RCT n = 283, RR 2.99; 95% CI 2.04, 4.37).
Authors' conclusions
Most trials have been designed and reported poorly, resulting in a lack of evidence for potentially beneficial treatments. There is a desperate need for large well conducted studies that evaluate long‐term effects of current therapies. We suggest the creation of an international platform to improve quality and standardization of future trials in order to inform clinical practice.
PICOs
Plain language summary
Interventions for Old World cutaneous leishmaniasis
Old World cutaneous leishmaniasis (OWCL) is a disfiguring and stigmatising disease occuring in areas of the Mediterranean, Middle East and Asia, caused by a parasitic infection transmitted by sandflies. Pentavalent antimonial drugs such as sodium stibogluconate (Pentostam, Stibanate) and meglumine antimoniate (Glucantime), have been used since the 1940s as the main first‐line therapeutic agents for cutaneous leishmaniasis worldwide. However, many different treatments for OWCL have been described.
We assessed 49 trials involving different interventions. In Leishmania major infections there was good evidence of benefit for the use of 200 mg oral fluconazole for 6 weeks, topical paromomycin + 12% methylbenzethonium chloride (MBCL), photodynamic therapy and oral pentoxifylline as an adjuvant therapy to intramuscular meglumine antimoniate. However, compared with other interventions there was not enough good evidence for the use of intralesional zinc sulphate weekly compared with antimonials, and topical 15% paromomycin +12% MBCL for 28 days compared with photodynamic therapy. There was good trial evidence of benefit for the use of 200 mg oral itraconazole for 6 weeks in Leishmania tropica infections, and to support the use of intralesional sodium stibogluconate and thermotherapy rather than intramuscular stibogluconate. There was good RCT evidence for not supporting the use of topical 5% imiquimod cream combined with antimonials.
The major drawback associated with intralesional treatments is local pain which causes significant patient discomfort. Intramuscular or intravenous drugs are associated with more severe adverse effects. While there is no general consensus on optimal treatment, alternatives to intramuscular or intravenous treatments are under active investigation. Efficacious, well tolerated and inexpensive oral agents are clearly needed in OWCL because we still do not have an ideal treatment that can treat all target species with few serious adverse effects.
The current evidence for the treatment of OWCL has many limitations and there is much scope for improving the design and reporting of clinical trials. None of the studies reported the degree of functional and aesthetic impairment and only two assessed the quality of life. Since resources are limited for clinical research into neglected diseases there is a need to prioritise and carry out properly designed clinical trials.
We suggest the creation of an international platform to improve the quality and standardization of future trials in order to develop a better evidence‐based approach.
