For optimal diagnosis, three punch biopsies should be obtained. The first sample should be submitted in formalin for histopathology, the second rolled on a glass slide then fixed with methanol and stained for Giemsa for touch preparation, and the third submitted in Roswell Park Memorial Institute (RPMI) media for culture and PCR analysis. Histopathology is up to 70 % sensitive in the detection of intracellular amastigotes. Cultures are positive within 4 weeks in over 80 % of cases in which organisms are identified on histology, and in almost 30 % of cases negative on histology. Fine-needle aspirates and dermal scrapings may be used for cultures in lieu of punch biopsy. PCR offers a detection rate up to 97 % and, unlike culture and histology, provides speciation which is important for treatment [3]. The United States Centers for Disease Control and Prevention (CDC) provides RPMI media and evaluation of biopsy specimens for histology, culture, touch preparations, and PCR free of charge. Details regarding collection and submission of specimens can be accessed online at: http://​www.​cdc.​gov/​parasites/​leishmaniasis/​resources/​pdf/​cdc_​-diagnosis_​guide_​leishmaniasis_​nov.​2015.​pdf [4].

The major toxicities of systemic pentavalent antimonials (Sb^v, sodium stibogluconate, and meglumin antimoniate) are cardiac arrhythmias, hepatitis, pancreatitis; minor effects include arthralgias and myalgias. The adverse effects of amphotericin B include infusion reactions, renal failure, hypokalemia, and myocarditis. Miltefosine is associated with renal and hepatic toxicity as well as gastrointestinal side effects and teratogenicity. Paromomycin is an aminoglycoside associated with hepatic transaminitis and rare ototoxicity. Pentamadine may cause hypotension, hyperglycemia or hypoglycemia, and gastrointestinal side effects. Azole antifungals can be hepatotoxic. Thus, ECG, LFT, blood urea nitrogen and creatinine, blood glucose, potassium, and amylase and lipase should be evaluated prior to and during systemic treatment for CL and MCL [5].

In one study, both intramuscular stibogluconate and oral miltefosine showed greater than 80 % cure rates for CL caused by L. major. Another study, however, showed only 45 % efficacy for intramuscular stibogluconate (20 mg/kg for 21 days), whereas intralesional stibogluconate (five injections of 2–5 mL every 5–7 days) was 75 % effective, and thermotherapy (radiofrequency waves applied once at 50 °C for 30 s), a second-line therapy, was 70 % effective for Old World CL. A randomized, placebo-controlled trial of paromomycin ointment (with or without gentamicin ointment) demonstrated over 80 % efficacy in the treatment of Old World CL due to L. major. A study performed in Yemen reported CO₂ slush applied once or twice was over 90 % effective for the treatment of Old World CL. Finally, cryotherapy was shown to be cost-effective and cured 84 % of lesions with minimal scarring and side effects following weekly treatments for 1–4 weeks.