Tuberculosis - United States, 2023.

After 27 years of declining U.S. tuberculosis (TB) case counts, the number of TB cases declined considerably in 2020, coinciding with the COVID-19 pandemic. For this analysis, TB case counts were obtained from the National TB Surveillance System. U.S. Census Bureau population estimates were used to calculate rates overall, by jurisdiction, birth origin, race and ethnicity, and age group. Since 2020, TB case counts and rates have increased each year. During 2023, a total of 9,615 TB cases were provisionally reported by the 50 U.S. states and the District of Columbia (DC), representing an increase of 1,295 cases (16%) as compared with 2022. The rate in 2023 (2.9 per 100,000 persons) also increased compared with that in 2022 (2.5). Forty states and DC reported increases in 2023 in both case counts and rates. National case counts increased among all age groups and among both U.S.-born and non-U.S.-born persons. Although TB incidence in the United States is among the lowest in the world and most U.S. residents are at minimal risk, TB continues to cause substantial global morbidity and mortality. This postpandemic increase in U.S. cases highlights the importance of continuing to engage communities with higher TB rates and their medical providers in TB elimination efforts and strengthening the capacity in public health programs to carry out critical disease control and prevention strategies.

Trends in tuberculosis clinicians' adoption of short-course regimens for latent tuberculosis infection.

Objective: Little is known about regimen choice for latent tuberculosis infection in the United States. Since 2011, the Centers for Disease Control and Prevention has recommended shorter regimens-12 weeks of isoniazid and rifapentine or 4 months of rifampin-because they have similar efficacy, better tolerability, and higher treatment completion than 6-9 months of isoniazid. The objective of this analysis is to describe frequencies of latent tuberculosis infection regimens prescribed in the United States and assess changes over time. Methods: Persons at high risk for latent tuberculosis infection or progression to tuberculosis disease were enrolled into an observational cohort study from September 2012-May 2017, tested for tuberculosis infection, and followed for 24 months. This analysis included those with at least one positive test who started treatment. Results: Frequencies of latent tuberculosis infection regimens and 95% confidence intervals were calculated overall and by important risk groups. Changes in the frequencies of regimens by quarter were assessed using the Mann-Kendall statistic. Of 20,220 participants, 4,068 had at least one positive test and started treatment: 95% non-U.S.-born, 46% female, 12% <15 years old. Most received 4 months of rifampin (49%), 6-9 months of isoniazid (32%), or 12 weeks of isoniazid and rifapentine (13%). Selection of short-course regimens increased from 55% in 2013 to 81% in late 2016 (p < 0.001). Conclusions: Our study identified a trend towards adoption of shorter regimens. Future studies should assess the impact of updated treatment guidelines, which have added 3 months of daily isoniazid and rifampin to recommended regimens.

Tuberculosis - United States, 2022.

Incidence of reported tuberculosis (TB) decreased gradually in the United States during 1993-2019, reaching 2.7 cases per 100,000 persons in 2019. Incidence substantially declined in 2020 to 2.2, coinciding with the COVID-19 pandemic (1). Proposed explanations for the decline include delayed or missed TB diagnoses, changes in migration and travel, and mortality among persons susceptible to TB reactivation (1). Disparities (e.g., by race and ethnicity) in TB incidence have been described (2). During 2021, TB incidence partially rebounded (to 2.4) but remained substantially below that during prepandemic years, raising concerns about ongoing delayed diagnoses (1). During 2022, the 50 U.S. states and the District of Columbia (DC) provisionally reported 8,300 TB cases to the National Tuberculosis Surveillance System. TB incidence was calculated using midyear population estimates and stratified by birth origin and by race and ethnicity. During 2022, TB incidence increased slightly to 2.5 although it remained lower than during prepandemic years.* Compared with that in 2021, TB epidemiology in 2022 was characterized by more cases among non-U.S.-born persons newly arrived in the United States; higher TB incidence among non-Hispanic American Indian or Alaska Native (AI/AN) and non-Hispanic Native Hawaiian or other Pacific Islander (NH/OPI) persons and persons aged ≤4 and 15-24 years; and slightly lower incidence among persons aged ≥65 years. TB incidence appears to be returning to prepandemic levels. TB disparities persist; addressing these disparities requires timely TB diagnosis and treatment to interrupt transmission and prevention of TB through treatment of latent TB infection (LTBI).

Comparison of three tests for latent tuberculosis infection in high-risk people in the USA: an observational cohort study.

BACKGROUND: Treatment of latent tuberculosis infection is an important strategy to prevent tuberculosis disease. In the USA, three tests are used to identify latent tuberculosis infection: the tuberculin skin test (TST) and two IFN-γ release assays (T-SPOT.TB and QuantiFERON). To our knowledge, few large studies have compared all three tests among people at high risk of latent tuberculosis infection or progression to tuberculosis disease. We aimed to assess test agreement between IFN-γ release assays and TST to provide guidance on their use in important risk groups. METHODS: In this observational cohort study, we enrolled participants at high risk of latent tuberculosis infection or progression to tuberculosis disease at ten US sites with 18 affiliated clinics, including close contacts of infectious tuberculosis cases, people born in countries whose populations in the USA have high (≥100 cases per 100 000 people) or moderate (10-99 cases per 100 000 people) tuberculosis incidence, and people with HIV. Participants were interviewed about demographics and medical risk factors, and all three tests were administered to each participant. The primary endpoints for this study were the proportions of positive test results by test type stratified by risk group and test concordance by risk group for participants with valid results for all three test types. The study is registered at ClinicalTrials.gov, NCT01622140. FINDINGS: Between July 12, 2012, and May 5, 2017, 26 292 people were approached and 22 131 (84·2%) were enrolled in the study. Data from 21 846 (98·7%) participants were available for analysis, including 3790 (17·3%) born in the USA and 18 023 (82·5%) born outside the USA. Among non-US-born participants overall, the RR comparing the proportions of TST-positive results (7476 [43·2%] of 17 306 participants) to QuantiFERON-positive results (4732 [26·5%] of 17 882 participants) was 1·6 (95% CI 1·6-1·7). The risk ratio (RR) for the comparison with the proportion of T-SPOT.TB-positive results (3693 [21·6%] of 17 118 participants) was 2·0 (95% CI 1·9-2·1). US-born participants had less variation in the proportions of positive results across all tests. The RRs for the proportion of TST-positive results (391 [10·9%] of 3575 participants) compared with the proportion of QuantiFERON-positive results (445 [12·0%] of 3693 participants) and T-SPOT.TB-positive results (295 [8·1%] of 3638 participants) were 0·9 (95% CI 0·8-1·0) and 1·3 (1·2-1·6), respectively. 20 149 (91·0%) of 21 846 participants had results for all three tests, including 16 712 (76%) non-US-born participants. Discordance between TST and IFN-γ release assay results varied by age among non-US-born participants and was greatest among the 848 non-US-born children younger than 5 years. 204 (87·2%) of 234 non-US-born children younger than 5 years with at least one positive test were TST-positive and IFN-γ release assay-negative. The proportion of non-US-born participants who were TST-negative but IFN-γ release assay-positive ranged from one (0·5%) of 199 children younger than 2 years to 86 (14·5%) of 594 participants aged 65 years and older (ptrend<0·0001). Test agreement was higher between the two IFN-γ release assays than between TST and either IFN-γ release assay, regardless of birthplace. κ agreement was particularly low between TST and IFN-γ release assays in non-US-born children younger than 5 years. INTERPRETATION: Our findings support the preferential use of IFN-γ release assays for the diagnosis of latent tuberculosis in high-risk populations, especially in very young and older people born outside the USA. FUNDING: US Centers for Disease Control and Prevention.

Interferon-γ Release Assays in Children <15 Years of Age.

OBJECTIVES: The tuberculin skin test (TST) has been preferred for screening young children for latent tuberculosis infection (LTBI) because of concerns that interferon-γ release assays (IGRAs) may be less sensitive in this high-risk population. In this study, we compared the predictive value of IGRAs to the TST for progression to tuberculosis disease in children, including those <5 years old. METHODS: Children <15 years old at risk for LTBI or progression to disease were tested with TST, QuantiFERON-TB Gold In-Tube test (QFT-GIT), and T-SPOT.TB test (T-SPOT) and followed actively for 2 years, then with registry matches, to identify incident disease. RESULTS: Of 3593 children enrolled September 2012 to April 2016, 92% were born outside the United States; 25% were <5 years old. Four children developed tuberculosis over a median 4.3 years of follow-up. Sensitivities for progression to disease for TST and IGRAs were low (50%-75%), with wide confidence intervals (CIs). Specificities for TST, QFT-GIT, and T-SPOT were 73.4% (95% CI: 71.9-74.8), 90.1% (95% CI: 89.1-91.1), and 92.9% (95% CI: 92.0-93.7), respectively. Positive and negative predictive values for TST, QFT-GIT, and T-SPOT were 0.2 (95% CI: 0.1-0.8), 0.9 (95% CI: 0.3-2.5), and 0.8 (95% CI: 0.2-2.9) and 99.9 (95% CI: 99.7-100), 100 (95% CI: 99.8-100), and 99.9 (95% CI: 99.8-100), respectively. Of 533 children with TST-positive, IGRA-negative results not treated for LTBI, including 54 children <2 years old, none developed disease. CONCLUSIONS: Although both types of tests poorly predict disease progression, IGRAs are no less predictive than the TST and offer high specificity and negative predictive values. Results from this study support the use of IGRAs for children, especially those who are not born in the United States.

Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial.

RATIONALE: Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown. OBJECTIVES: We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment. METHODS: Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase. MEASUREMENTS AND MAIN RESULTS: A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration-time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively). CONCLUSIONS: Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629).

What is the most reliable solid culture medium for tuberculosis treatment trials?

We conducted a prospective study to determine which solid medium is the most reliable overall and after two months of therapy to detect Mycobacterium tuberculosis complex (MTB). MTB isolation and contamination rates on LJ and Middlebrook 7H10 and 7H11 agar with and without selective antibiotics were examined in a single laboratory and compared against a constructed reference standard and MGIT 960 results. Of 50 smear positive adults with pulmonary TB enrolled, 45 successfully completed standard treatment. Two spot sputum specimens were collected before treatment and at week 8 and one spot specimen each at weeks 2, 4, 6, and 12. The MTB recovery rate among all solid media for pre-treatment specimens was similar. After 8 weeks, selective (S) 7H11 had the highest positivity rate. Latent class analysis was used to construct the primary reference standard. The 98.7% sensitivity of 7H11S (95% Wilson confidence interval 96.4%-99.6%) was highest among the 5 solid media (P = 0.003 by bootstrap); the 82.6% specificity of 7H10S (95% CI 75.7%-87.8%) was highest (P = 0.098). Our results support 7H11S as the medium of choice. Further studies in different areas where recovery and contamination are likely to vary, are recommended.

How we determined the most reliable solid medium for studying treatment of tuberculosis.

Phase 2 clinical trials for tuberculosis (TB) treatment require reliable culture methods to determine presence or absence of Mycobacterium tuberculosis (Mtb) over the course of therapy, as these trials are based primarily on bacteriological endpoints. We evaluate which of 5 solid media is most reliable: Lowenstein-Jensen (LJ) egg-base medium and 4 Middlebrook agar media (nonselective 7H10 and 7H11 and selective 7H10 and 7H11). We analyze 393 specimens from 50 HIV-negative Ugandan adults with newly-diagnosed, pulmonary TB and high acid-fast bacillus smear grade. Specimens were collected every 2-4 weeks during the first 12 weeks of therapy. We compare the results for each culture to 2 composite reference standards--one that was deemed positive if any solid culture was positive for Mtb and another based on latent-class analysis. Both reference standards established that the 2 selective Middlebrook media most reliably determine the presence or absence of Mtb (P < 0.003), largely because of their lower contamination rates. We also showed that results on Middlebrook media were similar to each other, while LJ was most frequently discordant. Contaminated results appeared more likely to be truly negative than to harbor undetected Mtb.

Clinical incidence of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection as a proxy measure for MRSA transmission in acute care hospitals.

BACKGROUND: The incidence of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection has been used as a proxy measure for MRSA transmission, but incidence calculations vary depending on whether active surveillance culture (ASC) data are included. OBJECTIVE: To evaluate the relationship between incidences of MRSA colonization or infection calculated with and without ASCs in intensive care units and non-intensive care units. SETTING: A Veterans Affairs medical center. METHODS: From microbiology records, incidences of MRSA colonization or infection were calculated with and without ASC data. Correlation coefficients were calculated for the 2 measures, and Poisson regression was used to model temporal trends. A Poisson interaction model was used to test for differences in incidence trends modeled with and without ASCs. RESULTS: The incidence of MRSA colonization or infection calculated with ASCs was 4.9 times higher than that calculated without ASCs. Correlation coefficients for incidences with and without ASCs were 0.42 for intensive care units, 0.59 for non-intensive care units, and 0.48 hospital-wide. Trends over time for the hospital were similar with and without ASCs (incidence rate ratio with ASCs, 0.95 [95% confidence interval, 0.93-0.97]; incidence rate ratio without ASCs, 0.95 [95% confidence interval, 0.92-0.99]; P = .68). Without ASCs, 35% of prevalent cases were falsely classified as incident. CONCLUSIONS: At 1 Veterans Affairs medical center, the incidence of MRSA colonization or infection calculated solely on the basis of clinical culture results commonly misclassified incident cases and underestimated incidence, compared with measures that included ASCs; however, temporal changes were similar. These findings suggest that incidence measured without ASCs may not accurately reflect the magnitude of MRSA transmission but may be useful for monitoring transmission trends over time, a crucial element for evaluating the impact of prevention activities.

Sustained reduction in the clinical incidence of methicillin-resistant Staphylococcus aureus colonization or infection associated with a multifaceted infection control intervention.

OBJECTIVE: To assess the impact and sustainability of a multifaceted intervention to prevent methicillin-resistant Staphylococcus aureus (MRSA) transmission implemented in 3 chronologically overlapping phases at 1 hospital. DESIGN: Interrupted time-series analyses. SETTING: A Veterans Affairs hospital in the northeastern United States. PATIENTS AND PARTICIPANTS: Individuals admitted to acute care units from October 1, 1999, through September 30, 2008. To calculate the monthly clinical incidence of MRSA colonization or infection, the number of MRSA-positive cultures obtained from a clinical site more than 48 hours after admission among patients with no MRSA-positive clinical cultures during the previous year was divided by patient-days at risk. Secondary outcomes included clinical incidence of methicillin-sensitive S. aureus colonization or infection and incidence of MRSA bloodstream infections. INTERVENTIONS: The intervention--implemented in a surgical ward beginning October 2001, in a surgical intensive care unit beginning October 2003, and in all acute care units beginning July 2005--included systems and behavior change strategies to increase adherence to infection control precautions (eg, hand hygiene and active surveillance culturing for MRSA). RESULTS: Hospital-wide, the clinical incidence of MRSA colonization or infection decreased after initiation of the intervention in 2001, compared with the period before intervention (P = .002), and decreased by 61% (P < .001) in the 7-year postintervention period. In the postintervention period, the hospital-wide incidence of MRSA bloodstream infection decreased by 50% (P = .02), and the proportion of S. aureus isolates that were methicillin resistant decreased by 30% (P < .001). CONCLUSIONS: Sustained decreases in hospital-wide clinical incidence of MRSA colonization or infection, incidence of MRSA bloodstream infection, and proportion of S. aureus isolates resistant to methicillin followed implementation of a multifaceted prevention program at one Veterans Affairs hospital. Findings suggest that interventions designed to prevent transmission can impact endemic antimicrobial resistance problems.