Abstract
Literature Highlights is a digest of notable papers recently published in the leading respiratory journals. Coverage includes shorter regimen for TB treatment; mapping the geographical evolution of TB incidence; diagnostic packages for active case finding for TB; TB burden estimation in settings with high levels of HIV; and digital approaches for TB treatment adherence.
Shorter TB treatment strategies
BACKGROUND: Due to adherence issues, the standard 6-month rifampicin-based regimen has underperformed in some national TB treatment programmes, but is a cure possible with shorter regimens?
LATEST STUDY: This adaptive, randomised, non-inferiority, open-label trial in 674 adults (aged 18–65 years) compared standard treatment, or a strategy involving treatment with a range of initial 8-week regimens.1 The trial involved four groups on different initial regimens (each regimen also included isoniazid, pyrazinamide and ethambutol), extended treatment for persistent clinical disease, monitoring after treatment and retreatment for relapse. The primary outcome was a composite of death, ongoing treatment or active disease at Week 96. Of the four trial groups, non-inferiority was finally assessed in two with complete enrolment. A primary-outcome event occurred in 3.9% of participants in the standard-treatment group, as compared to 11.4% in rifampicin-linezolid strategy group (adjusted difference: 7.4 percentage points; 97.5% CI 1.7 to 13.2; non-inferiority not met) and 5.8% in the bedaquiline-linezolid strategy group (adjusted difference: 0.8 percentage points; 97.5% CI −3.4 to 5.1; non-inferiority met). In conclusion, a strategy involving an 8-week regimen of bedaquiline-linezolid-isoniazid-pyrazinamide-ethambutol was non-inferior to standard treatment, was associated with a shorter total duration of treatment and had no evident safety concerns.
NEXT STEPS: The results of this trial suggest a shift in TB management to a strategy involving initial minimum duration of treatment for most patients, with extended treatment for persistent disease and monitoring to detect relapse. However, further evaluation, including in HIV-positive participants, is warranted.
(Reported by Mateja Jankovic Makek)
Mapping the geographical evolution of TB incidence
BACKGROUND: The incidence of TB displays clearly stratified heterogeneity among different country types at different stages of development. Countries at similar stages of development can acquire insights on TB control from nations at higher stages or types of development.
LATEST STUDY: Using a Geotree model, the authors used data from 173 countries and territories to explore the geospatial temporal processes affecting TB incidence from 2010 to 2019.2 Countries were grouped into country types (low, lower-middle, upper-middle and high-income) and development stages (reflecting urbanisation rates and sociodemographic indexes). The analysis showed a marked heterogeneity by country type and development stage in the decline of TB incidence, as visualised using the Geotree model. The most significant average decline in TB incidence observed, surpassing 45%, was among high-income countries in the upper-middle development stage. Conversely, within each country type, low-income countries (Type I) exhibited a minimal average reduction of approximately 13% in TB incidence.
NEXT STEPS: Countries at similar stages of development or within the same type can benefit from the experiences of similar countries in their control of TB. Additional research using a more comprehensive range of socio-economic indicators may help to further disentangle the complex geospatial temporal processes of TB.
(Reported by Gustavo Amorim)
Comparison of two diagnostic packages for active case-finding for TB
BACKGROUND: Despite advances in TB diagnostics, almost 40% of patients remain undiagnosed or unreported globally. These ‘missing’ cases are important as they serve as a reservoir for transmission of TB. Thus, effective active case-finding (ACF) is needed.
LATEST STUDY: This open-labelled, randomised controlled trial screened 5,274 individuals in Cape Town, South Africa for TB symptoms.3 A total of 584 individuals with HIV infection or TB symptoms were randomised (1:1) to test for same-day smear microscopy or on-site DNA-based molecular diagnosis (GeneXpert; Cepheid, Sunnyvale, CA, USA). The primary aim was to determine whether GeneXpert led to significantly shorter time-to-treatment initiation. Secondary aims included feasibility and detection of probably infectious people. TB was culture-confirmed in 58 (9.9%) individuals. GeneXpert was associated with a more rapid time to treatment initiation (8 days vs. 41 days, P = 0.002) and a shorter median time to treatment of probably infectious patients (7 days vs. 24 days, P = 0.02). Although GeneXpert detected only 52% of individuals with culture-positive TB, it did detect a higher proportion of probably infectious people (94.1% vs. 23.5%, P < 0.001) than smear microscopy. The major limitation of the study is a limited sample size from a single-centre in an HIV-endemic country.
NEXT STEPS: The results of this study argue for the implementation of portable DNA-based diagnosis for ACF of probably infectious TB patients. However, a larger multicentric study assessing this screening model, but also the impact of the model on disease burden and mortality, is needed.
(Reported by Mateja Jankovic Makek)
TB burden estimation in settings with HIV epidemics
BACKGROUND: Estimating the burden of TB is challenging due to detection gaps in many settings and significant uncertainties around key epidemiological characteristics. In countries with high HIV prevalence, these difficulties are further amplified by the complex interactions of the two conditions and the highly heterogenous characteristics of people living with HIV.
LATEST STUDY: The authors designed a mathematical model and calibration framework to estimate TB incidence, prevalence and mortality in 12 African countries with high levels of TB-HIV that had a national TB prevalence survey.4 They demonstrated that it is possible to capture accurate TB epidemic dynamics in such settings by carefully integrating the dynamics of population immunocompetence with a TB transmission model. The authors also provided a method to estimate the proportion of TB incidence due to recent infection, an indicator that is critical to guide the TB response and identify the most effective control interventions. The challenges of high computational complexity and significant uncertainty were addressed by utilising novel state-of-the-art Bayesian inference methods from the field of astronomical modelling.
NEXT STEPS: The publicly available methods and code developed by the authors could be reused to perform further analyses in high HIV burden settings, including estimating the effects of TB- and/or HIV-specific interventions or projecting the future TB epidemic trajectory under different control scenarios.
(Reported by Romain Ragonnet)
Digital approaches for TB treatment adherence
BACKGROUND: Long-duration regimens for TB treatment can lead to poor adherence, which has serious consequences, including relapse, drug resistance and increased mortality.
LATEST STUDY: In this minireview, the authors have assessed the advantages and disadvantages of digital adherence support tools.5 These include simple tools such as text reminders, and more complex technologies such as ingestible sensors and digital pillboxes, with/without medication event reminders (MERMs), or synchronous or asynchronous video-observed treatment (sVOT or aVOT). Their analysis included treatment effectiveness (e.g., treatment completion rates), along with acceptability and cost-effectiveness. As expected, MERM was associated with improved rates of cure and improved adherence. However, in contrast to previous reviews, VOT was also found to be effective in improving adherence, possibly because studies on aVOT were included. Furthermore, in contrast to previous findings, two-way SMS improved treatment adherence in a low-income setting, particularly in high-risk patients.
NEXT STEPS: The authors identify the need to better understand behaviour related to adherence. By integrating behavioural science alongside digital technology, there is an opportunity to further improve adherence to treatment.
(Reported by Hugh Blackbourn)
References
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