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SettingThe impact of the genetic characteristics of Mycobacterium tuberculosis on the clustering of multidrug-resistant tuberculosis (MDR-TB) has not been analyzed together with clinical and demographic characteristics.ObjectiveTo determine factors associated with genotypic clustering of MDR-TB in a community-based study.DesignWe measured the proportion of clustered cases among MDR-TB patients and determined the impact of clinical and demographic characteristics and that of three M. tuberculosis genetic characteristics: lineage, drug resistance-associated mutations, and rpoA and rpoC compensatory mutations.ResultsOf 174 patients from California and Texas included in the study, the number infected by East-Asian, Euro-American, Indo-Oceanic and East-African-Indian M. tuberculosis lineages were respectively 70 (40.2%), 69 (39.7%), 33 (19.0%) and 2 (1.1%). The most common mutations associated with isoniazid and rifampin resistance were respectively katG S315T and rpoB S531L. Potential compensatory mutations in rpoA and rpoC were found in 35 isolates (20.1%). Hispanic ethnicity (OR 26.50, 95%CI 3.73-386.80), infection with an East-Asian M. tuberculosis lineage (OR 30.00, 95%CI 4.20-462.40) and rpoB mutation S531L (OR 4.03, 95%CI 1.05-23.10) were independent factors associated with genotypic clustering.ConclusionAmong the bacterial factors studied, East-Asian lineage and rpoB S531L mutation were independently associated with genotypic clustering, suggesting that bacterial factors have an impact on the ability of M. tuberculosis to cause secondary cases.

RATIONALE AND OBJECTIVES: Identifying and treating persons with latent tuberculosis (TB) infection (LTBI) at high risk for developing TB is part of the current TB elimination strategy. There are no specific criteria, other than medical risks, to designate groups as high risk for developing TB. We hypothesized that, if location-based screenings were done in communities where persons with genotypically clustered Mycobacterium tuberculosis resided, then persons with LTBI from recent transmission and with undiagnosed TB could be identified. METHODS: Location-based TB screenings were done in partnership with multiple community-based organizations using resources previously used for other types of screening. MAIN RESULTS: Location-based screenings identified one person with TB for every 83 screened, and one person with LTBI for every five screened. The yield of this targeted screening program for discovering persons with TB and LTBI exceeded what would be expected from nontargeted screening in a county with a TB incidence of 5.7 per 100,000 population. CONCLUSIONS: Genotyping combined with geographic information systems analysis can potentially be used to define high-risk status and to define areas for location-based TB screenings. [ABSTRACT FROM AUTHOR]

Rationale: Diagnosis of latent tuberculosis infection (LTBI) is currently based on the tuberculin skin test. The enzyme-linked immunospot assay (ELISPOT) is a new blood test to diagnose LTBI.Objective: To compare the ELISPOT and the tuberculin skin test for detecting LTBI in contacts of patients with tuberculosis.Methods: Prospective study of 413 contacts of patients with tuberculosis.Measurements and Main Results: Because there is no gold standard for LTBI, the sensitivity and specificity of the ELISPOT and tuberculin skin test cannot be directly measured. For each contact, we therefore estimated the likelihood of having LTBI by calculating a contact score that quantified exposure to and infectiousness of the index case. We analyzed the relationship of contact score to ELISPOT and tuberculin skin test results. The likelihood of a positive ELISPOT (p = 0.0005) and a tuberculin skin test (p = 0.01) increased significantly with rising contact scores. The contact score was more strongly related to the ELISPOT than to the tuberculin skin test results, although this difference was not statistically significant. Among U.S.-born persons and those who were not vaccinated with bacille Calmette-Guérin, approximately 30% had positive ELISPOT or tuberculin skin test results. Foreign-born, bacille Calmette-Guérin-vaccinated persons were significantly more likely to have a positive tuberculin skin test than a positive ELISPOT result (p < 0.0001).Conclusions: Compared with the tuberculin skin test, the ELISPOT appears to be at least as sensitive for diagnosis of LTBI in contacts of patients with tuberculosis. [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.)

Underprioritization of mental health is a global problem and threatens the decades-long progress of the US President's Emergency Plan for AIDS Relief (PEPFAR) program. In recent years, mental health has become globally recognized as a part of universal healthcare, making this an opportune moment for the global community to integrate mental health services into routine programming. PEPFAR is well positioned to lead by example. We conceptualized 5 key strategies that might help serve as a framework to support mental health programming as part of PEPFAR's current 5-year strategic plan. PEPFAR and the global community have an opportunity to identify mental health service gaps and interweave global mental health priorities with actions to end the HIV and TB epidemics by 2030.

Tuberculosis (TB) is the leading cause of death among persons with HIV. In 2022, an estimated 167,000 TB-related deaths occurred globally among persons with HIV. TB preventive treatment (TPT) helps prevent TB disease and is recommended for persons at high risk for developing TB, including those with HIV. TPT, when taken with antiretroviral treatment (ART), can reduce TB-attributable deaths among persons with HIV. In 2018, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) program committed to offer one course of TPT to all eligible clients receiving ART. This analysis describes trends in TPT initiation and completion among PEPFAR-supported programs in 36 countries in Africa, Central and South America, and Asia during fiscal years (FYs) 2017-2023. Overall, TPT initiation rates peaked in FY19, a possible sign of programmatic saturation. TPT initiation among clients who had been on ART <6 months reached 59%, and overall completion rates up to 87% were reported. Approximately 13 million persons with HIV have completed TPT since FY17, but widespread adoption of shorter regimens, patient-centered approaches, and electronic medical record systems might be needed to ensure full TPT coverage. Through PEPFAR's partnership with national HIV programs, TPT has become the standard of care for persons with HIV., 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.

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.

Mumbai, India's second largest city, has one of the highest prevalences of drug-resistant tuberculosis* (DRTB) in the world. Treatment for DRTB takes longer and is more complicated than treatment for drug-susceptible tuberculosis (TB). Approximately 300 persons receive a new DRTB diagnosis each year in Mumbai's Dharavi slum † ; historically, fewer than one half of these patients complete DRTB treatment. As nationwide restrictions to mitigate the COVID-19 pandemic were implemented, a program to facilitate uninterrupted DRTB care for patients receiving treatment was also implemented. A comprehensive tool and risk assessment provided support to DRTB patients and linked those who relocated outside of Dharavi during the pandemic to DRTB care at their destination. During May 2020-September 2022, a total of 973 persons received DRTB treatment in Dharavi, including 255 (26%) who relocated during treatment. Overall, 25 (3%) DRTB patients were lost to follow-up, a rate substantially lower than the rate before the pandemic (18%). Proactive planning and implementation of simple tools retained patients on treatment during periods of travel restrictions and relocations, improving programmatic outcomes. This approach might aid public health programs serving migrant populations or patients receiving treatment for DRTB during public health emergencies., 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.

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: Co-management of HIV-TB coinfection remains a challenge globally. Addressing TB among people living with HIV (PLHIV) is a key priority for the Government of India (GoI). In 2016, GoI implemented single-window services to prevent and manage TB in PLHIV. To strengthen HIV-TB service delivery, case-based e-learning was introduced to health care providers at Antiretroviral Therapy centres (ARTc)., Methods: We implemented a hub and spoke model to deliver biweekly, virtual, case-based e-learning at select ARTc (n = 115), from four states of India-Delhi, Uttar Pradesh, Andhra Pradesh and Tamil Nadu. We evaluated feasibility and acceptability of case-based e-learning and its impact on professional satisfaction, self-efficacy, knowledge retention using baseline and completion surveys, session feedback, pre-and post-session assessments. We reviewed routine programmatic data and patient outcomes to assess practices among participating ARTc., Results: Between May 2018 and September 2020, 59 sessions were conducted with mean participation of 55 spokes and 152 participants. For 95% and 88% of sessions ≥ 80% of respondents agreed that topics were clear and relevant to practice, and duration of session was appropriate, respectively. Session participants significantly improved in perceived knowledge, skills and competencies (+ 8.6%; p = 0.025), and technical knowledge (+ 18.3%; p = 0.04) from baseline. Participating ARTc increased TB screening (+ 4.2%, p < 0.0001), TB diagnosis (+ 2.7%, p < 0.0001), ART initiation (+ 4.3%, p < 0.0001) and TB preventive treatment completion (+ 5.2%, p < 0.0001)., Conclusion: Case-based e-learning is an acceptable and effective modus of capacity building and developing communities of practice to strengthen integrated care. E-learning could address demand for accessible and sustainable continuing professional education to manage complex diseases, and thereby enhance health equity. We recommend expansion of this initiative across the country for management of co-morbidities as well as other communicable and non-communicable diseases to augment the existing capacity building interventions by provide continued learning and routine mentorship through communities of practice., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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.)

Persistent gaps exist in healthcare workers' capacity to address HIV and tuberculosis in Asia and Africa due to constraints in resources and knowledge. Project ECHO (Extension for Community Healthcare Outcomes) leverages video-enabled technology to build workforce capacity and promote collaboration through mentorship and case-based learning. To understand current perceptions of ECHO participants and develop a comprehensive evaluation framework for ECHO implementation, we utilized modified appreciative inquiry guided focus group discussions (FGD) in India and Tanzania and called it SCORE (Strengths, Challenges, Opportunities, Results, and Evaluation). Content and thematic analysis of transcripts from FGDs and key-informant interviews triangulated perceptions of diverse stakeholders about ECHO implementation and identified key elements for development of the framework. The perceived strengths (S) were capacity building and establishing communities of practice. The perceived challenges (C) included securing resources, engaging leadership, and building systems for monitoring impact. Improved internet connectivity, addressing logistical challenges, encouraging session interactivity, and having strategic scale-up plans were perceived opportunities (O). Additionally, gathering measurable results (R) led to development of a comprehensive evaluation (E) framework. Contextualizing and facilitating SCORE with qualitative analysis of findings 6-12 months post-ECHO implementation may serve as a best practice to assess mid-course corrections to improve ECHO implementation quality., (Published by Elsevier Ltd.)

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.

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.)

India has a high burden of drug-resistant tuberculosis (DR TB) and many cases go undetected by current drug susceptibility tests (DSTs). This study was conducted to identify rifampicin (RIF) and isoniazid (INH) resistance associated genetic mutations undetected by current clinical diagnostics amongst persons with DR TB in Chennai, India. Retrospectively stored 166 DR TB isolates during 2013-2016 were retrieved and cultured in Löwenstein-Jensen medium. Whole genome sequencing (WGS) and MGIT DST for RIF and INH were performed. Discordant genotypic and phenotypic sensitivity results were repeated for confirmation and the discrepant results considered final. Further, drug resistance-conferring mutations identified through WGS were analyzed for their presence as targets in current WHO-recommended molecular diagnostics. WGS detected additional mutations for rifampicin and isoniazid resistance than WHO-endorsed line probe assays. For RIF, WGS was able to identify an additional 10% (15/146) of rpoB mutant isolates associated with borderline rifampicin resistance compared to MGIT DST. WGS could detect additional DR TB cases than commercially available and WHO-endorsed molecular DST tests. WGS results reiterate the importance of the recent WHO revised critical concentrations of current MGIT DST to detect low-level resistance to rifampicin. WGS may help inform effective treatment selection for persons at risk of, or diagnosed with, DR TB., 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 Tamilzhalagan, Shanmugam, Selvaraj, Suba, Suganthi, Moonan, Surie, Sathyanarayanan, Gomathi, Jayabal, Sachdeva, Selvaraju, Swaminathan, Tripathy, Hall and Ranganathan.)

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.)

Objective: To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled-nursing facility (SNF), and the strategies that controlled transmission., Design, Setting, and Participants: This cohort study was conducted during March 22-May 4, 2020, among all staff and residents at a 780-bed SNF in San Francisco, California., Methods: Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPSs) in units with confirmed cases. Cases were confirmed by real-time reverse transcription-polymerase chain reaction testing for SARS-CoV-2, and whole-genome sequencing (WGS) was used to characterize viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact with a confirmed case; restricting movement between units; implementing surgical face masking facility-wide; and the use of recommended PPE (ie, isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases., Results: Of 725 staff and residents tested through targeted testing and serial PPSs, 21 (3%) were SARS-CoV-2 positive: 16 (76%) staff and 5 (24%) residents. Fifteen cases (71%) were linked to a single unit. Targeted testing identified 17 cases (81%), and PPSs identified 4 cases (19%). Most cases (71%) were identified before IPC interventions could be implemented. WGS was performed on SARS-CoV-2 isolates from 4 staff and 4 residents: 5 were of Santa Clara County lineage and the 3 others were distinct lineages., Conclusions: Early implementation of targeted testing, serial PPSs, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF.

Introduction: The United States Centers for Disease Control and Prevention (CDC), through U.S. President's Emergency Plan for AIDS Relief (PEPFAR), supports a third of all people receiving HIV care globally. CDC works with local partners to improve methods to find, treat, and prevent HIV and tuberculosis. However, a shortage of trained medical professionals has impeded efforts to control the HIV epidemic in Sub-Saharan Africa and Asia. The Project Extension for Community Healthcare Outcomes (ECHO TM ) model expands capacity to manage complex diseases, share knowledge, disseminate best practices, and build communities of practice. This manuscript describes a practical protocol for an evaluation framework and toolkit to assess ECHO implementation. Methods and Analysis: This mixed methods, developmental evaluation design uses an appreciative inquiry approach, and includes a survey, focus group discussion, semi-structured key informant interviews, and readiness assessments. In addition, ECHO session content will be objectively reviewed for accuracy, content validity, delivery, appropriateness, and consistency with current guidelines. Finally, we offer a mechanism to triangulate data sources to assess acceptability and feasibility of the evaluation framework and compendium of monitoring and evaluation tools. Expected impact of the study on public health: This protocol offers a unique approach to engage diverse group of stakeholders using an appreciative inquiry process to co-create a comprehensive evaluation framework and a compendium of assessment tools. This evaluation framework utilizes mixed methods (quantitative and qualitative data collection tools), was pilot tested in Tanzania, and has the potential for contextualized use in other countries who plan to evaluate their Project ECHO implementation., Competing Interests: BBS is Associate Director of Project ECHO, of the ECHO Institute, located in Albuquerque, University of New Mexico. 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 © 2021 Ghosh, Roth, Massawe, Mtete, Lusekelo, Pinsker, Seweryn, Moonan and Struminger.)

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: Coronavirus disease 2019 (COVID-19) continues to cause significant morbidity and mortality worldwide. Correctional and detention facilities are at high risk of experiencing outbreaks. We aimed to evaluate cohort-based testing among detained persons exposed to laboratory-confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in order to identify presymptomatic and asymptomatic cases., Methods: During 1-19 May 2020, 2 testing strategies were implemented in 12 tiers or housing units of the Cook County Jail, Chicago, Illinois. Detained persons were approached to participate in serial testing (n = 137) and offered tests at 3 time points over 14 days (day 1, days 3-5, and days 13-14). The second group was offered a single test and interview at the end of a 14-day quarantine period (day 14 group) (n = 87)., Results: 224 detained persons were approached for participation and, of these, 194 (87%) participated in ≥1 interview and 172 (77%) had ≥1 test. Of the 172 tested, 19 were positive for SARS-CoV-2. In the serial testing group, 17 (89%) new cases were detected, 16 (84%) on day 1, 1 (5%) on days 3-5, and none on days 13-14; in the day 14 group, 2 (11%) cases were identified. More than half (12/19; 63%) of the newly identified cases were presymptomatic or asymptomatic., Conclusions: Our findings highlight the utility of cohort-based testing promptly after initiating quarantine within a housing tier. Cohort-based testing efforts identified new SARS-CoV-2 asymptomatic and presymptomatic infections that may have been missed by symptom screening alone., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

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.

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.)

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.

In a Perspective on the research article from Jacobson and colleagues, Amitabh Suthar and colleagues from the Centers for Disease Control and Prevention discuss the importance of and considerations for developing real-time and large-scale reporting systems for tracking and controlling antimicrobial resistance., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: ABS is a member of the Editorial Board of PLOS Medicine.

Of patients with multidrug-resistant tuberculosis (MDR TB), <50% complete treatment. Most treatment failures for patients with MDR TB are due to death during TB treatment. We sought to determine the proportion of deaths during MDR TB treatment attributable to TB itself. We used a structured verbal autopsy tool to interview family members of patients who died during MDR TB treatment in India during January-December 2016. A committee triangulated information from verbal autopsy, death certificate, or other medical records available with the family members to ascertain the underlying cause of death. For 66% of patient deaths (47/71), TB was the underlying cause of death. We assigned TB as the underlying cause of death for an additional 6 patients who died of suicide and 2 of pulmonary embolism. Deaths during TB treatment signify program failure; accurately determining the cause of death is the first step to designing appropriate, timely interventions to prevent premature deaths.

Background: Tuberculosis (TB) patients face substantial delays prior to treatment initiation, and out of pocket (OOP) expenditures often surpass the economic productivity of the household. We evaluated the pre-diagnostic cost and health seeking behaviour of new adult pulmonary TB patients registered at Primary Health Centres (PHCs) in Vellore district, Tamil Nadu, India., Methods: This descriptive study, part of a randomised controlled trial conducted in three rural Tuberculosis Units from Dec 2012 to Dec 2015, collected data on number of health facilities, dates of visits prior to the initiation of anti-tuberculosis treatment, and direct OOP medical costs associated with TB diagnosis. Logistic regression analysis examined the factors associated with delays in treatment initiation and OOP expenditures., Results: Of 880 TB patients interviewed, 34.7% presented to public health facilities and 65% patients sought private health facilities as their first point of care. The average monthly individual income was $77.79 (SD 57.14). About 69% incurred some pre-treatment costs at an average of $39.74. Overall, patients experienced a median of 6 days (3-11 IQR) of time to treatment initiation and 21 days (10-30 IQR) of health systems delay. Age ≤ 40 years (aOR: 1.73; CI: 1.22-2.44), diabetes (aOR: 1.63; CI: 1.08-2.44) and first visit to a private health facility (aOR: 17.2; CI: 11.1-26.4) were associated with higher direct OOP medical costs, while age ≤ 40 years (aOR: 0.64; CI: 0.48-0.85) and first visit to private health facility (aOR: 1.79, CI: 1.34-2.39) were associated with health systems delay., Conclusion: The majority of rural TB patients registering at PHCs visited private health facilities first and incurred substantial direct OOP medical costs and delays prior to diagnosis and anti-tuberculosis treatment initiation. This study highlights the need for PHCs to be made as the preferred choice for first point of contact, to combat TB more efficiently.

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%.

Current US guidelines recommend longer treatment for tuberculosis (TB) caused by pyrazinamide-resistant organisms (e.g., Mycobacterium bovis) than for M. tuberculosis TB. We compared treatment response times for patients with M. bovis TB and M. tuberculosis TB reported in the United States during 2006-2013. We included culture-positive, pulmonary TB patients with genotyping results who received standard 4-drug treatment at the time of diagnosis. Time to sputum-culture conversion was defined as time between treatment start date and date of first consistently culture-negative sputum. We analyzed 297 case-patients with M. bovis TB and 30,848 case-patients with M. tuberculosis TB. After 2 months of treatment, 71% of M. bovis and 65% of M. tuberculosis TB patients showed conversion of sputum cultures to negative. Likelihood of culture conversion was higher for M. bovis than for M. tuberculosis, even after controlling for treatment administration type, sex, and a composite indicator of bacillary burden.

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.