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Background: This thematic scoping review of publications sought to understand the global impact of COVID-19 on tuberculosis (TB), interpret the scope of resonating themes, and offer policy recommendations to stimulate TB recovery and future pandemic preparedness., Data Sources: Publications were captured from three search engines, PubMed, EBSCO, and Google Scholar, and applicable websites written in English from January 1, 2020, to April 30, 2023., Study Selection: Our scoping review was limited to publications detailing the impact of COVID-19 on TB. Original research, reviews, letters, and editorials describing the deleterious and harmful--yet sometimes positive--impact of COVID-19 (sole exposure) on TB (sole outcome) were included. The objective was to methodically categorize the impacts into themes through a comprehensive review of selected studies to provide significant health policy guidance., Data Extraction: Two authors independently screened citations and full texts, while the third arbitrated when consensus was not met. All three performed data extraction., Data Synthesis/results: Of 1,755 screened publications, 176 (10%) covering 39 countries over 41 months met the inclusion criteria. By independently using a data extraction instrument, the three authors identified ten principal themes from each publication. These themes were later finalized through a consensus decision. The themes encompassed TB's care cascade, patient-centered care, psychosocial issues, and health services: 1) case-finding and notification (n = 45; 26%); 2) diagnosis and laboratory systems (n = 19; 10.7%) 3) prevention, treatment, and care (n = 22; 12.2%); 4) telemedicine/telehealth (n = 12; 6.8%); 5) social determinants of health (n = 14; 8%); 6) airborne infection prevention and control (n = 8; 4.6%); 7) health system strengthening (n = 22; 13%); 8) mental health (n = 13; 7.4%); 9) stigma (n = 11; 6.3%); and 10) health education (n = 10; 5.7%)., Limitations: Heterogeneity of publications within themes., Conclusions: We identified ten globally generalizable themes of COVID-19's impact on TB. The impact and lessons learned from the themed analysis propelled us to draft public health policy recommendations to direct evidence-informed guidance that strengthens comprehensive global responses, recovery for TB, and future airborne pandemic preparedness., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0548.

Chitin is an abundant, carbon-rich polymer in the marine environment. Chitinase activity has been detected in spent media of Synechococcus WH7803 cultures-yet it was unclear which specific enzymes were involved. Here we delivered a CRISPR tool into the cells via electroporation to generate loss-of-function mutants of putative candidates and identified ChiA as the enzyme required for the activity detected in the wild type., (© 2023. The Author(s).)

Introduction: Tuberculosis (TB) is a leading infectious cause of global morbidity and mortality, affecting nearly a quarter of the human population and accounting for over 10 million deaths each year. Over the past several decades, TB incidence and mortality have gradually declined, but 2021 marked a threatening reversal of this trend highlighting the importance of accurate diagnosis and effective treatment of all forms of TB., Areas Covered: This review summarizes advances in TB diagnostics, addresses the treatment of people with TB infection and TB disease including recent evidence for treatment regimens for drug-susceptible and drug-resistant TB, and draws attention to special considerations in children and during pregnancy., Expert Opinion: Improvements in diagnosis and management of TB have expanded the available options for TB control. Molecular testing has enhanced the detection of TB disease, but better diagnostics are still needed, particularly for certain populations such as children. Novel treatment regimens have shortened treatment and improved outcomes for people with TB. However, important questions remain regarding the optimal management of TB. Work must continue to ensure the potential of the latest developments is realized for all people affected by TB.

Marine picocyanobacteria Prochlorococcus and Synechococcus , the most abundant photosynthetic cells in the oceans, are generally thought to have a primarily single-celled and free-living lifestyle. However, while studying the ability of picocyanobacteria to supplement photosynthetic carbon fixation with the use of exogenous organic carbon, we found the widespread occurrence of genes for breaking down chitin, an abundant source of organic carbon that exists primarily as particles. We show that cells that encode a chitin degradation pathway display chitin degradation activity, attach to chitin particles, and show enhanced growth under low light conditions when exposed to chitosan, a partially deacetylated soluble form of chitin. Marine chitin is largely derived from arthropods, which underwent major diversifications 520 to 535 Mya, close to when marine picocyanobacteria are inferred to have appeared in the ocean. Phylogenetic analyses confirm that the chitin utilization trait was acquired at the root of marine picocyanobacteria. Together this leads us to postulate that attachment to chitin particles allowed benthic cyanobacteria to emulate their mat-based lifestyle in the water column, initiating their expansion into the open ocean, seeding the rise of modern marine ecosystems. Subsequently, transitioning to a constitutive planktonic life without chitin associations led to cellular and genomic streamlining along a major early branch within Prochlorococcus . Our work highlights how the emergence of associations between organisms from different trophic levels, and their coevolution, creates opportunities for colonizing new environments. In this view, the rise of ecological complexity and the expansion of the biosphere are deeply intertwined processes.

Coral reefs are increasingly ecologically destabilized across the globe due to climate change. Behavioural plasticity in corallivore behaviour and short-term trophic ecology in response to bleaching events may influence the extent and severity of coral bleaching and subsequent recovery potential, yet our understanding of these interactions in situ remains unclear. Here, we investigated interactions between corallivory and coral bleaching during a severe high thermal event (10.3-degree heating weeks) in Belize. We found that parrotfish changed their grazing behaviour in response to bleaching by selectively avoiding bleached Orbicella spp. colonies regardless of bleaching severity or coral size. For bleached corals, we hypothesize that this short-term respite from corallivory may temporarily buffer coral energy budgets by not redirecting energetic resources to wound healing, and may therefore enable compensatory nutrient acquisition. However, colonies that had previously been heavily grazed were also more susceptible to bleaching, which is likely to increase mortality risk. Thus, short-term respite from corallivory during bleaching may not be sufficient to functionally rescue corals during prolonged bleaching. Such pairwise interactions and behavioural shifts in response to disturbance may appear small scale and short term, but have the potential to fundamentally alter ecological outcomes, especially in already-degraded ecosystems that are vulnerable and sensitive to change.

Background: Hepatitis C virus (HCV) and hepatitis B virus (HBV) coinfection are associated with increased mortality in people with HIV (PWH), and hyperglycemia is a common comorbidity in PWH. In this study, we used routinely collected clinical data to assess the associations between HBV and HCV seropositivity with all-cause mortality and whether this relationship differs by hyperglycemia status., Methods: Eligible participants included adult PWH (≥15 years) who initiated antiretroviral therapy between May 2005 and June 2016 in Myanmar. HBV and HCV serostatus and hyperglycemia were measured at enrollment to HIV care using HBV surface antigen, HCV antibody tests, and random blood glucose (≥140 mg/dL), respectively., Results: Among 27 722 PWH, 2260 (8%) were HBV seropositive, 2265 (9%) were HCV seropositive, 178 (0.6%) were HBV-HCV seropositive, and 1425 (5%) had hyperglycemia. During the median follow-up (interquartile range) of 3.1 (1.5-5.1) years, 3655 (13%) PWH died, and the overall mortality rate was 3.8 (95% CI, 3.7-3.9) per 100-person-years (PY). The mortality rate (per 100 PY) among PWH who were HBV seropositive was 4.6, among PWH who were HCV seropositive it was 5.1, and among PWH who were HBV-HCV seropositive it was 7.1. When stratified by glycemic status, the mortality rate was higher among patients with hyperglycemia compared with those with euglycemia (5.4 vs 4.0 per 100 PY), and the difference in mortality rate between patients with hyperglycemia and euglycemia was highest among those with HCV seropositivity (9.8 vs 5.0 per 100 PY)., Conclusions: Increased mortality rates associated with HBV and HCV seropositivity in PWH differed by their glycemic status. PWH with HCV seropositivity and hyperglycemia had the highest mortality rates., Competing Interests: Potential conflicts of interest. All 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., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Competing Interests: KGC declares salary support to serve as US Agency for International Development (USAID) senior TB scientific advisor through an Inter-governmental Personnel Act award between Emory University and the USAID. FN and AZ acknowledge support from the EU European & Developing Countries Clinical Trials Partnership-funded Pan-African Network for Rapid Research, Response, Relief and Preparedness for infectious diseases epidemics (PANDORA-ID-NET), Central African Network on Tuberculosis, HIV/AIDS and Malaria (CANTAM-3), and East African Consortium for Clinical Research (EACCR3) programmes. AZ is in receipt of a UK National Institutes for Health Research Senior Investigator award and is a Mahathir Foundation Science Award and Pascoal Mocumbi Prize laureate. All other authors declare no competing interests. The views expressed in this Comment are entirely those of the authors and do not reflect the views of their respective institutions.

Competing Interests: KGC declares salary support to serve as US Agency for International Development (USAID) senior tuberculosis scientific advisor through an intergovernmental personnel act award between Emory University and USAID. AZ, FN, and DY-M acknowledge support from the EU-EDCTP funded PANDORA-ID-NET, CANTAM-3, and EACCR-3 programmes. AZ is in receipt of a UK National Institute for Health Research Senior Investigator Award. JBN acknowledges support from the US National Institutes of Health (NIH) Fogarty International Center (grants 1R25TW011217-01, 1R21TW011706-01, and 1D43TW010937-01A1) and NIH National Institute of Allergy and Infectious Diseases (grant U01 AI096299). All other authors declare no competing interests. All authors have a specialist interest in global epidemics of COVID-19, tuberculosis, and HIV. The views expressed in this editorial are entirely those of the authors and do not reflect the views of their respective institutions.

Isolates of the marine picocyanobacteria, Prochlorococcus and Synechococcus , are often accompanied by diverse heterotrophic "contaminating" bacteria, which can act as confounding variables in otherwise controlled experiments. Traditional microbiological methods for eliminating contaminants, such as direct streak-plating, are often unsuccessful with this particular group of microorganisms. While they will grow in pour plates, colonies often remain contaminated with heterotrophic bacteria that can migrate through the soft agar. Additionally, axenic clones of picocyanobacteria can be recovered via dilution-to-extinction in liquid medium, but the efficiency of recovery is low, often requiring large numbers of 96-well plates. Here, we detail a simple and effective protocol for rendering cultures of Synechococcus and Prochlorococcus strains free of bacterial contaminants while at the same time yielding clonal isolates. We build on the fact that co-culture with specific heterotrophs-"helper heterotrophs"-is often necessary to grow colonies of picocyanobacteria from single cells in agar. Suspecting that direct physical contact between the helper and the picocyanobacterial cells was not necessary for the "helper effect," we developed a protocol in which the helper cells are embedded in soft agar pour plates, a filter overlaid on the surface, and a picocyanobacterial culture is diluted and then spotted on top of the filter. With this approach, motile contaminants cannot swim to the colonies, and it is possible to obtain the expected number of colonies from a given input (i.e., a Poisson distribution of colonies with an expected value equal to the input number of cells), thus ensuring clonal colonies. Using this protocol, we rendered three strains of Synechococcus , two strains of Prochlorococcus , and 19 new strains of Synechococcus from coastal seawater clonal and free of heterotrophic bacteria. The simplicity of this approach should expand the repertoire of axenic picocyanobacterial strains available for controlled physiological experiments. It will also enable the study of microdiversity in populations of picocyanobacteria by facilitating large-scale isolation of picocyanobacterial clones from a single source, including direct isolation from natural seawater., 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 Kearney, Coe, Castro and Chisholm.)

Objectives: Low BMI and hyperglycemia are each important risk factors for tuberculosis (TB). However, the contribution of synergy between low BMI and hyperglycemia to risk of TB among people living with HIV (PWH) is unexplored. We compared TB incidence among PWH with different exposure profiles to low BMI (BMI < 18.5 kg/m2) and hyperglycemia (random blood glucose ≥140 mg/dl)., Design and Methods: We conducted a cohort study using data of PWH (≥15 years) who enrolled in Myanmar's Integrated HIV Care Program between 2011 and 2017. We used their follow-up data until 2018 to determine TB incidence., Results: Among 20 865 PWH included in this study, 7610 (36%) had low BMI only, 1324 (6%) had hyperglycemia only, and 465 (2%) patients had concurrent low BMI and hyperglycemia (joint exposure) at baseline. During a median follow-up of 2.2 years (interquartile range: 0.5, 4.2), 3628 (17%) developed TB [6.7, 95% confidence interval (CI): 6.5,7.0 cases per 100 person-years (PY)]. TB incidence among PWH with joint exposure was 21.0 (95% CI: 18.0, 24.7), with low BMI only was 10.9 (95% CI: 10.4, 11.4), with hyperglycemia only was 5.2 (95% CI: 4.4, 6.3) and with no exposure was 4.6 (95% CI: 4.4, 4.9) cases per 100 PY. The attributable proportion of incident TB due to synergy between low BMI and hyperglycemia was 0.23 (95% CI: 0.06, 0.36)., Conclusion: Synergy between low BMI and hyperglycemia was associated with increased excess TB incidence in PWH. TB preventive treatment, nutritional support, and hyperglycemia management should be evaluated as interventions to reduce TB risk in PWH with joint exposure., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: An elevated risk of tuberculosis (TB) disease in persons who have received tumor necrosis factor alpha inhibitor medications (TNF-α inhibitors) has been reported for nearly two decades, but clinical diagnostic features and outcomes of TB in this population remain poorly described., Methods: We analyzed national surveillance data for TB cases among persons aged 15 years and older reported in the United States during 2010-2017 and associated mortality data reported through 2019 to describe the clinical characteristics of those receiving TNF-α inhibitors., Results: Of 70 129 TB cases analyzed, 504 (0.7%) of the patients had TNF-α inhibitor use reported at TB diagnosis. Patients with TNF-α inhibitor use at TB diagnosis were more likely than TB patients not receiving TNF-α inhibitors to have TB diagnosed in extrapulmonary sites in conjunction with pulmonary sites (28.8% vs 10.0%, P  < .001). Patients receiving TNF-α inhibitors were less likely to have acid-fast bacilli noted on sputum smear microscopy (25.6% vs 39.1%, P  = .04), and more likely to have drug-resistant disease (13.5% vs 10.0%, P  < .001). TB-attributed deaths did not significantly differ between patients receiving and not receiving TNF-α inhibitors (adjusted odds ratio, 1.46 [95% confidence interval, .95-2.26])., Conclusions: Clinicians evaluating TNF-α inhibitor-treated patients should have a high index of suspicion for TB and be aware that extrapulmonary or sputum smear-negative TB disease is more common in these patients. No significantly diminished survival of TB patients treated with TNF-α inhibitor therapy before TB diagnosis was noted., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The coronavirus disease (COVID-19) pandemic has had unprecedented negative effects on global health and economies, drawing attention and resources from many other public health services. To minimize negative effects, the parallels, lessons, and resources from existing public health programs need to be identified and used. Often underappreciated synergies relating to COVID-19 are with tuberculosis (TB). COVID-19 and TB share commonalities in transmission and public health response: case finding, contact identification, and evaluation. Data supporting interventions for either disease are, understandably, vastly different, given the diseases' different histories. However, many of the evolving issues affecting these diseases are increasingly similar. As previously done for TB, all aspects of congregate investigations and preventive and therapeutic measures for COVID-19 must be prospectively studied for optimal evidence-based interventions. New attention garnered by the pandemic can ensure that knowledge and investment can benefit both COVID-19 response and traditional public health programs such as TB programs.

Background: The KwaZulu-Natal (KZN) province of South Africa has the highest prevalence of HIV infection in the world. Viral load (VL) testing is a crucial tool for clinical and programmatic monitoring. Within uMkhanyakude district, VL suppression rates were 91% among patients with VL data; however, VL performance rates averaged only 38·7%. The objective of this study was to determine if enhanced clinic processes and community outreach could improve VL monitoring within this district., Methods: A packaged intervention was implemented at three rural clinics in the setting of the KZN HIV AIDS Drug Resistance Surveillance Study. This included file hygiene, outreach, a VL register and documentation revisions. Chart audits were used to assess fidelity. Outcome measures included percentage VL performed and suppressed. Each rural clinic was matched with a peri-urban clinic for comparison before and after the start of each phase of the intervention. Monthly sample proportions were modelled using quasi-likelihood regression methods for over-dispersed binomial data., Results: Mkuze and Jozini clinics increased VL performance overall from 33·9% and 35·3% to 75·8% and 72·4%, respectively which was significantly greater than the increases in the comparison clinics (RR 1·86 and 1·68, p < 0·01). VL suppression rates similarly increased overall by 39·3% and 36·2% (RR 1·84 and 1·70, p < 0·01). The Chart Intervention phase showed significant increases in fidelity 16 months after implementation., Conclusions: The packaged intervention improved VL performance and suppression rates overall but was significant in Mkuze and Jozini. Larger sustained efforts will be needed to have a similar impact throughout the province.

On March 15, 2020 Puerto Rico implemented non-pharmaceutical interventions (NPIs), including a mandatory curfew, as part of a state of emergency declaration to prevent the community transmission of the SARS-CoV-2 virus. The strict enforcement of this curfew was extended through May 25, with a gradual relaxation beginning on May 1. This report summarizes an assessment of these early mitigation measures on the progression of the COVID-19 pandemic in the island. From March 15 to May 15, 2020, 70,656 results of molecular (RT-PCR) tests were reported to the Puerto Rico Department of Health. Of these, 1,704 were positive, corresponding to 1,311 individuals with COVID-19 included in the study. We derived the epidemic growth rates (r) and the corresponding reproductive numbers (R) from the epidemic curve of these 1,311 individuals with laboratory-confirmed diagnosis of COVID-19 using their date of test collection as a proxy for symptoms onset. Through May 31, 2020, there were 143 COVID-19 associated deaths in Puerto Rico, for a case fatality risk of 10.9%. We compared the observed cases and deaths with Gompertz model projections had the mitigation measures not been implemented. The number of daily RT-PCR-confirmed cases peaked on March 30 (85 cases), showing a weekly cyclical trend, with lower counts on weekends and a decreasing secular trend since March 30. The initial exponential growth rate (r) was 15.87% (95% CI: 7.59%, 24.15%), corresponding to R of 1.82 (95% CI:1.37, 2.30). After March 30, the r value reverted to an exponential decay rate (negative) of -2.95% (95% CI: -4.99%, -0.92%), corresponding to R of 0.93 (95% CI: 0.86, 0.98). We estimate that, had the initial growth rate been maintained, a total of 6,155 additional COVID-19 cases would have occurred by May 15, with 211 additional COVID-19 deaths by May 31. These findings are consistent with very effective implementation of early NPIs as mitigation measures in Puerto Rico. These results also provide a baseline to assess the impact of the transition from mitigation to subsequent containment stages in Puerto Rico., Competing Interests: The authors have declared that no competing interests exist.

Background: South Africa is home to the world's largest HIV epidemic. Throughout the world, incarcerated individuals have a higher prevalence of HIV than the general public, and South Africa has one of the highest rates of incarceration in sub-Saharan Africa. In spite of this, little has been published about the burden of HIV and how care is delivered in South African correctional facilities., Objective: To estimate the prevalence of people living with HIV and identify initiation and retention in the HIV cascade of care across five correctional facilities., Methods: Cross-sectional retrospective analysis of 30,571 adult inmates who participated in a tuberculosis screening and HIV counseling and testing campaign in South African correctional facilities (January 1, 2014-January 31, 2015). Descriptive statistics were used to estimate the proportion and 95% confidence intervals of HIV. Proportions of persons retained and lost at each step in the HIV cascade of care under this intervention were calculated. Poisson regression with robust variance estimates were used, and clustering by facility was accounted for in all analyses., Results: Results of the screening campaign found previously undiagnosed HIV among 13.0% of those consenting to screening, with a total estimated HIV prevalence of 17.7% (n = 3,184, 95% CI: 17.2-18.3%) in the sample. When examining the overall cascade of care, 48.3% of those with HIV initiated care, and overall 45.6% of persons who entered care qualified for ART initiated treatment. A Poisson regression accounting for clustering by facility found HIV high risk groups within the population such as women (aRR = 1.72, 95% CI: 1.57, 1.89), those over 35 years of age (aRR = 2.43, 95% CI: 1.53, 3.85), and people incarcerated less than one year (aRR = 1.41, 95% CI: 1.19, 1.67)., Conclusion: In this setting, routine screening is recommended, and measures are needed to ensure that persons diagnosed are adequately linked to and retained in care., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Diabetes might confer a modestly increased risk of latent tuberculosis infection, which without treatment can progress to active tuberculosis disease. Three recent analyses of the National Health and Nutrition Examination Survey found a positive association between diabetes and a positive test for Mycobacterium tuberculosis infection. This study examines whether prevalence of a positive test still varies by diabetes status after stratifying by race/ethnicity., Methods: This cross-sectional analysis used the public-use National Health and Nutrition Examination Survey 2011-2012 data sets and was conducted in 2018-2019. Interview and examination results for 5,560 adult participants yielded estimates for 219 million U.S. adults in the 4 largest race/ethnicity groups. The weighted prevalence of positive tuberculin skin test or interferon-gamma release assay by diabetes status was ascertained in each group., Results: Among white and black adults, diabetes was associated with no difference in positive skin test prevalence and little difference in positive interferon-gamma release assay prevalence. The positive assay prevalence difference was +14.5% (95% CI=2.3%, 26.7%) among Hispanic and +9.9% (95% CI=1.2%, 18.6%) among Asian adults, when comparing those with diabetes with those with neither diabetes nor prediabetes. Based on assay results, 23.6% (95% CI=14.0%, 36.9%) of Hispanic and 27.2% (95% CI=19.6%, 36.5%) of Asian adults with diabetes also had latent tuberculosis infection., Conclusions: Hispanic and Asian subpopulation results drove much of the previously reported positive association between diabetes and a positive test for M. tuberculosis infection. Hispanic and Asian adults with diabetes might particularly benefit from screening and treatment for latent tuberculosis infection., (Published by Elsevier Inc.)

In June 2017, the World Health Organization issued the Guidelines on Ethical Issues in Public Health Surveillance. Using the frame of public health ethics, the guidance declared that countries have an affirmative duty to undertake surveillance and that the global community had an obligation to support those countries whose resources limited their capacity. The centrality of TB surveillance has long been recognized as a matter of public health practice and ethics. Nevertheless, contemporary global realities make clear that TB surveillance falls far short of the goal of uniform notification. It is this reality that necessitated the paradoxical turn to research studies that require informed consent and human subjects' ethical review, the very burdens that mandated notification were designed to overcome.

SETTING: Lebanon is a relatively low TB-burden country, but has a high proportion of extrapulmonary tuberculosis (EPTB). Concern has been expressed that Syrian-born refugees could add to the TB burden and rates of EPTB: since 2011, >1 000 000 Syrian refugees have entered Lebanon. OBJECTIVE: The Lebanese National Tuberculosis Programme (NTP) sought to identify factors for the high proportion of EPTB and to assess the potential impact of Syrian refugees. DESIGN: NTP line-listed data from 2014-2015 were analyzed with logistic regression identified risk factors for EPTB. A trend analysis for 2011-2015 assessed TB burden by nationality and site of TB. RESULTS: Of 1347 reported TB cases from 2014 to 2015, 507 (38%) were EPTB and 46% were Lebanese. In analysis limited to Lebanese-born, the proportion of EPTB cases was relatively stable, 47% in 2011 and 52% in 2015. Modeling identified risk factors for EPTB as being female (aOR 1.79, 95%CI 1.39-2.32) and 5-15 years old (aOR 3.31, 95%CI 1.47-7.45) compared with children aged <5 years. Between 2011 and 2015, the proportion of TB cases among Syrian-born increased from 3% in 2011 to 21% in 2015 ( P < 0.001); however, the proportion of EPTB versus PTB cases among Syrians remained stable ( P = 0.264). CONCLUSION: Syrian TB cases increased almost 10-fold in five years (2011-2015) but their contribution to EPTB did not change. The high proportion of EPTB in Lebanon and those aged 5-15 years merits further investigation.

Background: A single 2-year National Health and Nutrition Examination Survey (NHANES) cycle is designed to provide accurate and stable estimates of conditions with prevalence of at least 10%. Recent NHANES-based estimates of a tuberculin skin test (TST) ≥10 mm in the noninstitutionalized US civilian population are at most 6.3%., Methods: NHANES included a TST in 1971-1972, 1999-2000, and 2011-2012. We examined the robustness of NHANES-based estimates of the US population prevalence of a skin test ≥10 mm with a bias analysis that considered the influence of non-US birth distributions and within-household skin test results, reclassified borderline-positive results, and adjusted for TST item nonresponse., Results: The weighted non-US birth distribution among NHANES participants was similar to that in the overall US population; further adjustment was unnecessary. We found no evidence of bias due to sampling multiple participants per household. Prevalence estimates changed 0.3% with reclassification of borderline-positive TST results and 0.2%-0.3% with adjustment for item nonresponse., Conclusions: For estimating the national prevalence of a TST ≥10 mm during these three survey cycles, a conventional NHANES analysis using the standard participant weights and masked design parameters that are provided in the public-use datasets appears robust. See video abstract at, http://links.lww.com/EDE/B636.

SETTING: Sixteen South African correctional facilities. OBJECTIVE: To determine the prevalence of and risk factors for tuberculosis (TB) in South African correctional facilities using data collected during a TB screening program in South African correctional facilities in 2015. DESIGN: Inmates in 16 South African correctional facilities were screened for TB from January to December 2015. Inmates reporting ≥1 TB symptom or having an abnormal computer-assisted digital chest X-ray (CXR) provided sputum. Abnormal CXRs were interpreted by a radiologist. Sputum was tested for Mycobacterium tuberculosis using Xpert ® MTB/RIF. Data from 16 South African correctional facilities were used in regression analysis, and prevalence estimates calculated for 12 South African correctional facilities with >30% screening coverage. RESULTS: In 12 South African correctional facilities included in the prevalence estimates, 837 inmates had TB disease (2653/100 000) as indicated by current TB treatment or screening-identified TB by radiologist or Xpert. Previous TB was associated with increased odds of screening-identified TB in HIV-positive inmates (OR 4.3, 95%CI 2.5-7.3). For HIV-negative inmates, previous TB (adjusted OR [aOR] 4.9, 95%CI 1.7-14.1) and self-reported symptoms vs. none (1 symptom, aOR 8.8, 95%CI 1.2-67.7; >2 symptoms, aOR 21.7, 95%CI 3.0-158.8) were independently associated with increased odds of screening-identified TB. CONCLUSIONS: Routine TB screening, including CXR, is needed in South African correctional facilities to identify and refer inmates with active TB.

Background: Tuberculosis (TB) Regional Training and Medical Consultation Centers (RTMCCs) were established in 2005 for TB medical consultation, training and education in the United States. A medical consultation database (MCD) captured all consultations provided by RTMCCs; we report on those provided from June 1, 2010 to May 31, 2014., Methods: All MCD consultations during 2010-2014 were categorized into: provider type, setting, consultation topic, and patient age. We analyzed data frequencies and performed subgroup analyses by RTMCC, by TB incidence for the geographical area, and by year of consultation. End-user satisfaction was assessed by a 2016 telephone evaluation of RTMCC services., Results: A total of 11,074 consultations were delivered, with 10,754 (97.1%) in the U.S. and its current or former territories. Of these, 6018 (56%) were for high, 2443 (22.7%) for medium, and 2293 (21.3%) for low TB incidence settings. Most were for adults (81.3%) and answered within 24 h (96.2%). Nearly 2/3 consultations originated from health departments; providers included mostly physicians (44.3%) or nurses (37.6%). Common consult categories included TB disease (47.7%), case management (29.8%), latent TB infection (19.3%), diagnosis (16.1%), pharmacology (14.7%) and adverse side effects (14.3%). Among adverse side effects, hepatotoxicity was most common (39.6%). Volume and nature of consult requests remained relatively stable over the four-year period. Feedback from a 2016 CDC evaluation indicated overall satisfaction with RTMCC medical consultation services., Conclusion: RTMCCS were an important source of TB medical consultation over the time-frame of this assessment and provided quality expert consultation within 24 h. RMTCCs represent a reservoir of TB subject-matter expertise in the United States., (© 2019 Published by Elsevier Ltd.)

We used tuberculosis genotyping results to derive estimates of prevalence of latent tuberculosis infection in the United States. We estimated <1% prevalence in 1,981 US counties, 1%-<3% in 785 counties, and >3% in 377 counties. This method for estimating prevalence could be applied in any jurisdiction with an established tuberculosis surveillance system.

Background: Following a concerted public health response to the resurgence of tuberculosis (TB) in the United States in the late 1980s, annual TB incidence decreased substantially. However, no estimates exist of the number and cost savings of TB cases averted., Methods: TB cases averted in the United States during 1995-2014 were estimated: Scenario 1 used a static 1992 case rate; Scenario 2 applied the 1992 rate to foreign-born cases, and a pre-resurgence 5.1% annual decline to US-born cases; and a statistical model assessed human immunodeficiency virus and TB program indices. We applied the cost of illness to estimate the societal benefits (costs averted) in 2014 dollars., Results: During 1992-2014, 368 184 incident TB cases were reported, and cases decreased by two thirds during that period. In the scenarios and statistical model, TB cases averted during 1995-2014 ranged from approximately 145 000 to 319 000. The societal benefits of averted TB cases ranged from US$3.1 to US$6.7 billion, excluding deaths, and from US$6.7 to US$14.5 billion, including deaths., Conclusions: Coordinated efforts in TB control and prevention in the United States yielded a remarkable number of TB cases averted and societal economic benefits. We illustrate the value of concerted action and targeted public health funding.

Background: Reexamining the prevalence of persons infected with tuberculosis (TB) is important to determine trends over time. In 2011-2012 a TB component was included in the National Health and Nutrition Examination Survey (NHANES) to estimate the reservoir of persons infected with TB., Methods: Civilian, noninstitutionalized U.S. population survey participants aged 6 years and older were interviewed regarding their TB history and eligibility for the tuberculin skin test (TST) and interferon gamma release assay (IGRA) blood test. Once eligibility was confirmed, both tests were conducted. Prevalence and numbers of TST positive (10 mm or greater), IGRA positive, and both TST and IGRA positive were calculated by adjusting for the complex survey design after applying corrections for item nonresponse and digit preference in TST induration measurements. To examine TST positivity over time, data from NHANES 1999-2000 were reanalyzed using the same statistical methods. The TST was performed using Tubersol, a commercially available purified protein derivative (PPD), rather than PPD-S, which was the antigen used in NHANES 1999-2000. Prior patient history of TB vaccination was not collected in this study nor were patients examined for the presence of a Bacillus of Calmette and Guerin (BCG) vaccine scar., Results: For NHANES 2011-2012, TST and IGRA results were available for 6,128 (78.4%) and 7,107 (90.9%) eligible participants, respectively. There was no significant difference between the percentage of the U.S. population that was TST positive in 2011-2012 (4.7% [95% CI 3.4-6.3]; 13,276,000 persons) compared with 1999-2000 (4.3%; 3.5-5.3). In 2011-2012 the percentage that was IGRA positive was 5.0% (4.2-5.8) and double TST and IGRA positivity was 2.1% (1.5-2.8). The point estimate of IGRA positivity prevalence in foreign-born persons (15.9%; 13.5-18.7) was lower than for TST (20.5%; 16.1-25.8) in 2011-2012. The point estimate of IGRA positivity prevalence in U.S.-born persons (2.8%; 2.0-3.8) was higher than for TST (1.5%; 0.9-2.6)., Conclusions: No statistically significant decline in the overall estimated prevalence of TST positivity was detected from 1999-2000 to 2011-2012. The prevalence of TB infection, whether measured by TST or IGRA, remains lower among persons born in the United States compared with foreign-born persons.

The lack of capacity to provide laboratory confirmation of a diagnosis of tuberculosis disease (TB) is contributing to enormous gaps in the ability to find, treat and follow TB patients. WHO estimates that globally only about 57% of the notified new cases of pulmonary TB in 2012 and about 19% of rifampicin-resistant TB cases were laboratory confirmed. The Cepheid Xpert(®) MTB/RIF assay has been credited with revolutionizing laboratory testing to aid in the diagnosis of TB and rifampicin-resistant TB. This semi-automated test can detect both the causative agent of TB and mutations that confer rifampicin resistance from clinical specimens within 2 h after starting the test. In this article, we review the performance of the test, its pathway to regulatory approval and endorsement, guidelines for its use and lessons learned from the implementation of the test in low-burden, high-resource countries and in high-burden, low-resource countries.

In March 2012, in response to reports of tuberculosis (TB) resistant to all anti-TB drugs, the World Health Organization convened an expert consultation that identified issues to be resolved before defining a new category of highly drug-resistant TB. Proposed definitions are ambiguous, and extensive drug resistance is encompassed by the already defined extensively drug-resistant (XDR) TB. There is no evidence that proposed totally resistant TB differs from strains encompassed by XDR TB. Susceptibility tests for several drugs are poorly reproducible. Few laboratories can test all drugs, and there is no consensus list of all anti-TB drugs. Many drugs are used off-label for highly drug resistant TB, and new drugs formulated to combat resistant strains would render the proposed category obsolete. Labeling TB strains as totally drug resistant might lead providers to think infected patients are untreatable. These challenges must be addressed before defining a new category for highly drug-resistant TB.

We present a mathematical transmission model of tuberculosis in the USA. The model is calibrated to recent trends of declining incidence in the US-born and foreign-born populations and is used in assessing relative impacts of treatment of latently infected individuals on elimination time, where elimination is defined as annual incidence <1 case/million. Provided current control efforts are maintained, elimination in the US-born population can be achieved before the end of this century. However, elimination in the foreign-born population is unlikely in this timeframe even with higher rates of targeted testing and treatment of residents of and immigrants to the USA with latent tuberculosis infection. Cutting transmission of disease as an interim step would shorten the time to elimination in the US-born population but foreign-born rates would remain above the elimination target.

Operational research in low-income countries has a key role in filling the gap between what we know from research and what we do with that knowledge-the so-called know-do gap, or implementation gap. Planned research that does not tangibly affect policies and practices is ineffective and wasteful, especially in settings where resources are scarce and disease burden is high. Clear parameters are urgently needed to measure and judge the success of operational research. We define operational research and its relation with policy and practice, identify why operational research might fail to affect policy and practice, and offer possible solutions to address these shortcomings. We also propose measures of success for operational research. Adoption and use of these measures could help to ensure that operational research better changes policy and practice and improves health-care delivery and disease programmes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Infectious respiratory pathogens were the suspected cause of 480 outbreaks investigated by the Centers for Disease Control and Prevention's Epidemic Intelligence Service officers during 1946-2005. All epidemic-assistance investigation reports and associated articles from scientific journals were reviewed. Investigations identified 25 different infectious respiratory pathogens including, most frequently, tuberculosis, influenza, and legionellosis. Other bacterial-, viral-, and fungal-related pathogens also were identified. Epidemic-assistance investigations were notable for first identifying Legionnaires disease and Pontiac fever, hantavirus pulmonary syndrome, and new strains of human and avian influenza, as well as emerging challenges (e.g., multidrug-resistant tuberculosis and pneumococcus). The investigations provided clinical insights into such diseases as pulmonary anthrax and identified high risks of serious respiratory illnesses for persons infected with human immunodeficiency virus, other immunocompromised persons, and persons with diabetes. They identified settings placing persons at high risk of acquiring disease, including nursing homes, prisons, homeless shelters, and hospitals. Travel also placed persons at risk. Key environmental factors related to spread of diseases and occupational risks for brucellosis and psittacosis were identified. The outbreak investigations constitute a wealth of prevention experience and provide the basis for recommendations to mitigate outbreaks and reduce future risks.

Background: Since 1953, through the cooperation of state and local health departments, the U.S. Centers for Disease Control and Prevention (CDC) has collected information on incident cases of tuberculosis (TB) disease in the United States. In 2009, TB case rates declined -11.4%, compared to an average annual -3.8% decline since 2000. The unexpectedly large decline raised concerns that TB cases may have gone unreported. To address the unexpected decline, we examined trends from multiple sources on TB treatment initiation, medication sales, and laboratory and genotyping data on culture-positive TB., Methods: We analyzed 142,174 incident TB cases reported to the U. S. National Tuberculosis Surveillance System (NTSS) during January 1, 2000-December 31, 2009; TB control program data from 59 public health reporting areas; self-reported data from 50 CDC-funded public health laboratories; monthly electronic prescription claims for new TB therapy prescriptions; and complete genotyping results available for NTSS cases. Accounting for prior trends using regression and time-series analyses, we calculated the deviation between observed and expected TB cases in 2009 according to patient and clinical characteristics, and assessed at what point in time the deviation occurred., Results: The overall deviation in TB cases in 2009 was -7.9%, with -994 fewer cases reported than expected (P < .001). We ruled out evidence of surveillance underreporting since declines were seen in states that used new software for case reporting in 2009 as well as states that did not, and we found no cases unreported to CDC in our examination of over 5400 individual line-listed reports in 11 areas. TB cases decreased substantially among both foreign-born and U.S.-born persons. The unexpected decline began in late 2008 or early 2009, and may have begun to reverse in late 2009. The decline was greater in terms of case counts among foreign-born than U.S.-born persons; among the foreign-born, the declines were greatest in terms of percentage deviation from expected among persons who had been in the United States less than 2 years. Among U.S.-born persons, the declines in percentage deviation from expected were greatest among homeless persons and substance users. Independent information systems (NTSS, TB prescription claims, and public health laboratories) reported similar patterns of declines. Genotyping data did not suggest sudden decreases in recent transmission., Conclusions: Our assessments show that the decline in reported TB was not an artifact of changes in surveillance methods; rather, similar declines were found through multiple data sources. While the steady decline of TB cases before 2009 suggests ongoing improvement in TB control, we were not able to identify any substantial change in TB control activities or TB transmission that would account for the abrupt decline in 2009. It is possible that other multiple causes coincident with economic recession in the United States, including decreased immigration and delayed access to medical care, could be related to TB declines. Our findings underscore important needs in addressing health disparities as we move towards TB elimination in the United States.

Background: In accordance with WHO guidelines, people with HIV infection in Botswana receive daily isoniazid preventive therapy against tuberculosis without obtaining a tuberculin skin test, but duration of prophylaxis is restricted to 6 months. We aimed to assess effectiveness of extended isoniazid therapy., Methods: In our randomised, double-blind, placebo-controlled trial we enrolled adults infected with HIV aged 18 years or older at government HIV-care clinics in Botswana. Exclusion criteria included current illness such as cough and an abnormal chest radiograph without antecedent tuberculosis or pneumonia. Eligible individuals were randomly allocated (1:1) to receive 6 months' open-label isoniazid followed by 30 months' masked placebo (control group) or 6 months' open-label isoniazid followed by 30 months' masked isoniazid (continued isoniazid group) on the basis of a computer-generated randomisation list with permuted blocks of ten at each clinic. Antiretroviral therapy was provided if participants had CD4-positive lymphocyte counts of fewer than 200 cells per μL. We used Cox regression analysis and the log-rank test to compare incident tuberculosis in the groups. Cox regression models were used to estimate the effect of antiretroviral therapy. The trial is registered at ClinicalTrials.gov, number NCT00164281., Findings: Between Nov 26, 2004, and July 3, 2009, we recorded 34 (3·4%) cases of incident tuberculosis in 989 participants allocated to the control group and 20 (2·0%) in 1006 allocated to the continued isoniazid group (incidence 1·26% per year vs 0·72%; hazard ratio 0·57, 95% CI 0·33-0·99, p=0·047). Tuberculosis incidence in those individuals receiving placebo escalated approximately 200 days after completion of open-label isoniazid. Participants who were tuberculin skin test positive (ie, ≥5 mm induration) at enrolment received a substantial benefit from continued isoniazid treatment (0·26, 0·09-0·80, p=0·02), whereas participants who were tuberculin skin test-negative received no significant benefit (0·75, 0·38-1·46, p=0·40). By study completion, 946 (47%) of 1995 participants had initiated antiretroviral therapy. Tuberculosis incidence was reduced by 50% in those receiving 360 days of antiretroviral therapy compared with participants receiving no antiretroviral therapy (adjusted hazard ratio 0·50, 95% CI 0·26-0·97). Severe adverse events and death were much the same in the control and continued isoniazid groups., Interpretation: In a tuberculosis-endemic setting, 36 months' isoniazid prophylaxis was more effective for prevention of tuberculosis than was 6-month prophylaxis in individuals with HIV infection, and chiefly benefited those who were tuberculin skin test positive., Funding: US Centers for Disease Control and Prevention and US Agency for International Development., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We reflect on remarkable accomplishments in global tuberculosis (TB) control and identify persistent obstacles to the successful elimination of TB from the United States and globally. One hundred and twenty nine years after Koch's discovery of the etiologic agent of TB, this health scourge continues to account for 9.4 million cases and 1.7 million deaths annually worldwide. Implementation of the Directly Observed Treatment Short-course strategy from 1995 through 2009 has saved 6 million lives. TB control is increasingly being achieved in countries with high-income economies, yet TB continues to plague persons living in countries with low-income and lower-middle-income economies. To accelerate progress against the global effects of disease caused by TB and achieve its elimination, we must bridge 3 key gaps in implementation, knowledge, and ambition.

Rapid expansion of the standardised approach to tuberculosis diagnosis and treatment that is recommended by WHO allowed more than 36 million people to be cured between 1995 and 2008, averting up to 6 million deaths. Yet tuberculosis remains a severe global public health threat. There are more than 9 million new cases every year worldwide, and the incidence rate is falling at less than 1% per year. Although the overall target related to the Millennium Development Goals of halting and beginning to reverse the epidemic might have already been reached in 2004, the more important long-term elimination target set for 2050 will not be met with present strategies and instruments. Several key challenges persist. Many vulnerable people do not have access to affordable services of sufficient quality. Technologies for diagnosis, treatment, and prevention are old and inadequate. Multidrug-resistant tuberculosis is a serious threat in many settings. HIV/AIDS continues to fuel the tuberculosis epidemic, especially in Africa. Furthermore, other risk factors and underlying social determinants help to maintain tuberculosis in the community. Acceleration of the decline towards elimination of this disease will need invigorated actions in four broad areas: continued scale-up of early diagnosis and proper treatment for all forms of tuberculosis in line with the Stop TB Strategy; development and enforcement of bold health-system policies; establishment of links with the broader development agenda; and promotion and intensification of research towards innovations., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Context: Worldwide emergence of extensively drug-resistant tuberculosis (XDR-TB) has raised global public health concern, given the limited therapy options and high mortality., Objectives: To describe the epidemiology of XDR-TB in the United States and to identify unique characteristics of XDR-TB cases compared with multidrug-resistant TB (MDR-TB) and drug-susceptible TB cases., Design, Setting, and Patients: Descriptive analysis of US TB cases reported from 1993 to 2007. Extensively drug-resistant TB was defined as resistance to isoniazid, a rifamycin, a fluoroquinolone, and at least 1 of amikacin, kanamycin, or capreomycin based on drug susceptibility test results from initial and follow-up specimens., Main Outcome Measures: Extensively drug-resistant TB case counts and trends, risk factors for XDR-TB, and overall survival., Results: A total of 83 cases of XDR-TB were reported in the United States from 1993 to 2007. The number of XDR-TB cases declined from 18 (0.07% of 25 107 TB cases) in 1993 to 2 (0.02% of 13 293 TB cases) in 2007, reported to date. Among those with known human immunodeficiency virus (HIV) test results, 31 (53%) were HIV-positive. Compared with MDR-TB cases, XDR-TB cases were more likely to have disseminated TB disease (prevalence ratio [PR], 2.06; 95% confidence interval [CI], 1.19-3.58), less likely to convert to a negative sputum culture (PR, 0.55; 95% CI, 0.33-0.94), and had a prolonged infectious period (median time to culture conversion, 183 days vs 93 days for MDR-TB; P < .001). Twenty-six XDR-TB cases (35%) died during treatment, of whom 21 (81%) were known to be HIV-infected. Mortality was higher among XDR-TB cases than among MDR-TB cases (PR, 1.82; 95% CI, 1.10-3.02) and drug-susceptible TB cases (PR, 6.10; 95% CI, 3.65-10.20)., Conclusion: Although the number of US XDR-TB cases has declined since 1993, coinciding with improved TB and HIV/AIDS control, cases continue to be reported each year.