Advanced pulmonary tuberculosis in Alameda County: Ten-year incidence and risk factors.

Background: Advanced pulmonary tuberculosis (APT) may reflect delays in tuberculosis (TB) diagnosis and contribute to ongoing disease transmission and poor outcomes. We characterized trends and factors associated with APT over ten years in a high TB-burden county within the United States. Methods: We evaluated microbiologically and clinically confirmed TB cases reported to the Alameda County Public Health Department during 2010-2019. APT was defined as the presence of cavitation on chest imaging and positive acid-fast bacilli sputum smear. Over the ten-year period, we determined overall incidence and annual trends, and conducted multivariable logistic regression to identify sociodemographic and clinical factors associated with APT. Results: We included 997 cases with pulmonary TB, of which 128 (12.8 %) had APT. The 10-year incidence of APT was 8.8 cases per 100,000, with no significant change in proportion over time. The median age of cases with APT were 50 years (IQR 32-61), 68 % were male, and 78.9 % were non-US-born. On multivariable assessment, APT cases were more likely than non-APT cases to use drugs in the past year (aOR 2.43, 95 % CI 1.10-35.09), to have diabetes (aOR 2.51, 95 % CI: 1.59-3.96), and be HIV negative (aOR 9.32 versus HIV positive, 95 % CI 1.87-169.77). While US nativity was not significantly associated with APT, it was an effect modifier. In stratified analysis, APT was more likely among those with drug-use in the last year among US-born, while diabetes was associated with APT among non-US-born individuals. Conclusions: APT remains a substantial proportion of TB cases. Efforts to increase awareness and access to care are needed for key risk groups including those with recent drug use or diabetes, with consideration of cultural and linguistic factors given differences by US nativity.

Epidemiology of Chronic Hepatitis B Virus Infection, Alameda County, California, 2017-2021.

CONTEXT: In the United States, chronic hepatitis B (CHB) virus infection predominantly affects ethnic minorities and vulnerable populations. OBJECTIVE: We analyzed surveillance data to describe CHB epidemiology to guide hepatitis B virus (HBV) elimination efforts in Alameda County. DESIGN: Persons with CHB during 2017-2021 were identified by ≥2 positive HBV tests (ie, HBsAg, HbeAg, and HBV DNA) ≥180 days apart using data from California Reportable Disease Information Exchange. Persons with CHB were stratified by age, race/ethnicity, zip code-based Healthy Places Index (HPI), and federally designated Medically Underserved Areas (MUA). Comparisons of reported CHB prevalence between groups utilized z test; comparisons between MUA regions utilized chi-square testing. RESULTS: A total of 8122 persons with CHB were identified; reported 5-year CHB prevalence was 0.53% (95% confidence interval: 0.52%-0.54%). Reported CHB 5-year prevalence was significantly higher among persons aged 50 to 69 years old than persons aged 30 to 49 years old (0.99%, 0.78%; P < .001) and Asians, Native Hawaiian/Pacific Islanders, African Americans compared to Whites (1.22%, 0.56%, 0.18%, 0.06%; P < .001). Reported CHB 5-year prevalence in the 2 lowest and most disadvantaged HPI quartiles was significantly higher than the 2 highest quartiles (0.55%, 0.68%, 0.37%, 0.42%; P < .001). The 1918 persons with CHB in MUA, compared to 5859 non-MUA persons, were significantly more likely to be African American (7%, 3%; P < .001) and from the lowest HPI quartile (79%, 19%; P < .001). CONCLUSIONS: Reported CHB 5-year prevalence in Alameda County was 1.5 times the national prevalence estimates, and reported prevalence was highest among Asians and persons in more disadvantaged areas. Analysis of local CHB surveillance data can guide public health efforts toward HBV elimination.

Tuberculosis and Chronic Hepatitis B Virus Infection Screening Among Non-US-Born Persons in an Integrated Health System in California.

Background: Tuberculosis infection (TBI) and chronic hepatitis B virus (HBV) infection disproportionately affect non-US-born persons. Early identification and treatment are critical to reduce transmission, morbidity, and mortality, but little is known about screening in the United States. Methods: We conducted a cross-sectional study in a large integrated California health system in September 2022 assessing TBI and HBV screening among persons aged ≥18 years who were born in countries with high TB burden (TB disease incidence rates ≥20/100 000 population) and/or HBV burden (hepatitis B surface antigen seroprevalence >2%). Results: Of 510 361 non-US-born persons born in countries with high TB burden, 322 027 (63.1%) were born in countries with high HBV burden and 188 334 (36.9%) in countries with only high TB burden. Among persons born in countries with high TB and HBV burden, 29.6% were screened for TBI, 64.5% for HBV, and 23.4% for TBI and HBV; 9.9% had TBI and 3.1% had HBV infection. Among persons born in countries with high TB burden only, 27.9% were screened for TBI and 7.5% had TBI. Conclusions: Among non-US-born persons from countries with high TB and HBV burden, we found low screening rates and elevated prevalence of TBI and chronic HBV infection. Cotesting for TBI and HBV infection in non-US-born persons from countries with high TB and HBV burden might improve outcomes by identifying persons who warrant TBI treatment, HBV treatment, or HBV vaccination. Increased screening is the first step in reducing health inequities and overall disease burden.

Characterization of Individuals With Hepatitis B Virus-Related Cirrhosis in a Large Integrated Health Care Organization, 2008-2019.

CONTEXT: Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), is a risk factor for cirrhosis. The management of HBV-related cirrhosis is challenging, with guidelines recommending treatment initiation and regular monitoring for those affected. OBJECTIVE: Our study characterized Kaiser Permanente Southern California patients with HBV-related cirrhosis and assessed whether they received recommended laboratory testing and imaging monitoring. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: We identified KPSC members aged ≥18 years with CHB (defined by 2, consecutive positive hepatitis B surface antigens ≥6 months apart) from 2008 to 2019. Of these patients, we further identified patients with potential HBV-related cirrhosis through ICD-10 code diagnosis, adjudicated via chart review. MAIN OUTCOME MEASURES: Age, race/ethnicity, laboratory tests (eg, alanine aminotransferase [ALT]), and hepatocellular carcinoma (HCC) screening (based on standard screening recommendations via imaging) were described in those with HBV-related cirrhosis versus those without. RESULTS: Among patients with CHB, we identified 65 patients with HBV-related cirrhosis over ~8 years. Diabetes was the most common comorbidity and was approximately 3 times more prevalent among patients with cirrhosis compared to patients without cirrhosis (21.5% vs. 7.1%). Of the 65 patients with cirrhosis, 72.3% (N = 47) received treatment. Generally, we observed that liver function tests (eg, ALT) were completed frequently in this population, with patients completing a median of 10 (6, 16) tests/year. All patients with cirrhosis had ≥1 ALT completed over the study period, and almost all cirrhotic patients (N = 64; 98.5%) had ≥1 HBV DNA test. However, the proportion of yearly imaging visits completed varied across the study years, between 64.0% in 2012 and 87.5% in 2009; overall, 35% (N = 23) completed annual imaging. CONCLUSIONS: Our findings suggest that among patients with HBV-related cirrhosis, at the patient-level, completed imaging orders for HCC screening were sub-optimal. However, we observed adequate disease management practices through frequent liver function tests, linkage to specialty care, image ordering, and shared EHR between KPSC providers.

Screening Practices and Risk Factors for Co-Infection with Latent Tuberculosis and Hepatitis B Virus in an Integrated Healthcare System - California, 2008-2019.

BACKGROUND: Hepatitis B virus (HBV) and latent tuberculosis infection are associated with a significant global burden, but both are underdiagnosed and undertreated. We described the screening patterns and risk factors for co-infection with latent tuberculosis and HBV within a large healthcare system. METHODS: Using data from Kaiser Permanente Southern California during 2008-2019, we described HBV infections, defined as a positive HBV surface antigen, e-antigen, or DNA test, and latent tuberculosis, defined as a positive Mantoux tuberculin skin test or interferon-gamma release assay test. We estimated adjusted odds ratios (aOR) for co-infection among screened adults with either infection. RESULTS: Among 1997 HBV patients screened for latent tuberculosis, 23.1% were co-infected, and among 35,820 patients with latent tuberculosis screened for HBV, 1.3% were co-infected. Among HBV patients, co-infection risk was highest among Asians compared with White race/ethnicity (29.4% vs 5.7%, aOR 4.78; 95% confidence interval [CI], 2.75-8.31), and persons born in a high-incidence country compared with low-incidence countries (31.0% vs 6.6%; aOR 4.19; 95% CI, 2.61-6.73). For patients with latent tuberculosis, risk of co-infection was higher among Asian (aOR 9.99; 95% CI, 5.79-17.20), or Black race/ethnicity (aOR 3.33; 95% CI, 1.78-6.23) compared with White race/ethnicity. Persons born in high-incidence countries had elevated risk of co-infection compared with persons born in low-incidence countries (aOR 2.23; 95% CI, 1.42-3.50). However, Asians or persons born in high-incidence countries were screened at similar rates to other ethnicities or persons born in low-incidence countries. CONCLUSIONS: Latent tuberculosis risk is elevated among HBV patients, and vice versa. Risk of co-infection was highest among persons born in high-incidence countries and Asians. These findings support recent guidelines to increase HBV and tuberculosis screening, particularly among persons with either infection.

On-treatment risks of cirrhosis and hepatocellular carcinoma among a large cohort of predominantly non-Asian patients with non-cirrhotic chronic hepatitis B.

Background & Aims: The vast majority of studies evaluating differences in on-treatment risks of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) have been conducted in Asia. Data on the course of CHB on antiviral therapy among predominantly non-Asian populations is less well described. We aimed to evaluate overall risks of cirrhosis and HCC and the influence of baseline factors on this risk among a predominantly non-Asian cohort of patients with CHB in the US. Methods: Using longitudinal data from the national Veterans Affairs database, we evaluated the incidence of cirrhosis or HCC among adults with non-cirrhotic CHB on continuous antiviral therapy. Cumulative incidence functions and adjusted Cox proportional hazards models employed competing risks methods and evaluated overall risk and predictors of developing cirrhosis or HCC while on treatment. Results: Among 2,496 patients with non-cirrhotic CHB (39.1% African American, 38.4% non-Hispanic White, 18.8% Asian, mean age 58.0 ± 13.4 years), the overall incidences of cirrhosis and HCC were 3.99 per 100 person-years (95% CI 3.66-4.35) and 0.43 per 100 person-years (95% CI 0.33-0.54), respectively. The highest incidences of cirrhosis and HCC were observed in non-Hispanic White patients (5.74 and 0.52 per 100 person-years, respectively), which were significantly higher than in Asian patients (1.93 and 0.17 per 100 person-years, respectively, p <0.0001). On multivariate regression, only baseline FIB-4 score was consistently associated with long-term risk of cirrhosis or HCC. Conclusions: Using a longitudinal cohort of predominantly non-Asian Veterans with non-cirrhotic CHB on antiviral therapy (an understudied population), we provide important epidemiological data to describe long-term risks of cirrhosis and HCC. Impact and implications: In one of the largest studies to date of a predominantly non-Asian cohort of patients with non-cirrhotic chronic hepatitis B, we provide important epidemiological data describing the long-term risks of cirrhosis and hepatocellular carcinoma among patients on antiviral therapies. Among this understudied population, the overall incidence of cirrhosis was 3.99 per 100-person-years (95% CI 3.66-4.35) and of HCC was 0.43 per 100-person-years (95% CI 0.33-0.54). These data also emphasize the importance of continued monitoring and HCC surveillance among CHB patients who are maintained on antiviral therapies.

Cardiovascular Disease Risk and Statin Use Among Adults with Metabolic Dysfunction Associated Fatty Liver Disease.

BACKGROUND: A leading cause of mortality in fatty liver disease is cardiovascular disease. Metabolic dysfunction-associated fatty liver disease (MAFLD) is new terminology that classifies fatty liver due to metabolic dysfunction attributable to obesity and associated complications. We evaluated atherosclerotic cardiovascular disease (ASCVD) risk and statin use in adults with MAFLD. METHODS: This was a retrospective study of the 2011-2018 National Health and Nutrition Examination Survey. Adults with MAFLD were identified using established criteria: presence of hepatic steatosis (US Fatty Liver Index>30) plus ≥1 of the following: 1) body mass index >25 kg/m2 in non-Asians or >23 kg/m2 in Asians, 2) diabetes mellitus, and 3) ≥2 metabolic risk factors. Cardiovascular disease risk was estimated using the validated 10-year ASCVD risk score. Statin use was assessed in intermediate and high 10-year ASCVD risk groups. RESULTS: Prevalence of MAFLD was 34.8% (95% confidence interval [CI], 33.9%-35.8%), comprising 54.4% males, 27.9% aged 65 years and older, and 38.2% non-Hispanic white. Among adults with MAFLD, 23.3% and 23.0% had intermediate and high 10-year ASCVD risk, respectively. Compared with females, males were more likely to have high 10-year ASCVD risk (28.7% vs 16.1%, adjusted odds ratio 5.24, 95% CI, 3.87-7.10, P < .01). In intermediate and high ASCVD risk groups, overall statin use was 48.3% (95% CI, 46.1-51.3). CONCLUSIONS: Over 46% of adults with MAFLD had intermediate or high 10-year ASCVD risk. Statin use was underutilized at 48.3% in those meeting statin criteria. These findings are alarming given the high cardiovascular disease risk and low statin use in this cohort.

Epidemiology of Culture-Negative Pulmonary Tuberculosis-Alameda County, 2010-2019.

CONTEXT: Patients with culture-negative pulmonary TB (PTB) can face delays in diagnosis that worsen outcomes and lead to ongoing transmission. An understanding of current trends and characteristics of culture-negative PTB can support earlier detection and access to care. OBJECTIVE: Describe epidemiology of culture-negative PTB. DESIGN, SETTING, PARTICIPANTS: We utilized Alameda County TB surveillance data from 2010 to 2019. Culture-negative PTB cases met clinical but not laboratory criteria for PTB per US National Tuberculosis Surveillance System definitions. We calculated trends in annual incidence and proportion of culture-negative PTB using Poisson and weighted linear regression, respectively. We further compared demographic and clinical characteristics among culture-negative versus culture-positive PTB cases. RESULTS: During 2010-2019, there were 870 cases of PTB, of which 152 (17%) were culture-negative. The incidence of culture-negative PTB declined by 76%, from 1.9/100 000 to 0.46/100 000 ( P for trend <.01), while the incidence of culture-positive PTB reduced by 37% (6.5/100 000 to 4.1/100 000, P for trend =.1). Culture-negative PTB case-patients were more likely than culture-positive PTB case-patients to be younger (7.9% were children <15 years old vs 1.1%; P < .01), recent immigrants within 5 years of arrival (38.2% vs 25.5%; P < .01), and have a TB contact (11.2% vs 2.9%; P < .01). Culture-negative PTB case-patients were less likely than culture-positive PTB case-patients to be evaluated because of TB symptoms (57.2% vs 74.7%; P < .01) or have cavitation on chest imaging (13.1% vs 38.8%; P < .01). At the same time culture-negative PTB case-patients were less likely to die during TB treatment (2.0% vs 9.6%; P < .01). CONCLUSIONS: The incidence of culture-negative PTB disproportionately declined compared with culture-positive TB and raises concern for gaps in detection. Expansion of screening programs for recent immigrants and TB contacts and greater recognition of risk factors may increase detection of culture-negative PTB.

Prevalence of hepatitis B virus (HBV) and latent tuberculosis co-infection and risk of drug-induced liver injury across two large HBV cohorts in the United States.

The epidemiology of latent tuberculosis and hepatitis B virus (HBV-LTBI) co-infection among U.S. populations is not well studied. We aim to evaluate LTBI testing patterns and LTBI prevalence among two large U.S. cohorts of adults with chronic HBV (CHB). Adults with CHB in the Chronic Hepatitis Cohort Study (CHeCS) and Veterans Affairs national cohort were included in the analyses. Prevalence of HBV-LTBI co-infection was defined as the number of HBV patients with LTBI divided by the number of HBV patients in a cohort. Multivariable logistic regression evaluated odds of HBV-LTBI co-infection among CHB patients who underwent TB testing. Among 6019 CHB patients in the CHeCS cohort (44% female, 47% Asian), 9.1% were tested for TB, among whom 7.7% had HBV-LTBI co-infection. Among HBV-LTBI co-infected patient, only 16.7% (n = 7) received LTBI treatment, among whom 28.6% (n = 2) developed DILI. Among 12,928 CHB patients in the VA cohort (94% male, 42% African American, 39% non-Hispanic white), 14.7% were tested for TB, among whom 14.5% had HBV-LTBI. Among HBV-LTBI co-infected patient, 18.6% (n = 51) received LTBI treatment, among whom 3.9% (n = 3) developed DILI. Presence of cirrhosis, race/ethnicity, and country of birth were observed to be associated with odds of HBV-LTBI co-infection among CHB patients who received TB testing. In summary, among two large distinct U.S. cohorts of adults with CHB, testing for LTBI was infrequent despite relatively high prevalence of HBV-LTBI co-infection. Moreover, low rates of LTBI treatment were observed among those with HBV-LTBI co-infection.

Tuberculosis Disease Among Adults Aged 65 Years and Older: Alameda County, California, 2016-2019.

Background: Older adults aged ≥65 years old represent an increasing proportion of tuberculosis (TB) cases in the United States, but limited evidence exists on the characteristics and treatment outcomes that differentiate them from younger adults. Methods: We evaluated Alameda County TB surveillance data from 2016 to 2019 and abstracted public health charts for older adult TB cases. Clinical presentation and treatment outcomes were compared in older and younger adults (15-64 years), and multivariable logistic regression was conducted to assess risk factors for TB treatment noncompletion among older adults. Results: Of 517 TB cases, 172 (33.2%) were older adults and 101 were ≥75 years old. Compared to younger adults, older TB cases were more likely to be non-US-born, and have diabetes. For diagnosis, older adults were more likely to have negative interferon-gamma release assays (24.6% vs 16.0%; P = .01) and were less likely to have cavitary disease (18.6% vs 26.7%; P < .001). One third of older adults experienced an adverse event; older adults were less likely to complete TB treatment (77.7% vs 88.4%; P = .002) and were more likely to die during TB treatment (16.3% vs 2.9%; P < .01), especially among those ≥75 years old, who had a mortality rate of 22.9%. In multivariable analysis, dementia was significantly associated with treatment noncompletion (adjusted odds ratio, 5.05; 95% confidence interval, 1.33-20.32; P = .02). Conclusions: Diabetes, negative diagnostic tests, and poor treatment outcomes were more prevalent in older adult TB cases. A greater understanding of their TB presentation and comorbidities will inform interventions to improve outcomes among older adults.

Review of Updated Hepatitis B Vaccine Recommendations and Potential Challenges With Implementation.

Hepatitis B virus (HBV) infection is a vaccine-preventable disease associated with substantial morbidity and mortality. Although safe and effective hepatitis B vaccines are available, an increased number of adults must receive the hepatitis B vaccine in order to reach the goal of the US Department of Health and Human Services for HBV elimination. Previous guidelines from the US Centers for Disease Control and Prevention (CDC) for hepatitis B vaccination among adults utilized a risk-based approach that may have contributed to decreased uptake of the vaccine because the recommendations were difficult to adopt into clinical practice and assumed patients would recognize and disclose their risk factors. Based on review of epidemiologic and cost-effectiveness data, the CDC now recommends that all adults 19 to 59 years old receive the hepatitis B vaccine; however, a risk-based approach to hepatitis B vaccination was retained among adults age 60 years and older because universal vaccination in this age group would not lead to substantial reductions in acute HBV cases and be cost-effective. Implementation of these expanded hepatitis B vaccination recommendations in clinical and public health practice may pose challenges, including ensuring effective HBV screening practices, quality measures to track coverage of the hepatitis B vaccine, utilization of hepatitis B vaccines that have the highest completion rates for the vaccine series in a real-world setting, and sustained efforts to vaccinate high-risk groups such as individuals experiencing incarceration, utilizing sexually transmitted disease clinics, and injecting illicit drugs.

Risk of drug-induced liver injury in chronic hepatitis B and tuberculosis co-infection: A systematic review and meta-analysis.

Patients with tuberculosis (TB) disease treated with multi-drug regimens are at risk of developing drug induced liver injury (DILI), and DILI risk might be even higher in patients with underlying liver disease. We aimed to evaluate whether underlying chronic hepatitis B virus (HBV) and TB co-infection are associated with a higher risk of TB therapy-related DILI. We conducted a systematic review and meta-analysis using MEDLINE/PubMed from inception to 31 December 2021. Primary outcome assessed was development of DILI following multi-drug TB treatment. Meta-analysis using random-effects models were utilized to evaluate whether underlying chronic HBV was associated with increased risk of DILI in patients undergoing active TB treatment. A total of 10 studies met inclusion criteria to be analysed, among which 520 patients had HBV-TB co-infection and 2988 patients had active TB disease without HBV. Prevalence of DILI was 21.9% in HBV-TB co-infected patients and 11.9% in TB patients without HBV. On meta-analysis, HBV-TB co-infected patients had significantly higher risk of DILI when treated with TB therapies compared with TB patients without HBV (pooled risk ratio 1.98, 95% CI 1.38-2.83, I2  = 68%). Sub-analysis of prospective cohort studies conducted after year 2000 detected a pooled risk ratio of 2.75 (95% CI 2.10-3.59, I2  = 0%). In conclusion, HBV-TB co-infected patients undergoing multi-drug TB therapy have 2-3 times higher risk of DILI compared with TB patients without HBV. Routine HBV screening prior to initiation of TB therapy is critical for early identification of HBV-TB co-infection, so that clinicians can modify TB and HBV treatment and management to reduce risks of DILI.

Prevalence of Hepatitis B Virus and Latent Tuberculosis Coinfection in the United States.

CONTEXT: Underlying chronic hepatitis B virus (HBV) infection increases the risk of drug-induced liver injury (DILI) when receiving tuberculosis therapies. Prevalence of HBV and latent tuberculosis infection (LTBI) coinfection is not well reported and no studies have evaluated testing patterns for and prevalence of HBV-LTBI coinfection in the United States. OBJECTIVE: To evaluate patterns of HBV and LTBI testing and prevalence of HBV-LTBI coinfection in the United States. DESIGN: Retrospective cohort study. SETTING: Quest Diagnostics clinical laboratory data, 2014-2020. PATIENTS: Chronic HBV infection was defined as any combination of 2 positive HBV surface antigen, HBV e antigen, or detectable HBV DNA tests at least 6 months apart. LTBI was defined as a positive QuantiFERON-TB or T-SPOT.TB test without evidence of active tuberculosis infection. MAIN OUTCOME MEASUREMENTS: Testing patterns for chronic HBV infection and LTBI and prevalence of HBV-LTBI coinfection were evaluated from 2016 through 2020 and stratified by age, sex, and race and ethnicity. RESULTS: Among 89 259 patients with chronic HBV infection, 9508 (10.7%) were tested for LTBI, among whom prevalence of HBV-LTBI coinfection was 19.6%, more than twice the observed prevalence of LTBI in patients with no chronic HBV infection in our cohort. Among 394 817 LTBI patients, 127 414 (32.3%) were tested for HBV, among whom prevalence of HBV-LTBI coinfection was 1.5%, approximately 3 times higher than prevalence of HBV infection in patients with no LTBI. The HBV-LTBI coinfection prevalence was highest among Asian Americans and older individuals. LIMITATIONS: The HBV-LTBI coinfection prevalence was likely underestimated because of suboptimal awareness and testing among at-risk populations. CONCLUSION: Among US individuals with chronic HBV infection or LTBI, prevalence of HBV-LTBI coinfection is substantial and highlights the need of testing for HBV-LTBI coinfection to mitigate risk of DILI associated with tuberculosis medications in patients with chronic HBV infection.

Global trends and the impact of chronic hepatitis B and C on disability-adjusted life years.

BACKGROUND AND AIMS: Advances in hepatitis B virus (HBV) and hepatitis C virus (HCV) therapies have improved morbidity and mortality, but global disparities in viral hepatitis outcomes remain. We evaluate global trends in the impact of HBV and HCV on disability-adjusted life years (DALYs). METHODS: Using data from the 2010-2019 Global Burden of Diseases Study (GBD), overall all-cause DALYs for patients with acute HBV or HCV, HBV- or HCV-related cirrhosis, and HBV- or HCV-related hepatocellular carcinoma (HCC) was calculated as the sum of years of life lost because of premature death and years lived with disability. DALYs were presented as age-standardized rates per 100 000 population stratified by age and sex. RESULTS: From 2010 to 2019, the overall global impact of HBV on DALYs per 100 000 decreased from 27.6 to 20.9 for acute HBV and 168.6 to 129.8 for HBV-related cirrhosis but remained stable for HBV-related HCC. The impact of HCV on DALYs per 100 000 decreased from 5.23 to 3.3 for acute HCV, 159.2 to 146.2 for HCV-related cirrhosis, and 37.5 to 34.9 for HCV-related HCC. We observed significant differences in the impact of HBV and HCV on DALYs when stratified by world regions. CONCLUSION: Decreases in HBV and HCV DALYs from 2010 to 2019 were observed. Disparities in DALY improvements across world regions suggest unequal access to viral hepatitis care and treatment. Achieving goals of viral hepatitis elimination will require enhanced prevention efforts and funding for high-burden regions and regions that have not had substantial reductions in DALYs because of HBV and HCV.

A narrative review of tuberculosis in the United States among persons aged 65 years and older.

Tuberculosis (TB) is a preventable infectious disease that confers significant morbidity, mortality, and psychosocial challenges. As TB incidence in the United States (U.S.) decreased from 9.7/100,000 to 2.2/100,000 from 1993 to 2020, the proportion of cases occurring among adults aged 65 and older increased. We conducted a review of published literature in the U.S. and other similar low-TB-burden settings to characterize the epidemiology and unique diagnostic challenges of TB in older adults. This narrative review also provides an overview of treatment characteristics, outcomes, and research gaps in this patient population. Older adults had a 30% higher likelihood of delayed TB diagnosis, with contributing factors such as acid-fast bacilli sputum smear-negative disease (56%) and non-classical clinical presentation. At least 90% of TB cases among older adults resulted from reactivation of latent TB infection (LTBI), but guidance around when to screen and treat LTBI in these patients is lacking. In addition, routine TB testing methods such as interferon-gamma release assays were two times more likely to have false-negative results among older adults. Advanced age was also often accompanied by complex comorbidities and impaired drug metabolism, increasing the risk of treatment failure (23%) and death (19%). A greater understanding of the unique factors of TB among older adults will inform clinical and public health efforts to improve outcomes in this complex patient population and TB control in the U.S.

Screening Practices for Latent Tuberculosis Infection in Clinical Trials Evaluating Treatments for Chronic Hepatitis B Virus Infection.

Latent tuberculosis infection (LTBI) prevalence among adults with chronic hepatitis B (CHB) is two times higher than LTBI prevalence in the general adult population. Although newer CHB treatments evaluated in clinical trials modulate the immune system and potentially increase LTBI reactivation risk, it is unknown whether CHB clinical trials are screening for LTBI. We describe LTBI screening practices in CHB clinical trials. We utilized the ClinicalTrials.gov website to identify clinical trials that evaluated CHB treatments. CHB treatments were categorized according to LTBI reactivation risk as unknown, low, moderate, and high-risk. Tuberculosis burden among countries in which CHB clinical trials were conducted were defined using World Health Organization definitions. Of 651 CHB clinical trials identified, 452 (69%) were included in the final cohort, among which 337 (75%), 108 (24%), and 7 (1%) evaluated CHB medications with a low, unknown, and moderate LTBI reactivation risk, respectively. A total of 330 (73.0%) CHB clinical trials reviewed were conducted in high TB burden countries. Three (0.6%) CHB trials reviewed screened for LTBI; one each among CHB treatments with low, moderate, and high LTBI reactivation risk. Although nearly 75% of all CHB clinical trials were conducted in high TB burden countries and 25% of trials evaluated CHB treatments with an unknown LTBI reactivation risk, less than 1% of trials screened for LTBI. Consideration should be given to screen for LTBI among CHB clinical trials given high prevalence of co-infection and potential for increased LTBI reactivation risk with CHB treatments evaluated.

Global incidence and mortality of hepatitis B and hepatitis C acute infections, cirrhosis and hepatocellular carcinoma from 2010 to 2019.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) contribute to significant healthcare burden globally. We aim to provide an updated and comprehensive analysis of global trends in the incidence and mortality of HBV and HCV related acute infections, cirrhosis and hepatocellular carcinoma (HCC). Estimates of annual cause-specific disease incidence and mortality for HBV and HCV were analysed using the 2010-2019 Global Burden of Diseases, Injuries and Risk Factors Study database. Three distinct disease states were evaluated: acute infections, cirrhosis and HCC. Age-standardized disease incidence and mortality were presented per 100,000 population and stratified by age, sex, year and 21 world regions. From 2010 to 2019, overall incidence of acute HBV declined by 19.3% (95% CI 4.1-32.0, p < .05) and HBV cirrhosis declined by 15.0% (95% CI 9.8-20.7, p < .05). Incidence of HCV cirrhosis increased by 5.6% (95% CI 0.3-10.2, p < .05) and HCV HCC remained stable. Incidence of acute HCV declined until 2015, after which it began increasing. From 2010 to 2019, overall mortality for HBV cirrhosis and HCV cirrhosis declined, whereas mortality for acute infections and HCC remained stable. Major differences in HBV and HCV incidence and mortality trends were observed when stratified by world regions. In conclusion, while our analyses of global trends in HBV and HCV incidence and mortality demonstrate encouraging trends, disparities in disease epidemiology were observed across world regions. These observations will identify regions and populations where greater focus and resources are needed to continue progressing towards viral hepatitis elimination.

Epidemiology of Coronavirus Disease 2019 at a County Jail-Alameda County, California, March 2020-March 2021.

CONTEXT: Coronavirus disease 2019 (COVID-19) incidence rates are 2- to 5-fold higher among persons incarcerated in the United States than in the general population. PROGRAM OR POLICY: We describe an outbreak investigation of COVID-19 at a jail (jail A) in Alameda County during March 2020-March 2021. IMPLEMENTATION: To prevent COVID-19 cases among incarcerated persons and employees, staff at jail A and the county public health department worked to develop and recommend infection control measures implemented by jail A including, but not limited to, face covering use among incarcerated persons and staff; cohorting incarcerated persons at a higher risk of severe COVID-19 in dedicated housing units; quarantining all newly detained individuals for 14 days; and offering testing for all symptomatic incarcerated persons, newly incarcerated persons at day 2 and day 10, and all persons who resided in a housing unit where a COVID-19 case was detected. EVALUATION: A total of 571 COVID-19 cases were detected among incarcerated persons at jail A during March 2020-March 2021, which represented a total incidence of 280 per 1000 population, 5 times higher than the rate in Alameda County. Of the 571 cases among incarcerated persons, 557 (98%) were male; 415 (73%) were aged 18 to 40 years; 249 (44%) were Latino; and 180 (32%) were African American; 354 (62%) were not symptomatic; and 220 (39%) had no comorbidities. Less than 2% of infected incarcerated persons were hospitalized, and no deaths were reported. DISCUSSION: COVID-19 disproportionately impacted persons incarcerated at jail A, with higher numbers among Latinos and African Americans. Implementation of COVID-19 infection control and testing measures, and collaboration between public health, law enforcement, and health care providers may have, in part, led to reductions in morbidity and mortality associated with COVID-19 at jail A.

Public Health Expenditures and Clinical and Social Complexity of Tuberculosis Cases-Alameda County, California, July-December 2017.

CONTEXT: Alameda County, California, is a high tuberculosis (TB) burden county that reported a TB incidence rate of 8.1 per 100 000 during 2017. It is the only high TB burden California county that does not have a public health-funded TB clinic. OBJECTIVE: To describe TB public health expenditures and clinical and social complexities of TB case-patients. DESIGN, SETTING, AND PARTICIPANTS: Public health surveillance of confirmed and possible TB case-patients reported to Alameda County Public Health Department during July 1, 2017, to December 31, 2017. Social complexity status was categorized for all case-patients using surveillance data; clinical complexity status, either by surveillance definition or by the Charlson Comorbidity Index (CCI), was categorized only for confirmed TB case-patients. MAIN OUTCOME MEASURES: Total public health and per patient expenditures were stratified by insurance status. Cohen's kappa assessed concordance between clinical complexity definitions. All comparisons were conducted using Fisher's exact or Kruskal-Wallis tests. RESULTS: Of 81 case-patients reported, 68 (84%) had confirmed TB, 29 (36%) were socially complex, and 15 (19%) were uninsured. Total public health expenditures were $487 194, and 18% of expenditures were in nonlabor domains, 57% of which were for TB treatment, diagnostics, and insurance, with insured patients also incurring such expenditures. Median per patient expenditures were significantly higher for uninsured and government-insured patients than for privately insured patients ($7007 and $5045 vs $3704; P = .03). Among confirmed TB case-patients, 72% were clinically complex by surveillance definition and 53% by the CCI; concordance between definitions was poor (κ = 0.25; 95% confidence interval, 0.03-0.46). CONCLUSIONS: Total public health expenditures approached $500 000. Most case-patients were clinically complex, and about 20% were uninsured. While expenditures were higher for uninsured case-patients, insured case-patients still incurred TB treatment, diagnostic, and insurance-related expenditures. State and local health departments may be able to use our expenditure estimates by insurance status and description of clinically complex TB case-patients to inform efforts to allocate and secure adequate funding.