Use of Digital Technology to Enhance Tuberculosis Control: Scoping Review

Use of Digital Technology to Enhance Tuberculosis Control: Scoping Review Background: Tuberculosis (TB) is the leading cause of death from a single infectious agent, with around 1.5 million deaths reported in 2018, and is a major contributor to suffering worldwide, with an estimated 10 million new cases every year. In the context of the World Health Organization’s End TB strategy and the quest for digital innovations, there is a need to understand what is happening around the world regarding research into the use of digital technology for better TB care and control. Objective: The purpose of this scoping review was to summarize the state of research on the use of digital technology to enhance TB care and control. This study provides an overview of publications covering this subject and answers 3 main questions: (1) to what extent has the issue been addressed in the scientific literature between January 2016 and March 2019, (2) which countries have been investing in research in this field, and (3) what digital technologies were used? Methods: A Web-based search was conducted on PubMed and Web of Science. Studies that describe the use of digital technology with specific reference to keywords such as TB, digital health, eHealth, and mHealth were included. Data from selected studies were synthesized into 4 functions using narrative and graphical methods. Such digital health interventions were categorized based on 2 classifications, one by function and the other by targeted user. Results: A total of 145 relevant studies were identified out of the 1005 published between January 2016 and March 2019. Overall, 72.4% (105/145) of the research focused on patient care and 20.7% (30/145) on surveillance and monitoring. Other programmatic functions 4.8% (7/145) and electronic learning 2.1% (3/145) were less frequently studied. Most digital health technologies used for patient care included primarily diagnostic 59.4% (63/106) and treatment adherence tools 40.6% (43/106). On the basis of the second type of classification, 107 studies targeted health care providers (107/145, 73.8%), 20 studies targeted clients (20/145, 13.8%), 17 dealt with data services (17/145, 11.7%), and 1 study was on the health system or resource management. The first authors’ affiliations were mainly from 3 countries: the United States (30/145 studies, 20.7%), China (20/145 studies, 13.8%), and India (17/145 studies, 11.7%). The researchers from the United States conducted their research both domestically and abroad, whereas researchers from China and India conducted all studies domestically. Conclusions: The majority of research conducted between January 2016 and March 2019 on digital interventions for TB focused on diagnostic tools and treatment adherence technologies, such as video-observed therapy and SMS. Only a few studies addressed interventions for data services and health system or resource management. (J Med Internet Res 2020;22(2):e15727) doi: 10.2196/15727 KEYWORDS tuberculosis; mHealth; eHealth; medical informatics https://www.jmir.org/2020/2/e15727 J Med Internet Res 2020 | vol. 22 | iss. 2 | e15727 | p. 1 (page number not for citation purposes) XSL FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH Lee et al diagnostic delays and prevent further transmission in the Introduction community [6]. Background In 2018, the WHO released a general classification on DHIs that are applicable to all conditions [7]. This classification is Tuberculosis (TB) is among the top 10 causes of death organized by the targeted primary user: clients, health care worldwide, the leading cause from a single infectious agent, providers, health systems or resource managers, and data above HIV or AIDS, and the leading killer of people with HIV services. First, clients are the potential or current users of health [1]. The most vulnerable people are the poorest, with 95% of services. Second, health care providers are members of the cases and 98% of deaths occurring in low- and middle-income health workforce who deliver health services. Third, health countries [2]. Although most TB deaths are preventable if system managers and resource managers are involved in detected and treated at an early stage, TB still caused an administrative or surveillance works, including supply chain estimated 1.5 million deaths in 2018 [1]. management, health financing, and human resource In September 2015, the Global TB Program of the World Health management. Finally, data services consist of supporting a wide Organization (WHO) developed an agenda for action on digital range of activities related to data collection, management, use, health exploring what contributions can be offered by this and exchange. technology to the care and control of TB. This agenda Objective highlighted opportunities and the latest information available on the use of digital health technology to combat TB [3]. Its To achieve the End TB Strategy milestones for 2020 and use was categorized into 4 types of function. First, patient care 2025—TB incidence needs to be falling by 10% per year by and electronic directly observed therapy (eDOT), mainly refer 2025, and the proportion of people with TB who die from the to TB screening, TB diagnosis, and treatment adherence. As disease needs to fall to 6.5% by 2025—as well as the 2030 to part of the latter, eDOT concerns the general recommendation 2035 global targets, digital health is considered critical [3]. In of supervising and supporting patients when they take their TB other words, the existing approaches to patient care, surveillance drugs, thus ensuring the regular intake of medicines at home and monitoring, program management, and e-learning could be and the avoidance of daily or frequent visits to clinics. Second, strengthened by the utilization of digital health technologies, surveillance and monitoring covering health information system including mobile phones, big data, genetic algorithms, and management, measurement of the burden of TB disease and artificial intelligence. death, and the monitoring of drug resistance. Third, program The goal of this scoping review was to provide an overview of management includes items such as drug stock management the publications covering this subject. The results of this study systems, the development of norms, and training. Fourth, could ultimately be applied to enhance the use of digital electronic learning (e-learning) is the function by which technology in TB control more sustainably and effectively. This electronic media and devices are used as tools for improving study answers 3 main questions. First, to what extent has the access to training, communication, and interaction [4]. subject been covered in the scientific literature between January Previously, directly observed therapy was the standard of care 2016 and March 2019? Second, which countries were investing to ensure treatment adherence by patients throughout their long in research in this field? Finally, what digital technologies were treatment duration and monitoring for adverse drug effects [5]. used? The study compares results based on 2 types of However, ensuring patients’ adherence to the full course of classifications: one by function and the other by targeted user. medications has traditionally been a critical challenge in TB treatment as patients needed to be observed by a health provider Methods in a health facility, or the health provider, including community workers, had to visit the patients daily. After the introduction Scoping Review of digital health technology, eDOT became a significant part A scoping review documents the entire process in sufficient of digital health interventions (DHIs). Many studies were detail, which could be replicated by other scholars (Textbox 1). conducted around video-observed therapy (VOT), SMS, and It assigns a more precise meaning to ambiguous terms and mobile apps. In 2010, the GeneXpert Mycobacterium includes them in search criteria, which makes this review tuberculosis (MTB)/rifampicin (RIF) assay was introduced, evidence based. In addition, a scoping review excludes the after which an increasing number of studies assessed digital quality of papers from the selection criteria, meaning that it is health technology in the identification of active TB cases. Most less biased in the inclusion criteria [8]. high-income countries use digital diagnostic tools to reduce Textbox 1. Five processes of scoping review. 1. Identify the research question with a broad approach. 2. Identify relevant studies. 3. Study selection. 4. Chart the data by synthesizing and interpreting the qualitative data. 5. Collate, summarize, and report the results. https://www.jmir.org/2020/2/e15727 J Med Internet Res 2020 | vol. 22 | iss. 2 | e15727 | p. 2 (page number not for citation purposes) XSL FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH Lee et al Following the framework of a standard scoping review, this 2016 to March 2019. This date range was selected to cover the work first identified research questions that were as wide as period after the WHO recommended date for worldwide possible to include all of the relevant studies on the use of digital adoption of the new End TB Strategy in 2016. On the basis of health technology for TB care and control. Afterwards, relevant the inclusion and exclusion criteria, the articles collected were studies were collected from 2 major databases pertinent to global screened for relevance. The first selection was made by health, followed by the process of study selection. Finally, the reviewing the titles and abstracts of the articles. English, findings were categorized into 4 types of interventions following Chinese, and French languages were considered for selection, logic derived from 2 WHO-recommended approaches. One by whereas Russian was excluded. A final selection was made after function, including patient care, surveillance and monitoring, reviewing the full texts. program management, and e-learning [4], and the other by the Of the original 1005 articles, 333 were excluded as duplicate primary targeted user, such as clients, health care providers, studies, and 449 did not meet the inclusion criteria based on the health system or resource managers, and data services [5]. title and abstract. As a result, 223 articles were assessed in full. Articles were eligible for inclusion if they focused on the use Search Strategy of digital health technologies in TB patient care, surveillance, To identify all relevant studies, a comprehensive search strategy programmatic function, or e-learning. Articles on bovine TB, was developed to include, but not be confined to, (tuberculosis TB drug development, epidemiology of TB, or evaluation on OR tuberculosis infection OR TB OR tuberculosis disease OR the quality of technology were excluded. After full reading of mycobacterium tuberculosis) AND (digital OR ehealth OR the 223 articles, 62 were excluded, and 1 article (in Russian) mhealth OR technology OR telemedicine OR mobile OR big without English or Chinese summary was also excluded. A total data OR artificial intelligence OR real-time OR video). These of 15 articles, which were not available in full text, but for which search terms were used to identify relevant literature in 2 only the conference abstracts or summary existed, were primary databases, PubMed and Web of Science. excluded. Of the original 1005, 527 studies did not meet the Study Selection inclusion criteria (511 were not relevant, 15 were not available with full-text, and 1 was in Russian). Therefore, a total of 145 The scoping review included articles covering both quantitative studies, including 140 in English and 5 in Chinese, were finally and qualitative research, systematic reviews, editorials and identified as relevant (see Multimedia Appendix 1 [3,6,9-150]). viewpoints, and correspondence indexed in the PubMed or Web Figure 1 summarizes the flow of literature search and screening. of Science databases. The publication dates ranged from January Figure 1. Flowchart of literature search and screening. https://www.jmir.org/2020/2/e15727 J Med Internet Res 2020 | vol. 22 | iss. 2 | e15727 | p. 3 (page number not for citation purposes) XSL FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH Lee et al diagnosis, treatment, and care support (Table 1). A total of 30 Data Synthesis studies used digital technology in surveillance and monitoring, In the analysis, a descriptive numerical summary is provided including electronic medical records and information systems; to present the following information: author/s, publication year, 7 focused on program management, and 3 focused on e-learning. study type, geographic region of the study, the first author’s affiliation country, digital health technology domain, Using the other WHO classification of the use of digital interventions of digital technology, and the main results. The technology in health by targeted user, of the 145 studies, 107 geographic origin of the papers was categorized according to (73.8%) studies focused on health care providers, 20 (13.8%) the World Bank regional grouping, which includes East Asia studies targeted clients, 17 (11.7%) studies data services, and and Pacific, Latin America and Caribbean, North America, 1 (0.7%) study the health system or resource managers. The Sub-Saharan Africa, Europe and Central Asia, Middle East and vast majority of scientific literature targeted health care North Africa, and South Asia [151]. Papers that did not focus providers compared with patients or general health system on a specific region or country or studies on more than one managers. region were classified as global. The extracted data were Using the other WHO classification of the use of digital extrapolated into a data charting form in a Microsoft Excel file. technology in health by targeted user, of the 145 studies, 107 (73.8%) studies focused on health care providers, 20 (13.8%) Results studies targeted clients, 17 (11.7%) studies data services, and 1 (0.7%) study the health system or resource managers. The Main Results vast majority of scientific literature targeted health care In the assessment by function, 105 studies identified the primary providers compared with patients or general health system use of digital technology as TB patient care. This included TB managers. Table 1. Four types of interventions. Intervention type and digital health technology References Patient care GeneXpert [1-11] Chest x-ray [12-22] Polymerase chain reaction [23-31] Video directly observed therapy [32-49] text messages [50-60] Mobile phone apps [61-70] Artificial intelligence [71-73] Novel technologies [74-102] Surveillance and monitoring Health information system webpages (eg, OUT-TB, e-TB, ETR.Net, TB portals, and TB Genova network) [103-133] Program management [134-140] Electronic learning Digital platform for chest x-ray training [141] Educational video [142] Mobile app [143] that the United States was the country with the highest number First Authors’ Affiliation of publications on this topic. Out of the 30 studies published in In this study, the first author’s affiliation is defined by the the United States, 11 had a geographic focus on regions outside country of the author’s academic institution rather than the of North America, including Sub-Saharan Africa, Latin America, nationality of the author. The first author’s affiliation included and Caribbean regions. China and India were the second and both high- and low-income countries. In terms of frequency of third countries in terms of the number of publications when the publications, the following countries were identified: the United first author’s affiliation was used as a criterion. Considering the States, China, India, the United Kingdom), Canada, South burden of disease, it is not unusual to see the growing interests Africa, Switzerland, South Korea, and Italy. Figure 2 shows of China and India in the use of digital health technology in TB. https://www.jmir.org/2020/2/e15727 J Med Internet Res 2020 | vol. 22 | iss. 2 | e15727 | p. 4 (page number not for citation purposes) XSL FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH Lee et al Figure 2. Number of publications by first author’s affiliation. to read SMS messages, especially women, because of the high Types of Digital Technology prevalence of illiteracy [15]. Of the 105 studies on patient care, 62 analyzed the use of digital A total of 30 studies on surveillance and monitoring revealed technology in diagnosis and 43 its use in treatment adherence. the absence of standardized health information systems to collect Among the 62 studies on digital technology for diagnosis, 16 data on the care and control of TB [16,17]. Digital records were on GeneXpert MTB/RIF, which is today considered the demonstrated fewer data quality issues than paper-based records test of choice for early and rapid diagnosis of TB [10,11]. The [18] and improved patient management [19]. However, newly other studies were on digital chest x-ray (CXR) with the recruited health care workers had low confidence to use digital computer-aided detection of TB (n=14), digital real-time health technologies. To enhance national or global TB polymerase chain reaction technologies (n=11), artificial surveillance and monitoring systems, some studies (n=14/30) intelligence (n=3), deep learning or machine learning (n=2), a tested Web-based platforms, the connectivity of diagnostic dot-blot system (n=1), computational modeling (n=1), and technologies, and standardized health information systems. mobile 3D-printed induration (n=1), among others (n=13). Existing systems include OUT-TB Web, e-TB Manager, A total of 39 studies undertook a mobile health (mHealth) ETR.Net, TB Portals, and TB Genova network. In addition, approach to analyze the use of mobile phones in TB treatment artificial neural networks, big data analysis, Web-based surveys, adherence. This approach included VOT (n=19), SMS (n=9), and mathematical modeling (10/30) were used to predict the mobile apps (n=6), voice calls (n=2), mobile phone 3D-printed flow of TB patients. The remaining 2 studies examined TB drug induration (n=1), and framework studies on mHealth for TB susceptibility testing based on next-generation sequencing and treatment (n=2). In the 19 studies on VOT, a cost and impact whole-genome sequencing. analysis on VOT showed that VOT could save up to 58% of A total of 7 studies addressed the intervention of digital costs, in addition to alleviating inconvenience and cost when technology in program management. Three studies looked into visiting the treatment center [12,13]. VOT demonstrated a the e-learning aspect of digital technology, with 1 examining a promising adherence rate, which is practical and enables patients mobile phone app [20], another a Web-based training course in remote areas to have easy access to treatment. The challenges on CXR [21], and the third a multilingual educational video on of VOT lie in patient confidentiality, the management of adverse latent TB [22]. In conclusion, Figure 3 summarizes the major drug reactions, and technical issues [14]. Patients may be unable types of digital technology for TB that are discussed in this scoping review. https://www.jmir.org/2020/2/e15727 J Med Internet Res 2020 | vol. 22 | iss. 2 | e15727 | p. 5 (page number not for citation purposes) XSL FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH Lee et al Figure 3. Types of digital technology. MTB: mycobacterium tuberculosis; RIF: rifampicin. Another reason could be the nature of academic research papers. Discussion Standard study design in health science journals prefers interventions that are comparatively discrete and well The findings of this scoping review suggest that the overall standardized. This is the reason why most researchers prefer to research efforts on the use of digital health technologies in TB focus on straightforward outcomes of interventions and on strict care and control between January 2016 and March 2019 were methodological approaches. In fact, specific diagnostic tools focused disproportionately on patient care (105/145, 72.4%) and VOT were the subject of a substantial number of studies, and surveillance (30/145, 20.7%), and were aimed essentially and tools such as GeneXpert MTB/RIF, VOT, and SMS were at benefiting health care providers (107/145, 73.8% of all more frequently assessed under randomized controlled trial studies). (RCT) conditions. Complex interventions such as Web-based Only 1 study called for increased patient support focus after platforms, mobile apps, e-learning, or health information reviewing 24 TB-related apps in use [9]. This study argued that systems, which go beyond testing of an individual tool, are less apps for TB patient care had minimal functionality, primarily likely to be studied through RCTs and therefore, to be the targeted frontline health care workers, and focused on data preferred theme for a researcher. collection. Few apps were developed for use by patients, and Regarding the categorization of digital health research efforts none were designed to support TB patients’ involvement in and through the lens of targeted users, a disproportionate 73.8% of management of their care. A total of 3 studies out of 145 studies (107/145) focused on health care providers. Some other integrated perspectives of both health care providers and patients areas, for instance health systems or resource managers, are into their analysis. These findings show a clear trend in the currently not well covered by research efforts. More importantly, present literature on digital health technology for TB. It centers very few studies have focused on clients revealing the need to on feedback by health professionals, rather than TB patients, further explore the use of digital technology in TB care from a in utilizing digital health technology. different and more person-centered perspective to truly identify Using the TB-specific categorization by function, despite the benefits that these tools can bring to clients. recognition of its importance, only 7 studies were devoted to Multifunctionality of Digital Technology program management and only 3 to e-learning. One of the 7 studies on program management developed a general framework The main results categorized the existing literature by 2 types on all priority products and concepts of digital health of taxonomy. Each DHI was classified into 1 of only 4 options technologies in TB [23]. Some policy reports suggested scaling for the sake of simplifying the analysis. However, the possibility up investment in digital health to enhance TB control [152]. In of overlap in technological function must be considered. In the assessment of the frequency of research based on the other words, some digital technologies no longer have a single TB-specific categorization of themes, 1 reason for the scarcity function or are targeting a single user but instead have of studies on programmatic challenges could be the inclusion multifunctionality and can target different types of users. of TB drug management in studies outside of the TB field. This For instance, for the purpose of analysis, GeneXpert MTB/RIF scoping review did not count studies without any keywords was considered under the category of patient care. However, at referring to TB; therefore, other studies, which may have the same time, it could serve as a tool for the surveillance of referred to TB program management but without the keyword drug resistance. In the past, it was impossible to connect TB could have been overlooked. Similarly, the inclusion of gray microscopy to a database. Since 2010, however, GeneXpert has literature, such as project reports of executive groups, could enabled the synchronization of all data into the database once have increased the percentage of studies targeting health system the test results are available. Therefore, both health professionals managers and data services. However, this was outside the aims and data services can obtain benefits from the use of a rapid of this scoping review. diagnostic technology. Similarly, TB surveillance tools can be https://www.jmir.org/2020/2/e15727 J Med Internet Res 2020 | vol. 22 | iss. 2 | e15727 | p. 6 (page number not for citation purposes) XSL FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH Lee et al used to manage the health system. OUT-TB Web provides terms of epidemiological trends and patient populations. Thus, surveillance services such as customizable heat maps for it is necessary to focus further on high-burden countries where visualizing TB and drug-resistance cases. In addition, it serves digital technology has not yet been studied properly; these may program management functions such as the allocation of include WHO-identified high-burden countries such as Angola, financial, technical, and human resources [24]. Furthermore, Bangladesh, DR Congo, Ethiopia, Kenya, Myanmar, Nigeria, reports from the ETR.Net surveillance platform were used to and Vietnam. inform and guide resource allocation at the facilities [25]. Added Value of This Study Another good example of double targets is that of VOT. In this The strengths of this review consist of the high number of study, VOT was categorized depending on the primary function studies included and the breadth of the analysis based on 2 of the technology. It was considered an intervention for health different taxonomies of functions and targets. It summarizes care providers if the primary purpose was consultations between the range of research activity on the use of digital technology remote clients and health care providers (WHO category 2.4.1). to enhance TB control between January 2016 and March 2019. If VOT was to ensure treatment adherence by transmitting The findings highlight a need to expand knowledge and research targeted alerts and reminders, then it was considered to be a in health system management and data services, with a view on tool targeting clients (WHO category 1.1.3). The difference in targeting clients rather than mainly health care workers. A the targeted user clearly shows various perspectives in discussion on the multifunctionality of digital technology also understanding the functions of a single technology. provides added value in regard to different perspectives to examine various functions of a single technology. Limitations and Direction for Further Research This review has some limitations. One is related to the first Conclusions author’s affiliation. To capture which countries invested the Our findings suggest that the major hubs of research on digital most in research in this field, we simplified the analysis by health for TB include the United States, as well as China and equating the first author’s affiliation with a country. However, India. It is presumably because of available resources and high the first author’s affiliation represents neither the nationality of disease prevalence, respectively. An interesting observation the author nor the affiliation of the other authors if there are derived from the study is the multifunctionality of digital more. Another limitation relates to the search strategy that could technology. Unlike single-function tools in the past, an be further refined. The literature search only included 2 major increasing number of digital health technologies carry multiple databases. Some articles and gray literature presented functions. Out of 145 studies, 105 (72.4%) addressed patient exclusively in other databases or websites could have been care as the main focus of digital health technology, and 30 missed, although we suspect that they may not have had a (20.7%) targeted surveillance. Program management and significant impact on the findings. e-learning were 2 underrepresented topics of research. Looking at the findings from a target perspective, compared with studies Future research should fill the gaps that we unveiled, particularly targeting health care providers, studies on health system in the areas of data services, health system management, and managers and data services were limited as were, of particular client focus. Potential research topics that have not been well concern, those addressing clients. Therefore, more research and investigated to date include sustainable financing of digital development are necessary to arrive at a broader understanding health technologies used for TB, surveillance of TB diagnosis of the full potential of digital technology in the TB field. We equipment stocks, TB drug forecasting, and reporting on suggest that future research should focus on program counterfeit or substandard drugs (WHO classification 3.2) [5]. management, e-learning, and surveillance, with enhanced focus In addition, it seems worth exploring the role of other e-learning on the clients, the ultimate beneficiaries, to enhance the tools such as the application of game techniques to education, effectiveness of care, prevention, and control of TB and augmented reality, and 3D learning environments. contribute to its elimination. Furthermore, not all findings in a high- or a low-resource country may apply to another country in a different situation in Acknowledgments The study was conducted as part of YL’s Master’s thesis in Global Health at the University of Geneva. Authors' Contributions MR contributed to analysis, review, and editing throughout the writing process, and AF provided guidance and approval of the manuscript for publication. 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[doi: 10.1016/j.chest.2017.08.225] Abbreviations CXR: chest x-ray DHI: digital health intervention eDOT: electronic directly observed therapy e-learning: electronic learning mHealth: mobile health MTB: mycobacterium tuberculosis RCT: randomized controlled trial RIF: rifampicin TB: tuberculosis VOT: video-observed therapy WHO: World Health Organization Edited by G Eysenbach; submitted 19.09.19; peer-reviewed by N Riccardi, I Mircheva; comments to author 15.10.19; revised version received 22.10.19; accepted 22.10.19; published 13.02.20 Please cite as: Lee Y, Raviglione MC, Flahault A J Med Internet Res 2020;22(2):e15727 URL: https://www.jmir.org/2020/2/e15727 doi: 10.2196/15727 PMID: ©Yejin Lee, Mario C Raviglione, Antoine Flahault. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 13.02.2020. 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Use of Digital Technology to Enhance Tuberculosis Control: Scoping Review

Journal of Medical Internet Research, Volume 22 (2) – Feb 13, 2020

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©Yejin Lee, Mario C Raviglione, Antoine Flahault. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 13.02.2020.
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Abstract

Background: Tuberculosis (TB) is the leading cause of death from a single infectious agent, with around 1.5 million deaths reported in 2018, and is a major contributor to suffering worldwide, with an estimated 10 million new cases every year. In the context of the World Health Organization’s End TB strategy and the quest for digital innovations, there is a need to understand what is happening around the world regarding research into the use of digital technology for better TB care and control. Objective: The purpose of this scoping review was to summarize the state of research on the use of digital technology to enhance TB care and control. This study provides an overview of publications covering this subject and answers 3 main questions: (1) to what extent has the issue been addressed in the scientific literature between January 2016 and March 2019, (2) which countries have been investing in research in this field, and (3) what digital technologies were used? Methods: A Web-based search was conducted on PubMed and Web of Science. Studies that describe the use of digital technology with specific reference to keywords such as TB, digital health, eHealth, and mHealth were included. Data from selected studies were synthesized into 4 functions using narrative and graphical methods. Such digital health interventions were categorized based on 2 classifications, one by function and the other by targeted user. Results: A total of 145 relevant studies were identified out of the 1005 published between January 2016 and March 2019. Overall, 72.4% (105/145) of the research focused on patient care and 20.7% (30/145) on surveillance and monitoring. Other programmatic functions 4.8% (7/145) and electronic learning 2.1% (3/145) were less frequently studied. Most digital health technologies used for patient care included primarily diagnostic 59.4% (63/106) and treatment adherence tools 40.6% (43/106). On the basis of the second type of classification, 107 studies targeted health care providers (107/145, 73.8%), 20 studies targeted clients (20/145, 13.8%), 17 dealt with data services (17/145, 11.7%), and 1 study was on the health system or resource management. The first authors’ affiliations were mainly from 3 countries: the United States (30/145 studies, 20.7%), China (20/145 studies, 13.8%), and India (17/145 studies, 11.7%). The researchers from the United States conducted their research both domestically and abroad, whereas researchers from China and India conducted all studies domestically. Conclusions: The majority of research conducted between January 2016 and March 2019 on digital interventions for TB focused on diagnostic tools and treatment adherence technologies, such as video-observed therapy and SMS. Only a few studies addressed interventions for data services and health system or resource management. (J Med Internet Res 2020;22(2):e15727) doi: 10.2196/15727 KEYWORDS tuberculosis; mHealth; eHealth; medical informatics https://www.jmir.org/2020/2/e15727 J Med Internet Res 2020 | vol. 22 | iss. 2 | e15727 | p. 1 (page number not for citation purposes) XSL FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH Lee et al diagnostic delays and prevent further transmission in the Introduction community [6]. Background In 2018, the WHO released a general classification on DHIs that are applicable to all conditions [7]. This classification is Tuberculosis (TB) is among the top 10 causes of death organized by the targeted primary user: clients, health care worldwide, the leading cause from a single infectious agent, providers, health systems or resource managers, and data above HIV or AIDS, and the leading killer of people with HIV services. First, clients are the potential or current users of health [1]. The most vulnerable people are the poorest, with 95% of services. Second, health care providers are members of the cases and 98% of deaths occurring in low- and middle-income health workforce who deliver health services. Third, health countries [2]. Although most TB deaths are preventable if system managers and resource managers are involved in detected and treated at an early stage, TB still caused an administrative or surveillance works, including supply chain estimated 1.5 million deaths in 2018 [1]. management, health financing, and human resource In September 2015, the Global TB Program of the World Health management. Finally, data services consist of supporting a wide Organization (WHO) developed an agenda for action on digital range of activities related to data collection, management, use, health exploring what contributions can be offered by this and exchange. technology to the care and control of TB. This agenda Objective highlighted opportunities and the latest information available on the use of digital health technology to combat TB [3]. Its To achieve the End TB Strategy milestones for 2020 and use was categorized into 4 types of function. First, patient care 2025—TB incidence needs to be falling by 10% per year by and electronic directly observed therapy (eDOT), mainly refer 2025, and the proportion of people with TB who die from the to TB screening, TB diagnosis, and treatment adherence. As disease needs to fall to 6.5% by 2025—as well as the 2030 to part of the latter, eDOT concerns the general recommendation 2035 global targets, digital health is considered critical [3]. In of supervising and supporting patients when they take their TB other words, the existing approaches to patient care, surveillance drugs, thus ensuring the regular intake of medicines at home and monitoring, program management, and e-learning could be and the avoidance of daily or frequent visits to clinics. Second, strengthened by the utilization of digital health technologies, surveillance and monitoring covering health information system including mobile phones, big data, genetic algorithms, and management, measurement of the burden of TB disease and artificial intelligence. death, and the monitoring of drug resistance. Third, program The goal of this scoping review was to provide an overview of management includes items such as drug stock management the publications covering this subject. The results of this study systems, the development of norms, and training. Fourth, could ultimately be applied to enhance the use of digital electronic learning (e-learning) is the function by which technology in TB control more sustainably and effectively. This electronic media and devices are used as tools for improving study answers 3 main questions. First, to what extent has the access to training, communication, and interaction [4]. subject been covered in the scientific literature between January Previously, directly observed therapy was the standard of care 2016 and March 2019? Second, which countries were investing to ensure treatment adherence by patients throughout their long in research in this field? Finally, what digital technologies were treatment duration and monitoring for adverse drug effects [5]. used? The study compares results based on 2 types of However, ensuring patients’ adherence to the full course of classifications: one by function and the other by targeted user. medications has traditionally been a critical challenge in TB treatment as patients needed to be observed by a health provider Methods in a health facility, or the health provider, including community workers, had to visit the patients daily. After the introduction Scoping Review of digital health technology, eDOT became a significant part A scoping review documents the entire process in sufficient of digital health interventions (DHIs). Many studies were detail, which could be replicated by other scholars (Textbox 1). conducted around video-observed therapy (VOT), SMS, and It assigns a more precise meaning to ambiguous terms and mobile apps. In 2010, the GeneXpert Mycobacterium includes them in search criteria, which makes this review tuberculosis (MTB)/rifampicin (RIF) assay was introduced, evidence based. In addition, a scoping review excludes the after which an increasing number of studies assessed digital quality of papers from the selection criteria, meaning that it is health technology in the identification of active TB cases. Most less biased in the inclusion criteria [8]. high-income countries use digital diagnostic tools to reduce Textbox 1. Five processes of scoping review. 1. Identify the research question with a broad approach. 2. Identify relevant studies. 3. Study selection. 4. Chart the data by synthesizing and interpreting the qualitative data. 5. Collate, summarize, and report the results. https://www.jmir.org/2020/2/e15727 J Med Internet Res 2020 | vol. 22 | iss. 2 | e15727 | p. 2 (page number not for citation purposes) XSL FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH Lee et al Following the framework of a standard scoping review, this 2016 to March 2019. This date range was selected to cover the work first identified research questions that were as wide as period after the WHO recommended date for worldwide possible to include all of the relevant studies on the use of digital adoption of the new End TB Strategy in 2016. On the basis of health technology for TB care and control. Afterwards, relevant the inclusion and exclusion criteria, the articles collected were studies were collected from 2 major databases pertinent to global screened for relevance. The first selection was made by health, followed by the process of study selection. Finally, the reviewing the titles and abstracts of the articles. English, findings were categorized into 4 types of interventions following Chinese, and French languages were considered for selection, logic derived from 2 WHO-recommended approaches. One by whereas Russian was excluded. A final selection was made after function, including patient care, surveillance and monitoring, reviewing the full texts. program management, and e-learning [4], and the other by the Of the original 1005 articles, 333 were excluded as duplicate primary targeted user, such as clients, health care providers, studies, and 449 did not meet the inclusion criteria based on the health system or resource managers, and data services [5]. title and abstract. As a result, 223 articles were assessed in full. Articles were eligible for inclusion if they focused on the use Search Strategy of digital health technologies in TB patient care, surveillance, To identify all relevant studies, a comprehensive search strategy programmatic function, or e-learning. Articles on bovine TB, was developed to include, but not be confined to, (tuberculosis TB drug development, epidemiology of TB, or evaluation on OR tuberculosis infection OR TB OR tuberculosis disease OR the quality of technology were excluded. After full reading of mycobacterium tuberculosis) AND (digital OR ehealth OR the 223 articles, 62 were excluded, and 1 article (in Russian) mhealth OR technology OR telemedicine OR mobile OR big without English or Chinese summary was also excluded. A total data OR artificial intelligence OR real-time OR video). These of 15 articles, which were not available in full text, but for which search terms were used to identify relevant literature in 2 only the conference abstracts or summary existed, were primary databases, PubMed and Web of Science. excluded. Of the original 1005, 527 studies did not meet the Study Selection inclusion criteria (511 were not relevant, 15 were not available with full-text, and 1 was in Russian). Therefore, a total of 145 The scoping review included articles covering both quantitative studies, including 140 in English and 5 in Chinese, were finally and qualitative research, systematic reviews, editorials and identified as relevant (see Multimedia Appendix 1 [3,6,9-150]). viewpoints, and correspondence indexed in the PubMed or Web Figure 1 summarizes the flow of literature search and screening. of Science databases. The publication dates ranged from January Figure 1. Flowchart of literature search and screening. https://www.jmir.org/2020/2/e15727 J Med Internet Res 2020 | vol. 22 | iss. 2 | e15727 | p. 3 (page number not for citation purposes) XSL FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH Lee et al diagnosis, treatment, and care support (Table 1). A total of 30 Data Synthesis studies used digital technology in surveillance and monitoring, In the analysis, a descriptive numerical summary is provided including electronic medical records and information systems; to present the following information: author/s, publication year, 7 focused on program management, and 3 focused on e-learning. study type, geographic region of the study, the first author’s affiliation country, digital health technology domain, Using the other WHO classification of the use of digital interventions of digital technology, and the main results. The technology in health by targeted user, of the 145 studies, 107 geographic origin of the papers was categorized according to (73.8%) studies focused on health care providers, 20 (13.8%) the World Bank regional grouping, which includes East Asia studies targeted clients, 17 (11.7%) studies data services, and and Pacific, Latin America and Caribbean, North America, 1 (0.7%) study the health system or resource managers. The Sub-Saharan Africa, Europe and Central Asia, Middle East and vast majority of scientific literature targeted health care North Africa, and South Asia [151]. Papers that did not focus providers compared with patients or general health system on a specific region or country or studies on more than one managers. region were classified as global. The extracted data were Using the other WHO classification of the use of digital extrapolated into a data charting form in a Microsoft Excel file. technology in health by targeted user, of the 145 studies, 107 (73.8%) studies focused on health care providers, 20 (13.8%) Results studies targeted clients, 17 (11.7%) studies data services, and 1 (0.7%) study the health system or resource managers. The Main Results vast majority of scientific literature targeted health care In the assessment by function, 105 studies identified the primary providers compared with patients or general health system use of digital technology as TB patient care. This included TB managers. Table 1. Four types of interventions. Intervention type and digital health technology References Patient care GeneXpert [1-11] Chest x-ray [12-22] Polymerase chain reaction [23-31] Video directly observed therapy [32-49] text messages [50-60] Mobile phone apps [61-70] Artificial intelligence [71-73] Novel technologies [74-102] Surveillance and monitoring Health information system webpages (eg, OUT-TB, e-TB, ETR.Net, TB portals, and TB Genova network) [103-133] Program management [134-140] Electronic learning Digital platform for chest x-ray training [141] Educational video [142] Mobile app [143] that the United States was the country with the highest number First Authors’ Affiliation of publications on this topic. Out of the 30 studies published in In this study, the first author’s affiliation is defined by the the United States, 11 had a geographic focus on regions outside country of the author’s academic institution rather than the of North America, including Sub-Saharan Africa, Latin America, nationality of the author. The first author’s affiliation included and Caribbean regions. China and India were the second and both high- and low-income countries. In terms of frequency of third countries in terms of the number of publications when the publications, the following countries were identified: the United first author’s affiliation was used as a criterion. Considering the States, China, India, the United Kingdom), Canada, South burden of disease, it is not unusual to see the growing interests Africa, Switzerland, South Korea, and Italy. Figure 2 shows of China and India in the use of digital health technology in TB. https://www.jmir.org/2020/2/e15727 J Med Internet Res 2020 | vol. 22 | iss. 2 | e15727 | p. 4 (page number not for citation purposes) XSL FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH Lee et al Figure 2. Number of publications by first author’s affiliation. to read SMS messages, especially women, because of the high Types of Digital Technology prevalence of illiteracy [15]. Of the 105 studies on patient care, 62 analyzed the use of digital A total of 30 studies on surveillance and monitoring revealed technology in diagnosis and 43 its use in treatment adherence. the absence of standardized health information systems to collect Among the 62 studies on digital technology for diagnosis, 16 data on the care and control of TB [16,17]. Digital records were on GeneXpert MTB/RIF, which is today considered the demonstrated fewer data quality issues than paper-based records test of choice for early and rapid diagnosis of TB [10,11]. The [18] and improved patient management [19]. However, newly other studies were on digital chest x-ray (CXR) with the recruited health care workers had low confidence to use digital computer-aided detection of TB (n=14), digital real-time health technologies. To enhance national or global TB polymerase chain reaction technologies (n=11), artificial surveillance and monitoring systems, some studies (n=14/30) intelligence (n=3), deep learning or machine learning (n=2), a tested Web-based platforms, the connectivity of diagnostic dot-blot system (n=1), computational modeling (n=1), and technologies, and standardized health information systems. mobile 3D-printed induration (n=1), among others (n=13). Existing systems include OUT-TB Web, e-TB Manager, A total of 39 studies undertook a mobile health (mHealth) ETR.Net, TB Portals, and TB Genova network. In addition, approach to analyze the use of mobile phones in TB treatment artificial neural networks, big data analysis, Web-based surveys, adherence. This approach included VOT (n=19), SMS (n=9), and mathematical modeling (10/30) were used to predict the mobile apps (n=6), voice calls (n=2), mobile phone 3D-printed flow of TB patients. The remaining 2 studies examined TB drug induration (n=1), and framework studies on mHealth for TB susceptibility testing based on next-generation sequencing and treatment (n=2). In the 19 studies on VOT, a cost and impact whole-genome sequencing. analysis on VOT showed that VOT could save up to 58% of A total of 7 studies addressed the intervention of digital costs, in addition to alleviating inconvenience and cost when technology in program management. Three studies looked into visiting the treatment center [12,13]. VOT demonstrated a the e-learning aspect of digital technology, with 1 examining a promising adherence rate, which is practical and enables patients mobile phone app [20], another a Web-based training course in remote areas to have easy access to treatment. The challenges on CXR [21], and the third a multilingual educational video on of VOT lie in patient confidentiality, the management of adverse latent TB [22]. In conclusion, Figure 3 summarizes the major drug reactions, and technical issues [14]. Patients may be unable types of digital technology for TB that are discussed in this scoping review. https://www.jmir.org/2020/2/e15727 J Med Internet Res 2020 | vol. 22 | iss. 2 | e15727 | p. 5 (page number not for citation purposes) XSL FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH Lee et al Figure 3. Types of digital technology. MTB: mycobacterium tuberculosis; RIF: rifampicin. Another reason could be the nature of academic research papers. Discussion Standard study design in health science journals prefers interventions that are comparatively discrete and well The findings of this scoping review suggest that the overall standardized. This is the reason why most researchers prefer to research efforts on the use of digital health technologies in TB focus on straightforward outcomes of interventions and on strict care and control between January 2016 and March 2019 were methodological approaches. In fact, specific diagnostic tools focused disproportionately on patient care (105/145, 72.4%) and VOT were the subject of a substantial number of studies, and surveillance (30/145, 20.7%), and were aimed essentially and tools such as GeneXpert MTB/RIF, VOT, and SMS were at benefiting health care providers (107/145, 73.8% of all more frequently assessed under randomized controlled trial studies). (RCT) conditions. Complex interventions such as Web-based Only 1 study called for increased patient support focus after platforms, mobile apps, e-learning, or health information reviewing 24 TB-related apps in use [9]. This study argued that systems, which go beyond testing of an individual tool, are less apps for TB patient care had minimal functionality, primarily likely to be studied through RCTs and therefore, to be the targeted frontline health care workers, and focused on data preferred theme for a researcher. collection. Few apps were developed for use by patients, and Regarding the categorization of digital health research efforts none were designed to support TB patients’ involvement in and through the lens of targeted users, a disproportionate 73.8% of management of their care. A total of 3 studies out of 145 studies (107/145) focused on health care providers. Some other integrated perspectives of both health care providers and patients areas, for instance health systems or resource managers, are into their analysis. These findings show a clear trend in the currently not well covered by research efforts. More importantly, present literature on digital health technology for TB. It centers very few studies have focused on clients revealing the need to on feedback by health professionals, rather than TB patients, further explore the use of digital technology in TB care from a in utilizing digital health technology. different and more person-centered perspective to truly identify Using the TB-specific categorization by function, despite the benefits that these tools can bring to clients. recognition of its importance, only 7 studies were devoted to Multifunctionality of Digital Technology program management and only 3 to e-learning. One of the 7 studies on program management developed a general framework The main results categorized the existing literature by 2 types on all priority products and concepts of digital health of taxonomy. Each DHI was classified into 1 of only 4 options technologies in TB [23]. Some policy reports suggested scaling for the sake of simplifying the analysis. However, the possibility up investment in digital health to enhance TB control [152]. In of overlap in technological function must be considered. In the assessment of the frequency of research based on the other words, some digital technologies no longer have a single TB-specific categorization of themes, 1 reason for the scarcity function or are targeting a single user but instead have of studies on programmatic challenges could be the inclusion multifunctionality and can target different types of users. of TB drug management in studies outside of the TB field. This For instance, for the purpose of analysis, GeneXpert MTB/RIF scoping review did not count studies without any keywords was considered under the category of patient care. However, at referring to TB; therefore, other studies, which may have the same time, it could serve as a tool for the surveillance of referred to TB program management but without the keyword drug resistance. In the past, it was impossible to connect TB could have been overlooked. Similarly, the inclusion of gray microscopy to a database. Since 2010, however, GeneXpert has literature, such as project reports of executive groups, could enabled the synchronization of all data into the database once have increased the percentage of studies targeting health system the test results are available. Therefore, both health professionals managers and data services. However, this was outside the aims and data services can obtain benefits from the use of a rapid of this scoping review. diagnostic technology. Similarly, TB surveillance tools can be https://www.jmir.org/2020/2/e15727 J Med Internet Res 2020 | vol. 22 | iss. 2 | e15727 | p. 6 (page number not for citation purposes) XSL FO RenderX JOURNAL OF MEDICAL INTERNET RESEARCH Lee et al used to manage the health system. OUT-TB Web provides terms of epidemiological trends and patient populations. Thus, surveillance services such as customizable heat maps for it is necessary to focus further on high-burden countries where visualizing TB and drug-resistance cases. In addition, it serves digital technology has not yet been studied properly; these may program management functions such as the allocation of include WHO-identified high-burden countries such as Angola, financial, technical, and human resources [24]. Furthermore, Bangladesh, DR Congo, Ethiopia, Kenya, Myanmar, Nigeria, reports from the ETR.Net surveillance platform were used to and Vietnam. inform and guide resource allocation at the facilities [25]. Added Value of This Study Another good example of double targets is that of VOT. In this The strengths of this review consist of the high number of study, VOT was categorized depending on the primary function studies included and the breadth of the analysis based on 2 of the technology. It was considered an intervention for health different taxonomies of functions and targets. It summarizes care providers if the primary purpose was consultations between the range of research activity on the use of digital technology remote clients and health care providers (WHO category 2.4.1). to enhance TB control between January 2016 and March 2019. If VOT was to ensure treatment adherence by transmitting The findings highlight a need to expand knowledge and research targeted alerts and reminders, then it was considered to be a in health system management and data services, with a view on tool targeting clients (WHO category 1.1.3). The difference in targeting clients rather than mainly health care workers. A the targeted user clearly shows various perspectives in discussion on the multifunctionality of digital technology also understanding the functions of a single technology. provides added value in regard to different perspectives to examine various functions of a single technology. Limitations and Direction for Further Research This review has some limitations. One is related to the first Conclusions author’s affiliation. To capture which countries invested the Our findings suggest that the major hubs of research on digital most in research in this field, we simplified the analysis by health for TB include the United States, as well as China and equating the first author’s affiliation with a country. However, India. It is presumably because of available resources and high the first author’s affiliation represents neither the nationality of disease prevalence, respectively. An interesting observation the author nor the affiliation of the other authors if there are derived from the study is the multifunctionality of digital more. Another limitation relates to the search strategy that could technology. Unlike single-function tools in the past, an be further refined. The literature search only included 2 major increasing number of digital health technologies carry multiple databases. Some articles and gray literature presented functions. Out of 145 studies, 105 (72.4%) addressed patient exclusively in other databases or websites could have been care as the main focus of digital health technology, and 30 missed, although we suspect that they may not have had a (20.7%) targeted surveillance. Program management and significant impact on the findings. e-learning were 2 underrepresented topics of research. Looking at the findings from a target perspective, compared with studies Future research should fill the gaps that we unveiled, particularly targeting health care providers, studies on health system in the areas of data services, health system management, and managers and data services were limited as were, of particular client focus. Potential research topics that have not been well concern, those addressing clients. Therefore, more research and investigated to date include sustainable financing of digital development are necessary to arrive at a broader understanding health technologies used for TB, surveillance of TB diagnosis of the full potential of digital technology in the TB field. We equipment stocks, TB drug forecasting, and reporting on suggest that future research should focus on program counterfeit or substandard drugs (WHO classification 3.2) [5]. management, e-learning, and surveillance, with enhanced focus In addition, it seems worth exploring the role of other e-learning on the clients, the ultimate beneficiaries, to enhance the tools such as the application of game techniques to education, effectiveness of care, prevention, and control of TB and augmented reality, and 3D learning environments. contribute to its elimination. Furthermore, not all findings in a high- or a low-resource country may apply to another country in a different situation in Acknowledgments The study was conducted as part of YL’s Master’s thesis in Global Health at the University of Geneva. Authors' Contributions MR contributed to analysis, review, and editing throughout the writing process, and AF provided guidance and approval of the manuscript for publication. 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[doi: 10.1016/j.chest.2017.08.225] Abbreviations CXR: chest x-ray DHI: digital health intervention eDOT: electronic directly observed therapy e-learning: electronic learning mHealth: mobile health MTB: mycobacterium tuberculosis RCT: randomized controlled trial RIF: rifampicin TB: tuberculosis VOT: video-observed therapy WHO: World Health Organization Edited by G Eysenbach; submitted 19.09.19; peer-reviewed by N Riccardi, I Mircheva; comments to author 15.10.19; revised version received 22.10.19; accepted 22.10.19; published 13.02.20 Please cite as: Lee Y, Raviglione MC, Flahault A J Med Internet Res 2020;22(2):e15727 URL: https://www.jmir.org/2020/2/e15727 doi: 10.2196/15727 PMID: ©Yejin Lee, Mario C Raviglione, Antoine Flahault. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 13.02.2020. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research, is properly cited. The complete bibliographic information, a link to the original publication on http://www.jmir.org/, as well as this copyright and license information must be included. https://www.jmir.org/2020/2/e15727 J Med Internet Res 2020 | vol. 22 | iss. 2 | e15727 | p. 15 (page number not for citation purposes) XSL FO RenderX

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