“Red-leg” syndrome commonly refers to the hyperemia of the ventral skin that accompanies systemic infection in amphibians. Saprophytic, gram-negative bacteria such as Aeromonas, Pseudomonas, Proteus, and Citrobacter spp typically cause red-leg. Viruses, fungi, and other pathogens may cause similar lesions. Ventral hyperemia is a nonspecific sign and may also be seen with toxicosis. Malnourished, newly acquired amphibians that are maintained in poor-quality water or other inappropriate environmental conditions are particularly susceptible. Clinical signs include lethargy; emaciation; ulcerations of the skin, nose, and toes; and characteristic cutaneous pinpoint hemorrhages of the legs and abdomen. Hemorrhages may also occur in the skeletal muscles, tongue, and nictitating membrane. In acute cases, these signs may be absent. Histologic evidence of systemic infection may include inflammatory or necrotic foci in the liver, spleen, and other coelomic organs. Blood or, if present, coelomic fluid, should be cultured prior to beginning therapy. Individuals can be treated initially with enrofloxacin (5–10 mg/kg, PO or IM, sid), oxytetracycline (50 mg/kg, PO, bid), or chloramphenicol (50 mg/kg, PO, bid) prior to receiving culture and sensitivity results. If fungal infection is suspected, a 0.01% itraconazole bath (5 min, sid for 8 days) may be effective.
Mycobacteriosis, caused by acid-fast bacilli including Mycobacterium fortuitum, M marinum, and M xenopi, occurs principally in debilitated amphibians. While often an infection of the integument, ingestion of infectious organisms may also lead to GI disease and systemic infection. Affected amphibians may exhibit gray nodules in the skin, liver, kidneys, spleen, lungs, and other coelomic organs. Infected amphibians may eat well but still lose weight. Acid-fast bacilli may be detected in feces and oropharyngeal mucus. A premortem diagnosis can be made by finding acid-fast bacilli in animals with external lesions. Culture of mycobacteria requires special media such as Lowenstein-Jensen agar but is frequently unsuccessful. Treatment is not recommended for this potentially zoonotic disease.
Chlamydiosis is a serious infection of amphibians. Based on histologic lesions and the presence of inclusion bodies these infections were originally attributed to Chlamydophila psittaci. Using molecular methods such as PCR, it has since been shown that other species of Chlamydia have been associated with these infections including C pneumonia, C abortus, and Chlamydia suis. Chlamydia spp have also been found in apparently healthy frogs, which raises the question as to whether or not these animals may be a reservoir or vector for these infectious organisms. The disease was originally recognized in a mass mortality of African clawed frogs (Xenopus laevis) fed uncooked beef livers. Infected frogs may die peracutely or exhibit lethargy, disequilibrium, cutaneous depigmentation, petechiae, and edema. Histologically, intracytoplasmic basophilic inclusion bodies can be identified in sinusoidal lining cells of the liver and spleen. Secondary bacterial infections are frequently present in affected amphibians and must be treated appropriately. Antibiotic treatment including doxycycline (5–10 mg/kg, PO, sid) or oxytetracycline (50 mg/kg, PO, sid) may be effective against chlamydial infection.
Many of the fungi that infect amphibians are difficult to distinguish grossly as they produce similar clinical effects, including lethargy and skin ulcerations. Some fungi can be identified via the examination of a wet mount prepared from a skin scraping, while others require culture, histology, and special stains. Treatment includes proper hygiene and the use of topical or systemic antifungal agents such as itraconazole. Other antifungal drugs such as fluconazole may also be effective.
Chytridiomycosis is the most serious fungal infection in amphibians and has been implicated in the decline of frog populations in many parts of the world, as changes in climate are favorable for this pathogen. It is caused by Batrachochytrium dendrobatidis, a fungus that feeds on keratin found in the outer epidermal layers of the skin. Amphibians are the only known vertebrate host for any of the chytrid fungi. Mobile zoospores contribute to the loss of whole populations of amphibians. Clinical signs include anorexia, lethargy, excessive shedding of skin, pupillary miosis, and muscle incoordination. Visualizing the spherical, single-celled organisms in skin scrapings stained with Wright's-Giemsa or Gram stains using a light microscope is diagnostic, but the organisms are not always readily seen. On histopathology zoosporangia containing zoospores are associated with hyperkeratosis and underlying dermal infection. Treatment includes the topical administration of itraconazole (0.01% bath for 5 min, sid for 10–11 days) and maintaining animals well within their normal thermal range. Systemic antifungal drugs appear to be ineffective in treating this infection of the epidermis.
Saprolegniasis refers to disease caused by several genera of opportunistic fungi or “water molds” that infect the gills and/or skin of aquatic and larval amphibians. When in water, newly affected animals appear to have a whitish cotton-like growth on their skin. As the fungal mat ages, it may become greenish due to the presence of algae. Once removed from water, the fungal mat collapses and is difficult to see. Other signs include lethargy, respiratory distress, anorexia, and weight loss. Skin ulcerations may occur as the infection progresses. A diagnosis of saprolegniasis is made by finding hyphae and the thin-walled zoospores in a skin scrape. Treatment with a malachite green dip (67 mg/L for 15 sec, sid for 2–3 days) or copper sulfate (500 mg/L for 2 min, sid for 5 days, then once weekly until healed) may be effective. Secondary bacterial and parasitic infections may be present in animals with dermal ulcers. Poor water quality conditions should be corrected.
Chromomycosis is caused by pigmented or black fungi from several genera (eg, Cladosporium, Fonsecaea, Phialophora, Ochroconis, and Wangiella). These fungi may be found in organic substrates such as topsoil and decaying plant matter. Signs may include anorexia, weight loss, granulomatous skin lesions or ulcers, coelomic distention, and neurologic disease. Diagnosis is usually made postmortem by finding disseminated granulomas with pigmented fungal cells and hyphae. Culture is frequently unsuccessful; histopathology may be necessary to confirm the diagnosis. Treatment using itraconazole (10 mg/kg, PO, sid for 30 days) may be given, but the prognosis is poor once the infection is disseminated.
Many of the protozoa and metazoa found in and on amphibians are not associated with disease unless the host amphibian is stressed or immunocompromised. Recently caught or transported amphibians are particularly susceptible to parasitism, as are those kept in poor hygienic conditions and outside their POTZ. Parasites with indirect life cycles tend to die out when wild-caught amphibians are brought into captivity if the intermediate or final host is not present. Conversely, infections by parasites with a direct life cycle may be magnified in a closed environment. Excellent hygiene is essential for parasite control and includes the routine removal of sloughed skin, fecal material, uneaten food, and carcasses from animal enclosures.
External parasites may be found by close examination of amphibians using magnification and a bright, cool light. A skin scrape or biopsy may be required to identify parasites causing nodules or epidermal lesions. Internal parasites are often identified through examination of fresh fecal samples. Some small frogs are translucent enough to allow the visualization of nematodes using transillumination. In some cases, metazoan and protozoan parasites are found only at necropsy. Finding flagellates, ciliates, and opalinids in the feces is normal and does not require treatment in healthy amphibians. While many larval nematodes found in the feces are nonpathogenic, treatment is recommended because pathogenic and nonpathogenic species cannot be readily distinguished.
Rhabdiasis, caused by the lungworm Rhabdias sp, commonly causes pulmonary damage and secondary infections in captive amphibians. This nematode has a direct life cycle with free-living phases. Adult worms live in the lungs where they deposit larvated eggs that are coughed up, swallowed, and then excreted into the environment. Infective L3 larvae then burrow through the skin of a new host where they mature and migrate to the lungs. Affected animals may appear anorectic, thin, and generally debilitated. A premortem diagnosis may be made by finding ova or worms in oral and nasal secretions. Infection should be suspected when nematode larva and larvated eggs are found in fresh feces from an animal with clinical signs. When rhabdiasis is suspected, treatment using fenbendazole (100 mg/kg, PO, sid for 2 days then repeated 12–14 days later) or ivermectin (200–400 μg/kg, PO, once, repeated 12–14 days later) is recommended. Following the second of each 2-day fenbendazole treatment or each dose of ivermectin, the animals should be moved into a newly established environment to prevent reinfection from free-living life stages.
The capillarid nematode Pseudocapillaroides xenopi burrows into the skin and is known to affect colonies of the aquatic African clawed frog. Signs include discoloration, roughening, pitting, and ulceration of the skin. As the infection progresses, lethargy, anorexia, and sloughing of the skin occur. Diagnosis is made by finding small, white nematodes beneath the mucus on the skin; skin scrapings may show larvae and ova. Treatment by adding thiabendazole (0.1 g/L) to the water may be effective. Levamisole and other anthel-mintics may also be effective. Frequent water changes with removal of shed skin containing the parasite are required in order to prevent the amplification and spread of infection to cage mates.
Renal adenocarcinomas (Lucké tumors) are relatively common in leopard frogs (Rana pipiens) wild-caught in the northeastern and north central USA. Few frogs with tumors are seen in the summer because viral replication is temperature-dependent. Virus particles and inclusion bodies are seen when frogs are in hibernation, at 41–50°F (5–10°C). Metastasis of the tumor to liver, lungs, and other organs is common; both the primary and metastatic tumors can become very large. There is no treatment. The neoplasm is a model of herpesvirus-induced cancer.
Iridoviruses (which include the genus Ranavirus) have been identified as the cause of mass mortality in wild populations of amphibians across the world. Ranaviruses, which include frog virus 3, tadpole edema virus, and iridovirus, are highly virulent and may produce 100% mortality in tadpoles or adults. Several of these viruses cause acute necrosis of leukocytes and lymphoid tissue that can be seen in most organs histologically. Some cause lesions very similar to those of bacterial dermato-septicemias. The original viral lesions may be overwhelmed by secondary invaders, and many outbreaks of “red-leg” may have had an underlying and undiagnosed viral infection. There is no treatment for iridoviral disease other than supportive care and appropriate treatment for the secondary infections with bacteria or fungi.
Last full review/revision July 2011 by Brent R. Whitaker, MS, DVM