Prophylactic Efficacy of Hyperimmune Bovine Colostral Antiadhesin Antibodies Against Enterotoxigenic Escherichia coli Diarrhea: A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Trial.

Background: Tip-localized adhesive proteins of bacterial fimbriae from diverse pathogens confer protection in animal models, but efficacy in humans has not been reported. Enterotoxigenic Escherichia coli (ETEC) commonly elaborate colonization factors comprising a minor tip adhesin and major stalk-forming subunit. We assessed the efficacy of antiadhesin bovine colostral IgG (bIgG) antibodies against ETEC challenge in volunteers. Methods: Adults were randomly assigned (1:1:1) to take oral hyperimmune bIgG raised against CFA/I minor pilin subunit (CfaE) tip adhesin or colonization factor I (CFA/I) fimbraie (positive control) or placebo. Two days before challenge, volunteers began a thrice-daily, 7-day course of investigational product administered in sodium bicarbonate 15 minutes after each meal. On day 3, subjects drank 1 × 109 colony-forming units of colonization factor I (CFA/I)-ETEC strain H10407 with buffer. The primary efficacy endpoint was diarrhea within 120 hours of challenge. Results: After enrollment and randomization, 31 volunteers received product, underwent ETEC challenge, and were included in the per protocol efficacy analysis. Nine of 11 placebos developed diarrhea, 7 experiencing moderate to severe disease. Protective efficacy of 63% (P = .03) and 88% (P = .002) was observed in the antiadhesin bIgG and positive control groups, respectively. Conclusions: Oral administration of anti-CFA/I minor pilin subunit (CfaE) antibodies conferred significant protection against ETEC, providing the first clinical evidence that fimbrial tip adhesins function as protective antigens.

Sudden cardiac death associated with physical exertion in the US military, 2005-2010.

BACKGROUND: Sudden cardiac death associated with physical exertion (SCD/E) is a complicated pathophysiological event. This study aims to calculate the incidence rate of SCD/E in the US military population from 2005 to 2010, to characterise the demographic and cardiovascular risk profiles of decedents, and to evaluate aetiologies of and circumstances surrounding the deaths. METHODS: Perimortem and other relevant data were collected from the Armed Forces Medical Examiners Tracking System, Armed Forces Health Longitudinal Technology Application, and Defense Medical Epidemiology Database for decedents meeting SCD/E case definition. Incidence rates were calculated and compared using negative binomial regression. RESULTS: The incidence of SCD/E in the Active Component (ie, full-time active duty) US military from 2005 to 2010 was 1.63 per 100 000 person-years (py): 0.98 and 3.84 per 100 000 py in those aged <35 and ≥35 years, respectively. Atherosclerotic cardiovascular disease was the leading cause of death overall (55%) and in the ≥35-year age group (78%), whereas the leading cause of death in the <35-year age group (31%) could not be precisely determined and was termed idiopathic SCD/E (iSCD/E). SCD/E was more common in males than females (incidence rate ratio (IRR) = 5.28, 95% CI 2.16 to 12.93) and more common in blacks than whites (IRR=2.60, 95% CI 1.81 to 3.72). All female cases were black. CONCLUSIONS: From 2005 to 2010, the incidence of SCD/E in US military members aged <35 years was similar to most reported corresponding civilian SCD rates. However, the leading cause of death was iSCD/E and not cardiomyopathy. Improved surveillance and age-based prevention strategies may reduce these rates.

Adenovirus-associated deaths in US military during postvaccination period, 1999-2010.

Adenoviruses are frequent causes of respiratory disease in the US military population. A successful immunization program against adenovirus types 4 and 7 was terminated in 1999. Review of records in the Mortality Surveillance Division, Armed Forces Medical Examiner System, identified 8 deaths attributed to adenovirus infections in service members during 1999-2010.

Volunteer challenge with enterotoxigenic Escherichia coli that express intestinal colonization factor fimbriae CS17 and CS19.

Human challenges with enterotoxigenic Escherichia coli (ETEC) have broadened our understanding of this important enteropathogen. We report findings from the first challenge studies using ETEC-expressing colonization factor fimbria CS17 and CS19. LSN03-016011/A (LT, CS17) elicited a dose-dependent effect, with the upper dose (6 × 10(9) organisms) causing diarrhea in 88% of recipients. WS0115A (LTSTp, CS19) also showed a dose response, with a 44% diarrhea rate at 9 × 10(9) organisms. Both strains elicited homologous antifimbrial and anti-LT antibody seroconversion. These studies establish the relative pathogenicity of ETEC expressing newer class 5 fimbriae and suggest suitability of the LT|CS17-ETEC challenge model for interventional trials.

Development of indicators to assess economic vulnerabilities to changes in ecosystem services: case study of counties in Maryland, USA.

We develop indicators showing the relative environmental burdens that human activities place on locales for a given level of economic benefits. The main purpose is to develop tools that allow us to examine the potential vulnerabilities within economies to changes in resource conditions. The indicators of pollution emission or resource consumption per job can be used to identify potential challenges to resource and industry managers and to compare areas in terms of their ability to adapt to change. For example, if a large number of area jobs are dependent on abundant water, this indicates a vulnerability to a reduction in water availability for industrial use. We develop a case study for 23 counties and 1 city in Maryland to examine the usefulness and limitations of the indicators. Our case study demonstrates that the indicators provide an informative view into patterns of local economic activity and use of an area's environmental goods and services. In contrast to patterns for total environmental burdens (e.g., total SO2 emissions) that are typically reported, the rates of environmental burden per job are not simply correlated with high or low economic output. Thus, the indicators represent distinct patterns of environmental burdens per job that reflect reliance on environmental services. The indicators have some limitations when used at this fine scale because they can misrepresent conditions in counties in which economic sectors are dominated by one or a few businesses. For this reason, the indicators are best used as a regional screening tool.