Tuberculosis Preventive Treatment Research Articles

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.

People 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. We 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. The 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. The 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.

Effectiveness of preventive treatment among different age groups and Mycobacterium tuberculosis infection status: a systematic review and individual-participant data meta-analysis of contact tracing studies.

Tuberculosis is a preventable disease. However, there is debate regarding which individuals would benefit most from tuberculosis preventive treatment and whether these benefits vary in settings with a high burden and low burden of tuberculosis. We aimed to compare the effectiveness of tuberculosis preventive treatment in exposed individuals of differing ages and Mycobacterium tuberculosis infection status while considering tuberculosis burden of the settings. In this systematic review and individual-participant meta-analysis, we investigated the development of incident tuberculosis in people closely exposed to individuals with tuberculosis. We searched for studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase. We restricted our search to cohort studies; case-control studies and outbreak reports were excluded. Two reviewers evaluated titles, abstracts, and full text articles for eligibility. At each stage, two reviewers discussed discrepancies and re-evaluated articles until a consensus was reached. Individual-participant data and a pre-specified list of variables, including characteristics of the exposed contact, the index patient, and environmental characteristics, were requested from authors of all eligible studies; contacts exposed to a drug-resistant tuberculosis index patient were excluded. The primary study outcome was incident tuberculosis. We estimated adjusted hazard ratios (aHRs) for incident tuberculosis with mixed-effects Cox regression models with a study-level random effect. We estimated the number-needed-to-treat (NNT) to prevent one person developing tuberculosis. Propensity score matching procedures were used in all analyses. This study is registered with PROSPERO (CRD42018087022). After screening 25 358 records for eligibility, 439 644 participants from 32 cohort studies were included in the individual-participant data meta-analysis. Participants were followed for 1 396 413 person-years (median of 2·7 years [IQR 1·3-4.4]), during which 2496 people were diagnosed with incident tuberculosis. Overall, effectiveness of preventive treatment was 49% (aHR 0·51 [95% CI 0·44-0·60]). Participants with a positive tuberculin-skin-test (TST) or IFNγ release assay (IGRA) result at baseline benefitted from greater protection, regardless of age (0·09 [0·05-0·17] in children younger than 5 years, 0·20 [0·15-0·28] in individuals aged 5-17 years, and 0·17 [0·13-0·22] in adults aged 18 years and older). The effectiveness of preventive treatment was greater in high-burden (0·31 [0·23-0·40]) versus low-burden (0·58 [0·47-0·72]) settings. The NNT ranged from 9 to 34 depending on age among participants with a positive TST or IGRA in both high-burden and low-burden settings; among all contacts (regardless of TST or IGRA test result), the NNT ranged from 29 to 43 in high-burden settings and 213 to 455 in low-burden settings. Our findings suggest that a risk-targeted strategy prioritising contacts with evidence of M tuberculosis infection might be indicated in low-burden settings, and a broad approach including all contacts should be considered in high-burden settings. Preventive treatment was similarly effective among contacts of all ages. None.

Screening hemodialysis patients for tuberculosis in Sudan

ObjectivesTo estimate the prevalence of latent tuberculosis infection (LTBI) and the need for TB preventive treatment (TPT) among hemodialysis (HD) patients in Sudan. MethodsWe screened patients in a single HD center by two-step tuberculin skin test (TST), symptom survey, physical examination and chest radiography (CXR). ResultsThe survey included 204 patients, five of whom (2.5%) had history of previously treated TB. The proportion of TST positive patients was 12.3% after the first test and increased to 21.1% after the second test. Patients previously treated for TB were more likely to have positive TST (80 vs 20.1%, p = 0.01). We screened 184 patients for TB disease; 16.3% were symptomatic, 15.8% had CXR abnormality and 6.5% were symptomatic with CXR abnormality. Additionally, 13.6% of patients had physical signs consistent with extra-pulmonary TB without symptoms or CXR abnormality. Based on these findings, high probability of pulmonary and extra-pulmonary TB was found in 38.6% and 13.6% of patients respectively and they were referred for bacteriological confirmation. We diagnosed LTBI and prescribed TPT to 9.2% of screened patients. ConclusionIn this cohort of Sudanese HD patients, 21.1% were positive after two-step TST and 52.2% were considered to have high probability of TB disease.

Costs of non-multidrug-resistant pulmonary tuberculosis and of preventive treatment in Germany – An update

BackgroundOnly 4076 new cases of tuberculosis (TB) were reported in Germany in 2022; of those 184 were multidrug-resistant TB (MDR-/RR-TB). MethodsBased on the current therapy guidelines of the German Central Committee against Tuberculosis and most recent renumeration data of the Statutory Health Insurances (SHI), this study estimates the mean in- and outpatient costs per adult infectious pulmonary non-MDR-TB patient, together with costs arising from Rifampicin (RIF)-based short-course options of tuberculosis preventive treatment (TPT) of their close contacts. ResultsFrom the insurance perspective, the mean inpatient cost (rounded) per adult case was 6138 EUR (SD±2810 EUR) for standard therapy; the cost of primary outpatient treatment only amounted to 1930 EUR and the cost of outpatient treatment post-hospital to 1093 EUR. The mean weighted cost was 6377 EUR (SD±2357 EUR), a drop of 27 % vs. 2019. This is mainly due to a decrease in hospitalizations of 5.6 %, and, given hospital treatment, by a 95 EUR decrease in the per-day reimbursement rate for TB patients who are hospitalized for at least 14 days. In contrast, the mean costs of TPT per person were 466 EUR (RIF solely over 4 months) and 423 EUR (RIF combined with Isoniazid over 3 months). ConclusionWhile costs for active non-MDR-TB treatment in Germany have clearly decreased thanks to increased engagement on the part of the private practice sector and lower reimbursement rates in hospital, the comparatively high costs of short-course TPT have surprisingly significant economic impact. This negative development can be countered through diligent selection of close contacts persons of infectious TB cases before using IGRA testing to detect latent TB, to minimize the number of those persons who are tested falsely determined to be at risk and needlessly undergo TPT.

Factors associated with tuberculosis among PLHIV: An observational study in a Government Medical College in West Bengal, India

BackgroundTuberculosis (TB) is one of the leading causes of significant morbidity and mortality among the People Living with Human Immune-deficiency Virus (PLHIV) in India. Reducing TB burden among PLHIV is a priority area under the National TB Elimination Program (NTEP). MethodologyWe analyzed the routinely collected data from an Anti-Retro-viral Treatment Centre (ARTC) of Malda Medical College, West Bengal with an aim of identifying the factors associated with TB prevalence among the PLHIV. All 739 PLHIV who attended the ARTC during 2020–2022, were included in this study. ResultsMean age of the study participants was 34 years (SD:13). 47.9 % PLHIV received Co-trimoxazole Prophylaxis Treatment (CPT) whereas 67.7 % PLHIV received TB preventive treatment (TPT). Transgender [2.9 (1.4–6)], Males [3.7 (1.8–7.9)], Widow/Separated [2.5 (1.2–5.4)], Living with 2–4 Family members [1.6 (1–2.7)], CD4 count less than 200 [1.9 (1.1–3.2)], those who received CPT [17 (7.1–40.8)] and those who didn't receive TPT [1.6 (1–2.6)] were independently associated with increased risk of developing TB. There was no significant association of Age with TB diagnosis among the PLHIV. ConclusionsIt is evident from this study, that introduction of TPT and improving CD4 count by Anti-retroviral Treatment is the key intervention to reduce TB burden among PLHIV. The study found significant association of CPT with TB. Further study may be conducted to determine the actual reason for such association.

Conversion or reversion of interferon gamma release assays for Mycobacterium tuberculosis infection: a systematic review and meta-analysis.

Interferon-gamma release assays (IGRA) are widely used for diagnosis of latent tuberculosis infection. However, with repeat testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation. We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and subject characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors. The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% CI 6.1-8.5%) or 22.8% (20.1-25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (35.7-56.4%) or 19.6% (9.2-31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [0.1-3.5%]). IGRA results in the borderline positive or negative range were associated with increased risk of conversion or reversion (pooled OR: conversion, 4.15 [3.00-5.30]; reversion, 4.06 [3.07-5.06]). BCG vaccination was associated with decreased risk of conversion (0.70, 0.56-0.84), cigarette smoking with decreased risk of reversion (0.44, 0.06-0.82), and female sex with decreased risk of either conversion or reversion (conversion, 0.66 [0.58-0.75]; reversion, 0.46 [0.31-0.61]). IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis preventive treatment. Re-testing of people with indeterminate results is probably not indicated, since indeterminate results seldom revert to positive.

Optimizing the cascade of prevention to protect people from tuberculosis: A potential game changer for reducing global tuberculosis incidence.

The provision of tuberculosis preventive treatment is one of the critical interventions to reduce tuberculosis incidence and ultimately eliminate the disease, yet we still miss appropriate tools for an impactful intervention and treatment coverage remains low. We used recent data, epidemiological estimates, and research findings to analyze the challenges of each step of the cascade of tuberculosis prevention that currently delay the strategy implementation. We addressed research gaps and implementation bottlenecks that withhold key actions in tuberculosis case finding, testing for tuberculosis infection, provision of preventive treatment with safer, shorter regimens and supporting people to complete their treatment. Empowering communities to generate demand for preventive therapy and other prevention services in a holistic manner and providing adequate financial support to sustain implementation are essential requirements. The adoption of an effective, universal monitoring and evaluation system is a prerequisite to provide general and granular insight, and to steer progress of the tuberculosis infection strategy at global and local level.

Adherence to preventive treatment for latent tuberculosis infection in close contacts of pulmonary tuberculosis patients: A cluster-randomized controlled trial in China

ObjectivesThis study examined adherence rates to tuberculosis preventive treatment (TPT) among close contacts of individuals with pulmonary tuberculosis (PTB) and identified factors associated with TPT adherence in China. MethodsA multicenter, cluster-randomized, open-label control trial was carried out across three sites involving 34 counties in China. Close contacts of bacteriologically confirmed rifampin and isoniazid-susceptible PTB cases were identified and screened for latent tuberculosis infection (LTBI). Eligible participants were randomly assigned to either the 3H2P2 group, which consisted of a 3-month, twice-weekly regimen of rifapentine and isoniazid, or the 6H group, which entailed a 6-month daily regimen of isoniazid. To assess the factors influencing adherence, a two-level logistic regression model was utilized. ResultsOut of the 2434 close contacts who initiated TPT, 2121 (87.1%) completed the regimen. Of the 313 individuals who did not complete TPT, 60.1% refused to continue, and 27.8% discontinued due to adverse effects. The two-level logistic regression model revealed several factors associated with enhanced TPT adherence: enrollment in the 3H2P2 group (odds ratio [OR] = 2.09), management by a TB dispensary responsible for TPT (OR = 2.55), supervision by healthcare workers (OR = 6.40), and clinician incentives (OR = 2.49). Conversely, the occurrence of any adverse effects (OR = 0.08) was identified as a risk factor for nonadherence. ConclusionAdministering TPT to individuals with LTBI is feasible among close contacts. Adherence to TPT can be enhanced through shorter, safer treatment regimens and supportive interventions, such as directly supervised therapy for TPT recipients and incentives for healthcare providers managing TPT.

An Effective Health System Approach to End TB: Implementing the Double X Strategy in Vietnam.

Countries that are high burden for TB must reverse the COVID-19 pandemic's devastating effects to accelerate progress toward ending TB. Vietnam's Double X (2X) strategy uses chest radiography (CXR) and GeneXpert (Xpert) rapid diagnostic testing to improve early detection of TB disease. Household contacts and vulnerable populations (e.g., individuals aged 60 years and older, smokers, diabetics, those with alcohol use disorders, and those previously treated for TB) with and without TB symptoms were screened in community campaigns using CXRs, followed by Xpert for those with a positive screen. In public non-TB district facilities, diabetics, respiratory outpatients, inpatients with lung disease, and other vulnerable populations underwent 2X evaluation. During COVID-19 restrictions in Vietnam, the 2X strategy improved access to TB services by decentralization to commune health stations, the lowest level of the health system, and enabling self-screening using a quick response mobile application. The number needed to screen (NNS) with CXRs to diagnose 1 person with TB disease was calculated for all 2X models and showed the highest yield among self-screeners (11 NNS with CXR), high yield for vulnerable populations in communities (60 NNS) and facilities (19 NNS), and moderately high yield for household contacts in community campaigns (154 NNS). Computer-aided diagnosis for CXRs was incorporated into community and facility implementation and improved physicians' CXR interpretations and Xpert referral decisions. Integration of TB infection and TB disease evaluation increased eligibility for TB preventive treatment among household contacts, a major challenge during implementation. The 2X strategy increased the rational use of Xpert, employing a health system-wide approach that reached vulnerable populations with and without TB symptoms in communities and facilities for early detection of TB disease. This strategy was effectively adapted to different levels of the health system during COVID-19 restrictions and contributed to post-pandemic TB recovery in Vietnam.

Tuberculosis preventive treatment in eight SEAR countries – Current practices, implementation challenges and operations research priorities

ObjectivesCountries in the South East Asian region face similar challenges in control of infectious diseases. There is limited access to experiences and learnings of neighboring countries. The Indian Council - of Medical Research (ICMR) has established a Regional Enabler for the South-East Asia Research Collaboration for Health (RESEARCH) Platform for South East Asian Region (SEAR) countries to address the above issues. This paper discusses about current practices, implementation challenges and operations research priorities of Tuberculosis Preventive therapy (TPT) in eight SEAR countries. MethodsA three day workshop on “Capacity Building for TB Research under Programmatic Settings”. was conducted under the aegis of this RESEARCH platform jointly ICMR and the Union which was participated by eight SEAR countries. Data were collected from a semi-structured questionnaire prior to the workshop and open discussions during the workshop. ResultsThe various challenges faced for TPT implementation were broadly categorized as poor demand and low level of acceptance by the beneficiary, low level of acceptance to provide TPT among the providers, challenges in ruling out active TB, issues with supply and supply chain management of diagnostic tests and drugs. Many operations research priorities like person centric TPT driven models, capacity building for improving cascade of care for latent TB infection, health system strengthening and effective risk communication were identified. ConclusionFull implementation of the TPT guidelines requires focused attention and coordinated action from all stakeholders of the country to attain the full benefit of TB preventive therapy and the ultimate TB elimination goal.

Mixed methods study on latent tuberculosis among agate stone workers and advocacy for testing silica dust exposed individuals in India

The 2021 tuberculosis (TB) preventive treatment guidelines in India included silicosis as a screening group, yet latent TB infection (LTBI) testing for silica-dust-exposed individuals is underemphasized. Focusing on an estimated 52 million silica-dust-exposed workers, particularly agate-stone workers in Khambhat, Gujarat, our study aims to estimate LTBI prevalence, identify predictors, and gather insights from TB and silicosis experts. Employing a sequential explanatory mixed-methods approach, a cross-sectional study involved 463 agate-stone workers aged ≥ 20 years in Khambhat, using IGRA kits for LTBI testing. In-depth interviews with experts complemented quantitative findings. Among agate-stone workers, 58% tested positive for LTBI, with predictors including longer exposure, type of work, and BCG vaccination. Our findings reveal a nearly double burden of LTBI compared to the general population, particularly in occupations with higher silica dust exposure. Experts advocate for including silica-dust-exposed individuals in high-risk groups for LTBI testing, exploring cost-effective alternatives like improved skin sensitivity tests, and shorter TB preventive treatment regimens to enhance compliance. Future research should explore upfront TB preventive treatment for silica-dust-exposed individuals with high LTBI prevalence and optimal exposure duration. This study underscores the urgent need for policy changes and innovative approaches to TB prevention among silica-dust-exposed populations, impacting global occupational health strategies.

Loss to follow-up among people living with HIV on tuberculosis preventive treatment at four regional referral hospitals, Uganda, 2019–2021

IntroductionTuberculosis (TB) remains the leading cause of death among people living with HIV (PLHIV). TB preventive treatment (TPT) can prevent active TB infection in PLHIV for several years after it is completed. During 2019–2021, the six-month course of TPT (using isoniazid) was the most readily available in Uganda; however, program data indicated a TPT program loss to follow-up (LTFU) rate of 12 % during this period. We evaluated factors associated with TPT LTFU among PLHIV in four regional referral hospitals (RRHs) in Uganda from 2019 to 2021. MethodsWe abstracted program data from TPT registers on patient LTFU at Masaka, Mbale, Mubende, and Jinja RRHs. Additional data collected included client demographics, duration on HIV antiretroviral therapy (ART), year of TPT initiation, adherence, and point of entry. LTFU was defined as the failure to finish six consecutive months of isoniazid without stopping for more than two months at a time. We conducted bivariate analysis using the chi-square test for independence. Variables with p < 0.05 in bivariate analysis were included in a logistic regression model to establish independent factors associated with LTFU. ResultsOverall, 24,206 clients were started on TPT in the four RRHs. Their median age was 40 years (range, 1–90 years), and 15,962 (66 %) were female. A total of 22,260 (92 %) had TPT adherence >95 %. Independent factors associated with LTFU included being on ART for <3 months (AOR: 3.1, 95 % CI: 2.1–4.5) and 20–24 years (AOR: 4.7, 95 % CI: 1.9–12) or 25–29 years (AOR: 3.3, 95 % CI: 1.3–8.2) compared to 15–19 years. ConclusionsPLHIV just starting ART and young adults had higher odds of being LTFU from TPT during 2019–2021 in the four RRHs. Close follow-up of PLHIV aged 20–29 years and those newly initiated on ART could improve TPT completion.

Tuberculosis preventive treatment among the household contacts of tuberculosis patients – Coverage and correlates in a block of Murshidabad district, West Bengal: A cross-sectional study

BackgroundIndia started implementing tuberculosis preventive treatment (TPT) among all household contacts of Tuberculosis (TB) cases, as a globally accepted strategy for elimination of TB. ObjectivesWe aimed to assess the extent of TPT coverage and adherence; ascertain the reasons for non-initiation and non-adherence; and to determine the correlates of coverage. MethodsWe conducted a cross-sectional study in a block of Murshidabad district, West Bengal during September–November’2023. A calculated sample of 301 eligible household contacts of ‘index cases’ (microbiologically-confirmed drug-sensitive pulmonary TB) registered during October’22 to March’23 were studied. We interviewed the participants/respondents with pre-designed schedule and prior informed consent. Descriptive and inferential statistics were applied through Statistical Package for Social Sciences (version 20). ResultsOf 301 contacts, 179(59.5%) individually traced/counseled at the household; 238 (79.1%) were screened for TB symptoms. TPT initiation was 74.8% (225/301) with 47.1% within seven days of treatment initiation of index case; TPT not offered by health personnel (59.2%) being major reason for non-initiation. Completion rate with adherence to full course was 69.3% (156/225); perceived lack of need (50.7%) and migration (21.7%) being major reasons for non-adherence. Overall coverage of full course TPT among total eligible contacts was only 51.8% (156/301). On multivariable logistic regression; male gender (aOR = 1.982; 95% CI = 1.004–3.915), contacts with individual tracing/counseling (aOR = 13.507; 95% CI = 6.781–26.906) and who had symptoms screening (aOR = 5.694; 95% CI = 2.223–14.587) predicted significantly higher TPT coverage. ConclusionCascade of care indicators for TPT remains suboptimal in the area and indicates need for further strengthening of programmatic aspects of its implementation.

Tuberculosis infection among close contacts of patients with pulmonary tuberculosis in China: a population-based, multicentered study

ObjectivesLimited information is currently available on the prevalence of and risk factors for tuberculosis infection (TBI) among close contacts of patients with pulmonary TB (PTB) in China. In this study, we estimated the burden of TBI among close contacts using QuantiFERON-TB Gold In-Tube assay (QFT) and identified factors associated with TB transmission among this high-risk population. MethodsFrom January 1, 2018 to August 31, 2020, we identified laboratory-confirmed patients with PTB from a population-based, multicentered, cluster-randomized control trial for tuberculosis preventive treatment. Close contacts of these patients were identified, interviewed, and tested using the QFT assay. We estimated TBI prevalence and calculated ORs and 95% CIs for TBI risk factors. ResultsA total of 3138 index cases and 8117 close contacts were identified. Of these contacts, 36 had PTB (a prevalence of 443.51 cases/100 000 population). Among the remaining 7986 close contacts; 3124 (39.12%) reported a positive QFT result. QFT positivity was significantly associated with older age (adjusted OR, 1.77; [95% CI, 1.27–2.47], 2.20; [95% CI, 1.59–3.05], and 2.74; [95% CI, 1.96–3.82]) for age groups: 35–44, 45–54, and 55–64, respectively) when compared with a younger age group: 5–14; longer contact duration (adjusted OR, 1.44; 95% CI, 1.22–1.69); and sharing of a bedroom (adjusted OR, 1.39; 95% CI, 1.18–1.65). DiscussionOur findings indicate a high TBI burden among the close contacts of PTB. The results also highlighted that contact tracing and investigation for TBI are necessary and beneficial, particularly for those who are older, have had a longer contact duration, and share a bedroom.

Tuberculosis preventive treatment uptake among people living with HIV during COVID-19 period in Addis Ababa, Ethiopia: a retrospective data review

BackgroundScreening for tuberculosis (TB) and providing TB preventive treatment (TPT) along with antiretroviral therapy is key components of human immune deficiency virus (HIV) care. The uptake of TPT during the coronavirus disease 2019 (COVID-19) period has not been adequately assessed in Addis Ababa City Administration. This study aimed at assessing TPT uptake status among People living with HIV (PLHIV) newly initiated on antiretroviral therapy during the COVID-19 period at all public hospitals of Addis Ababa City Administration, Ethiopia.MethodsA retrospective data review was conducted from April-July 2022. Routine District Health Information System 2 database was reviewed for the period from April 2020-March 2022. Proportion and mean with standard deviation were computed. Logistic regression analysis was conducted to assess factors associated with TPT completion. A p-value of < 0.05 was considered statistically significant.ResultsA total of 1,069 PLHIV, aged 18 years and above were newly initiated on antiretroviral therapy, and of these 1,059 (99.1%) underwent screening for TB symptoms. Nine hundred twelve (86.1%) were negative for TB symptoms. Overall, 78.8% (719) of cases who were negative for TB symptoms were initiated on TPT, and of these 70.5% and 22.8% were completed and discontinued TPT, respectively. Of 719 cases who were initiated on TPT, 334 (46.5%) and 385 (53.5%) were initiated on isoniazid plus rifapentine weekly for three months and Isoniazid preventive therapy daily for six months, respectively. PLHIV who were initiated on isoniazid plus rifapentine weekly for three months were more likely to complete TPT (adjusted odds ratio [AOR],1.68; 95% confidence interval [CI], 1.01, 2.79) compared to those who were initiated on Isoniazid preventive therapy daily for six months.ConclusionWhile the proportion of PLHIV screened for TB was high, TPT uptake was low and far below the national target of achieving 90% TPT coverage. Overall a considerable proportion of cases discontinued TPT in this study. Further strengthening of the programmatic management of latent TB infection among PLHIV is needed. Therefore, efforts should be made by the Addis Ababa City Administration Health Bureau authorities and program managers to strengthen the initiation and completion of TPT among PLHIV in public hospitals.

Pharmacokinetics of standard versus high-dose rifampin for tuberculosis preventive treatment: A sub-study of the 2R2 randomized controlled trial

BackgroundPharmacokinetic data of rifampin, when used for tuberculosis preventive treatment (TPT) are not available. We aimed to describe the pharmacokinetics of rifampin used for TPT, at standard and higher doses, and to assess predictors of rifampin exposure. MethodsA pharmacokinetic sub-study was performed in Bandung, Indonesia among participants in the 2R2 randomized trial, which compared TPT regimens of 2 months of high-dose rifampin at 20 mg/kg/day (2R20) and 30 mg/kg/day (2R30), with 4 months of standard-dose rifampin at 10 mg/kg/day (4R10) in adolescents and adults. Intensive pharmacokinetic sampling was performed after 2–8 weeks of treatment. Pharmacokinetic parameters were assessed non-compartmentally. Total exposure (AUC0-24) and peak concentration (Cmax) between arms were compared using one-way ANOVA and Tukey's post-hoc tests. Multivariable linear regression analyses were used to assess predictors of AUC0-24 and Cmax. ResultsWe enrolled 51 participants in this study. In the 4R10, 2R20, and 2R30 arms, the geometric mean AUC0-24 was 68.0, 186.8, and 289.9 h⋅mg/L, and Cmax was 18.4, 36.7, and 54.4 mg/L, respectively; high interindividual variabilities were observed. Compared with the 4R10 arm, AUC0-24 and Cmax were significantly higher in the 2R20 and 2R30 arms (P < 0.001). Drug doses, body weight, and female sex were predictors of higher rifampin AUC0-24 and Cmax (P < 0.05). AUC0-24 and Cmax values were much higher than those previously reported in persons with TB disease. ConclusionsDoubling and tripling the rifampin dose led to three- and four-fold higher exposure compared to standard dose. Pharmacokinetic/pharmacodynamic modelling and simulations are warranted to support trials of shortening the duration of TPT regimens with high-dose rifampin.

Predictors of positive tuberculin skin test in neonates exposed to pulmonary tuberculosis.

Neonates are at risk of nosocomial tuberculosis (TB) infection from health care workers (HCWs) in neonatal care facilities, which can progress to severe TB diseases. Tuberculin skin test (TST) is commonly used for TB diagnosis, but its accuracy in neonates is influenced by various factors, including bacilli Calmette-Guérin (BCG) vaccination. This study aimed to identify predictors of positive TSTs in neonates exposed to HCWs with pulmonary TB. A retrospective observational study was conducted to compare the frequency of predictors between TST-positive and TST-negative neonates. Demographic, epidemiological, and clinical data of neonates exposed to TB, along with that of HCW and household contacts, were collected retrospectively through contact investigations with the Korean National TB Surveillance System (KNTSS) database. TSTs using 2 tuberculin units of purified protein derivative RT23 were performed on exposed neonates at the end of preventive TB treatment. Firth logistic regression was performed to identify predictors of TST positivity. Contact investigations revealed that 152 neonates and 54 HCWs were exposed to infectious TB index cases in 3 neonatal care facilities. Of 152 exposed neonates, 8 (5.3%) had positive TST results. Age of 6 days or more at the initial exposure is a statistically significant predictor of positive TST (Firth coefficient 2.1, 95% confidence interval 0.3-3.9, P = 0.024); BCG vaccination showed no statistical significance in both univariable and multivariable analysis. Sex, prematurity, exposure duration, duration from initial exposure to contact investigation, and isoniazid preventive treatment duration were not significant predictors. Age at the initial exposure is a significant predictor of positive TST in neonates exposed to active pulmonary TB. Given the complexities of TST interpretation, including false positives due to BCG vaccination, careful risk assessment is necessary for appropriate decision-making and resource allocation in the management of neonatal TB exposure.

Overcoming barriers to scaling up tuberculosis preventive treatment for household contacts

Overcoming barriers to scaling up tuberculosis preventive treatment for household contacts

Routine tuberculosis contact investigation yield and preventive treatment cascade in central Ethiopia

IntroductionThere is a global gap between tuberculosis incident cases and the notified cases. Active household contact investigation is one of the strategies to narrow this gap. It has the advantage of giving early diagnosis and preventive treatment to vulnerable and eligible groups. This study assessed the practice of contact investigation and tuberculosis preventive treatment adherence in central Ethiopia. MethodA cross-sectional study covering all registered bacteriologically confirmed pulmonary tuberculosis patients and their close contacts was conducted in central Ethiopia from January 1, 2022, to December 30, 2022. ResultA total of 1372 household contacts were declared by the index cases. From these 79.44 % (1090) contacts received a one-time tuberculosis screening giving a total of four (0.36 %) active TB cases. Among 484 household contacts of drug-resistant tuberculosis index cases, 5.53 % (14) had presumptive tuberculosis and 0.79 % (2) had active tuberculosis. While among 837 household contacts of drug-susceptible tuberculosis index cases presumptive TB cases were 1.91 % (16) and active TB cases were 0.23 % (2). Of the 142 eligible under 15 children 81.69 % (116) had started tuberculosis preventive treatment and 84.48 % (98) completed the treatment. On multivariable logistic regression, the associated factor for tuberculosis preventive treatment non-adherence was age 2–5 years (aOR, 0.02, 95 % CI (0.002–0.20) and age 5–15 years (aOR, 0.04,95 % CI (0.002–0 0.95)) P=<0.05). ConclusionThere was low contact screening practice in the DR-TB index cases as compared to national and global targets. The yield of routine contact investigation was low and it indicates the quality of screening. Tuberculosis preventive treatment initiation and completion rates were also low as compared to those of many other countries and global achievements which need further improvement, especially for completion. Alternative mechanisms should be planned to increase the yield of tuberculosis screening and tuberculosis preventive treatment adherence.