Tuberculosis Preventive Treatment Research Articles

Tuberculosis Preventive Treatment for Pregnant People With Human Immunodeficiency Virus in South Africa: A Modeling Analysis of Clinical Benefits and Risks.

Although prior studies of tuberculosis-preventive treatment (TPT) for pregnant people with human immunodeficiency virus (PPWH) report conflicting adverse pregnancy outcome (APO) risks, international guidelines recommend TPT for PPWH. We used a microsimulation model to evaluate 5 TPT strategies among PPWH receiving antiretroviral therapy in South Africa: No TPT; 6 months of isoniazid (6H) or 3 months of isoniazid-rifapentine (3HP) during pregnancy (Immediate 6H or Immediate 3HP) or post partum (Deferred 6H or Deferred 3HP). The primary outcomes were maternal, fetal/infant, and combined deaths from causes potentially influenced by TPT (maternal tuberculosis, maternal hepatotoxicity, stillbirth, low birth weight [LBW], and infant tuberculosis). Tuberculosis during pregnancy confers 250% and 81% higher modeled risks of stillbirth and LBW, respectively. In lower-risk or higher-risk scenarios, immediate TPT confers 38% lower or 92% higher risks of stillbirth and 16% lower or 35% higher risks of LBW. Immediate TPT would minimize deaths among PPWH. When TPT confers higher stillbirth and LBW risks, immediate TPT would produce the most combined maternal and fetal/infant deaths, even with low maternal CD4 cell count and high tuberculosis incidence. If immediate TPT yields a <4% or <20% increase in stillbirth or LBW, immediate TPT would produce fewer combined deaths than deferred TPT (sensitivity analysis range, <2%-22% and <11%-120%, respectively). If APO risks are below identifiable thresholds, TPT during pregnancy could decrease combined maternal and fetal/infant deaths. Given uncertainty around isoniazid's risks, and the low threshold at which APO risks could outweigh benefits from tuberculosis deaths averted, studies of newer TPT regimens among PPWH are warranted to inform guidelines.

Incidence of active tuberculosis in HIV-infected individuals not receiving universal tuberculosis preventive treatment

Incidence of active tuberculosis in HIV-infected individuals not receiving universal tuberculosis preventive treatment

Modeling and analysis of transmission dynamics of tuberculosis with preventive treatment and vaccination strategies in China

In China, approximately 350 million people with latent tuberculosis infection (LTBI) are the major source of new TB cases, meanwhile, BCG vaccination for newborns and children under five fails to fully arrest the TB epidemic due to the mechanisms of vaccine failure. It is expected that widespread TB preventive treatment (TPT) and new vaccination strategies may be solutions to end TB. This work allows for TPT and vaccination strategies in a nonlinear age-structured SVEIR model with nonexponential residence times to exploit the interventions for ending TB in China. Global stability analysis reveals that the target model preserves the threshold-value dynamics in terms of the basic reproduction number so that some existing results are extended, moreover, the model is applied to fit the data of TB cases in China. Furthermore, sensitivity analysis for endemic steady state suggests that four potentially feasible interventions (i.e., amplifying the inhibition effect of infectious individuals by limiting range of their mobility, shortening the treatment duration for patients, adopting BCG revaccination and enhancing the rate of TPT) can lower the steady level of infectious individuals at endemic steady state and delay its arrival time. Finally, several multifaceted strategies composed of these interventions are compared via emulational experiments. We conclude that the target of End TB Strategy by 2035 in China would be reached just by the multifaceted strategy with moderate intensity if BCG revaccination, the duration of TPT for 2 months and a 40% completion rate are realized. This investigation sheds light on the fantastic potential applications of new TPT and vaccination strategies.

Strengthening and standardizing the preventive treatment for tuberculosis in comprehensive medical facilities

Preventive treatment of high-risk groups for tuberculosis is an important part of tuberculosis prevention and control strategies, and comprehensive medical facilities have an important role to play. This issue of the journal published the "Expert consensus on tuberculosis preventive treatment for individuals at high risk of developing active diseases from latent tuberculosis infection in comprehensive medical facilities". The consensus defined the target population for tuberculosis preventive treatment, recommended the timing of treatment initiation and optional treatment regimens for different groups, and put forward suggestions for the management of preventive treatment. It helped to guide the comprehensive medical facilities to provide more standardized tuberculosis preventive treatment. This article discussed the background and clinical significance of the consensus.

Expert consensus on tuberculosis preventive treatment for individuals at high risk of developing active diseases from latent tuberculosis infection in comprehensive medical facilities

Expert consensus on tuberculosis preventive treatment for individuals at high risk of developing active diseases from latent tuberculosis infection in comprehensive medical facilities

Comprehensive Tuberculosis Screening and Treatment at a Prison in Central Papua Province, Indonesia.

Incarcerated people have been reported to have higher rates of tuberculosis (TB) than the general population. However, TB is rarely reported among incarcerated people in correctional facilities in Mimika District, in Central Papua Province of Indonesia. This study aims to describe the outcomes of comprehensive screening and treatment of TB disease and latent TB infection (LTBI) within a prison in Mimika. In response to a newly reported case of TB within a prison, a facility-wide comprehensive screening and treatment program was carried out for both TB disease and LTBI between September 2021 and June 2022. We evaluated the outcomes of the screening intervention, including the number of people found to have TB and LTBI and the number and proportion of people who started and completed TB-preventive treatment at the facility. A total of 403 incarcerated people and facility staff participated in the comprehensive screening program. Ten participants were found to have TB disease, all of whom commenced treatment. LTBI was detected in 256 (64%) participants, 251 (98%) of whom completed TB-preventive treatment. Comprehensive screening revealed a high prevalence of TB disease and LTBI in this prison. Completion of treatment for TB disease and latent TB infection was high. These outcomes suggest a role for routine search-treat-prevent strategies for TB in this setting.

Cost-effectiveness of screening with transcriptional signatures for incipient TB among U.S. migrants.

Host-response-based transcriptional signatures (HrTS) have been developed to identify "incipient tuberculosis (TB)". No study has reported the cost-effectiveness of HrTS for post-arrival migrant screening programs in low-incidence countries. To assess the potential health impact and cost-effectiveness of HrTS for post-arrival TB infection screening among new migrants in the United States. We used a discrete-event simulation model to compare four strategies: (1) no screening for TB infection or incipient TB; (2) 'IGRA-only', screen all with interferon gamma release assay (IGRA), provide TB preventive treatment for IGRA-positives; (3) 'IGRA-HrTS', screen all with IGRA followed by HrTS for IGRA-positives, provide incipient TB treatment for individuals testing positive with both tests; and (4) 'HrTS-only', screen all with HrTS, provide incipient TB treatment for HrTS-positives. We assessed outcomes over the lifetime of migrants entering the U.S. in 2019, assuming HrTS met the WHO Target Product Profile (TPP) optimal criteria. We conducted sensitivity analyses to evaluate the robustness of results. The IGRA-only strategy dominated the HrTS-based strategies under both healthcare sector and societal perspectives, with an incremental cost-effectiveness ratio of $78,943 and $89,431 per quality-adjusted life-years (QALY) gained, respectively. This conclusion was robust to varying costs ($15-300) and characteristics of HrTS, and the willingness-to-pay threshold ($30,000-150,000/ QALY gained), but sensitive to the rate of decline in TB progression risk after U.S. entry. Our findings suggest that HrTS meeting the WHO TPP is unlikely to be a cost-effective component of post-arrival screening for migrants entering the U.S.

Clinical characteristics and mortality of tuberculosis among adults living with HIV/AIDS: A single center, retrospective cohort study in Thailand.

Tuberculosis (TB) among people living with HIV/AIDS (PLWHA) contributes substantially to morbidity and mortality, particularly in high TB burden countries. Our objective is to investigate the clinical characteristics and mortality rates associated with TB among adult PLWHA over a 10-year period at an urban HIV clinic situated in a high TB burden country. A retrospective cohort study was conducted in 2022. The primary endpoints were clinical characteristics and mortality rate of TB, determined as per 100 person-years among adult PLWHA, presented with a 95% confidence interval. Univariable and multivariable Cox proportional regression analyses were performed to determine risk factors for TB mortality. From January 2012-December 2022, 155 PLWHA receiving a diagnosis of TB were enrolled. The median age was 29 (26.5-48.5) years, and the median CD4 + T cell count was 141 (41.8-252.8) cells/µL, with 60.0% of patients with TB manifesting as disseminated infection. The most involved organs were pulmonary (89.7%), lymph nodes (39.4%) and pleura (14.8%). The treatment outcomes exhibited success in 63.2% of cases, relapse in 5.2%, loss to follow up in 17.4% and death in 14.2%. The overall mortality rate was 18.8 per 100 person-years. Multivariable analyses showed significant factors affecting mortality, including lymph node involvement (adjusted HR 3.5; 95% CI 1.1-10.8) and thrombocytopenia (adjusted HR 74.2; 95% CI 10.0-551.4). TB in PLWHA, commonly presenting as disseminated infection, contributes to high mortality. Lymph node involvement and thrombocytopenia are significant factors contributing to mortality. Tuberculosis preventive treatment should be considered for improved prevention strategies among PLWHA, particularly in high TB burden countries.

Agreement between Mycobacterium tuberculosis antigen-based skin test and interferon-gamma release assay in elderly individuals aged ≥65 years in China

ObjectivesTo determine the agreement of Mycobacterium tuberculosis (TB) antigen-based skin test (TBST) with interferon-gamma release assay (IGRA) in elderly individuals aged ≥65 years beyond instruction for use in China. MethodsBased on the baseline survey of randomized controlled trial with the objective of exploring suitable regimens for TB preventive treatment, M. tuberculosis infection was tested using TBST and IGRA in parallel in rural residents aged 50–70 years using a cross-sectional study design. ResultsA total of 21 219 participants with both TBST and IGRA results were included in this analysis. The concordance between TBST and IGRA was 89.4% (95% CI, 89.0–89.8%) with a kappa coefficient of 0.61 (95% CI, 0.60–0.62). In those aged ≥65 years, the concordance was 86.5% (95% CI, 85.6–87.4%) with a kappa coefficient of 0.55 (95% CI, 0.52–0.58). 21.2% (35/165) of the participants with indeterminate IGRA results were TBST positive, and nine of them were aged ≥65 years. Discussion: The consistent agreement between TBST and IGRA in individuals aged ≥65 years suggests that TBST has the potential to be used in the elderly with age beyond instruction for use in China. The respective diagnostic performance of each test will be analysed when the longitudinal data on incident TB is obtained in the future.

The significance of preventive treatment for tuberculosis infection in children

Objective: to evaluate the value of tuberculosis preventive treatment (PTT) in children with tuberculosis infection. Material and methods. As part of a continuous study, a cohort of 200 children from 1 to 17 years old taken for clinical observation in group VI A (positive test result with the recombinant tuberculosis allergen [ATR]) was analyzed. All children underwent additional examination methods to exclude the local form of tuberculosis: physical examination, laboratory clinical and biochemical tests of blood and urine, multislice computed tomography of the chest organs and, according to clinical recommendations, PTT was proposed, which the parents of 65 children refused. Study groups: 1 — those with no family contact with a patient with tuberculosis (ТВ) (n=70): 2 — those with contact with a patient with ТВ (n=65), in group 3 included children whose parents refused PTT, despite the presence of indications (n=65), incl. 14 children were from Tl lesions. Children group 1 and 2 received PTT. Control over the PTT was carried out on the "Yandex.Teleconference". Results. As a result of comparison of the three groups, reliable data were obtained on the effectiveness of PTT according to the criteria of preventing the disease and reducing the results of the ATR test. A significantly high percentage of sick children in group 3 was established, compared with children from group 1 (p=0.008; x2=18.6). When assessing the dynamics of the results of immunodiagnostic tests in children of the group 1 who received PTT, a decrease in the test with ATR was significantly more often observed compared to children without PTT(p=0.001; x2=17.2). It is worth noting that children had satisfactory tolerability of the drugs; no adverse events were observed in patients with daily video recording. Conclusion. A conclusion was made about the need for preventive work with parents of children who refused preventive treatment to increase their level of adherence, the need to evaluate the effectiveness of PTT courses using primary and additional criteria, including the importance of controlled PTT.

Tuberculosis Preventive Treatment (TPT) in India: A Qualitative Review

Tuberculosis Preventive Treatment (TPT) in India: A Qualitative Review

Test and treat approach for tuberculosis infection amongst household contacts of drug-susceptible pulmonary tuberculosis, Mumbai, India.

Mumbai is one of the most densely populated areas in the world and is a major contributor to the tuberculosis (TB) epidemic in India. A test and treat approach for TB infection (TBI) amongst household contacts (HHC) is part of the national policy for TB preventive treatment (TPT). However, in practice, the use of interferon-gamma release assay (IGRA) tests for infection are limited, and prevalence of TBI in Mumbai is not known. We conducted a cross-sectional study among HHCs exposed to persons with microbiologically-confirmed, drug-susceptible pulmonary TB that were notified for antituberculosis treatment in Mumbai, India during September-December, 2021. Community-based field workers made home visits and offered IGRA (QuantiFERON-TB® Gold In-Tube Plus) tests to HHC aged 5 years and older. After ruling out active TB disease, HHC with IGRA-positive test results were referred for TPT. All HHC were monitored for at least 24 months for progression to active TB disease. Among 502 HHCs tested, 273 (54%) had IGRA-positive results. A total of 254 (93%) were classified as TBI and were eligible for TPT, of which 215 (85%) initiated TPT, and 194 (90%) completed TPT successfully. There was substantial variation in rates of TBI per household. In 32% of households, all HHC (100%) were IGRA positive and in 64% of households >50% of HHC were infected. In all, 22 HHCs (4%; 22/558) were diagnosed with TB disease; of these, five HHC were diagnosed during follow up, of which three were IGRA positive and had no evidence of disease at initial screening but chose not to initiate TPT. A test and treat strategy for HHC resulted in the detection of a substantial proportion of TBI and secondary TB cases. Home-based IGRA testing led to high participation rates, clinical evaluations, TPT initiation, and early diagnoses of additional secondary cases. A community-focused, test and treat approach was feasible in this population and could be considered for broader implementation.

Improving access to tuberculosis preventive treatment for children in Ethiopia: designing a home-based contact management intervention for the CHIP-TB trial through formative research

BackgroundTuberculosis (TB) preventive treatment (TPT) is a long-standing recommendation for children exposed to TB but remains poorly implemented. Home-based contact management may increase access and coverage of TPT among children exposed to TB in their households.MethodsSixty in-depth interviews were conducted with key informants including program managers, TB providers (known as TB focal persons), health extension workers and caregivers whose children had recently engaged with TB prevention services in Oromia, Ethiopia in 2021 to understand the barriers and facilitators to providing home-based TB prevention services for children aged < 15 years. Thematic content analysis was conducted including systematically coding each interview.ResultsHome-based services were considered a family-centered intervention, addressing the time and financial constraints of clients. Stakeholders proposed a task-shared intervention between health extension workers and facility-based TB focal persons. They recommended that TB services be integrated into other home-based services, including HIV, nutrition, and vaccination services to reduce workload on the already overstretched health extension workers. Community awareness was considered essential to improve acceptability of home-based services and TPT in general among community members.ConclusionsDecentralization of TPT should be supported by task-sharing initiation and follow up between health extension workers and facility-based TB focal persons and integration of home-based services. Active community engagement through several existing mechanisms can help improve acceptability for both home-based interventions and TPT promotion overall for children.Trial registrationThe results presented here were from formative research related to the CHIP-TB Trial (Identifier NCT04369326) registered on April 30, 2020. This qualitative study was separately registered at NCT04494516 on 27 July 2020.

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

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. 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. The analysis compared tuberculosis infection screening and TPT, to no screening, considering a combination of M tuberculosis infection tests and TPT regimens. We quantified health effects as reductions in tuberculosis cases, tuberculosis deaths, and disability-adjusted life-years (DALYs). We assessed costs from a tuberculosis programme perspective. We report intervention cost-effectiveness as the incremental costs per DALY averted, and tested how results changed across subgroups of the target population. Compared with no intervention, an intervention incorporating tuberculin skin testing and treatment with 3 months of isoniazid and rifapentine would avert 31 (95% uncertainty interval 14-56) lifetime tuberculosis cases and 4·1 (1·4-5·8) lifetime tuberculosis deaths per 1000 individuals, and cost US$242 per DALY averted. All test and regimen combinations were cost-effective compared with no screening. Younger age, longer incarceration, and more recent prison release were each associated with significantly greater health benefits and more favourable cost-effectiveness ratios, although the intervention was cost-effective for all subgroups examined. M tuberculosis infection screening and TPT for individuals who were formerly incarcerated appears cost-effective, and would provide valuable health gains. National Institutes of Health. For the Portuguese translation of the abstract see Supplementary Materials section.

Facilitators and barriers to initiating and completing tuberculosis preventive treatment among children and adolescents living with HIV in Uganda: a qualitative study of adolescents, caretakers and health workers

IntroductionPeople living with HIV (PLHIV) have a 20-fold risk of tuberculosis (TB) disease compared to HIV-negative people. In 2021, the uptake of TB preventive treatment among the children and adolescents living with HIV at the Baylor-Uganda HIV clinic was 45%, which was below the national target of 90%. Minimal evidence documents the enablers and barriers to TB preventive treatment (TPT) initiation and completion among children and adolescents living with HIV(CALHIV). We explored the facilitators and barriers to TPT initiation and completion among CALHIV among adolescents aged 10-19years and caretakers of children below 18years.MethodsWe conducted a qualitative study from February 2022 to March 2023, at three paediatric and adolescent HIV treatment centers in Uganda. In-depth interviews were conducted at TPT initiation and after completion for purposively selected health workers, adolescents aged 10–19 years living with HIV, and caretakers of children aged below 18years.ResultsThe desire to avoid TB disease, previous TB treatment, encouragement from family members, and ministry of health policies emerged as key facilitators for the children and adolescents to initiate TPT. Barriers to TPT initiation included; TB and HIV-related stigma, busy carer and adolescent work schedules, reduced social support from parents and family, history of drug side effects, high pill burden and fatigue, and perception of not being ill. TPT completion was enabled by combined TPT and ART refill visits, delivery of ART and TPT within the community, and continuous education and counseling from health workers. Reported barriers to TPT completion included TB and HIV-related stigma, long waiting time. Non-disclosure of HIV status by caretakers to CALHIV and fear of side effects was cited by health workers as a barrier to starting TPT. Facilitators of TPT initiation and completion reported by healthcare workers included patient and caretaker health education, counselling about benefits of TPT and risk of TB disease, having same appointment for TPT and ART refill to reduce patient waiting time, adolescent-friendly services, and appointment reminder phone calls.ConclusionThe facilitators and barriers of TPT initiation and completion among CALHIV span from individual, to health system and structural factors. Health education about benefits of TPT and risk of TB, social support, adolescent-friendly services, and joint appointments for TPT and ART refill are major facilitators of TPT initiation and completion among CALHIV in Uganda.

Evaluating the implementation of weekly rifapentine-isoniazid (3HP) for tuberculosis prevention among people living with HIV in Uganda: A qualitative evaluation of the 3HP Options Trial.

Three months of isoniazid-rifapentine (3HP) is being scaled up for tuberculosis (TB) preventive treatment (TPT) among people living with HIV (PLHIV) in high-burden settings. More evidence is needed to identify factors influencing successful 3HP delivery. We conducted a qualitative assessment of 3HP delivery nested within the 3HP Options Trial, which compared three optimized strategies for delivering 3HP: facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), and patient choice between facilitated DOT and facilitated SAT at the Mulago HIV/AIDS clinic in Kampala, Uganda. We conducted 72 in-depth interviews among PLHIV purposively selected to investigate factors influencing 3HP acceptance and completion. We conducted ten key informant interviews with healthcare providers (HCPs) involved in 3HP delivery to identify facilitators and barriers at the clinic level. We used post-trial 3HP delivery data to assess sustainability. We conducted an inductive thematic analysis and aligned the emergent themes with the RE-AIM framework dimensions to report implementation outcomes. Understanding the need for TPT, once-weekly dosing, shorter duration, and perceived 3HP safety enhanced acceptance overall. Treatment monitoring by HCPs and reduced risk of HIV status disclosure enabled DOT acceptance. Dosing autonomy enabled SAT acceptance. Switching between DOT and SAT as required enabled acceptance for patient choice. Dosing reminders, reimbursement for clinical visits, and social support enabled 3HP completion; pill burden, side effects, and COVID-19-related treatment restrictions hindered completion. All HCPs were trained and participated in 3HP delivery with high fidelity. Training, care integration, and collaboration among HCPs enabled, whereas initial concerns about 3HP safety among HCPs delayed 3HP adoption and implementation. SAT was maintained post-trial; DOT was discontinued due to inadequate ongoing financial support beyond the study period. Facilitated delivery strategies made 3HP treatment convenient for PLHIV and were feasible and implemented with high fidelity by HCPs. However, the costs of 3HP facilitation may limit wider scale-up.

Incidence Rate and Risk Factors for Developing Active Tuberculosis Among People Living With HIV in Georgia 2019-2020 Cohort.

Tuberculosis (TB) is a leading cause of morbidity and mortality among people with HIV (PHIV) globally. Our study is the first to evaluate TB incidence and its risk factors among PHIV in the country of Georgia, where previously no data were available. A retrospective cohort study was conducted among persons newly diagnosed with HIV in Georgia during 2019-2020. Active TB incidence was calculated within a minimum of 2-year follow-up period from HIV diagnosis. Cox proportional hazard model was used for evaluating risk factors for TB development. The median age in the final cohort of 1165 PHIV was 38 (interquartile range, 30-48) and 76.3% were male. Twenty-nine percent of patients had a CD4 cell count <200 at HIV diagnosis and 89.9% initiated antiretroviral therapy (ART). TB incidence rate was 10/1000 person-years (p-y; 95% confidence interval [CI], 9.6-10.4), with rates being higher within several subgroups, mainly: PHIV aged 40-49 years (17.5/1 000 p-y [95% CI, 16.8-18.2]); those not receiving ART (22/1000 p-y [95% CI, 20.9-23.1]); those with CD4 < 200 at baseline (28/1000 p-y [95% CI, 27.4-28.6]); and those who developed AIDS (29.1/1 000 p-y [95% CI, 28.6-29.6]). Age (aHR, 1.2; 95% CI, 1.03-1.39; P = .01) and AIDS diagnosis (aHR, 3.2; 95% CI, 3.06-27.9; P = .001) were associated with TB development, whereas high CD4 count was protective against TB (aHR, 0.18; 95% CI, .06-.61; P = .005). Study results highlight an imperative role of CD4 cell count management and the need for early HIV diagnosis and timely initiation of ART to ensure an effective immune response against tuberculosis, stressing the need for further in-depth evaluation of the TB preventive treatment delivery system's efficiency and gaps.

Treatment of psoriasis with biologic and non-biologic targeted therapies in patients with latent tuberculosis infection or at risk for tuberculosis disease progression: Recommendations from a SPIN-FRT expert consensus.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a significant global health problem. In immunocompetent individuals, the microorganism can remain in a latent, non-contagious form, however, it may become active under conditions of immunosuppression. Tumour necrosis factor (TNF) inhibitors, which are frequently used for the management of immune-mediated disorders like psoriasis, have been associated with a significantly increased risk of reactivating latent TB. Consequently, international guidelines recommend TB screening and preventive treatment before starting anti-TNF therapy. These recommendations have extended to IL-12/23, IL-17, IL-23 and TYK2 inhibitors under a caution principle, despite their different mechanisms of action. However, current evidence suggests that some of these agents are arguably not associated with an increased risk of TB reactivation or development of TB disease after infection, which calls for a critical reassessment of these guidelines. We have conducted a literature search evaluating the risk of TB reactivation associated with these innovative therapies, integrating findings from both randomized clinical trials and real-world evidence. The identified evidence is limited but the low number of identified cases of reactivation with IL-17 and IL-23 inhibitors prompts reconsidering the need for preventive treatment for latent TB in all cases, regardless of biologic class or individual patient's risk of TB reactivation or drug toxicity. This review, along with the clinical insight of a panel of experts on behalf of the SPIN-FRT, led to the development of these consensus recommendations for managing psoriasis treatment in patients with latent TB infection or at risk of TB infection, who are receiving or are intended to receive biologic and non-biologic targeted therapies. These recommendations highlight the need for updates to the existing guidelines, aiming to provide a more differentiated approach that reflects the evolving landscape of psoriasis treatment and its implications for TB management.

Expanding Xpert MTB/RIF Ultra® and LF-LAM testing for diagnosis of tuberculosis among HIV-positive adults admitted to hospitals in Tanzania and Mozambique: a randomized controlled trial (the EXULTANT trial)

IntroductionTuberculosis (TB) is an important cause of morbidity and mortality among people living with HIV (PLHIV). Current WHO-recommended strategies for diagnosing TB among hospitalized PLHIV rely on symptom screening and disease severity to assess eligibility for urine lipoarabinomannan lateral flow (LF-LAM) and molecular testing. Despite these recommendations, autopsy studies show a large burden of undiagnosed TB among admitted PLHIV. The EXULTANT trial aims to assess the impact of an expanded screening strategy using three specimens (sputum, stool, and urine) for TB diagnosis among PLHIV admitted to hospitals in two high HIV and TB burden African countries.MethodsThis is a multicenter, pragmatic, individually randomized controlled trial conducted across eleven hospitals in Tanzania and Mozambique. Participants in the intervention arm will be tested with Xpert MTB/RIF Ultra® from expectorated sputum, stool, and urine samples, with additional urine LF-LAM testing in the first 24 h after hospital admission, irrespective of the presence of the symptoms. The control arm will implement the WHO standard of care recommendations. Hospitalized adults (≥ 18 years) with a confirmed HIV-diagnosis, irrespective of antiretroviral (ART) therapy status or presence of TB symptoms will be assessed for eligibility at admission. Patients with a pre-existing TB diagnosis, those receiving anti-tuberculosis therapy or tuberculosis preventive treatment in the 6 months prior to enrolment, and those transferred from other hospitals will not be eligible. Also, participants admitted for traumatic reasons such as acute abdomen, maternal conditions, scheduled surgery, having a positive SARS-CoV2 test will be ineligible. The primary endpoint is the proportion of participants with microbiologically confirmed TB starting treatment within 3 days of enrolment.DiscussionThe EXULTANT trial investigates rapid implementation after admission of a new diagnostic algorithm using Xpert MTB/RIF Ultra® in several non-invasive specimens, in addition to LF-LAM, in hospitalized PLHIV regardless of TB symptoms. This enhanced strategy is anticipated to detect frequently missed TB cases in this population and is being evaluated as an implementable and scalable intervention.Trial registrationTrial reference number: NCT04568967 (ClinicalTrials.gov) registered on 2020–09-29.

Disseminated, fatal reactivation of bovine tuberculosis in a patient treated with adalimumab: a case report and review of the literature.

Tumor necrosis factor inhibitors (TNFi) are known to increase the risk of tuberculosis (TB) reactivation, though cases involving Mycobacterium bovis are rarely reported. We describe a case of disseminated TB with M. bovis in a 78-year-old woman with a negative Interferon-Gamma-Release Assay (IGRA), taking adalimumab due to rheumatoid polyarthritis, which resulted in a fatal outcome. The atypical clinical and histopathological features were initially interpreted as sarcoidosis. The case occurred in Switzerland, an officially bovine tuberculosis-free country. The whole genome sequence of the patient's cultured M. bovis isolate was identified as belonging to the animal lineage La1.2, the main genotype in continental Europe, but showed significant genetic distance from previously sequenced Swiss cattle strains. In a literature review, four cases of bovine tuberculosis reactivation under TNFi treatment were identified, with pulmonal, oral and intestinal manifestations. Similar to our patient, two cases presented a negative IGRA before TNFi initiation, which later converted to positive upon symptomatic presentation of M. bovis infection. This case highlights the diagnostic challenges of TB in immunosuppressed patients, the limited sensitivity of IGRA, and the importance of considering TB reactivation even in regions declared free of bovine tuberculosis. Detailed patient histories, including potential exposure to unpasteurized dairy products, are essential for guiding preventive TB treatment before TNFi initiation.