Bracelet- and self-directed observational therapy for control of tuberculosis: study protocol for a cluster randomized controlled trial

Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis (MTB). Tuberculosis is diagnosed by identifying MTB bacteria in clinical specimens. A complete medical evaluation must include a medical history, a physical examination, a chest X-ray, and microbiological examination of sputum or another appropriate sample. The disease that has compromised health for 1000 years is one of the greatest global public health challenges of our time [1, 2]. TB is among the “top 10” causes of mortality from disease [3, 4]. In 2014, six million cases of TB were reported to the World Health Organization (WHO). Worldwide, almost one third of all affected people are infected with M. tuberculosis, the bacterium that causes TB; eight million people develop TB annually and 1.8 million die of the disease [3]. The greatest disease burdens are found in the poorest populations that have the fewest resources to devote to TB control. China has the second largest TB burden worldwide, accounting for 12% of all cases [5, 6]. Lack of medication adherence to TB treatment regimens and inappropriate prescription practices are important contributing factors to treatment failures and the development of multidrug-resistant (MDR) TB [7, 8] which is now a major threat to the progress made in global TB treatment in recent years. In the 2010 National Tuberculosis Prevalence Survey, 20% of TB patients treated by the public health system—using national TB case-management approaches—were lost to follow-up or were not taking their medications regularly [9, 10]. Therefore, the Chinese medical community needs to implement more effective medication adherence strategies. We cannot confirm that China will meet this target [11], especially considering the increasing numbers of newly diagnosed TB cases, particularly of multidrug-resistant tuberculosis (MDR-TB) [12]. MDR-TB is TB caused by bacteria resistant to treatment by at least two of the most powerful first-line anti-TB medications (drugs), oniazid and rifampin. Some forms of TB, termed extensively drug-resistant TB (XDR-TB), are also resistant to second-line medications.

The increasing incidence of MDR-TB (more contagious, more severe, and deadlier than other forms of TB) in China indicates that the road toward TB control remains long. The problem is not confined to China; worldwide, the spread of MDR-TB is a real threat to TB control [13], even in the United States, a developed country. In San Diego, 22% of TB cases reported in 2012 were resistant to at least one of the four major TB drugs; in New York City, the number of MDR-TB cases in 2012 was twice that in 2007 [14]. The WHO reports that China has the highest disease burden worldwide, followed (in order) by India, Russia, and South Africa. To conduct directly observed therapy (DOT) more effectively, we propose implementing bracelet and self-directed observational therapy, designed to improve TB treatment outcomes in low-resource environments.

China has a high burden of MDR-TB; approximately 54,000 (range: 48,000–61,000) pulmonary cases of MDR-TB were reported in 2013 [15, 16]. A key step [17] in TB control is the establishment of a TB database that can be used to develop effective strategies for TB medication adherence [18]. Critically, the effective way toward TB control is compliance with medication regimens; the need to endure long-term treatment remains a severe problem. Many factors compromise compliance with treatment regimens [19]. Poor health knowledge, a lack of understanding of the benefits afforded by treatment, side effects, and cost are major barriers to treatment success [20]. Almost 12% of patients in Jiangsu Province, China failed to take at least 10% of their prescribed doses of anti-TB medications; this was especially common when life resources were limited [21]. A study conducted in Hebei Province revealed that 46% of patients failed to take at least 10% of their doses. Several other Chinese studies have reported low levels of treatment adherence by patients with TB [21, 22]. To prevent treatment interruptions, new approaches are needed to overcome barriers within the social and health service contexts.

The applications of mobile information technology continue to multiply, perhaps affording the opportunity to bridge the gaps described above, and, in so doing, to enhance the means by which TB may be controlled in China. We seek to offer hope to both patients suffering from TB and to public health bodies seeking better TB control. We believe that mobile technologies may improve medication adherence, deliver education, and send behavioral intervention reminders.

One third of the world’s population is thought to be infected with TB. New infections develop in about 1% of the population each year. In 2014, there were 9.6 million cases of active TB that resulted in 1.5 million deaths. More than 95% of deaths occurred in developing countries. About 80% of people in many Asian and African countries test positive by the tuberculin test; the figure in the United States is 5 to 10%. Any improvement in TB treatment is important in terms of both public health and economics. Improved control and management of TB can lead to better treatment outcomes, thereby decreasing health inequalities, morbidity, mortality, and the economic costs associated with the disease. However, there are several difficulties with the proposed study design. Complications in this project include the developmental costs, the schedule, and the quality of, and the period needed to become used to the wearing of, a bracelet. Another difficulty is widely implementing BSDOT for TB treatment in these low-resource environments as the current administrative management systems in these areas remains underdeveloped. Use of the bracelet seeks to improve medication adherence among TB patients. However, as the technology will be used in low-resource settings, several constraints, including patient educational and income levels and their capacities to treat and control TB, must be relaxed. In terms of access to education, we will train village physicians to understand the program goals, to operate the devices, and to be more familiar with the pathology and clinical features of TB. Thus, the village physicians will be able to tell participants how to use their devices. The low average income of patients constitutes another critical constraint; we will seek to limit the cost of each device to below US$20. The National Bureau of Statistics of the People’s Republic of China (http://​data.​stats.​gov.​cn/​easyquery.​htm?​cn=​C01&​zb=​A0A0A&​sj=​2014) reported that per-capita disposable income of Chinese citizens was US$1613 in 2014. Thus, the device cost would seem reasonable. The economic status of TB patients declines rapidly over time because of the cost of their hospitalization and associated expenses as well as the management of side effects. If adherence to a TB medication plan can be improved, the social cost savings will be much greater than the cost of treatment. It will also be necessary to aim to reduce the cost of the device used to improve medication adherence. Directly observed therapy (DOT) has effectively controlled TB epidemics in China, and is freely available to infected individuals. Thus, if the smartphone application improves medication adherence, we would ask the government to provide free smartphones to TB patients living in low-resource environments. This would reduce device costs. Another constraint is that TB is difficult to both treat and control. Our study region contains ethnic minorities of minimally developed societies. Many patients treat TB using traditional herbs or folk prescriptions, or do not treat TB at all. Such vulnerable populations require special attention.

If our BSDOT strategy is successful, it can be implemented in remote areas (villages or mountainous regions) to improve the quality of overall health care and to ensure better TB control.

There are several very important limitations in this study that should be mentioned. Firstly, and most obvious, the use of this approach will require access to a smartphone which also requires electricity, access to the Internet, and cell phone reception in the treatment area. Secondly, in rural areas, the WHO DOT treatment may be complicated by the availability of resources; thus, this would render this intervention useless in such settings.