In 2020, a total of 92 tuberculosis (TB) cases were reported in Seattle and King County, Washington, 5% fewer than the median of 97 (range = 94 –132) reported during the same period 2015–2019 and 30% fewer than 132 cases reported in 2019. Interviews and chart reviews were completed as part of a public health investigation. This activity was reviewed by Centers for Disease Control and Prevention (CDC) and was conducted consistent with applicable federal law and CDC policy. Results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests performed prior to TB diagnosis were available to TB public health officials for 40 (43%) patients with TB: 3 had a positive result; 37 had negative results, with 12 having been tested twice or more. We were not able to verify SARS-CoV-2 testing status or results prior to TB diagnosis for 52 TB cases. We attempted to reach out to all pulmonary TB cases diagnosed in March 2020 or later and were able to interview 29 patients by telephone or in person about how pandemic coronavirus disease 2019 (COVID-19) affected their medical care. Four of them stated that their TB diagnosis had been delayed because of pandemic-related problems. Of these, 3 waited to seek care because of fear of contracting COVID-19, and one, patient 1, was told that she probably had COVID-19 by at least 2 healthcare providers. The stories of the following 3 patients who had prolonged respiratory illnesses with fever illustrate the delays in TB diagnosis during the COVID-19 pandemic.

After reviewing their experiences with an interferon gamma release assay (IGRA) for annually testing emergency responders, Gamsky and colleagues reported excessive positive results, with 27.4% (7 years cumulative) for one subset of workers (1). The positive results were deemed false, based on retesting to the point of reversion to negative. | The results from all the cellular immunity tests for Mycobacterium tuberculosis infection (i.e., the skin test with either of two tuberculin solutions and the two commercial IGRA methods) are influenced by biological factors and technical problems with the tests. Although more than 80 years of experience with the current tuberculin skin test (TST) method has taught us to anticipate problems, we are in the early phases of learning about the IGRA methods. Gamsky already reported a high rate of false-positive IGRA results that were attributed to endotoxin-contaminated blood collection tubes at his setting during 2007; substituting new tubes corrected the problem (2). He did not indicate whether those earlier data were included in the present study, although the periods overlap.

BACKGROUND: In the Federated States of Micronesia (FSM) and then the Republic of the Marshall Islands (RMI), levofloxacin pharmacokinetics (PK) were studied in children receiving directly observed once-daily regimens (10 mg/kg, age <5 years; 15 20 mg/kg, age ≤5 years) for either multidrug-resistant tuberculosis (MDR TB) disease or latent infection after MDR TB exposure, to inform future dosing strategies. METHODS: Blood samples were collected at 0 (RMI only), 1, 2, and 6 hours (50 children, aged 6 months to 15 years) after oral levofloxacin at >6 weeks of treatment. Clinical characteristics and levofloxacin Cmax, elimination half-life (t1/2), and area under the curve from 0 to 24 hours (AUC0-24 hours * microg/mL) were correlated to determine optimal dosage and to examine associations. Population PK and target attainment were modeled. With results from FSM, dosages were increased in RMI toward the target maximal drug concentration (Cmax) for Mycobacterium tuberculosis, 8-12 microg/ml. RESULTS: Cmax correlated linearly with per-weight dosage. Neither Cmax nor t1/2 was associated with gender, age, body mass index, concurrent medications, or pre-dose meals. At levofloxacin dosage of 15-20 mg/kg, Cmax ≥ 8 microg/ml was observed, and modeling corroborated a high target attainment across the ratio of the area under the free-concentration-versus-time curve to minimum inhibitory concentration (fAUCss,0-24/MIC) values. CONCLUSIONS: Levofloxacin dosage should be 15-20 mg/kg for Cmax ≥ 8 microg/ml and a high target attainment across fAUCss,0-24/MIC values in children ≥2 years of age.

BACKGROUND: With the emergence of multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB), surgery, which had been replaced by short-course chemotherapy, is again being considered a viable treatment option. OBJECTIVE: To assess the literature on the effectiveness of surgical interventions in the treatment of drug-resistant TB. METHODS: Medline, EMBASE, and PubMed were searched from 1975 to April 2012 in addition to hand searching reference lists, and the International Journal of Tuberculosis and Lung Disease. Potentially relevant studies were assessed according to pre-defined eligibility criteria: MDR- and XDR-TB patients undergoing surgical and non-surgical treatment. Treatment outcomes were extracted according to internationally accepted definitions and included in meta-analyses using random effects models. RESULTS: Summary meta-analysis of 24 comparison studies revealed a significant association between surgery and successful treatment compared to non-surgical interventions (OR 2.24, 95%CI 1.68-2.97). A meta-analysis from 23 single-arm studies demonstrated that respectively 92% (95%CI 88.1-95) and 87% (95%CI 83-91) of surgical patients achieved successful short- and long-term outcomes. Subgroup analyses showed that favorable surgical outcomes were associated with increased drug resistance in studies reporting surgical and non-surgical treatment outcomes. CONCLUSIONS: While the results suggest that surgical intervention is associated with successful treatment outcomes in patients with drug-resistant TB, there is insufficient evidence to recommend surgery plus chemotherapy over chemotherapy alone, to evaluate the potential harm from surgery and to determine the optimal conditions for surgery. Controlled studies are needed to better assess the effectiveness of surgery and to investigate other contextual issues.

Molebogeng Rangaka and colleagues1 have comprehensively reviewed the prognostic characteristics of interferon-γ release assays (IGRAs). Their findings show that the advantages of these assays are not offset by any loss of ability to predict development of tuberculosis in people with latent Mycobacterium tuberculosis infection. | Studies that directly compared the assay with the tuberculin skin test confirm the low accuracy of both for estimation of prognosis; tuberculosis will never develop in most people with a positive result from either test, but tuberculosis will develop in some who had negative results. Although the accuracy of both tests is disappointing, IGRAs are no worse—and for some comparisons are better—than tuberculin skin test. | In USA, the benefits of IGRAs support their wide adoption. First, most of our tuberculosis caseload has shifted to BCG-vaccinated immigrant groups, and IGRAs have greater specificity in this group.2 Our experience in San Francisco, CA—where IGRAs have replaced tuberculin skin test in most settings—is that the proportion of immigrants and homeless people with positive test results decreased substantially after switching the in tests (table). The subsequent decrease in medical assessment improves efficiency and cost-effectiveness and fewer patients are inconvenienced by treatment and its toxic effects than if tuberculin skin test was used. The studies reviewed by Rangaka and colleagues report that IGRAs offer these benefits with fewer false-negative results than tuberculin skin test.

The treatment of tuberculosis (TB) is complicated by drug-induced hepatotoxicity, with reported rates ranging widely, from approximately 3 to 25%, depending on the hepatotoxicity definitions, the regimens, the methodologies, and the study populations (1). Several recent studies utilizing American Thoracic Society (ATS) or similar transaminase criteria for hepatotoxicity place the rate at about 3 to 13% (2–5). However, not all increases in serum alanine aminotransferase concentration (ALT) indicate true drug-induced liver injury (DILI). Hepatic adaptation (i.e., temporary stress or mild injury to the liver) occurs in 20% or more of patients treated with anti-TB medications (1, 6). Current recommendations (1, 7) are to obtain baseline biochemical testing in all patients being treated for TB, and then to target those deemed to be at risk for drug-induced liver injury for serial ALT monitoring. Because we lack a robust evidence base, these recommendations are based on observational studies and expert opinion. We need more data—and could readily generate a wealth of data—to help guide TB drug hepatotoxicity monitoring strategies. | In this issue of the Journal, Singanayagam and colleagues from Imperial College London (ICL) (pp. 653–659) provided a fresh look at monitoring for hepatotoxicity during anti-TB treatment (8). In a single-center retrospective cohort study, they monitored 288 patients for hepatotoxicity. They compared the utility of a uniform scheme of measuring the baseline and the 2-week serum ALT concentrations to that of the ATS recommendations, which target only patients with putative hepatotoxicity-predictive factors for serial biochemical monitoring after a baseline test (1, 7). Intensive early ALT monitoring in the ICL study detected DILI within 2 weeks in about 4% of patients, but was poor at predicting who would be among the 3% of patients having DILI later (8). The forecasting ability of the ATS putative predictive clinical factors for DILI (1, 7) was similarly mediocre.

In a recent edition of the Journal, Sherman and colleagues reported that compared to other groups of | health care workers, hospital housekeepers had the | highest rate of tuberculin skin test conversion during routine surveillance at a tertiary care hospital.1 | We found the same while investigating a nosocomial | multidrug-resistant tuberculosis outbreak at an urban community hospital in the early 1990s.2 Our | point-estimate of the period-adjusted conversion rate | for the housekeepers was 9.4 times the rate for hospital personnel who did not work in patient care areas, | such as clerical staff in medical records. We referenced two earlier reports of occupational skin test | surveillance with fi ndings similar to ours.3,4

PURPOSE OF REVIEW: The testing and treatment of children at risk for Mycobacterium tuberculosis infection represents an important public health priority in the United States. Until recently, diagnosis has relied upon the tuberculin skin test (TST). New interferon-gamma release assays (IGRAs) offer improvements over TST, but these tests have not been studied in children until recently. RECENT FINDINGS: Evidence regarding IGRA performance in children is accumulating rapidly. Overall, the findings demonstrate performance of IGRAs equivalent or superior to that of the TST. However, IGRAs have biological limitations similar to TST and some technical problems of their own, and critical gaps in our knowledge remain. SUMMARY: Current evidence supports usage of IGRAs in children aged 5 years or older. IGRAs are preferred over TST when specificity is paramount or wherein patients might fail to return for TST reading. Evidence for use in children aged less than 5 years is insufficient at this time: the sensitivity is poorly defined, and TST is preferred for testing these children. Future IGRA research should focus on children aged less than 5 years for informing expanded usage in this vulnerable population.