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To understand circumstances of tuberculosis transmission that strain public health resources, we systematically reviewed Centers for Disease Control and Prevention (CDC) staff reports of US outbreaks in which CDC participated during 2002-2008 that involved ≥3 culture-confirmed tuberculosis cases linked by genotype and epidemiology. Twenty-seven outbreaks, representing 398 patients, were reviewed. Twenty-four of the 27 outbreaks involved primarily US-born patients; substance abuse was another predominant feature of outbreaks. Prolonged infectiousness because of provider- and patient-related factors was common. In 17 outbreaks, a drug house was a notable contributing factor. The most frequently documented intervention to control the outbreak was prioritizing contacts according to risk for infection and disease progression to ensure that the highest risk contacts were completely evaluated. US-born persons with reported substance abuse most strongly characterized the tuberculosis outbreaks in this review. Substance abuse remains one of the greatest challenges to controlling tuberculosis transmission in the United States. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We investigated a cluster of tuberculosis (TB) cases among persons using methamphetamines in Snohomish County, Washington, to determine the extent of the outbreak, examine whether methamphetamine use contributed to TB transmission, and implement strategies to prevent further infections. METHODS: We screened contacts to find and treat persons with TB disease or infection. We then formed a multidisciplinary team to engage substance abuse services partners and implement outreach strategies including novel methods for finding contacts and a system of incentives and enablers to promote finding, screening, and treating patients with TB and their infected contacts. RESULTS: We diagnosed and completed treatment with 10 persons with TB disease. Eight of 9 adult patients and 67% of their adult contacts reported using methamphetamines. Of the 372 contacts, 319 (85.8%) were screened, 80 (25.1%) were infected, 71 (88.8%) started treatment for latent infection, and 57 (80.3%) completed treatment for latent infection. CONCLUSIONS: Collaborative approaches integrating TB control, outreach, incentives, and enablers resulted in high rates of treatment adherence and completion among patients and infected contacts. TB control programs should collaborate with substance abuse programs to address addiction, overcome substance abuse-related barriers to treatment, treat TB, and prevent ongoing transmission. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Case investigation and contact tracing (CI/CT) are fundamental public health efforts widely used during the COVID-19 pandemic to mitigate transmission. This study investigated how state, local, and tribal public health departments used CI/CT during the COVID-19 pandemic, including CI/CT methodology, staffing models, training and support, and efforts to identify or prioritize populations disproportionately affected by COVID-19., Methods: During March and April 2022, we conducted key informant interviews with up to 3 public health officials from 43 state, local, and tribal public health departments. From audio-recorded and transcribed interviews, we used the framework method to analyze key themes., Results: Major adjustments to CI/CT protocols during the pandemic included (1) prioritizing populations for outreach; (2) implementing automated outreach for nonprioritized groups, particularly during COVID-19 surges; (3) discontinuing contact tracing and focusing exclusively on case investigation; and (4) adding innovations to provide additional support. Key informants also discussed the utility of having backup staffing to support overwhelmed public health departments and spoke to the difficulty in "right-sizing" the public health workforce, with COVID-19 surges leaving public health departments understaffed as case rates rose and overstaffed as case rates fell., Conclusions: When addressing future epidemics or outbreaks, public health officials should consider strategies that improve the effectiveness of CI/CT efforts over time, such as prioritizing populations based on disproportionate risk, implementing automated outreach, developing models that provide flexible additional staffing resources as cases rise and fall among local public health departments, incorporating demographic data in laboratory reporting, providing community connections and support, and having a system of self-notification of contacts., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: We sought to (1) document how health departments (HDs) developed COVID-19 case investigation and contact tracing (CI/CT) interview scripts and the topics covered, and (2) understand how and why HDs modified those scripts., Design: Qualitative analysis of CI/CT interview scripts and in-depth key informant interviews with public health officials in 14 HDs. Collected scripts represent 3 distinct points (initial, the majority of which were time stamped May 2020; interim, spanning from September 2020 to August 2021; and current, as of April 2022)., Setting: Fourteen state, local, and tribal health jurisdictions and Centers for Disease Control and Prevention (CDC)., Participants: Thirty-six public health officials involved in leading CI/CT from 14 state, local, and tribal health jurisdictions (6 states, 3 cities, 4 counties, and 1 tribal area)., Main Outcome Measure: Interview script elements included in CI/CT interview scripts over time., Results: Many COVID-19 CI/CT scripts were developed by modifying questions from scripts used for other communicable diseases. Early in the pandemic, scripts included guidance on isolation/quarantine and discussed symptoms of COVID-19. As the pandemic evolved, the length of scripts increased substantially, with significant additions on contact elicitation, vaccinations, isolation/quarantine recommendations, and testing. Drivers of script changes included changes in our understanding of how the virus spreads, risk factors and symptoms, new treatments, new variants, vaccine development, and adjustments to CDC's official isolation and quarantine guidance., Conclusions: Our findings offer suggestions about components to include in future CI/CT efforts, including educating members of the public about the disease and its symptoms, offering mitigation guidance, and providing sufficient support and resources to help people act on that guidance. Assessing the correlation between script length and number of completed interviews or other quality and performance measures could be an area for future study., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The U.S. Centers for Disease Control and Prevention (CDC) received surveillance data on how many people tested positive for SARS-CoV-2, but there was little information about what individuals did to mitigate transmission. To fill the information gap, we conducted an online, probability-based survey among a nationally representative panel of adults living in the United States to better understand the behaviors of individuals following a positive SARS-CoV-2 test result. Given the low response rates commonly associated with panel surveys, we assessed how well the survey data aligned with CDC surveillance data from March, 2020 to March, 2022. We used CDC surveillance data to calculate monthly aggregated COVID-19 case counts and compared these to monthly COVID-19 case counts captured by our survey during the same period. We found high correlation between our overall survey data estimates and monthly case counts reported to the CDC during the analytic period ( r : +0.94; p  < 0.05). When stratified according to demographic characteristics, correlations remained high. These correlations strengthened our confidence that the panel survey participants were reflective of the cases reported to CDC and demonstrated the potential value of panel surveys to inform decision making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Matulewicz, Vohra, Crawford-Crudell, Oeltmann, Moonan, Taylor, Couzens and Weiss.)

Because of constrained personnel time, the Philadelphia Department of Public Health (Philadelphia, PA, USA) adjusted its COVID-19 contact tracing protocol in summer 2021 by prioritizing recent cases and limiting staff time per case. This action reduced required staff hours to prevent each case from 21-30 to 8-11 hours, while maintaining program effectiveness.

Using a nationally representative panel survey, we examined isolation behaviors among persons in the United States who had positive SARS-CoV-2 test results during January 2021-March 2022. Compared with persons who received provider-administered results, persons with home-based results had 29% (95% CI 5%-47%) lower odds of following isolation recommendations.

Background: Public health programs varied in ability to reach people with coronavirus disease 2019 (COVID-19) and their contacts to encourage separation from others. For both adult case patients with COVID-19 and their contacts, we estimated the impact of contact tracing activities on separation behaviors from January 2020 until March 2022., Methods: We used a probability-based panel survey of a nationally representative sample to gather data for estimates and comparisons., Results: An estimated 64 255 351 adults reported a positive severe acute respiratory syndrome coronavirus 2 test result; 79.6% isolated for ≥5 days, 60.2% isolated for ≥10 days, and 79.2% self-notified contacts. A total of, 24 057 139 (37.7%) completed a case investigation, and 46.2% of them reported contacts to health officials. More adults who completed a case investigation isolated than those who did not complete a case investigation (≥5 days, 82.6% vs 78.2%, respectively; ≥10 days, 69.8% vs 54.8%; both P < .05). A total of 84 946 636 adults were contacts of a COVID-19 case patient. Of these, 73.1% learned of their exposure directly from a case patient; 49.4% quarantined for ≥5 days, 18.7% quarantined for ≥14 days, and 13.5% completed a contact tracing call. More quarantined among those who completed a contact tracing call than among those who did not complete a tracing call (≥5 days, 61.2% vs 48.5%, respectively; ≥14 days, 25.2% vs 18.0%; both P < .05)., Conclusions: Engagement in contact tracing was positively correlated with isolation and quarantine. However, most adults with COVID-19 isolated and self-notified contacts regardless of whether the public health workforce was able to reach them. Identifying and reaching contacts was challenging and limited the ability to promote quarantining, and testing., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Case investigation and contact tracing (CI/CT) is a critical part of the public health response to COVID-19. Individuals' experiences with CI/CT for COVID-19 varied based on geographic location, changes in knowledge and guidelines, access to testing and vaccination, as well as demographic characteristics including age, race, ethnicity, income, and political ideology. In this paper, we explore the experiences and behaviors of adults with positive SARS-CoV-2 test results, or who were exposed to a person with COVID-19, to understand their knowledge, motivations, and facilitators and barriers to their actions. We conducted focus groups and one-on-one interviews with 94 cases and 90 contacts from across the United States. We found that participants were concerned about infecting or exposing others, which motivated them to isolate or quarantine, notify contacts, and get tested. Although most cases and contacts were not contacted by CI/CT professionals, those who were reported a positive experience and received helpful information. Many cases and contacts reported seeking information from family, friends, health care providers, as well as television news and Internet sources. Although participants reported similar perspectives and experiences across demographic characteristics, some highlighted inequities in receiving COVID-19 information and resources., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Combining genomic and geospatial data can be useful for understanding Mycobacterium tuberculosis transmission in high-burden tuberculosis (TB) settings. We performed whole-genome sequencing on M. tuberculosis DNA extracted from sputum cultures from a population-based TB study conducted in Gaborone, Botswana, during 2012-2016. We determined spatial distribution of cases on the basis of shared genotypes among isolates. We considered clusters of isolates with ≤5 single-nucleotide polymorphisms identified by whole-genome sequencing to indicate recent transmission and clusters of ≥10 persons to be outbreaks. We obtained both molecular and geospatial data for 946/1,449 (65%) participants with culture-confirmed TB; 62 persons belonged to 5 outbreaks of 10-19 persons each. We detected geospatial clustering in just 2 of those 5 outbreaks, suggesting heterogeneous spatial patterns. Our findings indicate that targeted interventions applied in smaller geographic areas of high-burden TB identified using integrated genomic and geospatial data might help interrupt TB transmission during outbreaks.

We combined field-based data with mathematical modeling to estimate the effectiveness of smartphone-enabled COVID-19 exposure notification in Pennsylvania, USA. We estimated that digital notifications potentially averted 7-69 cases/1,000 notifications during November 8, 2020-January 2, 2021. Greater use and increased compliance could increase the effectiveness of digital notifications.

Background: The COVID-19 pandemic has disrupted the diagnosis, treatment, and care for tuberculosis (TB). Delays in seeking TB care may result in increased community transmission and unfavorable treatment outcomes. We sought to understand the influence of the COVID-19 pandemic on the proportion of patients with TB who delayed seeking the diagnosis and care for TB and explore the reasons for their postponement., Methods: We surveyed a representative sample of outpatients treated for pulmonary TB from June to November 2020 using an anonymous standardized questionnaire. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CIs) of factors associated with the postponement of TB care. We used routinely collected surveillance data to assess trends of TB reports before and after the emergence of COVID-19 (2017-2019 vs. 2020-2022) in Tianjin, China., Results: Among 358 participants who were diagnosed with pulmonary TB during the COVID-19 response, 61 (17%) postponed seeking TB diagnosis due to COVID-19, with 39 (64%) citing fear as the primary reason. Female sex (aOR:2.0; 95% CI: 1.1-3.7), previous antituberculosis treatment (aOR:3.2; 95%CI: 1.4-7.6), and TB diagnosis during the first-level response (aOR = 3.2, 1.7-6.2) were associated with the postponement. Among all 518 participants receiving antituberculosis treatment, 57 (11%) had postponed their regular healthcare visits due to COVID-19, 175 (34%) received no treatment supervision, and 32 (6%) experienced treatment interruption. Compared to 2017-2019, reported pulmonary TB declined by 36.8% during the first-level response to COVID-19, 23.5% during the second-level response, 14% during the third-level response in 2020, and 4.3% in 2021., Conclusion: The COVID-19 response reduced the number of people who sought and received diagnosis, treatment, and care for TB in Tianjin, China. Integrative programs to ensure access and continuity of TB services should be considered and dual testing for SARS-CoV-2 and M. tuberculosis may facilitate finding cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Yu, Zhang, Shang, Chen, Pang, Oeltmann, Moonan, Chen and Zhang.)

Objective: Healthcare facilities are a well-known high-risk environment for transmission of M. tuberculosis , the etiologic agent of tuberculosis (TB) disease. However, the link between M. tuberculosis transmission in healthcare facilities and its role in the general TB epidemic is unknown. We estimated the proportion of overall TB transmission in the general population attributable to healthcare facilities., Methods: We combined data from a prospective, population-based molecular epidemiologic study with a universal electronic medical record (EMR) covering all healthcare facilities in Botswana to identify biologically plausible transmission events occurring at the healthcare facility. Patients with M. tuberculosis isolates of the same genotype visiting the same facility concurrently were considered an overlapping event. We then used TB diagnosis and treatment data to categorize overlapping events into biologically plausible definitions. We calculated the proportion of overall TB cases in the cohort that could be attributable to healthcare facilities., Results: In total, 1,881 participants had TB genotypic and EMR data suitable for analysis, resulting in 46,853 clinical encounters at 338 healthcare facilities. We identified 326 unique overlapping events involving 370 individual patients; 91 (5%) had biologic plausibility for transmission occurring at a healthcare facility. A sensitivity analysis estimated that 3%-8% of transmission may be attributable to healthcare facilities., Conclusions: Although effective interventions are critical in reducing individual risk for healthcare workers and patients at healthcare facilities, our findings suggest that development of targeted interventions aimed at community transmission may have a larger impact in reducing TB.

Vermont contact tracing consistently identified people at risk for coronavirus disease 2019 (COVID-19). However, the prevalence ratio (PR) of COVID-19 among contacts compared with noncontacts when viral transmission was high (PR, 13.5 [95% confidence interval {CI}, 13.2-13.9]) was significantly less than when transmission was low (PR, 49.3 [95% CI, 43.2-56.3])., Competing Interests: Potential conflicts of interest. M. F. has received support from the Vermont Department of Health. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Background: Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and might induce niacin deficiency. In 2017, Malawi scaled up continuous isoniazid preventive treatment (IPT) for tuberculosis prevention among people living with HIV. In addition, an under-diversified diet based on subsistence maize, as is commonly the case in Malawi, is a risk factor for pellagra. We aimed to investigate whether large-scale isoniazid exposure in Malawi contributed to the cumulative risk for pellagra in a nutritionally vulnerable population., Methods: We did a matched case-control study to evaluate the association between daily, continuous isoniazid exposure and pellagra. We matched sequentially enrolled patients with pellagra each with four control participants by sex and age from referral dermatology centres in three IPT scale-up districts in Malawi (Lilongwe, Blantyre, and Zomba) to evaluate isoniazid as a risk for pellagra using multivariable conditional logistic regression. We established a community clinic referral system surrounding the dermatology clinic in each district to enhance case-finding and included all patients with pellagra, regardless of referral status. The primary outcome was dermatologist-diagnosed pellagra. We calculated the interval between isoniazid initiation and rash onset and assessed 30-day clinical outcomes after multi-B vitamin treatment containing 300 mg nicotinamide daily., Findings: Between Feb 5 and Aug 9, 2019, we enrolled 197 patients with pellagra and 781 matched controls. Isoniazid exposure was associated with an increased risk of pellagra (adjusted odds ratio 42·6 [95% CI 13·3-136·6]). Significant covariates included HIV infection, referral status, food insecurity, underweight, excess alcohol consumption, and, among women, lactation. The median time from isoniazid initiation to rash onset was shorter during the season of food scarcity (5 months [IQR 3-7]) compared with the harvest season (9 months [8-11]; hazard ratio 7·2 [95% CI 3·2-16·2], log-rank p<0·0001). Those with isoniazid-associated pellagra who discontinued isoniazid and adhered to multi-B vitamin treatment showed 30-day clinical improvement., Interpretation: Continuous IPT scale-up and the annual period of food scarcity both increased the risk of pellagra in Malawi. Use of shorter rifamycin-based regimens for tuberculosis prevention and food fortification in populations with undernutrition might reduce this risk. Niacin-containing multi-B vitamin co-administration with isoniazid as pellagra prevention is worth exploring further., Funding: This study was supported by the President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention under project 7173., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Mycobacterium tuberculosis transmission dynamics in high-burden settings are poorly understood. Growing evidence suggests transmission may be characterized by extensive individual heterogeneity in secondary cases (i.e., superspreading), yet the degree and influence of such heterogeneity is largely unknown and unmeasured in high burden-settings. We conducted a prospective, population-based molecular epidemiology study of TB transmission in both an urban and rural setting of Botswana, one of the highest TB burden countries in the world. We used these empirical data to fit two mathematical models (urban and rural) that jointly quantified both the effective reproductive number, [Formula: see text], and the propensity for superspreading in each population. We found both urban and rural populations were characterized by a high degree of individual heterogeneity, however such heterogeneity disproportionately impacted the rural population: 99% of secondary transmission was attributed to only 19% of infectious cases in the rural population compared to 60% in the urban population and the median number of incident cases until the first outbreak of 30 cases was only 32 for the rural model compared to 791 in the urban model. These findings suggest individual heterogeneity plays a critical role shaping local TB epidemiology within subpopulations., (© 2022. The Author(s).)

Importance: Evidence of the impact of COVID-19 case investigation and contact tracing (CICT) programs is lacking, but policy makers need this evidence to assess the value of such programs., Objective: To estimate COVID-19 cases and hospitalizations averted nationwide by US states' CICT programs., Design, Setting, and Participants: This decision analytical model study used combined data from US CICT programs (eg, proportion of cases interviewed, contacts notified or monitored, and days to case and contact notification) with incidence data to model outcomes of CICT over a 60-day period (November 25, 2020, to January 23, 2021). The study estimated a range of outcomes by varying assumed compliance with isolation and quarantine recommendations. Fifty-nine state and territorial health departments that received federal funding supporting COVID-19 pandemic response activities were eligible for inclusion. Data analysis was performed from July to September 2021., Exposure: Public health case investigation and contact tracing., Main Outcomes and Measures: The primary outcomes were numbers of cases and hospitalizations averted and the percentage of cases averted among cases not prevented by vaccination and other nonpharmaceutical interventions., Results: In total, 22 states and 1 territory reported all measures necessary for the analysis. These 23 jurisdictions covered 42.5% of the US population (approximately 140 million persons), spanned all 4 US Census regions, and reported data that reflected all 59 federally funded CICT programs. This study estimated that 1.11 million cases and 27 231 hospitalizations were averted by CICT programs under a scenario where 80% of interviewed cases and monitored contacts and 30% of notified contacts fully complied with isolation and quarantine guidance, eliminating their contributions to future transmission. As many as 1.36 million cases and 33 527 hospitalizations could have been prevented if all interviewed cases and monitored contacts had entered into and fully complied with isolation and quarantine guidelines upon being interviewed or notified. Across both scenarios and all jurisdictions, CICT averted an estimated median of 21.2% (range, 1.3%-65.8%) of the cases not prevented by vaccination and other nonpharmaceutical interventions., Conclusions and Relevance: These findings suggest that CICT programs likely had a substantial role in curtailing the pandemic in most jurisdictions during the 2020 to 2021 winter peak. Differences in outcomes across jurisdictions indicate an opportunity to further improve CICT effectiveness. These estimates demonstrate the potential benefits from sustaining and improving these programs.

Seventy percent of tuberculosis (TB) cases in the United States occur among non-US-born persons; cases usually result from reactivation of latent TB infection (LTBI) likely acquired before the person's US arrival. We conducted a prospective study among US immigrant visa applicants undergoing the required overseas medical examination in Vietnam. Consenting applicants >15 years of age were offered an interferon-γ release assay (IGRA); those 12-14 years of age received an IGRA as part of the required examination. Eligible participants were offered LTBI treatment with 12 doses of weekly isoniazid and rifapentine. Of 5,311 immigrant visa applicants recruited, 2,438 (46%) consented to participate; 2,276 had an IGRA processed, and 484 (21%) tested positive. Among 452 participants eligible for treatment, 304 (67%) initiated treatment, and 268 (88%) completed treatment. We demonstrated that using the overseas medical examination to provide voluntary LTBI testing and treatment should be considered to advance US TB elimination efforts.

Context: The implementation of case investigation and contact tracing (CICT) for controlling COVID-19 (caused by SARS-CoV-2 virus) has proven challenging due to varying levels of public acceptance and initially constrained resources, especially enough trained staff. Evaluating the impacts of CICT will aid efforts to improve such programs., Objectives: Estimate the number of COVID-19 cases and hospitalizations averted by CICT and identify CICT processes that could improve overall effectiveness., Design: We used data on the proportion of cases interviewed, contacts notified or monitored, and days from testing to case and contact notification from 14 jurisdictions to model the impact of CICT on cumulative case counts and hospitalizations over a 60-day period. Using the Centers for Disease Control and Prevention's COVIDTracer Advanced tool, we estimated a range of impacts by assuming either contacts would quarantine only if monitored or would do so upon notification of potential exposure. We also varied the observed program metrics to assess their relative influence., Results: Performance by jurisdictions varied widely. Jurisdictions isolated between 12% and 86% of cases (including contacts that became cases) within 6 to 10 days after infection. We estimated that CICT-related reductions in transmission ranged from 0.4% to 32%. For every 100 remaining cases after other nonpharmaceutical interventions were implemented, CICT averted between 4 and 97 additional cases. Reducing time to case isolation by 1 day increased averted case estimates by up to 15 percentage points. Increasing the proportion of cases interviewed or contacts notified by 20 percentage points each resulted in at most 3 or 6 percentage point improvements in averted cases., Conclusions: We estimated that CICT reduced the number of COVID-19 cases and hospitalizations among all jurisdictions studied. Reducing time to isolation produced the greatest improvements in impact of CICT., Competing Interests: No conflicts of interest to report.

Introduction: Case investigation and contact tracing are important tools to limit the spread of SARS-CoV-2, particularly when implemented efficiently. Our objective was to evaluate participation in and timeliness of COVID-19 contact tracing and whether these measures changed over time. Methods: We retrospectively assessed COVID-19 case investigation and contact tracing surveillance data from the Washington State centralized program for August 1-31, 2020 and October 1-31, 2020. We combined SARS-CoV-2 testing reports with contact tracing data to compare completeness, reporting of contacts, and program timeliness. Results: For August and October respectively, 4,600 (of 12,521) and 2,166 (of 16,269) individuals with COVID-19 were referred to the state program for case investigation. Investigators called 100% of referred individuals; 65% (August) and 76% (October) were interviewed. Of individuals interviewed, 33% reported contacts in August and 45% in October, with only mild variation by age, sex, race/ethnicity, and urbanicity. In August, 992 individuals with COVID-19 reported a total of 2,584 contacts (mean, 2.6), and in October, 739 individuals reported 2,218 contacts (mean, 3.0). Among contacts, 86% and 78% participated in interviews for August and October. The median time elapsed from specimen collection to contact interview was 4 days in August and 3 days in October, and from symptom onset to contact interview was 7 days in August and 6 days in October. Conclusions: While contact tracing improved with time, the proportion of individuals disclosing contacts remained below 50% and differed minimally by demographic characteristics. The longest time interval occurred between symptom onset and test result notification. Improving elicitation of contacts and timeliness of contact tracing may further decrease SARS-CoV-2 transmission., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bonacci, Manahan, Miller, Moonan, Lipparelli, DiFedele, Davis, Lash and Oeltmann.)

Objectives: We sought to quantify the proportion of contacts reported by persons with COVID-19 through a short message service (SMS)-linked survey in comparison to the proportion of contacts reported during a follow-up phone-interview. We also sought to assess improvement in contact tracing timeliness associated with sending SMS-linked surveys., Study Design: During December 4-15, 2020, persons identified as COVID-19 cases whose data was entered into Marin County's contact tracing database on even days received a SMS-linked survey and persons whose data was entered on odd days did not; all were called for case investigation and contact tracing. Chi-square test and Fisher's exact test were used to compare demographic data. Chi-square test was used to contrast categorical outcomes, and Wilcoxon's rank-sum test was used for continuous outcomes., Results: Among 350 SMS-linked survey recipients, 85 (24%) responded and 4 (1%) reported contacts using the survey; an additional 303 contacts were reported during phone interviews. Without phone interviews, 99% of reported contacts would have been missed. There was no meaningful difference between study arms in the proportion of contacts notified within 48 h., Conclusions: This SMS-linked survey had low participation and was not useful for identifying contacts. Phone interviews remained crucial for COVID-19 contact tracing., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Ltd on behalf of The Royal Society for Public Health.)

Objective: To evaluate participation in COVID-19 case investigation and contact tracing in central Washington State between June 15 and July 12, 2020., Methods: In this retrospective observational evaluation we combined SARS-CoV-2 RT-PCR and antigen test reports from the Washington Disease Reporting System with community case investigation and contact tracing data for 3 health districts (comprising 5 counties) in central Washington State. All 3 health districts have large Hispanic communities disproportionately affected by COVID-19., Results: Investigators attempted to call all referred individuals with COVID-19 (n = 4,987); 71% were interviewed. Of those asked about close contacts (n = 3,572), 68% reported having no close contacts, with similar proportions across ethnicity, sex, and age group. The 968 individuals with COVID-19 who named specific contacts (27% of those asked) reported a total of 2,293 contacts (mean of 2.4 contacts per individual with COVID-19); 85% of listed contacts participated in an interview., Conclusions: Most individuals with COVID-19 reported having no close contacts. Increasing community engagement and public messaging, as well as understanding and addressing barriers to participation, are crucial for CICT to contribute meaningfully to controlling the SARS-CoV-2 pandemic., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Importance: Contact tracing is a multistep process to limit SARS-CoV-2 transmission. Gaps in the process result in missed opportunities to prevent COVID-19., Objective: To quantify proportions of cases and their contacts reached by public health authorities and the amount of time needed to reach them and to compare the risk of a positive COVID-19 test result between contacts and the general public during 4-week assessment periods., Design, Setting, and Participants: This cross-sectional study took place at 13 health departments and 1 Indian Health Service Unit in 11 states and 1 tribal nation. Participants included all individuals with laboratory-confirmed COVID-19 and their named contacts. Local COVID-19 surveillance data were used to determine the numbers of persons reported to have laboratory-confirmed COVID-19 who were interviewed and named contacts between June and October 2020., Main Outcomes and Measures: For contacts, the numbers who were identified, notified of their exposure, and agreed to monitoring were calculated. The median time from index case specimen collection to contact notification was calculated, as were numbers of named contacts subsequently notified of their exposure and monitored. The prevalence of a positive SARS-CoV-2 test among named and tested contacts was compared with that jurisdiction's general population during the same 4 weeks., Results: The total number of cases reported was 74 185. Of these, 43 931 (59%) were interviewed, and 24 705 (33%) named any contacts. Among the 74 839 named contacts, 53 314 (71%) were notified of their exposure, and 34 345 (46%) agreed to monitoring. A mean of 0.7 contacts were reached by telephone by public health authorities, and only 0.5 contacts per case were monitored. In general, health departments reporting large case counts during the assessment (≥5000) conducted smaller proportions of case interviews and contact notifications. In 9 locations, the median time from specimen collection to contact notification was 6 days or less. In 6 of 8 locations with population comparison data, positive test prevalence was higher among named contacts than the general population., Conclusions and Relevance: In this cross-sectional study of US local COVID-19 surveillance data, testing named contacts was a high-yield activity for case finding. However, this assessment suggests that contact tracing had suboptimal impact on SARS-CoV-2 transmission, largely because 2 of 3 cases were either not reached for interview or named no contacts when interviewed. These findings are relevant to decisions regarding the allocation of public health resources among the various prevention strategies and for the prioritization of case investigations and contact tracing efforts.

Background: Isoniazid preventive therapy (IPT) against tuberculosis (TB) is a life-saving intervention for people living with HIV (PLHIV). In September 2017, Malawi began programmatic scale-up of IPT to eligible PLHIV in five districts with high HIV and TB burden. We measured the frequency and timeliness of early-phase IPT implementation to inform quality-improvement processes., Methods and Findings: We applied a two-stage cluster design with systematic, probability-proportional-to-size sampling of six U.S. Centers for Disease Control and Prevention (CDC)-affiliated antiretroviral therapy (ART) centers operating in the urban areas of Lilongwe and Blantyre, Malawi (November 2017). ART clinic patient volume determined cluster size. Within each cluster, we sequentially sampled approximately 50 PLHIV newly enrolled in ART care. We described a quality-of-care cascade for intensive TB case finding (ICF) and IPT in PLHIV. PLHIV newly enrolled in ART care were eligibility-screened for hepatitis and peripheral neuropathy, as well as for TB disease using a standardized four-symptom screening tool. Among eligible PLHIV, the overall weighted IPT initiation rate was 70% (95% CI: 46%-86%). Weighted IPT initiation among persons aged <15 years (30% [95% CI: 12%-55%]) was significantly lower than among persons aged ≥15 years (72% [95% CI: 47%-89%]; Rao-Scott chi-square P = 0.03). HIV-positive children aged <5 years had a weighted initiation rate of only 13% (95% CI: 1%-79%). For pregnant women, the weighted initiation rate was 67% (95% CI: 32%-90%), similar to non-pregnant women aged ≥15 years (72% [95% CI: 49%-87%]). Lastly, 95% (95% CI: 92%-97%) of eligible PLHIV started ART within one week of HIV diagnosis, and 92% (95% CI: 73%-98%) of patients receiving IPT began on the same day as ART., Conclusions: Early-phase IPT uptake among adults at ART centers in Malawi was high. Child uptake needed improvement. National programs could adapt this framework to evaluate their ICF-IPT care cascades., Competing Interests: The authors have declared that no competing interests exist.

Tuberculosis (TB) elimination requires interrupting transmission of Mycobacterium tuberculosis. We used a multidisciplinary approach to describe TB transmission in 2 sociodemographically distinct districts in Botswana (Kopanyo Study). During August 2012-March 2016, all patients who had TB were enrolled, their sputum samples were cultured, and M. tuberculosis isolates were genotyped by using 24-locus mycobacterial interspersed repetitive units-variable number of tandem repeats. Of 5,515 TB patients, 4,331 (79%) were enrolled. Annualized TB incidence varied by geography (range 66-1,140 TB patients/100,000 persons). A total of 1,796 patient isolates had valid genotyping results and residential geocoordinates; 780 (41%) patients were involved in a localized TB transmission event. Residence in areas with a high burden of TB, age <24 years, being a current smoker, and unemployment were factors associated with localized transmission events. Patients with known HIV-positive status had lower odds of being involved in localized transmission.

Background: Pellagra is caused by niacin (vitamin B3) deficiency and manifested by a distinctive dermatitis. Isoniazid is critical for treating tuberculosis globally and is a component of most regimens to prevent tuberculosis. Isoniazid may contribute to pellagra by disrupting intracellular niacin synthesis. In 2017, Malawian clinicians recognized a high incidence of pellagra-like rashes after scale-up of isoniazid preventive treatment (IPT) to people living with HIV (PLHIV). This increase in pellagra incidence among PLHIV coincided with a seasonal period of sustained food insecurity in the region, which obscured epidemiological interpretations. Although isoniazid has been implicated as a secondary cause of pellagra for decades, no hypothesis-driven epidemiological study has assessed this relationship in a population exposed to isoniazid. We developed this case-control protocol to assess the association between large-scale isoniazid distribution and pellagra in Malawi. Methods: We measure the relative odds of having pellagra among isoniazid-exposed people compared to those without exposure while controlling for other pellagra risk factors. Secondary aims include measuring time from isoniazid initiation to onset of dermatitis, comparing niacin metabolites 1-methylnicotinamide (1-MN), and l-methyl-2-pyridone-5-carboxamide (2-PYR) in urine as a proxy for total body niacin status among subpopulations, and describing clinical outcomes after 30-days multi-B vitamin (containing 300 mg nicotinamide daily) therapy and isoniazid cessation (if exposed). We aim to enroll 197 participants with pellagra and 788 age- and sex-matched controls (1:4 ratio) presenting at three dermatology clinics. Four randomly selected community clinics within 3-25 km of designated dermatology clinics will refer persons with pellagra-like symptoms to one of the study enrollment sites for diagnosis. Trained study dermatologists will conduct a detailed exposure questionnaire and perform anthropometric measurements. A subset of enrollees will provide a casual urine specimen for niacin metabolites quantification and/or point-of-care isoniazid detection to confirm whether participants recently ingested isoniazid. We will use conditional logistic regression, matching age and sex, to estimate odds ratios for the primary study aim. Discussion: The results of this study will inform the programmatic scale-up of isoniazid-containing regimens to prevent tuberculosis., Competing Interests: AW was employed by the company McKing Consulting Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Nabity, Mponda, Gutreuter, Surie, Williams, Sharma, Schnaubelt, Marshall, Kirking, Zimba, Sunguti, Chisuwo, Chiwaula, Gregory, da Silva, Odo, Jahn, Kalua, Nyirenda, Girma, Mpunga, Buono, Maida, Kim, Gunde, Mekonnen, Auld, Muula and Oeltmann.)

Contact tracing is a strategy implemented to minimize the spread of communicable diseases (1,2). Prompt contact tracing, testing, and self-quarantine can reduce the transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (3,4). Community engagement is important to encourage participation in and cooperation with SARS-CoV-2 contact tracing (5). Substantial investments have been made to scale up contact tracing for COVID-19 in the United States. During June 1-July 12, 2020, the incidence of COVID-19 cases in North Carolina increased 183%, from seven to 19 per 100,000 persons per day* (6). To assess local COVID-19 contact tracing implementation, data from two counties in North Carolina were analyzed during a period of high incidence. Health department staff members investigated 5,514 (77%) persons with COVID-19 in Mecklenburg County and 584 (99%) in Randolph Counties. No contacts were reported for 48% of cases in Mecklenburg and for 35% in Randolph. Among contacts provided, 25% in Mecklenburg and 48% in Randolph could not be reached by telephone and were classified as nonresponsive after at least one attempt on 3 consecutive days of failed attempts. The median interval from specimen collection from the index patient to notification of identified contacts was 6 days in both counties. Despite aggressive efforts by health department staff members to perform case investigations and contact tracing, many persons with COVID-19 did not report contacts, and many contacts were not reached. These findings indicate that improved timeliness of contact tracing, community engagement, and increased use of community-wide mitigation are needed to interrupt SARS-CoV-2 transmission., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Mycobacterium tuberculosis complex (MTBC) is divided into several major phylogenetic lineages, with differential distribution globally. Using population-based data collected over a three year period, we performed 24-locus Mycobacterial Interspersed Repeat Unit - Variable Number Tandem Repeat (MIRU-VNTR) genotyping on all culture isolates from two districts of the country that differ in tuberculosis (TB) incidence (Gaborone, the capital, and Ghanzi in the Western Kalahari). The study objective was to characterize the molecular epidemiology of TB in these districts. Overall phylogenetic diversity mirrored that reported from neighboring Republic of South Africa, but differences in the two districts were marked. All four major lineages of M. tuberculosis were found in Gaborone, but only three of the four major lineages were found in Ghanzi. Strain diversity was lower in Ghanzi, with a large proportion (38%) of all isolates having an identical MIRU-VNTR result, compared to 6% of all isolates in Gaborone with the same MIRU-VNTR result. This study demonstrates localized differences in strain diversity by two districts in Botswana, and contributes to a growing characterization of MTBC diversity globally., (Published by Elsevier B.V.)

Setting: Twenty-two clinics providing HIV care and treatment in Botswana where tuberculosis (TB) and HIV comorbidity is as high as 49%., Objectives: To assess eligibility of TB preventive treatment (TPT) at antiretroviral therapy (ART) initiation and at four follow-up visits (FUVs), and to describe the TB prevalence and associated factors at baseline and yield of TB diagnoses at each FUV., Design: A prospective study of routinely collected data on people living with HIV (PLHIV) enrolled into care for the Xpert ® MTB/RIF Package Rollout Evaluation Study between 2012 and 2015., Results: Of 6041 PLHIV initiating ART, eligibility for TPT was 69% (4177/6041) at baseline and 93% (5408/5815); 95% (5234/5514); 96% (4869/5079); and 97% (3925/4055) at FUV1, FUV2, FUV3, and FUV4, respectively. TB prevalence at baseline was 11% and 2%, 3%, 3% and 6% at each subsequent FUV. At baseline, independent risk factors for prevalent TB were CD4 <200 cells/mm 3 (aOR = 1.4, P = 0.030); anemia (aOR = 2.39, P < 0.001); cough (aOR = 11.21, P < 0.001); fever (aOR = 2.15, P = 0.001); and weight loss (aOR = 2.60, P = 0.002)., Conclusion: Eligibility for TPT initiation is higher at visits post-ART initiation, while most cases of active TB were identified at ART initiation. Missed opportunities for TB further compromises TB control effort among PLHIV in Botswana., Competing Interests: Conflicts of interest: none declared., (© 2020 The Union.)

Contact investigation is one public health measure used to prevent tuberculosis by identifying and treating persons exposed to Mycobacterium tuberculosis. Contact investigations are a major tenet of global tuberculosis elimination efforts, but for many reasons remain ineffective. We describe a novel neighbor-based approach to reframe contact investigations.

Tuberculosis caused by concurrent infection with multiple Mycobacterium tuberculosis strains (i.e., mixed infection) challenges clinical and epidemiologic paradigms. We explored possible transmission mechanisms of mixed infection in a population-based, molecular epidemiology study in Botswana during 2012-2016. We defined mixed infection as multiple repeats of alleles at >2 loci within a discrete mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) result. We compared mixed infection MIRU-VNTR results with all study MIRU-VNTR results by considering all permutations at each multiple allele locus; matched MIRU-VNTR results were considered evidence of recently acquired strains and nonmatched to any other results were considered evidence of remotely acquired strains. Among 2,051 patients, 34 (1.7%) had mixed infection, of which 23 (68%) had recently and remotely acquired strains. This finding might support the mixed infection mechanism of recent transmission and simultaneous remote reactivation. Further exploration is needed to determine proportions of transmission mechanisms in settings where mixed infections are prevalent.

The End TB Strategy envisions a world free of tuberculosis-zero deaths, disease and suffering due to tuberculosis by 2035. This requires reducing the global tuberculosis incidence from >1250 cases per million people to <100 cases per million people within the next two decades. Expanding testing and treatment of tuberculosis infection is critical to achieving this goal. In high-burden countries, like India, the implementation of tuberculosis preventive treatment (TPT) remains a low priority. In this analysis article, we explore potential challenges and solutions of implementing TPT in India. The next chapter in tuberculosis elimination in India will require cost-effective and sustainable interventions aimed at tuberculosis infection. This will require constant innovation, locally driven solutions to address the diverse and dynamic tuberculosis epidemiology and persistent programme monitoring and evaluation. As new tools, regimens and approaches emerge, midcourse adjustments to policy and practice must be adopted. The development and implementation of new tools and strategies will call for close collaboration between local, national and international partners-both public and private-national health authorities, non-governmental organisations, research community and the diagnostic and pharmaceutical industry. Leading by example, India can contribute to global knowledge through operational research and programmatic implementation for combating tuberculosis infection., Competing Interests: Competing interests: None declared.

Background: The Global Fund encourages operational research (OR) in all its grants; however very few reports describe this aspect. In India, Project Axshya was supported by a Global Fund grant to improve the reach and visibility of the government Tuberculosis (TB) services among marginalised and vulnerable communities. OR was incorporated to build research capacity of professionals working with the national TB programme and to generate evidence to inform policies and practices., Objectives: To describe how Project Axshya facilitated building OR capacity within the country, helped in addressing several TB control priority research questions, documented project activities and their outcomes, and influenced policy and practice., Methods: From September 2010 to September 2016, three key OR-related activities were implemented. First, practical output-oriented modular training courses were conducted (n = 3) to build research capacity of personnel involved in the TB programme, co-facilitated by The Union, in collaboration with the national TB programme, WHO country office and CDC, Atlanta. Second, two large-scale Knowledge, Attitude and Practice (KAP) surveys were conducted at baseline and mid-project to assess the changes pertaining to TB knowledge, attitudes and practices among the general population, TB patients and health care providers over the project period. Third, studies were conducted to describe the project's core activities and outcomes., Results: In the training courses, 44 participant teams were supported to develop research protocols on topics of national priority, resulting in 28 peer-reviewed scientific publications. The KAP surveys and description of project activities resulted in 14 peer-reviewed publications. Of the published papers at least 12 have influenced change in policy or practice., Conclusions: OR within a Global Fund supported TB project has resulted in building OR capacity, facilitating research in areas of national priority and influencing policy and practice. We believe this experience will provide guidance for undertaking OR in Global Fund projects.

The proportion of tuberculosis (TB) patients tested for the human immunodeficiency virus (HIV) in the state of Ra-jasthan, India, is limited by the availability of HIV testing facilities. Rajasthan implemented a policy of initiating TB-HIV diagnosis at all health institutions in July 2013. The number of TB diagnostic facilities increased from 33 to 63 in Banswara District and from 22 to 68 in Jhunjhunu District, while the number of HIV testing facilities in these districts increased from 1 to 53 and from 10 to 81, respectively, after the policy implementation. The proportion of TB patients tested for HIV increased by respectively 27% and 19%.

During 2012-2015, 10 of 24 patients infected with matching genotypes of Mycobacterium tuberculosis received care at the same hospital in Gaborone, Botswana. Nosocomial transmission was initially suspected, but we discovered plausible sites of community transmission for 20 (95%) of 21 interviewed patients. Active case-finding at these sites could halt ongoing transmission.

Setting: Ho Chi Minh City (HCMC), Viet Nam. Objective: To evaluate a new integrated service model for human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS) care. Design: In HCMC, co-located services, including voluntary HIV counseling and testing (VCT), HIV treatment at out-patient clinics (OPC), and methadone maintenance therapy (MMT) for persons who inject drugs, have operated under different administrative structures. In the context of decreasing international financial support, integration of these services into one administrative structure with reduced staff occurred in seven districts in HCMC between October 2013 and June 2014. We used a pre-post study design to compare service-related outcomes from routinely collected data at health facilities 6 months before and 6 months after integration. Results: The proportion of HIV-infected persons linked from VCT to OPCs was unchanged or increased following integration. A higher percentage of patients eligible for antiretroviral therapy (ART) were started on ART. The proportion of ART patients lost to follow-up remained unchanged. The proportions of MMT patients who tested positive for heroin or other substances decreased or were unchanged. Conclusions: VCT, OPC and MMT service delivery quality remained the same or improved during the 6 months following the integration. Expansion of the integrated model should be considered for HIV-related services.

Introduction: Poverty and poor nutrition are associated with the risk of developing tuberculosis (TB). Socioeconomic factors may interfere with anti-tuberculosis treatment compliance and its outcome. We examined whether providing nutritional support (monthly supply of rice and lentil beans) to TB patients who live below the poverty line was associated with TB treatment outcome., Methods: This was a retrospective cohort study of sputum smear-positive pulmonary TB patients living below the poverty line (income of <$1.25 per day) registered for anti-tuberculosis treatment in two rural districts of West Bengal, India during 2012 to 2013. We compared treatment outcomes among patients who received nutritional support with those who did not. A log-binomial regression model was used to assess the relation between nutritional support and unsuccessful treatment outcome (loss-to-follow-up, treatment failure and death)., Results: Of 173 TB patients provided nutritional support, 15 (9%) had unsuccessful treatment outcomes, while 84 (21%) of the 400 not provided nutrition support had unsuccessful treatment outcomes (p < 0.001). After adjusting for age, sex and previous treatment, those who received nutritional support had a 50% reduced risk of unsuccessful treatment outcome than those who did not receive nutritional support (Relative Risk: 0.51; 95% Confidence Intervals: 0.30 - 0.86)., Conclusion: Under programmatic conditions, monthly rations of rice and lentils were associated with lower risk of unsuccessful treatment outcome among impoverished TB patients. Given the relatively small financial commitment needed per patient ($10 per patient per month), the national TB programme should consider scaling up nutritional support among TB patients living below the poverty line.

To find 'missing' tuberculosis (TB) cases, in November 2014 we trained private practitioners (PPs) and Ayurvedic practitioners (APs; Indian system of medicine) in Bilaspur district, India, to identify patients with presumptive TB and refer them to sputum microscopy centres. To reinforce this training, we sent weekly text message reminders during January-March 2015. All 50 APs and 23 of 29 PPs participated. The number of patients with presumptive TB referred by the PPs and APs increased from 38 (January-March 2014) to 104 (January-March 2015), and the number of smear-positive TB patients diagnosed increased from 5 to 16, a 220% increase. While the intervention increased the number of referrals, it did not impact case detection at district level, due to the short duration of the intervention and the non-dominant private sector.

Introduction: Mycobacterium tuberculosis (Mtb) is transmitted from person to person via airborne droplet nuclei. At the community level, Mtb transmission depends on the exposure venue, infectiousness of the tuberculosis (TB) index case and the susceptibility of the index case's social network. People living with HIV infection are at high risk of TB, yet the factors associated with TB transmission within communities with high rates of TB and HIV are largely undocumented. The primary aim of the Kopanyo study is to better understand the demographic, clinical, social and geospatial factors associated with TB and multidrug-resistant TB transmission in 2 communities in Botswana, a country where 60% of all patients with TB are also infected with HIV. This manuscript describes the methods used in the Kopanyo study., Methods and Analysis: The study will be conducted in greater Gaborone, which has high rates of HIV and a mobile population; and in Ghanzi, a rural community with lower prevalence of HIV infection and home to the native San population. Kopanyo aims to enrol all persons diagnosed with TB during a 4-year study period. From each participant, sputum will be cultured, and for all Mtb isolates, molecular genotyping (24-locus mycobacterial interspersed repetitive units-variable number of tandem repeats) will be performed. Patients with matching genotype results will be considered members of a genotype cluster, a proxy for recent transmission. Demographic, behavioural, clinical and social information will be collected by interview. Participant residence, work place, healthcare facilities visited and social gathering venues will be geocoded. We will assess relationships between these factors and cluster involvement to better plan interventions for reducing TB transmission., Ethics: Ethical approval from the Independent Review Boards at the University of Pennsylvania, US Centers for Disease Control and Prevention, Botswana Ministry of Health and University of Botswana has been obtained., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Rationale: Excess alcohol use (EAU) is associated with adverse TB treatment outcomes., Objective: We investigated the relationship between EAU and death among TB patients 15 years and older prescribed anti-TB treatment in the United States., Design: Using data reported to the National Tuberculosis Surveillance System for 1997-2012, we calculated adjusted odds ratios and excess attributable risk percent for death among TB patients with reported EAU., Results: EAU was associated with death among patients younger than 65. The excess attributable risk percent for death among those with reported EAU for those younger than 65 was >35%., Conclusions: Interventions to reduce EAU in patients <65 years may reduce deaths.

Background: The World Health Organization recommends direct observation of treatment (DOT) to support patients with tuberculosis (TB) and to ensure treatment completion. As per national programme guidelines in India, a DOT provider can be anyone who is acceptable and accessible to the patient and accountable to the health system, except a family member. This poses challenges among children with TB who may be more comfortable receiving medicines from their parents or family members than from unfamiliar DOT providers. We conducted a non-inferiority trial to assess the effect of family DOT on treatment success rates among children with newly diagnosed TB registered for treatment during June-September 2012., Methods: We randomly assigned all districts (n = 30) in Gujarat to the intervention (n = 15) or usual-practice group (n = 15). Adult family members in the intervention districts were given the choice to become their child's DOT provider. DOT was provided by a non-family member in the usual-practice districts. Using routinely collected clinic-based TB treatment cards, we compared treatment success rates (cured and treatment completed) between the two groups and the non-inferiority limit was kept at 5%., Results: Of 624 children with newly diagnosed TB, 359 (58%) were from intervention districts and 265 (42%) were from usual-practice districts. The two groups were similar with respect to baseline characteristics including age, sex, type of TB, and initial body weight. The treatment success rates were 344 (95.8%) and 247 (93.2%) (p = 0.11) among the intervention and usual-practice groups respectively., Conclusion: DOT provided by a family member is not inferior to DOT provided by a non-family member among new TB cases in children and can attain international targets for treatment success., Trial Registration: Clinical Trials Registry-India, National Institute of Medical Statistics (Indian Council of Medical Research) CTRI/2015/09/006229.

Background: In India, the National Health Mission has provided one mobile medical unit (MMU) per district in the state of Punjab to provide primary health care services for difficult-to-reach populations., Objectives: To determine the number of patients with presumptive tuberculosis (TB) and the number of TB cases detected and treated among patients who used the MMU services from May to December 2012 in Mohali district, Punjab, India., Methods: A cross-sectional study was conducted and registers of the out-patient, laboratory, radiology, and TB departments of the MMU were reviewed to determine the number of persons presumed to have TB and the number of persons diagnosed with TB., Results: Of 8346 patients who attended the MMUs, 663 (8%) had symptoms suggestive of TB. Among those with TB symptoms, 540 (81%) were evaluated for pulmonary TB using sputum examination or chest X-ray. In total, 58 (11%) patients had clinical or laboratory evidence of pulmonary TB, of whom 21 (36%) started anti-tuberculosis treatment., Conclusion: As MMUs are an integral part of the general public health system, these units have the potential to detect TB cases among difficult-to-reach populations. Additional research is required to optimise the diagnosis of TB at MMUs and to increase rates of TB treatment initiation.

Objective: To assess prevalence and occupational risk factors of latent TB infection and history of TB disease ascribed to work in a healthcare setting in western Kenya., Methods: We conducted a cross-sectional survey among healthcare workers in western Kenya in 2013. They were recruited from dispensaries, health centres and hospitals that offer both TB and HIV services. School workers from the health facilities' catchment communities were randomly selected to serve as the community comparison group. Latent TB infection was diagnosed by tuberculin skin testing. HIV status of participants was assessed. Using a logistic regression model, we determined the adjusted odds of latent TB infection among healthcare workers compared to school workers; and among healthcare workers only, we assessed work-related risk factors for latent TB infection., Results: We enrolled 1005 healthcare workers and 411 school workers. Approximately 60% of both groups were female. A total of 22% of 958 healthcare workers and 12% of 392 school workers tested HIV positive. Prevalence of self-reported history of TB disease was 7.4% among healthcare workers and 3.6% among school workers. Prevalence of latent TB infection was 60% among healthcare workers and 48% among school workers. Adjusted odds of latent TB infection were 1.5 times higher among healthcare workers than school workers (95% confidence interval 1.2-2.0). Healthcare workers at all three facility types had similar prevalence of latent TB infection (P = 0.72), but increasing years of employment was associated with increased odds of LTBI (P < 0.01)., Conclusion: Healthcare workers at facilities in western Kenya which offer TB and HIV services are at increased risk of latent TB infection, and the risk is similar across facility types. Implementation of WHO-recommended TB infection control measures are urgently needed in health facilities to protect healthcare workers., (© 2015 John Wiley & Sons Ltd.)

The transcontinental spread of multidrug-resistant (MDR) tuberculosis is poorly characterized in molecular epidemiologic studies. We used genomic sequencing to understand the establishment and dispersion of MDR Mycobacterium tuberculosis within a group of immigrants to the United States. We used a genomic epidemiology approach to study a genotypically matched (by spoligotype, IS6110 restriction fragment length polymorphism, and mycobacterial interspersed repetitive units-variable number of tandem repeat signature) lineage 2/Beijing MDR strain implicated in an outbreak of tuberculosis among refugees in Thailand and consecutive cases within California. All 46 MDR M. tuberculosis genomes from both Thailand and California were highly related, with a median difference of 10 single-nucleotide polymorphisms (SNPs). The Wat Tham Krabok (WTK) strain is a new sequence type distinguished from all known Beijing strains by 55 SNPs and a genomic deletion (Rv1267c) associated with increased fitness. Sequence data revealed a highly prevalent MDR strain that included several closely related but distinct allelic variants within Thailand, rather than the occurrence of a single outbreak. In California, sequencing data supported multiple independent introductions of WTK with subsequent transmission and reactivation within the state, as well as a potential super spreader with a prolonged infectious period. Twenty-seven drug resistance-conferring mutations and 4 putative compensatory mutations were found within WTK strains. Genomic sequencing has substantial epidemiologic value in both low- and high-burden settings in understanding transmission chains of highly prevalent MDR strains., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Lack of trust in government-supported services after the death of a health care worker with symptoms of Ebola resulted in ongoing Ebola transmission in 2 Liberia counties. Ebola transmission was facilitated by attempts to avoid cremation of the deceased patient and delays in identifying and monitoring contacts.

Introduction: Data are limited regarding tuberculosis (TB) and latent TB infection prevalence in Rwandan health facilities., Methods: We conducted a cross-sectional survey among healthcare workers (HCWs) in Kigali during 2010. We purposively selected the public referral hospital, both district hospitals, and randomly selected 7 of 17 health centers. School workers (SWs) from the nearest willing public schools served as a local reference group. We tested for latent TB infection (LTBI) using tuberculin skin testing (TST) and asked about past TB disease. We assessed risk of LTBI and past history of TB disease associated with hospital employment. Among HCWs, we assessed risk associated with facility type (district hospital, referral hospital, health center), work setting (inpatient, outpatient), and occupation., Results: Age, gender, and HIV status was similar between the enrolled 1,131 HCWs and 381 SWs. LTBI was more prevalent among HCWs (62%) than SWs (39%). Adjusted odds of a positive TST result were 2.71 (95% CI 2.01-3.67) times greater among HCWs than SWs. Among HCWs, there was no detectable difference between prevalence of LTBI according to facility type, work setting, or occupation., Conclusion: HCWs are at greater risk of LTBI, regardless of facility type, work setting, or occupation. The current status of TB infection control practices should be evaluated in the entire workforce in all Rwandan healthcare facilities.

A review of 26 tuberculosis outbreaks in the United States (2002-2011) showed that initial source case-patients had long infectious periods (median 10 months) and were characterized by substance abuse, incarceration, and homelessness. Improved timeliness of diagnosis and thorough contact investigations for such cases may reduce the risk for outbreaks.