Objectives

We assessed attitudes and perceptions and willingness to accept (WTA) varying incentive structures for completing tuberculosis (TB) diagnostic evaluation among patients in Uganda.

Methods

We surveyed 177 adult patients undergoing TB evaluation at 10 health centers between September 2018 and March 2019. We collected household sociodemographic information and assessed attitudes and perceptions of incentives. We surveyed patients regarding their willingness to complete TB diagnostic evaluation in exchange for incentives ranging in value from 500 Ugandan shillings (USh) to 25 000USh (~$0.15-$6.75). We compared associations between WTA and patient characteristics using ordered logistic regression.

Results

Participant willingness to return to the health center to complete TB diagnostic evaluation increased proportionally with incentive amount. The median participant accepted between 2000 and 5000 USh. Cash (52%) and transportation vouchers (34%) were the most popular incentive types. Half of respondents preferred unconditional incentives; for a multiday evaluation, 84% preferred conditioning incentive receipt upon returning to the health center. In multivariate models, we found the pairwise difference between the third and lowest income quartile (aOR = 2.38, 95% CI: 1.20-4.69; P = .01), younger age, and difficulty returning to the health center to be significantly associated with WTA higher incentive thresholds.

Conclusions

In Uganda, incentives such as cash transfers or transportation vouchers are an acceptable intervention for facilitating adherence to TB diagnostic evaluation. Household income is associated with preferred incentive structure and amount, especially for those at the cusp of the poverty threshold who are more likely to prefer unconditional and higher valued incentives. Targeted and context-specific socioeconomic supports for at-risk patients are needed to optimize outcomes.

Background

Newer molecular testing platforms are now available for deployment at lower-level community health centers. There are limited data on facility- and health worker-level factors that would promote successful adoption of such platforms for rapid tuberculosis (TB) testing and treatment initiation. Our study aimed to assess readiness to implement onsite molecular testing at community health centers in Uganda, a high TB burden country in sub-Saharan Africa.

Methods

To understand implementation readiness, we conducted a qualitative assessment guided by the Consolidated Framework for Implementation Research (CFIR) at 6 community health centers in central and eastern Uganda between February and April 2018. We conducted 23 in-depth, semi-structured interviews with health workers involved in TB care at each health center to assess TB-related work practices and readiness to adopt onsite molecular testing using the GeneXpert Edge platform. Interviews were transcribed verbatim and coded for thematic analysis.

Results

Participants (N=23) included 6 nurses/nursing assistants, 6 clinicians, 6 laboratory directors/technicians, 1 medical officer, 2 health center directors, and 2 other health workers involved in TB care. Health workers described general enthusiasm that on-site molecular testing could lead to greater efficiencies in TB diagnosis and treatment, including faster turn- around time for TB test results, lack of need for trained laboratory technicians to interpret results, and reduced need to transport sputum specimens to higher level facilities. However, health workers also expressed concerns about implementation feasibility. These included uncertainty about TB infection risk, safety risks from disposal of hazardous waste, a lack of local capacity to provide timely troubleshooting and maintenance services, and concerns about the security of GeneXpert devices and accessories. Health workers also expressed the need for backup batteries to support testing or charging when wall power is unstable.

Conclusion

Our study generated a nuanced understanding of modifiable contextual barriers and led to direct revisions of implementation strategies for onsite molecular testing. The findings highlight that novel diagnostics should be implemented along with health system co-interventions that address contextual barriers to their effective uptake. Pre-implementation assessment of stakeholder perspectives, collaborative work processes, and institutional contexts is essential when introducing innovative technology in complex health care settings.

Introduction

Catastrophic costs incurred by tuberculosis (TB) patients have received considerable attention, however little is known about costs and pathways to care after a negative TB evaluation.

Materials and methods

We conducted a cross-sectional study of 70 patients with a negative TB evaluation at four community health centres in rural and peri-urban Uganda. Patients were traced 9 months post-evaluation using contact information from TB registers. We collected information on healthcare visits and implemented locally-validated costing questionnaires to assess the financial impact of their symptoms post-evaluation.

Results

Of 70 participants, 57 (81%) were traced and 53 completed the survey. 31/53 (58%) surveyed participants returned to healthcare facilities post-evaluation, making a median of 2 visits each (interquartile range [IQR] 1-3). 11.3% (95%CI 4.3-23.0%) of surveyed patients and 16.1% (95%CI 5.5-33.7%) of those returning to healthcare facilities incurred catastrophic costs (i.e., spent >20% annual household income). Indirect costs related to lost work represented 80% (IQR 32-100%) of total participant costs.

Conclusions

Patients with TB symptoms who experience financial catastrophe after negative TB evaluation may represent a larger absolute number of patients than those suffering from costs due to TB. They may not be captured by existing definitions of non-TB catastrophic health expenditure.

Social protection interventions have the potential to accelerate progress towards global tuberculosis (TB) targets. We piloted a screening and linkage program at four community health centers (HC) to enroll adults seeking TB diagnostic evaluation services into existing government-supported social protection programs in Uganda. From May-December 2021, health center staff were asked to screen adults being evaluated for TB for eligibility for government-supported social protection programs, and to refer eligible people to a sub-county community development office (CDO) responsible for enrolling community members into government-supported social protection programs. Linkage was facilitated with a transportation reimbursement via mobile money and referral documentation confirming program eligibility. We assessed feasibility using programmatic data and conducted post-intervention surveys to understand experiences with the linkage program. Of 855 people undergoing TB evaluation, 655 (76%) adults met criteria for at least one government-supported social protection program. 25 (4%) of those were not interested in referral; the rest were referred to their local CDO. While 386 (61%) of the 630 participants reported to the CDO seeking social protection enrolment, only 122 (32%) of those were ultimately enrolled into a social protection scheme, representing only 19% (n = 655) of those eligible. In surveys conducted among 97 participants, 46 of the 60 (77%) people who reported that they sought enrollment at the CDO were not enrolled into a social protection program. Reasons provided for non-enrollment among these 46 participants were either unknown (n = 25, 54%) or due to operational challenges at the CDO including a lack of human resources or available groups to join in the social protection program (n = 20, 43%). 61 survey participants (63%) indicated that they would not have sought social protection enrollment without the referral program. Overall, we found that most adults seeking TB diagnostic evaluation are eligible for and interested in obtaining government-supported social protection. We found facilitated linkage from HCs to CDOs offering social protection services to be feasible, however ultimate enrollment into programs was limited. Additional research is needed to identify strategies to improve access to existing social protection programs for eligible TB-affected individuals. Trial Registration: Pan African Clinical Trials Registry (PACTR201906852160014).

Background

Mitigating financial barriers to tuberculosis (TB) diagnosis and treatment is a core priority of the global TB agenda. We evaluated the impact of a cash transfer intervention on completion of TB testing and treatment initiation in Uganda.

Methods

We conducted a pragmatic complete stepped wedge randomised trial of a one-time unconditional cash transfer at 10 health centres between September 2019 and March 2020. People referred for sputum-based TB testing were enrolled to receive UGX 20 000 (∼USD 5.39) upon sputum submission. The primary outcome was the number initiating treatment for micro-bacteriologically confirmed TB within 2 weeks of initial evaluation. The primary analysis included cluster-level intent-to-treat and per-protocol analyses using negative binomial regression.

Results

4288 people were eligible. The number diagnosed with TB initiating treatment was higher in the intervention period versus the pre-intervention period (adjusted rate ratio (aRR)=1.34) with a 95% CI of 0.62-2.91 (p=0.46), indicating a wide range of plausible true intervention effects. More were referred for TB testing (aRR=2.60, 95% CI 1.86-3.62; p<0.001) and completed TB testing (aRR=3.22, 95% CI 1.37-7.60; p=0.007) per National Guidelines. Results were similar but attenuated in per-protocol analyses. Surveys revealed that while the cash transfer supported testing completion, it was insufficient to address long-term underlying social/economic barriers.

Interpretation

While it is uncertain whether a single unconditional cash transfer increased the number of people diagnosed and treated for TB, it did support higher completion of diagnostic evaluation in a programmatic setting. A one-time cash transfer may offset some but not all of the social/economic barriers to improving TB diagnosis outcomes.

Background

Many high burden countries are scaling-up GeneXpert® MTB/RIF (Xpert) testing for tuberculosis (TB) using a hub-and-spoke model. However, the effect of scale up on reducing TB has been limited. We sought to characterize variation in implementation of referral-based Xpert TB testing across Uganda, and to identify health system factors that may enhance or prevent high-quality implementation of Xpert testing services.

Methods

We conducted a cross-sectional study triangulating quantitative and qualitative data sources at 23 community health centers linked to one of 15 Xpert testing sites between November 2016 and May 2017 to assess health systems infrastructure for hub-and-spoke Xpert testing. Data sources included a standardized site assessment survey, routine TB notification data, and field notes from site visits.

Results

Challenges with Xpert implementation occurred at every step of the diagnostic evaluation process, leading to low overall uptake of testing. Of 2192 patients eligible for TB testing, only 574 (26%) who initiated testing were referred for Xpert testing. Of those, 54 (9.4%) were Xpert confirmed positive just under half initiated treatment within 14 days (n = 25, 46%). Gaps in required infrastructure at 23 community health centers to support the hub-and-spoke system included lack of refrigeration (n = 14, 61%) for sputum testing and lack of telephone/mobile communication (n = 21, 91%). Motorcycle riders responsible for transporting sputum to Xpert sites operated variable with trips once, twice, or three times a week at 10 (43%), nine (39%) and four (17%) health centers, respectively. Staff recorded Xpert results in the TB laboratory register at only one health center and called patients with positive results at only two health centers. Of the 15 Xpert testing sites, five (33%) had at least one non-functioning module. The median number of tests per day was 3.57 (IQR 2.06-4.54), and 10 (67%) sites had error/invalid rates > 5%.

Conclusions

Although Xpert devices are now widely distributed throughout Uganda, health system factors across the continuum from test referral to results reporting and treatment initiation preclude effective implementation of Xpert testing for patients presenting to peripheral health centers. Support for scale up of innovative technologies should include support for communication, coordination and health systems integration.

Rationale

Many high-burden countries are scaling-up Xpert MTB/RIF using a hub-and-spoke model. We evaluated the quality of care for patients undergoing TB evaluation at microscopy centers (spokes) linked to Xpert testing sites (hubs) in Uganda.

Objectives

To characterize the extent to which patients were receiving care in accordance with international and national guidelines.

Methods

We conducted a prospective cohort study of all adults with presumptive pulmonary TB at 24 health centers linked to Xpert testing sites. Health center staff photographed TB registers, and uploaded photos to a secure server bi-weekly. We assessed the proportion of patients (1) initiating testing; (2) completing testing; and (3) treated for confirmed TB within 14 days.

Measurements and main results

Between January to December 2017, 6744 patients underwent evaluation for pulmonary TB. Only 1316 patients had sputum referred for Xpert testing, including 1075/3229 (33.3%) people living with HIV and 241/3515 (6.9%) without HIV. Of 119 patients confirmed to have TB by Xpert testing, 44 (36%) did not initiate treatment. There were significant losses along the entire diagnostic cascade of care, with only 5330/6744 (79.0%) patients having samples referred for sputum-based testing, 2978/5330 (55.9%) patients completing recommended testing if referred, and 313/418 (74.9%) patients initiating treatment within 14 days if confirmed to have TB.

Conclusions

Although coverage of Xpert testing services across Uganda is high, the quality of care delivered to patients undergoing TB evaluation remains poor. Further research is needed to identify health system interventions to facilitate uptake of Xpert testing and high-quality care.

Background

Pre-treatment loss to follow-up is common for patients diagnosed with tuberculosis (TB) in high-burden countries. Delivering test results by Short-Messaging-Service (SMS) is increasingly being considered as a solution, but there is limited information about its feasibility as a public health tool in low resourced settings.

Objective

We sought to assess the feasibility of utilizing SMS technology to deliver TB test results during routine TB diagnostic evaluation in Uganda.

Methods

We conducted a single arm interventional pilot study at four community health centers in Uganda that referred sputum samples to a district hospital for GeneXpert-MTB/RIF (Xpert) testing (Cepheid, USA). Using existing GxAlert-software (SystemOne,USA), we set up an automated SMS platform to send Xpert results to patients and referring health centers. We assessed each step of the SMS delivery cascade for consecutive patients who presented to these four community health centers between December 2015 and March 2016 and underwent Xpert testing.

Results

Of 233 patients enrolled, 161 (69%) had phone numbers recorded on individual Xpert referral forms. Phone numbers were entered into Xpert device software in the correct format for 152 (94%) patients. GxAlert-software generated an automated SMS reporting Xpert results for 151 (99%) patients and delivered it successfully to mobile phone service providers for 145/151 (96%). Of the 123 patients reached by phone to determine receipt of test results, 114 (93%) confirmed SMS receipt. SMS-based delivery of Xpert results was verified for 114/233 (49%) patients overall. In contrast, phone calls to health centers confirmed that health centers received messages for 222/233 (95%) patients.

Conclusion

Reporting Xpert results via automated SMS is technically feasible and results in approximately half of patients receiving their test results immediately. Additional research should be done to address process inefficiencies in order to maximize impact of this technology and link its successful utilization to improved patient outcomes.

Background

Decentralised molecular testing for tuberculosis could reduce missed diagnoses and losses to follow-up in high-burden settings. The aim of this study was to evaluate the cost and cost-effectiveness of the Xpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB) study strategy, a multicomponent strategy including decentralised molecular testing for tuberculosis, in Uganda.

Methods

We conducted a costing and cost-effectiveness analysis nested in a pragmatic cluster-randomised trial of onsite (decentralised) versus hub-and-spoke (centralised) testing for tuberculosis with Xpert MTB/RIF Ultra (Xpert) in 20 community health centres in Uganda. We collected empirical data on the cost of the XPEL-TB strategy (decentralised Xpert testing, workflow redesign, and performance feedback) and routine tuberculosis testing (onsite smear microscopy with specimen transport for centralised Xpert testing) from the health system perspective. Time-and-motion studies were performed to estimate activity-based service costs. Cost-effectiveness was assessed as the incremental cost (2019 US$) per tuberculosis diagnosis and per 14-day treatment initiation.

Findings

The XPEL-TB study ran from Oct 22, 2018, to March 1, 2020. Effectiveness and cost-effectiveness outcomes were assessed from Dec 1, 2018, to Nov 30, 2019 and included 4867 women and 3139 men. On a per-test basis, the cost of decentralised ($20·46, range $17·85-25·72) and centralised ($18·20, range $16·58-24·25) Xpert testing was similar. However, decentralised testing resulted in more patients receiving appropriate Xpert testing, so the per-patient cost of decentralised testing was higher: $20·28 (range $17·68-25·48) versus $9·59 (range $7·62-14·34). The XPEL-TB strategy was estimated to cost $1332 (95% uncertainty range $763-5558) per incremental tuberculosis diagnosis and $687 ($501-1207) per incremental patient initiating tuberculosis treatment within 14 days. Cost-effectiveness was reduced in sites performing fewer than 150-250 tests annually.

Interpretation

The XPEL-TB strategy facilitated higher rates of Xpert testing for tuberculosis at a similar per-test cost and modest incremental cost per tuberculosis diagnosis and treatment initiation. Decentralised Xpert testing, with appropriate implementation supports, should be scaled up to clinics with sufficient testing volume to support a single-module device.

Funding

The National Heart, Lung, and Blood Institute.

Background

Sputum-based testing is a barrier to increasing access to molecular diagnostics for tuberculosis (TB). Many people with TB are unable to produce sputum, and sputum processing increases assay complexity and cost. Tongue swabs are emerging as an alternative to sputum, but performance limits are uncertain.

Methods

From June 2022 to July 2023, we enrolled 397 consecutive adults with cough >2 weeks at 2 health centers in Kampala, Uganda. We collected demographic and clinical information, sputum for TB testing (Xpert MTB/RIF Ultra and 2 liquid cultures), and tongue swabs for same-day quantitative polymerase chain reaction (qPCR) testing. We evaluated tongue swab qPCR diagnostic accuracy versus sputum TB test results, quantified TB targets per swab, assessed the impact of serial swabbing, and compared 2 swab types (Copan FLOQSWAB and Steripack spun polyester).

Results

Among 397 participants, 43.1% were female, median age was 33 years, 23.5% were diagnosed with human immunodeficiency virus, and 32.0% had confirmed TB. Sputum Xpert Ultra and tongue swab qPCR results were concordant for 98.2% (95% confidence interval [CI]: 96.2-99.1) of participants. Tongue swab qPCR sensitivity was 92.6% (95% CI: 86.5 to 96.0) and specificity was 99.1% (95% CI: 96.9 to 99.8) versus microbiological reference standard. A single tongue swab recovered a 7-log range of TB copies, with a decreasing recovery trend among 4 serial swabs. Swab types performed equivalently.

Conclusions

Tongue swabs are a promising alternative to sputum for molecular diagnosis of TB, with sensitivity approaching sputum-based molecular tests. Our results provide valuable insights for developing successful tongue swab-based TB diagnostics.