Pharmacokinetics of terbinafine in little brown myotis (Myotis lucifugus) infected with Pseudogymnoascus destructans

Court, Michael H.; Robbins, Alison H.; Whitford, Anne M.; Beck, Erika V.; Tseng, Flo S.; Reeder, DeeAnn M.

doi:10.2460/ajvr.78.1.90

Cited by 15 publications

(11 citation statements)

References 22 publications

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“…included both topical, oral and implanted treatments for hosts as well as attempts to reduce the environmental pathogen reservoir and delay transmission. Several treatments have now been tested in vitro, in vivo or in situ 133,135,[154][155][156][157][158] , including antifungal chemicals, volatile organic compounds, probiotic microbes, biopolymers and vaccines (reviewed elsewhere 153,155 ). Currently, only one probiotic treatment and a vaccine have been shown to reduce mortality in a single species, M. lucifugus 135,155 ; however, no treatment has been deployed on a landscape scale.…”

Section: Box 1 | Ecosystem Impacts Of White-nose Syndromementioning

confidence: 99%

Ecology and impacts of white-nose syndrome on bats

2021

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White-nose syndrome (WNS) is a fungal disease in bats and one of the most devastating infectious disease outbreaks in wild mammals to emerge over the past century 1-15. WNS was first detected in 2007 by biologists who discovered an abnormal mortality event at a cave in Albany County, New York (NY), USA, while conducting routine bat population monitoring surveys 16. Bats that were still alive were covered in a white fungus, which was most noticeable on their muzzles, ears and wings, thus leading to the disease being named WNS 17,18. Following this discovery, inspection of nearby hibernation sites (hibernacula) led to similar findings and further examination of photos collected from previous winter surveys revealed that bats at another nearby site had visible signs of infection with the fungus in the winter of 2005-2006. Thus, the earliest evidence of this disease in North America is on 16 February 2006 in Howes Cave, NY 17. Histological examination of dead and dying bats later identified the likely causative agent as Geomyces destructans 19 , a novel fungus that was unknown to science before its discovery in North America 17. Based on DNA sequence data from other Geomyces spp. and related fungi, G. destructans was reclassified as Pseudogymnoascus destructans 16,17,20 in 2013. P. destructans is a multi-host psychrophilic ascomycete 20 in the order Onygenales, which contains many other pathogenic and environmentally resilient fungi. Molecular evidence suggests that P. destructans has evolved with Eurasian bat communities, with which it has coexisted for millenia 21,22 , to become a specialist pathogen that relies primarily on living bat tissue for growth and replication 22-24. The investment in parasitic traits has led to physiological and ecological trade-offs 22-26 , which make P. destructans both reliant on but also well adapted to infecting the epidermal tissue of hibernating bats during the winter 26,27. While bat communities across Eurasia experience greatly reduced WNS disease severity with no evidence of mass mortality 28,29 , naive host communities in North America experienced unprecedented population declines 1-15 on first exposure to this virulent pathogen 26,27. Routine monitoring and retrospective photo documentation of bat populations enabled biologists to estimate the timing of P. destructans' introduction to North America with some certainty, making this disease emergence unique among other wildlife diseases. Early detection enabled the spread of P. destructans across North America to be tracked and the impacts of the pathogen on hosts to be accurately assessed. Building on this information, the first decade of WNS research has led to considerable advances in the understanding of the closely tied interactions between P. destructans and its hosts compared with other emerging wildlife diseases over similar timescales 30,31. In this Review, we describe the origins, distribution, seasonal life history, pathogenesis, and the impacts and persistence of bats with P. destructans across the globe. Finally, we...

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Section: Box 1 | Ecosystem Impacts Of White-nose Syndromementioning

confidence: 99%

Ecology and impacts of white-nose syndrome on bats

2021

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“…While non-lethal diagnostic tools offer the opportunity to follow the progression of skin pathology, prior experience with WNS pathology scores may be used to predict the outcome of infection in a diseased bat. With intensive research for treatment of WNS in North America [ 24 ], ability to predict patient prognosis becomes imperative. Lacking sufficient sample sizes for statistical model evaluation, case report experience might provide valuable information.…”

Section: Introductionmentioning

confidence: 99%

White-nose syndrome pathology grading in Nearctic and Palearctic bats

et al. 2017

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While white-nose syndrome (WNS) has decimated hibernating bat populations in the Nearctic, species from the Palearctic appear to cope better with the fungal skin infection causing WNS. This has encouraged multiple hypotheses on the mechanisms leading to differential survival of species exposed to the same pathogen. To facilitate intercontinental comparisons, we proposed a novel pathogenesis-based grading scheme consistent with WNS diagnosis histopathology criteria. UV light-guided collection was used to obtain single biopsies from Nearctic and Palearctic bat wing membranes non-lethally. The proposed scheme scores eleven grades associated with WNS on histopathology. Given weights reflective of grade severity, the sum of findings from an individual results in weighted cumulative WNS pathology score. The probability of finding fungal skin colonisation and single, multiple or confluent cupping erosions increased with increase in Pseudogymnoascus destructans load. Increasing fungal load mimicked progression of skin infection from epidermal surface colonisation to deep dermal invasion. Similarly, the number of UV-fluorescent lesions increased with increasing weighted cumulative WNS pathology score, demonstrating congruence between WNS-associated tissue damage and extent of UV fluorescence. In a case report, we demonstrated that UV-fluorescence disappears within two weeks of euthermy. Change in fluorescence was coupled with a reduction in weighted cumulative WNS pathology score, whereby both methods lost diagnostic utility. While weighted cumulative WNS pathology scores were greater in the Nearctic than Palearctic, values for Nearctic bats were within the range of those for Palearctic species. Accumulation of wing damage probably influences mortality in affected bats, as demonstrated by a fatal case of Myotis daubentonii with natural WNS infection and healing in Myotis myotis. The proposed semi-quantitative pathology score provided good agreement between experienced raters, showing it to be a powerful and widely applicable tool for defining WNS severity.

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“…Over the past 15 years, extensive research has revealed much about the disease ecology of WNS, including the interactions between the pathogen, environments where bats hibernate, and the physiology of hibernating bats (see 12 for recent comprehensive review). Research efforts have also focused on testing potential management actions aimed to reduce transmission or spread, lower disease severity, or improve survival 15 – 18 . One of the challenging aspects of managing WNS is that the pathogen persists in the environment where bats hibernate, exposing bats to infection at the start of each hibernation season 19 , 20 .…”

Section: Introductionmentioning

confidence: 99%

Experimental inoculation trial to determine the effects of temperature and humidity on White-nose Syndrome in hibernating bats

Frick

Johnson

Cheng

et al. 2022

Sci Rep

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Disease results from interactions among the host, pathogen, and environment. Inoculation trials can quantify interactions among these players and explain aspects of disease ecology to inform management in variable and dynamic natural environments. White-nose Syndrome, a disease caused by the fungal pathogen, Pseudogymnoascus destructans (Pd), has caused severe population declines of several bat species in North America. We conducted the first experimental infection trial on the tri-colored bat, Perimyotis subflavus, to test the effect of temperature and humidity on disease severity. We also tested the effects of temperature and humidity on fungal growth and persistence on substrates. Unexpectedly, only 37% (35/95) of bats experimentally inoculated with Pd at the start of the experiment showed any infection response or disease symptoms after 83 days of captive hibernation. There was no evidence that temperature or humidity influenced infection response. Temperature had a strong effect on fungal growth on media plates, but the influence of humidity was more variable and uncertain. Designing laboratory studies to maximize research outcomes would be beneficial given the high costs of such efforts and potential for unexpected outcomes. Understanding the influence of microclimates on host–pathogen interactions remains an important consideration for managing wildlife diseases, particularly in variable environments.

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Pharmacokinetics of terbinafine in little brown myotis (Myotis lucifugus) infected with Pseudogymnoascus destructans

Cited by 15 publications

References 22 publications

Ecology and impacts of white-nose syndrome on bats

Ecology and impacts of white-nose syndrome on bats

White-nose syndrome pathology grading in Nearctic and Palearctic bats

Experimental inoculation trial to determine the effects of temperature and humidity on White-nose Syndrome in hibernating bats

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