How can we improve latent tuberculosis infection management using behaviour change wheel: a systematic review

Abstract Background To ensure the effective delivery of latent tuberculosis infection (LTBI) care, it is vital to overcome potential challenges in LTBI management. This systematic review aims to identify the barriers and interventions to improve LTBI management using the Capability, Opportunity, and Motivation-Behaviour (COM-B) model and Behaviour Change Wheel (BCW). Methods A systematic literature search was performed on five electronic databases from database inception to 3 November 2021. A two-step technique was used in the data synthesis process: (i) the barriers of LTBI management were identified using the COM-B model, followed by (ii) mapping of intervention functions from BCW to address the identified barriers. Results Forty-seven eligible articles were included in this review. The findings highlighted the need for a multifaceted approach in tackling the barriers in LTBI management across the public, provider and system levels. The barriers were summarized into suboptimal knowledge and misperception of LTBI, as well as stigma and psychosocial burden, which could be overcome with a combination of intervention functions, targeting education, environment restructuring, persuasion, modelling, training, incentivization and enablement. Conclusions The remedial strategies using BCW to facilitate policy reforms in LTBI management could serve as a value-added initiative in the global tuberculosis control and prevention program.


Introduction
Tuberculosis (TB) is one of the leading causes of mortality worldwide, affecting approximately 10.6 million of the global population, with more than 1.6 million death cases reported in 2021. 1 As such, early diagnosis and treatment of TB cases by knowledgeable and skilled healthcare providers are key in addressing this global health issue.To strengthen TB service delivery, the Capability, Opportunity, and Motivation-Behaviour (COM-B) model has been applied to identify and address the barriers in TB management, particularly in improving TB case detection. 2,3This model has been used with the behaviour change wheel (BCW) to identify intervention functions and policy categories, which facilitate improvement in health delivery and services. 4n response, the World Health Organization (WHO) has taken the lead to accelerate global effort in TB eradication through the WHO END TB Strategy. 5In addition to active TB case finding and treatment, it also advocates the prioritization of latent tuberculosis infection (LTBI) management as LTBI could be the reservoir for future TB cases. 5,6Therefore, prevention of TB reactivation through LTBI treatment and management in specific high-risk populations is one of the milestones proposed at the United Nations High-Level Meeting. 1 One issue identified in LTBI management was the lack of understanding and awareness of LTBI testing and treatment among healthcare providers and the general public, particularly populations from countries where TB is common. 7,8

Study selection and data extraction
Two reviewers (YJW and SWHL) independently screened titles and abstracts of references.Full texts of identified studies were independently assessed and reviewed in accordance with the eligibility criteria.Reasons for excluded studies are found in Supplementary Appendix 4.
Data were extracted using a predeveloped data collection form.Extracted data included: first author, year of publication, location of the study, study population, questionnaire structure, KAP category, survey questions with the corresponding responses by one reviewer (YJW).The findings were cross-checked by second reviewer (SWHL), with disagreement resolved by discussion or adjudication by a third reviewer (KYN).

Risk of bias evaluation
As there were no standardized or validated tools to evaluate the risk of bias in KAP survey, 14,15 we adapted the checklist developed by Hoy and colleagues since it was consistent with the screening criteria for KAP survey proposed by Agarwal and colleagues (Supplementary Appendix 5). 14,16ta synthesis A three-step process was applied for data synthesis.First, we extracted and coded each question from the KAP questionnaire as described previously where they were categorized as either knowledge, attitude or practice.We then identified the target audience, which the questionnaires were administered to, i.e. general public, provider or system.These were further sorted into the COM-B model domains: (i) physical capability, (ii) psychological capability, (iii) automatic motivation, (iv) reflective motivation, (v) physical opportunity or (vi) social opportunity.We subsequently mapped these domains to the BCW to determine which intervention function could be used to address the identified barriers.All data analysis was performed in Microsoft Excel (Richmond, USA).

Study characteristics
The literature search identified 5221 studies for evaluation, 74 were screened for inclusion and 47 eligible studies were included in this study (Fig. 1). 10, Thesstudies had invited a total of 35 694 participants, with 22 991 responses, of which 22 802 were fully completed.The response rates for each survey varied, ranging from 72.7% to as high as 100% full completion.Only eight out of 47 studies were conducted in countries that are listed in the WHO Global High Burden Country lists 2021-2025, 1 namely Brazil (n = 2), China (n = 2), India (n = 1), Peru (n = 1), South Africa (n = 1) and Thailand (n = 1) (Table 1 and Supplementary Appendix 6). 24,29,41,45,50,52,56,62In the mixed method study, only the survey-based section of the study was extracted for this review.

Barriers to LTBI management
To aid in the interpretation and implementation of our results, we categorized the barriers to LTBI management into the public, provider or system level (Fig. 2). 4 The specific details of each domain and number of studies were summarized in Table 2 and Supplementary Appendix 8.A narrative summary is presented below.

Reflective motivation
Reflective motivation was another aspect which could be targeted in improving LTBI screening, diagnosis and treatment.Screening and testing hesitancy for LTBI was noted especially among the general public as they were not aware of the risk of LTBI and TB reactivation. 10,25,26,29,30,32,41,42,46,48,50,56,59imilarly, LTBI treatment was not well accepted by the general public and healthcare providers, as they were concerned about the effectiveness and risk of LTBI treatment. 19,20,26,29,30,34,36,38,41,42,45,48,51,52,54,58,61As such, there is a need to enforce LTBI testing and treatment policy to guide appropriate decision-making in LTBI practice. 19,20,44,49tomatic motivation LTBI was often associated with psychosocial burden, such as worries, stress, anxiety and embarrassment. 21,25,27,33,36,41,42,62 I was reported that healthcare workers who had LTBI suffered from higher anticipated psychosocial distress compared to public who had LTBI. 27To address this, better support system could be established to ensure the psychological, mental, emotional and social well-being of individuals with LTBI.

Social opportunity
Stigma with the fear of judgement has greatly impacted the health and well-being of LTBI affected communities. 21,25,27,36,52,56The concerns arose during their treatment process and clinic visits, with the worries of being discriminated by their community.This social impact was more evident among healthcare providers and migrant communities because of their social status. 27,59ysical opportunity The low acceptability of LTBI treatment was primarily attributed to the concerns over the side effects and prolonged treatment duration for this asymptomatic condition. 10,20,25,26,33,38,41,45,47,48,52,54In addition, the lack of resources and support for healthcare providers in LTBI management such as funding and screening availability has to be overcome in ensuring the continuity and good quality of LTBI services. 19,23,28,33,58ing behaviour change wheel to address LTBI barriers In response to the barriers above, seven of the nine intervention functions in the BCW, namely education, persuasion, incentivization, training, environmental restructuring, modelling and enablement, were selected to guide improvement in LTBI management (Table 2 & Supplementary Appendix 9). 4

Physical capability
As healthcare providers reported a lack of experience and standardization in LTBI practice, additional training should be conducted.Some topics of interest should include identification of LTBI, especially for the high-risk populations. 23,28,32,40,49,53,55,57,60From the perspective of environment restructuring, prompts and cues such as an LTBI checklist can be prepared for healthcare providers attending individuals at risk of LTBI. 23,28,32,40,49,53,55,57,60In addition, faculty mentoring or modelling can be implemented.Experienced senior healthcare providers could be the mentors to juniors in managing LTBI cases.

Psychological capability
34][35][36][37][38][39]41,42,44,45,[48][49][50][51][52][53][54][55][56]59 Education was identified to be an important intervention to improve healthcare providers and the general public's awareness towards LTBI.While they are better informed with the importance of LTBI screening and treatment, this helps to encourage their acceptance of LTBI care.Education can be delivered in the forms of community campaigns, regular seminar, courses and professional training.This can go hand in hand with an environment restructuring, such as public health campaigns through mass media.Other opportunities include the use of influencers and advocators who could act as the role model (modelling), to raise public awareness towards LTBI.

Reflective motivation
One key strategy towards the eradication of TB and LTBI is the need for LTBI screening and treatment uptake.,61 Relevant information on LTBI could be shared through verbal discussion together with visual aids such as infographics or pamphlets.Given that many will experience catastrophic costs, incentivization such as food or travel vouchers can be provided to individuals accepting LTBI screening and treatment. 38Incentives can also be offered to healthcare providers who attend to LTBI cases. 10,19,20,30,32,34,42,45,48,50,51,54,56,58,61Meanwhile, enablement allows psychosocial support services, counselling sessions or social support network to be given to individuals with LTBI.This is where modelling can be applied as well, to which LTBI treatment completers can be the mentors to support those who are new to the treatment. 20,29,30,36,38,41,42,48,52,58,61

Automatic motivation
Individuals with LTBI including healthcare providers were troubled by psychosocial impact due to LTBI. 21,25,27,33,36,41,42,62 Tis could be attributed to the misunderstanding and misperception towards LTBI.With community education on LTBI, general public and healthcare providers can be better informed about LTBI.This helps to overcome the stress, anxiety and embarrassment associated with LTBI.This intervention can be coupled with enablement for psychosocial support to be provided to individuals with LTBI.In addition, modelling helps to alleviate distress among individuals with LTBI, where individuals who have undergone LTBI screening and treatment could be the guidance for those who are new to LTBI care.

Social opportunity
As stigma is one of the concerns for healthcare providers and individuals with LTBI, 21,25,27,36,52,56,59 education and enablement are essential strategies to cope with potential discrimination stem from LTBI.Education can be conducted through community campaigns for better public awareness, whereas enablement in the form of social support can be offered not only to individual with LTBI but also their caregivers, family and close friends.Knowledge coupled with social support can work synergistically in tackling stigma in LTBI.

Physical opportunity
In response to the concerns over LTBI treatment, 10,20,24-26, 33,35,38,41,45,47,48,52,54,62 targeted education can be reinforced through training for the healthcare providers.They could in turn share the information (education) with individuals eligible for LTBI treatment during the consultation and counselling sessions.To address the issues on time constraint, financial and logistic challenges in accessing LTBI care, incentivization in the forms of food and travel vouchers or financial aids can be provided to subsidize the direct non-medical costs needed to access LTBI services. 33,38emuneration can be offered to healthcare providers and healthcare facilities that provide LTBI care with strict adherence to LTBI guidelines. 30In addition, persuasion can be applied to encourage healthcare providers to actively participate in LTBI practice and training.Environment restructuring will also be needed to ensure sufficient funding is available to increase the coverage of LTBI screening in local health facilities. 19,23,28,33,58

Main finding of this study
To our best knowledge, this is the first systematic review incorporating theoretical rationale with the COM-B model to identify the gaps in LTBI management.The complex structure of barriers to LTBI management can be summarized as suboptimal knowledge (physical capability) and misperception of LTBI (reflective motivation and physical opportunity), stigma (social opportunity) and psychosocial burden (automatic motivation).As the barriers of LTBI management were inter-related with one another, our findings suggest the need of a multifaceted approach guided by the intervention functions from the BCW to address the shortfall in LTBI care.

What is already known on this topic
Active TB disease continues to persist in many countries, largely because of the on-going reactivation of LTBI.As such, TB elimination will require extensive screening and treatment of LTBI.The primary benefit of LTBI treatment is that it can effectively reduce the risk of developing active TB disease in specific high-risk populations.Unfortunately, this is not often seen among the individual(s) with LTBI and their communities.The gaps in LTBI management were known to be attributed to individual, provider and systemic factors. 7,8These include patients' worries about the negative impact of LTBI treatment, a lack of knowledge among healthcare providers in LTBI testing and treatment and a low prioritization of LTBI management in the healthcare system. 7n view of these, a holistic view of the barriers to LTBI management would be beneficial for improvements targeting individual (patient and public), provider and system levels to be formulated.

What this study adds
We found that holistic strategies targeting knowledge, socioeconomic and cultural gaps should be adopted to facilitate the implementation of LTBI management.In order to achieve this, the BCW was used as an inclusive and holistic guidance in pivoting interventions for behaviour change at various levels, including the policies, service, healthcare providers, patients and the public.The BCW also incorporates socio-economic and cultural aspects into its intervention functions to address the social determinants of health that play an important role in health outcomes. 4For example, low acceptability to LTBI treatment could be attributed to the misunderstanding on the protective effect of BCG vaccine (psychological capability), 17,18,20,21,25,26,31,33,34,37,39,44,46,48,51,55,59 misperception on the risk of treatment (reflective motivation), 19,20,26,29,30,34,36,38,41,42,45,48,51,52,54,58,61 concerns over the side effects of medications (physical opportunity), 10,20,25,26,33,38,41,47,52,54 psychosocial distress (automatic motivation) 21,25,27,33,36,41,42,62 and the fear of stigma (social opportunity). 21,25,27,36,52,56,59Using BCW, education, environment restructuring, persuasion and modelling were identified to address the misunderstanding, misperception and concerns over LTBI treatment.Incentivization and enablement were equally important to provide financial and social support to overcome the distress and stigma among individuals with LTBI.Hence, a combination of intervention functions was required to resolve the underlying barriers to LTBI treatment hesitancy.
While there is no standalone intervention in addressing the barriers, it was observed that education is the fundamental strategy to target behaviour change in LTBI management.Nevertheless, we need to take the study setting into consideration.For example, there are differences in resource distribution and healthcare priorities in high TB burden countries compared to low-incidence countries. 63,64Therefore, there is a need to tailor appropriate educational modules for different settings, in order to optimize the impact of educational intervention.
As the BCW targets changes and improvements across various levels, this implies the importance of multidisciplinary collaboration to tackle the barriers in LTBI management.However, the role of community personnel such as community healthcare workers and pharmacists in LTBI management has not been fully explored.We have only identified one study which recruited community healthcare workers, 56 and one study that recruited pharmacists as part of the study cohort. 18The participation of healthcare providers from all disciplines for LTBI training should be encouraged to share the professional responsibilities in providing quality LTBI care across all levels of health service delivery.
This review has highlighted the importance of collective efforts from all parties to improve LTBI care.Overall, it is essential to raise the awareness of active TB disease and LTBI as a public health emergency and increase political commitment to this neglected disease.This is to ensure that TB prevention and control can be achieved, in accomplishing the targets of ending global TB epidemic by the next decade.

Limitations of this study
There are several limitations which need to be considered.First, we included only articles published in English.As such, relevant publications in other languages might have been missed out, despite our extensive literature search.Furthermore, the substantial heterogeneity in the included studies, in terms of research aims, sampling techniques, questionnaire designs, questionnaire validation process and response rates could potentially affect the quality of overall data.Non-response bias, attrition bias and the possibility of self-selecting bias among the participants might be inevitable in survey studies.We conducted the risk of bias assessment meticulously, where none of the studies was reported to have a high risk of bias.

Conclusion
The findings from this review highlight potential strategies to better guide changes and improvements in policies for better delivery of LTBI management.Through a successful implementation of LTBI care, this can serve as an important stepping stone to accomplish the milestone of WHO END TB Strategy.

Fig. 1
Fig. 1 PRISMA flow diagram showing the selection of included studies.

Fig. 2
Fig. 2 Barriers to LTBI management at system, provider and general public level mapped on to the subcomponents of COM-B model.

Table 1
Study characteristics of the included studies TB: tuberculosis; the US: The United States; LTBI: latent tuberculosis infection; HCW: healthcare worker; the UK: The United Kingdom; TNF: tumour necrosis factor; TBESC: Tuberculosis Epidemiologic Studies Consortium; HIV: human immunodeficiency virus; TST: tuberculin skin test; IGRA: interferon gamma release assay; NTP: National Tuberculosis Programme; IPT: isoniazid preventive therapy; PLWH: people living with HIV; HCV: hepatitis C virus; QFT-G: QuantiFERON-TB Gold a Some questions did not receive full response, but the questions were not specified b

Table 2
Overview of results: Summary of barriers with corresponding intervention functions across levels (public, provider, and system) and theoretical component