1. Why Fungal infections  2 million species of fungi on earth about 600 have caused disease.  Most infections are caused by the genera Trichophyton, Candida, Aspergillus and Cryptococcus.  Globally, > 300 M people afflicted with a serious fungal infection  25 milllion are at high risk of dying or losing their sight.  2 M deaths each year

2. Clinical Symptoms Oral and oesophageal thrush – unpleasant, reduced food intake and weight loss. ABPA and SAFS – breathlessness with severe asthma, reducing work capability especially for manual workers, co-morbidity issues with smoke from home cooking.Antifungal treatment 60- 80% effective. Chronic pulmonary aspergillosis – progressive breathlessness and weight loss, with significant hospitalisation and medication costs (typically mis-directed). Fungal eye infection – usually results in unilateral blindness as diagnosis late, good outcome if treated early. Diagnosis requires expert input; treatment intensive initially but unaffordable for most afflicted. Candida vaginitis – mis-diagnosis and anxiety major problems; impaired sex life and therefore relationship issues.

3. Aspergillus  About 200 species have been identified. Aspergillus molds are found throughout the world and are the most common type of fungi in the environment. About 16 species of Aspergillus molds are known to be dangerous to humans, causing disease and infection. 1. Aspergillus clavatus 2. Aspergillus flavus 3. Aspergillus fumigatus 4. Aspergillus glaucus 5. Aspergillus nidulans 6. Aspergillus niger 7. Aspergillus oryzae 8. Aspergillus terreus 9. Aspergillus ustus 10. Aspergillus versicolor

6. Mortality  Invasive aspergillosis – 50% mortality treated, >99% if not. Diagnosis difficult; treatment often too late, and only partially effective. 200,000 cases 100,000 deaths annually.  Chronic pulmonary aspergillosis – Over 3 million affected worldwide. Diagnosis often confused with TB, and requires radiology and aspergillus antibody test; 30% mortality in 6 months, often by coughing up blood. Treatment partially successful but long term. 450,000 deaths per year.  SAFS – increased risk of asthmatic death (estimated to be 350,000 annually worldwide.  Cryptococcal meningitis – 20% death rate in the USA, >50% in Africa. 600,000 deaths annually. Diagnosis simple with antigen test, but often late and appropriate medication not available.  Candida bloodstream infection - ~40% mortality, treated. Diagnosis by blood culture. Treatment straightforward, best drugs expensive. 120,000 deaths per year.

7. Coast  Objectives: In this study we determined the incidence and direct inpatient and outpatient costs of systemic fungal infections (candidiasis, aspergillosis, cryptococcosis, histoplasmosis) in 1998.  Results: For 1998, the projected average incidence was 306 per million US population, with candidiasis accounting for 75% of cases. The estimated total direct cost was $2.6 billion and the average per-patient attributable cost was $31,200. The most commonly reported comorbid diagnoses with fungal infections (HIV/AIDS, neoplasms, transplants ) accounted for only 45% of all infections. Conclusion : The cost burden is high for systemic fungal infections. Additional attention should be given to the 55% with fungal disease and other comorbid diagnoses.

8. Major obstacles preventing better diagnosis  Doctors and health professionals need education to consider a fungal diagnosis, and it is usually not clinically obvious. Manchester is a good place to start  Many fungal diagnostic tests are insensitive, some are not specific and large parts of the world have none.  The largest problem for most of the global population is simply unavailability of testing :  Expensive tests  Lack of standardization and validation of tests in different countries leading to uncertainty about diagnostic performance.

9. Summary of current test PCR for aspergillus only in reference labs

10. Volatile biomarkers Clinical Environmental Health and Toxic Exposures edited by John Burke Sullivan, Gary R. Krieger

14. http://journals.plos.org/plospathogens/ar ticle?id=10.1371/journal.ppat.1003743  Aspergillus fumigatus Conidia Are Dispersed More Efficiently in the Air Than Those of Most Other Molds  Aspergillus fumigatus conidia accumulate 1,8-dihydroxynaphthalene melanin in their cell wall, have a blue-green color [19], [20], and are notorious for their high dispersibility. The slightest air current can cause conidia to disperse due to their remarkable hydrophobicity, and these airborne conidia are protected from ultraviolet irradiation due to the melanin in their cell wall[20]. One study has estimated the emission rate of A. fumigatus conidia from an undisturbed compost pile to be 8– 11×10 3 cfu/m 2 /s at the mean wind speed of 1 m/s [21], which indicates how efficiently conidia are dispersed with the slightest agitation. Figure 2A shows an aerosol cloud over a disturbed compost pile. A majority of the microbial growth on a plate of agar medium briefly exposed to the air at the site was that of A. fumigatus (Figure 2B). Although all fungal spores produced on aerial hyphae or conidiophores are hydrophobic, the degree varies from mild to highly hydrophobic [22] which impacts the efficiency of spore dispersibility. A. fumigatus conidia are considerably more hydrophobic than those of other aspergilli such as A. nidulans. This requires more caution in the handling of A. fumigatus cultures than other fungi to prevent contamination of surrounding areas in the laboratory (Figure 2C, D). Conidial hydrophobicity is conferred by the surface rodlet layer encoded by the rodA gene [23]. In addition to dispersal of airborne conidia, conidia imbedded in soil may also be effectively transported from one place to another by swarming soil bacteria such as Paenibacillus vortex.P. vortex facilitates the dispersal of A. fumigatus more efficiently than other fungal species that have similarly sized conidia such as Penicillium expansum or P. citrinum [24]. Conidial surface proteins are crucial for the passive dispersal of A. fumigatus by the bacteria since proteinase K treatment of conidia abolished the conidia-bacterial interaction. Undoubtedly, A. fumigatusconidia are also being passively dispersed via rodents, insects, and worms but the impact of A. fumigatus spread by these means has not been studied.[19][20] [21]Figure 2AFigure 2B[22]Figure 2C, D[23][24]

15. http://www.sciencedirect.com/science/ article/pii/S135223100900658X  Abstract  Information on the particle size distribution of bioaerosols emitted from open air composting operations is valuable in evaluating potential health impacts and is a requirement for improved dispersion simulation modelling. The membrane filter method was used to study the particle size distribution of Aspergillus fumigatus spores in air 50 m downwind of a green waste compost screening operation at a commercial facility. The highest concentrations (approximately 8 × 10 4 CFU m −3 ) of culturable spores were found on filters with pore diameters in the range 1–2 μm which suggests that the majority of spores are emitted as single cells. The findings were compared to published data collected using an Andersen sampler. Results were significantly correlated (p < 0.01) indicating that the two methods are directly comparable across all particles sizes forAspergillus spores.

16. References  http://cid.oxfordjournals.org/content/46/3/327.1.full.pdf+h tml http://cid.oxfordjournals.org/content/46/3/327.1.full.pdf+h tml  Diagnosis of fungal disease- some global issues ( Denning, Edinburgh 2015) Diagnosis of fungal disease- some global issues  http://www.life- worldwide.org/assets/uploads/files/Wilson%202002%20Val ueHealth%20- %20Direct%20Cost%20and%20incidence%20of%20systemi c%20fungal%20infections.pdf http://www.life- worldwide.org/assets/uploads/files/Wilson%202002%20Val ueHealth%20- %20Direct%20Cost%20and%20incidence%20of%20systemi c%20fungal%20infections.pdf  http://www.life-worldwide.org/ http://www.life-worldwide.org/  http://www.idsociety.org/Organism/ http://www.idsociety.org/Organism/