A site assessment tool for inpatient controlled human infection models for enteric disease pathogens

The use of the controlled human infection model to facilitate product development and to advance understanding of host-pathogen interactions is of increasing interest. While administering a virulent (or infective) organism to a susceptible host necessitates an ongoing evaluation of safety and ethical considerations, a central theme in conducting these studies in a safe and ethical manner that yields actionable data is their conduct in facilities well-suited to address their unique attributes. To that end, we have developed a framework for evaluating potential sites in which to conduct inpatient enteric controlled human infection model to ensure consistency and increase the likelihood of success.publishedVersio

Incidence of Norovirus-Associated Medical Encounters among Active Duty United States Military Personnel and Their Dependents

<div><p>Background</p><p>Norovirus is a leading cause of gastroenteritis episodes and outbreaks in US military deployments, but estimates of endemic disease burden among military personnel in garrison are lacking.</p><p>Methods</p><p>Diagnostic codes from gastroenteritis-associated medical encounters of active duty military personnel and their beneficiaries from July 1998–June 2011 were obtained from the Armed Forces Health Surveillance Center. Using time-series regression models, cause-unspecified encounters were modeled as a function of encounters for specific enteropathogens. Model residuals (representing unexplained encounters) were used to estimate norovirus-attributable medical encounters. Incidence rates were calculated using population data for both active duty and beneficiary populations.</p><p>Results</p><p>The estimated annual mean rate of norovirus-associated medically-attended visits among active duty personnel and their beneficiaries was 292 (95% CI: 258 to 326) and 93 (95% CI: 80 to 105) encounters per 10,000 persons, respectively. Rates were highest among beneficiaries <5 years of age with a median annual rate of 435 (range: 318 to 646) encounters per 10,000 children. Norovirus was estimated to cause 31% and 27% of all-cause gastroenteritis encounters in the active duty and beneficiary populations, respectively, with over 60% occurring between November and April. There was no evidence of any lag effect where norovirus disease occurred in one population before the other, or in one beneficiary age group before the others.</p><p>Conclusions</p><p>Norovirus is a major cause of medically-attended gastroenteritis among non-deployed US military active duty members as well as in their beneficiaries.</p></div

Median seasonal year norovirus-attributable encounters per 10,000 beneficiary persons by age group (with ranges), July 2001–June 2011.

<p>Median seasonal year norovirus-attributable encounters per 10,000 beneficiary persons by age group (with ranges), July 2001–June 2011.</p

Norovirus-attributable encounters by season and population.

<p>Norovirus-attributable encounters by season and population.</p

All-cause, cause-unspecified (CU) and norovirus-attributable encounters by age group.

<p>All-cause, cause-unspecified (CU) and norovirus-attributable encounters by age group.</p

Pathogen-based categories of diagnostic codes used to identify gastroenteritis-associated medical encounters, supplied by the United States Armed Forces Health Surveillance Center, July 1998–June 2011.

<p>Pathogen-based categories of diagnostic codes used to identify gastroenteritis-associated medical encounters, supplied by the United States Armed Forces Health Surveillance Center, July 1998–June 2011.</p

Coded medical encounters by population and cause category.

<p>Coded medical encounters by population and cause category.</p

Weekly percent of total norovirus-attributable medical encounters; 5-week moving average by week of year and population.

<p>The percentage of estimated norovirus-attributable medical encounters for each week of the year were calculated for each population/age group as follows: the number of encounters occurring in a given week was averaged over the entire study period for each respective group, then expressed as a percentage of the sum of all weekly averages for that population/age group. Five-week moving averages of these values were calculated and plotted for each population/age group. AD: Active duty; DB: Dependent beneficiary; age group range in years.</p

Norovirus-attributable encounters per 10,000 US military active duty (AD) members and their dependent beneficiaries (DB) by seasonal year, July 1998–June 2011.

<p>Norovirus-attributable encounters per 10,000 US military active duty (AD) members and their dependent beneficiaries (DB) by seasonal year, July 1998–June 2011.</p