Masahiro Narita

Background: Latent tuberculosis - infection (LTBI) reactivation accounts for most tuberculosis (TB) cases in the United States (U.S.). Expanding primary care LTBI services can improve detection and treatment, but real-world implementation is not well described. Objective: Describe how LTBI screening and treatment workflows are operationalized into practice in diverse U.S. primary care health systems. Design: Descriptive, multi-site study. Setting: Four U.S. primary care health systems participating in the U.S. Centers for Disease Control and Prevention (CDC) Tuberculosis Epidemiologic Studies Consortium III (TBESC-III, 2020-2022). Patients: Patients visiting any study site (N = 3,522,077). Measurements: Electronic medical record (EMR) data on patient demographics, TB test type, and results. Using narrative reporting and study documentation, LTBI care workflows were summarized by site into six domains: patient registration, TB testing evaluation, TB testing, TB disease assessment, LTBI diagnosis, and LTBI treatment. Results: Sites implemented recommended practices for testing and treatment: interferon-gamma release assays were the predominant test, and short-course rifamycin-based regimens were the primary treatment. Follow-up care practices and documentation of treatment outcomes varied. Country of birth was not consistently recorded at all sites, limiting TB screening capability based on nativity. Physician training, EMR decision-support tools, and patient education resources differed in scope and availability. Limitations: Descriptive design using self-reported workflows; may not generalize to all primary care settings or reflect physician-level variations. Conclusion: We provide a descriptive snapshot showing how LTBI care workflows varied in approach and consistency at four primary care systems with integrated LTBI services. These real-world examples may serve as templates for U.S. primary care systems seeking to expand TB testing and treatment. Primary Funding Source: U.S. Centers for Disease Control and Prevention (TBESC-III).

Background: Treating asymptomatic tuberculosis (TB) infection prevents TB disease and is critical for TB elimination in the United States (U.S.). In the U.S., TB disease disproportionately affects those born outside of the U.S. The quality of TB preventive care in primary care settings for non-U.S.-born populations is poorly characterized. We aimed to measure gaps in TB preventive care among non-U.S.-born persons receiving primary care at community health clinics across the U.S. Method: We conducted a retrospective cohort study at 12 community health clinics in the U.S. Per clinic, individual-level demographic and TB clinical data were extracted for approximately 700 non-U.S.-born persons aged ≥18 years seeking care between June and December 2019. We constructed a care cascade describing gaps in TB infection testing and treatment and used multivariable mixed effects logistic models to evaluate associations between individual and clinic-level characteristics and observed gaps. Results: Among 8460 non-U.S.-born individuals included, 68% were female, and the median age was 50 years (interquartile range 38–63). Of those included, 2765 (33%) had a TB infection test ordered. Among 1022 with a positive test, 787 (77%) were diagnosed with TB infection, of whom 377 (48%) were offered preventive treatment. Among 173 who were treated at study clinics, 141 (82%) completed treatment. Conclusions: Gaps in testing and treatment initiation for non-U.S.-born individuals were pervasive at the 12 community health clinics in this study. Research is needed to identify strategies that increase TB preventive care among populations who face the disproportionate burden of disease. Article summary: In this multi-site study of U.S. community health clinics, substantial gaps in tuberculosis infection testing and treatment initiation were identified for non-U.S.-born persons, a population that bears the disproportionate burden of TB disease in the U.S.

Importance: Tuberculosis (TB) was the leading infectious cause of death worldwide in 2023. Most US TB cases represent reactivation of latent TB infection (LTBI). Because LTBI treatment is approximately 90% effective for preventing TB disease, LTBI screening and treatment are primary strategies for US TB elimination. The Tuberculosis Epidemiologic Studies Consortium-III (TBESC-III) supports US TB elimination efforts by addressing LTBI among individuals at higher risk of infection seeking care in US primary care clinics. Objective: To characterize and measure outcomes across a longitudinal LTBI care cascade, from proportion of persons at higher risk through testing, diagnosis, and treatment. Design: Longitudinal study using patient-level electronic health record (EHR) data. Setting: Primary care clinics serving at least 10,000 non–US-born individuals annually from countries with high TB disease incidence rates (defined as ≥10 cases per 100,000 persons among expatriates living in the US). Participants: Persons at higher risk of TB infection, defined as non-US birth or, if unknown, a non-English language preference, who had a visit during the study period at a participating clinic. Intervention(s) (for clinical trials) or Exposure(s) (for observational studies): Not relevant Main Outcome(s) and Measure(s): Among participants without prior TB or LTBI testing, diagnosis, or treatment documented (ie, cascade eligible), we determined proportions: tested for TB infection, with available test results, with positive results, chest imaging ordered, LTBI diagnoses, and with LTBI treatment prescribed, started, and completed. Percentages were averaged across four sites representing multiple clinics. Results: Of 3.5 million persons seeking care, on average, 48% were at higher risk of TB infection, and 69% of these were cascade eligible. Among cascade eligible individuals, 14% were tested; 92% of those tested had available results, with 17% testing positive. Of those testing positive, 82% underwent chest imaging; 70% met LTBI diagnostic criteria. Among those diagnosed, 61% were prescribed treatment; 87% started treatment, with 56% completing treatment. Conclusions and Relevance: Although an average of 17% of participants tested had TB infection, most (average, 86%) higher-risk individuals were not tested; an average of 39% of those diagnosed were not prescribed treatment, and nearly half (average, 44%) did not complete treatment. Targeted interventions to increase LTBI testing and treatment completion among higher-risk individuals could facilitate more preventive treatment and reductions in TB-associated morbidity.

Case investigation and contact tracing (CICT) is a longstanding cornerstone of public health disease control efforts for a wide array of communicable diseases, though the content of CICT varies substantially depending on the infection to which it is applied, the epidemiologic circumstances, and interventions available to control an epidemic. In this article, we discuss how CICT is currently used in public health communicable disease, sexually transmitted infection/human immunodeficiency virus, and tuberculosis control programs. We then review how CICT might be modernized, considering issues such as community and health care organization engagement, workforce development, public health program organizational structure, data information systems, case prioritization, and the content to CICT.

Background: In the United States, tuberculosis (TB) incidence rates are highest among adults aged ≥65 years. We performed this study to evaluate outcomes of older patients undergoing treatment for TB disease, including the frequency of adverse events related to TB treatment. Methods: This study evaluated adult patients who were diagnosed with pulmonary TB from 2009 to 2014 in King County, Washington. Patient characteristics, manifestation of TB, and treatment outcomes in different age groups were compared. Frequency and type of adverse events that resulted in treatment interruption were evaluated and patients aged ≥65 years were compared with selected younger patients. Results: There were 403 patients who met the study criteria, 111 of whom were aged ≥65 years. Older patients were significantly less likely to have cavitation on chest radiographs. Patients aged ≥65 years were less likely to complete TB treatment (76.6% vs 94.9%, P < .0001) and were more likely to die during treatment (18.9% vs 2.1%, P < .0001). The difference in these outcomes was heightened for those aged ≥75 years compared with those aged <75 years. Those aged ≥75 years were also more likely to have an adverse event attributable to TB medication and were more likely to have an adverse event later in therapy. Regardless of age, pyrazinamide was responsible for the majority of adverse reactions. Conclusions: Adults aged ≥65 years with pulmonary TB had less-advanced disease but a higher risk of complications during treatment such as death or adverse events. This effect was most pronounced among those aged ≥75 years.

Research is critical for developing HIV and tuberculosis (TB) programming for U.S. African-born communities, and depends on successful recruitment of African-born people. From January 2014 to June 2016, we recruited African-born people for HIV and TB research in King County, Washington. We compared the characteristics of study participants and the underlying populations of interest, and assessed recruitment strategies. Target enrollment for the HIV study was 167 participants; 51 participants (31%) were enrolled. Target enrollment for the TB study was 218 participants; 38 (17%) were successfully recruited. Of 249 prior TB patients we attempted to contact by phone, we reached 72 (33%). Multiple recruitment strategies were employed with variable impact. Study participants differed from the underlying populations in terms of gender, country of origin and language. Inequities in research participation and in meaningful opportunities for such participation may exacerbate existing health disparities.

SETTING: QuantiFERON^®-TB Gold Plus (QFT-Plus), recently approved for use in the United States, is a new-generation QuantiFERON assay that differs from its predecessors in that it uses an additional antigen tube containing peptides to elicit both CD8⁺ and CD4⁺ T-lymphocyte responses. OBJECTIVE: To assess the sensitivity of QFT-Plus compared with QuantiFERON^®-TB Gold In-Tube (QFT-GIT) in participants with active TB. DESIGN: Adult patients with active TB at three US and two Japanese sites were eligible for this study if they had culture-confirmed TB and were either untreated or had received 14 days of anti-tuberculosis treatment. RESULTS: We enrolled 164 participants, nine of whom had indeterminate results. Excluding indeterminate values, there were 150 QFT-GIT-positive results among 159 tests and 146 QFT-Plus-positive results among 157 tests, with sensitivities of respectively 94.3% (95%CI 89.5–97.4) and 93.02% (95%CI 87.8–96.5%). The estimated sensitivities for the two tests were not significantly different (P = 0.16). Overall test agreement was 98.7%, with a κ statistic of 0.89 (95%CI 0.75–1.00). CONCLUSION: In this multisite study, we found that QFT-Plus had similar sensitivity to QFT-GIT in adult patients with active TB.

Rationale: Data are limited regarding the safety of 12-dose once-weekly isoniazid (H, 900 mg) plus rifapentine (P, 900 mg) (3HP) for latent infection treatment during pregnancy. Objectives: To assess safety and pregnancy outcomes among pregnant women who were inadvertently exposed to study medications in two latent tuberculosis infection trials (PREVENT TB or iAdhere) evaluating 3HP and 9 months of daily isoniazid (H, 300 mg) (9H). Methods: Data from reproductive-age (15–51 yr) women who received one or more study dose of 3HP or 9H in either trial were analyzed. Drug exposure during pregnancy occurred if the estimated date of conception was on or before the last dose date. Results: Of 126 pregnancies (125 participants) that occurred during treatment or follow-up, 87 were exposed to study drugs. Among these, fetal loss was reported for 4/31 (13%) and 8/56 (14%), 3HP and 9H, respectively (difference, 13% − 14% = −1%; 95% confidence interval = −17% to +18%) and congenital anomalies in 0/20 and 2/41 (5%) live births, 3HP and 9H, respectively (difference, 0% − 5% = −5%; 95% confidence interval = −18% to +16%). All fetal losses occurred in pregnancies of less than 20 weeks. Of the total 126 pregnancies, fetal loss was reported in 8/54 (15%) and 9/72 (13%), 3HP and 9H, respectively; and congenital anomalies in 1/37 (3%) and 2/56 (4%) live births, 3HP and 9H, respectively. The overall proportion of fetal loss (17/126 [13%]) and anomalies (3/93 [3%]) were similar to those estimated for the United States, 17% and 3%, respectively. Conclusions: Among reported pregnancies in these two latent tuberculosis infection trials, there was no unexpected fetal loss or congenital anomalies. These data offer some preliminary reassurance to clinicians and patients in circumstances when these drugs and regimens are the best option in pregnancy or in women of child-bearing potential. This work used the identifying trial registration numbers NCT00023452 and NCT01582711, corresponding to the primary clinical trials PREVENT TB and iAdhere (Tuberculosis Trials Consortium Study 26 and 33).