Researching the future: scenarios to explore the future of human genome editing.

BACKGROUND: Forward-looking, democratically oriented governance is needed to ensure that human genome editing serves rather than undercuts public values. Scientific, policy, and ethics communities have recognized this necessity but have demonstrated limited understanding of how to fulfill it. The field of bioethics has long attempted to grapple with the unintended consequences of emerging technologies, but too often such foresight has lacked adequate scientific grounding, overemphasized regulation to the exclusion of examining underlying values, and failed to adequately engage the public. METHODS: This research investigates the application of scenario planning, a tool developed in the high-stakes, uncertainty-ridden world of corporate strategy, for the equally high-stakes and uncertain world of the governance of emerging technologies. The scenario planning methodology is non-predictive, looking instead at a spread of plausible futures which diverge in their implications for different communities' needs, cares, and desires. RESULTS: In this article we share how the scenario development process can further understandings of the complex and dynamic systems which generate and shape new biomedical technologies and provide opportunities to re-examine and re-think questions of governance, ethics and values. We detail the results of a year-long scenario planning study that engaged experts from the biological sciences, bioethics, social sciences, law, policy, private industry, and civic organizations to articulate alternative futures of human genome editing. CONCLUSIONS: Through sharing and critiquing our methodological approach and results of this study, we advance understandings of anticipatory methods deployed in bioethics, demonstrating how this approach provides unique insights and helps to derive better research questions and policy strategies.

Community-Associated Outbreak of COVID-19 in a Correctional Facility - Utah, September 2020-January 2021.

Transmission of SARS-CoV-2, the virus that causes COVID-19, is common in congregate settings such as correctional and detention facilities (1-3). On September 17, 2020, a Utah correctional facility (facility A) received a report of laboratory-confirmed SARS-CoV-2 infection in a dental health care provider (DHCP) who had treated incarcerated persons at facility A on September 14, 2020 while asymptomatic. On September 21, 2020, the roommate of an incarcerated person who had received dental treatment experienced COVID-19-compatible symptoms*; both were housed in block 1 of facility A (one of 16 occupied blocks across eight residential units). Two days later, the roommate received a positive SARS-CoV-2 test result, becoming the first person with a known-associated case of COVID-19 at facility A. During September 23-24, 2020, screening of 10 incarcerated persons who had received treatment from the DHCP identified another two persons with COVID-19, prompting isolation of all three patients in an unoccupied block at the facility. Within block 1, group activities were stopped to limit interaction among staff members and incarcerated persons and prevent further spread. During September 14-24, 2020, six facility A staff members, one of whom had previous close contact† with one of the patients, also reported symptoms. On September 27, 2020, an outbreak was confirmed after specimens from all remaining incarcerated persons in block 1 were tested; an additional 46 cases of COVID-19 were identified, which were reported to the Salt Lake County Health Department and the Utah Department of Health. On September 30, 2020, CDC, in collaboration with both health departments and the correctional facility, initiated an investigation to identify factors associated with the outbreak and implement control measures. As of January 31, 2021, a total of 1,368 cases among 2,632 incarcerated persons (attack rate = 52%) and 88 cases among 550 staff members (attack rate = 16%) were reported in facility A. Among 33 hospitalized incarcerated persons, 11 died. Quarantine and monitoring of potentially exposed persons and implementation of available prevention measures, including vaccination, are important in preventing introduction and spread of SARS-CoV-2 in correctional facilities and other congregate settings (4).

Rapid Spread of SARS-CoV-2 in a State Prison After Introduction by Newly Transferred Incarcerated Persons - Wisconsin, August 14-October 22, 2020.

SARS-CoV-2, the virus that causes COVID-19, can spread rapidly in prisons and can be introduced by staff members and newly transferred incarcerated persons (1,2). On September 28, 2020, the Wisconsin Department of Health Services (DHS) contacted CDC to report a COVID-19 outbreak in a state prison (prison A). During October 6-20, a CDC team investigated the outbreak, which began with 12 cases detected from specimens collected during August 17-24 from incarcerated persons housed within the same unit, 10 of whom were transferred together on August 13 and under quarantine following prison intake procedures (intake quarantine). Potentially exposed persons within the unit began a 14-day group quarantine on August 25. However, quarantine was not restarted after quarantined persons were potentially exposed to incarcerated persons with COVID-19 who were moved to the unit. During the subsequent 8 weeks (August 14-October 22), 869 (79.4%) of 1,095 incarcerated persons and 69 (22.6%) of 305 staff members at prison A received positive test results for SARS-CoV-2. Whole genome sequencing (WGS) of specimens from 172 cases among incarcerated persons showed that all clustered in the same lineage; this finding, along with others, demonstrated that facility spread originated with the transferred cohort. To effectively implement a cohorted quarantine, which is a harm reduction strategy for correctional settings with limited space, CDC's interim guidance recommendation is to serial test cohorts, restarting the 14-day quarantine period when a new case is identified (3). Implementing more effective intake quarantine procedures and available mitigation measures, including vaccination, among incarcerated persons is important to controlling transmission in prisons. Understanding and addressing the challenges faced by correctional facilities to implement medical isolation and quarantine can help reduce and prevent outbreaks.

Changes in Tuberculosis Disparities at a Time of Decreasing Tuberculosis Incidence in the United States, 1994-2016.

OBJECTIVES: To assess national progress in reducing disparities in rates of tuberculosis (TB) disease, which disproportionately affects minorities. METHODS: We used Centers for Disease Control and Prevention (CDC) surveillance data and US Census data to calculate TB rates for 1994 through 2016 by race/ethnicity, national origin, and other TB risk factors. We assessed progress in reducing disparities with rate ratios (RRs) and indexes of disparity, defined as the average of the differences between subpopulation and all-population TB rates divided by the all-population rate. RESULTS: Although TB rates decreased for all subpopulations, RRs increased or stayed the same for all minorities compared with Whites. For racial/ethnic groups, indexes of disparity decreased from 1998 to 2008 (P < .001) but increased thereafter (P = .33). The index of disparity by national origin increased an average of 1.5% per year. CONCLUSIONS: Although TB rates have decreased, disparities have persisted and even increased for some populations. To address the problem, the CDC's Division of TB Elimination has focused on screening and treating latent TB infection, which is concentrated among minorities and is the precursor for more than 85% of TB cases in the United States.

Tuberculosis in Jails and Prisons: United States, 2002-2013.

OBJECTIVES: To describe cases and estimate the annual incidence of tuberculosis in correctional facilities. METHODS: We analyzed 2002 to 2013 National Tuberculosis Surveillance System case reports to characterize individuals who were employed or incarcerated in correctional facilities at time they were diagnosed with tuberculosis. Incidence was estimated with Bureau of Justice Statistics denominators. RESULTS: Among 299 correctional employees with tuberculosis, 171 (57%) were US-born and 82 (27%) were female. Among 5579 persons incarcerated at the time of their tuberculosis diagnosis, 2520 (45%) were US-born and 495 (9%) were female. Median estimated annual tuberculosis incidence rates were 29 cases per 100 000 local jail inmates, 8 per 100 000 state prisoners, and 25 per 100 000 federal prisoners. The foreign-born proportion of incarcerated men 18 to 64 years old increased steadily from 33% in 2002 to 56% in 2013. Between 2009 and 2013, tuberculosis screenings were reported as leading to 10% of diagnoses among correctional employees, 47% among female inmates, and 42% among male inmates. CONCLUSIONS: Systematic screening and treatment of tuberculosis infection and disease among correctional employees and incarcerated individuals remain essential to tuberculosis prevention and control.

Interpreter usage and associations with latent tuberculosis infection treatment acceptance and completion in the USA among non-U.S.-born persons, 2012-2017.

BACKGROUND: Latent tuberculosis infection (LTBI) screening and treatment interventions that are tailored to optimize acceptance among the non-U.S.-born population are essential for U.S. tuberculosis elimination. We investigated the impact of medical interpreter use on LTBI treatment acceptance and completion among non-U.S.-born persons in a multisite study. METHODS: The Tuberculosis Epidemiologic Studies Consortium was a prospective cohort study that enrolled participants at high risk for LTBI at ten U.S. sites with 18 affiliated clinics from 2012 to 2017. Non-U.S.-born participants with at least one positive tuberculosis infection test result were included in analyses. Characteristics associated with LTBI treatment offer, acceptance, and completion were evaluated using multivariable logistic regression with random intercepts to account for clustering by enrollment site. Our primary outcomes were whether use of an interpreter was associated with LTBI treatment acceptance and completion. We also evaluated whether interpreter usage was associated treatment offer and whether interpreter type was associated with treatment offer, acceptance, or completion. RESULTS: Among 8,761 non-U.S.-born participants, those who used an interpreter during the initial interview had a significantly greater odds of accepting LTBI treatment than those who did not use an interpreter. There was no association between use of an interpreter and a clinician's decision to offer treatment or treatment completion once accepted. Characteristics associated with lower odds of treatment being offered included experiencing homelessness and identifying as Pacific Islander persons. Lower treatment acceptance was observed in Black and Latino persons and lower treatment completion by participants experiencing homelessness. Successful treatment completion was associated with use of shorter rifamycin-based regimens. Interpreter type was not associated with LTBI treatment offer, acceptance, or completion. CONCLUSIONS: We found greater LTBI treatment acceptance was associated with interpreter use among non-U.S.-born individuals.

Racial, Ethnic, Sex, and Age Differences in COVID-19 Cases, Hospitalizations, and Deaths Among Incarcerated People and Staff in Correctional Facilities in Six Jurisdictions, United States, March-July 2020.

OBJECTIVES: To examine disparities by sex, age group, and race and ethnicity in COVID-19 confirmed cases, hospitalizations, and deaths among incarcerated people and staff in correctional facilities. METHODS: Six U.S. jurisdictions reported data on COVID-19 confirmed cases, hospitalizations, and deaths stratified by sex, age group, and race and ethnicity for incarcerated people and staff in correctional facilities during March 1- July 31, 2020. We calculated incidence rates and rate ratios (RR) and absolute rate differences (RD) by sex, age group, and race and ethnicity, and made comparisons to the U.S. general population. RESULTS: Compared with the U.S. general population, incarcerated people and staff had higher COVID-19 case incidence (RR = 14.1, 95% CI = 13.9-14.3; RD = 6,692.2, CI = 6,598.8-6,785.5; RR = 6.0, CI = 5.7-6.3; RD = 2523.0, CI = 2368.1-2677.9, respectively); incarcerated people also had higher rates of COVID-19-related deaths (RR = 1.6, CI = 1.4-1.9; RD = 23.6, CI = 14.9-32.2). Rates of COVID-19 cases, hospitalizations, and deaths among incarcerated people and corrections staff differed by sex, age group, and race and ethnicity. The COVID-19 hospitalization (RR = 0.9, CI = 0.8-1.0; RD = -48.0, CI = -79.1- -16.8) and death rates (RR = 0.8, CI = 0.6-1.0; RD = -11.8, CI = -23.5- -0.1) for Black incarcerated people were lower than those for Black people in the general population. COVID-19 case incidence, hospitalizations, and deaths were higher among older incarcerated people, but not among staff. CONCLUSIONS: With a few exceptions, living or working in a correctional setting was associated with higher risk of COVID-19 infection and resulted in worse health outcomes compared with the general population; however, Black incarcerated people fared better than their U.S. general population counterparts.

Characteristics of multidrug-resistant tuberculosis in Namibia.

BACKGROUND: To describe the epidemiology and possible risk factors for the development of multidrug-resistant tuberculosis (MDR-TB) in Namibia. METHODS: Using medical records and patient questionnaires, we conducted a case-control study among patients diagnosed with TB between January 2007 and March 2009. Cases were defined as patients with laboratory-confirmed MDR-TB; controls had laboratory-confirmed drug-susceptible TB or were being treated with WHO Category I or Category II treatment regimens. RESULTS: We enrolled 117 MDR-TB cases and 251 TB controls, of which 100% and 2% were laboratory-confirmed, respectively. Among cases, 97% (113/117) had been treated for TB before the current episode compared with 46% (115/251) of controls (odds ratio [OR] 28.7, 95% confidence interval [CI] 10.3-80.5). Cases were significantly more likely to have been previously hospitalized (OR 1.9, 95% CI 1.1-3.5) and to have had a household member with MDR-TB (OR 5.1, 95% CI 2.1-12.5). These associations remained significant when separately controlled for being currently hospitalized or HIV-infection. CONCLUSIONS: MDR-TB was associated with previous treatment for TB, previous hospitalization, and having had a household member with MDR-TB, suggesting that TB control practices have been inadequate. Strengthening basic TB control practices, including expanding laboratory confirmation, directly observed therapy, and infection control, are critical to the prevention of MDR-TB.

Multidrug-Resistant Tuberculosis in U.S.-Bound Immigrants and Refugees.

Rationale: Approximately two-thirds of new cases of tuberculosis (TB) in the United States are among non-U.S.-born persons. Culture-based overseas TB screening in U.S.-bound immigrants and refugees has substantially reduced the importation of TB into the United States, but it is unclear to what extent this program prevents the importation of multidrug-resistant TB (MDR-TB). Objectives: To study the epidemiology of MDR-TB in U.S.-bound immigrants and refugees and to evaluate the effect of culture-based overseas TB screening in U.S.-bound immigrants and refugees on reducing the importation of MDR-TB into the United States. Methods: We analyzed data of immigrants and refugees who completed overseas treatment for culture-positive TB during 2015-2019. We also compared mean annual number of MDR-TB cases in non-U.S.-born persons within 1 year of arrival in the United States between 1996-2006 (when overseas screening followed a smear-based algorithm) and 2014-2019 (after full implementation of a culture-based algorithm). Results: Of 3,300 culture-positive TB cases identified by culture-based overseas TB screening in immigrants and refugees during 2015-2019, 122 (3.7%; 95% confidence interval [CI], 3.1-4.1) had MDR-TB, 20 (0.6%; 95% CI, 0.3-0.9) had rifampicin-resistant TB, 382 (11.6%; 95% CI, 10.5-12.7) had isoniazid-resistant TB, and 2,776 (84.1%; 95% CI, 82.9-85.4) had rifampicin- and isoniazid-susceptible TB. None were diagnosed with extensively drug-resistant TB. All 3,300 persons with culture-positive TB completed treatment overseas; of 70 and 11 persons who were treated overseas for MDR-TB and rifampicin-resistant TB, respectively, none were diagnosed with TB disease at postarrival evaluation in the United States. Culture-based overseas TB screening in U.S.-bound immigrants and refugees prevented 24.4 MDR-TB cases per year from arriving in the United States, 18.2 cases more than smear-based overseas TB screening. The mean annual number of MDR-TB cases among non-U.S.-born persons within 1 year of arrival in the United States decreased from 34.6 cases in 1996-2006 to 19.5 cases in 2014-2019 (difference of 15.1; P < 0.001). Conclusions: Culture-based overseas TB screening in U.S.-bound immigrants and refugees substantially reduced the importation of MDR-TB into the United States.

Hospitalizations for COVID-19 Among US People Experiencing Incarceration or Homelessness.

Importance: People experiencing incarceration (PEI) and people experiencing homelessness (PEH) have an increased risk of COVID-19 exposure from congregate living, but data on their hospitalization course compared with that of the general population are limited. Objective: To compare COVID-19 hospitalizations for PEI and PEH with hospitalizations among the general population. Design, Setting, and Participants: This cross-sectional analysis used data from the Premier Healthcare Database on 3415 PEI and 9434 PEH who were evaluated in the emergency department or were hospitalized in more than 800 US hospitals for COVID-19 from April 1, 2020, to June 30, 2021. Exposures: Incarceration or homelessness. Main Outcomes and Measures: Hospitalization proportions were calculated. and outcomes (intensive care unit admission, invasive mechanical ventilation [IMV], mortality, length of stay, and readmissions) among PEI and PEH were compared with outcomes for all patients with COVID-19 (not PEI or PEH). Multivariable regression was used to adjust for potential confounders. Results: In total, 3415 PEI (2952 men [86.4%]; mean [SD] age, 50.8 [15.7] years) and 9434 PEH (6776 men [71.8%]; mean [SD] age, 50.1 [14.5] years) were evaluated in the emergency department for COVID-19 and were hospitalized more often (2170 of 3415 [63.5%] PEI; 6088 of 9434 [64.5%] PEH) than the general population (624 470 of 1 257 250 [49.7%]) (P < .001). Both PEI and PEH hospitalized for COVID-19 were more likely to be younger, male, and non-Hispanic Black than the general population. Hospitalized PEI had a higher frequency of IMV (410 [18.9%]; adjusted risk ratio [aRR], 1.16; 95% CI, 1.04-1.30) and mortality (308 [14.2%]; aRR, 1.28; 95% CI, 1.11-1.47) than the general population (IMV, 88 897 [14.2%]; mortality, 84 725 [13.6%]). Hospitalized PEH had a lower frequency of IMV (606 [10.0%]; aRR, 0.64; 95% CI, 0.58-0.70) and mortality (330 [5.4%]; aRR, 0.53; 95% CI, 0.47-0.59) than the general population. Both PEI and PEH had longer mean (SD) lengths of stay (PEI, 9 [10] days; PEH, 11 [26] days) and a higher frequency of readmission (PEI, 128 [5.9%]; PEH, 519 [8.5%]) than the general population (mean [SD] length of stay, 8 [10] days; readmission, 28 493 [4.6%]). Conclusions and Relevance: In this cross-sectional study, a higher frequency of COVID-19 hospitalizations for PEI and PEH underscored the importance of adhering to recommended prevention measures. Expanding medical respite may reduce hospitalizations in these disproportionately affected populations.

Public health response to a multidrug-resistant tuberculosis outbreak among Guatemalans in Tennessee, 2007.

BACKGROUND: In June 2007, the Tennessee Department of Health notified the Centers for Disease Control and Prevention of four multidrug-resistant tuberculosis (MDR TB) cases in individuals of Guatemalan descent, and requested onsite epidemiologic assistance to investigate this outbreak. METHODS: A case was defined as either culture-confirmed MDR TB with a drug-susceptibility pattern closely resembling that of the index case, or a clinical diagnosis of active TB disease and corroborated contact with a person with culture-confirmed MDR TB. Medical records were reviewed, and patients and their contacts were interviewed. RESULTS: Five secondary TB cases were associated with the index case. Of 369 contacts of the index case, 189 (51%) were evaluated. Of those, 97 (51%) had positive tuberculin skin test (TST) results, 79 (81%) began therapy for latent TB infection (LTBI), and 38 (48%) completed LTBI therapy. CONCLUSION: Despite consistent follow up by public health officials, a low proportion of patients diagnosed with LTBI completed therapy. Clinicians and public health practitioners who serve immigrant communities should be vigilant for MDR TB.

Prevalence of tuberculosis infection in the United States population: the national health and nutrition examination survey, 1999-2000.

RATIONALE: The goal for tuberculosis (TB) elimination in the United States is a TB disease incidence of less than 1 per million U.S. population by 2010, which requires that the latent TB infection (LTBI) prevalence be less than 1% and decreasing. OBJECTIVES: To estimate the prevalence of LTBI in the U.S. population. METHODS AND MEASUREMENTS: Interviews and medical examinations, including tuberculin skin testing (TST), of 7,386 individuals were conducted in 1999-2000 as part of the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the civilian, noninstitutionalized U.S. population. LTBI was defined as a TST measurement of >/=10 mm. Associations of age, race/ethnicity, sex, poverty, and birthplace were assessed. Results among the 24- to 74-year-old subgroup were compared with NHANES 1971-1972 data. MEASUREMENTS AND MAIN RESULTS: Estimated LTBI prevalence was 4.2%; an estimated 11,213,000 individuals had LTBI. Among 25- to 74-year-olds, prevalence decreased from 14.3% in 1971-1972 to 5.7% in 1999-2000. Higher prevalences were seen in the foreign born (18.7%), non-Hispanic blacks/African Americans (7.0%), Mexican Americans (9.4%), and individuals living in poverty (6.1%). A total of 63% of LTBI was among the foreign born. Among the U.S. born, after adjusting for confounding factors, LTBI was associated with non-Hispanic African-American race/ethnicity, Mexican American ethnicity, and poverty. A total of 25.5% of persons with LTBI had been previously diagnosed as having LTBI or TB, and only 13.2% had been prescribed treatment. CONCLUSIONS: In addition to basic TB control measures, elimination strategies should include targeted evaluation and treatment of individuals in high-prevalence groups, as well as enhanced support for global TB prevention and control.

Tuberculosis among healthcare personnel, United States, 2010-2016.

We describe characteristics of US healthcare personnel (HCP) diagnosed with tuberculosis (TB). Among 64,770 adults with TB during 2010-2016, 2,460 (4%) were HCP. HCP with TB were more likely to be born outside of the United States, and less likely to have TB attributed to recent transmission, than non-HCP.

Investigation of Mycobacterium tuberculosis transmission aboard the U.S.S. Ronald Reagan, 2006.

Pulmonary tuberculosis (TB) was diagnosed in a sailor aboard the U.S.S. Ronald Reagan; an investigation was conducted to determine a screening strategy for 1,172 civilian passengers who were aboard during a temporary guest rider program. Sailors were screened for latent TB infection (LTBI) and TB disease. A case-control study was conducted among sailors to determine factors associated with new LTBI. No secondary TB disease was identified; 13% of close contacts had new LTBI. Factors associated with new LTBI among sailors were having been born outside the United States (adjusted odds ratio = 2.80; 95% confidence interval, 1.55--5.07) and being a carrier air wing member (adjusted odds ratio = 2.89; 95% confidence interval, 1.83--4.58). Among 38 civilian passengers berthed near the patient, 1 (3%) had LTBI. The investigation results indicated that Mycobacterium tuberculosis transmission was minimal and eliminated unnecessary TB screening for 1,134 civilians which saved public health resources.

Access to Reproductive Health Services and Maternal Perceptions on Family Planning in an Indigenous Guatemalan Valley.

Objective. To identify reproductive health barriers and perceptions regarding family planning among mothers in ten rural communities of Guatemala. Methods. Data were collected from 85 women in a Nutrition Recuperation Project (NRP) conducted by a freestanding nonprofit clinic in Palajunoj Valley, Guatemala. All nonpregnant women participating in the NRP were eligible for enrollment in this study, and NRP staff members aided in their enrollment. Participants were interviewed and data were entered into a structured questionnaire. Data analysis was conducted using R version 1.1.456. Results. After asking participants if they believed fertility is higher on certain days, only 5 women (5.9%) correctly identified these days as occurring in the middle of the menstrual cycle. 35 women (41.2%) practiced some form of family planning, and 27 (31.8%) reported that they do not know of a place where they could obtain a contraceptive method. Conclusion. There is a lack of education regarding family planning methods in this valley, and the levels of contraception use are below average for rural Guatemala. These findings may implicate substantial health risks for women and children in the valley, and they support the pertinence of education-based interventions in the area of reproductive health behaviors.

Sex-Dependent Influence of Developmental Toxicant Exposure on Group B Streptococcus-Mediated Preterm Birth in a Murine Model.

Infectious agents are a significant risk factor for preterm birth (PTB); however, the simple presence of bacteria is not sufficient to induce PTB in most women. Human and animal data suggest that environmental toxicant exposures may act in concert with other risk factors to promote PTB. Supporting this "second hit" hypothesis, we previously demonstrated exposure of fetal mice (F1 animals) to the environmental endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to an increased risk of spontaneous and infection-mediated PTB in adult animals. Surprisingly, adult F1males also confer an enhanced risk of PTB to their control partners. Herein, we used a recently established model of ascending group B Streptococcus (GBS) infection to explore the impact of a maternal versus paternal developmental TCDD exposure on infection-mediated PTB in adulthood. Group B Streptococcus is an important contributor to PTB in women and can have serious adverse effects on their infants. Our studies revealed that although gestation length was reduced in control mating pairs exposed to low-dose GBS, dams were able to clear the infection and bacterial transmission to pups was minimal. In contrast, exposure of pregnant F1females to the same GBS inoculum resulted in 100% maternal and fetal mortality. Maternal health and gestation length were not impacted in control females mated to F1males and exposed to GBS; however, neonatal survival was reduced compared to controls. Our data revealed a sex-dependent impact of parental TCDD exposure on placental expression of Toll-like receptor 2 and glycogen production, which may be responsible for the differential impact on fetal and maternal outcomes in response to GBS infection.

Impact of Choice of Test for Latent Tuberculosis Infection on Treatment Acceptance and Completion.

OBJECTIVE: The aim of this study is to assess whether choice of test for tuberculosis (TB) infection affects decisions to accept and complete treatment among contacts to TB cases. METHODS: Retrospective study is conducted in which TB contacts, ⩾15 years old during 2005 and 2009, were tested for infection with either a tuberculin skin test (TST) or an interferon-gamma release assay test, the QuantiFERON-TB Gold In-Tube (QFT-GIT). RESULTS: Of 658 persons with valid test results, 185 (28%) had positive results, including 128 of 406 (32%) who had TST and 57 of 252 (23%) who received QFT-GIT. Treatment acceptance was 43 of 57 (75%) among QFT-GIT-positive and 97 of 128 (76%) among TST-positive persons (risk ratio [RR] = 1.0, 95% confidence interval [CI], 0.83-1.2). Treatment completion was 56% among QFT-GIT-positive (32 of 57) and 59% (75 of 128) among TST-positive persons (RR = 0.96, 95% CI, 0.73-1.26). DISCUSSION: Our study showed no difference in proportions of TB contacts ⩾15 years old with positive TST results who accepted or completed LTBI treatment compared with those with positive QFT-GIT results. Future studies should include high-risk persons with no known TB exposure, who constitute the main reservoir for TB cases in the United States.

Monitoring intervention fidelity of a lifestyle behavioral intervention delivered through telehealth.

BACKGROUND: Technology-based lifestyle behavioral interventions (i.e., telehealth, mHealth, eHealth, and/or digital health) are becoming an alternative standard of care and possess several advantages over traditional clinical settings such as convenience, cost, and the ability to tailor plans and feedback to a participant's individual needs. These technology-based interventions also present unique challenges to intervention fidelity due to extra elements involved in executing the intervention. Intervention fidelity monitoring is essential to ensure internal and external validity, yet the development and utilization of fidelity protocols is under-reported in the literature. The purpose of this paper is to describe the intervention fidelity protocol for the 24-START study, a behavior change intervention delivered through telephone and internet. This paper also discusses the results of a pilot audit conducted to determine the feasibility of monitoring adherence to the fidelity protocol. METHODS: The 24-START fidelity protocol was developed in accordance with the five fidelity areas outlined by the NIH Behavior Change Consortium (NIH BCC) including: design of study, provider training, delivery of treatment, receipt of treatment, and enactment of treatment. The fidelity strategies provided by the NIH BCC in each area were tailored to fit the specific design of the 24-START study. Twenty-six total fidelity strategies were developed in accordance with the five areas and a corresponding fidelity monitoring plan was created. Because these strategies are only beneficial if implemented, the fidelity monitoring plan was developed to ensure the fidelity strategies are consistently implemented over the course of the intervention. RESULTS: A pilot audit of nine participant files was conducted to test the feasibility of the fidelity protocol developed. Out of the nine participant files reviewed, 89% of scheduled phone calls between a telehealth coach and participant were successfully completed. Of the completed calls, telehealth coaches delivered the intervention as intended 85.3% of the time, and 74% of planned secondary contacts made through the internet were delivered successfully. Additionally, between treatment group dosing was found to be equal. Several weak areas in the fidelity protocol were identified for improvement. The results were satisfactory and the audit was deemed feasible for ongoing use. CONCLUSIONS: The NIH BCC provides a valuable framework for telehealth interventions to develop fidelity protocols ultimately contributing to improved internal and external validity, better translation of results, increased transparency, and increased opportunities for replication within the field. The 24-START pilot audit found the fidelity protocol efficacious and feasible while also identifying areas of weakness in need of revision. The refined protocol will continue to be utilized throughout the data collection phase. Future telehealth interventions should develop and disclose fidelity protocols to improve the overall quality and standard of telehealth interventions.

Severe or fatal liver injury in 50 patients in the United States taking rifampin and pyrazinamide for latent tuberculosis infection.

BACKGROUND: Severe liver injuries were attributed to the rifampin and pyrazinamide (RZ) regimen after it was recommended for treating latent tuberculosis infection. Implicating RZ as the likeliest cause required excluding alternative causes. METHODS: US health departments reported data on patients who died or were hospitalized for liver disease within 1 month after taking RZ for latent tuberculosis infection from October 1998 through March 2004. The circumstances were investigated on site for each case. Illness characteristics, reasons for RZ treatment, doses and frequency of administration of pyrazinamide, monitoring during treatment, and causes of liver injury were determined. RESULTS: Liver injury was attributable to RZ use for all 50 patients reported, 12 of whom died. For 47 patients, RZ was the likeliest cause of liver injury. The median patient age was 44 years (range, 17-73 years). Thirty-two patients (64%) were male. Seven (16%) of 43 patients tested had hepatitis C virus antibodies, 1 (2%) of 45 had chronic hepatitis B, 3 (14%) of 22 had positive results of HIV serologic tests, 34 (71%) of 48 had alcohol use noted, and 33 (66%) of 50 were taking additional hepatotoxic medications. Six patients, 2 of whom died, had no predictors for liver disease. Patients who died were older (median age, 52 vs. 42 years; P=.08) and took a greater number of other medications (median number of medications, 4 vs. 2; P=.05) than did those who recovered, but these 2 factors were correlated (P<.01). Thirty-one patients (62%) were monitored according to guidelines, 9 of whom died. CONCLUSIONS: RZ was the likeliest cause of most of these liver injuries, some of which were fatal in spite of monitoring. Fatality was predicted by age or use of other medications, but none of the cofactors showed promise as a reliable clinical predictor of severe liver injury.