Tuberculosis (TB) remains a major global public health threat, but its burden is not evenly distributed, with specific challenges emerging at the regional and national levels. In Egypt, TB persists as a significant public health issue, even amidst global improvements in diagnosis and treatment. The World Health Organization (WHO) reports that Egypt has an estimated TB incidence of 11 cases for every 100,000 people, with treatment success rates below the global goal of 90% with an estimated mortality rate (including TB among HIV-positive people) of 3.1 deaths per 100,000 population in 2022. This translates to approximately 3,300 deaths annually, positioning Egypt's TB mortality burden lower than the global average and reflecting the impact of the country's sustained national TB control efforts [1]. Despite this achievement, TB remains a persistent public health threat, and these figures underscore the critical need to address drivers of mortality, such as treatment non-adherence and the rise of drug-resistant strains, to accelerate the decline in TB-related deaths [2]. Tackling these issues is crucial for improving treatment outcomes and lowering the TB burden in Egypt [3].

In Egypt, the sociocultural landscape significantly exacerbates the risk of TB treatment non-compliance, a problem whose scale is reflected in national treatment success rates that often fall short of WHO targets. Deeply entrenched stigma, fueled by misconceptions that TB is a shameful disease or a divine punishment, drives patients, particularly women, to conceal their diagnosis and avoid clinic visits to prevent social ostracization and protect family honor [4]. This is compounded by widespread health illiteracy and cultural beliefs that prioritize traditional remedies over biomedical treatment, leading patients to abandon therapy once initial symptoms subside. Furthermore, the substantial economic burden of treatment, including lost wages from frequent clinic visits and costs of transportation and nutritious food—forces many low-income earners to choose between their health and their livelihood [5]. The consequences of this non-adherence are severe at both the individual and public health levels, leading to increased drug resistance, higher mortality, and continued community transmission, as untreated or partially treated patients, even those initially sputum-negative, remain a reservoir for the bacillus, perpetuating a cycle of disease and poverty that poses a major obstacle to national TB control efforts [6].

Beyond individual financial hardship, structural weaknesses within the healthcare system itself also play a big role in non-compliance. Long distances to treatment centers, frequent drug shortages, and lack of patient counseling are key challenges. Egypt’s centralized TB control program, though effective in urban settings, has trouble reaching rural areas, where patients often experience delays in diagnosis and fragmented care. Moreover, the absence of patient-centered approaches, such as limited health education and poor communication between providers and patients, worsens non-adherence [7]. Improving decentralized care, expanding telemedicine options, and better training for healthcare workers could help close these gaps [8]. Compounding these systemic and economic factors are patient-related issues, such as lack of knowledge, stigma, and other health conditions, which make it even harder for patients to stick to their treatment. Many TB patients in Egypt are not fully aware of how serious the disease is or the risks of incomplete treatment [9].

Selecting sputum-negative TB patients as the study population is twofold, addressing a critical gap in both clinical management and public health strategy. Firstly, sputum-negative TB often presents with milder or atypical symptoms, leading to delayed diagnosis and a potential underestimation of disease severity by both patients and clinicians; this diagnostic ambiguity can foster complacency, making this group particularly vulnerable to non-adherence as they may feel less ill and therefore less motivated to complete the lengthy treatment regimen [10]. Secondly, from a public health perspective, while sputum-negative patients are considered less infectious, they still contribute significantly to community transmission, especially if their treatment is interrupted, which can lead to relapses and potential progression to contagious sputum-positive disease [11]. Therefore, understanding and addressing the unique adherence challenges in this understudied but epidemiologically important patient group is essential for developing targeted interventions that not only improve individual outcomes but also ultimately disrupt the chain of TB transmission within the community.

Finally, the framework of the current study is contextualized within Egypt's unique socioeconomic and health-system environment, acknowledging that external factors like poverty, limited social support, and healthcare access are not merely background variables but active determinants that directly shape the individual perceptions and self-efficacy. This integrated approach allows the study to move beyond a simple description of factors and toward an explanatory model of how cognitive, behavioral, and environmental dynamics interact to drive compliance or non-compliance [12]. In Egypt, where alternative medicine and self-medication are widespread, some patients stop taking prescribed TB medications and turn to unproven remedies instead [10]. Programs to monitor drug safety and better patient counseling on managing side effects are crucial for improving adherence [13].

Understanding treatment adherence dynamics in Egypt requires a comprehensive approach that specifically includes sputum-negative TB patients, as their unique diagnostic and psychosocial challenges create distinct barriers to care [3]. This focus is critical because, unlike their smear-positive counterparts, sputum-negative patients often face significant diagnostic delays in the Egyptian healthcare system, which can erode trust in the medical establishment and de-motivate patients from the outset of their long and arduous treatment regimen. Furthermore, the absence of confirmatory bacteriological evidence can exacerbate social stigma, thereby weakening the crucial social support network that is a known pillar of treatment adherence. Consequently, excluding this significant patient subgroup would yield an incomplete and potentially biased understanding of adherence factors, as the drivers of non-compliance for them may differ qualitatively [5,6].

Therefore, a thorough investigation of the factors affecting compliance and non-compliance must intentionally integrate the sputum-negative experience to ensure that future supportive interventions in Egypt are equitable, inclusive, and effectively tailored to the needs of the entire TB patient population. This study aimed to assess the factors affecting compliance and non-compliance among patients with TB.

The study aimed to assess factors affecting treatment compliance and non-compliance among patients with TB. The current study offers important insights into how sociodemographic factors, clinical presentation, knowledge levels, and treatment adherence interact among TB patients in Egypt. Our findings reveal several key patterns that deserve further discussion considering recent evidence from similar settings.

The results confirm a critical educational and economic divide between compliant and non-compliant patients. The high illiteracy rate among non-compliant patients (almost double) presents a fundamental challenge in a context characterized by diverse educational levels. This underscores the need for contextually appropriate health awareness programs that do not rely solely on literacy but utilize simple visual and auditory tools, aligning with the framework proposed by Hargreaves et al. [18]. The financial burden, indicated by most non-compliant patients reporting insufficient income for treatment, reflects the reality of poverty and catastrophic health expenditures in a health system reliant on out-of-pocket payments. This forces patients to choose between working to secure their livelihood and adhering to clinic appointments, a dilemma highlighted by studies in Egypt [5].

The differences in nutritional status confirm that malnutrition increases drug toxicity and decreases treatment tolerance, as established in a clinical review of TB and undernutrition [19]. The significantly higher rate of normal BMI in the compliant group (87.5% vs. 52.5%) and their higher mean BMI (21.6 vs. 20.1) suggest that nutritional status is a critical biological determinant of treatment adherence. This relationship likely operates through a dual pathway: physiologically, adequate nutrition bolsters the immune system and provides the metabolic reserves necessary to tolerate and metabolize powerful TB drugs, reducing the severity of drug-related side effects that often lead to missed doses [10]. Simultaneously, a normal BMI may also be a proxy for better socioeconomic status, reflecting greater household food security and overall stability, which reduces the competing pressures of poverty that force patients to prioritize work or other survival needs over consistent treatment. Therefore, being loss of weight is not merely a symptom of TB but an active barrier to its cure, creating a vicious cycle where the disease worsens malnutrition, which in turn undermines the capacity to complete treatment [17].

BMI is not just an indicator, but a cornerstone of treatment success. The significant gap in BMI between the two groups emphasizes that malnutrition, prevalent in Egypt due to economic and dietary cultural factors, creates a vicious cycle: TB causes wasting, which weakens the body's ability to tolerate drugs and increases their toxicity [19], leading the patient to abandon treatment, which in turn worsens the disease and malnutrition. Therefore, integrating nutritional support into the TB treatment package is not a luxury, but a necessary investment in treatment efficacy, especially for the poorest segments of the population.

Furthermore, analysis of symptom severity shows significant differences in clinical profiles between the groups. Non-compliant patients faced more severe symptoms across various domains, a pattern quantified using a tool like the symptom-based scoring system in a community-based study in Guinea-Bissau [20]. The higher rates of anorexia, fever, and overall severe symptoms in non-compliant patients suggest a potential cycle where more severe symptoms lead to worse adherence. This fits with the "symptom-adherence paradox," where patients with more severe symptoms exhibit poorer adherence due to complex psychosocial factors, a dynamic noted in studies of TB-related stigma, such as the qualitative research on patient experiences in Egypt [10].

This creates a biologically vicious cycle: severe symptoms like fatigue and anorexia can directly reduce a patient's physical and cognitive capacity to adhere to treatment. Furthermore, the near-universal presence of cough in the non-compliant group may indicate a longer duration of illness or treatment failure, which itself is a consequence of non-adherence, thus creating a feedback loop that worsens health outcomes.

The nearly universal occurrence of cough in non-compliant patients may indicate delayed treatment initiation or treatment failure, as noted in recent TB monitoring reports. Forgetting medication and unmanaged side effects represent a significant behavioral and biological barrier. In an overburdened health system, patients may not receive adequate explanation or proactive support to handle expected drug side effects. This creates fear and avoidance of medication. Therefore, adopting practical strategies like reminder systems (e.g., text messages) and strengthening the Directly Observed Therapy (DOT) program with effective counseling can make a significant difference.

Regarding structural and health system factors, the data revealed significant challenges. While physician communication did not show a marked difference between groups, a stark contrast was observed in financial capacity, with far fewer non-compliant patients reporting sufficient income for treatment. This aligns with findings from a cross-sectional study in Indonesia [21], which identified catastrophic health expenses as a primary cause of TB treatment abandonment. Furthermore, the extreme fatigue reported by most non-compliant patients likely reflects both the disease's progression and the physical strain of managing work and treatment, a challenge highlighted in a qualitative study of Bangladeshi garment workers [22].

The study highlights key differences in factors affecting TB treatment adherence between compliant and non-compliant patients. Physical and behavioural factors emerged as significant barriers, with non-compliant patients significantly more likely to miss doses due to side effects and to forget to take their medication. This finding confirms that medication-related challenges, such as adverse effects and forgetfulness, play a crucial role in treatment adherence, as discussed in research on TB-related stigma and patient experiences [10]. Consequently, implementing better side-effect management protocols and reminder systems, such as mobile alerts or DOT, could significantly improve compliance rates, a strategy supported by the implementation framework [18].

The data revealed that structural barriers outweigh social support. The extreme financial constraint reported by non-compliant patients is a critical health-system and economic barrier, as poverty limits access to transportation, nutrition, and the ability to take time off work for clinic visits. The high rates of missed doses due to side effects indicate a biological and clinical management gap; unmanaged drug toxicity creates a physical aversion to medication. Meanwhile, the fact that social support showed no difference suggests that while culturally important, it is insufficient to overcome these profound structural and clinical obstacles [5].

Economic factors also strongly influenced adherence, with compliant patients more likely to have sufficient income for treatment. This underscores the impact of financial constraints on TB care, as poverty may limit access to transportation, nutrition, or other resources needed for consistent treatment, a finding consistent with the systematic review which identified cost as a major barrier across multiple studies [7]. In contrast, social factors like doctor encouragement and family support showed no significant differences between groups, indicating that while these elements are important, they may not be sufficient to overcome structural barriers like cost and medication challenges. This nuanced finding aligns with a cross-sectional study in Nigeria, which highlighted that clinical and structural factors often outweigh social support in determining treatment success [11].

The disparity in adherence levels further emphasizes the need for multifaceted interventions. Non-compliant patients had substantially higher rates of low adherence, suggesting that a combination of financial support, side-effect mitigation, and patient education is essential. This supports the call for integrated approaches—including subsidies for treatment costs, enhanced counselling on medication management, and community-based support systems—as outlined in the WHO's which champions patient-centred care and social protection to improve outcomes in vulnerable populations [13]. The medication regimen for TB is a more powerful tool for adherence than general disease knowledge. This points to a health-system mechanism where patient education may be too generic. The fact that most of non-compliant patients still possessed this knowledge yet did not adhere demonstrates a cultural and behavioural mechanism: knowledge is necessary but not sufficient, as it cannot compensate for a lack of resources or the presence of overwhelming structural barriers like cost and side effects [6].

The knowledge assessment in the current study uncovers major gaps, especially concerning treatment specifics. These results endorse the implementation of "knowledge-aware" TB programs which customize education according to patients' literacy levels and socioeconomic circumstances, as proposed in the implementation framework [18]. The sex difference in knowledge among compliant patients (where more than half of males versus one third of females showed adequate knowledge) contradicts some earlier findings and requires further investigation, possibly due to cultural issues limiting women's health information access, a dynamic noted in the qualitative study on TB-related stigma experienced by women in India [9].

The stark link between female sex and unsatisfactory knowledge in the compliant group reveals a cultural and gender-related barriers, where women may have less access to health information, lower general literacy, or less autonomy to engage with the healthcare system. The strong association between education and knowledge underscores a structural mechanism: health literacy is often dependent on general literacy. An educated individual is better equipped to navigate the health system and understand complex instructions, indicating that public education is a fundamental social determinant of health [23,24].

The finding revealed that compliance was higher among educated working and normal BMI patients. Most of the non-compliant patients had severe symptoms of TB. The factors that might lead to non-compliance were insufficient income for treatment, absence of somebody at home who helps in regulating treatment, decreased motivation for improved health as well as the lack of knowledge regarding diet regimen, smoking, and personal hygiene. These findings compel a paradigm shift in care towards integrated, biologically and socially informed interventions. For clinical nursing, nurses should provide anticipatory guidance, preparing patients for common side effects, and co-creating a simple, actionable management plan with patient-specific adherence counseling. This empowers patients and prevents treatment interruptions that lead to failure or drug resistance.

Concurrently, community health programming must transcend generic education by delivering "knowledge-aware" literacy-appropriate messaging and forging partnerships to mitigate structural barriers like transportation and treatment costs, thereby ensuring that vulnerable patients are supported by both the clinic and the community to successfully complete their treatment. In addition, development and use of low-literacy, high-impact tools. This includes visual aids, pictograms, and audio messages that convey practical, treatment-specific information. The nursing profession can directly dismantle the complex barriers to TB treatment adherence, dramatically improving patient outcomes and advancing public health goals in Egypt.

This study has several limitations that should be considered when interpreting the findings. First, the cross-sectional design captures data at a single point in time, which establishes associations but cannot determine causality between factors like knowledge, symptoms, and adherence. Second, the use of a single setting ACH and a relatively small sample size (n = 80) limits the generalizability of the results to the broader population of TB patients in Egypt or other contexts to validate and extend these findings. Third, the reliance on self-reported data for adherence, symptoms, and some socioeconomic factors is susceptible to social desirability bias and recall error, potentially leading to an overestimation of adherence and knowledge scores.

The future research recommends implementing integrated patient-centered interventions that combine tailored education on treatment management and side-effects with robust social support systems, such as DOT and community health workers, to address knowledge gaps and provide practical adherence assistance.