Assessing the efficacy and feasibility of a prophylactic treatment for chytridiomycosis Restricted; Files Only
Barnett, Katherine (Fall 2023)
Published
Abstract
Chytridiomycosis is an infectious disease of amphibians caused by the fungal parasite Batrachochytrium dendrobatidis (Bd). The global distribution of Bd poses an imminent conservation threat as the introduction of Bd has led to mass mortality events in many species of frog, even resulting in 90 species’ extinctions. Previous work found that exposure to non-infectious antigenic metabolites produced by Bd imperfectly immunizes frogs against the fungal parasite. Inducing acquired resistance (via vaccination or prophylaxis) is an impactful tool used for parasite elimination and eradication in public health, and vaccination in wildlife is increasingly applied for conservation and spillover disease prevention. For my dissertation, I combined laboratory experiments, disease modeling techniques, and a large-scale field manipulation experiment to determine the impacts of strain heterogeneity, host’s pathogen exposure history, and partial protection on the effectiveness of Bd prophylaxis for conservation-motivated disease control. I found that protection provided by Bd metabolite prophylaxis was sensitive to ecological factors such as pathogen strain and the host’s exposure history to Bd. Moreover, protection provided by Bd metabolites is partial, such that prophylactic treatment reduces infection intensities but does not completely block infections. Given this, I built a system-specific agent-based model to explore scenarios varying mode of prophylaxis protection, degree of treatment efficacy, and proportion of population treated. Lastly, I conducted a Before-After-Control-Impact field experiment to test the effectiveness of Bd metabolite prophylaxis when administered in natural populations. Unexpectedly, infection intensities significantly increased after Bd metabolite addition in field-treated frogs, as compared to frogs from ponds treated with a sham control. Model scenarios in which prophylaxis strongly boosts tolerance (i.e., a host’s ability to survive high infection intensities), with no or minimal increase in resistance, are consistent with this field result. While tolerance is challenging to measure empirically, we suggest future studies measure the net transmission potential of treated versus untreated individuals to better project how partial protection at the individual level scales to key epidemiological outcomes on the population level. Overall, this dissertation rigorously evaluates the effectiveness of Bd metabolite prophylaxis under relevant ecological conditions, and the results caution its use to slow chytridiomycosis-induced biodiversity loss until further studies validate the mechanism behind observed increased infection intensities in field-treated frogs.
Table of Contents
Introduction: Ecological and evolutionary challenges to wildlife vaccination.........1
1. Abstract......................................................................................................1
2. The Potential of Wildlife Vaccines.................................................................2
3. Objectives of Wildlife Vaccination.................................................................2
4. Vaccine Efficacy and Modes of Imperfection...................................................3
a. Waning Immunity........................................................................................4
b. Binary Immunity.........................................................................................5
c. Partial Immunity.........................................................................................5
5. Functional Mechanisms and Consequences of Imperfect Vaccines..................6
a. Anti-disease Vaccines.................................................................................6
b. Anti-infection and Anti-transmission Vaccines............................................7
6. Ecological and Logistical Challenges of Vaccination Exacerbated in Wildlife...9
7. Trait-Based Vaccination...........................................................................12
8. Modeling Wildlife Vaccination.................................................................12
9. Concluding Remarks...............................................................................13
10. Acknowledgments...................................................................................14
11. Glossary.................................................................................................15
12. References.............................................................................................17
Chapter 2: Asymmetric cross-strain protection for amphibians exposed to a fungal
metabolite prophylactic treatment...............................................................23
1. Abstract................................................................................................24
2. Introduction..........................................................................................24
3. Methods................................................................................................27
a. Frog husbandry .....................................................................................27
b. Batrachochytrium dendrobatidis (Bd) culture and Bd metabolite treatment
preparation.................................................................................................27
c. Study design..........................................................................................28
d. Molecular detection of Batrachochytrium dendrobatidis...........................29
e. Data analysis.........................................................................................29
4. Results.................................................................................................30
5. Discussion............................................................................................32
6. References............................................................................................35
Chapter 3: Fungal metabolites provide pre-exposure protection but no post-exposure
benefit or harm against Batrachochytrium dendrobatidis...............................39
1. Abstract...............................................................................................40
2. Introduction.........................................................................................40
3. Materials and Methods..........................................................................43
a. Egg collection and husbandry.................................................................43
b. Batrachochytrium dendrobatidis (Bd) culture and Bd metabolite treatment
preparation................................................................................................44
c. Study design.........................................................................................45
d. Molecular detection of Batrachochytrium dendrobatidis..........................46
e. Data analysis........................................................................................46
4. Results.................................................................................................47
5. Discussion............................................................................................49
6. Acknowledgements...............................................................................52
7. References............................................................................................53
Chapter 4: Prophylactic treatment for Batrachochytrium dendrobatidis increases
amphibian infection loads in natural populations: A possible consequence of
increased host survival. .............................................................................58
1. Abstract..............................................................................................59
2. Significance Statement........................................................................60
3. Introduction.......................................................................................61
4. Materials and Methods........................................................................65
a. Field trial............................................................................................65
i. Experimental design.......................................65
ii. Preparing and administering Batrachochytrium dendrobatidis (Bd)
metabolites.....................................................66
iii. Pond-level Bd infection prevalence and load......67
iv. Data analysis on Bd field trial swabs..................67
b. Bd-amphibian-vaccine model..............................................................68
i. Modes of protection........................................71
ii. Two-way interactions with tolerance................71
iii. Vaccination caused harm..................................72
5. Results..............................................................................................72
a. Field trial and challenge experiment....................................................72
b. Bd-amphibian-vaccine model.............................................................73
i. Modes of protection.......................................73
ii. Two-way interactions with tolerance...............73
iii. Vaccination caused harm.................................74
6. Discussion........................................................................................74
7. Acknowledgements............................................................................80
8. References........................................................................................81
9. Figures.............................................................................................87
10. Supporting Information.....................................................................92
a. Challenge Experiment.......................................................................92
i. Materials and Methods..................................92
1. Pre-intervention...............................................................................92
2. Post-intervention.............................................................................93
3. Data analysis...................................................................................93
ii. Results and Discussion.................................94
b. Figures...........................................................................................95
c. Table.............................................................................................113
d. References.....................................................................................121
Chapter 5: Conclusion..........................................................................123
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