This systematic review was conducted to synthesize existing evidence on the relationship between health literacy and treatment success in patients with multidrug-resistant tuberculosis (MDR-TB) between January 1, 2015, and October 11, 2025. This review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. All identified records were imported into Zotero ( https://www.zotero.org/accessed on 11 October 2025) for reference management and automatic duplicate removal.

A comprehensive literature search was performed in PubMed and Scopus databases on October 11, 2025. The search strategy combined Medical Subject Headings (MeSH) and free-text terms related to tuberculosis, health literacy, and treatment outcomes. The search key included a combination of keywords: “multidrug-resistant tuberculosis” OR “MDR-TB” OR “rifampicin-resistant tuberculosis” AND “health literacy” OR “health education” OR “health information” OR “self-care behavior” AND “treatment outcome” OR “treatment success” OR “adherence” OR “completion.”. Additional articles were identified by manually screening the reference lists of relevant studies and grey literature in WHO and World Bank repositories, as well as Google Scholar.

Studies were considered eligible if they investigated health literacy, patient knowledge, or educational interventions as determinants, mediators, or predictors of treatment adherence or treatment success among patients diagnosed with multidrug-resistant or rifampicin-resistant tuberculosis (MDR/RR-TB). Eligible studies included those employing quantitative, qualitative, or mixed-methods designs, published as peer-reviewed full-text articles in English between January 2015 and October 2025. Studies were excluded if they focused exclusively on drug-susceptible tuberculosis, lacked original outcome data (such as review articles, commentaries, editorials, or study protocols), or were conference abstracts without peer review.

Two independent reviewers screened the titles and abstracts of all retrieved records using predefined eligibility criteria in Rayyan AI software. ¹⁷ Discrepancies were resolved through discussion and consensus. Full texts of potentially relevant articles were then reviewed to confirm eligibility. A third reviewer verified the inclusion list to ensure completeness.

For each included study, the following data were extracted into a standardized Excel template: author, year, country, study design, study type, evaluation method, and outcomes ( Table 1). Data synthesis was performed through descriptive summary and thematic analysis of relationships between health literacy dimensions and MDR-TB treatment outcomes. This systematic review was not prospectively registered in the PROSPERO database.

A total of seven studies published between 2018 and 2025 met the inclusion criteria and were incorporated into the final synthesis ( Table 1). These studies were conducted across six low- and middle-income countries: India (n = 2), Uzbekistan (n = 1), Thailand (n = 1), Eswatini (n = 1), Peru (n = 1), and South Africa (n = 1) (see Table 1). Collectively, they represent diverse regional contexts of multidrug-resistant tuberculosis (MDR-TB) management and various methodological approaches, including one cluster randomized controlled trial, one case–control study, two cross-sectional analytical studies, and three qualitative investigations.

The interventions examined were heterogeneous in design and focus, reflecting multiple operationalizations of health literacy. Quantitative studies primarily assessed patient education, health literacy levels, self-care behaviours, and determinants of adherence using standardized questionnaires and statistical modelling. Qualitative research explored communication, counselling, and patient provider relationships through thematic and grounded theory approaches. Duration of interventions ranged from one month to forty-five months, indicating variability in the depth and sustainability of implementation across settings.

In South Africa, ¹⁸ a cluster randomized trial evaluated a digital adherence support system using Wisepill EvriMED with tiered feedback, demonstrating improved adherence rates compared to standard care. Cross-sectional studies in Peru ¹⁹ and Eswatini ²⁰ investigated nurse-led health education and the knowledge, attitudes, and practices of community treatment supporters, respectively. In India ²¹ and Uzbekistan, ²² qualitative studies assessed patient experiences with digital pillboxes and person-centered care models, emphasizing engagement and communication in MDR-TB management. A grounded theory study ²³ further highlighted the role of family and social support in adherence. Finally, a case–control study in Thailand ²⁴ identified limited health literacy as an independent predictor of MDR-TB occurrence, underscoring literacy’s influence on patient outcomes. Overall, the included studies captured a broad spectrum of literacy-related interventions, ranging from digital tools and educational counselling to person-centered frameworks, evaluated through both behavioural and clinical indicators of adherence and treatment success.

A primary finding of this review is the striking conceptual inconsistency in how health literacy is operationalized across the MDR-TB literature. We observed a conceptual blurring where “health literacy” was interchangeably used to describe patient knowledge, educational interventions, self-care behaviors, and communication skills. This conflation treats health literacy as both an input and an outcome, thereby complicating the synthesis of evidence and obscuring the true mechanistic role it plays. For instance, Study in Eswatini ²⁰ measured literacy via knowledge and attitudes, ²⁰ study in Peru ¹⁹ framed it as an educational intervention mediating social support. To advance this field, it is imperative to adopt a unified theoretical framework, such as Sørensen’s Integrated Model, which distinguishes between functional (accessing and understanding information), interactive (communicating and applying information), and critical (critically appraising information for informed decision-making) health literacy dimensions. ²⁵ The critical gap highlighted by our review is the complete absence of studies using validated, multidomain health literacy instruments tailored to the MDR-TB context. Without such tools, we cannot pinpoint which specific literacy dimension understanding drug side-effects (functional) or negotiating treatment with a provider (interactive) is most predictive of treatment success, thereby hindering the development of targeted interventions.

Beyond mere association, our synthesis elucidates the complex, multi-faceted mechanistic pathways through which health literacy influences MDR-TB outcomes. The evidence demonstrates that its role is not monolithic but context-dependent. It functions as a direct predictor, as shown study in Thailand ²⁴ where low health literacy independently doubled the odds of MDR-TB. More subtly, it acts as a mediator, exemplified study in Peru, ¹⁹ where health literacy was the crucial cognitive and skills-based mechanism that translated external social support into internalized motivation and actionable self-care behaviors, ultimately improving adherence. Furthermore, health literacy serves as a critical enabler for digital health technologies. The studies in India ²¹ and South Africa ¹⁸ demonstrate that the efficacy of digital pillboxes and adherence monitors is contingent upon a patient’s baseline literacy to interpret device alerts, understand their significance, and problem-solve technical issues. This novel insight moves the field beyond a simple linear correlation and positions health literacy as a dynamic competency that interacts with and amplifies other therapeutic factors.

The included studies evaluated a spectrum of intervention modalities, from digital pillboxes to person-centred counselling. Our analysis suggests that while technology-driven tools show promise for objective monitoring, the most profound impacts on long-term adherence likely stem from interactive, dialogue-based models. The Study in Uzbekistan ²² on person-centred care is paradigmatic; its effectiveness lies in its direct cultivation of interactive health literacy. By fostering open dialogue between patients and healthcare workers, ²⁶ it builds trust, mutual understanding, and shared decision-making, which in turn enhances intrinsic motivation and the problem-solving skills necessary to navigate a lengthy ²⁷ and arduous treatment course. ^{28, 29} A critical synthesis of these findings leads us to highlight that the most successful interventions are inherently multi-component. They do not seek to improve literacy in a vacuum but integrate literacy support within a broader framework that simultaneously addresses structural barriers such as stigma, ²³ nutritional support, and socioeconomic constraints, creating a holistic ecosystem for patient success.

The exclusive derivation of evidence from low- and middle-income countries (LMICs) ^{18, 23} underscores the global health equity dimensions of the MDR-TB challenge and rightly focuses attention on the settings where the burden is greatest. Our review clearly indicates that local context acts as a powerful effect modifier. The impact of a health literacy intervention is not determined solely by its design but is profoundly shaped by local health system structures, cultural beliefs about illness and medication, and the pervasive level of TB-related stigma, which varied significantly between the settings in Eswatini, ²⁰ Peru, ¹⁹ and India. ²¹ This necessitates a fundamental rejection of the “one-size-fits-all” approach. ³⁰ Strategies must be locally adapted and co-designed with communities to ensure cultural resonance ³¹ and address context-specific barriers. ²⁴ In this endeavour, the dual role of community health workers and peer supporters, as highlighted across multiple studies, ³² becomes indispensable. They act not only as literacy facilitators but also as cultural translators, effectively bridging the chasm between the formal health system and the patient’s lived experience. ³³

This review consolidates compelling evidence that strengthening health literacy is a viable and patient-centric strategy to improve MDR-TB treatment outcomes. It is a modifiable determinant that operates through direct, mediated, and enabling pathways and is most effectively bolstered through multi-component, person-centred interventions. However, these conclusions must be interpreted in the context of this review’s limitations. The small number of included studies (n = 7), their significant methodological heterogeneity (encompassing RCTs, cross-sectional, and qualitative designs), and the restriction to English-language publications may introduce selection bias and limit the generalizability of our findings. Furthermore, the conceptual fragmentation discussed earlier inherently constrains the robustness of any cross-study synthesis. These limitations, however, clearly chart the course for future research. There is an urgent need for prospective cohort studies that employ validated, multidimensional health literacy instruments to establish causal relationships and quantify the effect size of specific literacy dimensions. Concurrently, the field requires the development and rigorous evaluation of complex interventions specifically designed to target functional, interactive, and critical health literacy within MDR-TB care programs. Translating this evidence into practice demands that national TB programs move beyond passive information dissemination and instead integrate routine health literacy assessments and train healthcare providers in literacy-sensitive communication techniques. By doing so, we can leverage health literacy not just as a concept, but as a powerful, evidence-based tool to combat the global threat of MDR-TB.