The global impact of COVID-19 on tuberculosis: A thematic scoping review, 2020-2023.

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.

Updated considerations in the diagnosis and management of tuberculosis infection and disease: integrating the latest evidence-based strategies.

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.

Increased All-cause Mortality in People With HIV and Comorbidities: Hepatitis B and C Virus Seropositivity and Hyperglycemia in Myanmar, 2005-2017.

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.

Association of Tumor Necrosis Factor α Inhibitor Use with Diagnostic Features and Mortality of Tuberculosis in the United States, 2010-2017.

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.

Synergy between low BMI and hyperglycemia at baseline increases tuberculosis incidence among people living with HIV.

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.

Parallels and Mutual Lessons in Tuberculosis and COVID-19 Transmission, Prevention, and Control.

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.

Assessment of early mitigation measures against COVID-19 in Puerto Rico: March 15-May 15, 2020.

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.

HIV prevalence and the cascade of care in five South African correctional facilities.

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.

Tuberculosis Infection Among People With Diabetes: United States Population Differences by Race/Ethnicity.

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.

Robustness of NHANES Estimates of the US Prevalence of a Positive Tuberculin Skin Test.

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.

Tuberculosis Regional Training and Medical Consultation Centers in the United States: Characteristics, outcomes, and quality of medical consultations, June 1, 2010 - May 31, 2014.

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.

Simple Estimates for Local Prevalence of Latent Tuberculosis Infection, United States, 2011-2015.

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.