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BACKGROUND: Tuberculosis (TB) poses a significant risk to people with HIV (PWH), with heightened incidence and prevalence rates, especially in countries with a high TB burden. This study assesses the prevalence and incidence rates of TB among PWH during the COVID-19 pandemic, and on treatment outcomes in TB-HIV co-infections. METHODS: A retrospective study was conducted at Suddhavej Hospital, Faculty of Medicine, Mahasarakham University, Maha Sarakham, Thailand, from January 2020 to September 2023, involving newly diagnosed adult PWH. Data were collected on TB prevalence and incidence rates, with TB cases categorized as definite or possible. The primary outcomes were TB prevalence and incidence rates per 100,000 person-years of follow-up. RESULTS: Among 171 newly diagnosed PWH, the prevalence of TB was 5.85%, with an incidence rate of 4,568.71 per 100,000 person-years. All but one TB cases were diagnosed before antiretroviral therapy (ART) initiation. There was no incident TB during the follow-up period during ART. Nearly half of the TB cases required therapeutic trials without microbiological confirmation. CONCLUSIONS: The study revealed a high prevalence and incidence rate of TB among PWH during the COVID-19 pandemic, comparable to pre-pandemic rates in Thailand. The findings highlight the necessity of comprehensive TB screening prior to ART initiation and the cautious implementation of universal TB preventive therapy. The use of molecular diagnostics, in addition to symptom screening, can enhance TB diagnosis among PWH, though accessibility remains an issue in many regions.

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Tuberculosis (TB) contact tracing and TB preventive treatment are key tools in preventing the transmission of TB with the aim of eliminating the disease. Our study seeks to demonstrate how the infection spread from an individual patient to the entire community and how proactive contact tracing facilitated prompt diagnosis and treatment. Our work was conducted as a retrospective analysis of the spread of TB infection within the Roma community in the Czech Republic, following the case of an index patient who succumbed to pulmonary TB. Several levels of care and preventive and treatment measures are outlined. Confirming the identity of the Mycobacterium tuberculosis strain was achieved using molecular methods. Among the 39 individuals examined, TB disease was detected in eight patients and TB infection was detected in six patients. The investigation of contacts within this group yielded positive results in 36% of cases, necessitating treatment. The study's findings provide evidence that actively tracing individuals at risk can lead to early detection of cases, prompt treatment, and prevention of further disease transmission. The study also indicates that the highest risk of infection occurs within the sick person's household and that young children under the age of 5 are most susceptible to falling ill.

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BACKGROUND: Isoniazid preventive therapy (IPT) works to prevent tuberculosis (TB) among people living with HIV (PLHIV), but uptake remains low in Sub-Saharan Africa. In this analysis, we sought to identify barriers mid-level managers face in scaling IPT in Uganda and the mechanisms by which the SEARCH-IPT trial intervention influenced their abilities to increase IPT uptake. METHODS: The SEARCH-IPT study was a cluster randomized trial conducted from 2017-2021. The SEARCH-IPT intervention created collaborative groups of district health managers, facilitated by local HIV and TB experts, and provided leadership and management training over 3-years to increase IPT uptake in Uganda. In this qualitative study we analyzed transcripts of annual Focus Group Discussions and Key Informant Interviews, from a subset of SEARCH-IPT participants from intervention and control groups, and participant observation field notes. We conducted the analysis using inductive and deductive coding (with a priori codes and those derived from analysis) and a framework approach for data synthesis. RESULTS: When discussing factors that enabled positive outcomes, intervention managers described feeling ownership over interventions, supported by the leadership and management training they received in the SEARCH-IPT study, and the importance of collaboration between districts facilitated by the intervention. In contrast, when discussing factors that impeded their ability to make changes, intervention and control managers described external funders setting agendas, lack of collaboration in meetings that operated with more of a 'top-down' approach, inadequate supplies and staffing, and lack of motivation among frontline providers. Intervention group managers mentioned redistribution of available stock within districts as well as between districts, reflecting efforts of the SEARCH-IPT intervention to promote between-district collaboration, whereas control group managers mentioned redistribution within their districts to maximize the use of available IPT stock. CONCLUSIONS: In Uganda, mid-level managers' perceptions of barriers to scaling IPT included limited power to set agendas and control over funding, inadequate resources, lack of motivation of frontline providers, and lack of political prioritization. We found that the SEARCH-IPT intervention supported managers to design and implement strategies to improve IPT uptake and collaborate between districts. This may have contributed to the overall intervention effect in increasing the uptake of IPT among PLHIV compared to standard practice. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03315962 , Registered 20 October 2017.

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BACKGROUND: Isoniazid preventive therapy (IPT) is recommended for tuberculosis prevention yet data on the safety of first-trimester pregnancy exposure are limited. METHODS: Planned secondary analysis in a TB prevention trial of adverse pregnancy outcomes among participants assigned to 9-month IPT who became pregnant during (IPT-exposed) or after (unexposed) IPT. Regression models compared binary outcomes of a composite adverse outcome (any non-live birth, excluding induced abortion); preterm delivery <37 weeks; and low birth weight <2500 g) among exposure groups. Models were adjusted for latent TB infection, maternal age, CD4 count, and antiretroviral therapy (ART). RESULTS: In total, 128 participants had a known pregnancy outcome; 39 IPT-exposed and 89 unexposed. At pregnancy outcome, ART use was lower in IPT-exposed (79%) than unexposed women (98%). Overall, 29 pregnancies ended in a composite adverse outcome (25 spontaneous abortions, 2 stillbirths and 2 ectopic pregnancies), 15 preterm deliveries, and 10 infants with low birth weight. IPT was associated with the composite adverse outcome adjusting for covariates at enrollment (adjusted relative risk [aRR] 1.98; 95% confidence interval [CI] 1.15, 3.41), but the effect was attenuated when adjusted for covariates at pregnancy outcome (aRR 1.47; 95% CI .84, 2.55); IPT was not associated with preterm delivery (relative risk [RR] 0.87; 95% CI .32-2.42) or low birth weight (RR 1.01; 95% CI .29, 3.56). CONCLUSIONS: First-trimester IPT exposure was associated with nearly two-fold increased risk of fetal demise, mostly spontaneous abortion, though the association was attenuated when adjusted for covariates proximal to pregnancy outcome including ART use. Further study is needed to inform TB prevention guidelines.

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BACKGROUND: Inadequate numbers of children under five years of age who are exposed to tuberculosis (TB) in the home (child contact) are initiated on TB preventive treatment (TPT) in South Africa. We assessed barriers of initiating isoniazid preventive therapy (IPT) in this age group. METHODS: We conducted a qualitative study at two primary health clinics in the Ekurhuleni district in Gauteng Province. Between April and July 2019, we enrolled facility managers, TB staff and parents or legal guardians of child contacts (caregivers) attending for care, at the two facilities. Semi-structured questionnaires, facility observations and in-depth interviews using a semi-structured interview guide were used to collect data. Findings from the semi-structured questionnaires with facility staff and facility observations were summarized. Thematic analysis with a deductive approach was used to analyse the data from the in-depth interviews with caregivers. RESULTS: Two facility managers took part in the study and were assisted to complete the semi-structured questionnaires by TB staff. Fifteen caregivers aged between 18 and 43 years were interviewed of which 13 (87%) were female. Facility managers and TB staff (facility staff) felt that even though caregivers knew of family members who were on TB treatment, they delayed bringing their children for TB screening and TPT. Facility staff perceived caregivers as not understanding the purpose and benefits of TB prevention strategies such as TPT. Caregivers expressed the desire for their children to be screened for TB. However, caregivers lacked knowledge on TB transmission and the value of TB prevention in children at high risk of infection. CONCLUSION: While facility staff perceived caregivers to lack responsibility, caregivers expressed limited knowledge on the value of screening their children for TB as reasons for not accessing TB preventive services. Health education on TB transmission, screening, and TB prevention strategies at a community level, clinics, creches, schools and via media are important to achieve the global end TB goal of early detection and prevention of TB.

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OBJECTIVE: The primary objective of this study was to ascertain the acceptance, initiation, implementation and treatment completion rates of tuberculosis (TB) preventive therapy (TPT) using 3HP (INH-Rifapentine) among household contacts of microbiologically confirmed drug sensitive TB cases on anti-tubercular treatment under programmatic real-world settings. The secondary objectives were to estimate the prevalence and predictors of latent TB infection (LTBI) in household contacts of the index TB cases. We also ascertained the safety profile of the 3HP TPT regimen in the household contacts. METHODS: This prospective observational study was conducted at 10 TB chest clinics in Delhi, India during 2022-2023. Household contacts aged 14 and older who tested positive for TB infection on a Tuberculin Skin test were initiated on the 3HP regimen. Logistic regression was performed by including statistically significant independent variables in multiple prediction models. p < 0.05 was considered statistically significant. STATA, version 15.1, was used to compute all analyses. RESULTS: A total of 1067 (84.68%) eligible contacts of microbiologically confirmed, drug sensitive TB cases underwent screening with tuberculin skin test (TST), 614 (95.6%) LTBI positive contacts accepted the initiation of TPT, and 564 (91.8%) of those initiated on TPT completed the treatment. The major reason for refusal of screening was the lack of perception of risk of TB disease due to asymptomatic status. The prevalence of LTBI positivity through TST was 61.5% (95% CI, 58.5%, 64.4%). Adverse events were reported by 195 (31.8%) contacts initiated on 3HP of which 20 participants discontinued TPT. None of the sociodemographic factors showed a significant association with LTBI positivity (except age) or TPT completion rates. CONCLUSION: LTBI management with 3HP is feasible among adolescent and adult household contacts in India with high rates of adherence from initiation until treatment completion. The maximum attrition of participants occurred at the time of screening for LTBI using TST.

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INTRODUCTION: Tuberculosis (TB) is a leading infectious cause of global morbidity and mortality, affecting nearly a quarter of the human population and accounting for over 10 million deaths each year. Over the past several decades, TB incidence and mortality have gradually declined, but 2021 marked a threatening reversal of this trend highlighting the importance of accurate diagnosis and effective treatment of all forms of TB. AREAS COVERED: This review summarizes advances in TB diagnostics, addresses the treatment of people with TB infection and TB disease including recent evidence for treatment regimens for drug-susceptible and drug-resistant TB, and draws attention to special considerations in children and during pregnancy. EXPERT OPINION: Improvements in diagnosis and management of TB have expanded the available options for TB control. Molecular testing has enhanced the detection of TB disease, but better diagnostics are still needed, particularly for certain populations such as children. Novel treatment regimens have shortened treatment and improved outcomes for people with TB. However, important questions remain regarding the optimal management of TB. Work must continue to ensure the potential of the latest developments is realized for all people affected by TB.

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Tuberculosis infection (TBI) is defined as a state of infection in which individuals host live Mycobacterium tuberculosis with or without clinical signs of active TB. It is now understood as a dynamic process covering a spectrum of responses to infection resulting from the interaction between the TB bacilli and the host immune system. The global burden of TBI is about one-quarter of the world's population, representing a reservoir of approximately 2 billion people. On average, 5-10% of people who are infected will develop TB disease over the course of their lives, but this risk is enhanced in a series of conditions, such as co-infection with HIV. The End-TB strategy promotes the programmatic management of TBI as a crucial endeavor to achieving global targets to end the TB epidemic. The current development of new diagnostic tests capable of discriminating between simple TBI and active TB, combined with novel short-course preventive treatments, will help achieve this goal. In this paper, we present the current situation and recent developments of management of TBI and the operational challenges.

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OBJECTIVE: To summarise latent tuberculosis infection (LTBI) management strategies among household contacts of bacteriologically confirmed pulmonary tuberculosis (TB) patients in high-TB burden countries. METHODS: PubMed/MEDLINE (NCBI) and Scopus were searched (January 2006 to December 2021) for studies reporting primary data on LTBI management. Study selection, data management and data synthesis were protocol-driven (PROSPERO-CRD42021208715). Primary outcomes were the proportions of LTBI, initiating and completing tuberculosis preventive treatment (TPT). Reported factors influencing the LTBI care cascade were qualitatively synthesised. RESULTS: From 3694 unique records retrieved, 58 studies from 23 countries were included. Most identified contacts were screened (median 99%, interquartile range [IQR] 82%-100%; 46 studies). Random-effects meta-analysis yielded pooled proportions for: LTBI 41% (95% confidence interval [CI] 33%-49%; 21,566 tested contacts); TPT initiation 91% (95% CI 79%-97%; 129,573 eligible contacts, 34 studies); TPT completion 65% (95% CI 54%-74%; 108,679 TPT-initiated contacts, 28 studies). Heterogeneity was significant (I2 ≥ 95%-100%) and could not be explained in subgroup analyses. Median proportions (IQR) were: LTBI 44% (28%-59%); TPT initiation 86% (60%-100%); TPT completion 68% (44%-82%). Nine broad themes related to diagnostic testing, health system structure and functions, risk perception, documentation and adherence were considered likely to influence the LTBI care cascade. CONCLUSION: The proportions of household contacts screened, detected with LTBI and initiated on TPT, though variable was high, but the proportions completing TPT were lower indicating current strategies used for LTBI management in high TB burden countries are not sufficient.

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The objective was to implement CI under national tuberculosis programmatic conditions and to advocate for its scaling up. Contact investigation was implemented in 150 Basic Management Units identified across eight countries. The target populations (children <5 years and persons living with HIV (PLHIV)) were evaluated during home and clinic visits using standardized tools, clinical examinations and, according to each country, additional tests. Contacts with active TB received TB treatment and those eligible received TB preventive therapy (TPT). Data were collected each quarter using standardized forms. Meetings were organized with partners to share preliminary results and advocate for scaling up. From October 2020 to December 2021, 9049 home visits were performed. The proportions of children <5 years and PLHIV who were screened and diagnosed with active TB were, respectively, 2.6% and 10.1%. Ninety-three percent of children <5 years and 98% of PLHIV living at home received TPT or TB treatment, respectively. The scale-up for contact investigation partially or at national level in 2022 was effective in six of the eight countries included in the project. These results indicate that CI is feasible under programmatic conditions within the National TB Programs of African countries.

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BACKGROUND: Targeted testing and treatment (TTT) for latent tuberculosis (TB) infection (LTBI) is a recommended strategy to accelerate TB reductions and further TB elimination in the United States. Evidence on cost-effectiveness of TTT for key populations can help advance this goal. METHODS: We used a model of TB transmission to estimate the numbers of individuals who could be tested by interferon-γ release assay and treated for LTBI with 3 months of self-administered rifapentine and isoniazid (3HP) under various TTT scenarios. Specifically, we considered rapidly scaling up TTT among people who are non-US-born, diabetic, living with human immunodeficiency virus (HIV), homeless or incarcerated in California, Florida, New York, and Texas-states where more than half of US TB cases occur. We projected costs (from the healthcare system perspective, in 2018 dollars), 30-year reductions in TB incidence, and incremental cost-effectiveness (cost per quality-adjusted life-year [QALY] gained) for TTT in each modeled population. RESULTS: The projected cost-effectiveness of TTT differed substantially by state and population, while the health impact (number of TB cases averted) was consistently greatest among non-US-born individuals. TTT was most cost-effective among persons with HIV (from $2828/QALY gained in Florida to $11 265/QALY gained in New York) and least cost-effective among people with diabetes (from $223 041/QALY gained in California to $817 753/QALY in New York). CONCLUSIONS: The modeled cost-effectiveness of TTT for LTBI varies across states but was consistently greatest among people with HIV; moderate among people who are non-US-born, incarcerated, or homeless; and least cost-effective among people with diabetes.

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INTRODUCTION: In 2017, the Aurum Institute, with support from Unitaid, launched an initiative to expand short-course therapy for the prevention of tuberculosis (TB) in 12 high-burden countries. This study aimed to investigate the importance of "catalytic" effects beyond the original project timeframe when estimating cost-effectiveness of such large investments. METHODS: We estimated the cost-effectiveness of the IMPAACT4TB (I4TB) initiative from a health system perspective, using a 10-year time horizon. We first conservatively estimated costs using a "top-down" approach considering only the direct health benefits of providing TB preventive therapy to people initiating antiretroviral therapy (ART) through I4TB activities. We then re-estimated the incremental cost-effectiveness of I4TB incorporating the costs and health benefits of potential catalytic effects beyond the program itself. RESULTS: We estimated that TB preventive therapy through the I4TB initiative alone would prevent 14 201 cases of active TB and 1562 TB deaths over 10 years with an up-front investment of $52.5 million; the estimated incremental cost-effectiveness was $1580 per disability-adjusted life year (DALY) averted. If this initiative could achieve its desired catalytic effects, an additional 375 648 cases and 41 321 deaths could be averted, at an incremental cost of $546 million and cost-effectiveness of $713 per DALY averted. CONCLUSIONS: Our findings provide donors with reasonable evidence of value for money to support investment in short-course TB preventive therapy for people initiating ART in high-burden settings. Our study also illustrates the importance of considering long-term secondary ("catalytic") effects when evaluating the cost-effectiveness of large-scale initiatives designed to change a global policy landscape.

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After many years of TB 'control' and incremental progress, the TB community is talking about ending the disease, yet this will only be possible with a shift in the way we approach the TB response. While the Asia-Pacific region has the highest TB burden worldwide, it also has the opportunity to lead the quest to end TB by embracing the four areas laid out in this series: using data to target hotspots, initiating active case finding, provisioning preventive TB treatment, and employing a biosocial approach. The Stop TB Partnership's TB REACH initiative provides a platform to support partners in the development, evaluation and scale-up of new and innovative technologies and approaches to advance TB programs. We present several approaches TB REACH is taking to support its partners in the Asia-Pacific and globally to advance our collective response to end TB.

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BACKGROUND: Tuberculosis (TB) preventive therapy (TPT), including isoniazid preventive therapy (IPT), has been implemented within the Nigerian human immunodeficiency virus (HIV) programme since 2014. However, drug procurement and logistic support has remained the responsibility of the National Tuberculosis and Leprosy Control Programme. The US President's Emergency Plan for AIDS Relief-Nigeria (PEPFAR Nigeria) reviewed the key bottlenecks to TPT implementation in 2016. METHOD: The logistics of delivery of isoniazid (INH) were integrated with the antiretroviral (ARV) logistics management and information system (LMIS). Drug order and requisition forms at the facility level were revised to include INH, along with training on appropriate quantification and requisition of INH with ARVs. Support was provided for last mile delivery of INH directly to every implementing site, alongside ARV. REULTS: We observed an increasing trend in TPT uptake between the pre-and-post intervention periods: 6% in fiscal year (FY) 2015, 7% in FY2016 and 12% in FY2017. Overall, the logistical changes in the LMIS to include INH in 2016 led to a 69% increase in TPT by the end of FY2017; this was statistically significant. CONCLUSION: Addressing logistical challenges to TPT implementation will ensure that the TB and HIV programmes can tackle the increasing burden of TB infection in people living with HIV. We recommended that the provider-to-client stage of TPT implementation be driven by the HIV programme and that cross-communication between the two programmes be improved.

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Ending the tuberculosis (TB) epidemic by 2030 requires two key actions: rapid diagnosis and effective treatment of active TB and identification and treatment of latent TB infection to prevent progression to active disease. We introduce this perspective by documenting the growing importance of TB preventive therapy on the international agenda coupled with global data showing poor implementation of preventive activities in programmatic settings. We follow this with two principal objectives. The first is to examine implementation challenges around diagnosis and treatment of active TB. Within this, we include recent evidence about the continued morbidity and heightened mortality that persists after TB treatment is successfully completed, thus elevating the importance of TB preventive therapy. The second objective is to outline how current TB preventive therapy activities have been shaped and are managed and propose how these can be improved through research and innovation. This includes expanding and giving higher priority to certain high-risk groups including those with fibrotic lung lesions on chest X-ray, showcasing the need to develop and deploy new biomarkers to more accurately predict risk of disease and making shorter treatment regimens, especially with rifapentine-isoniazid, more user-friendly and widely available. Ending the TB epidemic requires not only cure of the disease but preventing it before it even begins.

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Tuberculosis (TB) has been a leading infectious cause of death worldwide for much of human history, with 1.6 million deaths estimated in 2017. The Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health has played an important role in understanding and responding to TB, and it has made particularly substantial contributions to prevention of TB with chemoprophylaxis. TB preventive therapy is highly efficacious in the prevention of TB disease, yet it remains underutilized by TB programs worldwide despite strong evidence to support its use in high-risk groups, such as people living with HIV and household contacts, including those under 5 years of age. We review the evidence for TB preventive therapy and discuss the future of TB prevention.

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