Assessment of intralesional cytokine profile of cutaneous leishmaniasis caused by Leishmania donovani in Sri Lanka.

BACKGROUND: Cytokines play a vital role in the host immune response to infection by initiating the healing process and/or accelerating the progression of the disease in cutaneous leishmaniasis (CL). Very little evidence is available on cytokine profiles and their regulatory function in CL patients in Sri Lanka. The aim of this study was to determine the cytokine expression pattern of IFN-γ, IL-4, IL-11 and IL-12p40 in CL patients and in healthy volunteers. Patients with suspected CL lesions attending to the Dermatology Clinic at the Anuradhapura Teaching Hospital were included in the study. Reverse transcription real time polymerase chain reaction (real-time RT-PCR) was performed to determine the relative expression level of target cytokines. Expression levels were quantified by 2- ∆∆CT equation. RESULTS: The expression of cytokines IFN-γ, IL-4, IL-11 and IL-12p40 were significantly higher in CL patients compared to healthy volunteers (p <  0.05). There was a significant association between the expression of IFN-γ and the duration of the lesion (p = 0.021). Wet CL lesions showed significantly higher expression of IL-4, IL-11 and IL-12p40 (p = 0.039, 0.018 and 0.021 respectively) compared to dry lesions. Papulo-nodular lesions showed significantly high expression of IFN-γ (p = 0.023). However, cytokine expression was not significantly associated with the number, size and the locations of lesions. CONCLUSIONS: The expression levels of all cytokines tested in the present study were significantly (p <  0.05) high in CL patients. Th1 response (IFN-γ and IL-12p40) had higher expression levels compared to Th2 (IL-4) and IL-11 in CL patients.

Efficacy, Safety and Cost-Effectiveness of Thermotherapy in the Treatment of Leishmania donovani-Induced Cutaneous Leishmaniasis: A Randomized Controlled Clinical Trial.

Leishmania donovani causes cutaneous leishmaniasis (CL) in Sri Lanka. Standard treatment is multiple, painful doses of intralesional sodium stibogluconate (IL-SSG). Treatment failures are increasingly reported, hence the need to investigate alternatives. Efficacy, safety, and cost-effectiveness of thermotherapy were assessed for the first time for L. donovani CL. A single blinded noninferiority randomized controlled trial was conducted on new laboratory-confirmed CL patients with single lesions (N = 213). Selected patients were randomly assigned to 1) test group (N = 98; single session of radiofrequency-induced heat therapy (RFHT) given at 50°C for 30 seconds) and 2) control group (N = 115; 1-3 mL IL-SSG given weekly, until cure/10 doses). Patients were followed-up fortnightly for 12 weeks to assess clinical cure. Cost of treatment was assessed using scenario building technique. Cure rates by 8, 10, and 12 weeks in RFHT group were 46.5%, 56.5%, and 65.9% as opposed to 28%, 40.8%, and 59.4% in IL-SSG group, with no major adverse events. Cure rate by RFHT was significantly higher at 8 weeks (P = 0.009, odds ratio [OR]: 2.236, confidence interval [CI]: 1.217-4.108) and 10 weeks (P = 0.035, OR: 1.881, CI: 1.044-3.388), but comparable thereafter. Cost of RFHT was 7 times less (USD = 1.54/patient) than IL-SSG (USD = 11.09/patient). A single application of RFHT is safe, cost-effective, and convenient, compared with multiple doses of IL-SSG in the treatment of L. donovani CL. Therefore, RFHT would be considered noninferior as per trial outcome when compared with standard IL-SSG therapy with multiple benefits for the patient and the national health care system.