Physiological and neurobehavioral effects of cholinesterase inhibition in healthy adults.

INTRODUCTION: Based on common pharmacodynamic mechanisms, recent efforts to develop second generation alternatives for organophosphate (OP) prophylaxis have expanded to include cholinesterase (ChE) inhibiting compounds traditionally approved for use in the treatment of Alzheimer's disease (AD). The primary purpose of this study was to determine the extent to which low-dose huperzine A, galantamine, or donepezil selectively inhibited acetylcholinesterase (AChE) versus butyrylcholinesterase (BChE) activity in healthy adults and whether such inhibition impacted neurobehavioral performance. METHODS: In addition to hourly red blood cell cholinesterase sampling, neurobehavioral function was assessed before and after a single oral dose of huperzine A (100 or 200 µg), galantamine (4 or 8 mg), donepezil (2.5 or 5mg), or placebo (n=12 subjects per drug/dose). RESULTS: Compared to placebo, both dosages of huperzine A and galantamine inhibited circulating AChE but not BChE. With the exception of huperzine A (200 µg), which maintained declarative recall performance across sessions, compounds did not improve neurobehavioral performance. Some aspects of neurobehavioral performance correlated with AChE activity, although associations may have reflected time of day effects. DISCUSSION: Although huperzine A and galantamine significantly inhibited AChE (and likely increased central acetylcholine levels), neither compound improved neurobehavioral performance. The latter was likely due to ceiling effects in this young, healthy test population. Under conditions of reduced cholinergic activity (e.g., Alzheimer's disease), AChE inhibition (and corresponding maintenance of cholinergic tone) could potentially maintain/augment some aspects of neurobehavioral function.

Development and implementation of a cohort review for latent tuberculosis infection.

The Centers for Disease Control and Prevention (CDC) recommends that, in low-incidence settings for tuberculosis (TB), health departments periodically review their cases of latent TB infection (LTBI). The objective of this study was to evaluate the design and implementation of an LTBI cohort review that can be used to assess program performance. The methods used for the LTBI cohort review were developed and modified from those described previously by the CDC for TB disease. A stratified random sample of LTBI cases was selected from three U.S. Army installations to compare program outcomes. A total of 295 TB tests were performed on 215 patients. Sixty-one (76%) of the 80 repeat tests performed were positive. Of the 194 patients who were recommended therapy, 146 (75%) initiated therapy and 114 (59%) completed therapy. The U.S. Army's TB control program can be improved by reducing unnecessary testing of low-risk groups, increasing completion of LTBI treatment, reducing treatment delays, and ensuring data accuracy. The LTBI cohort review should be performed at least annually at the installation level to improve the quality of TB control programs.

Tuberculosis trends in the U.S. Armed Forces, active component, 1998-2012.

Members of the Armed Forces represent a segment of the U.S. population that may be at increased risk for tuberculosis (TB) infection, disease, and transmission due to overseas service in endemic areas and residence in congregate settings. The purpose of this study was to examine recent surveillance trends and risk factors associated with TB disease in the active component U.S. military. The rate of TB in the U.S. military -0.6 per 100,000 population (n=128) over the interval from 1998 to 2012 - was lower than the age-adjusted rate among the U.S. population (adjusted rate ratio=0.20) over the same time interval. During the last five years of the surveillance period, the most common factor associated with the diagnosis of TB disease during military service was latent infection at time of accession; also, as many as nine (24%) cases of TB were associated with deployment to Iraq or other military exposures. TB control activities should continue to mitigate unique military exposures such as crowding during recruit training and deployments to TB endemic areas.

Using the tuberculosis cohort review to evaluate and improve the U.S. Army's tuberculosis control program.

The challenges of tuberculosis (TB) control in the U.S. military are similar to those in other low-incidence populations; in addition, the U.S. Military Health System must account for geographic separation, frequent staff turnover, deployments to TB-endemic areas, and residence in congregate settings. The objective of this evaluation was to use a TB cohort review process to assess indicators of the quality and effectiveness of the TB control program in the U.S. Army. Ten cases of TB disease occurred at U.S. Army installations in 2011; all were pulmonary. Two cases occurred among the active component U.S. Army, a rate of 0.4 per 100,000 population; no case was attributable to infection acquired during deployment. Eight (80%) were foreign born. Seven (70%) were smear positive and one (10%) had multi-drug resistant TB. One (10%) case died. All (100%) of the nine remaining cases completed therapy. The median time from onset of symptoms to diagnosis was 98 days, but there was substantial variability (range 21-444). This is the first report of the cohort review methodology being applied to a military population. Most performance indicators in the U.S. Army met or approached national standards.

Tuberculosis among nonimmigrant visitors to US Military installations.

BACKGROUND: Nonimmigrant visitors are not required to be evaluated for tuberculosis (TB) before entering the country. Little literature exists describing the challenges of TB control among this demographic. This report reviews the challenges in managing TB in this population on U.S. military installations. METHODS: Six cases were identified from reportable medical event reports. Information was obtained from public health personnel via phone interviews. Verified cases from 2004 to 2011 were included. RESULTS: Challenges were congruent among locations including: lack of procedures to screen for infection and disease among individuals at time of entry allowing one case to be admitted with acquired immunodeficiency syndrome and another concurrently on treatment for active TB; delays in the diagnosis of active TB as median time from entry to diagnosis was 62 days; and the need to conduct an effective contact investigation as the mean contact index was 77 including 1 secondary case of active TB. CONCLUSIONS: These cases emphasize the need for screening for TB in visitors from high-risk countries at time of entry, prompt diagnosis and treatment if found, procedures for evaluation of contacts, and interjurisdictional cooperation in large contact investigations. These challenges are common to nonimmigrants in both military and civilian settings.