Ruvandhi R. Nathavitharana

Background: Since 2020, Infectious Diseases Society of America/American Thoracic Society/Centers for Disease Control and Prevention guidelines have preferentially recommended ≤4-month rifamycin-based regimens for tuberculosis infection. Since 2022, recommendations have included all-oral 6-month regimens (bedaquiline, pretomanid, and high-dose linezolid [BPaL] or BPaL plus moxifloxacin [BPaL-M]) for drug-resistant disease and a 4-month regimen (rifapentine, isoniazid, and moxifloxacin [HPMZ]) for drug-susceptible disease. Yet implementation of new regimens often lags behind guidelines. This survey aimed to characterize tuberculosis treatment practices of infectious disease clinicians and barriers to utilizing these regimens. Methods: A survey about tuberculosis treatment practices was distributed to 1501 North American adult infectious disease physician members of the IDSA's Emerging Infections Network. Percentages of respondents were calculated for each question. Open comment data were qualitatively analyzed. Results: Three hundred forty-nine clinicians completed the survey. Ninety-three percent of respondents preferentially opted for ≤4-month regimens for tuberculosis infection, with only 12% expressing concerns about treatment effectiveness. In contrast, 1% selected HPMZ for pulmonary drug-susceptible disease, and 5% reported experience with HPMZ. For confirmed drug-resistant disease, 39% reported that they would use BPaL or BPaL-M, with 40% unsure about regimen choice. Forty-three percent reported uncertainty about effectiveness of 4- and 6-month regimens for drug-susceptible disease and drug-resistant disease. Qualitative analysis highlighted barriers to the use of newer regimens for tuberculosis disease, including concerns about treatment toxicities related to HPMZ or linezolid, medication interactions, and rifapentine and bedaquiline availability. Conclusions: While infectious disease physicians preferentially use shorter regimens for tuberculosis infection, uptake of newer regimens for tuberculosis disease is low due to concerns about effectiveness and treatment toxicities. Enhanced adverse effect management and monitoring and shared decision-making can optimize the implementation of newer tuberculosis disease treatment regimens.

While community health workers (CHWs) have important contributions to offer the South African health system and tuberculosis (TB) response, their expertise has been insufficiently valued in quality improvement and policy development processes. Realizing the full benefits of CHWs require community systems for health that are responsive to their needs, however, important gaps remain in our knowledge of how to achieve this. In this Lessons and Experiences article, we describe our experiences and reflections from applying a participatory action research (PAR) framework to empower CHWs in a rural, underserved setting as champions in the South African TB response. Using two action-reflection cycles, this civil society initiative surfaced CHWs perspectives on local TB care, provided spaces for collaboration through dialogue, enabled co-developing innovative actions responding to identified gaps, and strengthened CHWs capacity to engage in collective advocacy for strengthening their role in the national response. CHWs champions identified TB stigma as an under addressed local TB challenge, and identified inadequate training, occupational hazards and unfair remuneration as key impediments to their effectiveness as CHWs. Community theatre productions and multi-pronged advocacy campaigns helped create conditions that led to changes in services at their local clinic, provincial CHWs employment policy, and support from national policymakers. We identified key lessons and recommendations on four common participatory research challenges that can inform future applications of PAR for CHWs empowerment. First, time and reflexivity discussions promoted trust. Second, we supported emancipatory power development through capacity-strengthening, building networks, developing accessible materials on CHWs policy, and harnessing momentum from shorter-term actions towards higher-impact actions. Third, we challenged narrow definitions of scalability that prioritize replicating outputs of CHWs labour without power-shifting engagements. Fourth, CHWs participation barriers (e.g. language and technology) exacerbated by the COVID-19 pandemic necessitated multiple options for engagement. This work demonstrates how PAR can lead to innovative actions addressing local care barriers and national workforce challenges by leveraging relationship-building, reflexive engagement, emancipatory power dimensions, resisting extractive norms and adapting to challenges.

Background: The duration of infectiousness following pulmonary tuberculosis treatment initiation remains uncertain. We aimed to assess whether a bundled intervention designed to decrease respiratory exposure was feasible and would reduce new tuberculosis infections in household contacts (HHCs). Methods: We conducted a pilot cluster-randomized controlled trial with a hybrid type 1 effectiveness-implementation design in Santiago, Chile. Random allocation was performed, and 2 healthcare districts were assigned to the intervention (n = 180 HHCs) and 1 to standard of care (n = 149 HHCs). Eligible participants were people newly diagnosed with pulmonary tuberculosis and their HHCs. The intervention included education, mask use, household ventilation, and nightly separation of tuberculosis patients, for 2 weeks. Intervention adherence was evaluated weekly. Effectiveness was assessed at the individual level with QuantiFERON®-TB Gold Plus (QFT) test conversions in HHCs at 12-week follow-up. Results: Between October 2021 and December 2023, 384 HHCs and 157 people with tuberculosis were enrolled. Overall, 56.3% of contacts were women, with a mean age of 34.6 years and a baseline QFT positivity of 32.3%. A total of 216 contacts had negative QFT result at baseline, with 179 (82.9%) completing follow-up. QuantiFERON®-TB Gold Plus conversions occurred in 11 (12.8%) and 10 (10.8%) HHCs from the intervention and control arms, respectively (incidence risk ratio 1.10, 95% CI .71–1.71, P = .849). Good adherence to the respiratory bundle was reported by 53% of participants on day 7 and 54% on day 14. Conclusions: Isolation and restrictive measures after tuberculosis treatment initiation proved challenging and did not reduce tuberculosis infections in HHCs, suggesting limited benefit for transmission control.

Introduction: Fewer than 50% of people with tuberculosis receive a molecular WHO-recommended rapid diagnostic test (mWRD). We performed a mixed-methods systematic review to categorise barriers and enablers that affect mWRD use and impact and evaluate mWRD implementation strategies. Parts of this review informed the WHO standard: Universal Access to Tuberculosis Diagnostics. Methods: We searched multiple databases without language restrictions until 29 July 2022. We included studies that used qualitative, quantitative or mixed methods study designs. Four reviewers independently screened studies and extracted data. We categorised studies as thick or thin depending on whether authors analysed findings beyond a descriptive list of barriers or enablers and demonstrated insights into participants’ perspectives. We appraised study quality by adapting the Standards for Reporting Implementation Studies statement. We synthesised data using a thematic approach and used GRADE-CERQual to assess confidence in the findings. Results: We identified 54 high-thickness studies from 18 countries, including public and private healthcare settings. Implementation strategies included engaging patients, training and supporting clinicians, building infrastructure and interactive assistance. Examples included remote outreach programmes, community testing, longitudinal clinician engagement, auxiliary workers, multicomponent strategies, performance feedback, improving health information management to strengthen care linkage and diagnostic network improvement. We had high or moderate confidence in our findings. Conclusion: Innovative and contextually relevant implementation strategies are needed for tuberculosis programmes to realise the benefits of improved accuracy and diagnostic expediency that mWRDs offer. Multicomponent strategies that centre equity and longitudinal health worker training across the diagnostic cascade must be prioritised.

BACKGROUND: The FAST (Find cases Actively, Separate safely and Treat effectively) TB infection control (TB-IC) strategy decreases the time-to-TB diagnosis and treatment. We examined healthcare workers’ (HCW) perceptions of FAST implementation at a tertiary referral hospital in Lima, Peru. METHODS: From August 2016 to December 2019, we conducted 24 interviews and four focus groups ( n = 14) with a diverse population of HCWs and other stakeholders involved throughout the TB care cascade. We used inductive analysis to identify emergent themes, used Dedoose to code transcripts accordingly, and developed a narrative using reflexive thematic analysis. RESULTS: We identified three emergent themes: 1) FAST impact on TB care, 2) FAST impact on TB-IC and 3) FAST impact on hospital culture. FAST was felt to improve the speed of TB screening, diagnosis and treatment. TB specialists recognized that by expediting diagnosis and treatment, FAST likely decreased transmission. Healthcare workers appreciated that FAST improved care coordination along the TB care cascade. FAST changed hospital culture related to the prioritization of TB-IC. CONCLUSION: HCWs perceived that FAST, implemented by a dedicated external team, was an acceptable and effective TB-IC strategy that improved care coordination and overall TB quality of care.

Background: Most drug-resistant tuberculosis occurs due to transmission of unsuspected or ineffectively treated drug-resistant tuberculosis. The duration of treatment to stop person-to-person spread of drug-resistant tuberculosis is uncertain. We evaluated the impact of novel regimens, including BPaL (bedaquiline, 1200-mg linezolid, and pretomanid), on drug-resistant tuberculosis transmission, using the human–guinea pig (H-GP) transmission model. Methods: In experiment 1, patients initiated an optimized drug-resistant tuberculosis regimen including bedaquiline and linezolid. In experiment 2, patients initiated the BPaL regimen. We measured baseline infectivity for each cohort by exhausting ward air to one of two guinea pig exposure rooms (control group), each containing 90 guinea pigs, for 8 patient-days. Then, after 72 hours of treatment, ward air was exhausted to the second guinea pig exposure room for 8 patient-days (intervention group). The infectiousness of each cohort was compared by performing tuberculin skin tests in guinea pigs at baseline (before treatment) and 6 weeks after the exposure period. Results: In experiment 1, before treatment, 5 patients with drug-resistant tuberculosis infected 24 of 90 guinea pigs (26.7%) (control group). After treatment (72 hours after drug initiation), the same patients infected 25 of 90 guinea pigs (27.8%) (intervention group) (P > .99). In experiment 2, before treatment, 9 patients with drug-resistant tuberculosis infected 40 of 90 guinea pigs (44.4%) (control group). After treatment (beginning 72 hours after drug initiation), the same patients infected 0 of 90 guinea pigs (0%) (intervention group) (P < .0001). Conclusions: In this study, drug-resistant tuberculosis drug regimens, including bedaquiline and standard-dose linezolid for 72 hours, did not decrease drug-resistant tuberculosis transmission. In contrast, transmission was rapidly and completely inhibited in patients treated with BPaL for 72 hours, suggesting an early and profound impact on transmission.

Background: Respiratory isolation of people with pulmonary tuberculosis (TB), including after treatment initiation, is used to prevent community-based transmission; yet guidelines on duration are limited and implementation is heterogeneous. This systematic review synthesized evidence on respiratory isolation for TB to inform National TB Coalition of America guidelines. Methods: After searching 6 databases, 8 reviewers screened and extracted data in duplicate on effects of respiratory isolation compared to no isolation or masking. Studies were stratified by outcomes: TB infection or disease in contacts, mortality, hospitalization duration, patient and health system costs, and impact on mental health or stigma. We used a convergent integrated approach to synthesize quantitative and qualitative findings and assess limitations. Results: Seventeen studies were included. There were limited data directly comparing isolation to non-isolation interventions, including effects after treatment initiation. One randomized controlled trial suggested treatment in a sanatorium versus at home did not affect TB incidence in contacts. Modeling studies suggest isolation may reduce transmission but relied on various assumptions, and isolation was implemented alongside other interventions. Descriptive, mixed-methods, and qualitative studies described adverse impacts of isolation on employment, education, food/housing security, and mental health due to transmission fears, stigma, and social isolation. Impacts were compounded in marginalized groups including Indigenous and incarcerated persons. Conclusions: Data to support current isolation practices, particularly after effective treatment initiation, to reduce TB transmission in communities are limited. Public health guidance should weigh the negative impacts on people with TB against decreased community transmission to make evidence-based decisions about respiratory isolation.

Determining the extent and duration of infectiousness of individuals with pulmonary tuberculosis (TB) is critical for various aspects of TB care, including decisions regarding isolation. Studies suggest considerable heterogeneity in infectiousness of people with pulmonary TB. Pre-treatment, measures of bacillary burden including sputum smear microscopy, culture time-to-positivity, and Xpert MTB/RIF cycle threshold (Ct) value, predict the risk of transmission to contacts. Index patients with smear negative disease pose lower infectious risk than those who have smear-positive disease, and household contact infection is more likely with index patients who have lower Xpert Ct values. Newer tools that enable detection of Mycobacterium tuberculosis complex (Mtb complex) from cough aerosol sampling and face mask sampling may be better predictors of contact infection risk. Clinical factors such as cough strength and frequency, and presence of cavitation on chest imaging, may also assist with risk prediction. Post-treatment, smear and culture status are poor predictors of infectiousness. While the exact duration of infectiousness post treatment initiation remains uncertain, data from human-to-guinea pig transmission studies and clinical studies suggest effective treatment results in a rapid decline in infectiousness, irrespective of smear or culture conversion. This is largely supported by early bactericidal activity and transcriptomic studies, and cough aerosol sampling studies, although a subset of patients may have persistent cough aerosol positivity. These findings can enable a more nuanced approach to isolation decision making, while further research studies are awaited.