Characterization of Recalcitrant Dermatophytosis in a Multicenter Study in Sri Lanka.

A changing clinical scenario of dermatophytosis has been observed in Sri Lanka during the past few years. In keeping with the trend described in India, an increase in the number of chronic, relapsing, and recalcitrant infections has been noted. The objective of our study was to assess the therapeutic response of dermatophytosis to standard antifungal treatment in Sri Lanka and to identify possible contributory factors in cases showing inadequate therapeutic response. A descriptive, observational, cross-sectional study was carried out in nine hospitals, representing each province. Over 6 months, patients with dermatophytosis on glabrous skin were included. All subjects underwent skin scrapings for mycological studies and were treated with a standard course of antifungals for a specific period. In those patients who achieved complete clearance, recurrences were noted. The study included 796 patients, of whom 191 (24%) had symptoms for more than 3 months at presentation. A total of 519 patients (65.2%) had multiple-site involvement, and 503 (63.2%) had evidence of prior use of topical steroids. Skin scrapings were positive for fungal elements in the direct smears of 659 patients (82.8%), and the predominant dermatophyte isolated was Trichophyton mentagrophytes (65.6%). Partial responders after 10 weeks of treatment and recurrences after complete clearance were significantly greater in the group that used topical steroids before presentation (P < 0.001). This study highlights the magnitude of the threat of an inadequate therapeutic response in dermatophytosis in Sri Lanka, and identifies steroid misuse, and the shift of the predominant fungal species to T. mentagrophytes as possible causative factors.

Therapeutic Response to Thermotherapy in Cutaneous Leishmaniasis Treatment Failures for Sodium Stibogluconate: A Randomized Controlled Proof of Principle Clinical Trial.

Treatment failure to intralesional sodium stibogluconate (IL-SSG) is a health challenge for cutaneous leishmaniasis (CL) in Sri Lanka. A randomized controlled proof of principle clinical trial, with two arms (viz., radio frequency-induced heat therapy [RFHT] by a ThermoMed™ device (Model 1.8, Thermosurgery Technologies, Inc., Phoenix, AZ) and thermotherapy by a handheld exothermic crystallization thermotherapy for CL [HECT-CL] device) was conducted on 40 CL treatment failures to IL-SSG, from three hospitals in Tangalle, Hambantota, and Anuradhapura, from January 2017 to January 2018, followed up for 180 days post-thermotherapy with a final follow-up in February 2020. Intention-to-treat cure rates were calculated at day 90 (initial cure rate) and at day 180 (final cure rate) posttreatment. Radio frequency-induced heat therapy group: the initial cure rate was 100% (20/20) and the final cure rate was 95% (19/20), with one patient relapsing. The HECT-CL group: both the initial and final cure rates were 80% (16/20), with no relapses and one excluded from the trial. In February 2020 (1.6-3 years posttreatment), 27 traceable patients (RFHT = 16, HECT-CL = 11) remained healed. Second-degree burns were observed with RFHT in 65% (13/20), with HECT-CL in 15% (3/20), which completely resolved subsequently. The cure rates between the two treatment groups were comparable (P = 0.15). Radio frequency-induced heat therapy consumed less time and required only a single hospital visit. Handheld exothermic crystallization thermotherapy for CL is potentially usable at community settings with both being less costly than IL-SSG. This study is the first proof that thermotherapy is an efficacious and safe treatment for CL patients in Sri Lanka, complicated by treatment failure to IL-SSG.

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.

Cutaneous leishmaniasis in Sri Lanka: effect on quality of life.

BACKGROUND: The quality of life in many patients is affected by skin lesions. Cutaneous leishmaniasis (CL), the commonest form of leishmaniasis, is no exception. In Sri Lanka, CL is an emerging parasitological condition with over 3,000 cases within the last decade. Lesions are often seen on exposed parts of the body which may cause social stigma, and hence a study was done to assess the changes in quality of life of CL patients. METHOD: A total of 294 patients (200 civilians and 94 army personnel) answered a previously validated Sinhala self-administered Dermatology Life Quality Index (DLQI) questionnaire and an interviewer-administered questionnaire. RESULTS: From the majority of the civilian population, 47% had no effect on their quality of life due to CL lesions, 33.5% were affected in a small way, 12.5% were affected moderately, 6.5% suffered in a large way, and 0.5% (one patient) were extremely affected due a large ulcerative lesion being on the face. The effect on quality of life was negligible in the majority of army patients as well (35.1% no effect, 31.9% small effect), with a few patients affected moderately and very largely (22.3 and 10.6%, respectively). The most affected domain in patients was symptoms and feeling 1.27 ± 1.400 (mean ± SD), and the least was the relationships domain 0.27 ± 0.625. CONCLUSION: CL does not seem to affect the quality of life in the majority of Sri Lankan patients when compared to CL in other parts of the world or other skin diseases.

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.

Clinico-Epidemiological Patterns of Cutaneous Leishmaniasis Patients Attending the Anuradhapura Teaching Hospital, Sri Lanka.

Cutaneous leishmaniasis (CL) caused by Leishmania donovani is an endemic vector-borne disease in Sri Lanka. Over 2,500 cases have been reported since 2000 and the number of CL cases has dramatically increased annually. Total 57 clinically suspected CL patients attending the dermatology clinic in Anuradhapura Teaching Hospital were recruited from January to June 2015. Slit skin smears and skin biopsies were taken from each of the subjects. Clinical and epidemiological data were obtained using interviewer administered questionnaire. Forty-three (75.4%) patients among 57 were confirmed positive for L. donovani. The majority of infected patients was males (P=0.005), and the most affected age group was 21-40 years. Soldiers in security forces, farmers, and housewives were identified as high risk groups. The presence of scrub jungles around the residence or places of occupation (P=0.003), the presence of sandflies (P=0.021), and working outsides more than 6 hr per day (P=0.001) were significantly associated with CL. The number of lesions ranged from 1-3, and the majority (76%) of the patients had a single lesion. Upper and lower extremities were the prominent places of lesions, while the wet type of lesions were more prevalent in females (P=0.022). A nodular-ulcerative type lesion was common in both sexes. The presence of sandflies, scrub jungles, and outdoor activities contributed to spread of Leishmania parasites in an endemic pattern. Implementation of vector control programs together with health education with regard to transmission and prevention of CL are necessary to control the spread of this infection.