Timely treatment initiation of free drug-resistant tuberculosis care in Nigeria? : a mixed methods study of patient experience, socio-demographic characteristics and health system factors

Background: Detection and treatment coverage for drug-resistant tuberculosis (DR-TB) in Nigeria are persistently low despite the implementation of free diagnostic and treatment services since 2011. Nigeria has a high burden for tuberculosis, ranking 6th globally with 4.3% drug resistance in new, and 15% in retreatment cases. The World Health Organization classifies the country as a high burden for TB, DR-TB, and HIV, with a prevalence of 219 and 11 per 100,000 population for TB and DR-TB, and 1.28 per 1,000 population HIV. Without treatment, mortality from tuberculosis is approximately 70% within ten years, increasing with HIV co-infection and drug resistance - and decreasing to below 5% with treatment.  DR-TB survival rates are lower, and treatment is longer, costlier, and more toxic; this may pose different challenges to both patients and health systems than is the case for drug-sensitive (DS-) TB. However, treatment response and survival are positively impacted by early detection and treatment initiation, ideally within four weeks of diagnosis, especially with HIV co-infection. Socio-demographic characteristics often interact in complex ways with systemic factors, to increase vulnerability and disadvantage – these interactions are particularly well examined through an equity of health access framework and could offer policy-relevant analyses and recommendations. This study explores patient and health system barriers and facilitators to diagnosis and treatment for DR-TB in Nigeria. Methods: This is a sequential transformative mixed-methods study. First, a mixed-methods systematic review identified barriers and facilitators affecting diagnosis and treatment for DR-TB in sub-Saharan Africa. A subsequent qualitative meta-synthesis was used to examine in more depth the patient, community, and health system barriers to TB care. The results of the systematic reviews were used to refine our conceptual framework and to guide the design and the analysis of the subsequent empirical study. The adapted conceptual framework is based on the Levesque framework for patient-centred healthcare access, which conceptualises access to care as having health system and patient dimensions.  This study also included a retrospective cohort analysis of patients diagnosed in 2015 (n= 996 ) using National secondary data, and a DR-TB care cascade analysis of the period between 2013 and 2017.  We used descriptive statistics, logistic regression and other tests of association to measure the relationship between variables categorical. The qualitative phase used a case study design to examine the dynamics of care from patients' perspectives (n= 86 participants, N= 7 focus group discussions (FGD), 5 in-depth interviews (IDIs) with diagnosed and untreated patients), their relatives (n= 19 participants, N= 1 FGD, 7 IDIs  ), community members (n=23 in 2 FGDs), healthcare workers (n= 5 IDIs ), and program managers (n= 29 IDIs) in four States in Nigeria. We analysed our qualitative data using thematic analysis. Results: Our mixed methods systematic review and qualitative meta-synthesis revealed barriers and facilitators to DR-TB care at the health system and patient levels. Health system laboratory and clinic operational issues, poor provider knowledge and attitudes and information management were some barriers. Facilitators included newer diagnostic tools, decentralisation of services and free cost of care. At the patient level, loss to follow-up before or during care due to negative public sector care perceptions, gender, family, work or school commitments and using private sector care were some barriers. Facilitators were HIV positivity, having more symptoms, and financial support.  Our quantitative findings revealed some improvement but inadequate progress in diagnosis and treatment coverage in Nigeria between 2013 and 2017.  Our cascade analysis showed significant dropouts between each stage of care, starting with testing and ending with treatment completion. On average, between 2013-2017, 80% of estimated cases did not access testing; 75% of those who test were not diagnosed; 36% of those diagnosed were not initiated on treatment and 23% of these did not finish treatment. In 2015, children and patients in Northern Nigeria had odds of 0.3 [95% CI 0.1-0.7] and 0.4 [0.3-0.5] of completing treatment once diagnosed; compared with adults and patients in Southern Nigeria; while males were shown to have a 1.34 [95% CI 1.0-1.7] times greater chance of completing treatment after diagnosis compared to females.. Geographic locations and levels of care were associated with ever receiving treatment and or timely treatment. Our qualitative data and document review identified barriers to care at individual, family, community, and health systems levels. Some patient socio-demographic groups had inequitable access. While patients were mostly treated equally at the facility level, some patients experienced more difficulty accessing care based on their gender, age, occupation, educational level and religion. Parental and spousal influences affected patients, particularly children, and women, and were sometimes barriers to care. Other factors that likely hampered access include the absence of considerations for patients’ access rights and protection in the treatment guidelines and workers manuals. Patients were mostly unaware of the causes of DR-TB disease and the availability of free care. Health worker numbers and training, clinic, and operational laboratory issues limited patients’ access at the health system level. The main facilitators to care included family support, patient financial support, and free treatment.  Conclusions: Despite the provision of free DR-TB testing and treatment in Nigeria since 2011, coverage for diagnosis and treatment remain persistently low. Our literature review identified many of the same access factors affecting both DS-TB and DR-TB. However, DR-TB had peculiar challenges due to complexities in pre- treatment procedures, and in toxicities as a result of the medications themselves.  This study was designed to investigate the access factors impacting DR-TB treatment initiation identified in literature. However, our findings showed that the biggest barriers to DR-TB care were essentially in access to testing and diagnosis, making any advances in diagnostic technology and treatment regimens of little benefit to DR-TB patients in Nigeria. Several patient and health system factors were shown to impede access to DR-TB care, particularly for certain groups of patients. Most DR-TB patients are not accessing testing and do not get diagnosed, often due to a lack of information. Also, DR-TB policies, structures and processes are not always equitable, especially for rural dwellers, children and women. Findings from our mixed methods study provided the additional insights needed by policymakers and implementing partners to address systemic disparities and provide more equitable services based on the population's needs. Eliminating barriers that negatively impact timely access to care should be an urgent priority for the TB program in Nigeria. In Nigeria's low case-finding and treatment coverage, interventions should target equity and ease of access, specifically for the barriers identified at the patient and health system levels.

Keyphrases: Diagnostic, Diagnosis and treatment, Drug-resistant tuberculosis, Nigeria, Mixed methods, Sub-Saharan Africa, Qualitative meta-synthesis, Access to care, Global Health, Equity, Health systems, Systematic review, Barriers and facilitators, Cascade of care