Log in

Human Pythiosis: Emergence of Fungal-Like Organism

  • Review
  • Published:
Mycopathologia Aims and scope Submit manuscript

Abstract

Pythiosis is an emerging infectious disease caused by the aquatic oomycete Pythium insidiosum, a fungal-like organism. It is believed that P. insidiosum’s zoospores, its infected form, play major role in pathogenesis. Vascular and ocular infections are the most common clinical manifestation in humans. It is difficult to establish the diagnosis given its relatively rarity and difficulty to distinguish P. insidiosum from other molds. Delay in diagnosis and treatment has been associated with poor outcomes. High index of suspicion is the key, particularly in thalassemia patients with arterial insufficiency and patients with fungal keratitis/endophthalmitis without improvement on antifungal therapy. Tissue culture and zoospore induction remain gold standard for diagnosis; however, DNA-based method should be performed simultaneously. The combination of radical surgery, antifungal agents, and immunotherapy has been recommended. It was previously believed that surgery with negative surgical margins was the essential to survive in vascular pythiosis; however, it was recently found that patients could have residual disease despite documented negative surgical margins as infected clot may be dislodged to proximal arterial sites prior to surgery. Serum β-d-glucan (BG) has been used to monitor disease response after treatment initiation in vascular pythiosis. A significant decrease in BG levels within 2 weeks after surgery is indicative of the absence of residual infection. Unfortunately, monitoring tools for ocular pythiosis are not yet available. Itraconazole plus terbinafine have generally been used in P. insidiosum-infected patients; however, antibacterial agents, including azithromycin and linezolid, have also been used with favorable outcomes in ocular disease. Recently, azithromycin or clarithromycin plus doxycyclin were used in two relapsed vascular pythiosis patients with good outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Gaastra W, Lipman LJ, De Cock AW, Exel TK, Pegge RB, Scheurwater J, et al. Pythium insidiosum: an overview. Vet Microbiol. 2010;146(1–2):1–16.

    Google Scholar 

  2. Bridges CH, Emmons CW. A phycomycosis of horses caused by Hyphomyces destruens. J Am Vet Med Assoc. 1961;138:579–89.

    Google Scholar 

  3. Austwick PK, Copland JW. Swamp cancer. Nature. 1974;250(461):84.

    CAS  Google Scholar 

  4. Chandler FWW, Kaplan W, Ajello LA. Color atlas and textbook of the histopathology of mycotic diseases. Chicago: Year Book Medical Publishers; 1980.

    Google Scholar 

  5. De Cock AW, Mendoza L, Padhye AA, Ajello L, Kaufman L. Pythium insidiosum sp. nov., the etiologic agent of pythiosis. J Clin Microbiol. 1987;25(2):344–9.

    Google Scholar 

  6. Shipton WA. Pythium destruens sp. nov., an agent of equine pythiosis. J Med Vet Mycol. 1987;25(3):137–51.

    CAS  Google Scholar 

  7. Kwon-Chung KJ. Phylogenetic spectrum of fungi that are pathogenic to humans. Clin Infect Dis. 1994;19(Suppl 1):S1–7.

    Google Scholar 

  8. Hudspeth DSS, Nadler SA, Hudspeth MES. A COX2 molecular phylogeny of the peronosporomycetes. Mycologia. 2000;92:674–84.

    CAS  Google Scholar 

  9. Martin FN. Phylogenetic relationships among some Pythium species inferred from sequence analysis of the mitochondrially encoded cytochrome oxidase II gene. Mycologia. 2000;92:711–27.

    CAS  Google Scholar 

  10. Dick MW. Straminipilous fungi: systematics of the Peronosporomycetes including accounts of the marine straminipilous protist, the plasmodiophorids and similar organisms. London: Kluwer Academic Publishers; 2001.

    Google Scholar 

  11. Kammarnjesadakul P, Palaga T, Sritunyalucksana K, Mendoza L, Krajaejun T, Vanittanakom N, et al. Phylogenetic analysis of Pythium insidiosum Thai strains using cytochrome oxidase II (COX2) DNA coding sequences and internal transcribed spacer regions (ITS). Med Mycol. 2011;49(3):289–95.

    CAS  Google Scholar 

  12. Worasilchai N, Permpalung N, Chindamporn A. High-resolution melting analysis: a novel approach for clade differentiation in Pythium insidiosum and pythiosis. Med Mycol. 2018;56(7):868–76.

    CAS  Google Scholar 

  13. Thianprasit M, editor. Cutaneous pythiosis in human-being. In: Siriraj 100th academic meeting. Mahidol University: Bangkok, Thailand; 1988. pp. 18–22 April.

  14. Sathapatayavongs B, Leelachaikul P, Prachaktam R, Atichartakarn V, Sriphojanart S, Trairatvorakul P, et al. Human pythiosis associated with thalassemia hemoglobinopathy syndrome. J Infect Dis. 1989;159(2):274–80.

    CAS  Google Scholar 

  15. Krajaejun T, Sathapatayavongs B, Pracharktam R, Nitiyanant P, Leelachaikul P, Wanachiwanawin W, et al. Clinical and epidemiological analyses of human pythiosis in Thailand. Clin Infect Dis. 2006;43(5):569–76.

    Google Scholar 

  16. Permpalung N, Worasilchai N, Manothummetha K, Torvorapanit P, Ratanawongphaibul K, Chuleerarux N, et al. Clinical outcomes in ocular pythiosis patients treated with a combination therapy protocol in Thailand: a prospective study. Med Mycol. 2019;57(8):923–28.

    CAS  Google Scholar 

  17. Chitasombat MN, Petchkum P, Horsirimanont S, Sornmayura P, Chindamporn A, Krajaejun T. Vascular pythiosis of carotid artery with meningitis and cerebral septic emboli: a case report and literature review. Med Mycol Case Rep. 2018;21:57–62.

    Google Scholar 

  18. Laohapensang K, Rerkasem K, Chotirosniramit N. Mini-laparotomy for repair of infrarenal abdominal aortic aneurysm. Int Angiol. 2005;24(3):238–44.

    CAS  Google Scholar 

  19. Permpalung N, Worasilchai N, Plongla R, Upala S, Sanguankeo A, Paitoonpong L, et al. Treatment outcomes of surgery, antifungal therapy and immunotherapy in ocular and vascular human pythiosis: a retrospective study of 18 patients. J Antimicrob Chemother. 2015;70(6):1885–92.

    CAS  Google Scholar 

  20. Reanpang T, Orrapin S, Orrapin S, Arworn S, Kattipatanapong T, Srisuwan T, et al. Vascular pythiosis of the lower extremity in northern Thailand: 10 years’ experience. Int J Low Extrem Wounds. 2015;14(3):245–50.

    Google Scholar 

  21. Sermsathanasawadi N, Praditsuktavorn B, Hongku K, Wongwanit C, Chinsakchai K, Ruangsetakit C, et al. Outcomes and factors influencing prognosis in patients with vascular pythiosis. J Vasc Surg. 2016;64(2):411–7.

    Google Scholar 

  22. Worasilchai N, Permpalung N, Chongsathidkiet P, Leelahavanichkul A, Mendoza AL, Palaga T, et al. Monitoring anti-Pythium insidiosum IgG antibodies and (1→3)-beta-d-glucan in vascular pythiosis. J Clin Microbiol. 2018;56(8):e00610–8.

    CAS  Google Scholar 

  23. Agarwal S, Iyer G, Srinivasan B, Agarwal M, Kumar SP, Therese LK. Clinical profile of pythium keratitis: perioperative measures to reduce risk of recurrence. Br J Ophthalmol. 2018;102(2):153–7.

    Google Scholar 

  24. Agarwal SIG, Srinivasan B, Benurwar S, Agarwal M, Narayanan N, Lakshmipathy M, Radhika N, Rajagopal R, Krishnakumar S. Clinical profile, risk factors and outcome of medical, surgical and adjunct interventions in patients with Pythium insidiosum keratitis. Br J Ophthalmol. 2019;103(3):296–300.

    Google Scholar 

  25. Bagga B, Sharma S, Madhuri Guda SJ, Nagpal R, Joseph J, Manjulatha K, et al. Leap forward in the treatment of Pythium insidiosum keratitis. Br J Ophthalmol. 2018;102(12):1629–33.

    Google Scholar 

  26. Hasika R, Lalitha P, Radhakrishnan N, Rameshkumar G, Prajna NV, Srinivasan M. Pythium keratitis in South India: incidence, clinical profile, management, and treatment recommendation. Indian J Ophthalmol. 2019;67(1):42–7.

    Google Scholar 

  27. Kunavisarut S, Nimvorapan T, Methasiri S. Pythium corneal ulcer in Ramathibodi Hospital. J Med Assoc Thail. 2003;86(4):338–42.

    Google Scholar 

  28. Mittal R, Jena SK, Desai A, Agarwal S. Pythium insidiosum keratitis: histopathology and rapid novel diagnostic staining technique. Cornea. 2017;36(9):1124–32.

    Google Scholar 

  29. Sharma S, Balne PK, Motukupally SR, Das S, Garg P, Sahu SK, et al. Pythium insidiosum keratitis: clinical profile and role of DNA sequencing and zoospore formation in diagnosis. Cornea. 2015;34(4):438–42.

    Google Scholar 

  30. Lohnoo T, Yingyong W, Kumsang Y, Payattikul P, Jaturapaktrarak C, Chailurkit LO, et al. Seroprevalence of anti-Pythium insidiosum antibodies in the Thai population. Med Mycol. 2019;57(3):284–90.

    CAS  Google Scholar 

  31. Triscott JA, Weedon D, Cabana E. Human subcutaneous pythiosis. J Cutan Pathol. 1993;20(3):267–71.

    CAS  Google Scholar 

  32. He H, Liu H, Chen X, Wu J, He M, Zhong X. Diagnosis and treatment of Pythium Insidiosum corneal ulcer in a chinese child: a case report and literature review. Am J Case Rep. 2016;17:982–8.

    Google Scholar 

  33. Hilton RE, Tepedino K, Glenn CJ, Merkel KL. Swamp cancer: a case of human pythiosis and review of the literature. Br J Dermatol. 2016;175(2):394–7.

    CAS  Google Scholar 

  34. Hung C, Leddin D. Keratitis caused by Pythium insidiosum in an immunosuppressed patient with Crohn’s disease. Clin Gastroenterol Hepatol. 2014;12(10):A21–2.

    Google Scholar 

  35. Franco DM, Aronson JF, Hawkins HK, Gallagher JJ, Mendoza L, McGinnis MR, et al. Systemic Pythium insidiosum in a pediatric burn patient. Burns. 2010;36(5):e68–71.

    Google Scholar 

  36. Bosco Sde M, Bagagli E, Araujo JP Jr, Candeias JM, de Franco MF, Alencar Marques ME, et al. Human pythiosis, Brazil. Emerg Infect Dis. 2005;11(5):715–8.

    Google Scholar 

  37. Tanhehco TY, Stacy RC, Mendoza L, Durand ML, Jakobiec FA, Colby KA. Pythium insidiosum keratitis in Israel. Eye Contact Lens. 2011;37(2):96–8.

    Google Scholar 

  38. Bernheim D, Dupont D, Aptel F, Dard C, Chiquet C, Normand AC, et al. Pythiosis: case report leading to new features in clinical and diagnostic management of this fungal-like infection. Int J Infect Dis. 2019;86:40–3.

    Google Scholar 

  39. Calvano TP, Blatz PJ, Vento TJ, Wickes BL, Sutton DA, Thompson EH, et al. Pythium aphanidermatum infection following combat trauma. J Clin Microbiol. 2011;49(10):3710–3.

    Google Scholar 

  40. Farmer AR, Murray CK, Driscoll IR, Wickes BL, Wiederhold N, Sutton DA, et al. Combat-related Pythium aphanidermatum invasive wound infection: case report and discussion of utility of molecular diagnostics. J Clin Microbiol. 2015;53(6):1968–75.

    Google Scholar 

  41. Ri M. Investigations into the biology of three ‘phycomycotic’ agents pathogenic for horses in Australia. Mycopathologia. 1983;81(1):23–8.

    Google Scholar 

  42. Mendoza L, Ajello L, McGinnis MR. Infections caused by the Oomycetous pathogen Pythium insidiosum. J Mycol Med. 1996;6(4):151–64.

    Google Scholar 

  43. de Sousa M. Immune cell functions in iron overload. Clin Exp Immunol. 1989;75(1):1–6.

    Google Scholar 

  44. Gordeuk VR, Ballou S, Lozanski G, Brittenham GM. Decreased concentrations of tumor necrosis factor-alpha in supernatants of monocytes from homozygotes for hereditary hemochromatosis. Blood. 1992;79(7):1855–60.

    CAS  Google Scholar 

  45. Wanachiwanawin W, Mendoza L, Visuthisakchai S, Mutsikapan P, Sathapatayavongs B, Chaiprasert A, et al. Efficacy of immunotherapy using antigens of Pythium insidiosum in the treatment of vascular pythiosis in humans. Vaccine. 2004;22(27–28):3613–21.

    CAS  Google Scholar 

  46. Ud-Naen S, Tansit T, Kanistanon D, Chaiprasert A, Wanachiwanawin W, Srinoulprasert Y. Defective cytokine production from monocytes/macrophages of E-beta thalassemia patients in response to Pythium insidiosum infection. Immunobiology. 2019;224(3):427–32.

    CAS  Google Scholar 

  47. Krajaejun T, Khositnithikul R, Lerksuthirat T, Lowhnoo T, Rujirawat T, Petchthong T, et al. Expressed sequence tags reveal genetic diversity and putative virulence factors of the pathogenic oomycete Pythium insidiosum. Fungal Biol. 2011;115(7):683–96.

    CAS  Google Scholar 

  48. Intaramat A, Sornprachum T, Chantrathonkul B, Chaisuriya P, Lohnoo T, Yingyong W, et al. Protein A/G-based immunochromatographic test for serodiagnosis of pythiosis in human and animal subjects from Asia and Americas. Med Mycol. 2016;54(6):641–7.

    CAS  Google Scholar 

  49. Krajaejun T, Chongtrakool P, Angkananukul K, Brandhorst TT. Effect of temperature on growth of the pathogenic oomycete Pythium insidiosum. Southeast Asian J Trop Med Public Health. 2010;41(6):1462–6.

    Google Scholar 

  50. Reinprayoon U, Permpalung N, Kasetsuwan N, Plongla R, Mendoza L, Chindamporn A. Lagenidium sp. ocular infection mimicking ocular pythiosis. J Clin Microbiol. 2013;51(8):2778–80.

    Google Scholar 

  51. Mendoza L, Newton JC. Immunology and immunotherapy of the infections caused by Pythium insidiosum. Med Mycol. 2005;43(6):477–86.

    CAS  Google Scholar 

  52. Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev. 2000;13(2):236–301.

    CAS  Google Scholar 

  53. Rees CA. Disorders of the skin. Equine internal medicine. 2nd ed. Philadelphia: Saunders; 2004.

    Google Scholar 

  54. Grooters AM. Pythiosis and zygomycosis. Equine infectious diseases. Amsterdam: Elsevier; 2007.

    Google Scholar 

  55. Pracharktam R, Changtrakool P, Sathapatayavongs B, Jayanetra P, Ajello L. Immunodiffusion test for diagnosis and monitoring of human pythiosis insidiosi. J Clin Microbiol. 1991;29(11):2661–2.

    CAS  Google Scholar 

  56. **dayok T, Piromsontikorn S, Srimuang S, Khupulsup K, Krajaejun T. Hemagglutination test for rapid serodiagnosis of human pythiosis. Clin Vaccine Immunol. 2009;16(7):1047–51.

    CAS  Google Scholar 

  57. Krajaejun T, Kunakorn M, Niemhom S, Chongtrakool P, Pracharktam R. Development and evaluation of an in-house enzyme-linked immunosorbent assay for early diagnosis and monitoring of human pythiosis. Clin Diagn Lab Immunol. 2002;9(2):378–82.

    Google Scholar 

  58. Chareonsirisuthigul T, Khositnithikul R, Intaramat A, Inkomlue R, Sriwanichrak K, Piromsontikorn S, et al. Performance comparison of immunodiffusion, enzyme-linked immunosorbent assay, immunochromatography and hemagglutination for serodiagnosis of human pythiosis. Diagn Microbiol Infect Dis. 2013;76(1):42–5.

    CAS  Google Scholar 

  59. Worasilchai N, Leelahavanichkul A, Permpalung N, Kuityo C, Phaisanchatchawan T, Palaga T, et al. Antigen host response differences between the animal-type strain and human-clinical Pythium insidiosum isolates used for serological diagnosis in Thailand. Med Mycol. 2019;57(4):519–22.

    CAS  Google Scholar 

  60. Chindamporn A, Vilela R, Hoag KA, Mendoza L. Antibodies in the sera of host species with pythiosis recognize a variety of unique immunogens in geographically divergent Pythium insidiosum strains. Clin Vaccine Immunol. 2009;16(3):330–6.

    CAS  Google Scholar 

  61. Grooters AM, Gee MK. Development of a nested polymerase chain reaction assay for the detection and identification of Pythium insidiosum. J Vet Intern Med. 2002;16(2):147–52.

    Google Scholar 

  62. Schurko AM, Mendoza L, de Cock AW, Bedard JE, Klassen GR. Development of a species-specific probe for Pythium insidiosum and the diagnosis of pythiosis. J Clin Microbiol. 2004;42(6):2411–8.

    CAS  Google Scholar 

  63. Worasilchai N, Chaumpluk P, Chakrabarti A, Chindamporn A. Differential diagnosis for pythiosis using thermophilic helicase DNA amplification and restriction fragment length polymorphism (tHDA-RFLP). Med Mycol. 2018;56(2):216–24.

    CAS  Google Scholar 

  64. Thitithanyanont A, Mendoza L, Chuansumrit A, Prachartam R, Laothamatas J, Sathapatayayongs B, Lolekha S, Ajello L. Use of an immunogenic therapeutic vaccine to treat a life-threatening human arteritic infection caused by Pythium insidiosum. Clin Infect Dis. 1998;27:1394–400.

    CAS  Google Scholar 

  65. Narkwiboonwong TTK, Watanakijthavonkul K, Paocharern P, Singsakul A, Wongsa A, Woracharoensri N, Worasilchai N, Chindamporn A, Panoi A, Methipisit T, Sithinamsuwan P. Cerebral pythiosis: a case report of Pythium insidiosum infection presented with brain abscess. J Infect Dis Antimicrob Agents. 2011;28:129–32.

    Google Scholar 

  66. Susaengrat N, Torvorapanit P, Plongla R, Chuleerarux N, Manothummetha K, Tuangsirisup J, et al. Adjunctive antibacterial agents as a salvage therapy in relapsed vascular pythiosis patients. Int J Infect Dis. 2019;88:27–30.

    CAS  Google Scholar 

  67. Krajaejun T, Pracharktam R, Wongwaisayawan S, Rochanawutinon M, Kunakorn M, Kunavisarut S. Ocular pythiosis: is it under-diagnosed? Am J Ophthalmol. 2004;137(2):370–2.

    Google Scholar 

  68. Anutarapongpan O, Thanathanee O, Worrawitchawong J, Suwan-Apichon O. Role of confocal microscopy in the diagnosis of Pythium insidiosum keratitis. Cornea. 2018;37(2):156–61.

    Google Scholar 

  69. Shenep JL, English BK, Kaufman L, Pearson TA, Thompson JW, Kaufman RA, et al. Successful medical therapy for deeply invasive facial infection due to Pythium insidiosum in a child. Clin Infect Dis. 1998;27(6):1388–93.

    CAS  Google Scholar 

  70. Argenta JS, Santurio JM, Alves SH, Pereira DI, Cavalheiro AS, Spanamberg A, et al. In vitro activities of voriconazole, itraconazole, and terbinafine alone or in combination against Pythium insidiosum isolates from Brazil. Antimicrob Agents Chemother. 2008;52(2):767–9.

    CAS  Google Scholar 

  71. Cavalheiro AS, Maboni G, de Azevedo MI, Argenta JS, Pereira DI, Spader TB, et al. In Vitro activity of terbinafine combined with caspofungin and azoles against Pythium insidiosum. Antimicrob Agents Chemother. 2009;53(5):2136–8.

    CAS  Google Scholar 

  72. Loreto ES, Mario DA, Denardi LB, Alves SH, Santurio JM. In vitro susceptibility of Pythium insidiosum to macrolides and tetracycline antibiotics. Antimicrob Agents Chemother. 2011;55(7):3588–90.

    CAS  Google Scholar 

  73. Rawn CDSM. Protecion of Pythium Speccies Against Antibacterial Antibiotics by Cholesterol. Physiology and Biochemistry. 1987;77:319–23.

    CAS  Google Scholar 

  74. Rawn CDVJL. Mechanism of antibacterial antibiotic sensitivity in Pythium ultimum. J Gen Microbiol. 1978;108:133–9.

    CAS  Google Scholar 

  75. Mahl DL, de Jesus FP, Loreto E, Zanette RA, Ferreiro L, Pilotto MB, et al. In vitro susceptibility of Pythium insidiosum isolates to aminoglycoside antibiotics and tigecycline. Antimicrob Agents Chemother. 2012;56(7):4021–3.

    CAS  Google Scholar 

  76. Muralidharan G, Micalizzi M, Speth J, Raible D, Troy S. Pharmacokinetics of tigecycline after single and multiple doses in healthy subjects. Antimicrob Agents Chemother. 2005;49(1):220–9.

    CAS  Google Scholar 

  77. Loreto ES, Tondolo JS, Pilotto MB, Alves SH, Santurio JM. New insights into the in vitro susceptibility of Pythium insidiosum. Antimicrob Agents Chemother. 2014;58(12):7534–7.

    Google Scholar 

  78. Jesus FP, Ferreiro L, Loreto ES, Pilotto MB, Ludwig A, Bizzi K, et al. In vitro synergism observed with azithromycin, clarithromycin, minocycline, or tigecycline in association with antifungal agents against Pythium insidiosum. Antimicrob Agents Chemother. 2014;58(9):5621–5.

    Google Scholar 

  79. Jesus FP, Loreto ES, Ferreiro L, Alves SH, Driemeier D, Souza SO, et al. In vitro and in vivo antimicrobial activities of minocycline in combination with azithromycin, clarithromycin, or tigecycline against Pythium insidiosum. Antimicrob Agents Chemother. 2016;60(1):87–91.

    CAS  Google Scholar 

  80. Mendoza L, Mandy W, Glass R. An improved Pythium insidiosum-vaccine formulation with enhanced immunotherapeutic properties in horses and dogs with pythiosis. Vaccine. 2003;21(21–22):2797–804.

    Google Scholar 

  81. Hensel P, Greene CE, Medleau L, Latimer KS, Mendoza L. Immunotherapy for treatment of multicentric cutaneous pythiosis in a dog. J Am Vet Med Assoc. 2003;223(2):215–8.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ariya Chindamporn.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Handling Editor: Ferry Hagen.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Permpalung, N., Worasilchai, N. & Chindamporn, A. Human Pythiosis: Emergence of Fungal-Like Organism. Mycopathologia 185, 801–812 (2020). https://doi.org/10.1007/s11046-019-00412-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11046-019-00412-0

Keywords

Navigation