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BackgroundShort-course tuberculosis (TB) prevention regimens, including 12 weeks of isoniazid and rifapentine (3HP), are increasingly used in high-TB-burden countries. Despite established safety and tolerability in efficacy trials, 3HP-related adverse events (AEs) could differ in routine settings. Real-world data on AE type, frequency, and timing are crucial for health systems considering 3HP programmatic scale-up.MethodsWe reviewed AEs among people with human immunodeficiency virus (HIV) participating in a pragmatic implementation trial of facilitated 3HP taken by directly observed therapy (DOT) or self-administered therapy (SAT) in Kampala, Uganda, and classified them using the Common Terminology Criteria for Adverse Events. We assessed AE timing and summarized related clinical actions including laboratory tests, diagnoses made, medications prescribed, and treatment interruptions.ResultsAmong 1655 people with HIV treated between July 2020 and September 2022, 270 (16.3%) reported 451 events; main issues included general (7%), nervous system (6%), musculoskeletal (5%), gastrointestinal (5%), and dermatologic (3%) disorders. Most (61%) occurred within 6 weeks of initiating 3HP. Among those with events, 211 (78%) required further clinician evaluation, 202 (75%) required laboratory testing, 102 (38%) had medications prescribed, 40 (15%) had treatment paused, and 14 (5%) discontinued 3HP. Women, those multidimensionally impoverished, and DOT recipients were more likely to report an AE. SAT users and later enrollees were more likely to have 3HP interrupted or stopped due to an AE.ConclusionsIn a routine setting, 3HP was safe, with 16% of people with HIV reporting AEs and only 3% requiring temporary or permanent treatment interruption. These findings support 3HP expansion in routine HIV/AIDS care settings for TB prevention. Clinical Trials Registration. NCT03934931.

BackgroundExpanding access to shorter regimens for tuberculosis (TB) prevention, such as once-weekly isoniazid and rifapentine taken for 3 months (3HP), is critical for reducing global TB burden among people living with HIV (PLHIV). Our coprimary hypotheses were that high levels of acceptance and completion of 3HP could be achieved with delivery strategies optimized to overcome well-contextualized barriers and that 3HP acceptance and completion would be highest when PLHIV were provided an informed choice between delivery strategies.Methods and findingsIn a pragmatic, single-center, 3-arm, parallel-group randomized trial, PLHIV receiving care at a large urban HIV clinic in Kampala, Uganda, were randomly assigned (1:1:1) to receive 3HP by facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between facilitated DOT and facilitated SAT using a shared decision-making aid. We assessed the primary outcome of acceptance and completion (≥11 of 12 doses of 3HP) within 16 weeks of treatment initiation using proportions with exact binomial confidence intervals (CIs). We compared proportions between arms using Fisher's exact test (two-sided α = 0.025). Trial investigators were blinded to primary and secondary outcomes by study arm. Between July 13, 2020, and July 8, 2022, 1,656 PLHIV underwent randomization, with equal numbers allocated to each study arm. One participant was erroneously enrolled a second time and was excluded in the primary intention-to-treat analysis. Among the remaining 1,655 participants, the proportion who accepted and completed 3HP exceeded the prespecified 80% target in the DOT (0.94; 97.5% CI [0.91, 0.96] p < 0.001), SAT (0.92; 97.5% CI [0.89, 0.94] p < 0.001), and Choice (0.93; 97.5% CI [0.91, 0.96] p < 0.001) arms. There was no difference in acceptance and completion between any 2 arms overall or in prespecified subgroup analyses based on sex, age, time on antiretroviral therapy, and history of prior treatment for TB or TB infection. Only 14 (0.8%) participants experienced an adverse event prompting discontinuation of 3HP. The main limitation of the study is that it was conducted in a single center. Multicenter studies are now needed to confirm the feasibility and generalizability of the facilitated 3HP delivery strategies in other settings.ConclusionsShort-course TB preventive treatment was widely accepted by PLHIV in Uganda, and very high levels of treatment completion were achieved in a programmatic setting with delivery strategies tailored to address known barriers.Trial registrationClinicalTrials.gov NCT03934931.

Tuberculosis of the spine (Pott’s disease) has the potential for causing severe disability if not identified and treated early. Tuberculosis preventive therapy (TPT) is the standard of care for under-fives who have been in contact with an infectious case of tuberculosis but do not have tuberculosis. We report the case of a 2 year old child whose mother was managed for tuberculosis but was not given TPT and went onto develop tuberculosis of the spine. She responded positively to antituberculosis therapy. CC –BY 4.0 We highlight the missed opportunity for TPT at various points of contact of this child with the health care system. We recommend the integration of services at primary health care level and the training/retraining of health care workers in TB care with specific emphasis on contact tracing/TPT. Health education for the general population on tuberculosis is als important.

Abstract Background Tuberculosis preventive therapy is vital in caring for HIV-positive individuals, as it prevents the progression from latent tuberculosis infection to tuberculosis disease. The aim of the study is to assess the completion of tuberculosis preventive therapy and associated factors among clients receiving antiretroviral therapy in Debre Berhan town, Ethiopia, in 2022. Method Institutional based cross sectional study was conducted. Random sampling methods were used to select both study participants and health facilities. Both bivariate and multivariate logistic regression analyses were performed. P-values less than 0.05 were statistically significant. Result The study found that, 83% of participants were completed tuberculosis preventive therapy. Completed tuberculosis preventive therapy was associated with no adverse drug events, taking first-line ART, and good ART adherence. Conclusion According to the Ethiopian ART guidelines, the study found a low completion rate of tuberculosis preventive therapy among HIV-positive clients on antiretroviral therapy. Factors like no adverse drug events, first-line antiretroviral regimen, and good adherence were significantly associated with completing tuberculosis preventive therapy.

Background: Tuberculosis preventive therapy is vital in caring for HIV-positive individuals, as it prevents the progression from latent tuberculosis infection to tuberculosis disease. The aim of the study is to assess the completion of tuberculosis preventive therapy and associated factors among clients receiving antiretroviral therapy in Debre Berhan town, Ethiopia, in 2022. Method: Institutional based cross sectional study was conducted. Random sampling methods were used to select both study participants and health facilities. Both bivariate and multivariate logistic regression analyses were performed. P-values less than 0.05 were statistically significant. Result: The study found that, 83% of participants were completed tuberculosis preventive therapy. Completed tuberculosis preventive therapy was associated with no adverse drug events, taking first-line ART, and good ART adherence. Conclusion: According to the Ethiopian ART guidelines, the study found a low completion rate of tuberculosis preventive therapy among HIV-positive clients on antiretroviral therapy. Factors like no adverse drug events, first-line antiretroviral regimen, and good adherence were significantly associated with completing tuberculosis preventive therapy. [ABSTRACT FROM AUTHOR]

BackgroundPeople living with HIV (PLHIV) have an increased risk of developing active tuberculosis (TB). To reduce the burden of TB among PLHIV, the World Health Organization (WHO) recommends systematic TB screening followed by (1) confirmatory TB testing for all who screen positive and (2) TB preventive therapy (TPT) for all TPT-eligible PLHIV who screen negative. Symptom-based screening remains the standard of care in most high TB burden settings, including Uganda. Despite having high sensitivity for active TB among antiretroviral-naïve PLHIV, symptom screening has poor specificity; as such, many high-risk PLHIV without active TB are not referred for TPT. C-reactive protein (CRP) is a promising alternative strategy for TB screening that has comparable sensitivity and higher specificity than symptom screening, and was endorsed by WHO in 2021. However, the impact of CRP-based TB screening on TB burden for PLHIV remains unclear.MethodsTB SCRIPT (TB Screening Improves Preventive Therapy Uptake) is a phase 3, multi-center, single-blinded, individual (1:1) randomized controlled trial evaluating the effectiveness of CRP-based TB screening on clinical outcomes of PLHIV. The trial aims to compare the effectiveness of a TB screening strategy based on CRP levels using a point-of-care (POC) assay on 2-year TB incidence and all-cause mortality (composite primary trial endpoint) and prevalent TB case detection and uptake of TPT (intermediate outcomes), relative to symptom-based TB screening (current practice).DiscussionThis study will be critical to improving selection of eligible PLHIV for TPT and helping guide the scale-up and integration of TB screening and TPT activities. This work will enable the field to improve TB screening by removing barriers to TPT initiation among eligible PLHIV, and provide randomized evidence to inform and strengthen WHO guidelines.Trial registrationClinicalTrials.gov NCT04557176. Registered on September 21, 2020.

ObjectiveTo assess the prevalence of severe transaminitis precluding tuberculosis (TB) preventive therapy (TPT) initiation for people with HIV (PWH) in a high TB/HIV burden setting.Design/methodsWe conducted a secondary analysis of data from a prospective cohort study of PWH with pre-antiretroviral therapy (ART) CD4 + counts 350 cells/μl or less undergoing systematic TB screening from two HIV clinics in Uganda. For this analysis, we excluded patients with culture-confirmed TB and patients without aspartate transaminase (AST) or alanine transaminase (ALT) levels measured within three months of enrollment. We compared the proportion of patients with any transaminitis (AST or ALT greater than one times the upper limit of normal ULN) and severe transaminitis (AST or ALT >3 times ULN) for patients screening negative for TB by symptoms and for those screening negative by C-reactive protein (CRP). We also assessed the proportion of patients with transaminitis by self-reported alcohol consumption.ResultsAmong 313 participants [158 (50%) women, median age 34 years (IQR 27-40)], 75 (24%) had any transaminitis and six (2%) had severe transaminitis. Of 32 of 313 (10%) who screened negative for TB by symptoms, none had severe transaminitis. In contrast, six-times more PWH screened negative for TB by CRP (194 of 313; 62%), of whom only four (2.1%) had severe transaminitis. Differences in the proportion with any and severe transaminitis according to alcohol consumption were not statistically significant.ConclusionPrevalence of severe transaminitis was low among PWH without culture-confirmed TB in this setting, and is therefore, unlikely to be a major barrier to scaling-up TPT.

The provision of tuberculosis-preventive therapy (TPT) to vulnerable populations is critical for global control. Shorter-course TPT regimens are highly effective and improve completion rates. Despite incorporation of 1 month of rifapentine and isoniazid into global guidelines, current US TPT guidelines do not include this as a recommended regimen, but should. [ABSTRACT FROM AUTHOR]

Abstract Background Screening for Tuberculosis (TB) is a critical tactic for minimizing the prevalence of illness within schools. Tuberculosis Preventive Therapy (TPT), in turn, effectively staves off the development of TB from latent tuberculosis infection (LTBI). Unfortunately, there is limited research on LTBI and TPT among students. This study aimed to assess LTBI among freshmen in Changping District and advocate for the implementation of TPT. Methods The prospective study collected data from 12 educational institutions within the Changping District of Beijing. The Kolmogorov − Smirnov test and other statistical methods were used for statistical analysis, $${x}^{2}$$ x 2 was obtained using the formula $${x}^{2}=$$ x 2 = nΣA2/nRnC-1, df = (C-1) (R-1). We analyzed potential factors impacting the LTBI rate, and scrutinized the possible causes behind the low application of TPT and its efficacy for LTBI treatment, China. Results Among 19,872 freshmen included in this study, 18 active TB cases (91 per 10,0000) and 2236 LTBI cases (11.6% of 19,223) were identified, respectively. Furthermore, of those with LTBI, 1045 (5.4% of 19,223) showed a strong positive for purified protein derivative (PPD), but only 312 opted for TB preventive treatment. There appeared to be no significant difference in the prevalence of LTBI and TPT rate between male and female students. Concurrently, 11 (71 per 100,000) and 7 (158 per 100,000) cases of active tuberculosis were identified in 6 universities and 6 higher vocational colleges, respectively. Interestingly, almost all freshmen who underwent TPT came from universities, suggesting a statistically significant disparity in TPT rate (χ2 = 139.829, P

Objectives: Limited evidence exists regarding the impact of adherence to diverse tuberculosis (TB) preventive therapy (TPT) regimens on TB risk in individuals with TB infections (TBIs). This study aimed to examine the association between adherence to three TPT regimens and TB incidence. Methods: This population-based retrospective cohort study used South Korean national health insurance data to identify individuals who were newly diagnosed with TBI between 2015 and 2020. TB incidence was compared among the different TPT regimens used. Treatment adherence was evaluated using the medication possession ratio (MPR). Results: The study involved 220,483 individuals with TBI, with half undergoing TPT. Over a mean 3.17-year follow-up, 2,430 cases of active TB were observed. TPT was associated with a 14% reduction in TB incidence risk in the entire study population with varying levels of TB risk. Non-adherence (MPR

Background: Screening for Tuberculosis (TB) is a critical tactic for minimizing the prevalence of illness within schools. Tuberculosis Preventive Therapy (TPT), in turn, effectively staves off the development of TB from latent tuberculosis infection (LTBI). Unfortunately, there is limited research on LTBI and TPT among students. This study aimed to assess LTBI among freshmen in Changping District and advocate for the implementation of TPT. Methods: The prospective study collected data from 12 educational institutions within the Changping District of Beijing. The Kolmogorov − Smirnov test and other statistical methods were used for statistical analysis, x 2 was obtained using the formula x 2 = nΣA2/nRnC-1, df = (C-1) (R-1). We analyzed potential factors impacting the LTBI rate, and scrutinized the possible causes behind the low application of TPT and its efficacy for LTBI treatment, China. Results: Among 19,872 freshmen included in this study, 18 active TB cases (91 per 10,0000) and 2236 LTBI cases (11.6% of 19,223) were identified, respectively. Furthermore, of those with LTBI, 1045 (5.4% of 19,223) showed a strong positive for purified protein derivative (PPD), but only 312 opted for TB preventive treatment. There appeared to be no significant difference in the prevalence of LTBI and TPT rate between male and female students. Concurrently, 11 (71 per 100,000) and 7 (158 per 100,000) cases of active tuberculosis were identified in 6 universities and 6 higher vocational colleges, respectively. Interestingly, almost all freshmen who underwent TPT came from universities, suggesting a statistically significant disparity in TPT rate (χ2 = 139.829, P < 0.001) between these two types of educational institutions. Meanwhile, as for the age-wise distribution of latent infection among 17–20 years old freshmen, the LTBI rate exhibited 10.5%, 11.6%, 12.1% and 13.5%, respectively. Correlation between LTBI rate, the strong positive rate was statistically significant among different ages (χ2 = 34.559, P < 0.001). Over a follow-up period of 2 years, three students were diagnosed with active tuberculosis, one of which was resistant to rifampicin. All three students manifested a strong positive for PPD and declined preventive treatment during TB screening. Conclusions: The data indicates a high rate of LTBI amongst students in areas with a heavy TB burden, potentially leading to cross-regional TB transmission due to the migration of students. Education level might contribute to the limited uptake of TPT. Therefore, improving the implementation of TB preventive treatments is crucial in controlling and preventing TB across schools. [ABSTRACT FROM AUTHOR]

BackgroundRecently, a 3-month (12-dose) regimen of weekly isoniazid and rifapentine (3HP) was recommended by the World Health Organization for the prevention of tuberculosis (TB) among people living with HIV (PLHIV) on common antiretroviral therapy regimens. The best approach to delivering 3HP to PLHIV remains uncertain.MethodsWe developed a three-armed randomized trial assessing optimized strategies for delivering 3HP to PLHIV. The trial will be conducted at the Mulago Immune Suppression Syndrome (i.e., HIV/AIDS) clinic in Kampala, Uganda. We plan to recruit 1656 PLHIV, randomized 1:1 to each of the three arms (552 per arm). Using a hybrid type 3 effectiveness-implementation design, this pragmatic trial aims to (1) compare the acceptance and completion of 3HP among PLHIV under three delivery strategies: directly observed therapy (DOT), self-administered therapy (SAT), and informed patient choice of either DOT or SAT (with the assistance of a decision aid); (2) to identify processes and contextual factors that influence the acceptance and completion of 3HP under each delivery strategy; and (3) to estimate the costs and compare the cost-effectiveness of three strategies for delivering 3HP. The three delivery strategies were each optimized to address key barriers to 3HP completion using a theory-informed approach. We hypothesize that high levels of treatment acceptance and completion can be achieved among PLHIV in sub-Saharan Africa and that offering PLHIV an informed choice between the optimized DOT and SAT delivery strategies will result in greater acceptance and completion of 3HP. The design and planned evaluation of the delivery strategies were guided by the use of implementation science conceptual frameworks.Discussion3HP-one of the most promising interventions for TB prevention-will not be scaled up unless it can be delivered in a patient-centered fashion. We highlight shared decision-making as a key element of our trial design and theorize that offering PLHIV an informed choice between optimized delivery strategies will facilitate the highest levels of treatment acceptance and completion.Trial registrationClinicalTrials.gov: NCT03934931 ; Registered 2 May 2019.

Abstract Background Treatment of latent tuberculosis infection (LTBI) is effective in preventing progression to TB disease. This study aimed to synthesize available evidence on the efficacy, adherence, and safety of LTBI treatment in order to assist policymakers to design appropriate national treatment policies and treatment protocols. Method The PRISMA-NMA was used to review and report this research. Randomized controlled trials which compared the efficacy and safety of LTBI treatments were included. A systematic literature search was done to identify relevant articles from online databases PubMed/ MEDLINE, Embase, and Cochrane Center for Clinical Trial database (CENTRAL). The network meta-analysis was done using R- studio Version 1.4.1103. Result In this review, 42 studies were included, which enrolled 46,022 people who had recent contact with patients with active tuberculosis, evidence radiological of previous tuberculosis, tuberculin test equal or greater than 5 mm, radiographs that indicated inactive fibrotic or calcified parenchymal and/or lymph node lesions, had conversion to positive results on a tuberculin skin test, participants living with HIV, chronic Silicosis, immigrants, prisoners, old people, and pregnant women who were at risk for latent TB were included. The incidence of TB among people living with HIV who have taken 3RH as TPT was lower, followed by 48%,followed by 6H (41%). However, 3HP has also the potential to reduce the incidence of TB by 36% among HIV negative patients who had TB contact history. Patients’ adherence to TPT was higher among patients who have taken 4R (RR 1.38 95% CI 1.0,1.89) followed by 3RH (34%). The proportion of subjects who permanently discontinued a study drug because of an adverse event were three times higher in the 3RH treatment group. Furthermore, the risk of grade 3 and 4 liver toxicity was significantly higher in 9H followed by 1HP, and 6H. Conclusion From this review, it can be concluded 3RH and 6H has a significant impact on the reduction of TB incidence among PLWH and 3HP among HIV negative people who had TB contact history. However, combinations of rifampicin either with isoniazid were significantly associated with adverse events which resulted in permanent discontinuation among adult patients. Furthermore, grade 3 and 4 liver toxicity was more common in patents who have taken 9H, 1HP, and 6H. This may support the current recommended TPT regimen of 3HP, 3RH, and 6H.

During October 2016–March 2022, Uganda increased tuberculosis (TB) preventive therapy coverage among persons living with HIV from 0.6% to 88.8%. TB notification rates increased from 881.1 to 972.5 per 100,000 persons living with HIV. Timely TB screening, diagnosis, and earlier treatment should remain high priorities for TB/HIV prevention programming.

Latent tuberculosis (LTB) is now termed as tuberculosis infection (TBI). Prevention of active TB disease by treatment of tuberculosis infection is a critical component of the National Strategic Plan 2017-25 for TB Elimination in India by 2025. Programmatic Management of Tuberculosis Preventive Therapy (PMTPT) is a public health document while treatment of tuberculosis infection is essentially a clinical approach. Here we have attempted to address the gray areas answering from clinical viewpoint.

OBJECTIVE:Tuberculosis (TB) remains one of the leading causes of mortality and morbidity among people living with HIV. We sought to estimate the incidence of TB in a national database of HIV-infected patients receiving antiretroviral therapy (ART) in Botswana. DESIGN:A retrospective analysis of HIV-infected adult patients (≥18years) who initiated ART between 2011 and 2015 in the Botswana ART program. METHODS:Multivariable analysis using Cox regression included sex, age, viral load and CD4 counts. RESULTS:Of 45,729 patients, with a median follow-up of 1·7 years Q1, Q3: 0·5,3·1), 1,791 patients developed TB over a median of 1·5 years (Q1, Q3: 0·3,3·1) of follow-up (IR 1·9 per 100 py; 95% CI 1·8-2·0). At baseline, the median CD4+ T-cell count was 272 cells/μl (Q1:Q3 146, 403). The risk of TB was greatest within the first year of ART (IR 2·9 per 100 py; 95% CI 2·7-3·1) and in patients with CD4 counts below 50 cells/μl (IR 8·3/100 py; 95% CI 7·1-9·7). Patients with viral loads above 10,000 copies/ml at 3 months post ART initiation had two-times higher risk of TB, HR 2.5 (95% CI 1·8-2·3). CONCLUSIONS:We report a high incidence of TB within the first year of ART and in patients with advanced immunodeficiency. Improved screening strategies and virologic monitoring during this early period on ART, coupled with TB preventative treatment, will reduce the burden of TB.

Background: Treatment of latent tuberculosis infection (LTBI) is effective in preventing progression to TB disease. This study aimed to synthesize available evidence on the efficacy, adherence, and safety of LTBI treatment in order to assist policymakers to design appropriate national treatment policies and treatment protocols. Method: The PRISMA-NMA was used to review and report this research. Randomized controlled trials which compared the efficacy and safety of LTBI treatments were included. A systematic literature search was done to identify relevant articles from online databases PubMed/ MEDLINE, Embase, and Cochrane Center for Clinical Trial database (CENTRAL). The network meta-analysis was done using R- studio Version 1.4.1103. Result: In this review, 42 studies were included, which enrolled 46,022 people who had recent contact with patients with active tuberculosis, evidence radiological of previous tuberculosis, tuberculin test equal or greater than 5 mm, radiographs that indicated inactive fibrotic or calcified parenchymal and/or lymph node lesions, had conversion to positive results on a tuberculin skin test, participants living with HIV, chronic Silicosis, immigrants, prisoners, old people, and pregnant women who were at risk for latent TB were included. The incidence of TB among people living with HIV who have taken 3RH as TPT was lower, followed by 48%,followed by 6H (41%). However, 3HP has also the potential to reduce the incidence of TB by 36% among HIV negative patients who had TB contact history. Patients' adherence to TPT was higher among patients who have taken 4R (RR 1.38 95% CI 1.0,1.89) followed by 3RH (34%). The proportion of subjects who permanently discontinued a study drug because of an adverse event were three times higher in the 3RH treatment group. Furthermore, the risk of grade 3 and 4 liver toxicity was significantly higher in 9H followed by 1HP, and 6H. Conclusion: From this review, it can be concluded 3RH and 6H has a significant impact on the reduction of TB incidence among PLWH and 3HP among HIV negative people who had TB contact history. However, combinations of rifampicin either with isoniazid were significantly associated with adverse events which resulted in permanent discontinuation among adult patients. Furthermore, grade 3 and 4 liver toxicity was more common in patents who have taken 9H, 1HP, and 6H. This may support the current recommended TPT regimen of 3HP, 3RH, and 6H. [ABSTRACT FROM AUTHOR]

Mulugeta Russom,1– 3 Daniel YB Jeannetot,2 Sirak Tesfamariam,4 Bruno H Stricker,5 Katia Verhamme2 1Eritrean Pharmacovigilance Centre, National Medicines and Food Administration, Ministry of Health, Asmara, Eritrea; 2Department of Medical Informatics, Erasmus Medical Centre, Rotterdam, the Netherlands; 3European Program for Pharmacovigilance and Pharmacoepidemiology, University of Bordeaux, Bordeaux, France; 4Product Evaluation and Registration Unit, National Medicines and Food Administration, Ministry of Health, Asmara, Eritrea; 5Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the NetherlandsCorrespondence: Mulugeta Russom, Eritrean Pharmacovigilance Centre, National Medicines and Food Administration, Ministry of Health, P.O.Box: 212, Asmara, Eritrea, Tel +291 7197450, Email satiswt@gmail.comPurpose: In Eritrea, a 6-month isoniazid preventive therapy (IPT) was introduced in Eritrea in 2014 to prevent/reduce risk of incident tuberculosis in people living with HIV (PLHIV). The global and local uptake of IPT in newly enrolled PLHIV was reported to be low. Anecdotal reports showed that there was resistance from clinicians against its implementation. This study was therefore conducted to explore the factors that affect implementation of IPT in Eritrea from the perspectives of healthcare professionals.Materials and Methods: An exploratory qualitative study that used a framework content analysis using inductive approach was employed. Data were collected from a sample of HIV care clinic prescribers from regional and national referral hospitals through in-depth interviews. Senior program officers were also interviewed as key informants. A conceptual framework model was developed using a root cause analysis.Results: Overall, five themes and 13 sub-themes emerged from the in-depth interviews with healthcare professionals and key informants. Several multi-level causes/factors related to the healthcare system, HIV control program, healthcare professionals, patients and the product were identified as barriers to the implementation of IPT. Information gap on IPT and fear of isoniazid-induced liver injury were identified as the main reasons for the reluctance in administering IPT. It was observed that healthcare professionals had significant information gap that resulted in rumors and doubts on the benefits and risks of IPT, which ultimately caused reluctance on its implementation. Inadequate planning and operationalization during the introduction of IPT and inadequate laboratory setups were found to be the possible root causes for the aforementioned central problems.Conclusion: The root causes/factors for the limited implementation of IPT in Eritrea were mainly related to the HIV control program and the healthcare system. Adequate planning, operationalization and capacitation of the existing laboratory setups are recommended for a successful implementation of IPT.Keywords: isoniazid preventive therapy, tuberculosis preventive therapy, people living with HIV, implementation, limiting factors, barriers

Abstract Background People living with HIV (PLHIV) have an increased risk of developing active tuberculosis (TB). To reduce the burden of TB among PLHIV, the World Health Organization (WHO) recommends systematic TB screening followed by (1) confirmatory TB testing for all who screen positive and (2) TB preventive therapy (TPT) for all TPT-eligible PLHIV who screen negative. Symptom-based screening remains the standard of care in most high TB burden settings, including Uganda. Despite having high sensitivity for active TB among antiretroviral-naïve PLHIV, symptom screening has poor specificity; as such, many high-risk PLHIV without active TB are not referred for TPT. C-reactive protein (CRP) is a promising alternative strategy for TB screening that has comparable sensitivity and higher specificity than symptom screening, and was endorsed by WHO in 2021. However, the impact of CRP-based TB screening on TB burden for PLHIV remains unclear. Methods TB SCRIPT (TB Screening Improves Preventive Therapy Uptake) is a phase 3, multi-center, single-blinded, individual (1:1) randomized controlled trial evaluating the effectiveness of CRP-based TB screening on clinical outcomes of PLHIV. The trial aims to compare the effectiveness of a TB screening strategy based on CRP levels using a point-of-care (POC) assay on 2-year TB incidence and all-cause mortality (composite primary trial endpoint) and prevalent TB case detection and uptake of TPT (intermediate outcomes), relative to symptom-based TB screening (current practice). Discussion This study will be critical to improving selection of eligible PLHIV for TPT and helping guide the scale-up and integration of TB screening and TPT activities. This work will enable the field to improve TB screening by removing barriers to TPT initiation among eligible PLHIV, and provide randomized evidence to inform and strengthen WHO guidelines. Trial registration ClinicalTrials.gov NCT04557176. Registered on September 21, 2020.

Aim: A population pharmacokinetic (PPK) study of the correlation of adverse drug reactions (ADRs) with the 3HP regimen (weekly high‐dose rifapentine plus isoniazid for 12 doses) for latent tuberculosis infection (LTBI) remains lacking. The purpose of this study is to determine the association of rifapentine or isoniazid concentration and ADRs. Methods: This prospective, multicentre, observational study enrolled LTBI contacts receiving 3HP treatment between January 2017 and August 2020. The concentrations of rifapentine, isoniazid and their metabolites (25‐desacetyl‐rifapentine and acetyl‐isoniazid) in plasma samples collected monthly after 3HP treatment were determined. A PPK model was constructed to predict the maximum concentration (Cmax) and area under the concentration–time curve from 0 to 24 h (AUC). Their association with ADRs was evaluated by applying three multivariate logistic regression models with adjustment for various covariates. Results: A total of 415 LTBI cases were ultimately enrolled; 355 (85.5%) completed the 3HP treatment. Among them, 47 (11.3%) experienced systemic drug reactions and 291 (70.0%) experienced one or more flu‐like symptom. The plasma concentration–time profiles of isoniazid, rifapentine and their metabolites were adequately described by the developed models. A higher Cmax of isoniazid was significantly correlated with a higher risk of any ADR (adjusted odds ratio and 95% confidence interval: 3.04 [1.07–8.65]) and any or at least two flu‐like symptoms (all severity grades) (2.76 [1.06–7.17]). Conclusions: Isoniazid may be responsible for ADRs, especially flu‐like symptoms, during 3HP treatment. [ABSTRACT FROM AUTHOR]

Background: We describe tuberculosis (TB) disease among antiretroviral treatment (ART) eligible children living with HIV (CLHIV) in South Africa to highlight TB prevention opportunities.Methods: In our secondary analysis among 0- to 12-year-old ART-eligible CLHIV in five Eastern Cape Province health facilities from 2012 to 2015, prevalent TB occurred 90 days before or after enrollment; incident TB occurred >90 days after enrollment. Characteristics associated with TB were assessed using logistic and Cox proportional hazards regression with generalized estimating equations.Results: Of 397 enrolled children, 114 (28.7%) had prevalent TB. Higher-income proxy [adjusted odds ratio (aOR) 1.8 [95% confidence interval (CI) 1.3-2.6] for the highest, 1.6 (95% CI 1.6-1.7) for intermediate]; CD4+ cell count <350 cells/µl [aOR 1.6 (95% CI 1.1-2.2)]; and malnutrition [aOR 1.6 (95% CI 1.1-2.6)] were associated with prevalent TB. Incident TB was 5.2 per 100 person-years and was associated with delayed ART initiation [hazard ratio (HR) 4.7 (95% CI 2.3-9.4)], malnutrition [HR 1.8 (95% CI 1.1-2.7)] and absence of cotrimoxazole [HR 2.3 (95% CI 1.0-4.9)]. Among 362 children with data, 8.6% received TB preventive treatment.Conclusions: Among these CLHIV, prevalent and incident TB were common. Early ART, cotrimoxazole and addressing malnutrition may prevent TB in these children. [ABSTRACT FROM AUTHOR]

Abstract Background One of the main barriers of the management of household tuberculosis child contacts is the necessity for parents to bring healthy children to the facility. We assessed the feasibility of a community intervention for tuberculosis (TB) household child contact management and the conditions for its evaluation in a cluster randomized controlled trial in Cameroon and Uganda. Methods We assessed three dimensions of feasibility using a mixed method approach: (1) recruitment capability using retrospective aggregated data from facility registers; (2) acceptability of the intervention using focus group discussions with TB patients and in-depth interviews with healthcare providers and community leaders; and (3) adaptation, integration, and resources of the intervention in existing TB services using a survey and discussions with stakeholders. Results Reaching the sample size is feasible in all clusters in 15 months with the condition of regrouping 2 facilities in the same cluster in Uganda due to decentralization of TB services. Community health worker (CHW) selection and training and simplified tools for contact screening, tolerability, and adherence of preventive therapy were key elements for the implementation of the community intervention. Healthcare providers and patients found the intervention of child contact investigations and TB preventive treatment management in the household acceptable in both countries due to its benefits (competing priorities, transport cost) as compared to facility-based management. TB stigma was present, but not a barrier for the community intervention. Visit schedule and team conduct were identified as key facilitators for the intervention. Conclusions This study shows that evaluating a community intervention for TB child contact management in a cluster randomized trial is feasible in Cameroon and Uganda. Trial registration Clini calTr ials. gov NCT03832023 . Registered on February 6th 2019.

Abstract Background Global progress towards reducing tuberculosis (TB) incidence and mortality has consistently lagged behind the World Health Organization targets leading to a perception that large reductions in TB burden cannot be achieved. However, several recent and historical trials suggest that intervention efforts that are comprehensive and intensive can have a substantial epidemiological impact. We aimed to quantify the potential epidemiological impact of an intensive but realistic, community-wide campaign utilizing existing tools and designed to achieve a “step change” in the TB burden. Methods We developed a compartmental model that resembled TB transmission and epidemiology of a mid-sized city in India, the country with the greatest absolute TB burden worldwide. We modeled the impact of a one-time, community-wide screening campaign, with treatment for TB disease and preventive therapy for latent TB infection (LTBI). This one-time intervention was followed by the strengthening of the tuberculosis-related health system, potentially facilitated by leveraging the one-time campaign. We estimated the tuberculosis cases and deaths that could be averted over 10 years using this comprehensive approach and assessed the contributions of individual components of the intervention. Results A campaign that successfully screened 70% of the adult population for active and latent tuberculosis and subsequently reduced diagnostic and treatment delays and unsuccessful treatment outcomes by 50% was projected to avert 7800 (95% range 5450–10,200) cases and 1710 (1290–2180) tuberculosis-related deaths per 1 million population over 10 years. Of the total averted deaths, 33.5% (28.2–38.3) were attributable to the inclusion of preventive therapy and 52.9% (48.4–56.9) to health system strengthening. Conclusions A one-time, community-wide mass campaign, comprehensively designed to detect, treat, and prevent tuberculosis with currently existing tools can have a meaningful and long-lasting epidemiological impact. Successful treatment of LTBI is critical to achieving this result. Health system strengthening is essential to any effort to transform the TB response.

Abstract Background Less than 19% of those needing tuberculosis (TB) preventive treatment complete it, due to losses in several steps of the cascade of care for latent TB infection. A cluster randomized trial of a programmatic public health intervention to improve management of latent TB infection in household contacts was conducted in Rio de Janeiro. Interventions included contact registry, initial and in-service training, and a TB booklet. We conducted a follow-up study starting one month after the conclusion of this trial, to measure the effect of interventions implemented, and to identify remaining barriers and facilitators to latent TB infection treatment, from different perspectives. Methods In two health clinics in Rio de Janeiro that received the interventions in the trial, data for the latent TB infection cascade of care for household contacts was collected over a five-month period. The number of household contacts initiating treatment per 100 index-TB patients was compared with the cascade of care data obtained before and during the intervention trial. Semi-structured open-ended questionnaires were administered to healthcare workers, household contacts and index-TB patients regarding knowledge and perceptions about TB and study interventions. Results In this follow-up study, 184 household contacts per 100 index-TB patients were identified. When compared to the intervention period, there were 65 fewer household contacts per 100 index-TB patients, (95% CI -115, − 15) but the number starting latent TB infection treatment was sustained (difference -2, 95% CI -8,5). A total of 31 index-TB patients, 22 household contacts and 19 health care workers were interviewed. Among index-TB patients, 61% said all their household contacts had been tested for latent TB infection. All health care workers said it was very important to test household contacts, and 95% mentioned that possessing correct knowledge on the benefits of latent TB infection treatment was the main facilitator to enable them to recommend this treatment. Conclusion In this follow-up study, we observed a sustained effect of interventions to strengthen the latent TB infection cascade of care on increasing the number of household contacts starting latent TB infection treatment.

Background: A high prevalence of tuberculosis (TB) infection rates is followed by high rates of TB infection in children. The TB Preventive Treatment (TPT) for children with Isoniazid (INH) is one of the primary activities to improve TB cases by finding them early to prevent the transmission of TB to children. Purpose: This study aimed to describe the implementation of TPT with prophylactic INH among children in Surabaya. Methods: This research was a descriptive observational study with a case series design using secondary data on the provision of TPT in children, child TB cases in Surabaya City in 2016–2018, and a network of partnerships with hospitals/clinics/doctors’ private practices for the prevention and control of TB in the city of Surabaya in 2016–2018 as the population. The data were collected by in-depth interviews with the holders of the TB prevention and control program of Surabaya. The data were analyzed by comparing and describing the targets and achievements of the INH administration in children. Results: The implementation of INH for children in Surabaya is not optimal and has not reached the targets. The networking of health facilities with providers for the provision of TPT with INH for children is still low in Surabaya City. Conclusions: Delivery of INH for children in Surabaya has been implemented and has increased, however, it is not optimal because it has not reached the targeted districts/municipalities that determined.

Abstract Background Recently, a 3-month (12-dose) regimen of weekly isoniazid and rifapentine (3HP) was recommended by the World Health Organization for the prevention of tuberculosis (TB) among people living with HIV (PLHIV) on common antiretroviral therapy regimens. The best approach to delivering 3HP to PLHIV remains uncertain. Methods We developed a three-armed randomized trial assessing optimized strategies for delivering 3HP to PLHIV. The trial will be conducted at the Mulago Immune Suppression Syndrome (i.e., HIV/AIDS) clinic in Kampala, Uganda. We plan to recruit 1656 PLHIV, randomized 1:1 to each of the three arms (552 per arm). Using a hybrid type 3 effectiveness-implementation design, this pragmatic trial aims to (1) compare the acceptance and completion of 3HP among PLHIV under three delivery strategies: directly observed therapy (DOT), self-administered therapy (SAT), and informed patient choice of either DOT or SAT (with the assistance of a decision aid); (2) to identify processes and contextual factors that influence the acceptance and completion of 3HP under each delivery strategy; and (3) to estimate the costs and compare the cost-effectiveness of three strategies for delivering 3HP. The three delivery strategies were each optimized to address key barriers to 3HP completion using a theory-informed approach. We hypothesize that high levels of treatment acceptance and completion can be achieved among PLHIV in sub-Saharan Africa and that offering PLHIV an informed choice between the optimized DOT and SAT delivery strategies will result in greater acceptance and completion of 3HP. The design and planned evaluation of the delivery strategies were guided by the use of implementation science conceptual frameworks. Discussion 3HP—one of the most promising interventions for TB prevention—will not be scaled up unless it can be delivered in a patient-centered fashion. We highlight shared decision-making as a key element of our trial design and theorize that offering PLHIV an informed choice between optimized delivery strategies will facilitate the highest levels of treatment acceptance and completion. Trial registration ClinicalTrials.gov: NCT03934931 ; Registered 2 May 2019.

Background: One of the main barriers of the management of household tuberculosis child contacts is the necessity for parents to bring healthy children to the facility. We assessed the feasibility of a community intervention for tuberculosis (TB) household child contact management and the conditions for its evaluation in a cluster randomized controlled trial in Cameroon and Uganda. Methods: We assessed three dimensions of feasibility using a mixed method approach: (1) recruitment capability using retrospective aggregated data from facility registers; (2) acceptability of the intervention using focus group discussions with TB patients and in-depth interviews with healthcare providers and community leaders; and (3) adaptation, integration, and resources of the intervention in existing TB services using a survey and discussions with stakeholders. Results: Reaching the sample size is feasible in all clusters in 15 months with the condition of regrouping 2 facilities in the same cluster in Uganda due to decentralization of TB services. Community health worker (CHW) selection and training and simplified tools for contact screening, tolerability, and adherence of preventive therapy were key elements for the implementation of the community intervention. Healthcare providers and patients found the intervention of child contact investigations and TB preventive treatment management in the household acceptable in both countries due to its benefits (competing priorities, transport cost) as compared to facility-based management. TB stigma was present, but not a barrier for the community intervention. Visit schedule and team conduct were identified as key facilitators for the intervention. Conclusions: This study shows that evaluating a community intervention for TB child contact management in a cluster randomized trial is feasible in Cameroon and Uganda. Trial registration: Clini calTr ials. gov NCT03832023. Registered on February 6th 2019. [ABSTRACT FROM AUTHOR]

Introduction: A 6-month isoniazid as tuberculosis preventive therapy (TPT) for people living with HIV (PLHIV) was nationally introduced in Eritrea in 2014. However, its effectiveness in preventing tuberculosis (TB) and duration of protection was questioned by physicians. This study was, therefore, conducted to evaluate the impact of the isoniazid preventive therapy (IPT) primarily on the prevention of TB and duration of its protection in PLHIV. Methods: A retrospective cohort study was conducted that selected all eligible PLHIV attending HIV care clinics in all national and regional referral hospitals in Eritrea. Data was collected from patients' clinical cards using a structured data extraction sheet. The association between use of IPT and outcomes of interest was assessed using a Cox proportional hazard regression model and Kaplan–Meier curve. Results: A total of 6803 patients were selected, which accounted for 75% of all PLHIV-accessing HIV care clinics in Eritrea. About 76% of patients were exposed to IPT while the remaining 24% were unexposed. The mean follow-up time was 4.9 years (SD 1.4). The incidence rate of TB was 1.7 and 10 cases per 1000 person-years in the exposed and unexposed, respectively. The unexposed had a higher risk of incident TB (adjusted hazard ratio [aHR] 3.75, 95% confidence interval [CI] 2.89, 6.13) and all-cause mortality (HR 2.41, 95% CI 1.85, 3.14) compared to the exposed. A Kaplan–Meier curve showed that the exposed group had a higher TB-free follow-up probability (98.8%) compared to the unexposed (95%) at 65 months of follow-up (p < 0.001). IPT protection decreased rapidly 6 months after isoniazid completion. Conclusion: Use of a 6-month isoniazid as TPT was found to be effective in reducing incident TB in PLHIV-accessing HIV care clinics in Eritrea. However, the protection appeared to diminish soon, namely 6 months after completion of isoniazid, which warrants immediate attention from policy makers. [ABSTRACT FROM AUTHOR]

Introduction: In most developing countries, tuberculosis (TB) is the leading cause of mortality among people living with the Human Immunodeficiency Virus (PLHIV). Uganda implements TB preventive therapy (TPT) using Isoniazid but data are limited about TPT incompletion. We, therefore, assessed the magnitude of TPT incompletion and the associated factors among PLHIV in a large rural referral health facility in rural eastern Uganda. Methods and materials: We conducted a retrospective data review for PLHIV initiated on TPT between October 2018 and September 2019. The outcome variable was TPT incompletion defined as the failure to finish 6 consecutive months of Isoniazid or failure to finish 9 months of Isoniazid without stopping for more than 2 months at a time. We descriptively summarized numerical data using frequencies and percentages and compared differences in the outcome with independent variables using the Chi-square or fisher’s exact, and the Student’s t-tests. We used a generalized linear model to assess factors independently associated with TPT incompletion, reported using adjusted odds ratio (aOR) and 95% confidence interval (CI). Results: We enrolled 959 participants with a mean age of 41.1 ± 13.8 years, 561 (58.5%) were females, 663 (69.1%) married, 538 (56.1) travelled 5–10 km from their place of residence to the ART clinic, 293 (30.6%) had disclosed HIV status, 362 (37.7%) had been on ART for 5–9 years, and 923 (96.2%) were on first-line ART regimen. We found 26 (2.7%) participants had incomplete TPT. Non-adherence to ART clinic visits (aOR, 2.81; 95% CI, 1.09–7.73), history of switch in ART regimen (aOR, 9.33; 95% CI, 1.19–52.39), patient representation (aOR, 4.70; 95% CI, 1.35–13.99), and one unit increase in ongoing counselling session (aOR, 0.67; 95% CI, 0.46–0.91) were associated with TPT incompletion. Conclusion: We found low rates of TPT incompletion among PLHIV in rural eastern Uganda. Non-adherence to ART clinic visits, patient representation, and history of switch in ART regimen is associated with a higher likelihood of TPT incompletion while ongoing counselling is associated with a reduction in TPT incompletion. The health system should address non-adherence to ART clinic visits and patient representation, through ongoing psychosocial support.

Background: Global progress towards reducing tuberculosis (TB) incidence and mortality has consistently lagged behind the World Health Organization targets leading to a perception that large reductions in TB burden cannot be achieved. However, several recent and historical trials suggest that intervention efforts that are comprehensive and intensive can have a substantial epidemiological impact. We aimed to quantify the potential epidemiological impact of an intensive but realistic, community-wide campaign utilizing existing tools and designed to achieve a "step change" in the TB burden.Methods: We developed a compartmental model that resembled TB transmission and epidemiology of a mid-sized city in India, the country with the greatest absolute TB burden worldwide. We modeled the impact of a one-time, community-wide screening campaign, with treatment for TB disease and preventive therapy for latent TB infection (LTBI). This one-time intervention was followed by the strengthening of the tuberculosis-related health system, potentially facilitated by leveraging the one-time campaign. We estimated the tuberculosis cases and deaths that could be averted over 10 years using this comprehensive approach and assessed the contributions of individual components of the intervention.Results: A campaign that successfully screened 70% of the adult population for active and latent tuberculosis and subsequently reduced diagnostic and treatment delays and unsuccessful treatment outcomes by 50% was projected to avert 7800 (95% range 5450-10,200) cases and 1710 (1290-2180) tuberculosis-related deaths per 1 million population over 10 years. Of the total averted deaths, 33.5% (28.2-38.3) were attributable to the inclusion of preventive therapy and 52.9% (48.4-56.9) to health system strengthening.Conclusions: A one-time, community-wide mass campaign, comprehensively designed to detect, treat, and prevent tuberculosis with currently existing tools can have a meaningful and long-lasting epidemiological impact. Successful treatment of LTBI is critical to achieving this result. Health system strengthening is essential to any effort to transform the TB response. [ABSTRACT FROM AUTHOR]

Introduction: the World Health Organization (WHO) has recommended the use of tuberculosis preventive therapy (TPT) as part of a comprehensive care package for the reduction of tuberculosis (TB) incidence among people who are living with human immunodeficiency virus (PLWHA). When used optimally, TPT efficacy ranges between 60% and 90% among adults and children who are living with HIV. Despite the wide adoption of this intervention in South Africa, the country remains heavily burdened with high rates of TB/HIV co-infections, reported to be 59% in 2018. Reported challenges include low uptake and completion rates. This study aimed to determine the TPT completion rate and investigate the incidence of TB among antiretroviral therapy (ART) patients who were initiated on TPT., Methods: this descriptive cross-sectional retrospective cohort study was conducted among HIV-positive patients who were on ART, 18 years old and above, and had been initiated on TPT between June 2019 and June 2021 at the selected PHC facilities in Ekurhuleni East sub-District. We conducted record reviews and face-to-face interviews to collect data. These were captured onto a Microsoft Excel spreadsheet, cleaned, and coded before importation onto the Epiinfo version 7 statistical software package for statistical analyses., Results: the study found a majority of female participants, (60.5%). The median age of participants was 39.0 years (IQR=15), with most aged 50 years old and above, (21.3%). The treatment course of TPT was completed at the prescribed 12 months by 196 (30%) of the 395 participants. Only 12 (3%) of the participants were found to have TB, half 6 (50%) of which were breakthrough cases of TB. The reasons for non-completion of TPT included clinicians not offering it to patients, (46/276 (16.7%)). The barriers to TPT completion included not having a treatment supporter, (73.2%); p<0.001, while disclosure of positive HIV status was found to facilitate TPT completion (83.2%); p<0.001., Conclusion: the observed TPT completion rate of 30% needs to be addressed as it is far below the national threshold of 85%. The barriers and facilitators to TPT completion also require attention to help improve the TPT completion rate., Competing Interests: The authors declare no competing interests., (Copyright: Refiloe Mashego Malaka et al.)

As part of the END TB strategy, the World Health organization (WHO) recommends provision of tuberculosis preventive therapy (TPT) to all people at high risk of developing active TB disease. Patients with HIV-associated cryptococcal meningitis are severely immunocompromised and therefore should be eligible for TPT. In this commentary we discuss the challenges associated with starting tuberculosis preventive therapy in patients with HIV associated cryptococcal meningitis in a clinical setting, we highlight the benefit, existing gaps and research opportunities of tuberculosis preventive therapy in this patient population.

Background: Simplifying antiretroviral therapy for clinically stable people living with HIV (PLHIV) is important but insufficient to meet their health care needs, including prevention and treatment of tuberculosis and noncommunicable diseases, routine primary care, and family planning. Integrating these services into differentiated service delivery (DSD) platforms is a promising avenue to achieve such coverage. We propose a transition from an HIV-focused "DSD 1.0" to a patient-centered "DSD 2.0" that is inclusive of additional chronic care services for PLHIV. Discussion: The lack of coordination between HIV programs and these critical services puts a burden on both PLHIV and health systems. For individual patients, fractionated services increase cost and time, diminish the actual and perceived quality of care, and increase the risk that they will disengage from health care altogether. The burden on the health system is one of inefficiency and suboptimal outcomes resulting from the parallel systems required to manage multiple vertical programs. Conclusions: DSD 2.0 provides an opportunity for the HIV and Universal Health Coverage agendas--which can seem to be at odds--to achieve greater collective impact for patients and health systems by integrating strong vertical HIV, tuberculosis and family planning programs, and relatively weaker noncommunicable disease programs. Increasing coordination of care for PLHIV will increase the likelihood of achieving and sustaining UNAIDS9 goals of retention on antiretroviral therapy and viral suppression. Eventually, this shift to DSD 2.0 for PLHIV could evolve to a more person-centered vision of chronic care services that would also serve the general population. [ABSTRACT FROM AUTHOR]

Background: Less than 19% of those needing tuberculosis (TB) preventive treatment complete it, due to losses in several steps of the cascade of care for latent TB infection. A cluster randomized trial of a programmatic public health intervention to improve management of latent TB infection in household contacts was conducted in Rio de Janeiro. Interventions included contact registry, initial and in-service training, and a TB booklet. We conducted a follow-up study starting one month after the conclusion of this trial, to measure the effect of interventions implemented, and to identify remaining barriers and facilitators to latent TB infection treatment, from different perspectives.Methods: In two health clinics in Rio de Janeiro that received the interventions in the trial, data for the latent TB infection cascade of care for household contacts was collected over a five-month period. The number of household contacts initiating treatment per 100 index-TB patients was compared with the cascade of care data obtained before and during the intervention trial. Semi-structured open-ended questionnaires were administered to healthcare workers, household contacts and index-TB patients regarding knowledge and perceptions about TB and study interventions.Results: In this follow-up study, 184 household contacts per 100 index-TB patients were identified. When compared to the intervention period, there were 65 fewer household contacts per 100 index-TB patients, (95% CI -115, - 15) but the number starting latent TB infection treatment was sustained (difference -2, 95% CI -8,5). A total of 31 index-TB patients, 22 household contacts and 19 health care workers were interviewed. Among index-TB patients, 61% said all their household contacts had been tested for latent TB infection. All health care workers said it was very important to test household contacts, and 95% mentioned that possessing correct knowledge on the benefits of latent TB infection treatment was the main facilitator to enable them to recommend this treatment.Conclusion: In this follow-up study, we observed a sustained effect of interventions to strengthen the latent TB infection cascade of care on increasing the number of household contacts starting latent TB infection treatment. [ABSTRACT FROM AUTHOR]

Purpose of Review: Despite broad uptake of antiretroviral therapy (ART), tuberculosis (TB) incidence and mortality among people with HIV remain unacceptably high. Short-course regimens for TB, incorporating both novel and established drugs, offer the potential to enhance adherence and completion rates, thereby reducing the global TB burden. This review will outline short-course regimens for TB among patients with HIV. Recent Findings: After many years without new agents, there is now active testing of many novel drugs to treat TB, both for latent infection and active disease. Though not all studies have included patients with HIV, many have, and there are ongoing trials to address key implementation challenges such as potent drug-drug interactions with ART. Summary: The goal of short-course regimens for TB is to enhance treatment completion without compromising efficacy. Particularly among patients with HIV, studying these shortened regimens and integrating them into clinical care are of urgent importance. There are now multiple short-course regimens for latent infection and active disease that are safe and effective among patients with HIV. [ABSTRACT FROM AUTHOR]

Background Tuberculosis preventive therapy (TPT) is highly effective at preventing tuberculosis disease in household child contacts (<5 years), but is poorly implemented worldwide. In 2006, the World Health Organization recommended symptom-based screening as a replacement for tuberculin skin testing (TST) to simplify contact evaluation and improve implementation. We aimed to determine the effectiveness of this recommendation. Methods We conducted a pragmatic, cluster-randomized trial to determine whether contact evaluation using symptom screening improved the proportion of identified child contacts who initiated TPT, compared to TST-based screening, in Matlosana, South Africa. We randomized 16 clinics to either symptom-based or TST-based contact evaluations. Outcome data were abstracted from customized child contact management files. Results Contact tracing identified 550 and 467 child contacts in the symptom and TST arms, respectively (0.39 vs 0.32 per case, respectively; P =.27). There was no significant difference by arm in the adjusted proportion of identified child contacts who were screened (52% in symptom arm vs 60% in TST arm; P =.39). The adjusted proportion of identified child contacts who initiated TPT or tuberculosis treatment was 51.5% in the symptom clinics and 57.1% in the TST clinics (difference −5.6%, 95% confidence interval −23.7 to 12.6; P =.52). Based on the district's historic average of 0.7 child contacts per index case, 14% and 15% of child contacts completed 6 months of TPT in the symptom and TST arms, respectively (P =.89). Conclusions Symptom-based screening did not improve the proportion of identified child contacts evaluated or initiated on TPT, compared to TST-based screening. Further research is needed to identify bottlenecks and evaluate interventions to ensure all child contacts receive TPT. Clinical Trials Registration NCT03074799. [ABSTRACT FROM AUTHOR]

The 2021 Global Tuberculosis (TB) report shows slow progress towards closing the pediatric TB detection gap and improving the TB preventive treatment (TPT) coverage among child and adolescent contacts. This review presents the current knowledge around contact case management (CCM) in low-resource settings, with a focus on child contacts, which represents a key priority population for CCM and TPT. Compelling evidence demonstrates that CCM interventions are a key gateway for both TB case finding and identification of those in need of TPT, and their yield and effectiveness should provide a strong rationale for prioritization by national TB programs. A growing body of evidence is now showing that innovative models of care focused on community-based and patient-centered approaches to household contact investigation can help narrow down the CCM implementation gaps that we are currently facing. The availability of shorter and child-friendly TPT regimens for child contacts provide an additional important opportunity to improve TPT acceptability and adherence. Prioritization of TB CCM implementation and adequate resource mobilization by ministries of health, donors and implementing agencies is needed to timely close the gap.

Background: The World Health Organization recommends isoniazid preventive therapy (IPT) for people living with HIV (PLHIV) to prevent tuberculosis (TB), including pregnant women. Recent trial results suggest increased adverse pregnancy outcomes associated with IPT during pregnancy. Data are limited regarding programmatic IPT use in pregnant PLHIV. Methods: We assessed previous programmatic IPT during pregnancy among HIV-infected mothers on enrollment to an infant TB prevention trial in Kenya. Pregnancy IPT use was assessed by the estimated conception date assuming 38 weeks of gestation. Correlates of initiation and completion were analyzed by relative risk regression, using generalized linear models with log link and Poisson family adjusted for IPT initiation year. Results: Between August 15, 2016, to June 6, 2018, 300 HIV-infected women enrolled at 6 weeks postpartum. Two hundred twenty-four (74.7%) women reported previous IPT, of whom 155/224 (69.2%) had any pregnancy IPT use. Forty-five (29.0%) initiated preconception extending into early pregnancy, 41 (26.5%) initiated and completed during pregnancy, and 69 (44.5%) initiated in pregnancy and extended into early postpartum. The median gestational age at IPT pregnancy initiation was 15.1 weeks (interquartile range 8.3-28.4). Pregnancy/early postpartum IPT initiation was associated with new pregnancy HIV diagnosis [adjusted relative risk 1.9 95% confidence interval (CI): 1.6 to 2.2, P < 0.001]. Six-month IPT completion rates were high [147/160 (91.9%)] among women with sufficient time to complete before trial enrollment and similar among preconception or during pregnancy initiators [adjusted relative risk 0.93 (95% confidence interval: 0.83 to 1.04, P = 0.19)]. Conclusions: Programmatic IPT use was high in pregnant PLHIV, with frequent periconception and early pregnancy initiation. Programmatic surveillance could provide further insights on pregnancy IPT implementation and maternal and infant safety outcomes. [ABSTRACT FROM AUTHOR]

While tuberculosis (TB) preventive therapy among household contacts is effective at an individual level, its population-level impact on reducing TB incidence has been unclear. In this study, we aimed to assess, among the new tuberculosis patients started on treatment between 1 October, 2018 and 30 June, 2019 in the public health facilities of Udupi district (South India): i) the proportion with a ‘history of household TB exposure’ and ii) sociodemographic and clinical factors associated with it. We conducted a cross-sectional study involving record review and patient interviews. Of 565 TB patients, 273(48%) were interviewed. Of them, 71(26%, 95% CI: 21%–32%) patients had a ‘history of household TB exposure (ever)’ with about half exposed in the past five years of diagnosis. Considering a new TB case as a proxy for incident TB, and ‘history of household TB exposure’ a proxy for household transmission, and assuming 100% effectiveness of preventive therapy, we may infer that a maximum of 26% of the incident cases can be prevented by giving preventive therapy to all household contacts of TB patients. In multivariable analysis, females and tobacco users had a significantly higher prevalence of household TB exposure. If there are resource constraints, these subgroups may be prioritized.