Fungal diseases in the UK David W. Denning Director, NHS National Aspergillosis Centre University Hospital of South Manchester The University of Manchester President, Global Action Fund for Fungal Infections

Fungal infections Cutaneous i.e. athlete’s foot, ringworm and onychomycosis Mucosal i.e. oral or vulvovaginal thrush Chronic fungal infections such as chronic pulmonary aspergillosis Allergic i.e. allergic fungal sinusitis and allergic bronchopulmonary aspergillosis (ABPA) Invasive and life-threatening i.e. candidaemia, invasive aspergillosis and cryptococcal meningitis

Skin, hair and nails fungal infections 4th most prevalent chronic disease problem after dental caries, tension headache and migraine. 985 million people affected, 14.3% of the global population * Including fungal complications Vos et al, Lancet 2012;380:2163 www.GAFFI.org

Fungal hair infection – tinea capitis ~25% of children in schools all over Africa. Common in other communities ~200 million children affected – no good UK data May be disfiguring and painful, certainly affects children’s self esteem Griseofulvin or fluconazole therapy Transmissible www.GAFFI.org

Cutaneous fungal infections Ringworm, tinea versicolor, tinea pedis (athlete’s foot), onychomycosis Very common Terbinafine, itraconazole, fluconazole and griseofulvin all effective Transmissible www.GAFFI.org

Aspergillus otitis externa Chronic otitis affects 3-5% of the population (200-350 million) ~10% are fungal in origin, usually A. niger www.GAFFI.org

Allergic fungal sinusitis Chronic rhinitis 10-30% adults in UK 60,000 – 250,000 with allergic fungal rhinosinusitis Responsive to polyp removal, nasal steroids, saline douches and antibiotics Antifungals have a minor role www.GAFFI.org

Fungal keratitis Implantation disease, often injury related, farmers ~50% of keratitis in LMICs = fungal Numerous fungal species involved; Aspergillus and Fusarium predominate Diagnosis requires microscopy/histopathology + culture No diagnostic capability in most low resource countries including Africa www.GAFFI.org

Fungal keratitis may be increasing in the UK - Moorfields Ong et al. Am J Ophthamol 2016; 168:227. www.GAFFI.org

Sight-threatening infection caused by Fusarium mould 74

Vulvovaginal candidiasis (VVC) 55% of women have had VVC by mid 20’s 6-9% of women have VVC >4 times per year, Global estimate of the problem of recurrent VVC is ~137 million women annually (range 103 - 172M) aged 15-54 years UK estimate is ~ 1,000,000 affected Duration of recurrent VVC is highly variable, 1- 2 years commonly, sometimes >8 years. Denning et al. Lancet Infect Dis 2017. In press www.GAFFI.org

Other UK health burden statistics: Meningococcal (meningitis) disease – 805 cases in 2015/16 Malaria – 1,400 cases in 2015 TB – 5,758 cases in 2015 New HIV diagnoses - 6,151 in 2014 Breast cancer - 53,696 in 2013, 11,433 deaths Multiple sclerosis – 107,000 in 2016 Multiple sources

Pegorie et al, J Infect 2017;74:60

Risk groups and frequencies of invasive aspergillosis – different test performances Herbrecht, Ann NY Acad Sci 2012;1271:23

Invasive aspergillosis by finished consultant episodes www.aspergillus.org.uk

Invasive aspergillosis in lung disease patients - most probably being missed Pegorie et al, J Infect 2017;74:60

Invasive aspergillosis in critical care Pegorie et al, J Infect 2017;74:60

Aspergillus bronchitis Complicates cystic fibrosis and bronchiectasis Recurrent infection and/or mucus plugging Superficial invasion of the bronchial wall. 8,600 UK CF patients, 5,500 adults. Aspergilus bronchitis affects ~1,500 Non-CF patient burden unclear

Pneumocystis pneumonia in the UK – AIDS and non-AIDS [1:3 ratio] Maini et al, Emerg Infect Dis 2013;10:386

Important airborne fungi Alternaria Cladosporium Aspergillus Rhizopus

Common allergen exposures by month Twaroch et al, Allergy Asthma Immunol Res 2015:7:205

Skin prick testing for fungal asthma Cladosporium +ve O’Driscoll, unpublished

Mean sensitization score (mm) Fungal allergy is associated with more hospital admissions Non-Mould allergens No Hospital Admission Single Multiple Admissions 20.0 17.5 Mould allergens No Hospital Admission Single Multiple Admissions P= <0.0001   15.0 12.5 Mean sensitization score (mm) (Mean and 95% CI) 10.0 7.5 5.0 2.5 0.0 O’Driscoll et al, BMC Pulmonary Medicine 2005;5:4

7,104 young adults in 13 countries (11 Europe) Questionnaires, sensitisation to Alternaria and Cladosporium, assessment of homes, asthma evaluation (metacholine challenge). New onset asthma (n=355) Correlation with water damage and mould in the house Follow up 8.7 (5.9-11.7) years. Risk ratio for new asthma = 1.46 (water damage) and 1.3 (indoor moulds). Norback D, Occup Environ Med 2013;70:325-31.

‘Fungal asthma’ in the UK Pegorie et al, J Infect 2017;74:60