Fungal Diseases in the 21st Century: The Near and Far Horizons
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Abstract
Fungal diseases became a major medical problem in the second half of the
20th century when advances in modern medicine together with the HIV
epidemic resulted in large numbers of individuals with impaired immunity.
Fungal diseases are difficult to manage because they tend to be chronic,
hard to diagnose, and difficult to eradicate with antifungal drugs. This
essay considers the future of medical mycology in the 21st century,
extrapolating from current trends. In the near horizon, the prevalence of
fungal diseases is likely to increase, as there will be more hosts with
impaired immunity and drug resistance will inevitably increase after
selection by antifungal drug use. We can expect progress in the development
of new drugs, diagnostics, vaccines, and immunotherapies. In the far
horizon, humanity may face new fungal diseases in association with climate
change. Some current associations between chronic diseases and fungal
infections could lead to the establishment of fungi as causative agents,
which will greatly enhance their medical importance. All trends suggest
that the importance of fungal diseases will increase in the 21st century,
and enhanced human preparedness for this scourge will require more research
investment in this group of infectious diseases.
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References
1. Currie BP, Casadevall A. Estimation of the prevalence of Cryptococcus neoformans infection in New York City in 1991. The First National Conference on Human Retroviruses and Related Infections. 1993;Washington, D.C.
2. Fisher MC, Henk DA, Briggs CJ, Brownstein JS, Madoff LC, McCraw SL, Gurr SJ. Emerging fungal threats to animal, plant and ecosystem health. Nature. 2012;484(7393):186-94. nature10947 [pii]; doi: 10.1038/nature10947
3. Casadevall A. Fungi and the rise of mammals. PLoS Pathog. 2012;8(8):e1002808. PubMed PMID: 22916007. Pubmed Central PMCID: Pmc3420938. doi: 10.1371/journal.ppat.1002808
4. Robert VA, Casadevall A. Vertebrate endothermy restricts most fungi as potential pathogens. J Infect Dis. 2009;200(10):1623-6. doi: 10.1086/644642
5. Bergman A, Casadevall A. Mammalian endothermy optimally restricts fungi and metabolic costs. MBio. 2010;1(5). doi: 10.1128/mBio.00212-10
6. Casadevall A. Fungal virulence, vertebrate endothermy, and dinosaur extinction: is there a connection? Fungal Genet Biol. 2005;42(2):98-106.
7. Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG, White TC. Hidden killers: human fungal infections. Sci Transl Med. 2012;4(165):165rv13. 4/165/165rv13 [pii];doi: 10.1126/scitranslmed.3004404
8. Rodrigues ML, Albuquerque PC. Searching for a change: The need for increased support for public health and research on fungal diseases. PLoS Negl Trop Dis. 2018;12(6):e0006479. PubMed PMID: 29902170. Pubmed Central PMCID: Pmc6001980. doi: 10.1371/journal.pntd.0006479
9. Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS. 2009;23(4):525-30.
10. Gustafson TL, Kaufman L, Weeks R, Ajello L, Hutcheson RH, Jr., Wiener SL, Lambe DW, Jr., Sayvetz TA, Schaffner W. Outbreak of acute pulmonary histoplasmosis in members of a wagon train. Am J Med. 1981;71(5):759-65.
11. Andes D, Casadevall A. Insights into fungal pathogenesis from the iatrogenic epidemic of Exserohilum rostratum fungal meningitis. Fungal Genet Biol. 2013;61:143-5. PubMed PMID: 24012946. doi: 10.1016/j.fgb.2013.08.014
12. Stop neglecting fungi. Nat Microbiol. 2017;2:17120. PubMed PMID: 28741610. doi: 10.1038/nmicrobiol.2017.120
13. Gow NAR, Amin T, McArdle K, Brown AJP, Brown GD, Warris A, The Wtsa-Mmfi C. Strategic Research Funding: A Success Story for Medical Mycology. Trends Microbiol. 2018. PubMed PMID: 29909043. doi: 10.1016/j.tim.2018.05.014
14. Kyriakidis I, Tragiannidis A, Zundorf I, Groll AH. Invasive fungal infections in paediatric patients treated with macromolecular immunomodulators other than tumour necrosis alpha inhibitors. Mycoses. 2017;60(8):493-507. PubMed PMID: 28444889. doi: 10.1111/myc.12621
15. Tsiodras S, Samonis G, Boumpas DT, Kontoyiannis DP. Fungal infections complicating tumor necrosis factor alpha blockade therapy. Mayo Clin Proc. 2008;83(2):181-94. PubMed PMID: 18241628.
16. Datta K, Hamad M. Immunotherapy of Fungal Infections. Immunol Invest. 2015;44(8):738-76. PubMed PMID: 26575463. doi: 10.3109/08820139.2015.1093913
17. Edwards JE, Jr., Schwartz MM, Schmidt CS, Sobel JD, Nyirjesy P, Schodel F, Marchus E, Lizakowski M, DeMontigny EA, Hoeg J, Holmberg T, Cooke MT, Hoover K, Edwards L, Jacobs M, Sussman S, Augenbraun M, Drusano M, Yeaman MR, Ibrahim AS, Filler SG, Hennessey JP, Jr. A Fungal Immunotherapeutic Vaccine (NDV-3A) for Treatment of Recurrent Vulvovaginal Candidiasis-A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial. Clin Infect Dis. 2018;66(12):1928-36. PubMed PMID: 29697768. Pubmed Central PMCID: Pmc5982716. doi: 10.1093/cid/ciy185
18. Casadevall A, Pirofski LA. A Therapeutic Vaccine for Recurrent Vulvovaginal Candidiasis. Clin Infect Dis. 2018;66(12):1937-9. PubMed PMID: 29697770. 10.1093/cid/ciy188
19. Casadevall A, Pirofski LA. Immunoglobulins in defense, pathogenesis, and therapy of fungal diseases. Cell Host Microbe. 2012;11(5):447-56. S1931-3128(12)00101-1 [pii]; doi: 10.1016/j.chom.2012.04.004
20. Larsen RA, Pappas PG, Perfect JR, Aberg JA, Casadevall A, Cloud GA, James R, Filler S, Dismukes WE. A phase I evaluation of the safety and pharmacodynamic activity of a murine-derived monoclonal antibody 18B7 in subjects with treated cryptococcal meningitis. Antimicrob Agents Chemother. 2005; 49:952-8.
21. Zhao G, Zaidi TS, Bozkurt-Guzel C, Zaidi TH, Lederer JA, Priebe GP, Pier GB. Efficacy of Antibody to PNAG Against Keratitis Caused by Fungal Pathogens. Invest Ophthalmol Vis Sci. 2016;57(15):6797-804. PubMed PMID: 28002842. Pubmed Central PMCID: Pmc5215555. doi: 10.1167/iovs.16-20358
22. Wharton RE, Stefanov EK, King RG, Kearney JF. Antibodies generated against Streptococci protect in a mouse model of disseminated aspergillosis. J Immunol. 2015;194(9):4387-96. PubMed PMID: 25821219. Pubmed Central PMCID: Pmc4402265. doi: 10.4049/jimmunol.1401940
23. Miceli MH, Maertens J. Role of Non-Culture-Based Tests, with an Emphasis on Galactomannan Testing for the Diagnosis of Invasive Aspergillosis. Semin Respir Crit Care Med. 2015;36(5):650-61. PubMed PMID: 26398532. doi: 10.1055/s-0035-1562892
24. Temfack E, Kouanfack C, Mossiang L, Loyse A, Fonkoua MC, Molloy SF, Koulla-Shiro S, Delaporte E, Dromer F, Harrison T, Lortholary O. Cryptococcal Antigen Screening in Asymptomatic HIV-Infected Antiretroviral Naive Patients in Cameroon and Evaluation of the New Semi-Quantitative Biosynex CryptoPS Test. Front Microbiol. 2018;9:409. PubMed PMID: 29593675. Pubmed Central PMCID: Pmc5859387. doi: 10.3389/fmicb.2018.00409
25. Mery A, Sendid B, Francois N, Cornu M, Poissy J, Guerardel Y, Poulain D. Application of Mass Spectrometry Technology to Early Diagnosis of Invasive Fungal Infections. J Clin Microbiol. 2016;54(11):2786-97. PubMed PMID: 27605710. Pubmed Central PMCID: Pmc5078558. doi: 10.1128/jcm.01655-16
26. Gu Z, Buelow DR, Petraitiene R, Petraitis V, Walsh TJ, Hayden RT. Quantitative multiplexed detection of common pulmonary fungal pathogens by labeled primer polymerase chain reaction. Arch Pathol Lab Med. 2014;138(11):1474-80. PubMed PMID: 25357108. doi: 10.5858/arpa.2013-0592-OA
27. Buitrago MJ, Aguado JM, Ballen A, Bernal-Martinez L, Prieto M, Garcia-Reyne A, Garcia-Rodriguez J, Rodriguez-Tudela JL, Cuenca-Estrella M. Efficacy of DNA amplification in tissue biopsy samples to improve the detection of invasive fungal disease. Clin Microbiol Infect. 2013;19(6):E271-7. PubMed PMID: 23464751. doi: 10.1111/1469-0691.12110
28. Rolle AM, Hasenberg M, Thornton CR, Solouk-Saran D, Mann L, Weski J, Maurer A, Fischer E, Spycher PR, Schibli R, Boschetti F, Stegemann-Koniszewski S, Bruder D, Severin GW, Autenrieth SE, Krappmann S, Davies G, Pichler BJ, Gunzer M, Wiehr S. ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo. Proc Natl Acad Sci U S A. 2016;113(8):E1026-33. PubMed PMID: 26787852. Pubmed Central PMCID: Pmc4776455. doi: 10.1073/pnas.1518836113
29. Fisher MC, Hawkins NJ, Sanglard D, Gurr SJ. Worldwide emergence of resistance to antifungal drugs challenges human health and food security. Science. 2018;360(6390):739-42. PubMed PMID: 29773744. doi: 10.1126/science.aap7999
30. Bidaud AL, Chowdhary A, Dannaoui E. Candida auris: An emerging drug resistant yeast - A mini-review. J Mycol Med. 2018. PubMed PMID: 30030072. doi: 10.1016/j.mycmed.2018.06.007
31. Chowdhary A, Kathuria S, Xu J, Meis JF. Emergence of azole-resistant aspergillus fumigatus strains due to agricultural azole use creates an increasing threat to human health. PLoS Pathog. 2013;9(10):e1003633. PubMed PMID: 24204249. Pubmed Central PMCID: Pmc3812019. doi: 10.1371/journal.ppat.1003633
32. Abdolrasouli A, Rhodes J, Beale MA, Hagen F, Rogers TR, Chowdhary A, Meis JF, Armstrong-James D, Fisher MC. Genomic Context of Azole Resistance Mutations in Aspergillus fumigatus Determined Using Whole-Genome Sequencing. MBio. 2015;6(3):e00536. PubMed PMID: 26037120. Pubmed Central PMCID: Pmc4453006. doi: 10.1128/mBio.00536-15
33. Perfect JR. The antifungal pipeline: a reality check. Nat Rev Drug Discov. 2017;16(9):603-16. PubMed PMID: 28496146. Pubmed Central PMCID: Pmc5760994. doi: 10.1038/nrd.2017.46
34. Zhai B, Wu C, Wang L, Sachs MS, Lin X. The antidepressant sertraline provides a promising therapeutic option for neurotropic cryptococcal infections. Antimicrob Agents Chemother. 2012;56(7):3758-66. PubMed PMID: 22508310. Pubmed Central PMCID: Pmc3393448. doi: 10.1128/aac.00212-12
35. Villanueva-Lozano H, Trevino-Rangel RJ, Gonzalez GM, Hernandez-Rodriguez PA, Camacho-Ortiz A, Castillo-Reyna L, Galindo-Alvarado SG, Martinez-Resendez MF. Clinical evaluation of the antifungal effect of sertraline in the treatment of cryptococcal meningitis in HIV patients: a single Mexican center experience. Infection. 2018;46(1):25-30. PubMed PMID: 28815430. doi: 10.1007/s15010-017-1059-3
36. Jung EH, Meyers DJ, Bosch J, Casadevall A. Novel Antifungal Compounds Discovered in Medicines for Malaria Venture's Malaria Box. mSphere. 2018;3(2). PubMed PMID: 29564402. Pubmed Central PMCID: Pmc5853493. doi: 10.1128/mSphere.00537-17
37. Mayer FL, Kronstad JW. Discovery of a Novel Antifungal Agent in the Pathogen Box. mSphere. 2017;2(2). PubMed PMID: 28435886. Pubmed Central PMCID: Pmc5390095. doi: 10.1128/mSphere.00120-17
38. Enaud R, Vandenborght LE, Coron N, Bazin T, Prevel R, Schaeverbeke T, Berger P, Fayon M, Lamireau T, Delhaes L. The Mycobiome: A Neglected Component in the Microbiota-Gut-Brain Axis. Microorganisms. 2018;6(1). PubMed PMID: 29522426. Pubmed Central PMCID: Pmc5874636. doi: 10.3390/microorganisms6010022
39. Ghannoum MA, Jurevic RJ, Mukherjee PK, Cui F, Sikaroodi M, Naqvi A, Gillevet PM. Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLoS Pathog. 2010;6(1):e1000713. PubMed PMID: 20072605. Pubmed Central PMCID: Pmc2795202. doi: 10.1371/journal.ppat.1000713
40. Cui L, Morris A, Ghedin E. The human mycobiome in health and disease. Genome Med. 2013;5(7):63. PubMed PMID: 23899327. Pubmed Central PMCID: Pmc3978422. doi: 10.1186/gm467
41. Oever JT, Netea MG. The bacteriome-mycobiome interaction and antifungal host defense. Eur J Immunol. 2014;44(11):3182-91. PubMed PMID: 25256886. doi: 10.1002/eji.201344405
42. Ghannoum M. Cooperative Evolutionary Strategy between the Bacteriome and Mycobiome. MBio. 2016;7(6). PubMed PMID: 27935844. Pubmed Central PMCID: Pmc5111414. doi: 10.1128/mBio.01951-16
43. Kalan L, Loesche M, Hodkinson BP, Heilmann K, Ruthel G, Gardner SE, Grice EA. Redefining the Chronic-Wound Microbiome: Fungal Communities Are Prevalent, Dynamic, and Associated with Delayed Healing. MBio. 2016;7(5). PubMed PMID: 27601572. Pubmed Central PMCID: Pmc5013295. doi: 10.1128/mBio.01058-16
44. Vicencio AG, Santiago MT, Tsirilakis K, Stone A, Worgall S, Foley EA, Bush D, Goldman DL. Fungal sensitization in childhood persistent asthma is associated with disease severity. Pediatr Pulmonol. 2014;49(1):8-14. PubMed PMID: 23401301. doi: 10.1002/ppul.22779
45. Denning DW, Pashley C, Hartl D, Wardlaw A, Godet C, Del Giacco S, Delhaes L, Sergejeva S. Fungal allergy in asthma-state of the art and research needs. Clin Transl Allergy. 2014;4:14. PubMed PMID: 24735832. Pubmed Central PMCID: Pmc4005466. doi: 10.1186/2045-7022-4-14
46. Singh A, Ralhan A, Schwarz C, Hartl D, Hector A. Fungal Pathogens in CF Airways: Leave or Treat? Mycopathologia. 2018;183(1):119-37. PubMed PMID: 28770417. doi: 10.1007/s11046-017-0184-y
47. Alonso R, Pisa D, Aguado B, Carrasco L. Identification of Fungal Species in Brain Tissue from Alzheimer's Disease by Next-Generation Sequencing. J Alzheimers Dis. 2017;58(1):55-67. PubMed PMID: 28387676. doi: 10.3233/jad-170058
48. Pisa D, Alonso R, Rabano A, Rodal I, Carrasco L. Different Brain Regions are Infected with Fungi in Alzheimer's Disease. Sci Rep. 2015;5:15015. PubMed PMID: 26468932. Pubmed Central PMCID: Pmc4606562. doi: 10.1038/srep15015
49. Vargas SL, Ponce CA, Luchsinger V, Silva C, Gallo M, Lopez R, Belletti J, Velozo L, Avila R, Palomino MA, Benveniste S, Avendano LF. Detection of Pneumocystis carinii f. sp. hominis and viruses in presumably immunocompetent infants who died in the hospital or in the community. J Infect Dis. 2005;191(1):122-6. PubMed PMID: 15593013. doi: 10.1086/426451
50. Garcia-Solache MA, Casadevall A. Global warming will bring new fungal diseases for mammals. MBio. 2010;1(1). doi: 10.1128/mBio.00061-10
51. de SAGR, Souza W, Frases S. The hidden pathogenic potential of environmental fungi. Future Microbiol. 2017;12:1533-40. PubMed PMID: 29168657. doi: 10.2217/fmb-2017-0124
52. Cohen JM, Venesky MD, Sauer EL, Civitello DJ, McMahon TA, Roznik EA, Rohr JR. The thermal mismatch hypothesis explains host susceptibility to an emerging infectious disease. Ecol Lett. 2017;20(2):184-93. PubMed PMID: 28111904. doi: 10.1111/ele.12720
53. Paterson RR, Lima N. Thermophilic Fungi to Dominate Aflatoxigenic/Mycotoxigenic Fungi on Food under Global Warming. Int J Environ Res Public Health. 2017;14(2). PubMed PMID: 28218685. Pubmed Central PMCID: Pmc5334753. doi: 10.3390/ijerph14020199
54. Beatty GW. Immune reconstitution inflammatory syndrome. Emerg Med Clin North Am. 2010;28(2):393-407, Table. S0733-8627(10)00005-2 [pii]. doi: 10.1016/j.emc.2010.01.004
55. Casadevall A, Pirofski L. The damage-response framework of microbial pathogenesis. Nature Microbiol Rev. 2003;1:17-24.
56. Pirofski LA, Casadevall A. Immune-Mediated Damage Completes the Parabola: Cryptococcus neoformans Pathogenesis Can Reflect the Outcome of a Weak or Strong Immune Response. MBio. 2017;8(6). PubMed PMID: 29233901. Pubmed Central PMCID: Pmc5727418. doi: 10.1128/mBio.02063-17
57. Casadevall A, Coelho C, Alanio A. Mechanisms of Cryptococcus neoformans-Mediated Host Damage. Front Immunol. 2018;9:855. PubMed PMID: 29760698. Pubmed Central PMCID: Pmc5936990. doi: 10.3389/fimmu.2018.00855
58. Himmelreich U, Malik R, Kuhn T, Daniel HM, Somorjai RL, Dolenko B, Sorrell TC. Rapid etiological classification of meningitis by NMR spectroscopy based on metabolite profiles and host response. PLoS ONE. 2009;4(4):e5328. doi: 10.1371/journal.pone.0005328
59. Pfaller MA, Wolk DM, Lowery TJ. T2MR and T2Candida: novel technology for the rapid diagnosis of candidemia and invasive candidiasis. Future Microbiol. 2016;11(1):103-17. PubMed PMID: 26371384. doi: 10.2217/fmb.15.111
60. Sorrell TC, Wright LC, Malik R, Himmelreich U. Application of proton nuclear magnetic resonance spectroscopy to the study of Cryptococcus and cryptococcosis. FEMS Yeast Res. 2006;6(4):558-66.
61. Acharige MJT, Koshy S, Ismail N, Aloum O, Jazaerly M, Astudillo CL, Koo S. Breath-based diagnosis of fungal infections. J Breath Res. 2018;12(2):027108. PubMed PMID: 29109305. doi: 10.1088/1752-7163/aa98a1
62. Molloy SF, Chiller T, Greene GS, Burry J, Govender NP, Kanyama C, Mfinanga S, Lesikari S, Mapoure YN, Kouanfack C, Sini V, Temfack E, Boulware DR, Dromer F, Denning DW, Day J, Stone NRH, Bicanic T, Jarvis JN, Lortholary O, Harrison TS, Jaffar S, Loyse A. Cryptococcal meningitis: A neglected NTD? PLoS Negl Trop Dis. 2017;11(6):e0005575. PubMed PMID: 28662028. Pubmed Central PMCID: Pmc5490932. doi: 10.1371/journal.pntd.0005575