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Background To appropriately treat tuberculosis (TB) with regimens that combine novel and older drugs, evidence-based, context-specific strategies for drug-susceptibility testing (DST) will be required. Methods We created a Markov state-transition model of 100 000 adults with TB receiving a novel, fluoroquinolone (FQ)–containing regimen. We estimated clinical outcomes and resource utilization with no FQ-DST, universal FQ-DST, or FQ-DST only for patients with rifampin-resistant TB ("targeted FQ-DST"). We considered scenarios of stronger (South Africa) and weaker (Southeast Asia) correlation of fluoroquinolone resistance with rifampin resistance, with sensitivity analysis for other setting and regimen characteristics. Results Relative to no FQ-DST, targeted FQ-DST increased cure of FQ-resistant TB by 7.5% (interquartile range [IQR], 6.7%–9.2%) in South Africa and 1.7% (IQR, 0.7%–2.5%) in Southeast Asia. However, rare FQ resistance among the more prevalent rifampin-susceptible TB accounted for 50% of FQ-resistant TB in South Africa and 83% in Southeast Asia. As a result, universal FQ-DST further increased cure of FQ-resistant TB by 3.4% (IQR, 2.3%–5.4%) in South Africa and 5.8% (IQR, 5.1%–6.3%) in Southeast Asia. With targeted FQ-DST, 1 additional patient was cured per 50 (IQR, 42–70) tests in South Africa and 44 (IQR, 37–51) in Southeast Asia. When expanding from targeted to universal FQ-DST, 1 additional cure required 3500 (IQR, 2300–5500) tests in South Africa and 410 (IQR, 370–450) in Southeast Asia. Conclusions FQ-DST improved patient outcomes and was particularly important for high-risk patient groups and less robust regimens. A universal strategy was favored in generalized epidemics of fluoroquinolone resistance. [ABSTRACT FROM AUTHOR]

The article explores contact tracing, besides being a useful public health tool for both finding super spreaders and treating the exposed, is often central to learning about the dynamics of disease transmission. In their article in this issue of Clinical Infectious Diseases, Martinez and colleagues demonstrate this utility, by using contact investigation data to evaluate the association between tuberculosis (TB) and human immunodeficiency virus (HIV) from the perspective of TB transmission.

An essay is presented on the importance of green cards in improving the job opportunities in the U.S. Topics discussed include role of foreign investments in the overall development of the U.S. economy, importance of foreign investors and investment in the U.S. immigration law and the efforts of the U.S. Congress in making rules for easy visa processing of immigrants under the Immigration and Nationality Act of 1990 (INA).

The article discusses the unconstitutionality of government-ordered assassination against the U.S. citizens and its implications for due process in the country. It informs that U.S. President Barack Obama's administration has sanctioned the killing of the U.S. citizens involved in terrorist plots in January 2010 without due process of law. It mentions that this overreaching of governmental power threatens the due process that the U.S. Constitution guarantees to each citizen of the country.

Simpler, shorter, safer and more effective treatments for tuberculosis that are easily accessible to all people with tuberculosis are desperately needed. In 2016, the World Health Organization (WHO) developed target regimen profiles for the treatment of tuberculosis to make drug developers aware of both the important features of treatment regimens, and patient and programmatic needs at the country level. In view of recent ground-breaking advances in tuberculosis treatment, WHO has revised and updated these regimen profiles. We used a similar process as for the 2016 profiles, including a baseline treatment landscape analysis, an initial stakeholder survey, modelling studies estimating the impact and cost-effectiveness of novel tuberculosis treatment regimens, and an extensive stakeholder consultation. We developed target regimen profiles for the treatment of rifampicin-susceptible and rifampicin-resistant tuberculosis, as well as a pantuberculosis regimen that would be appropriate for patients with any type of tuberculosis. We describe the revised target regimen profile characteristics, with specific minimal and optimal targets to be met, rationale and justification, and aspects relevant to all target regimen profiles (drug susceptibility testing, adherence and forgiveness, treatment strategies, post-tuberculosis lung disease, and cost and access considerations). We discuss the trade-offs of proposed characteristics for decision-making at developmental or operational levels. We expect that, following these target regimen profile revisions, tuberculosis treatment developers will produce regimens that are quality-assured, affordable and widely available, and that meet the needs of affected populations. [ABSTRACT FROM AUTHOR]

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. A pan-TB regimen that met current target profiles was likely to initially outperform the standard of care; however, a rising prevalence of transmitted resistance to component drugs could make underperformance likely among subsequent cohorts. Although the pan-TB approach led to an increased prevalence of resistance to novel drugs, it was unlikely to cause accumulation of concurrent resistance to novel drugs and current first-line drugs. [ABSTRACT FROM AUTHOR]

Introduction In high-burden settings, low-complexity screening tests for tuberculosis (TB) could expand the reach of community-based case-finding efforts. The potential costs and cost-effectiveness of approaches incorporating these tests are poorly understood. Methods We developed a microsimulation model assessing 3 approaches to community-based case-finding in hypothetical populations (India-, South Africa-, The Philippines-, Uganda-, and Vietnam-like settings) with TB prevalence 4 times that of national estimates: (1) screening with a point-of-care C-reactive protein (CRP) test, (2) screening with a more sensitive "Hypothetical Screening test" (95% sensitive for Xpert Ultra-positive TB, 70% specificity; equipment/labor costs similar to Xpert Ultra, but using a $2 cartridge) followed by sputum Xpert Ultra if positive, or (3) testing all individuals with sputum Xpert Ultra. Costs are expressed in 2023 US dollars and include treatment costs. Results Universal Xpert Ultra was estimated to cost a mean $4.0 million (95% uncertainty range: $3.5 to $4.6 million) and avert 3200 (2600 to 3900) TB-related disability-adjusted life years (DALYs) per 100 000 people screened ($670 [The Philippines] to $2000 [Vietnam] per DALY averted). CRP was projected to cost $550 (The Philippines) to $1500 (Vietnam) per DALY averted but with 44% fewer DALYs averted. The Hypothetical Screening test showed minimal benefit compared to universal Xpert Ultra, but if specificity were improved to 95% and per-test cost to $4.5 (all-inclusive), this strategy could cost $390 (The Philippines) to $940 (Vietnam) per DALY averted. Conclusions Screening tests can meaningfully improve the cost-effectiveness of community-based case-finding for TB but only if they are sensitive, specific, and inexpensive. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has disrupted systems of care for infectious diseases—including tuberculosis—and has exposed pervasive inequities that have long marred efforts to combat these diseases. The resulting health disparities often intersect at the individual and community levels in ways that heighten vulnerability to tuberculosis. Effective responses to tuberculosis (and other infectious diseases) must respond to these realities. Unfortunately, current tuberculosis programmes are generally not designed from the perspectives of affected individuals and fail to address structural determinants of health disparities. We describe a person-centred, equity-oriented response that would identify and focus on communities affected by disparities, tailor interventions to the mechanisms by which disparities worsen tuberculosis, and address upstream determinants of those disparities. We detail four key elements of the approach (data collection, programme design, implementation, and sustainability). We then illustrate how organisations at multiple levels might partner and adapt current practices to incorporate these elements. Such an approach could generate more substantial, sustainable, and equitable reductions in tuberculosis burden at the community level, highlighting the urgency of restructuring post-COVID-19 health systems in a more person-centred, equity-oriented way. [ABSTRACT FROM AUTHOR]

This correction notice is for an article published in the journal Trials. The correction states that there was an error in the original article regarding the location of sputum collection, which was done at the TU instead of at home due to logistical constraints. The sample size section and statistical methods section were also modified to reflect changes in the non-inferiority interval and the non-inferiority margin for the primary outcome. Additionally, the author contribution section was updated to include a statement about the involvement of certain authors in the discussion related to the manuscript correction. [Extracted from the article]

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). Our model simulated cohorts of newly diagnosed tuberculosis patients, including drug susceptibility testing if performed, regimen assignment, discontinuation, adherence, costs, and resulting outcomes of durable cure (microbiological cure without relapse), need for retreatment, or death. We compared a pan-tuberculosis regimen meeting the WHO 2023 target regimen profile against the standard of care of separate rifampicin-susceptible and rifampicin-resistant regimens. We estimated incremental cures; averted deaths, secondary cases, and costs; and prices below which a pan-tuberculosis regimen would be cost saving. We also assessed scenarios intended to describe which mechanisms of benefit from a pan-tuberculosis regimen (including improved characteristics compared with the current rifampicin-susceptible and rifampicin-resistant regimens and improved regimen assignment and retention in care for patients with rifampicin-resistant tuberculosis) would be most impactful. Results are presented as a range of means across countries with the most extreme 95% uncertainty intervals (UIs) from the three UI ranges., Findings: Compared with the standard of care, a pan-tuberculosis regimen could increase the proportion of patients durably cured after an initial treatment attempt from 69-71% (95% UI 57-80) to 75-76% (68-83), preventing 30-32% of the deaths (20-43) and 17-20% of the transmission (9-29) that occur after initial tuberculosis diagnosis. Considering savings to the health system and patients during and after the initial treatment attempt, the regimen could reduce non-drug costs by 32-42% (22-49) and would be cost saving at prices below US$170-340 (130-510). A rifamycin-containing regimen that otherwise met pan-tuberculosis targets yielded only slightly less impact, indicating that most of the benefits from a pan-tuberculosis regimen resulted from its improvements upon the rifampicin-susceptible standard of care. Eliminating non-adherence and treatment discontinuation, for example via a long-acting injectable regimen, increased health impact and savings., Interpretation: In countries with a high tuberculosis burden, a shorter, highly efficacious, safe, and tolerable regimen to treat all tuberculosis could yield substantial health improvements and savings., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests TSR reports funding for work outside of this study from WHO. CFM was funded for work outside of this study by the Bill & Melinda Gates Foundation (TB MAC OPP1135288) and Unitaid (20193-3-ASCENT). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To provide accurate forecasts of the age distribution of people with HIV (PWH) in Kenya from 2025 to 2040., Design: Development of a compartmental model of HIV in Kenya, calibrated to historical estimates of HIV epidemiology., Methods: We forecasted changes in population size and age distribution of new HIV infections and PWH under the status quo and under scale-up of HIV services., Results: Without scale-up, new HIV infections were forecasted to fall from 34 000 (28 000-41 000) in 2,025 to 29 000 (15 000-57 000) in 2,040; the percentage of new infections occurring among persons over 30 increased from 33% (20-50%) to 40% (24-62%). The median age of PWH increased from 39 years (38-40) in 2025 to 43 years (39-46) in 2040, and the percentage of PWH over age 50 increased from 26% (23-29%) to 34% (26-43%). Under the full intervention scenario, new infections were forecasted to fall to 6,000 (3,000-12 000) in 2,040. The percentage of new infections occurring in people over age 30 increased to 52% (34-71%) in 2,040, and there was an additional shift in the age structure of PWH [forecasted median age of 46 (43-48) and 40% (33-47%) over age 50]., Conclusion: PWH in Kenya are forecasted to age over the next 15 years; improvements to the HIV care continuum are expected to contribute to the growing proportion of older PWH., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: With numerous trials investigating novel drug combinations to treat tuberculosis, we aimed to evaluate the extent to which future improvements in tuberculosis treatment regimens could offset potential increases in drug costs., Methods: In this modelling analysis, we used an ingredients-based approach to estimate prices at which novel regimens for rifampin-susceptible and rifampin-resistant tuberculosis treatment would be cost-neutral or cost-effective compared with standards of care in India, the Philippines, and South Africa. We modelled regimens meeting targets set in the WHO's 2023 Target Regimen Profiles (TRPs). Our decision-analytical model tracked cohorts of adults initiating rifampin-susceptible or rifampin-resistant tuberculosis treatment, simulating their health outcomes and costs accumulated during and following treatment under standard-of-care and novel regimen scenarios. Price thresholds included short-term cost-neutrality (considering only savings accrued during treatment), medium-term cost-neutrality (additionally considering savings from averted retreatments and secondary cases), and cost-effectiveness (incorporating willingness-to-pay for improved health outcomes)., Findings: Total medium-term costs per person treated using standard-of-care regimens were estimated at US$450 (95% uncertainty interval 310-630) in India, $560 (350-860) in the Philippines, and $730 (530-1090) in South Africa for rifampin-susceptible tuberculosis (current drug costs $46) and $2100 (1590-2810) in India, $2610 (2090-3280) in the Philippines, and $3790 (3090-4630) in South Africa for rifampin-resistant tuberculosis (current drug costs $432). A rifampin-susceptible tuberculosis regimen meeting the optimal targets defined in the TRPs could be cost-neutral in the short term at drug costs of $140 (90-210) per full course in India, $230 (130-380) in the Philippines, and $280 (180-460) in South Africa. For rifampin-resistant tuberculosis, short-term cost-neutral thresholds were higher with $930 (720-1230) in India, $1180 (980-1430) in the Philippines, and $1480 (1230-1780) in South Africa. Medium-term cost-neutral prices were approximately $50-100 higher than short-term cost-neutral prices for rifampin-susceptible tuberculosis and $250-550 higher for rifampin-resistant tuberculosis. Health system cost-neutral prices that excluded patient-borne costs were 45-70% lower (rifampin-susceptible regimens) and 15-50% lower (rifampin-resistant regimens) than the cost-neutral prices that included patient costs. Cost-effective prices were substantially higher. Shorter duration was the most important driver of medium-term savings with novel regimens, followed by ease of adherence., Interpretation: Improved tuberculosis regimens, particularly shorter regimens or those that facilitate better adherence, could reduce overall costs, potentially offsetting higher prices., Funding: WHO., Competing Interests: Declaration of interests TSR, CL, DWD, and EAK report funding from WHO. TSR and EAK report funding from the Bill & Melinda Gates Foundation. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)