Study characteristics

The majority of the included studies were conducted in South Africa (n=20), with Zimbabwe (n=3), Tanzania (n=3), Nigeria (n=2), Kenya (n=1) and Gabon (n=1) making up the rest. These six countries represent 49.5% of the 77 000 estimated DR-TB incident cases in Africa in 2018.2 There were 3 qualitative, 22 quantitative and 5 mixed-methods studies. Among the quantitative studies, there were 13 retrospective, 3 prospective and 1 mixed cohort studies, and 5 cross-sectional surveys. All of the three qualitative studies employed in-depth interviews, with one study including focus group discussions. Five studies examined access factors related to DR-TB treatment only, 9 on DR-TB diagnosis only and 16 focused on both diagnosis and treatment. Factors impacting access were identified at provider (n=30) and patient (n=24) levels. Sixteen studies explored the influence of diagnostic tools on laboratory turnaround time and on treatment initiation. Table 1 summarises the study characteristics for this review.

Quality appraisal

The results of our quality assessment are shown in online supplementary annex 2. Out of a total of 22 quantitative studies, 20 were classified as A, with 2 scoring B based on the STROBE criteria.14 The two qualitative studies scored A and B using the COREQ tool,15 with one study, graded a C, excluded. Using the MMAT tool,16 four studies were graded A and one as B in mixed methodology.

Provider factors affecting DR-TB diagnosis and treatment

In all 29 retained studies, the most dominant factors affecting DR-TB care were provider-related (table 2, figure 3). Our study highlighted a wide range of specific problems reflecting nearly all aspects of service delivery and health workforce with a few issues related to leadership and governance, and management of health products and information.

Service delivery was, by far, the most predominant provider-related barrier. Laboratory10 27–32 and clinic10 28 31 33 34 operational challenges, as well as centralisation of services7 28 30 32 35–39 and poor linkage between the public and private sector,29 32 hampered care. Inadequate provider knowledge, skill and adherence to national guidelines were also recurring themes.10 27–30 32 34 40–44 These are discussed in more detail in the context of the paired dimensions of access.

Patient-level factors influencing DR-TB diagnosis and treatment

Most patient-level barriers were related to predisposing characteristics including knowledge and perceptions,29 39 40 45 HIV status,7 38 43 44 presenting symptoms,44 46 gender44 46 and age27 43 44 46; and enabling characteristics including geographic location,10 27 28 30 43 47–49 life commitments29 32 40 and the ability to pay for transportation or services.29 32 39 40 A few need and health-seeking characteristics were also identified relating to treatment refusal,36 and choosing private sector care.10 32

Paired access dimensions

We have summarised access factors and recommendations from the reviewed studies into four paired dimensions (table 3).18

Acceptability/ability to seek

Our review found that although provider attitudes and practice were implicated, patients’ predisposing characteristics were predominant in influencing their decisions to use health services.18 25 26 Acceptability challenges were related to poor healthcare worker norms and attitude including confidentiality concerns, stigma and how the care patients received were influenced by their symptoms7 43 44 46 or sociodemographic characteristics.40 45 Patient’s ability to seek were influenced by their sociodemographic characteristics, personal, cultural and social values, disclosure, work and family commitments, use of private sector alternatives and fear of poor infection control.27 29–33 36 39 40 44 50 51

At the provider level, stigma and discrimination towards providers from other hospital workers, and from provider to patients compromised access to and quality of care.10 32 45

At the patient level, living with HIV had conflicting results. Some studies found no association between HIV status and having a DST done, nor with time to treatment.48 52 However, two studies found patients with HIV having overall higher odds of receiving a TB diagnosis.38 44 However, HIV-positive patients had longer times to treatment or were less likely to initiate treatment,7 43 except in one study where treatment initiation rates were higher than in HIV-negative patients.50 In qualitative studies, the fear of an HIV diagnosis delayed health-seeking, and some patients with HIV were seen to have an increased awareness of TB risk.32

Patients presenting with more than any two of TB symptoms (cough, fever, weight loss, night sweats), retreatment cases and undernourished children were more likely to be screened for TB on hospital presentation for other reasons than those presenting with fewer symptoms, new cases and well-nourished children, respectively.44 46 Smear-positive cases and more symptomatic patients were more likely to have a DST done.27 47 Half of the time, previous TB led to faster symptom recognition and care-seeking.32 In one study, being pregnant made accessing DR-TB care more difficult as providers refused to initiate any DR-TB-related care.32

Patient agency and persistence in demanding DR-TB testing where none was offered was noted as a facilitator to DR-TB healthcare, and this was linked to HIV positivity or prior knowledge of the disease, either through an earlier TB infection or knowing another patient with DR-TB.32

Results linking access to patient gender and age were largely inconclusive. In several studies, neither patient gender nor age were found to be associated with diagnosis timeliness or rates,27 30 52 nor with treatment initiation rates or timeliness.36 39 43 48 There were some indications that females44 46 or children whose mothers are the primary TB source,40 or younger age27 43 44 46 were less like to be diagnosed or treated (table 2). One study33 found children to be more likely to initiate treatment than adults.

One study noted other contextual patient factors that were seen to influence DR-TB care. In South Africa, ethnicity and cigarette smoking—with children failing to attend clinic appointments more frequently from coloured ethnicity and homes with cigarette smokers. No particular reason was given for these differences, however, it was acknowledged that these were markers for other socioeconomic and cultural factors needing further research.40

Availability/ability to reach

These were mostly related to service delivery, access to health products and patient tracking on the provider side and geographic access and life commitments on the patient side.18 25 26 Specific health system barriers were related to coverage, bed spaces and centralisation of services; inadequate availability and coverage of health products—equipment and technology, advanced diagnostics and medications; shortages of health personnel; clinic and laboratory errors.7 10 27 28 30–35 37–40 45 47 49 51–53 Patients were prevented from reaching health services when they lived in inaccessible locations or faraway distances, lack of social support and difficulty in transportation, poor sputum specimen, out-migration or death.27 32 33 36 37 40 42 45 49–51

Laboratory operational challenges were the most reoccurring barriers to care (figure 3). Specimen contamination, loss of viability, difficulty in packaging, batching, transportation and delivery of samples10 27 28 delayed diagnosis. Not requesting tests, incomplete records, delayed results were other barriers preventing patients form accessing care.10 28–32 Staff shortages, especially laboratory staff, contributed to diagnostic delays and patient waiting times.10 28 45 There were significant geographical variations, mostly in laboratory operations, which impacted referral, diagnosis and treatment rates.10 27 28 30 33 43 47–49 National programme support to health centres and using expedited mail service for sample transportation were helpful in reducing laboratory delays.28

Poor data management affected patient linkage to care and reporting. Errors including missing patient records in diagnosis or treatment registers, irretrievable request forms, incomplete data entry led to misplaced results, untraceable patients and poor linkage to care.10 28 31 33 34

Inadequate coverage and maintenance of diagnostic equipment, as well as power outages hampered diagnostic capacity10 28 44 45 and staff motivation.45 Where available, using the Xpert notification system improved team communication and facilitated diagnosis.31

Centralisation (in few specialised health centres) of GeneXpert MTB/RIF (Xpert) or other pretreatment requirements like X-rays, and a lack of integration, increased diagnosis time28 39 and resulted in negative patient experiences.45 Service decentralisation (widespread availability of services, and at the different healthcare levels) was, consequently shown to be a major facilitator of access (figure 3), reducing time to diagnosis and treatment and increasing diagnosis rates.7 30 32 35–38 However, patients initiating care at higher facilities had lower odds of getting tested or initiating treatment.36 44 50 Treatment initiation rate was highest among patients diagnosed directly through TB hospitals.43 In one setting, timeliness of treatment was higher among patients initiated as inpatients compared with outpatients.33

The public sector had longer waiting times pushing patients to access care in the private sector, with poor linkages between the two.29 32 Failure or delay in tracking patients, and unavailability of results at appointments prevented access.10 32

Access to newer diagnostics was the principal facilitator of access identified (figure 3). There was an overall consensus that the use of older diagnostic tests (eg, X-rays, drug susceptibility testing (DST) or line probe assay (LPA)), when compared with Xpert, was associated with longer times to diagnosis and treatment.7 28 37–39 41 43 51–53 With the exception of one study,35 Xpert implementation did not result in corresponding increases in diagnosis and treatment rates.7 37 43 54 Also, the average time to DR-TB care remained significantly higher than the national targets in most settings.33 39 41 43 52 53

At the patient level, several studies noted high rates of patients being lost to follow-up or dying before treatment due to non-referrals, data errors, prolonged pretreatment processes and delayed care-seeking.31 42 50

Geographical location of patients was also identified as an access barrier. Patients in an urban/formal settlement accessed care more compared with those in rural, informal settlements or prison. Other variations were likely linked to the healthcare location, as noted above.32 33 50 53 Significant variations in accessing diagnosis and treatment were due to geographical locations of the patients, with urban residence or proximity to care facility increasing likelihood of testing and treatment, as well as reducing time to results and treatment.10 27 28 30 43 47–49

Family, work or school commitments were seen to prevent or interrupt the care process, while the presence of family support enabled care-seeking.29 32 40

Affordability/ability to pay

The financial implications of services were mostly related to the enabling characteristics of patients to pay for care including transportation costs.18 25 26 In our review, we found difficulties in paying for transport to health facilities, and high opportunity costs borne by patients.32 40

Ease of access and cost of health services were some reasons for choice of facility. A lack of money for transport, travel time and numerous bus transfers influenced whether they returned to the facility after initial visit.29 39 40 Seeking care in the private sector was noted as contributing to the high costs of care for patients, as some go the public sector, where care was perceived as poor, only when they could no longer afford private care.32 In another study where high costs of care was noted, majority of the patients sought care in the private sector.29

Discussion

Our review synthesises the diverse knowledge base about obstacles to DR-TB care in SSA to create a consolidated understanding to inform practice. It highlighted several health system and patient barriers.

Our key findings include the role of rapid diagnostics and laboratory operational issues play in facilitating or impeding access. Rapid diagnostic tools, particularly Xpert, play a central role in accessing DR-TB diagnosis and treatment, and their absence would constitute a significant barrier to receiving care.28 38 39 The introduction of these tools has led to a significant reduction in times to care for DR-TB.7 38 39 43 51–53 However, although times were shortened, patients still experienced unnecessary delays in accessing care. The gains of rapid diagnostic technology have, so far, not translated into a commensurate increase in rates of detection and treatment.7 37 39 43 These were likely due to the range of laboratory operational errors identified,10 27–32 and which need to be targeted to improve case finding and treatment rates.

Our review data reveal several missed opportunities for screening and treatment initiation.7 32 34 46 These contribute to the global ‘missing cases’, perpetuate transmission and highlight critical gaps in the care cascade. For example, the inadequate linkage between the private and the public sector occur before access to testing and are beyond the scope of rapid diagnostics. They contribute to the persistence of low diagnostic and treatment rates despite Xpert implementation.

Results for age and sex were found to be divergent, as many studies found both factors not significant in impacting care. In the studies where age was significant, younger age was mostly a barrier,27 43 44 46 except in one study33 where the programme prioritised children and other high-risk groups for Xpert diagnosis and inpatient care. Where most studies found sex not associated with DR-TB care, some found being female or a child or a female patient with DR-TB to be a barrier to care.27 40 44 46 One study found females more likely to have earlier diagnosis, likely due to care-seeking behaviours.52

Several contextual factors like language, religion and culture were not identified by the studies included in this review. Geographic locations of the health centres and of the patients themselves were identified as influencing access to care, and this has been reported by other authors.55 56 Ethnicity and lifestyle were identified in one study to influence access, likely due to socioeconomic and cultural implications.40 The lack of qualitative data on the influence of sex and age on access makes it difficult to draw conclusions about whether the effects seen were due to contextual factors.

To improve patient-level barriers calls for a close examination of social determinants like poverty and geographic access as an addition to biomedical approaches, as recommended by the Commission on Social Determinants of Health (CSDH).57–59 The burdens of infectious diseases like TB are disproportionately borne by patients with certain sociodemographic characteristics. For example, rural patients bear higher treatment costs and report more difficulty with transport to health centres for treatment.60 61 Demographic characteristics such as gender, poverty or ethnicity often interact in complex ways, further increasing vulnerability and disadvantage.62 63 Inadequate knowledge of DR-TB disease and health services was also identified as a major cause of poor health-seeking behaviour among patients. Raising public awareness of symptoms and available resources may contribute to reducing these delays.

The biomedical approach, which focuses more on the use of technology to manage diseases needs to be combined with efforts to tackle root causes and social determinants of DR-TB disease.60 64

Our findings indicate that, in order to overcome prevailing barriers to care, innovative diagnostic tools and treatment require functional, efficient and accessible health systems to reach and track patients who are, themselves, informed and motivated. The high susceptibility of individuals getting harmed from DR-TB, due to the complex interaction between risk factors and available resources, is manifested in their inability to manage risks or recover from the disease effectively.63 This is corroborated by many of the reviewed studies in which diagnosed patients died before they could be initiated on life-saving treatment.31 36 42 50 This highlights the fact that DR-TB continues to be characterised by avoidable morbidity and deaths, especially in SSA, and must be treated with urgency. The raison d’être of rapid diagnostic methods is to improve these outcomes by facilitating quicker diagnosis and treatment. Xpert implementation did not translate to universal increases in diagnosis and treatment rates, presenting a significant setback and missed opportunity in the control of DR-TB.

Gaps in the capacity of the health system to deliver care need to be closed. This would require significant investments at lower levels of care towards more decentralised and ambulatory models of care. In order to fund these efforts, SSA governments need to prioritise and increase health investments and mobilise resources to fund TB control.

Strengths and limitations

The strengths of this review include the adaptation of our conceptual framework to align factors influencing DR-TB care with other well-known frameworks in the field of healthcare access and systems strengthening,18 25 26 using a mixed-methods approach.

This review has a few limitations. First, due to the heterogeneity of study methods and outcome variables, neither summary measures (eg, effect size) nor pooled analysis for specific interventions were determined, as the studies were not sufficiently comparable to each other. Another limitation is related to the location of the studies. Our search showed a dominance of studies from South Africa, with only two from Nigeria, and none from Angola, DR Congo, Ethiopia, Kenya, Mozambique, the other TB/DR-TB/HIV HBCs in the region. This may have affected the generalisability of our findings within the region, as there are likely other barriers in the different other settings that were not identified. However, the relatively higher HIV burden in South Africa, and the country’s quick adoption of newer diagnostics and medications could serve as an example for these other countries as they scale-up services for DR-TB.