Treatment of chytridiomycosis requires urgent clinical trials

Abstract

Effective and safe treatments of amphibian chytridiomycosis, caused by Batrachochytrium dendrobatidis (Bd), are needed to prevent mortality in captive programs, reduce the risk of disease spread, and better manage the disease in threatened wild populations. Bd is susceptible to a range of antifungal agents and low levels of heat (> 30°C) when tested in vitro, but there are few proven methods for clearing adult amphibians of Bd, and acute drug toxicity is a problem for tadpoles and juveniles. In postmetamorphic animals, heat (32 and 37°C) is the only well-supported treatment. Antifungal drugs have not undergone rigorous testing -for example, trials were small or lacked controls and thorough post-treatment testing. In addition, pharmacokinetic studies have not been performed so there are no data on blood or tissue levels of antifungal agents. However, itraconazole baths have been widely used in amphibian rescue and conservation programs and anecdotal evidence suggests that they are effective for adults and subadults. In an experimental trial with tadpoles, a low dose of itraconazole cleared Bd but may have been associated with cutaneous depigmentation. Fluconazole appeared safe for tadpoles as it did not cause mortality, and future attempts to find an effective dose may be worthwhile. Palliative restoration of blood sodium and potassium levels by administration of electrolyte solutions appears useful in frogs with clinical chytridiomycosis. Randomised and blinded clinical trials, which include basic pharmacological studies, are urgently needed to provide comparable evidence for the safety and efficacy of treatment options which are likely to vary with amphibian species. Priorities are to validate and optimize the use of heat and itraconazole regimes.

Reduced Itraconazole Concentration and Durations Are Successful in Treating <em>Batrachochytrium dendrobatidis</em> Infection in Amphibians

“…Some species and life stages are intolerant of itraconazole treatment, so before applying a large-scale treatment regime, captive managers should trial treatment on a small subset of individuals to determine safety and effectiveness. Testing the treated animals for at least four weeks after the completion of treatment is necessary to ensure eradication of low level infection 7 , and should be implemented after every treatment regimen.…”

“…Establishing and maintaining disease free colonies is a challenge for amphibian management facilities. The current chemotherapeutic methods for treating Bd infections, although effective, can be harmful to the animals being treated, and no single treatment method has been successful across species and age classes of amphibians 7 .…”

“…Few clinical trials of treatments for Bd infection have been performed 7 . The three most commonly used methods of treatment are heat therapy, chloramphenicol and itraconazole.…”

Treatment of amphibians infected with chytrid fungus: learning from failed trials with itraconazole, antimicrobial peptides, bacteria, and heat therapy

“…The urgent development of antifungal treatment protocols has resulted in several reports (Nichols et al 2000, Berger et al 2010, Bowerman et al 2010, Pessier & Mendelson 2010, Martel et al 2011, Tamukai et al 2011. Successful trials have been documented in peer-reviewed journals.…”

Elevated temperature clears chytrid fungus infections from tadpoles of the midwife toad, Alytes obstetricans

“…Hence, a treatment against Bd that has no such side effects would be of great benefit. Because growth and survival of Bd are highly sensitive to high temperature (Piotrowski, Annis and Longcore, 2004), Woodhams et al (2003) and Retallick and Miera (2007) (Berger et al, 2010). Here, we test whether tadpoles can also be treated against Bd infection by keeping them at an elevated temperature.…”