Neighborhood-level variability in asthma-related emergency department visits in Central Texas.

BACKGROUND: The extent to which incidence rates of asthma-related emergency department (ED) visits vary from neighborhood to neighborhood and predictors of neighborhood-level asthma ED visit burden are not well understood. OBJECTIVE: We aimed to describe the census tract-level spatial distribution of asthma-related ED visits in Central Texas and identify neighborhood-level characteristics that explain variability in neighborhood-level asthma ED visit rates. METHODS: Conditional autoregressive models were used to examine the spatial distribution of asthma-related ED visit incidence rates across census tracts in Travis County, Texas, and assess the contribution of census tract characteristics to their distribution. RESULTS: There were distinct patterns in ED visit incidence rates at the census tract scale. These patterns were largely unexplained by socioeconomic or selected built environment neighborhood characteristics. However, racial and ethnic composition explained 33% of the variability of ED visit incidence rates across census tracts. The census tract predictors of ED visit incidence rates differed by racial and ethnic group. CONCLUSIONS: Variability in asthma ED visit incidence rates are apparent at smaller spatial scales. Most of the variability in census tract-level asthma ED visit rates in Central Texas is not explained by racial and ethnic composition or other neighborhood characteristics.

Salinity stress increases the severity of ranavirus epidemics in amphibian populations.

The stress-induced susceptibility hypothesis, which predicts chronic stress weakens immune defences, was proposed to explain increasing infectious disease-related mass mortality and population declines. Previous work characterized wetland salinization as a chronic stressor to larval amphibian populations. Thus, we combined field observations with experimental exposures quantifying epidemiological parameters to test the role of salinity stress in the occurrence of ranavirus-associated mass mortality events. Despite ubiquitous pathogen presence (94%), populations exposed to salt runoff had slightly more frequent ranavirus related mass mortality events, more lethal infections, and 117-times greater pathogen environmental DNA. Experimental exposure to chronic elevated salinity (0.8-1.6 g l-1 Cl-) reduced tolerance to infection, causing greater mortality at lower doses. We found a strong negative relationship between splenocyte proliferation and corticosterone in ranavirus-infected larvae at a moderate elevation of salinity, supporting glucocorticoid-medicated immunosuppression, but not at high salinity. Salinity alone reduced proliferation further at similar corticosterone levels and infection intensities. Finally, larvae raised in elevated salinity had 10 times more intense infections and shed five times as much virus with similar viral decay rates, suggesting increased transmission. Our findings illustrate how a small change in habitat quality leads to more lethal infections and potentially greater transmission efficiency, increasing the severity of ranavirus epidemics.

Metabolites Involved in Immune Evasion by Batrachochytrium dendrobatidis Include the Polyamine Spermidine.

Amphibians have been declining around the world for more than four decades. One recognized driver of these declines is the chytrid fungus Batrachochytrium dendrobatidis, which causes the disease chytridiomycosis. Amphibians have complex and varied immune defenses against B. dendrobatidis, but the fungus also has a number of counterdefenses. Previously, we identified two small molecules produced by the fungus that inhibit frog lymphocyte proliferation, methylthioadenosine (MTA) and kynurenine (KYN). Here, we report on the isolation and identification of the polyamine spermidine (SPD) as another significant immunomodulatory molecule produced by B. dendrobatidis SPD and its precursor, putrescine (PUT), are the major polyamines detected, and SPD is required for growth. The major pathway of biosynthesis is from ornithine through putrescine to spermidine. An alternative pathway from arginine to agmatine to putrescine appears to be absent. SPD is inhibitory at concentrations of ≥10 µM and is found at concentrations between 1 and 10 µM in active fungal supernatants. Although PUT is detected in the fungal supernatants, it is not inhibitory to lymphocytes even at concentrations as high as 100 µM. Two other related polyamines, norspermidine (NSP) and spermine (SPM), also inhibit amphibian lymphocyte proliferation, but a third polyamine, cadaverine (CAD), does not. A suboptimal (noninhibitory) concentration of MTA (10 µM), a by-product of spermidine synthesis, enhances the inhibition of SPD at 1 and 10 µM. We interpret these results to suggest that B. dendrobatidis produces an "armamentarium" of small molecules that, alone or in concert, may help it to evade clearance by the amphibian immune system.

Seasonal dynamics and potential drivers of ranavirus epidemics in wood frog populations.

Epidemics in wildlife populations often display a striking seasonality. Ranaviruses can cause rapid, synchronous mass mortality events in populations of wood frog (Rana sylvatica) larvae in the summer. While there are several possible explanations for this pattern-from seasonal introductions of the virus to environmental stressors to windows of susceptibility to mortality from infection during development-most studies have focused on single factors in laboratory settings. We characterized the time course of ranavirus epidemics in eight ephemeral ponds in Connecticut, USA, measuring the prevalence and intensity of infections in wood frog larvae and Ranavirus DNA in water samples using environmental DNA methods. We found little evidence that the timing of pathogen introduction affected the timing of epidemics (rising prevalence) or the resulting die-offs. Instead, we observed a pulse in transmission asynchronous with die-offs; prevalence reached high levels (≥ 50%) up to 6 weeks before mortality was observed, suggesting that die-offs may be uncoupled from this pulse in transmission. Rather, mortality occurred when larvae reached later stages of development (hind limb formation) and coinciding water temperatures rose (≥ 15 °C), both of which independently increase pathogenicity (i.e., probability of host mortality) of infections in laboratory experiments. In summary, the strong seasonality of die-offs appears to be driven by development- and/or temperature-dependent changes in pathogenicity rather than occurring chronologically with pathogen introduction, after a pulse in transmission, or when susceptible host densities are greatest. Furthermore, our study illustrates the potential for eDNA methods to provide valuable insight in aquatic host-pathogen systems.

Phosphine Exposure Among Emergency Responders - Amarillo, Texas, January 2017.

Phosphine is a highly toxic gas that forms when aluminum phosphide, a restricted-use pesticide* typically used in agricultural settings, reacts with water. Acute exposure can lead to a wide range of respiratory, cardiovascular, and gastrointestinal symptoms, and can be fatal (1). On January 2, 2017, the Texas Department of State Health Services (DSHS) was notified by the Texas Panhandle Poison Center of an acute phosphine exposure incident in Amarillo, Texas. DSHS investigated potential occupational phosphine exposures among the 51 on-scene emergency responders; 40 (78.4%) did not use respiratory protection during response operations. Fifteen (37.5%) of these 40 responders received medical care for symptoms or as a precaution after the incident, and seven (17.5%) reported new or worsening symptoms consistent with phosphine exposure within 24 hours of the incident. Emergency response organizations should ensure that appropriate personal protective equipment (PPE) is used during all incidents when an unknown hazardous substance is suspected. Additional evaluation is needed to identify targeted interventions that increase emergency responder PPE use during this type of incident.

Hypertension among adults exposed to drinking water arsenic in Northern Chile.

BACKGROUND: A growing number of studies have identified an association between exposure to inorganic arsenic and hypertension. However, results have not been consistent across studies. Additional studies are warranted, given the global prevalence of both arsenic exposure and morbidity attributable to hypertension. METHODS: We analyzed data collected from October 2007-December 2010 for a population-based cancer case-control study in northern Chile. Data included lifetime individual arsenic exposure estimates and information on potential confounders for a total of 1266 subjects. Those self-reporting either a physician diagnosis of hypertension or use of an anti-hypertensive medication were classified as having hypertension (n=612). The association between hypertension and drinking water arsenic exposure was analyzed using logistic regression models. RESULTS: Compared to those in the lowest category for lifetime highest 5-year average arsenic exposure (<60µg/L), those in the middle (60-623µg/L) and upper (>623µg/L) exposure categories had adjusted hypertension ORs of 1.49 (95% CI: 1.09, 2.05) and 1.65 (95% CI: 1.18, 2.32), respectively. Similar results were observed in analyses of lifetime cumulative exposures and analyses restricted to exposures from the distant past. CONCLUSIONS: We identified evidence of increased odds of hypertension with exposure to arsenic in drinking water among study participants. Our findings add to the growing body of research supporting this association, which could have important public health implications.

Evaluating environmental DNA-based quantification of ranavirus infection in wood frog populations.

A variety of challenges arise when monitoring wildlife populations for disease. Sampling tissues can be invasive to hosts, and obtaining sufficient sample sizes can be expensive and time-consuming, particularly for rare species and when pathogen prevalence is low. Environmental DNA (eDNA)-based detection of pathogens is an alternative approach to surveillance for aquatic communities that circumvents many of these issues. Ranaviruses are emerging pathogens of ectothermic vertebrates linked to die-offs of amphibian populations. Detecting ranavirus infections is critical, but nonlethal methods have the above issues and are prone to false negatives. We report on the feasibility and effectiveness of eDNA-based ranavirus detection in the field. We compared ranavirus titres in eDNA samples collected from pond water to titres in wood frog (Lithobates sylvaticus; n = 5) tadpoles in sites dominated by this one species (n = 20 pond visits). We examined whether ranavirus DNA can be detected in eDNA from pond water when infections are present in the pond and if viral titres detected in eDNA samples correlate with the prevalence or intensity of ranavirus infections in tadpoles. With three 250 mL water samples, we were able to detect the virus in all visits with infected larvae (0.92 diagnostic sensitivity). Also, we found a strong relationship between the viral eDNA titres and titres in larval tissues. eDNA titres increased prior to observed die-offs and declined afterwards, and were two orders of magnitude higher in ponds with a die-off. Our results suggest that eDNA is useful for detecting ranavirus infections in wildlife and aquaculture.

Geophysiology of Wood Frogs: Landscape Patterns of Prevalence of Disease and Circulating Hormone Concentrations across the Eastern Range.

One of the major challenges for conservation physiologists is to determine how current or future environmental conditions relate to the health of animals at the population level. In this study, we measured prevalence of disease, mean condition of the body, and mean resting levels of corticosterone and testosterone in a total of 28 populations across the years 2011 and 2012, and correlated these measures of health to climatic suitability of habitat, using estimates from a model of the ecological niche of the wood frog's geographic range. Using the core-periphery hypothesis as a theoretical framework, we predicted a higher prevalence and intensity of infection of Batrachochytrium dendrobatidis (Bd) and ranaviruses, two major amphibian pathogens causing disease, and higher resting levels of circulating corticosterone, an indicator of allostatic load incurred from living in marginal habitats. We found that Bd infections were rare (2% of individuals tested), while infections with ranavirus were much more common: ranavirus-infected individuals were found in 92% of ponds tested over the 2 years. Contrary to our predictions, rates of infection with ranaviruses were positively correlated with quality of the habitat with the highest prevalence at the core of the range, and plasma corticosterone concentrations measured when frogs were at rest were not correlated with quality of the habitat, the prevalence of ranavirus, or the intensity of infection. Prevalence and mean viral titers of ranavirus infection were higher in 2012 than in 2011, which coincided with lower levels of circulating corticosterone and testosterone and an extremely early time of breeding due to relatively higher temperatures during the winter. In addition, the odds of having a ranavirus infection increased with decreased body condition, and if animals had an infection, viral titers were positively correlated to levels of circulating testosterone concentration. By resolving these patterns, experiments can be designed to test hypotheses about the mechanisms that produce them, such as whether transmission of the ranavirus and tolerance of the host are greater or whether virulence is lower in populations within core habitats. While there is debate about which metrics serve as the best bioindicators of population health, the findings of this study demonstrate the importance of long-term monitoring of multiple physiological parameters to better understand the dynamic relationship between the environment and the health of wildlife populations over space and time.

Active Tracing and Monitoring of Contacts Associated With the First Cluster of Ebola in the United States.

BACKGROUND: Following hospitalization of the first patient with Ebola virus disease diagnosed in the United States on 28 September 2014, contact tracing methods for Ebola were implemented. OBJECTIVE: To identify, risk-stratify, and monitor contacts of patients with Ebola. DESIGN: Descriptive investigation. SETTING: Dallas County, Texas, September to November 2014. PARTICIPANTS: Contacts of symptomatic patients with Ebola. MEASUREMENTS: Contact identification, exposure risk classification, symptom development, and Ebola. RESULTS: The investigation identified 179 contacts, 139 of whom were contacts of the index patient. Of 112 health care personnel (HCP) contacts of the index case, 22 (20%) had known unprotected exposures and 37 (30%) did not have known unprotected exposures but interacted with a patient or contaminated environment on multiple days. Transmission was confirmed in 2 HCP who had substantial interaction with the patient while wearing personal protective equipment. These HCP had 40 additional contacts. Of 20 community contacts of the index patient or the 2 HCP, 4 had high-risk exposures. Movement restrictions were extended to all 179 contacts; 7 contacts were quarantined. Seven percent (14 of 179) of contacts (1 community contact and 13 health care contacts) were evaluated for Ebola during the monitoring period. LIMITATION: Data cannot be used to infer whether in-person direct active monitoring is superior to active monitoring alone for early detection of symptomatic contacts. CONCLUSION: Contact tracing and monitoring approaches for Ebola were adapted to account for the evolving understanding of risks for unrecognized HCP transmission. HCP contacts in the United States without known unprotected exposures should be considered as having a low (but not zero) risk for Ebola and should be actively monitored for symptoms. Core challenges of contact tracing for high-consequence communicable diseases included rapid comprehensive contact identification, large-scale direct active monitoring of contacts, large-scale application of movement restrictions, and necessity of humanitarian support services to meet nonclinical needs of contacts. PRIMARY FUNDING SOURCE: None.