Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease.

Importance: Elimination of tuberculosis (TB) disease in the US hinges on the ability of tests to detect individual risk of developing disease to inform prevention. The relative performance of 3 available TB tests-the tuberculin skin test (TST) and 2 interferon-γ release assays (IGRAs; QuantiFERON-TB Gold In-Tube [QFT-GIT] and SPOT.TB [TSPOT])-in predicting TB disease development in the US remains unknown. Objective: To compare the performance of the TST with the QFT-GIT and TSPOT IGRAs in predicting TB disease in high-risk populations. Design, Setting, and Participants: This prospective diagnostic study included participants at high risk of TB infection (TBI) or progression to TB disease at 10 US sites between 2012 and 2020. Participants of any age who had close contact with a case patient with infectious TB, were born in a country with medium or high TB incidence, had traveled recently to a high-incidence country, were living with HIV infection, or were from a population with a high local prevalence were enrolled from July 12, 2012, through May 5, 2017. Participants were assessed for 2 years after enrollment and through registry matches until the study end date (November 15, 2020). Data analysis was performed in June 2023. Exposures: At enrollment, participants were concurrently tested with 2 IGRAs (QFT-GIT from Qiagen and TSPOT from Oxford Immunotec) and the TST. Participants were classified as case patients with incident TB disease when diagnosed more than 30 days from enrollment. Main Outcomes and Measures: Estimated positive predictive value (PPV) ratios from generalized estimating equation models were used to compare test performance in predicting incident TB. Incremental changes in PPV were estimated to determine whether predictive performance significantly improved with the addition of a second test. Case patients with prevalent TB were examined in sensitivity analysis. Results: A total of 22 020 eligible participants were included in this study. Their median age was 32 (range, 0-102) years, more than half (51.2%) were male, and the median follow-up was 6.4 (range, 0.2-8.3) years. Most participants (82.0%) were born outside the US, and 9.6% were close contacts. Tuberculosis disease was identified in 129 case patients (0.6%): 42 (0.2%) had incident TB and 87 (0.4%) had prevalent TB. The TSPOT and QFT-GIT assays performed significantly better than the TST (PPV ratio, 1.65 [95% CI, 1.35-2.02] and 1.47 [95% CI, 1.22-1.77], respectively). The incremental gain in PPV, given a positive TST result, was statistically significant for positive QFT-GIT and TSPOT results (1.64 [95% CI, 1.40-1.93] and 1.94 [95% CI, 1.65-2.27], respectively). Conclusions and Relevance: In this diagnostic study assessing predictive value, IGRAs demonstrated superior performance for predicting incident TB compared with the TST. Interferon-γ release assays provided a statistically significant incremental improvement in PPV when a positive TST result was known. These findings suggest that IGRA performance may enhance decisions to treat TBI and prevent TB.

Access to Benzathine Penicillin G Treatment for Persons With Syphilis, Maricopa County, Arizona, 2021.

BACKGROUND: As the incidence of syphilis continues to increase, examining benzathine penicillin G (BPG) treatment data provides valuable insight for public health strategies. This study analyzed the trends of where BPG is administered relative to the initial clinical site of syphilis diagnosis. Our findings are timely in the context of recent national BPG shortages. METHODS: The analysis included persons diagnosed with any syphilis stage in Maricopa County, Arizona, from January 1, 2021, to December 31, 2021. The Arizona surveillance database (PRISM) was the source of demographic, testing, and treatment data. RESULTS: Of a total of 4028 persons with syphilis, 3038 (75.4%) received at least 1 injection of BPG. Among persons who received an initial BPG injection, only 1719 (56.6%) were diagnosed and treated at the same clinical site type. The Maricopa County Sexually Transmitted Disease Clinic administered BPG to 48.8% (n = 1483) of persons with syphilis who received an initial injection. CONCLUSIONS: Our findings analyze trends in BPG administration that are likely due to treatment referral practices and medication cost. Administration of BPG is not guaranteed at the clinical site of diagnosis, highlighting concerns regarding access to BPG. A burden is placed on patients who are required to leave their diagnosing provider to seek syphilis treatment at other health facilities that administer BPG.

Treatment Completion With Three-Dose Series of Benzathine Penicillin Among People Diagnosed With Late Latent and Unknown Duration Syphilis, Maricopa County, Arizona.

BACKGROUND: Syphilis is a public health concern as cases are rising each year. If untreated, syphilis is associated with significant morbidity and risk of vertical transmission during pregnancy. For people with late latent and unknown duration stages, 3 injections of benzathine penicillin G (BPG) at 1-week intervals are recommended. Our study quantified treatment for people diagnosed with late latent and unknown duration syphilis in Maricopa County, Arizona with a secondary analysis of pregnant women to assess completion of 3 injections of BPG in multiple time intervals. METHODS: Maricopa County syphilis case data were extracted from the state-run database (PRISM). Records were reviewed for people with late latent and unknown duration syphilis during January 1, 2016, to December 31, 2021. Treatment types and time intervals between treatments were analyzed. RESULTS: Of a total of 14,924 people with syphilis reported in Maricopa County, 5372 (36.0%) were staged as late latent or unknown duration syphilis. Completion of 3 BPG injections in the time frame of 7 to 9 days was 42.9% (n = 2302). Completion among pregnant women (n = 406) with 3 injections was 68.7% (n = 279). CONCLUSIONS: The completion rate of 3 BPG injections for people with late latent or unknown duration syphilis is low. An unmet need exists to identify barriers to treatment including access to BPG and public health follow-up after the first injection. Prioritized effort is needed to identify and classify patients as having earlier stages of syphilis that require only 1 BPG injection.

Evaluation of the Latent Tuberculosis Care Cascade Among Public Health Clinics in the United States.

BACKGROUND: Tuberculosis (TB) elimination within the United States will require scaling up TB preventive services. Many public health departments offer care for latent tuberculosis infection (LTBI), although gaps in the LTBI care cascade are not well quantified. An understanding of these gaps will be required to design targeted public health interventions. METHODS: We conducted a cohort study through the Tuberculosis Epidemiologic Studies Consortium (TBESC) within 15 local health department (LHD) TB clinics across the United States. Data were abstracted on individuals receiving LTBI care during 2016-2017 through chart review. Our primary objective was to quantify the LTBI care cascade, beginning with LTBI testing and extending through treatment completion. RESULTS: Among 23 885 participants tested by LHDs, 46% (11 009) were male with a median age of 31 (interquartile range [IQR] 20-46). A median of 35% of participants were US-born at each site (IQR 11-78). Overall, 16 689 (70%) received a tuberculin skin test (TST), 6993 (29%) received a Quantiferon (QFT), and 1934 (8%) received a T-SPOT.TB; 5% (1190) had more than one test. Among those tested, 2877 (12%) had at least one positive test result (3% among US-born, and 23% among non-US-born, P < .01). Of 2515 (11%) of the total participants diagnosed with LTBI, 1073 (42%) initiated therapy, of whom 817 (76%) completed treatment (32% of those with LTBI diagnosis). CONCLUSIONS: Significant gaps were identified along the LTBI care cascade, with less than half of individuals diagnosed with LTBI initiating therapy. Further research is needed to better characterize the factors impeding LTBI diagnosis, treatment initiation, and treatment completion.

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.

Bridging the gap between evidence and policy for infectious diseases: How models can aid public health decision-making.

The dominant approach to decision-making in public health policy for infectious diseases relies heavily on expert opinion, which often applies empirical evidence to policy questions in a manner that is neither systematic nor transparent. Although systematic reviews are frequently commissioned to inform specific components of policy (such as efficacy), the same process is rarely applied to the full decision-making process. Mathematical models provide a mechanism through which empirical evidence can be methodically and transparently integrated to address such questions. However, such models are often considered difficult to interpret. In addition, models provide estimates that need to be iteratively re-evaluated as new data or considerations arise. Using the case study of a novel diagnostic for tuberculosis, a framework for improved collaboration between public health decision-makers and mathematical modellers that could lead to more transparent and evidence-driven policy decisions for infectious diseases in the future is proposed. The framework proposes that policymakers should establish long-term collaborations with modellers to address key questions, and that modellers should strive to provide clear explanations of the uncertainty of model structure and outputs. Doing so will improve the applicability of models and clarify their limitations when used to inform real-world public health policy decisions.

Chlamydia and gonorrhea diagnosis, treatment, personnel cost savings, and service delivery improvements after the implementation of express sexually transmitted disease testing in Maricopa County, Arizona.

BACKGROUND: The demand for low-cost sexually transmitted disease (STD) services in Maricopa County (Phoenix area) is high. Improved methods for STD/HIV testing are needed to increase the number of patients receiving testing. OBJECTIVES: The present study sought to evaluate an STD/HIV express testing (ET) option for patients identified as being at lower risk for infection. METHODS: Clients reporting current STD symptoms, contact to an infected partner, or health department referral were identified via questionnaire and routed to a traditional provider visit (PV); those not reporting these situations were routed to ET (laboratory-only). Demographics, treatment completion, and treatment intervals were compared among patients diagnosed as having chlamydia and gonorrhea through ET and PV encounters in September 2008 to July 2011. Personnel costs were compared for each of the 2 visit types. The number of clinic turn-aways for the 2-month time interval before the start of the program was compared with the 2-month interval at the end of the evaluation. RESULTS: Of the 36,946 clients seen at Maricopa County Department of Public Health, 7466 (20.2%) were patients seen through express visits. Overall chlamydia and gonorrhea positivity was lower among ET patients (527/7466; 7.1%) as compared with those tested through PVs (6323/29,480; 21.4%). Treatment completion rates were comparable but were higher among patients seen through PVs (99%) as compared with ET (94%). A savings of $2936 per 1000 patients seen was achieved when 20% of clients were routed through ET. Clinic turn-aways decreased significantly, from 159 clients during the 2 months before implementation of ET to 6 patients during the last 2 months of evaluation (96% reduction). CONCLUSIONS: This ET system included an effective patient routing process that provided an efficient way to increase access to STD testing among persons at lower risk, at a reduced cost per patient, while maintaining high treatment coverage.

An update on anti-Helicobacter pylori treatment in children.

Previous consensus statements have recommended one- to two-week proton pump inhibitor (PPI)-based triple therapies with clarithromycin and either amoxicillin or metronidazole as first-line treatments for children with Helicobacter pylori infection. The objective of the present review was to summarize data from pediatric studies that have examined treatment efficacy, safety, drug resistance and reinfection rates related to anti-H. pylori therapies. Data from a recent meta-analysis of pediatric studies were used along with the authors' existing databases and searches of individual studies. Regimens that were identified as greater than 80% efficacious in children included a two-week therapy with a nitroimidazole and amoxicillin in Europe; a two-week regimen of bismuth, amoxicillin and metronidazole in developed countries (except Spain); a one- to two-week regimen of a PPI, clarithromycin and amoxicillin in Northern Europe, Asia and the Middle East; and a two-week regimen of a PPI, clarithromycin and metronidazole in Canada. Although recommended as a first-line treatment in adults, two-week treatment with a PPI, clarithromycin and amoxicillin eradicated only 68% of H. pylori infections in North American children. Treatment efficacy was reduced in the presence of metronidazole and/or clarithromycin resistance. Further studies of anti-H. pylori treatments in children in North America and developing countries are warranted.