South Asian Epidemic of Antifungal Therapeutic Failures: Congress Proceedings and Take-home Messages. First International Congress of SAARCUM: South Asian Alliance against Recalcitrant Cutaneous Mycosis. 17 November 2018, Medanta – The Medicity, Gurugram, India

The nuisance of widespread failure of antifungal pharmacotherapy in the treatment of superficial cutaneous mycosis, especially dermatophytic infections has become daunting for practitioners across South Asia. Although multiple sporadic attempts at the regional/national level have been conducted to find a solution to this menace in India, the need of the hour was the formation of a dedicated international alliance that eventuated in the creation of the South Asian Alliance against Recalcitrant CUtaneous Mycosis (SAARCUM), coordinated by Dr Sidharth Sonthalia (Dermatologist) from India, and involving participation from South Asian countries including Nepal, Sri Lanka, Bangladesh, Thailand, and Singapore. The second essential aspect of such an alliance i.e. involvement of medical specialists other than dermatology was also ensured. Today, SAARCUM is a conglomeration of dermatologists, microbiologists, epidemiologists, senior scientists involved in mycology research, internists, pediatricians, and psychiatrists. DERMASOURCE INDIA (DSI), a well-known venture of dermatologists and management experts, credited with holding the first ever National Dermoscopy Conclave of India in 2015 followed by focused conclaves on niche areas like polycystic ovary syndrome (PCOS), platelet-rich plasma (PRP), psychodermatology, hair transplantation amongst others, and International Organizing partner for various Congresses held by different National Dermatology Associations/Societies (Nepal, University of Cairo, Spring Continental Congress of Dermatology, Tehran, and Sri Lankan College of Dermatologists – SLCD) organized the First International Congress of SAARCUM on 17th November, 2018 at Medanta – The Medicity, Gurugram, India [www.dermasourceindia.com]. The current DSI venture –First International Congress of SAARCUM – was governed by multi-regional and multi-specialty approach, the bare essentials to tackle the epidemic of antifungal therapeutic failures (AFTF) overwhelming South Asia and spreading across the globe. The scientific programme was delivered by including Chairpersons, 35 Speakers [Figure 1], 2 quiz masters, and presenters of 6 shortlisted Award papers and 5 E-Posters. International faculties included representatives from the National Societies of Dermatology of Nepal, Sri Lanka, and Bangladesh. Experienced faculties from different specialties contributed to multiple facets of clinical mycology.Figure 1: Eminent speakers at the DSI-SAARCUM CongressThe conference was attended by 162 delegates from across the length and breadth of India, and neighboring countries including Nepal, Bhutan, Bangladesh, and Sri Lanka. While the majority of delegates were dermatologists, a substantial number hailed from internal medicine and pediatrics, a positive trend since inclusion of all primary stake-holders is imperative to win this battle against mycoses. The scientific proceedings started with the Award Paper session. Out of 17 abstracts received, the 6 most meritorious papers pertaining to research in cutaneous mycology were presented by the residents [Figure 2]. The DSI-SAARCUM inter-collegiate postgraduate quiz – prelims were conducted and of the 11 participating teams, 4 teams were shortlisted for the finals.Figure 2: DSI-SAARCUM Residents' Award paper session with the Judges – Prof. MPS Sawhney (Head, SGT Medical College, Gurugram), Prof. Surabhi Dayal (Head, PGIMER, Rohtak), and Dr Nayani Madarasingha (Senior Joint Secretary SLCD, Sri Lanka)To stimulate and foster the learning potential of the delegates, DSI always holds a Pre- and Post-Test Analysis for all delegates. It included 30 questions (MCQs, Pictorial, Dermoscopic) directly related to cutaneous mycology, which were contributed by the Congress Speakers, on the premise that careful tending to their lectures would give away the answers one-by-one. The learning points from different lectures, dialogue sessions, and workshops are presented in this paper. Session I: THE MIRROR Chairpersons: Dr Sanjay Chaturvedi (Director-Professor, Community Medicine, UCMS) Dr Chetna Ghura (Senior Consultant Dermatologist, Metro Hospital, Faridabad) Dr VK Upadhyaya (Senior Consultant Dermatologist, Delhi) Dr Rahul Sharma, Associate Professor of Community Medicine, UCMS-GTBH, New Delhi, our first speaker gave a reality check on the problem statement, through his talk on “The changing landscape of superficial mycoses in South Asia.” Superficial mycoses affect 20–25% of the world's population There has been an alarming increase in the number of “recalcitrant/resistant” superficial mycoses, from India, South Asia, and globally in the last few years The cases constitute the “tip of the iceberg” and there lies a substantial paucity of evidence The environment, host, and agent factors are responsible for the changing landscape Environmental factors related to global warming Host factors related to immunity and socioeconomic and pharmacological factors Agent factors related to increased resistance of Trichophyton rubruml and increased prevalence of Trichophyton mentagrophytes, a zoophilic fungus, as the co-dominant pathogen along with T. rubrum Public health constitutes the way forward for addressing the changing landscape, through study of region and population specific variations in fungal species and drug sensitivity patterns, assessment of socioeconomic burden, capacity building for care and antifungal stewardship by all involved stakeholders. Dr Smriti Shrestha, Assistant Professor of Dermatology, Kathmandu Medical University, Nepal, deliberated on the aspect of “Antifungal Therapeutic Failure vs Resistance.” Last 5–6 years have seen a substantial rise in AFTF: Recalcitrant infections: persistence of clinically appreciable infection since the disease onset with none or sub-optimal response to an adequate treatment with systemic antifungal agents Chronic dermatophytoses: infections persisting beyond 6 months Recurrent infections: re-occurrence of lesions within <6 weeks of clinical cure Relapses: re-occurrence after 6–8 weeks of infection-free interval. Clinical (in vivo) resistance: failure to eradicate a fungal infection despite adequate administration of an antifungal agent with in vitro activity against the organism Mycological (in vitro) resistance: non-susceptibility of the fungus to standard doses of minimum inhibitory concentration (MIC) values of antifungals determined by CLSI/EUCAST (Clinical & Laboratory Standards Institute/European Committee on Antimicrobial Susceptibility Testing). In general, MIC >1 μg/ml is vaguely taken as cut-off suggestive of in vitro resistance. True drug resistance (although on a rise) contributes to a small proportion of AFTF Large scale and region-specific studies to define the variations in MIC levels of antifungals in dermatophytes are essential to provide data on the emergence of true drug resistance, and quantitative contribution of resistance to AFTF Drug pharmacokinetics and drug delivery to the site of infection might outweigh the impact of a susceptibility test result Itraconazole is not efficacious in the treatment of palmar and plantar dermatophytoses as drug levels achieved in sweat are negligible as compared to that in sebum Topical antifungals which penetrate deeper like ciclopirox olamine show better efficacy for tinea with involvement of vellus hair. Dr Abhishek Omchery, Consultant Dermatologist, Gurugram, further elaborated on “Mycological vs clinical resistance.” Mycological resistance: Primary or intrinsic: inherently resistant strain acquired from the external milieu Secondary: inherently resistant variant(s) is/are selected from a heterogeneous population or the susceptible strain mutates during treatment. The 90–60 rule: Infections due to in vitro susceptible isolates would respond to appropriate therapy in ∼90% of cases, whereas infections due to resistant isolates would respond in ∼60% of cases. In vitro resistance may not always predict the treatment outcome The time frame for suspecting a resistant fungal infection, despite giving an adequate dose and duration of treatment (having ruled out immunological and extraneous factors) should be taken as 4 weeks. PSYCHODRAMA ROLE PLAY Akin to all CMEs organized by team DSI, a 10-minute session of PSYCHODRAMA ROLE PLAY was held – the easiest and most effective mode of communicating a serious issue in a lighter vein. Enacted by Dr Deepak Jakhar and Dr Sidharth Sonthalia, this role play highlighted the dual consternation of skewed health awareness-empowerment of the new generation of patients, and the raging issue of topical steroid abuse contributing to antifungal therapy failures. Session II: BACK TO THE LABORATORY Chairpersons: Dr. Ajay Chopra (Prof & Head, Dermatology, ACMS, New Delhi) Dr. Anil Agarwal (Senior Consultant Dermatologist, Gurugram) Dr. Surabhi Dayal (Prof & Head, Dermatology, PGIMER, Rohtak) Dr Shukla Das, Director-Professor, Department of Microbiology and Incharge – Mycology Unit, UCMS-GTBH, Delhi enlightened everyone with less-known aspects of “Clinico-mycological evidence and host immune responses in chronic cutaneous mycoses.” Mycological and clinical cure as a target for complete cure should be the focus of all clinicians Dysregulated host immune responses are an important factor for resistant tinea infections The immune system tailors protective responses according to the microbial challenges, governed by different cytokines in the environment and the strength of T cell receptor –antigen interactions. Dendritic cells and CD4+ T cells can differentiate into classical Th1/Th2/Th17 or Tfh and iTreg cells Cell-mediated immunity can eliminate fungi but poor delayed type hypersensitivity or immune defects can prevent fungal clearance from the skin High IL-4 expressed due to sensitization to fungal antigen leads to high IgE (Th 1 – 2 shift), which leads to chronicity of the fungi IL-23 R is critical in enhancing Th17 population and promotes tissue inflammation, while Tregs m

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