ANIMAL MODEL OF HUMAN DISEASE
Sporotrichosis
Animal Model: Sporotrichosis in the Domestic Cat
Conltuted by William C. Barbee, MA, Adam Ewert, PhD, and Etta Macdonald Davidson, PhD, MD, Department of Microbiology, University of Texas Medical Branch, Galveston, Texas 77550.
Human Dises
Human sporotrichosis is most commonly encountered as an occupational disease in persons who have contact with vegetation or soil in which the etiologic agent, Sporotrichum schenckii, is growing as a saprophvte. The disease is usually subacute or chronic, with lesions often confined to the skin or subcutaneous tissues, and it is cosmopolitan in distribution. Animak Mods
Sporotrichosis in laboratorv animals was reviewed by Lurie.' The rat has long been considered the most susceptible of the laboratory animals, and intraperitoneal inoculation is a recognized biologic test for the presence of S. schenckii. According to Mariat and Drouhet,2 subcutaneous inoculation in the hamster may produce a disease somewhat similar to that seen in human cases. Investigators using mice have reported variable results. Scott et al.3 injected mice intratesticularly with a mycelial suspension of an isolate from dogs in order to obtain the tissue form and demonstrate pathogenicitv. Experimental use of dogs has also produced variable results. The susceptibility of guinea pigs to S. schenckii is equivocal, wthile the rabbit appears to be the most resistant of all laboratory animals.4 Infections involving the lymphatic system of monkevs have been produced.5'6 While a number of animals have been used to studv sporotrichosis experimentally, the disease produced has not closely resembled that seen in man. DeBeurmann, Gougerot, and Vaucher 7,8 reported use of the cat in Publication sponsored by the Registry of Comparatise Pathology of the Armed Forces Institute of Service Grant RR-00301 from the Division of Research Resources. US Department of Health, Education and Welfare, under the auspices of Unisersities Associated for Research and Education in Pathology, Inc. Insestigation supported by Grant Al-i 1871. the U-nited States-Japan Cooperatise Medical Science Program. National Institutes of Health. Mlr Barbee is the recipient of a \cLaughlin Fellowship from the U'niversity of Texas Medical Branch. Please address correspondence to Dr. Ewert.
Pathology and supported bv Public Health
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American Journal of Pathology
Figure 1-Hind limb of cat 40 days after exposure to yeast cell suspension of Sporotrichum schenckii. The lesion on the foot developed at the site of Inoculation. The secondary lesion on the leg coincides with one of the major afferent lymphatic vessels.
experimental infections with S. schenckii. These investigators stated that were relatively resistant to infection, but that newborn cats were quite susceptible. Results of our current research show that adult cats can be readily infected and that the course of the disease in many ways resembles that of human sporotrichosis. adult cats
Biologic Features of the Feline Model
Sporotrichum infections were produced in 18 of 20 adult cats of either sex. Cats were inoculated only with S. schenckii, or this organism was superimposed on animals infected with Brugia malayi, a nematode which produces lymphatic dysfunction. Primary wart-like lesions appeared at the inoculation site approximately 5 weeks after injection of a yeast cell suspension into one of the rear footpads. Secondary lesions generally appeared along the course of the afferent lymphatic vessels leading from the foot to the popliteal lymph node. Initially, these lesions were nodular but soon softened and ulcerated. By culturing sample tissues, the organ-
ism was shown to have disseminated to the viscera in 50% of the cases, but visceral lesions were seen in only 1 animal at necropsy. Figure 1 shows typical lesions along the afferent lymphatic vessels of the hind limb. The initial lesion developed at the point of inoculation on the hind foot. Figure 2 shows the proliferating Sporotrichum schenckii in a skin section taken near the site of infection at the time of necropsy 80
SPOROTRICHOSIS
Vol. 86, No. 1 January 1977
Figure
2-Sporotri-
chum schenckii in dermal area of skin section taken near thesite of infection at time of necropsy 80 days after infection (Gomori me- . thionine silver nitrate, x
283
4 '
1500).
davs after infection. Secondary lesions frequently developed at other points on the foot or along lymphatic vessels. Dilatation of superficial lymphatic vessels of the leg was often seen at necropsies performed from 40 to 100 days after inoculation of S. schenckii into the hind foot of a cat. S. schenckii was consistently cultured from both primary and secondary lesions during the course of the infection. At necropsy, cultures from the popliteal lvmph nodes draining the affected limb were also usually positive for S. schenckii. Conpanson With Human Disease and Potential Usefuness of the Model
This studv shows that the domestic cat can be readilv and consistently infected with a strain of Sporotrichum schenckii originally isolated from man. When introduced at the extremity of a limb, similar to usual human exposure, an initial lesion forms at the site of inoculation. As in many human cases, lesions frequently extend to lymphatic vessels draining that area. However, within the time limitation of these experiments, lesions are not usuallv evident in visceral organs although the organisms mav be present. With this model, regional lvmph nodes and lymphatic vessels can readilv be cultured for Sporotrichum at designated time intervals after exposure. Thus, the degree and speed of dissemination and the progres-
284
BARBEE ET AL.
American Journal of Pathology
sive pathology of both dermal lesions and lymphatic vessels can be determined. This model should also facilitate assessment of the efficacy of antifungal agents when applied topically or parenterally at varying time periods as the disease progresses. References 1. 2. 3.
4. 5. 6. 7. 8.
Lurie HI: Sporotrichosis. Human Infection With Fungi, Actinomycetes and Algae: Special edition of Handbuch der speziellen pathologischen Anatomie und Histologie 111/5. Edited by RD Baker, Berlin, Springer-Verlag, 1971, pp 614-675 Mariat F, Drouchet E: Sporotrichose experimentale du hamster: Observation de formes asteroides de Sporotrichum. Ann Inst Pasteur 86:485-492, 1954 Scott DW, Bentinck-Smith J, Hagerty GF: Sporotrichosis in three dogs. Cornell Vet 64:416-426, 1974 Braude AI, McConnell J, Douglas H. Fever from pathogenic fungi. J Clin Invest 39:1266-1276, 1960 Benham RW, Kesten B: Sporotrichosis: Its transmission to plants and animals. J Infect Dis 50:437458, 1932 Hopkins JG, Benham RW: Sporotrichosis in New York state. NY State J Med 32:595-681, 1932 DeBeurmann L, Gougerot H, Vaucher AB: Sporotrichose experimentale du chat. C R Soc Biol 66:338-340, 1909(1) DeBeurmann L, Gougerot H, Vaucher AB: Sporotrichose cutanees du chat. C R Soc Biol 66:370-372 1909(1)
Sporotrichosis
Animal Model: Sporotrichosis in the Domestic Cat
Conltuted by William C. Barbee, MA, Adam Ewert, PhD, and Etta Macdonald Davidson, PhD, MD, Department of Microbiology, University of Texas Medical Branch, Galveston, Texas 77550.
Human Dises
Human sporotrichosis is most commonly encountered as an occupational disease in persons who have contact with vegetation or soil in which the etiologic agent, Sporotrichum schenckii, is growing as a saprophvte. The disease is usually subacute or chronic, with lesions often confined to the skin or subcutaneous tissues, and it is cosmopolitan in distribution. Animak Mods
Sporotrichosis in laboratorv animals was reviewed by Lurie.' The rat has long been considered the most susceptible of the laboratory animals, and intraperitoneal inoculation is a recognized biologic test for the presence of S. schenckii. According to Mariat and Drouhet,2 subcutaneous inoculation in the hamster may produce a disease somewhat similar to that seen in human cases. Investigators using mice have reported variable results. Scott et al.3 injected mice intratesticularly with a mycelial suspension of an isolate from dogs in order to obtain the tissue form and demonstrate pathogenicitv. Experimental use of dogs has also produced variable results. The susceptibility of guinea pigs to S. schenckii is equivocal, wthile the rabbit appears to be the most resistant of all laboratory animals.4 Infections involving the lymphatic system of monkevs have been produced.5'6 While a number of animals have been used to studv sporotrichosis experimentally, the disease produced has not closely resembled that seen in man. DeBeurmann, Gougerot, and Vaucher 7,8 reported use of the cat in Publication sponsored by the Registry of Comparatise Pathology of the Armed Forces Institute of Service Grant RR-00301 from the Division of Research Resources. US Department of Health, Education and Welfare, under the auspices of Unisersities Associated for Research and Education in Pathology, Inc. Insestigation supported by Grant Al-i 1871. the U-nited States-Japan Cooperatise Medical Science Program. National Institutes of Health. Mlr Barbee is the recipient of a \cLaughlin Fellowship from the U'niversity of Texas Medical Branch. Please address correspondence to Dr. Ewert.
Pathology and supported bv Public Health
281
282
---
BARBEE ET AL. - . -- --
--
. .
American Journal of Pathology
Figure 1-Hind limb of cat 40 days after exposure to yeast cell suspension of Sporotrichum schenckii. The lesion on the foot developed at the site of Inoculation. The secondary lesion on the leg coincides with one of the major afferent lymphatic vessels.
experimental infections with S. schenckii. These investigators stated that were relatively resistant to infection, but that newborn cats were quite susceptible. Results of our current research show that adult cats can be readily infected and that the course of the disease in many ways resembles that of human sporotrichosis. adult cats
Biologic Features of the Feline Model
Sporotrichum infections were produced in 18 of 20 adult cats of either sex. Cats were inoculated only with S. schenckii, or this organism was superimposed on animals infected with Brugia malayi, a nematode which produces lymphatic dysfunction. Primary wart-like lesions appeared at the inoculation site approximately 5 weeks after injection of a yeast cell suspension into one of the rear footpads. Secondary lesions generally appeared along the course of the afferent lymphatic vessels leading from the foot to the popliteal lymph node. Initially, these lesions were nodular but soon softened and ulcerated. By culturing sample tissues, the organ-
ism was shown to have disseminated to the viscera in 50% of the cases, but visceral lesions were seen in only 1 animal at necropsy. Figure 1 shows typical lesions along the afferent lymphatic vessels of the hind limb. The initial lesion developed at the point of inoculation on the hind foot. Figure 2 shows the proliferating Sporotrichum schenckii in a skin section taken near the site of infection at the time of necropsy 80
SPOROTRICHOSIS
Vol. 86, No. 1 January 1977
Figure
2-Sporotri-
chum schenckii in dermal area of skin section taken near thesite of infection at time of necropsy 80 days after infection (Gomori me- . thionine silver nitrate, x
283
4 '
1500).
davs after infection. Secondary lesions frequently developed at other points on the foot or along lymphatic vessels. Dilatation of superficial lymphatic vessels of the leg was often seen at necropsies performed from 40 to 100 days after inoculation of S. schenckii into the hind foot of a cat. S. schenckii was consistently cultured from both primary and secondary lesions during the course of the infection. At necropsy, cultures from the popliteal lvmph nodes draining the affected limb were also usually positive for S. schenckii. Conpanson With Human Disease and Potential Usefuness of the Model
This studv shows that the domestic cat can be readilv and consistently infected with a strain of Sporotrichum schenckii originally isolated from man. When introduced at the extremity of a limb, similar to usual human exposure, an initial lesion forms at the site of inoculation. As in many human cases, lesions frequently extend to lymphatic vessels draining that area. However, within the time limitation of these experiments, lesions are not usuallv evident in visceral organs although the organisms mav be present. With this model, regional lvmph nodes and lymphatic vessels can readilv be cultured for Sporotrichum at designated time intervals after exposure. Thus, the degree and speed of dissemination and the progres-
284
BARBEE ET AL.
American Journal of Pathology
sive pathology of both dermal lesions and lymphatic vessels can be determined. This model should also facilitate assessment of the efficacy of antifungal agents when applied topically or parenterally at varying time periods as the disease progresses. References 1. 2. 3.
4. 5. 6. 7. 8.
Lurie HI: Sporotrichosis. Human Infection With Fungi, Actinomycetes and Algae: Special edition of Handbuch der speziellen pathologischen Anatomie und Histologie 111/5. Edited by RD Baker, Berlin, Springer-Verlag, 1971, pp 614-675 Mariat F, Drouchet E: Sporotrichose experimentale du hamster: Observation de formes asteroides de Sporotrichum. Ann Inst Pasteur 86:485-492, 1954 Scott DW, Bentinck-Smith J, Hagerty GF: Sporotrichosis in three dogs. Cornell Vet 64:416-426, 1974 Braude AI, McConnell J, Douglas H. Fever from pathogenic fungi. J Clin Invest 39:1266-1276, 1960 Benham RW, Kesten B: Sporotrichosis: Its transmission to plants and animals. J Infect Dis 50:437458, 1932 Hopkins JG, Benham RW: Sporotrichosis in New York state. NY State J Med 32:595-681, 1932 DeBeurmann L, Gougerot H, Vaucher AB: Sporotrichose experimentale du chat. C R Soc Biol 66:338-340, 1909(1) DeBeurmann L, Gougerot H, Vaucher AB: Sporotrichose cutanees du chat. C R Soc Biol 66:370-372 1909(1)
