|Year : 2016 | Volume
| Issue : 1 | Page : 1-2
Human pythiosis: Old wine in a new bottle
Jhaveri Microbiology Centre, Director of Laboratory Services LVPEI Network, L V Prasad Eye Institute, Hyderabad, Telangana, India
|Date of Web Publication||16-Jun-2016|
Jhaveri Microbiology Centre, Director of Laboratory Services LVPEI Network, L V Prasad Eye Institute, Hyderabad, Telangana
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Sharma S. Human pythiosis: Old wine in a new bottle. J Curr Res Sci Med 2016;2:1-2
It is not new in medical science that an old disease or a long forgotten infecting organism finds resurgence, often to the incredulity of scientists and the medical fraternity. Diseases confined to particular regions of the world emerge at other parts of the world and in different populations, or an organism that was not recognized makes itself obvious. Almost immediately, the reporting of such conditions takes a leap in medical literature. This editorial deals with one such disease known as pythiosis.
A large number of fungal species are associated with keratitis and the most frequent species involved almost worldwide are Fusarium and Aspergillus. However, what is intriguing is the fact that 10-23% of fungal isolates from fungal keratitis patients remain unidentified owing to lack of sporulation in culture. ,, These unknown fungi evade identification but have always been around, challenging the microbiologists. With advancement in identification techniques, they acquire a name that seems "new" when they are not!
Molecular microbiologists have been quick to adopt ribosomal DNA sequence analysis to determine the species of nonsporulating fungi.  Our institutional data that involved analysis of fungal keratitis patients seen over a decade (1991-2000) showed that 10-13% of fungal isolates were unidentifiable morphologically owing to lack of sporulation.  DNA sequencing of such isolates revealed the presence of Pythium insidiosum among them.  Not surprisingly, a euphoria-like situation prevailed among the laboratory staff from the illusion of finding something "new." This was rather short-lived with the realization that pythiosis had been described way back as a zoonotic disease, occasionally affecting humans.  Analysis of fifty nonsporulating fungi by DNA sequencing from India in 2008 had also listed Pythium to be one of the genera present. 
Clinical recognition of the condition among our cornea specialists was aided by the simultaneous recognition of P. insidiosum as a causative agent of fungal keratitis in our laboratory using colony characteristics, microscopic features, and phenotypic method of zoospore demonstration.  Seventy-four cases of Pythium keratitis have been diagnosed at our institute between January 2014 and December 2016 (unpublished data), which gives a prevalence of 5% of fungal keratitis associated with P. insidiosum. Going by the sporadic reports of keratitis associated with P. insidiosum in the literature from different countries, it is believed that the disease is underdiagnosed.  An outbreak of Pythium keratitis was reported from Thailand in 2009. All cases occurred in rainy season and had a history of exposure to contaminated water.
It turns out that Pythium spp. have a worldwide distribution and are found in soil and water. They are important plant pathogens, and one species P. insidiosum has been particularly associated with infections in humans and animals commonly called Pythiosis insidiosii. Pythiosis insidiosii of the subcutaneous tissues and intestines is characterized by granulomatous lesions that can grow rapidly and even be fatal. , Granuloma of horses occurring in rainy season has been particularly linked to this infection in India and the disease goes by the name "bursatee" in Hindi.  The other names ascribed to the disease in different parts of the world are "swamp cancer" or "leeches."  Most cases of human pythiosis are reported from Thailand. Severe form of systemic disease has been reported from patients with hemoglobinopathy syndromes such as thalassemia, leukemia.  Occasionally, the disease has been reported from Brazil, Haiti, Australia, New Zealand, and the United States. Horse pythiosis is reported to be endemic in Brazil.
Phylogenetic relationship of Pythium has been extensively studied. For this purpose, both ribosomal RNA gene (intergenic transcribed spacer regions 1 and 2 including intervening 5.8S gene) and partial sequence of cytochrome c oxidase subunit II (COX II) gene have been used.  Using maximum parsimony, neighbor-joining, maximum likelihood, and Bayesian analysis methods, these authors found P. insidiosum to be monophyletic in relation to other Pythium species. The study suggested an evolutionary proximity among all American isolates (Brazilian, Central American, and North American), which were grouped together. Compared to internal transcribed spacer, the COX II analysis showed greater phylogenetic information. It suggested a recent expansion of the American isolates from an Asian source. The two markers seemed to be entirely in agreement in terms of phylogenetic relationships between different isolates of P. insidiosum. Serodiagnosis using ELISA has been reported to be useful in the diagnosis of systemic human pythiosis associated with thalassemia. 
The class oomycetes is a group of fungus-like (parafungal) microorganisms that are closely related to the green algae in the kingdom Stramenopila. The main feature of oomycetes is the development of sporangia with biflagellate zoospores in aquatic atmosphere. The phylogenetic placement of these organisms is complex.  Physiologically, oomycetes lack ergosterol in their cytoplasmic membrane and exhibit intrinsic resistance to most antifungal compounds. Although some antifungal drugs have shown efficacy in vitro, the in vivo efficacy of these drugs in animal models and clinical pythiosis in humans and animals is not satisfactory.  The Pythium cell membrane lacks ergosterol and contains cellulose and β-glucan. Therefore, β-glucan inhibitor such as caspofungin seems to be effective in some cases. However, the infection seems to return on cessation of therapy.  Consequently, surgical treatment is often the only option. Recently, in vitro inhibition of P. insidiosum by antibacterial drugs such as azithromycin, clarithromycin, minocycline, tigecycline has been shown. ,
However, clinical efficacy of these drugs remains to be evaluated. Not surprisingly, with lack of effective drugs, researchers have investigated the efficacy of immunotherapy. In 1981, a killed vaccine was reported to be effective in 50% of the infected horses.  Another vaccine containing antigens secreted by P. insidiosum was also tested in horses and the efficacy of this vaccine was similar. In humans, immunotherapy was first successfully used in 1998 in a Thai boy who had a P. insidiosum vascular infection where surgery and antimycotic therapy did not work adequately.  In a major article including 102 cases of human pythiosis (cutaneous, subcutaneous, vacular, disseminated, and ocular) from Thailand in 2006, high morbidity and mortality was reported. Radical surgery was required in most cases for treatment. Vaccination was tried in 9/102 patients with inoperable disease and five of them responded favorably. Two of four patients with concomitant hemoglobin E disease and ocular pythiosis facing recurrence in corneal and scleral graft have also reportedly responded with no further recurrence. 
With increased awareness about the pathogenic role of P. insidiosum and availability of molecular methods for identification, we are likely to see a rise in reports of Pythium infections. Concomitant research to establish effective treatment for the condition is the need of the hour. On the prevention front, the role of public education to use personal protective equipment while working in swamps cannot be overemphasized.
| References|| |
Thomas PA. Current perspectives on ophthalmic mycoses. Clin Microbiol Rev 2003;16:730-97.
Gopinathan U, Sharma S, Garg P, Rao GN. Review of epidemiological features, microbiological diagnosis and treatment outcome of microbial keratitis: Experience of over a decade. Indian J Ophthalmol 2009;57:273-9.
Srinivasan M, Gonzales CA, George C, Cevallos V, Mascarenhas JM, Asokan B, et al.
Epidemiology and aetiological diagnosis of corneal ulceration in Madurai, south India. Br J Ophthalmol 1997;81:965-71.
Bagyalakshmi R, Therese KL, Prasanna S, Madhavan HN. Newer emerging pathogens of ocular non-sporulating molds (NSM) identified by polymerase chain reaction (PCR)-based DNA sequencing technique targeting internal transcribed spacer (ITS) region. Curr Eye Res 2008;33:139-47.
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;34:438-42.
Mendoza L, Hernandez F, Ajello L. Life cycle of the human and animal oomycete pathogen Pythium insidiosum
. J Clin Microbiol 1993;31:2967-73.
Krajaejun T, Pracharktam R, Wongwaisayawan S, Rochanawutinon M, Kunakorn M, Kunavisarut S. Ocular pythiosis: Is it under-diagnosed? Am J Ophthalmol 2004;137:370-2.
Pavletic MM, Miller RI, Turnwald GH. Intestinal infarction associated with canine phycomycosis. J Am Anim Hosp Assoc 1983;19:913-9.
Rinaldi MG, Seidenfeld SM, Fotherbell AM, McGough DA. Pythium insidiosu
m causes severe disease in a healthy boy. Mycol Observ 1989;9:7-8.
Vanittanakom N, Supabandhu J, Khamwan C, Praparattanapan J, Thirach S, Prasertwitayakij N, et al.
Identification of emerging human-pathogenic Pythium insidiosum
by serological and molecular assay-based methods. J Clin Microbiol 2004;42:3970-4.
Azevedo MI, Botton SA, Pereira DI, Robe LJ, Jesus FP, Mahl CD, et al.
Phylogenetic relationships of Brazilian isolates of Pythium insidiosum
based on ITS rDNA and cytochrome oxidase II gene sequences. Vet Microbiol 2012;159:141-8.
Mendoza L, Vilela R. The mammalian pathogenic oomycetes. Curr Fungal Infect Rep 2013;7:198-208.
Pereira DI, Santurio JM, Alves SH, Argenta JS, Pötter L, Spanamberg A, et al.
Caspofungin in vitro
and in vivo
activity against Brazilian Pythium insidiosum
strains isolated from animals. J Antimicrob Chemother 2007;60:1168-71.
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;55:3588-90.
Mahl DL, de Jesus FP, Loreto É, Zanette RA, Ferreiro L, Pilotto MB, et al. In vitro
susceptibility of Pythium insidiosum
isolates to aminoglycoside antibiotics and tigecycline. Antimicrob Agents Chemother 2012;56:4021-3.
Miller RI Treatment of equine phycomycosis by immunotherapy and surgery. Aust Vet J 1981;57:377-82.
Thitithanyanont A, Mendoza L, Chuansumrit A, Pracharktam R, Laothamatas J, Sathapatayavongs B, et al.
Use of an immunotherapeutic vaccine to treat a life-threatening human arteritic infection caused by Pythium insidiosum
. Clin Infect Dis 1998;27:1394-400.
Thanathanee O, Enkvetchakul O, Rangsin R, Waraasawapati S, Samerpitak K, Suwan-apichon O. Outbreak of Pythium keratitis during rainy season: A case series. Cornea 2013;32:199-204.