Molecular Analysis of Dermatophytes Suggests Spread of Infection Among Household Members Mahmoud A. Ghannoum, PhD; Pranab K. Mukherjee, PhD; Erin M. Warshaw, MD; Scott Evans, PhD; Neil J. Korman, MD, PhD; Amir Tavakkol, PhD, DipBact Practice Points When a patient presents with tinea pedis or onychomycosis, inquire if other household members also have the infection, investigate if they have a history of concomitant tinea pedis and onychomycosis, and examine for plantar scaling and/or nail discoloration. If the variables above areCUTIS observed, think about spread of infection and treatment options. Dermatophyte infection from the same strains may Drs. Ghannoum, Mukherjee, and Korman are from University be an important route for transmission of derma- Hospitals Case Medical Center, Cleveland, Ohio. Dr. Warshaw is from the University of Minnesota, Minneapolis, and Minneapolis Veterans tophytoses within a household. In this study, we AffairsDo Medical Center. Dr. Evans is from Notthe Harvard School of Public used molecularCopy methods to identify dermatophytes Health, Boston, Massachusetts. Dr. Tavakkol was from Novartis in members of dermatophyte-infected households Pharmaceuticals Corporation, East Hanover, New Jersey, and and evaluated variables associated with the currently is from Topica Pharmaceuticals, Inc, Los Altos, California. spread of infection. Fungal species were identi- This article was supported by a grant from Novartis Pharmaceuticals Corporation. Dr. Ghannoum has served as a consultant and/or fied by polymerase chain reaction (PCR) using speaker for and has received grants and contracts from Merck & Co, primers targeting the internal transcribed spacer Inc; Novartis Pharmaceuticals Corporation; Pfizer Inc; and Stiefel, (ITS) regions (ITS1 and ITS4). For strain differen- a GSK company. Dr. Mukherjee has served as a consultant and/ tiation, fungal DNA was probed with a ribosomal or speaker for and has received grants and contracts from Astellas DNA–specific probe (containing ITS1, 5.8S ribo- Pharma Inc; Gebauer Company; Great Lakes Pharmaceuticals, Inc; and Saval Pharmaceuticals. Dr. Warshaw has served as a consultant somal DNA, and ITS2) to detect restriction frag- and/or has conducted clinical trials for Clay-Park Labs Inc; Dermik ment length polymorphisms (RFLPs). Associations Laboratories, Inc; Fujisawa Pharmaceutical Company, Ltd; Glenmark; between the spread of a dermatophyte infection Novartis Pharmaceuticals Corporation; Shire; Teva Pharmaceutical and fungal/host variables were determined using Industries Ltd; and Tolmar Inc. Dr. Evans reports no conflict of 2 and logistic regression analyses. Among the interest. Dr. Korman serves as a consultant and speaker for and/or receives grant support from Abbott Laboratories; Amgen Inc; Astellas 50 households enrolled in this study, 18 included Pharma Inc; Celgene Corporation; Centocor Ortho Biotech Inc; multiple infected members (MIMs). Trichophyton Genentech, Inc; Genmab; Novartis Pharmaceuticals Corporation; rubrum was the most commonly isolated dermato- Peplin Ltd; and Watson Pharma Company. Dr. Tavakkol was an phyte species, followed by Trichophyton mentag- employee of Novartis Pharmaceuticals Corporation. rophytes and Epidermophyton floccosum. Sixteen Correspondence: Mahmoud A. Ghannoum, PhD, Center for Medical Mycology, University Hospitals of Cleveland and Case Western T rubrum strains (TR-A to TR-P) were identified, Reserve University, 11100 Euclid Ave, Cleveland, OH 44106 with spread of infection detected in 8 MIM house- ([email protected]). holds. Factors that were significantly (P,.05) WWW.CUTIS.COM VOLUME 91, MAY 2013 237 Copyright Cutis 2013. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Spread of Dermatophyte Infection in Households associated with the spread of infection included confirmed fungal infections were referred to their the presence of strains TR-B or TR-D, a history primary care physicians for appropriate treatment. of concomitant tinea pedis and onychomycosis, Household members were screened at 2 derma- and plantar scaling and/or nail discoloration. This tology centers (University Hospitals Case Medical study is unique in that it used molecular evidence Center, Cleveland, Ohio [site 1], and University to demonstrate the association of certain strains of Minnesota, Minneapolis [site 2]) and 2 podia- with the spread of dermatophyte infection among try centers (Blair Medical Associates, Altoona, members of the same household. Pennsylvania [site 3] and Joppa Foot Care, Parkville, Cutis. 2013;91:237-245. Maryland [site 4]). Participants were reimbursed for costs associated with their participation in the study. Enrolled participants met the following inclu- ermatophytes are fungi that can infect kerati- sion criteria: at least 2 members living in the same nous tissue, including the hair, skin, and nails, household, older than 14 years, and at least 1 mem- Dresulting in cutaneous mycoses called derma- ber with current tinea pedis and/or onychomycosis tophytoses, such as tinea or ringworm infections. as identified by clinical signs and positive KOH and Fungal infection of the nails is called onychomycosis culture of dermatophyte. Exclusion criteria included and infection of the feet is referred to as tinea pedis. treatment with over-the-counter or home remedies Onychomycosis is most often caused by dermato- within 4 weeks of the screening visit and use of phytes,1 namely Trichophyton rubrum (responsible for prescription oral or topical antifungal medications approximately 80% of nail infections), Trichophyton within 4 months of the screening visit. mentagrophytes, and Epidermophyton floccosum. Study Duration and Evaluation Criteria—The study Although onychomycosis can present in fingernails, was approved by an institutional review board at it most often affects the toenails.2,3 Tinea pedis all 4 study sites, and all participants completed an occurs in nearly 50% of patients with onychomy- approved consent form prior to enrollment. The date cosis4; in susceptible patients, many cases of toenail of the first participant’s visit was May 11, 2005, and fungus initially begin as tinea pedis.1,5 Tinea pedis the date of the last participant’s visit was January 9, and onychomycosis are widespreadCUTIS in developed 2006. The following evaluation criteria were used for countries, with nearly 10% of the population being enrolling participants: clinical signs of tinea pedis infected at any given time.3,6 and/or onychomycosis as well as positive mycologic Tinea pedis and onychomycosis are known to be KOH and culture. transmitted through direct or indirect contact with The study consisted of 1 clinic visit (visit 1) dur- infected skin lesions or a contaminated environ- ing which all IPs were evaluated by a dermatologist ment.7,8 Although attempts have been made to inves- or podiatrist for clinical signs of skin and/or toenail tigateDo the spread of dermatophyte Not infections among fungal infection.Copy Samples were then taken from IPs members of the same household,9 earlier analysis with clinical signs of onychomycosis and/or tinea precluded unequivocal demonstration of the spread pedis; if a positive culture and KOH was reported of infection due to a single strain because molecular for the IP, household members were contacted for techniques were not available. In this cross-sectional study enrollment. For each IP, personal and family phase 4 clinical trial, we isolated dermatophytes history of tinea pedis and/or onychomycosis was from infected members of enrolled households, typed recorded, clinical examination of whole-body skin the isolated strains using polymerase chain reac- was conducted, and samples were collected from the tion (PCR) and restriction fragment length poly- feet and/or toenails for mycologic culture and KOH. morphisms (RFLPs), and determined the association The IP was notified of the results of the mycologic of spread of infection with fungal- and disease- culture and KOH by telephone and letter. Following specific variables. isolation of a dermatophyte from the IP, additional household members were enrolled and evaluated Materials and Methods using the same evaluation criteria. Samples were Study Design—Households with at least 2 residents collected from household members within 4 weeks of and 1 individual (index person [IP]) with tinea pedis reporting the IP’s culture positivity. Any use of over- and/or onychomycosis were identified by screening. the-counter treatments, home remedies, or prescrip- Infection was confirmed clinically and mycologically tion oral or topical antifungal medications by non-IP (potassium hydroxide [KOH] and culture positive) in participants was documented. the IP; then other members within the same house- The clinical signs of tinea pedis included itching, hold were examined for tinea pedis and/or onycho- burning, redness, scaling, blisters, and tissue mac- mycosis using the same criteria. All participants with eration of toe webs. Clinical signs of onychomycosis 238 CUTIS® WWW.CUTIS.COM Copyright Cutis 2013. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Spread of Dermatophyte Infection in Households included discoloration, onycholysis (lifting of the ITS4.14 Hybridization signal was detected by chemi- nail from the nail bed), and hyperkeratosis (crum- luminescence. Isolates with the same band pattern bling subungual debris). Clinical signs