Is intra-lesional meglumine antimoniate (IL-MA) safe and efficacious compared to intra-lesional sodium stibogluconate (IL-SSG) in patients with cutaneous leishmaniasis in Sri Lanka?

Study settings: The study will be conducted in 4 hospital-based dermatology clinics situated in 4 CL endemic districts in Sri Lanka where a Consultant Dermatologist is stationed (Polonnaruwa, Hambantota, Kurunegala and Matale).

Method of randomisation: Randomisation to either arm will be done in blocks of 4 and 6 patients in each center using a random number generator.

Sample collection 1.Sample collection: Slit skin smear/scaping

Slit skin smears will be prepared taking skin samples (dermal scrapings) from the elevated active edge of the lesion. Three smears will be prepared on 2 or 3 slides (a cumulative smear area that covers >1000 high power fields), by a trained medical officer at the study setting dermatology clinic, the smears will then be air dried and stained with giemsa stain by a trained public health laboratory technician (PHLT) or a medical laboratory technician (MLT) who does routine CL testing at each selected hospital. Samples will be taken under aseptic conditions by scraping the active edge of the lesion. The stained smear will be examined microscopically under oil immersion lens (1000x) by the PHLT/MLT and presence of amastigotes will be reported as positive. This will fall under routine care provided by the PHLTs/MLTs in the hospital. The report will be issued to the dermatology clinic and subsequently to the patient adhering to routine procedure practiced in the hospital.

1. Punch Biopsy and PCR

In addition to SSS, a 3 mm punch biopsy will be taken from the active edge of the lesion under local anaesthesia, adhering to standard precautions by the treating medical officer after obtaining the slit skin smear. These samples will be inserted into a sterile Phosphate Buffered Saline (PBS) or DNA preservation buffer, stored in -20C, transported on ice to the department of Parasitology, Faculty of Medical Sciences, University of Sri Jayewardenepura, and stored at-20C until DNA is extracted for PCR to determine the species.

1. Treatment: Injection Procedure for intra-lesional antimonial products [Sodium Stibogluconate (SSG) & Meglumine Antimoniate (MA)]
   • Disinfect the lesion and 2 cm around the lesion with antiseptic
   • Withdraw the product (standard SSG/MA solution) aseptically directly from the ampoule
   • Dosage: Sufficient volume to cover the lesion (approx. 1ml for 1 cm²)
   • Inject into the lesion (intradermal) and induce blanching of the borders until the entire lesion is swollen.
   • Apply a topical antibiotic cream and cover the lesion after treatment
   • Repeat procedure every 7 (weekly) days until endpoint (scar formation) (Taken from SLCD newly updating guidelines with permission)

• Males and females aged 18 years and above.
• The patient should have a positive slit skin smear for Leishmania amastigotes before enrolling into the study. Patients should have 4 or less lesions and having the longest diameter of less than or equal to 4 cm.

• Patients having co-morbidities (diabetes mellitus, hypertension, ischemic heart disease, hormonal imbalances, immune system related diseases, allergies and any other chronic disease that could affect wound healing)
• Patients having previously treated or infected CL lesion/s
• Females who are pregnant, lactating or females of reproductive age (15-49 years) who are planning for a pregnancy
• Those who are living in a different endemic area
• The following persons will also be excluded: those with lesions > 4cm in diameter, having >4 lesions/person, if the lesion/s are/in the periorbital area, nose, pinna of ear, joints, overlying cartilage that requires treatment with IM-SSG/MA
• Any person who has travelled abroad to a leishmaniasis endemic country within the last year.