Year : 2016 | Volume
: 2 | 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
Jhaveri Microbiology Centre, Director of Laboratory Services LVPEI Network, L V Prasad Eye Institute, Hyderabad, Telangana
|How to cite this article:|
Sharma S. Human pythiosis: Old wine in a new bottle.J Curr Res Sci Med 2016;2:1-2
|How to cite this URL:|
Sharma S. Human pythiosis: Old wine in a new bottle. J Curr Res Sci Med [serial online] 2016 [cited 2023 Feb 6 ];2:1-2
Available from: https://www.jcrsmed.org/text.asp?2016/2/1/1/184113
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.
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