The Global Burden of Fungal Diseases David W. Denning National Aspergillosis Centre, University Hospital of South Manchester The University of Manchester Global Action Fund for Fungal Diseases
Cutaneous fungal infections 4 th 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. : www. GAFFI. org 216
Years lived with disability cutaneous fungal infections Hay et al. J Invest Dermatol 2014; 134: 1527: www. GAFFI. org
Fungal infections in AIDS www. GAFFI. org
Pneumocystis pneumonia Estimating the burden in AIDS People living with HIV 35, 500, 000 On ART 15, 052, 000 (42. 4%) Unprotected 20, 448, 000 CD 4<100 2, 760, 480 (13. 5%) www. GAFFI. org
Pneumocystis pneumonia Estimating the burden in AIDS Global burden calculated using a low/medium incidence PCP rate (Thailand) of 14. 75% = 407, 171 Ratanasuwan W et al, J Med Assc Thai 2005; 88: 335. : www. GAFFI. org
Pneumocystis burden increases with increasing GDP PCP TB Lowe et al, PLo. S One 2013; 8: e 69969. : www. GAFFI. org
Pneumocystis cases in 1, 000 HIV patients in the USA 1991 -2001 - happening despite being in care Morris et al, Emerg Infect Dis 2004; 10: 1713. www. GAFFI. org
PCP is reduced but not eliminated by ART Morris A et al, Emerg Infect Dis 2004; 10: 1713 : www. GAFFI. org
Pneumocystis pneumonia in the UK – all underlying diseases Maini et al, Emerg Infect Dis 2013; 10: 386. www. GAFFI. org
Missed diagnoses in AIDS Antinori S et al, Am J Clin Pathol 2009; 132: 221 www. GAFFI. org.
Fungal infections in AIDS www. GAFFI. org
Histoplasma capsulatum geography Moshi, Tanzania, 0. 9% disseminated histoplasmosis in 970 febrile inpatients - 67% DM patients HIV No map for Asia, Oceania or Australasia Lofgren et al. Trans Roy Soc Hyg Trop Med 2012; 106: 504. www. GAFFI. org
Fungal infections in hospitalised and critically ill patients www. GAFFI. org
Invasive fungal infections Disease Most common species Estimated Life. Threatening Infections / Year Location Mortality Rates (% in infected populations) Opportunistic Systemic Mycoses Invasive aspergillosis Aspergillus spp. Worldwide >200, 000 30– 95% Invasive candidiasis Candida spp. Worldwide >400, 000 46– 75% >1, 000 20 - 70% Cryptococcosis worldwide Cryptococcus neoformans varies by Candidaemia rate Mucormycosis If 5/100, 000 Rhizopus oryzae Pneumocystis jirovecii country from 2 to 26/100, 000 30 – 90% >10, 000 and worldwide global population 7 billion = 350, 000+ worldwide Brown et al. Sci Transl Med 2012; 4: 165 rv 13. >400, 000 20 - 80% www. GAFFI. org
Candidaemia reporting in the UK 1, 719 cases in 2012 ~25% Candida glabrata 1. 8% of bloodstream isolates 10 th most common www. hpa. org. uk/hpr/infections/bacteraemia. htm Voluntary surveillance system in England that collects laboratory reports of all microorganisms isolated (including fungi) at approximately 400 NHS and other laboratories www. GAFFI. org
Candidaemia in the UK 2. 95/100, 000 www. hpa. org. uk/hpr/infections/bacteraemia. htm www. GAFFI. org
Invasive candidiasis (IC) and candidaemia in the UK The pooled blood culture positivity rate in patients with IC was 0. 38 (95%CI: 0. 29 to 0. 46) And the proportion patients with IC who have candidaemia = 33% (most IC is intra-abdominal/peritonitis) Avni et al. J Clin Microbiol 2011; 49: 665; Nguyen et al. Clin Infect Dis 2012: 54: 1240 www. GAFFI. org
Invasive candidiasis (IC) and candidaemia in the UK The pooled blood culture positivity rate in patients with IC was 0. 38 (95%CI: 0. 29 to 0. 46) And the proportion patients with IC who have candidaemia = 33% (most IC is intra-abdominal/peritonitis) Therefore the rate of invasive candidiasis in the UK (excluding Scotland) = 1, 719/3 = 573 (candidaemia + IC) + 573 x 2/0. 38 = 3015 IC cases + 1, 719 -573 = 1146 candidaemia without IC = 4, 734 IC and candidaemia cases in the UK Avni et al. J Clin Microbiol 2011; 49: 665; Nguyen et al. Clin Infect Dis 2012: 54: 1240 www. GAFFI. org
Invasive candidiasis (IC) and candidaemia in the UK The pooled blood culture positivity rate in patients with IC was 0. 38 (95%CI: 0. 29 to 0. 46) And the proportion patients with IC who have candidaemia = 33% (most IC is intra-abdominal/peritonitis) Therefore the rate of invasive candidiasis in the UK (excluding Scotland) = 1, 719/3 = 573 (candidaemia + IC) + 573 x 2/0. 38 = 3015 IC cases + 1, 719 -573 = 1146 candidaemia without IC = 4, 734 IC and candidaemia cases in the UK Population of 58. 3 M Overall rate of 8. 1 /100, 000 Avni et al. J Clin Microbiol 2011; 49: 665; Nguyen et al. Clin Infect Dis 2012: 54: 1240 www. GAFFI. org
Invasive candidiasis (IC) and candidaemia in the world 1, 719 candidaemia cases = 4, 734 IC and candidaemia cases So if 350, 000 candidaemia cases in the world, then 963, 875 IC and candidaemia cases Probably an underestimate partly because of India – an estimated 675, 000 cases, based on a recent multicentre study in ICU www. GAFFI. org
Fungal infections in hospitalised and critically ill patients www. GAFFI. org
Aspergillus, IPA and COPD ~ 1. 3% of COPD admissions have invasive aspergillosis by culture ~ 22% of Aspergillus in COPD = invasive aspergillosis Guinea et al. Clin Microbiol Infect 2010; 16: 870. www. GAFFI. org
IA in COPD 58 of the 298 COPD admissions with a lower respiratory tract sample processed grew Aspergillus spp. 39 (3. 9%) had probable IA. Xu H et al. Clin Microbiol Infect 2012; 18: 403. www. GAFFI. org
Aspergillus, IPA and COPD Xu H et al. Clin Microbiol Infect 2012; 18: 403. www. GAFFI. org
COPD admissions (rate per 40+ years old) OECD Health Statistics 2013, ttp: //dx. doi. org/10. 1787/health-data-en. www. GAFFI. org
Fungal Infections in China ECCMID 2013. www. GAFFI. org
COPD in China 32, 800, 000 patients with COPD 11, 858, 100 admissions to hospital 154, 155 IA cases in COPD at a 1. 3% rate 462, 466 IA cases in COPD at a 3. 9% rate Zhu et al. ECCMID 2013; Abstr 3393. www. GAFFI. org
Fungal infections in hospitalised and critically ill patients www. GAFFI. org
Fungal disease of the lungs in outside the hospital www. GAFFI. org
Fungal keratitis • 1– 12 million affected worldwide, • Usually farmers and labourers • 4% children USA 11/100, 000 Denmark 0. 06/100, 000 UK 0. 034/100, 000 Hong Kong 6. 3/100, 000 India 13/100, 000 Bhutan 339/100, 000 Myanmar 710/100, 000 Nepal 799/100, 000 Deorukhkar S. Singapore Med J 2012; 53: 264. www. GAFFI. org
Chromoblastomycosis www. GAFFI. org
Aspergillus otitis externa • Acute otitis affects 1 in 250 people annually • 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 ~900 million adults 6. 8% have fungal rhinosinusitis ~25 million with fungal rhinosinusitis Responsive to polyp removal, nasal steroids, saline douches and antibiotics Antifungals have a minor role www. GAFFI. org
National burden estimates – countries covered Argentina, Austria, Australia, Belgium, Brazil, Canada, Chile, China, Czech Republic, Dominican Republic, Ecuador, Egypt, France, Germany, Guatemala, Hungary, India (3 topics), Indonesia, Iran, Iraq, Ireland, Israel, Jamaica, Jordan, Kenya, Mexico, Mongolia, Nepal, Netherlands, New Zealand, Nigeria, Qatar, Romania, Russia, Senegal, Singapore, South Korea, Spain, Sri Lanka, Saudi Arabia, South Korea, Tanzania, Thailand, Trinidad and Tobago, Uganda, UK, Ukraine, Uruguay, Vietnam, Zambia.
Conclusions • Burden of fungal disease is much greater than generally appreciated • Their impact on quality of life is not well studied • Estimations based on local epidemiological data and modelling a good start, but high quality epidemiological data are required • Country-specific estimates important for setting local priorities and garnering Global Fund and other support • Improved diagnosis is the key to better data and clinical outcomes • Chronic fungal infections (NCDs) need more attention generally www. GAFFI. org
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