Tehran University Medical Journal

Cutaneous leishmaniasis (CL) is an endemic parasitic disease of major health impact in many parts of the world and is caused by several species of the protozoan parasite Leishmania. Antimonial compounds (i.e glucantime and pentostam) are the first-line treatment for cutaneous leishmaniasis with emerging drug resistance as a problem. The control of Leishmania is further complicated by the emergence of drug-resistant parasites. In the clinical settings, resistance to SbV containing drugs is now well established and it was found to occur in South America, Europe, the Middle East and most notably in India. Clinical resistance to organic pentavalent antimonials, in the form of sodium stibogluconate (pentostam) or N-methylglucamine antimoniate (glucantime), has long been recognized. However, it is unknown whether the clinical failure of chemotherapy is attributable to the development of drug resistance mechanisms in the parasite or to a variety of host factors that might also contribute to low drug response. Reported rate of drug-resistance to antimonial compounds in Iran varies from 9.4% to 94.2% and there is not any comprehensive study on this issue. Indeed, in the endemic region treatment with SbV fails in more cases; thus, in general patients infected with resistant parasites are unresponsive although exceptions have been reported. This article aims to review the mechanisms of drug resistance to these compounds. The main resistance factors include genetical, enzymatic, intracellular (such as apoptosis and cytoskeleton changes) and resistance proteins. Also, mechanisms related to drug transport and intracellular activation are discussed. Various methods of drug resistance detection such as culture and molecular methods (i.e polymerase chain reaction) are reviewed. Although the exact mechanism of action glucantime is not clear, it seems that protein and gene factors involved in cellular drug entry are the main causes of drug resistance. Cross-sectional studies on meglumine antimoniate resistance in endemic areas of cutaneous leishmaniasis in Iran are highly recommended. Also, studies for evaluation of alternatives therapies for antimonial resistant cases are required.   

Background: Despite advances in diagnosis and treatment, leishmaniasis is now considered a severe public health problem, particularly in developing countries, such as Iran. Leishmaniasis is among the six most important, parasitic diseases of the world affecting 88 countries in almost every continent. The disease is complex with different clinical presentations such as visceral, cutaneous and mucocutaneous forms. Cutaneous leishmaniasis (CL) is the most common form of the disease in Iran. Antimony compounds are the first line treatment of CL. The treatment of leishmaniasis in endemic areas relies on chemotherapy, and in several parts of the world the mainstay remains the pentavalent antimony (SbV)-containing drugs Pentostam (sodium stibogluconate) and Glucantime (meglumine). There is no comprehensive study on treatment failure rate of this compounds. This study was designed to evaluate treatment failure rate and possible involving factors of antimonial resistance in CL to facilitate and improve treatment strategies of this disease.
Methods: All patients with CL referred to Skin Disease and Leishmaniasis Research Center (SDLRC), from October 2011 to October 2013, treated with antimony compounds were assessed in this study. Patient characteristics (gender, age and place of residence), number, type and location of the lesions, comorbidities and type of treatment were recorded and analyzed.
Results: Rate of treatment failure with Meglusan was 4.3%. Failure rate in men and in patients with previous history of cutaneous leishmaniasis was more than women or patients without CL history (P= 0.000, 0.024 respectively). The results of this study showed that treatment failure was higher in patients with systemic treatment than intralesional (IL) or combination therapy (both IL and systemic treatment) group but this difference was not statistically significant. Also, size and number of the lesions, wound infection, the patient's age, location, education and occupation do not have a significant correlation with treatment failure.
Conclusion: Greater treatment failure rate of Meglusan compared to Glucantime (4.3% versus< 1%, respectively) is an important issue to be considered in CL therapeutic strategy.