Faculty and Staff

The emergence of the disease chytridiomycosis caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd) has been implicated in dramatic global amphibian declines. Although many species have undergone catastrophic declines and/or extinctions, others appear to be unaffected or persist at reduced frequencies after Bd outbreaks. The reasons behind this variance in disease outcomes are poorly understood: differences in host immune responses have been proposed, yet previous studies suggest a lack of robust immune responses to Bd in susceptible species. Here, we sequenced transcriptomes from clutch-mates of a highly susceptible amphibian, Atelopus zeteki, with different infection histories. We found significant changes in expression of numerous genes involved in innate and inflammatory responses in infected frogs despite high susceptibility to chytridiomycosis.

We show evidence of acquired immune responses generated against Bd, including increased expression of immunoglobulins and major histocompatibility complex genes. In addition, fungal-killing genes had significantly greater expression in frogs previously exposed to Bd compared with Bd-naïve frogs, including chitinase and serine-type proteases. However, our results appear to confirm recent in vitro evidence of immune suppression by Bd, demonstrated by decreased expression of lymphocyte genes in the spleen of infected compared with control frogs. We propose susceptibility to chytridiomycosis is not due to lack of Bd-specific immune responses but instead is caused by failure of those responses to be effective. Ineffective immune pathway activation and timing of antibody production are discussed as potential mechanisms. However, in light of our findings, suppression of key immune responses by Bd is likely an important factor in the lethality of this fungus.

Background: While there is ample evidence for health risks associated with heat and other extreme weather events today, little is known about the impact of weather patterns on population health in preindustrial societies.

Objective: To investigate the impact of weather patterns on population health in Sweden before and during industrialization.

Methods: We obtained records of monthly mortality and of monthly mean temperatures and precipitation for Skellefteå parish, northern Sweden, for the period 1800-1950. The associations between monthly total mortality, as well as monthly mortality due to infectious and cardiovascular diseases, and monthly mean temperature and cumulative precipitation were modelled using a time series approach for three separate periods, 1800−1859, 1860-1909, and 1910-1950.

Results: We found higher temperatures and higher amounts of precipitation to be associated with lower mortality both in the medium term (same month and two-months lag) and in the long run (lag of six months up to a year). Similar patterns were found for mortality due to infectious and cardiovascular diseases. Furthermore, the effect of temperature and precipitation decreased over time.

Conclusions: Higher temperature and precipitation amounts were associated with reduced death counts with a lag of up to 12 months. The decreased effect over time may be due to improvements in nutritional status, decreased infant deaths, and other changes in society that occurred in the course of the demographic and epidemiological transition.

Contribution: The study contributes to a better understanding of the complex relationship between weather and mortality and, in particular, historical weather-related mortality.

Amphibians vary in their response to infection by the amphibian-killing chytrid fungus, Batrachochytrium dendrobatidis (Bd). Highly susceptible species are the first to decline and/or disappear once Bd arrives at a site. These competent hosts likely facilitate Bd proliferation because of ineffective innate and/or acquired immune defenses. We show that Atelopus zeteki, a highly susceptible species that has undergone substantial population declines throughout its range, rapidly and exponentially increases skin Bd infection intensity, achieving intensities that are several orders of magnitude greater than most other species reported. We experimentally infected individuals that were never exposed to Bd (n = 5) or previously exposed to an attenuated Bd strain (JEL427-P39; n = 3). Within seven days post-inoculation, the average Bd infection intensity was 18,213 zoospores (SE: 9,010; range: 0 to 66,928).

Both average Bd infection intensity and zoospore output (i.e., the number of zoospores released per minute by an infected individual) increased exponentially until time of death (t₅₀ = 7.018, p<0.001, t₄₆ = 3.164, p = 0.001, respectively). Mean Bd infection intensity and zoospore output at death were 4,334,422 zoospores (SE: 1,236,431) and 23.55 zoospores per minute (SE: 22.78), respectively, with as many as 9,584,158 zoospores on a single individual. The daily percent increases in Bd infection intensity and zoospore output were 35.4% (SE: 0.05) and 13.1% (SE: 0.04), respectively. We also found that Bd infection intensity and zoospore output were positively correlated (t₄₃ = 3.926, p<0.001). All animals died between 22 and 33 days post-inoculation (mean: 28.88; SE: 1.58). Prior Bd infection had no effect on survival, Bd infection intensity, or zoospore output. We conclude that A. zeteki, a highly susceptible amphibian species, may be an acute supershedder. Our results can inform epidemiological models to estimate Bd outbreak probability, especially as they relate to reintroduction programs.

Laboratory investigations into the amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd), have accelerated recently, given the pathogen’s role in causing the global decline and extinction of amphibians. Studies in which host animals were exposed to Bd have largely assumed that lab-maintained pathogen cultures retained the infective and pathogenic properties of wild isolates. Attenuated pathogenicity is common in artificially maintained cultures of other pathogenic fungi, but to date, it is unknown whether, and to what degree, Bd might change in culture. We compared zoospore production over time in two samples of a single Bd isolate having different passage histories: one maintained in artificial media for more than six years (JEL427-P39), and one recently thawed from cryopreserved stock (JEL427-P9). In a common garden experiment, we then exposed two different amphibian species, Eleutherodactylus coqui and Atelopus zeteki, to both cultures to test whether Bd attenuates in pathogenicity with in vitro passages. The culture with the shorter passage history, JEL427-P9, had significantly greater zoospore densities over time compared to JEL427-P39. This difference in zoospore production was associated with a difference in pathogenicity for a susceptible amphibian species, indicating that fecundity may be an important virulence factor for Bd. In the 130-day experiment, Atelopus zeteki frogs exposed to the JEL427-P9 culture experienced higher average infection intensity and 100% mortality, compared with 60% mortality for frogs exposed to JEL427-P39. This effect was not observed with Eleutherodactylus coqui, which was able to clear infection. We hypothesize that the differences in phenotypic performance observed with Atelopus zeteki are rooted in changes of the Bd genome. Future investigations enabled by this study will focus on the underlying mechanisms of Bd pathogenicity.

Background: Most excess deaths that occur during extreme hot weather events do not have natural heat recorded as an underlying or contributing cause. This study aims to identify the specific individuals who died because of hot weather using only secondary data. A novel approach was developed in which the expected number of deaths was repeatedly sampled from all deaths that occurred during a hot weather event, and compared with deaths during a control period. The deaths were compared with respect to five factors known to be associated with hot weather mortality. Individuals were ranked by their presence in significant models over 100 trials of 10,000 repetitions. Those with the highest rankings were identified as probable excess deaths. Sensitivity analyses were performed on a range of model combinations. These methods were applied to a 2009 hot weather event in greater Vancouver, Canada.

Results: The excess deaths identified were sensitive to differences in model combinations, particularly between univariate and multivariate approaches. One multivariate and one univariate combination were chosen as the best models for further analyses. The individuals identified by multiple combinations suggest that marginalized populations in greater Vancouver are at higher risk of death during hot weather.

Conclusions: This study proposes novel methods for classifying specific deaths as expected or excess during a hot weather event. Further work is needed to evaluate performance of the methods in simulation studies and against clinically identified cases. If confirmed, these methods could be applied to a wide range of populations and events of interest.

Background: Extreme heat is a public health challenge. The scarcity of directly comparable studies on the association of heat with morbidity and mortality and the inconsistent identification of threshold temperatures for severe impacts hampers the development of comprehensive strategies aimed at reducing adverse heat-health events.

Objectives: This quantitative study was designed to link temperature with mortality and morbidity events in Maricopa County, Arizona, USA, with a focus on the summer season.
Methods: Using Poisson regression models that controlled for temporal confounders, we assessed daily temperature–health associations for a suite of mortality and morbidity events, diagnoses, and temperature metrics. Minimum risk temperatures, increasing risk temperatures, and excess risk temperatures were statistically identified to represent different “trigger points” at which heat-health intervention measures might be activated.

Results: We found significant and consistent associations of high environmental temperature with all-cause mortality, cardiovascular mortality, heat-related mortality, and mortality resulting from conditions that are consequences of heat and dehydration. Hospitalizations and emergency department visits due to heat-related conditions and conditions associated with consequences of heat and dehydration were also strongly associated with high temperatures, and there were several times more of those events than there were deaths. For each temperature metric, we observed large contrasts in trigger points (up to 22°C) across multiple health events and diagnoses.

Conclusion: Consideration of multiple health events and diagnoses together with a comprehensive approach to identifying threshold temperatures revealed large differences in trigger points for possible interventions related to heat. Providing an array of heat trigger points applicable for different end-users may improve the public health response to a problem that is projected to worsen in the coming decades.

Background: Extreme heat is a leading weather-related cause of mortality in the United States, but little guidance is available regarding how temperature variable selection impacts heat–mortality relationships.
Objectives: We examined how the strength of the relationship between daily heat-related mortality and temperature varies as a function of temperature observation time, lag, and calculation method.
Methods: Long time series of daily mortality counts and hourly temperature for seven U.S. cities with different climates were examined using a generalized additive model. The temperature effect was modeled separately for each hour of the day (with up to 3-day lags) along with different methods of calculating daily maximum, minimum, and mean temperature. We estimated the temperature effect on mortality for each variable by comparing the 99th versus 85th temperature percentiles, as determined from the annual time series.

Results: In three northern cities (Boston, MA; Philadelphia, PA; and Seattle, WA) that appeared to have the greatest sensitivity to heat, hourly estimates were consistent with a diurnal pattern in the heat-mortality response, with strongest associations for afternoon or maximum temperature at lag 0 (day of death) or afternoon and evening of lag 1 (day before death). In warmer, southern cities, stronger associations were found with morning temperatures, but overall the relationships were weaker. The strongest temperature–mortality relationships were associated with maximum temperature, although mean temperature results were comparable.

Conclusions: There were systematic and substantial differences in the association between temperature and mortality based on the time and type of temperature observation. Because the strongest hourly temperature–mortality relationships were not always found at times typically associated with daily maximum temperatures, temperature variables should be selected independently for each study location. In general, heat-mortality was more closely coupled to afternoon and maximum temperatures in most cities we examined, particularly those typically prone to heat-related mortality.

Background: Environmental heat exposure is a public health concern. The impacts of environmental heat on mortality and morbidity at the population scale are well documented, but little is known about specific exposures that individuals experience.

Objectives: The first objective of this work was to catalyze discussion of the role of personal heat exposure information in research and risk assessment. The second objective was to provide guidance regarding the operationalization of personal heat exposure research methods.

Discussion: We define personal heat exposure as realized contact between a person and an indoor or outdoor environment that poses a risk of increases in body core temperature and/or perceived discomfort. Personal heat exposure can be measured directly with wearable monitors or estimated indirectly through the combination of time–activity and meteorological data sets. Complementary information to understand individual-scale drivers of behavior, susceptibility, and health and comfort outcomes can be collected from additional monitors, surveys, interviews, ethnographic approaches, and additional social and health data sets. Personal exposure research can help reveal the extent of exposure misclassification that occurs when individual exposure to heat is estimated using ambient temperature measured at fixed sites and can provide insights for epidemiological risk assessment concerning extreme heat.

Conclusions: Personal heat exposure research provides more valid and precise insights into how often people encounter heat conditions and when, where, to whom, and why these encounters occur. Published literature on personal heat exposure is limited to date, but existing studies point to opportunities to inform public health practice regarding extreme heat, particularly where fine-scale precision is needed to reduce health consequences of heat exposure.

The Arctic, even more so than other parts of the world, has warmed substantially over the past few decades. Temperature and humidity influence the rate of development, survival and reproduction of pathogens and thus the incidence and prevalence of many infectious diseases. Higher temperatures may also allow infected host species to survive winters in larger numbers, increase the population size and expand their habitat range. The impact of these changes on human disease in the Arctic has not been fully evaluated. There is concern that climate change may shift the geographic and temporal distribution of a range of infectious diseases. Many infectious diseases are climate sensitive, where their emergence in a region is dependent on climate-related ecological changes. Most are zoonotic diseases, and can be spread between humans and animals by arthropod vectors, water, soil, wild or domestic animals. Potentially climate-sensitive zoonotic pathogens of circumpolar concern include Brucella spp., Toxoplasma gondii, Trichinella spp., Clostridium botulinum, Francisella tularensis, Borrelia burgdorferi, Bacillus anthracis, Echinococcus spp., Leptospira spp., Giardia spp., Cryptosporida spp., Coxiella burnetti, rabies virus, West Nile virus, Hantaviruses, and tick-borne encephalitis viruses.

Background: Multiple methods are employed for modeling adaptation when projecting the impact of climate change on heat-related mortality. The sensitivity of impacts to each is unknown because they have never been systematically compared. In addition, little is known about the relative sensitivity of impacts to “adaptation uncertainty” (i.e., the inclusion/exclusion of adaptation modeling) relative to using multiple climate models and emissions scenarios.

Objectives: This study had three aims: a) Compare the range in projected impacts that arises from using different adaptation modeling methods; b) compare the range in impacts that arises from adaptation uncertainty with ranges from using multiple climate models and emissions scenarios; c) recommend modeling method(s) to use in future impact assessments.

Methods: We estimated impacts for 2070–2099 for 14 European cities, applying six different methods for modeling adaptation; we also estimated impacts with five climate models run under two emissions scenarios to explore the relative effects of climate modeling and emissions uncertainty.

Results: The range of the difference (percent) in impacts between including and excluding adaptation, irrespective of climate modeling and emissions uncertainty, can be as low as 28% with one method and up to 103% with another (mean across 14 cities). In 13 of 14 cities, the ranges in projected impacts due to adaptation uncertainty are larger than those associated with climate modeling and emissions uncertainty.

Conclusions: Researchers should carefully consider how to model adaptation because it is a source of uncertainty that can be greater than the uncertainty in emissions and climate modeling. We recommend absolute threshold shifts and reductions in slope.