Effectiveness and cost-effectiveness of a health systems intervention for latent tuberculosis infection management (ACT4): a cluster-randomised trial

Oxlade, Olivia; Benedetti, Andrea; Adjobimey, Mênonli; Alsdurf, Hannah; Anagonou, S.; Cook, Victoria; Fisher, Dina; Fox, Greg J.; Fregonese, Federica; Hadisoemarto, Panji Fortuna; Hill, Philip C.; Johnston, James C.; Khan, Faiz Ahmad; Long, Richard; Nguyen, Nhung Viet; Nguyen, Thu Anh; Obeng, Joseph; Ruslami, Rovina; Schwartzman, Kevin; Trajman, Anete; Valiquette, Chantal; Menzies, Dick

doi:10.1016/s2468-2667(20)30261-9

Cited by 23 publications

(29 citation statements)

References 24 publications

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“…Engaging community health workers may support this effort; Zawedde-Muyanja et al found improvements in screening of household contacts and initiation and completion of TPT among children in Uganda following training of community health workers [25] . Economic analysis of a multi-country (Benin, Canada, Ghana, Indonesia, and Vietnam) trial to strengthen management of household contacts of people with confirmed TB estimated a cost of the intervention and TPT-associated clinical care of CA$1348 per contact [26] . Investigators working in Vietnam calculated an incremental cost-effectiveness ratio of $544 per disability-adjusted life year averted for a serial screening program among household contacts of adults with smear-positive TB [27] .…”

Section: Discussionmentioning

confidence: 99%

Estimating the population at high risk for tuberculosis through household exposure in high-incidence countries: a model-based analysis

Ross¹,

Xie²,

Wang³

et al. 2021

eClinicalMedicine

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Background Household contacts of people with pulmonary tuberculosis (TB) have greater risk of developing TB. Recent guidelines conditionally recommended TB preventive treatment (TPT) for household contacts of any age living in TB high-incidence countries, expanding earlier guidance to provide TPT to household contacts under five. The all-age population of household contacts has not been estimated. Methods Our model-based estimation included 20 countries with >80% of incident TB globally in 2019. We developed country-specific distributions of household composition by age and sex using bootstrap resampling from health surveys and census data. We incorporated age-, sex-, year-, and location-specific estimates of pulmonary TB incidence from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 to estimate the population in each country sharing a household with someone with incident pulmonary TB, and quantified uncertainty using a Monte Carlo approach. Findings We estimate that 38 million [95% uncertainty interval (UI) 33- 43 million] individuals lived in a household with someone with incident pulmonary TB in 2019 in these 20 countries. Children under five made up 12% of the population with household exposure, while adults were 65%. Zimbabwe, Mozambique, Zambia, and Pakistan had the highest proportion of the population with household exposure, while India had the highest number of contacts (11·4 million, 95% UI 9·7-13·4 million). Interpretation Expanding TPT evaluation to household contacts of all ages in high-incidence countries could include a population more than 7-times larger than the under-5 contacts previously prioritized. This would substantially increase the impact of household contact investigation on reducing TB morbidity and mortality. Funding JMR is supported by the National Institute of Allergy and Infectious Diseases (K01 AI138620). This research was funded in part by a 2020 developmental grant from the University of Washington / Fred Hutch Center for AIDS Research, an NIH funded program under award number AI027757 which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, NIDDK. This work was funded in part by the National Science Foundation (DMS-1839116).

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Section: Discussionmentioning

confidence: 99%

Estimating the population at high risk for tuberculosis through household exposure in high-incidence countries: a model-based analysis

Ross¹,

Xie²,

Wang³

et al. 2021

eClinicalMedicine

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“…We are interested in detecting a difference between the proportion of HHC starting TPT in those randomized to the standard algorithm and each of the alternative regimens. The proportion starting TPT during phase 2 of ACT4 [ 26 , 27 ], at the same study sites, when solutions had been implemented and the barriers of TST and CXR had been resolved, will be used as the likely proportion in the standard arm. We consider that accepting to start treatment will likely be strongly influenced by other household members.…”

Section: Methods and Analysismentioning

confidence: 99%

“…This gave an intra-class correlation coefficient (ICC) or clustering effect of HHC of 0.33. Based on this ICC and an average of three HHC aged 5–50 years (observed in the ACT4 trial) [ 26 , 27 ], we can estimate the design effect as 1 + (household size-1)*ICC. We will assess differences across sites but expect randomization to reduce potential confounders.…”

Section: Methods and Analysismentioning

confidence: 99%

“…In the ACT4 trial [ 27 ], 60% of eligible HHC started a TPT regimen once the TST and CXR problems were resolved. We assume that 50% of HHC aged 5–50 would be eligible for TPT and that 60% of eligible HHC contacts in the standard arm would start therapy—for an overall initiation rate of 30% of participants randomized to the standard arm in this trial.…”

Section: Methods and Analysismentioning

confidence: 99%

“…Hence, we have calculated study power for each country (Table 2). For power calculations, costs are based on estimates from the WHO CHOICE database [30] and data gathered as part of prior studies (ACT4) [27]. The number enrolled to each arm (assuming one HHC per household, type 1 error = 0.05) within each country should provide more than 90% power to detect a significant difference in costs.…”

Section: Sample Sizementioning

confidence: 99%

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GeneXpert or chest-X-ray or tuberculin skin testing for household contact assessment (GXT): protocol for a cluster-randomized trial

Trajman

Adjobimey

Bastos

et al. 2022

Trials

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Background The World Health Organization recommends tuberculosis (TB) preventive treatment (TPT) for all people living with HIV (PLH) and household contacts (HHC) of index TB patients. Tests for TB infection (TBI) or to rule out TB disease (TBD) are preferred, but if not available, this should not be a barrier if access to these tests is limited for high-risk people, such as PLH and HHC under 5 years old. There is equipoise on the need for these tests in different risk populations, especially HHC aged over 5. Methods This superiority cluster-randomized multicenter trial with three arms of equal size compares, in Benin and Brazil, three strategies for HHC investigation aged 0–50: (i) tuberculin skin testing (TST) or interferon gamma release assay (IGRA) for TBI and if positive, chest X-Ray (CXR) to rule out TBD in persons with positive TST or IGRA; (ii) same as (i) but GeneXpert (GX) replaces CXR; and (iii) no TBI testing. CXR for all; if CXR is normal, TPT is recommended. All strategies start with symptom screening. Clusters are defined as HHC members of the same index patients with newly diagnosed pulmonary TBD. The main outcome is the proportion of HHC that are TPT eligible who start TPT within 3 months of the index TB patient starting TBD treatment. Societal costs, incidence of severe adverse events, and prevalence of TBD are among secondary outcomes. Stratified analyses by age (under versus over 5) and by index patient microbiological status will be conducted. All participants provide signed informed consent. The study was approved by the Research Ethic Board of the Research Institute of the McGill University Health Centre, the Brazilian National Ethical Board CONEP, and the “Comité Local d’Éthique Pour la Recherche Biomédicale (CLERB) de l’Université de Parakou,” Benin. Findings will be submitted for publication in major medical journals and presented in conferences, to WHO and National and municipal TB programs of the involved countries. Discussion This randomized trial is meant to provide high-quality evidence to inform WHO recommendations on investigation of household contacts, as currently these are based on very low-quality evidence. Trial registration ClinicalTrials.gov NCT04528823.

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Screening for Latent Tuberculosis Infection

Menzies

2023

JAMA Netw Open

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The US Preventive Services Task Force (USPSTF) has recommended screening of adults at increased risk for latent tuberculosis (TB) infection (LTBI). 1 This recommendation (B statement) is based on an evidence review 2 that found that available tests-in particular, the tuberculin skin test and interferon-γ release assays-were sufficiently accurate to identify persons with LTBI and that TB preventive treatment (TPT) regimens now recommended in the US 3 should provide moderate net benefit 1 to persons identified from screening. The USPSTF advised following the recommendations for testing in persons who have immunosuppression made by the American Thoracic Society and Centers for Disease Control and Prevention 2017 4 and recommendations for TPT made by the Centers for Disease Control and Prevention in 2020. 3 The USPSTF noted that this recommendation is for adults not included in other recommendations 3,4 for LTBI testing and treatment, such as persons living with HIV, persons about to receive a solid-organ transplantation or tumor necrosis factor-α inhibitors, or other groups at increased risk because of immune suppression. The task force also noted that this recommendation is not for contacts of persons with a recent diagnosis of active TB disease, who are generally investigated by public health services. Hence, these recommendations are focused on persons who are otherwise healthy but have increased likelihood (risk) of having TB infection. Although this includes some US-born persons, the vast majority of persons who will be affected by this recommendation are individuals who immigrated to the US from countries where TB incidence is much higher. On the basis of estimates of the prevalence of LTBI among persons in the US who were born outside the US, 5 this represents a very substantial increase from the number of persons now screened.Before starting screening, a reminder is needed. The USPSTF also recommends that to achieve the benefit of screening, it is important that persons who screen positive for LTBI receive follow-up and treatment 1 ; if TPT is not completed, then there will be no benefit of screening. Hence, a decision to implement screening for LTBI in any setting or for any population must include a commitment to ensure adequate follow-up of those with positive test results. 6 This includes medical and radiographic evaluation to exclude TB disease, offering TPT to all those who are eligible, and then education and counseling plus subsequent close follow-up of those who accept TPT, to ensure adherence as well as to detect and manage any adverse effects. Substantial time and resources are needed to ensure that care is well organized for all steps in the cascade to minimize losses, or a screening program will have far less benefit than expected. 6 Numerous studies have shown that there are substantial losses in the cascade of LTBI care, at the steps of initial identification of candidates for screening (testing), medical evaluation, and offering TPT, as well as acceptance and completion of TPT by individuals,...

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Effectiveness and cost-effectiveness of a health systems intervention for latent tuberculosis infection management (ACT4): a cluster-randomised trial

Cited by 23 publications

References 24 publications

Estimating the population at high risk for tuberculosis through household exposure in high-incidence countries: a model-based analysis

Estimating the population at high risk for tuberculosis through household exposure in high-incidence countries: a model-based analysis

GeneXpert or chest-X-ray or tuberculin skin testing for household contact assessment (GXT): protocol for a cluster-randomized trial

Screening for Latent Tuberculosis Infection

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