Home-based tuberculosis contact investigation in Uganda: a household randomised trial

Discussion

Active case-finding of undiagnosed individuals with TB in settings outside health facilities is a cornerstone of the Global Strategy to End TB, which seeks to eliminate TB as a public health threat by 2050 [22]. Research evaluating bold, new, patient-centred strategies is critical to advancing toward these targets. In this study, we carried out a rigorous evaluation of a novel patient-centred strategy to improve delivery and completion of household TB contact investigation, a prototypical approach to active case-finding endorsed by WHO [3]. In a real-world public health setting, only about one in five household eligible contacts completed TB evaluation, and there was no improvement with home sputum collection and automated SMS results reporting compared with TB evaluation in clinic.

Incomplete delivery of the intervention, including a low proportion of contacts successfully submitting sputum and receiving SMS, may have contributed to its lack of effectiveness in improving completion of TB evaluation by addressing previously documented distance and financial barriers to attending clinics [12, 23]. As previously reported, contacts and CHWs reported several challenges with home sputum collection, including difficulties for asymptomatic contacts in expectorating, limited private space to expectorate indoors, and a reluctance to expectorate outside because of stigma [18]. Even symptomatic contacts often failed to expectorate on the spot, and CHWs reported that leaving sputum containers to be collected later was unsuccessful. CHWs sometimes did not carry enough sputum containers for all eligible contacts. Although trained on safe sputum collection and transport [18] and equipped with particulate respirators, CHWs expressed fears of contracting TB by collecting and carrying sputum in their work bags. Finally, because intervention households were distributed among 17 CHWs, some CHWs only rarely collected sputum, limiting the opportunities to gain proficiency. Low success rates of sputum collection have been observed in other similar settings [9], including among PLWHs [24]. Future studies should evaluate strategies to promote health worker confidence and competence in sputum collection, including delivery of instructional videos via phones or tablet computers [25].

SMSs were successfully initiated for only half of intervention-arm contacts undergoing additional TB evaluation. In a previous, more detailed process evaluation of SMSs, we found that <20% of SMSs achieved their full effects, defined as being sent, delivered, read by the intended recipient, and having the message content understood and retained [19]. Participants reported several barriers to engaging with SMS, including sharing phones with friends and family; broken phones; an inability to read text messages; and a lack of familiarity with or attentiveness to SMS. Although systematic reviews suggest that two-way SMS may be more effective than one-way SMS [26], we also observed a low uptake of invitations to two-way SMS [19]. Previous SMS interventions for TB in low- and middle-income countries have mostly used SMS longitudinally for treatment support [27], rather than cross-sectionally to facilitate diagnostic evaluation as in this study, although there is evidence suggesting that transaction-focused SMS such as appointment reminders modestly increase clinic attendance in a variety of settings [28]. Participants in our study who confirmed receiving SMS stated that while they found SMS helpful, it could not replace in-person disclosure of results [29].

This is among the first randomised trials of a mobile health intervention for TB in a low-income country. As described previously, this intervention was developed with broad input from household contacts and health workers [12, 17, 30] and deployed on a widely-used, Open Source mobile survey platform. Nonetheless, we experienced substantial challenges adapting the application to the complexities of household contact investigation, a multilevel intervention requiring a series of contingent steps occurring at multiple times and locations. The logic required to generate automated SMSs was particularly complex, encompassing thousands of unique clinical and laboratory states to determine if TB evaluation was complete and send appropriate SMS content. This posed challenges for quality assurance testing that slowed identification of programming errors, including one that prevented some SMSs from being sent.

WHO has called for increased high-quality research on digital interventions for TB care [31]. Given the challenges with both patient engagement and delivery of digital interventions in this study [19, 32], there is a need to involve professional designers to improve how patients and providers interface with mobile health interventions. User-centred design is an internationally accepted standard for quality in developing information technology applications [33]. An evolution of this approach (termed “Human-Centred Design” or generically, “design-thinking”) is increasingly being applied to build health delivery systems that ensure participant engagement through methods that prioritise the needs of end-users throughout intervention development [34, 35].

Our study had several limitations. First, we may not have captured all diagnoses of prevalent TB among patients presenting to nonstudy (or study) clinics unbeknownst to CHWs; however, we believe under-ascertainment of clinic visits is unlikely because the contacts' clinic preferences mirrored those of the index patients, and a prior audit found clinic registers and the survey application to be highly concordant [10]. Second, although additional incident TB cases may be identified in the first 2 years after household contact screening, we did not review clinic registers for incident clinic evaluations or diagnoses of TB. We did however ask CHWs to record this information digitally, and they maintained close contact with index patients as part of concurrent treatment support activities. Third, although household TB contact investigation provides important opportunities for TB prevention through diagnosis and treatment of latent TB infection, these services are not currently standard-of-care in Uganda.

Our study also had several strengths. This is among the first studies of a patient-centred strategy to improve household contact investigation in a high-burden, low-income setting. As previously described [12, 17], we employed a stakeholder-engaged approach informed by the Behaviour Change Wheel framework and the Capability-Opportunity-Motivation-Behaviour theory to develop this implementation strategy [36], and we evaluated it in a real-world setting using both implementation and effectiveness metrics [37]. Although home-based, SMS-facilitated household contact investigation was no more effective than the standard-of-care, clinic-based contact investigation, we carried out a careful process evaluation using mixed methods to determine which components of the strategy did and did not work [15, 18, 20, 29]. As improving the quality of TB care assumes greater priority on the global TB research and programme agenda [38, 39], such multilevel, multimodal evaluations are critical to understanding the context, fidelity, and adaptability of new interventions.

Although fewer than one in five household contacts completed the TB evaluation across both study arms, the yield of prevalent, microbiologically confirmed TB was 1%, similar to that reported in a recent randomised trial in Vietnam [4]. This diagnostic yield was however lower than the 3.1–4.5% described in systematic reviews [6, 40]. Future studies should examine whether the yield of new TB diagnoses can be improved by reducing drop-out from each step of the contact investigation cascade, as demonstrated in clinic settings [41]. In addition, improving completion rates for TB evaluation increases opportunities for preventive treatment of latent TB infection among close contacts, as envisioned by new WHO guidelines [42]. The suboptimal results of implementation in this study highlight the many challenges of delivering complex, community-based interventions like contact investigation in low-income countries, even when facilitated by mobile health strategies. As the global community of TB practitioners and researchers continues its search for more effective approaches for finding and treating undiagnosed individuals with TB and preventing TB among those who have been exposed, there is critical need for research to address “know-do” gaps and equitably deliver integrated services that are safe, timely, effective, patient-centred, efficient, and affordable.