Effects of the COVID-19 pandemic on TB outcomes in the United States: a Bayesian analysis.

Background: Tuberculosis (TB) notifications and deaths in the United States fluctuated substantially during the COVID-19 pandemic. We analyzed multiple data sources to understand the factors contributing to these changes and estimated future TB trends.

Methods: We identified four mechanisms potentially contributing to observed TB trends during 2020-2023: immigration, respiratory contact rates, rates of accurate diagnosis and treatment initiation, and mortality rates for persons experiencing TB disease.

Contribution of Post-TB Sequelae to Life-Years Lost from TB Disease in the United States, 2015-2019.

Rationale: Individuals surviving TB disease may experience chronic sequelae that reduce survival and quality-of-life. These post-TB sequalae are not generally considered in estimates of the health impact of TB disease.

Objectives: To estimate the TB-attributable reductions in life expectancy and quality-adjusted life expectancy for individuals developing TB disease in the United States, including post-TB sequelae.

Effectiveness and Cost-Effectiveness of Expanded Targeted Testing and Treatment of Latent Tuberculosis Infection Among the Medicare Population in 2022.

Background: In the United States, older adults have elevated prevalence of latent tuberculosis infection (LTBI) and incidence of tuberculosis (TB).

Objective: To estimate the health benefits and cost-effectiveness of LTBI testing and treatment among the Medicare-eligible population.

Design: Model-based cost-effectiveness analysis.

A new method for detecting mixed Mycobacterium tuberculosis infection and reconstructing constituent strains provides insights into transmission.

Background: Mixed infection with multiple strains of the same pathogen in a single host can present clinical and analytical challenges. Whole genome sequence (WGS) data can identify signals of multiple strains in samples, though the precision of previous methods can be improved. Here, we present MixInfect2, a new tool to accurately detect mixed samples from Mycobacterium tuberculosis short-read WGS data.

Factors associated with tuberculosis treatment initiation among bacteriologically negative individuals evaluated for tuberculosis: An individual patient data meta-analysis.

Background: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians' decisions to initiate TB treatment when initial bacteriological test results are negative.

Methods And Findings: We performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613).

Tiled Amplicon Sequencing Enables Culture-free Whole-Genome Sequencing of Pathogenic Bacteria From Clinical Specimens.

Pathogen sequencing is an important tool for disease surveillance and demonstrated its high value during the COVID-19 pandemic. Viral sequencing during the pandemic allowed us to track disease spread, quickly identify new variants, and guide the development of vaccines. Tiled amplicon sequencing, in which a panel of primers is used for multiplex amplification of fragments across an entire genome, was the cornerstone of SARS-CoV-2 sequencing.

Surveillance for TB drug resistance using routine rapid diagnostic testing data: Methodological development and application in Brazil.

Effectively responding to drug-resistant tuberculosis (TB) requires accurate and timely information on resistance levels and trends. In contexts where use of drug susceptibility testing has not been universal (i.e.

TGV: suite of tools to visualize transmission graphs.

Graph structures are often used to visualize transmission networks generated using genomic epidemiological methods. However, tools to interactively visualize these graphs do not exist. A browser-based tool allowing users to load and interactively visualize transmission graphs was developed in JavaScript.

Signatures of transmission in within-host Mycobacterium tuberculosis complex variation: a retrospective genomic epidemiology study.

Background: Mycobacterium tuberculosis complex (MTBC) species evolve slowly, so isolates from individuals linked in transmission often have identical or nearly identical genomes, making it difficult to reconstruct transmission chains. Finding additional sources of shared MTBC variation could help overcome this problem. Previous studies have reported MTBC diversity within infected individuals; however, whether within-host variation improves transmission inferences remains unclear.

Effects of the COVID-19 pandemic on TB outcomes in the United States: a Bayesian analysis.

Background: Tuberculosis (TB) cases and deaths in the United States fluctuated substantially during the COVID-19 pandemic. We analyzed multiple data sources to understand the factors contributing to these changes and estimated future TB trends.

Methods: We identified four mechanisms potentially contributing to observed TB trends during 2020-2023: immigration, respiratory contact rates, rates of accurate diagnosis and treatment initiation, and mortality rates for persons with TB disease.

High mortality rates among individuals misdiagnosed with tuberculosis: a matched retrospective cohort study of individuals diagnosed with tuberculosis in Brazil.

We conducted a matched retrospective cohort study comparing mortality among individuals receiving a false-positive tuberculosis diagnosis (n=3701) to individuals correctly diagnosed with TB (n=8595) in Brazil from 2007-2016. Over an average 5.4-year follow-up period, we estimated a mortality rate ratio of 1.

Mass incarceration as a driver of the tuberculosis epidemic in Latin America and projected effects of policy alternatives: a mathematical modelling study.

Background: Tuberculosis incidence is increasing in Latin America, where the incarcerated population has nearly quadrupled since 1990. We aimed to quantify the impact of historical and future incarceration policies on the tuberculosis epidemic, accounting for effects in and beyond prisons.

Methods: In this modelling study, we calibrated dynamic compartmental transmission models to historical and contemporary data from Argentina, Brazil, Colombia, El Salvador, Mexico, and Peru, which comprise approximately 80% of the region's incarcerated population and tuberculosis burden.

Estimated Health and Economic Outcomes of Racial and Ethnic Tuberculosis Disparities in US-Born Persons.

Importance: Despite significant progress made toward tuberculosis (TB) elimination, racial and ethnic disparities persist in TB incidence and case-fatality rates in the US.

Objective: To estimate the health outcomes and economic cost of TB disparities among US-born persons from 2023 to 2035.

Design, Setting, And Participants: Generalized additive regression models projecting trends in TB incidence and case-fatality rates from 2023 to 2035 were fit based on national TB surveillance data for 2010 to 2019 in the 50 US states and the District of Columbia among US-born persons.

Implications of progressive lung damage and post-TB sequelae for the health benefits of prompt TB diagnosis in high HIV prevalence settings: a mathematical modeling analysis.

Background: Untreated pulmonary tuberculosis (TB) causes ongoing lung damage, which may persist after treatment. Conventional approaches for assessing TB health effects may not fully capture these mechanisms. We evaluated how TB-associated lung damage and post-TB sequalae affect the lifetime health consequences of TB in high HIV prevalence settings.

Projected health and economic effects of a pan-tuberculosis treatment regimen: a modelling study.

Background: A pan-tuberculosis regimen that could be initiated without knowledge of drug susceptibility has been proposed as an objective of tuberculosis regimen development. We modelled the health and economic benefits of such a regimen and analysed which of its features contribute most to impact and savings.

Methods: We constructed a mathematical model of tuberculosis treatment parameterised with data from the published literature specific to three countries with a high tuberculosis burden (India, the Philippines, and South Africa).

Cost-effectiveness and health impact of screening and treatment of Mycobacterium tuberculosis infection among formerly incarcerated individuals in Brazil: a Markov modelling study.

Background: Individuals who were formerly incarcerated have high tuberculosis incidence, but are generally not considered among the risk groups eligible for tuberculosis prevention. We investigated the potential health impact and cost-effectiveness of Mycobacterium tuberculosis infection screening and tuberculosis preventive treatment (TPT) for individuals who were formerly incarcerated in Brazil.

Methods: Using published evidence for Brazil, we constructed a Markov state transition model estimating tuberculosis-related health outcomes and costs among individuals who were formerly incarcerated, by simulating transitions between health states over time.

Molecular Epidemiology of Isoniazid-resistant in Port-au-Prince, Haiti.

Background: Isoniazid-resistant, rifampin-susceptible tuberculosis (Hr-TB) is associated with poor treatment outcomes and higher rates of acquisition of further drug resistance during treatment. Due to a lack of widespread diagnostics, Hr-TB is frequently undetected and its epidemiology is incompletely understood.

Methods: We studied the molecular epidemiology of Hr-TB among all patients diagnosed with culture-positive pulmonary tuberculosis between January 1 and June 30, 2017, at an urban referral tuberculosis clinic in Port-au-Prince, Haiti.

The long-term effects of domestic and international tuberculosis service improvements on tuberculosis trends within the USA: a mathematical modelling study.

Background: For settings with low tuberculosis incidence, disease elimination is a long-term goal. We investigated pathways to tuberculosis pre-elimination (incidence <1·0 cases per 100 000 people) and elimination (incidence <0·1 cases per 100 000 people) in the USA, where incidence was estimated at 2·9 per 100 000 people in 2023.

Methods: Using a mathematical modelling framework, we simulated how US tuberculosis incidence could be affected by changes in tuberculosis services in the countries of origin for future migrants to the USA, as well as changes in tuberculosis services inside the USA.

Risk factors underlying racial and ethnic disparities in tuberculosis diagnosis and treatment outcomes, 2011-19: a multiple mediation analysis of national surveillance data.

Background: Despite an overall decline in tuberculosis incidence and mortality in the USA in the past two decades, racial and ethnic disparities in tuberculosis outcomes persist. We aimed to examine the extent to which inequalities in health and neighbourhood-level social vulnerability mediate these disparities.

Methods: We extracted data from the US National Tuberculosis Surveillance System on individuals with tuberculosis during 2011-19.

Potential of Pan-Tuberculosis Treatment to Drive Emergence of Novel Resistance.

New tuberculosis (TB) drugs with little existing antimicrobial resistance enable a pan-TB treatment regimen, intended for universal use without prior drug-susceptibility testing. However, widespread use of such a regimen could contribute to an increasing prevalence of antimicrobial resistance, potentially rendering the pan-TB regimen ineffective or driving clinically problematic patterns of resistance. We developed a model of multiple sequential TB patient cohorts to compare treatment outcomes between continued use of current standards of care (guided by rifampin-susceptibility testing) and a hypothetical pan-TB approach.

Uncertainty in tuberculosis clinical decision-making: An umbrella review with systematic methods and thematic analysis.

Tuberculosis is a major infectious disease worldwide, but currently available diagnostics have suboptimal accuracy, particularly in patients unable to expectorate, and are often unavailable at the point-of-care in resource-limited settings. Test/treatment decision are, therefore, often made on clinical grounds. We hypothesized that contextual factors beyond disease probability may influence clinical decisions about when to test and when to treat for tuberculosis.