Large-scale chemical-genetics yields new M. tuberculosis inhibitor classes.

New antibiotics are needed to combat rising levels of resistance, with new Mycobacterium tuberculosis (Mtb) drugs having the highest priority. However, conventional whole-cell and biochemical antibiotic screens have failed. Here we develop a strategy termed PROSPECT (primary screening of strains to prioritize expanded chemistry and targets), in which we screen compounds against pools of strains depleted of essential bacterial targets. We engineered strains that target 474 essential Mtb genes and screened pools of 100-150 strains against activity-enriched and unbiased compound libraries, probing more than 8.5 million chemical-genetic interactions. Primary screens identified over tenfold more hits than screening wild-type Mtb alone, with chemical-genetic interactions providing immediate, direct target insights. We identified over 40 compounds that target DNA gyrase, the cell wall, tryptophan, folate biosynthesis and RNA polymerase, as well as inhibitors that target EfpA. Chemical optimization yielded EfpA inhibitors with potent wild-type activity, thus demonstrating the ability of PROSPECT to yield inhibitors against targets that would have eluded conventional drug discovery.

Challenges and strategies of frontline staff providing HIV services for inmates and releasees.

Linkages to services for HIV-infected inmates are critically important; however, little is known about the challenges faced by staff coordinating these linkages. This qualitative evaluation describes the challenges and strategies of frontline staff involved in HIV-related services for inmates and releasees participating in the Centers for Disease Control and Prevention/Health Resources and Services Administration Corrections Demonstration Project. Eight focus groups were held during a national meeting of community-based organizations. Content analysis revealed multiple themes. This evaluation emphasizes the lack of and difficulty obtaining services for this population. Staff recognize the role of security and safety when working in facilities and have identified methods to coordinate and communicate to facilitate their work. Communication with key partners and colleagues is important to understand the challenges and identify strategies; however, political advocacy is important for increased awareness and resources. Consideration of these issues within an ecological framework may help frontline staff translate findings to practice.

Resumption of smoking after release from a tobacco-free correctional facility.

Approximately 70% of incarcerated people smoke tobacco, and an estimated 12% of all smokers in the United States leave correctional facilities annually. Many facilities prohibit smoking, but no published study has measured the relapse to tobacco after release. In a study of 200 people with chronic health conditions reentering the community from jail, 165 (83%) were cigarette smokers. Of these, 129 were interviewed at 1 and/or 6 months after release. Self-reported sustained abstinence rates were 37.3% at the end of the first day, 17.7% for the first week, 13.7% for 1 month, and 3.1% for 6 months. These abstinence rates are lower than those reported after military basic training and medical hospitalization but similar to rates after inpatient psychiatric and addiction programs. More efforts and resources are needed to determine successful tobacco cessation interventions during incarceration and after release.

Facilitators and barriers to continuing healthcare after jail: a community-integrated program.

A cooperative, community-oriented "public health model of correctional healthcare" was developed to address the needs of persons temporarily displaced into jail from the community, and to improve the health and safety of the community. It emphasizes 5 key elements: early detection, effective treatment, education, prevention, and continuity of care. In the program, physicians and case managers are "dually based"-they work both at the jail and at community healthcare centers. This, together with discharge planning, promotes continuity of care for inmates with serious and chronic medical conditions. This report characterizes the health status and healthcare in this group, and identifies facilitators and barriers to engagement in primary medical and mental health care after release from jail.

Partners and processes in HIV services for inmates and ex-offenders. Facilitating collaboration and service delivery.

The elevated rates of HIV/AIDS among inmates are due in part to the high concentration of incarcerated persons with behavioral risk factors for HIV infection. Corrections, public health, and community-based organizations should partner to take full advantage of the opportunity to maximize effectiveness and efficiency in addressing HIV/AIDS in inmate populations. The purpose of this study is to document issues inhibiting collaboration, service delivery, and multisite evaluation as identified by members of the U.S. Centers for Disease Control and Prevention/Health Resources and Services Administration Corrections Demonstration Project (CDP). Examining the barriers (and identifying ways to resolve them) is important in developing and maintaining successful programs that ultimately benefit HIV-infected inmates and the communities to which they return.

Development and implementation of the cross-site evaluation of the CDC/HRSA corrections demonstration project.

U.S. prisons and jails have the nation's highest concentration of individuals infected with and at risk for HIV infection. Many correctional institutions offer 1-HIV care, but advances are oftentimes lost when individuals with a lack of health insurance and access to care are released into the community. In 1999 the Centers for Disease Control and Prevention and the Health Resources and Services Administration jointly funded seven health departments to address this need. These projects target soon-to-be-released inmates of jails, prisons, and juvenile facilities and offer enhanced discharge planning, case management, HIV prevention, disease screening, and staff training. The Evaluation and Program Support Center (EPSC) at Emory University and Abt Associates was funded to oversee a cross-site evaluation of these demonstration projects. This paper describes the process of developing a cross-site evaluation, the implementation of this evaluation, and lessons learned by the EPSC throughout this process.