Geotrichosis - An Opportunistic Mycosis of Humans And Animals

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1 Page38 Geotrichosis - An Opportunistic Mycosis of Humans And Animals Mahendra Pal*, Sunita Sejra**, Anand Sejra**, Sihin Tesfaye*** *Department of Microbiology and Veterinary Public Health, Addis Ababa University, Faculty of Veterinary Medicine, P.O. Box No. 34, Debre Zeit, Ethiopia. ** Department of Animal Husbandry, Government of Rajasthan, Tonk Road, Jaipur , India ***School of Veterinary Medicine, Wello University, P.O. Box No 1145, Desse, Ethiopia. Corresponding author: Rec.Date: Apr 19, :21; Accept Date: May 02, :14 Abstract Geotrichosis, primarily caused by Geotrichum candidum, is an emerging opportunistic mycosis and is reported from many countries of the world including India. The etiological agent is widely distributed in environment and is recovered from the soil, air, water, silage, milk, vegetables, and fruits. In addition, G. candidum can be isolated as part of the resident microflora in humans and animals. It can cause localized as well systemic disease in humans and animals including birds. Geotrichosis affects mainly the patients who are immunocompromised due to some underlying disease such as neoplasms, diabeties mellitus, leucosis, renal transplant and HIV. The clinical diagnosis must be supported by laboratory tests.direct microscopic demonstration of pathogen in clinical specimens and its repeated isolation in pure and luxuriant growth still remain the gold standard of diagnosis of geotrichosis in humans and animals. A number of drugs such as gention violet, nystatin, miconazole, ketoconazole, amphotericin B and voriconazole have been tried in the treatment of disease in humans as well as animals. The early diagnosis and prompt therapy is highly imperative in immunocompromised patient to prevent the complications. The application of Pal sunflower seed medium and Narayan stain for the study of yeasts including G.candium in Microbiology and Public Health Laboratory is advised. It is emphasized that growing role of G. candidum should be further studied in various clinical disorders of humans and animals. Key words: Geotrichosis, Geotrichum candidum, Immunocompromised host, Opportunistic fungus, Treatment Introduction Opportunistic mycoses are those diseases which exclusively occur in immunocompromised individuals whose immune system is suppressed due to many factors. The examples of such opportunistic fungal diseases are aspergillosis, fusariosis, geotichosis, pacilomycosis, rhodotoruliosis, trichosporonosis and zygomycosis (Pal, 2007). Such infections are life threatening and are associated with high rates of mortality. Among these infectious diseases, geotrichosis is a sporadic, infectious and opportunistic mycotic disease of humans and animals, which is caused chiefly by Geotrichum candidum, filamentous yeast like fungus which occurs as a saprobe in the environment (Pal, 2007). The first record of the disease in man goes back to the year 1809 when Link isolated G. candidum from a patient (Pal, 2007). The infection due to G. candidum has been reported from India as well from other countries of the world

2 Page39 (Webster, 1959; Sheehy et al, 1976; Kantardies et al., 1998; Pal and Verma, 2003; Mahapatra, 2005; Pal, 2007; Lee et al., 2010 and Figueredo et al., 2011). In humans, G. candidum is mainly responsible to respiratory diseases where as in animals,it mostly affects the skin, and the digestive tract (Dolensek et al., 1977; Ruiz et al., 1980; Reppas and Snoeck, 1999; Pal et al., 2002; Pal and Verma, 2003; Pal, 2005; Lee et al., 2010 and Figueredo et al., 2011). The present communication describes the growing significance of geotrichosis as an emerging opportunistic mycotic disease of humans as well as animals. Etiology Geotrichosis is primarily caused by Geotrichum candidum which is a eukaryotic, aerobic, motile, Gram positive, non-acid fast, and non-capsulated fungus. It is a filamentous mould that reproduces by segmentation of the hyphae into arthrospores giving rise to a yeast-like bud. It is sensitive to cycloheximide and cannot grow at 40 o C. Assimilation test is positive with glucose but negative with lactose, galactose and maltose. G. candidum belongs to class Hemiascomycetaeae, order Saccharomycetales, Family Dipodascaceae (De Hoog and Smith, 2004). The genus Geotrichum contains 13 species of which G. candidum is one of the most spread species causing infections in humans and in a wide variety of animals including birds (Rippon, 1988; Pal, 2007 and Figueredo et al., 2011). The fungus has been recovered from fruits, vegetables, milk, milk products, cereals, plants,silage, textiles, soil, sewage, water and air (Pal, 2007). It is also isolated as the part of the resident microflora in humans and animals (Rayan et al., 1990; Pal, 2007 and Pottier et al., 2008). Host Disease has been diagnosed in man, cattle, chicken, dog, goat, gorilla, horse, mouse, ocelot, penguin, pig, red flamingo, snake, and tortoise (Bendove and Ashe, 1952; Spanoghe et al., 1976; Jacobson, 1980, Ruiz et al., 1980; Rayan et al., 1990; Chahota et al., 2003; Pal et al., 2002; Pal, 2007; Lee et al., 2011 and Figueredo et al., 2011). Transmission Transmission of disease occurs by inhalation of infectious fungal cells through the respiratory tract from the saprobic environment. Ingestion of organisms in contaminated foods may also produce infection (Pal, 2007). Rarely, the fungus may enter the susceptible host following traumatic injury. In this context, Hrdy and co-workers (1995) reported traumatic joint infection in a person due to G. candidum. The patient had received a splinter injury to the metacarpophalangeal joint while cleaning a box to package graphs.

3 Page40 Disseminated geotrichosis is recorded in two dogs following multiple bite wounds from a wild raccoon (Rhyan et al., 1990). Clinical spectrum Man The affected person exhibits signs of intermittent fever, dullness, reduced appetite, mucopurulent sputum, hemoptysis, increased pulse rate, persistent pain in the abdomen, indigestion and decreased body weight (Pal, 2007). The infection of the skin, conjunctiva, oral cavity, respiratory tract, gastrointestinal tract, brain and joint can occur. Oral geotrichosis shows three clinical forms: pseudomembraneous, hyperplastic and palatine (Boniafaz et al., 2010). In mouth, there are white patches which clinically simulate to thrush (oral candidiasis). Patients with involvement of lungs show fever, asthma or cough with sputum which is sometime blood stained and is often gelatinous. The pulmonary form resembles to tuberculosis or chronic Klebiesella pneumonia. The abdominal pain, diarrhoea, blood and mucus in the stool are observed in gastrointestinal infection. Dissemination may occur in immunocompromised patients. Disease is fatal when disseminated (Pal, 2007). Animals In animals, clinical signs include dermatitis, mastitis, abortion, gastritis, enteritis, diarrhea, stomatitis, respiratory distress, fever, anorexia, besides pulmonary and renal disorders. Dissemination of infection is observed in dogs (Rayan et al., 1990). The fungus has been identified in the oral ulcers of a dog (Pal, 2005).Generalized disease in dog is manifested with signs of fever, coughing, poor appetite, progressive difficulty in breathing, excessive intake of water, jaundice and vomiting.very recently, Lee and coinvestigators (2010) diagnosed intestinal geotrichosis in a 4-year-old male German shepherd from Taiwan. The dog had a three month history of chronic watery diarrhoea, and also showed dehydration, emaciation and weight loss. Tonsillitis is recorded in a weaned pig by Lee and others in Alopecia, desquamation, and puritus localized mainly on the head and neck were frequently observed in equine affected with cutaneous geotrichosis (Figueredo et al., 2011). Epidemiology Geotrichosis is an infectious, non-contagious, opportunistic mycotic disease of worldwide distribution. The leukemia, diabetes mellitus, malignant disease, HIV/AIDS, organ transplantation, and Hodgkin s disease are the main predisposing conditions (Kwon-Chung and Bennett, 1992., Ng et al., 1994; Vergese and Ravichandran, 2003 and Pal, 2007). The disease is recorded in both sex and in all age groups. Most

4 Page41 clinical infections are reported in individuals who are immunocompromised. The disease can causes oral, pharyngeal, bronchial and intestinal disorders. It can also result in systemic infection particularly in immunosuppressed individuals.the fatal infections occur in immunocompromised patients who develop systemic disease. The prognosis of disease is poor with a mortality rate ranging from 50 to 90 %. The fungus Geotrichum candidum, the main etiological agent of disease, is a commensal in humans and part of the normal flora of the skin, mouth and gastrointestinal tract (Pal, 2007 and Pottier et al., 2008). The organism is isolated from 29 % of human faecal samples and from 18 % to 31 % of more than 2000 specimens of sputum, faeces, urine and vaginal discharges (Rippon, 1988 and Bonifaz et al., 2010). The prevalence of up to 2.5 % has been reported in patients with bronchomycosis (Reeves, 1941). Geotrichum candidum is also occasionally isolated from the healthy tissues of animals (Rosa et al., 2003). The fungus can invade the lung, heart, liver, spleen, bone marrow and lymph nodes (Pal, 2007). Mahapatra (2005) recorded co-infection of Geotrichum and Cryptosporidium in an AIDS patient. A case of G. candidum infection in a HIV patient was diagnosed by Pal (2007) who isolated the fungus from oral lesions on Pal sunflower seed medium and studied its morphology in Narayan stain. He also demonstrated the agent in the impression smear of oral scrapings by Periodic Acid Schiff (PAS) technique. Among domestic animals, cases of geotrichosis are encountered in dogs, horses, and cattle ( Pal et al.,2002; Pal and Verma,2003; Pal,2005, Lee et al., 2010,Figueredo et al,2011).most of cutaneous G.candidum infections in horses were described during spring ;and adults were more affected than the young animals. The lesions were mainly localized on the head and neck regions. Cutaneous geotrichosis should be included in the differential diagnosis of the skin infections of equines and laboratory tests are required to confirm the clinical diagnosis of disease ( Figueredo et al.,2011).further studies are required to study the epidemiology of geotrichosis as it is emerging as an opportunistic mycosis in humans. Diagnosis The clinical signs are not suggestive of the disease and hence the clinical diagnosis should be confirmed by direct demonstration of the fungus in the clinical material submitted to the laboratory. The specimen should be treated with 10-15% potassium hydroxide solution to detect the organism which appears as branched, septate hyphae and cylindrical, barrel- shaped conidia. The fungus can be easily isolated from clinical samples on Pal s sunflower seed medium (Pal, 1997), and Sabouraud dextrose agar with chloramphenicol at 30 C. The cycloheximide (actidione) should not be incorporated in the medium as it inhibits the growth of G. candidum (Kwon-Chung and Bennett, 1992). The identification of fungus is based on growth characteristics and morphology. The colony appears as white to cream colored with sweet odor (Pal, 2007). The detailed morphology of the fungal isolates can be studied in Narayan stain

5 Page42 developed by Pal (2004). The new stain contains 0.5 ml of 3 % aqueous solution of methylene blue, 4.0 ml of glycerin and 6.0 ml of dimethyl sulfoxide (DMSO). Culture in Narayan stain shows chains of smooth, septate hyphae with arthroconidia. Histopathological examination of tissues can indicate the presence of fungus when stained by Gomori methanamine silver (GMS) technique. FAT is also useful to detect the fungal pathogen in tissue sections (Pal, 2007). In humans, the thoracic radiograph may show multiple modular pulmonary densities. The enteroedoscopy of colon in intestinal geotrichosis in a dog reveals edema, erythema and loss of usual fine vascular pattern, with granularity of the mucosa of the descending column (Lee et al., 2010). The cutaneous, oral, pulmonary and systemic geotrichosis should be differentiated from dermatophytosis, thrush, tuberculosis, and colitis, respectively. The role of cytology and histopathology in the diagnosis of geotrichosis should be further studied. Chemotherapy Treatment with gentian violet, chrorexidine, miconazole, nystatin and ketoconazole has shown good response in cutaneous, bronchopulmonary, intestinal and joint geotrichosis (Dolensek et al., 1977; Sidhu et al., 1993; Pal, 2007 and Lee et al., 2010). Recently, Sfakianakis and co-workers (2007) reported the efficacy of amphotericin B and voriconazole in humans suffering with invasive cutaneous Geotrichum infection. However, the prognosis of disease is often grave in disseminated form. Attempts should be made to develop safe, cheap and potent drugs which can help in the management of geotrichosis. Control Control of geotrichosis can be achieved by making early diagnosis and instituting prompt treatment in immunocompromised patients, avoiding direct contact of traumatized skin with environmental materials, proper washing of fruits and vegetables before consumption, use of face mask in dusty places to prevent the entry of fungal aerosol and avoiding drinking raw or unpasteurized milk (Pal, 2007). In dairy animals, the injury to teat/s with the soil contaminated objects should be avoided and the rules of udder hygiene should be followed during milking. Refrences Bendrove, R. A. and Ashe, B. I Geotrichum septicemia. Archives of International Medicine 89: Bonifaz, A., Vazquez-Gonzalez, D., Macias, B., Paredes-Farrera, F., Hermandez, M. A., Arazia, J. and Ponce, R. M Oral geotrichosis: report of 12 cases. Journal of Oral Science 52: Chahota, R., Katoch, R., Mahajan, A. and Verma, S Clinical bovine mastitis caused by Geotrichum candidum. Veterinary Archives 71:

6 Page43 De-Hoog, G. S. and Smith, M. T Ribosomal gene phylogeny and species delimitation in Geotrichum and its teleomorph. Study Mycology 50: Dolensek, E. P., Napolitano, R. I. and Kazimifoff, J Gastrointestinal geotrichosis in six adult gorillas. Journal of American Veterinary Medical Association 171: Figueredo, L. A., Cafarchia, C. and Otranto, D Geotrichum candidum as etiological agent of horse dermatomycosis. Veterinary Microbiology 148: Hrdy, D. B. Nasser, N. N. and Rinaldi, M. G Traumatic joint infection due to Geotrichum candidum. Clinical Infectious Diseases 20: Jacobson, E. R Necrotising mycotic dermatitis in snakes: clinical and pathologic features. Journal of Veterinary and Medical Association 177: Kantardies, T., Kuzmanova, A., Baikushev, R., Zisova, L. and Velinov, T Isolation and identification of Geotrichum candidum as an etiologic agent of geotrichosis in Bulgaria.Folia Medicine 40: Kwon-Chung, K. J. and Bennett, J. E Medical Mycology. Lea and Febiger, Philadelphia. Pp Lee, E. J., Gaber, M. Turner, M., Ball, M. and Gaber, L Tonsilitis in a weaner pig associated with Geotrichum candidum. Journal of Veterinary Diagnostic Investigation 23: Lee, Y., Hsu, W., Lin, C., Shao, W. and Cheng, F Intestinal geotrichosis in a German shepherd. Turkey Journal of Veterinary Animal Science 34: Ng,K.P.,Soo-Hoo,T.S.,Koh,M.T.and Kwan,P.W.1994.Disseminated Geotrichum infection. Medical Journal of Malaysia 49: Pal, M Use of Pal s sunflower seed medium for an early diagnosis of cryptococcosis. Antiseptic 95: 175. Pal, M Efficacy of Narayan stains for morphological studies of moulds, yeasts and algae. Revista Iberoamericana de micologia 21: 219. Pal, M Role of Geotrichum candidum in canine oral ulcers. Revista Iberoamericana de Micologia 22: 183. Pal, M Veterinary and Medical Mycology. 1st edition. Published by Indian Council of Agricultural Research, New Delhi, India. Pp Pal, M., Lee, C. W. and Matsusaka, N Occurrence of Geotrichum candidum in two cases of canine dermatitis. Journal of Veterinary Clinics 19: Pal, M. and Verma, J. D Canine dermatitis caused by Geotrichum candidum. Livestock International 7: Pottier, I., Gente, S.,Vernoux, J. P. and Gueguen, M Safety assessment of dairy microorganisms: Geotrichum candidum. International Journal of Food Safety 126: Rayan, J. C., Stackhouse, L. A. and Davis, E. G., Disseminated geotrichosis in two dogs. Journal of American Veterinary Medical Association 197:

7 Page44 Reeves, R. J The incidence of bronchomycosis in the south.american Journal of Roentgenolgy 45: 513. Reppas, G. P. and Snoeck, T. D Cutaneous geotrichosis in a dog. Australian Veterinary Journal 77: Rippon, J. W Medical Mycology: The Pathogenic Fungi and the Pathogenic actinomycetes.w.b.saunders, Philadelphia. Pp Rosa, M., Cardozo, L. M., da Silva Pereira, J., Brooks, D. E., Martins, A. L., Florido, P. S. and Stussi, J. S Fungal flora of normal eyes of healthy horses from the state of Rio de Janeiro,Brazil. Veterinary Ophthalmolgy 6: Ruiz, J. M., Arteaga, E., Martinez, J., Rubio, E. M. and Torres, J. M Cutaneous and renal geotrichosis in a giant tortoise (Geochelone elephantopus). Sabouraudia 18: Sfakianakis, A., Krasagakis, K., Stefanidou, M., Maraki, S., Koutsopoulos, A., Kofteridis, D., Samonis, G. and Tosca, A Invasive cutaneous infection with Geotrichum candidum: sequential treatment with amphotericin B and voriconazole.medical Mycology 45: Sheehy, T. W., Honycutt, B. K. and Speneer, J. T Geotrichum septicemia. Journal of American Medical Association 235: Sidhu, R. K., Singh, K. B., Jand, S. K. and Joshi, D. V Cutaneous geotrichosis in a dog and its handler-a case report. Indian Journal of Animal health 32: 75. Spanoghe, L., Devos, A. and Viaene, N Cutaneous geotrichosis in the red flamingo (Phoenicopterus rubber). Sabouraudia 14: Verghese,S.and Ravichandran,P.2003.Geotrichum candidum infection in a renal transplant recipient. Indian journal of Nephrology 13: Webster, B. H Bronchopulmonary geotrichosis. A review with a report of four cases. Diseases of Chest 35:

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