Cookies Policy

This site uses cookies. By continuing to browse the site you are agreeing to our use of cookies.

I accept this policy

Find out more here

Side effects of itraconazole on post-metamorphic Alytes obstetricans after a cold stress

No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.
The full text of this article is not currently available.

Brill’s MyBook program is exclusively available on BrillOnline Books and Journals. Students and scholars affiliated with an institution that has purchased a Brill E-Book on the BrillOnline platform automatically have access to the MyBook option for the title(s) acquired by the Library. Brill MyBook is a print-on-demand paperback copy which is sold at a favorably uniform low price.

Access this article

+ Tax (if applicable)
Add to Favorites
You must be logged in to use this functionality

image of Amphibia-Reptilia

Itraconazole is the most widely used treatment against Batrachochytrium dendrobatidis (Bd), the fungal pathogen causing chytridiomycosis, a proximate cause of amphibian declines. Several side effects of itraconazole treatment, ranging in severity from depigmentation to death have been reported in different amphibian species and life stages, and these side effects were observed at commonly used dosages of itraconazole. However, no studies have investigated side-effects of itraconazole in conjunction with environmental stress. Post-metamorphic midwife toads (Alytes obstetricans) that were treated with itraconazole and subsequently exposed to a cold stress (exposure to 4°C cold water) had higher mortality rates compared to untreated individuals. Moreover, adults of booroolong frogs (Litoria booroolongensis) treated with itraconazole had a higher probability to become infected when subsequently exposed to Bd. Our results suggest that a post-metamorphosis itraconazole treatment of infected midwife toads combined with a subsequent release into the wild may be an ineffective disease mitigation strategy, as the cold stress during hibernation and/or exposure to Bd in the wild may reduce the hibernation emergence rate of treated individuals in this species.

Affiliations: 1: 1Department of Conservation Biology, Helmholtz Centre for Environmental Research – UFZ, Permoserstrasse 15, 04138 Leipzig, Germany ; 2: 2Department of System Ecotoxicology, Helmholtz Centre for Environmental Research – UFZ, Permoserstrasse 15, 04138 Leipzig, Germany ; 3: 3ECOLAB, Université de Toulouse, CNRS, INPT, UPS, Toulouse, France ; 4: 4TerrOïko, 2 rue Clémence Isaure, 31250 Revel, France ; 5: 5Institute of Zoology, Zoological Society of London, Regent’s Park, London, NW1 4RY, UK ; 6: 6Department of Infectious Disease Epidemiology, Imperial College London, London, W2 1PG, UK

*Corresponding author; e-mail:

Full text loading...


Data & Media loading...

1. Baláž V., Kubečková M., Civiš P., Rozínek R., Vojar J. (2013): "Fatal chytridiomycosis and infection loss observed in captive toads infected in the wild". Acta Vet. Brno Vol 82: 351-355. [Crossref]
2. Bates D., Maechler M., Bolker B., Walker S. (2015): "Fitting linear mixed-effects models using lme4". J. Stat. Software Vol 67 (1): 1-48.
3. Berger L., Speare R., Daszak P., Green D.E., Cunningham A.A., Goggin C.L., Slocombe R., Regan M.A., Hyatt A.D., McDonald K.R., Hines H.B., Lips K.R., Marantelli G., Parkes H. (1998): "Chytridiomycosis causes amphibian mortality associated with population declines in the rain forests of Australia and Central America". Proc. Natl Acad. Sci. USA Vol 95: 9031-9036. [Crossref]
4. Berger L., Speare R., Skerratt L.F. (2005): "Distribution of Batrachochytrium dendrobatidis and pathology in the skin of green tree frogs Litorria caerulea with severe chytridiomycosis". Dis. Aquat. Org. Vol 68: 65-70. [Crossref]
5. Berger L., Speare R., Pessier A., Voyles J., Skerratt L.F. (2010): "Treatment of chytridiomycosis requires urgent clinical trials". Dis. Aquat. Org. Vol 92: 165-174. [Crossref]
6. Blaustein A.R., Gervasi S.S., Johnson P.T.J., Hoverman J.T., Belden L.K., Bradley P.W., Xie G.Y. (2012): "Ecophysiology meets conservation: understanding the role of disease in amphibian population declines". Phil. Trans. R. Soc. B Vol 367: 1688-1707. [Crossref]
7. Bosch J., Sanchez-Tomé E., Fernández-Loras A., Olivier J.A., Fisher M.C., Garner T.W. (2015): "Successful elimination of a lethal wildlife infectious disease in nature". Biol. Lett. Vol 11 (11): 20150874. [Crossref]
8. Boyle D.G., Boyle D.B., Olsen V., Morgan J.A.T., Hyatt A.D. (2004): "Rapid quantitative detection of chytridiomycosis (Batrachochytrium dendrobatidis) in amphibian samples using real-time taqman PCR assay". Dis. Aquat. Org. Vol 60: 141-148. [Crossref]
9. Brannelly L.A., Richards-Zawacki C.L., Pessier A.P. (2012): "Clinical trials with itraconazole as a treatment for chytrid fungal infections in amphibians". Dis. Aquat. Org. Vol 101: 95-104. [Crossref]
10. Briggs C.J., Knapp R.A., Vredenburg V.T. (2010): "Enzootic and epizootic dynamics of the chytrid fungal pathogen of amphibians". Proc. Natl Acad. Sci. USA Vol 107: 9695-9700. [Crossref]
11. Cashins S.D., Grogan L.F., McFadden M., Hunter D., Harlow P.S., Berger L., Skerratt L.F. (2013): "Prior infection does not improve survival against the amphibian disease chytridiomycosis". PLoS ONE Vol 8 (2): e56747. [Crossref]
12. Collazos J., Mayo J., Martínez E., Díaz F. (1995): "Unusual liver toxicity due to the new antifungal agents fluconazole and itraconazole." Int. Hepatol. Commun. Vol 3: 112-115. [Crossref]
13. Daszak P., Cunningham A.A., Hyatt A.D. (2003): "Infectious disease and amphibian population declines". Divers. Distrib. Vol 9: 141-150. [Crossref]
14. Farrer R.A., Weinert L.A., Bielby J., Garner T.W.J., Balloux F., Clare F., Bosch J., Cunningham A.A., Weldon C., du Preez L.H., Anderson L., Kosakovsky Pond S.L., Shahar-Golan R., Henk D.A., Fisher M.C. (2011): "Multiple emergences of genetically diverse amphibian-infecting chytrids include a globalized hypervirulent recombinant lineage". Proc. Natl Acad. Sci. USA Vol 108: 18732-18736. [Crossref]
15. Fisher M.C., Schmidt B.R., Henle K., Schmeller D.S., Bosch J., Aanensen D.M. (2012): "RACE: risk assessment of chytridiomycosis to European amphibian biodiversity". Froglog Vol 101: 45-47.
16. Forzán M.J., Gunn H., Scott P. (2008): "Chytridiomycosis in an aquarium collection of frogs: diagnosis, treatment, and control". J. Zoo Wildlife Med. Vol 39: 406-411. [Crossref]
17. Gagliardo R., Crump P., Griffith E., Mendelson J., Ross H., Zippel K. (2008): "The principles of rapid responses for amphibian conservation, using the programmes in Panama as an example". Int. Zoo Yb. Vol 42: 125-135. [Crossref]
18. Garmyn A., Van Rooij P., Pasmans F., Hellebuyck T., Van Dem Broeck W., Haesebrouck F., Martel A. (2012): "Waterfowl: potential environmental reservoirs of the chytrid fungus Batrachochytrium dendrobatidis". PLoS ONE Vol 7 (4): e35038. [Crossref]
19. Garner T.W.J., Garcia G., Carroll B., Fisher M.C. (2009): "Using itraconazole to clear Batrachochytrium dendrobatidis infection and subsequent depigmentation of Alytes muletensis tadpoles". Dis. Aquat. Org. Vol 83: 257-260. [Crossref]
20. Georoff T.A., Moore R.P., Rodriguez C., Pessier A.P., Newton A.L., McAloose D., Calle P.P. (2013): "Efficacy of treatment and long-term follow-up of Batrachochytrium dendrobatidis PCR-positive anurans following itraconazole bath treatment". J. Zoo Wildlife Med. Vol 44: 395-403. [Crossref]
21. Hardy B.M., Pope K.L., Piova-Scott J., Brown R.N., Foley J.E. (2015): "Itraconazole treatment reduces Batrachochytrium dendrobatidis prevalence and increases overwinter field survival in juvenile Cascades frogs". Dis. Aquat. Org. Vol 112: 243-250. [Crossref]
22. Holden W.M., Ebert A.R., Canning P.F., Rollins-Smith L.A. (2014): "Evaluation of amphotericin B and chloramphenicol as alternative drugs for treatment of chytridiomycosis and their impacts on innate skin defenses". Appl. Environ. Microbiol. Vol 80: 4034-4041. [Crossref]
23. Hyatt A., Boyle D., Olsen V., Boyle D., Berger L., Obendorf D., Dalton A., Kriger K., Hero M., Hines H., Phillott R., Cambell R., Marantelli G., Gleason F., Colling A. (2007): "Diagnostic assays and sampling protocols for the detection of Batrachochytrium dendrobatidis". Dis. Aquat. Org. Vol 73: 175-192. [Crossref]
24. Jekel J.F., Katz D.L., Elmore J.G., Wild D. (2007): Epidemiology, Biostatistics and Preventive Medicine, 3rd Edition. Sauders Elsevier, Philadelphia, USA.
25. Jones M.E.B., Paddock D., Bender L., Allen J.L., Schrenzel M.S., Pessier A.P. (2012): "Treatment of chytridiomycosis with reduced-dose itraconazole". Dis. Aquat. Org. Vol 99: 243-249. [Crossref]
26. Lamirande E.W., Nichols D.K. (2001): "Effects of host age on susceptibility to cutaneous chytridiomycosis in blue-and-yellow poison dart frogs (Dendrobates tinctorius)". In: Proc. 6th International Symposium on the Pathology of Reptiles and Amphibians, p.  3-16. McKinnell R.G., Carlson D.L., Eds, University of Minnesota Printing Services, Saint Paul, MN.
27. Martel A., van Rooij P., Vercauteren G., Baert K., van Waeyenberghe L., Debacker P., Garner T.W., Woeltjes T., Ducatelle R., Haesebrouck F., Pasmans F. (2011): "Developing a safe antifungal treatment protocol to eliminate Batrachochytrium dendrobatidis from amphibians". Med. Mycol. Vol 49 (2): 143-149. [Crossref]
28. Muijsers M., Martel A., Van Rooij P., Baert K., Vercauteren G., Ducatelle R., De Backer P., Vercammen F., Haesebrouck F., Pasmans F. (2012): "Antibacterial therapeutics for the treatment of chytrid infection in amphibians: Columbus’s egg?" BMC Vet. Res. Vol 8: 175. [Crossref]
29. Nichols D.K., Lamirande E.W. (2000): Treatment of cutaneous chytridiomycosis in blue-and-yellow poison dart frogs (Dendrobates tinctorius). In: Workshop on Amphibian Disease. Cairns, Australia.
30. Nichols D.K., Lamirande E.W. (2000): "Treatment of cutaneous chytridiomycosis in blue-and-yellow poison dart frogs (Dendrobates tinctorius)". In: Proceedings: Getting the Jump on Amphibian Disease, Cairns, Australia, August 26-30 (Abstr.), p.  51.
31. Nichols D.K., Lamirande E.W. (2001): "Successful treatment of chytridiomycosis". Froglog Vol 46.
32. Parris M.J., Baud D.R. (2004): "Interactive effects of a heavy metal and chytridiomycosis on gray treefrog larvae (Hyla chrysoscelis)". Copeia Vol 2: 344-350. [Crossref]
33. Pessier A.P., Mendelson J.R., Eds (2010): A Manual for Control of Infectious Diseases in Amphibian Survival Assurance Colonies and Reintroduction Programs. IUCN/SSC Conservation Breeding Specialist Group, Apple Valley, MN.
34. R Core Team (2016): R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. Available at
35. Rachowicz L.J., Knapp R.A., Morgan J.A.T., Stice M.J., Vredenburg V.T., Parker J.M., Briggs C.J. (2006): "Emerging infectious disease as a proximate cause of amphibian mass mortality". Ecology Vol 87: 1671-1683. [Crossref]
36. Rosenblum E.B., Stajich J.E., Maddox N., Eisen M.B. (2008): "Global gene expression profiles for life stages of the deadly amphibian pathogen Batrachochytrium dendrobatidis". Proc. Natl Acad. Sci. USA Vol 105 (44): 17034-17039. [Crossref]
37. Schmeller D.S., Loyau A., Dejean T., Miaud C. (2011): "Using amphibians in laboratory studies: precautions against the emerging infectious disease chytridiomycosis". Lab. Anim. Vol 45: 25-30. [Crossref]
38. Schmeller D.S., Blooi M., Martel A., Garner T.W.J., Fisher M.C., Azemar F., Clares F.C., Leclerc C., Jäger L., Guevara-Nieto M., Loyau A., Pasmans F. (2014): "Microscopic aquatic predators strongly affect infection dynamics of a globally emerged pathogen". Curr. Biol. Vol 24: 176-180. [Crossref]
39. Solís R., Lobos G., Walker S., Fisher M., Bosch J. (2010): "Presence of Batrachochytrium dendrobatidis in feral populations of Xenopus laevis in Chile". Biol. Invasions Vol 12: 1641-1646. [Crossref]
40. Somchit N., Norshahida A.R., Hasiah A.H., Zuraini A., Sulaiman M.R., Noordin M.M. (2004): "Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study". Hum. Exp. Toxicol. Vol 23: 519-525. [Crossref]
41. Tamukai K., Une Y., Tominaga A., Suzuki K., Goka K. (2011): "Treatment of spontaneous chytridiomycosis in captive amphibians using itraconazole". J. Vet. Med. Sci. Vol 73: 155-159. [Crossref]
42. Tobler U., Schmidt B.R. (2010): "Within- and among-population variation in chytridiomycosis-induced mortality in the toad Alytes obstetricans". PLoS ONE Vol 5: e10927. [Crossref]
43. Une Y., Matsui K., Tamukai K., Goka K. (2012): "Eradication of the chytrid fungus Batrachochytrium dendrobatidis in the Japanese giant salamander Andrias japonicas". Dis. Aquat. Org. Vol 98: 243-247. [Crossref]
44. Van Rooij P., Martel A., D’Herde K., Brutyn M., Croubels S., Ducatelle R., Haesebrouck F., Pasmans F. (2012): "Germ tube mediated invasion of Batrachochytrium dendrobatidis in amphibian skin is host dependent". PLoS ONE Vol 7: e41481.
45. Venesky M.D., Raffel T.R., McMahon T.A., Rohr J.R. (2014): "Confronting inconsistencies in the amphibian-chytridiomycosis system: implications for disease management". Biol. Rev. Camb. Philos. Soc. Vol 89: 477-483. [Crossref]
46. Voyles J., Berger L., Young S., Speare R., Webb R., Warner J., Rudd D., Campbell R., Skerratt L.F. (2007): "Electrolyte depletion and osmotic imbalance in amphibians with chytridiomycosis". Dis. Aquat. Org. Vol 77: 113-118. [Crossref]
47. Voyles J., Young S., Berger L., Campbell C., Voyles W.F., Dinudom A., Cook D., Webb R., Alford R.A., Skerratt L.F., Speare R. (2009): "Pathogenesis of chytridiomycosis, a cause of catastrophic amphibian declines". Science Vol 326: 582-585. [Crossref]
48. Woodhams D.C., Bosch J., Briggs C.J., Cashins S., Davis L.R., Lauer A., Muths E., Puschendorf R., Schmidt B.R., Sheafor B., Voyles J. (2011): "Mitigating amphibian disease: strategies to maintain wild populations and control chytridiomycosis". Front. Zool. Vol 8: 8. [Crossref]
49. Woodhams D.C., Geiger C.C., Reinert L.K., Rollins-Smith L.A., Lam B., Harris R.N., Briggs C.J., Vredenburg V.T., Voyles J. (2012): "Treatment of amphibians infected with chytrid fungus: learning from failed trials with itraconazole, antimicrobial peptides, bacteria, and heat therapy". Dis. Aquat. Org. Vol 98: 11-25. [Crossref]

Article metrics loading...



Can't access your account?
  • Tools

  • Add to Favorites
  • Printable version
  • Email this page
  • Subscribe to ToC alert
  • Get permissions
  • Recommend to your library

    You must fill out fields marked with: *

    Librarian details
    Your details
    Why are you recommending this title?
    Select reason:
    Amphibia-Reptilia — Recommend this title to your library
  • Export citations
  • Key

  • Full access
  • Open Access
  • Partial/No accessInformation