Multidrug-resistant tuberculosis (MDR-TB) poses a huge challenge to public health system in terms of treatment costs and disease control[8]. In 2012, the China government laid out a program for the treatment and care of MDR-TB, suggesting hospitalization and community care (home isolation) for patient management. It recommended patients to be hospitalized for about 2 months, followed by community care until treatment completion[9]. However, this was constrained by the variance of medical resources, infrastructure and their availability in different areas of China. Home isolation schedule adherence is also poor due to catastrophic cost associated with the disease[10]. We conducted a survey with enrollment from 3 mid- to high-income cities of China to review and identify potential factors and their impacts on city patients. Suggestions on improving and enhancing future policy design were then made based on the findings.
Beijing is the capital of China. Shenzhen is a special administrative region and enjoys a prime geographic location. Jiangmen is part of the Guangdong province and is benefitting from its fast development. These 3 cities are characterized by a relatively high GDP with a correspondingly high cost of living.
4.1 Risk of transmission from home-discharged “mid-income” patients
It has been reported that effective treatment of MDR-TB patients can quickly reduce its contagiousness[11, 12]. Some studies focusing on treatment outcome also claimed ambulatory-based MDR-TB management is more cost effective than hospital-based schemes[13-15]. Theoretically three weeks of effective treatment is enough to have the infectiousness of MDR-TB significantly controlled[11, 16].
However, treating MDR-TB is far more complicated. It has been reported that pooled treatment success was about 60% in MDR-TB patients[17, 18]. In the absence of new drugs such as bedaquiline, delamanid and linezolid, the success treatment outcome of MDR-TB with standardized second-line regimen in China before 2018 was only about 50%[19, 20]. We doubted that part of the MDR-TB patient with treatment failure were turned into XDR-TB in the end and undermined a large part of the efforts made in disease control. It has been reported that high rates of transmission from patients to exposed persons occurred when treatment regimens were ‘ineffective’[11]. Dheda, et al. reported that highly drug-resistant strains were spreading in the community from home-discharged patients and generating secondary cases with poor treatment outcomes[21].
Recent studies from China using genomic epidemiological approach have shown that new infection was the main cause of MDR-TB, and smear-negative tuberculosis patients are also part of the source of transmission[22-25]. It is unclear how many of the patients still on treatment regimen were contributing to the spread of the disease.
Therefore, the risk of transmission is a challenge that needs to be addressed immediately. Our study showed that about 80% (61) MDR-TB patients were hospitalized and 74% (57) of them were smear positive at the time of admission. Average hospital stay for these patients were 2 weeks, which is below the suggested length of inpatient care. 36.4% (28) patients returned to work and participated in social activities immediately afterwards. This is especially true for those who were married and were the bread earner. Findings in our study showed a substantial difference in the ratio between the married (48%) and singles (9%) in returning to work during the suggested home isolation period. "If I do not go to work, the family has not enough income, and I might be out of job and cannot pay the premium on my own. Without insurance coverage, I have to absorb all costs of medical treatment. This is the vicious outcome my family and I cannot afford." A MDR-TB patient who worked as a taxi driver told us. This behavior, however, posed an alarming transmission threat to the community. Performance-linked incentives can be provided from care provider’s level down to include patients to promote treatment adherence on a two-sided monitoring basis.
4.2 Financial hardship and catastrophic cost
The costs for treating MDR-TB were reported to range from US$1,218 to US$83,365 per case[8, 26]. This includes treatment cost, and other indirect costs such as transport cost and income loss. Potential loss of insurance coverage as a result of job lost could further aggravated these patients’ financial burden. Despite constant efforts the China Government made in health care measures trying to ease financial difficulties, but many kinds of medicine are not provided free of charge, especially new effective medicines such as linezolid and cycloserine. Many MDR-TB patients reflected that one of the major problems from the illness was still financial hardship[27-29]
Many studies have proved total cost spent on treating MDR-TB to be catastrophic for patients from most low- and middle-income families[30, 31].Surprisingly we found the middle working class were struck the hardest financially. Their relatively high cost of living, with an expensive-to-treat disease left them with a drained disposable household income. Their urge to return to work despite treatment status was the most alarming among all income groups.
Our study showed a direct relationship between the proportion of patients failing community care and the increase in foreseeable self-borne medical expenses. From the perspective of insurance coverage, 100% of patients obtaining self-paid commercial insurance and 46% of patients under UEBMI / URBMI returned to work before they were supposed to do so. Under UEBMI, employer has to pay 75% of premium for the employee. If one is out of job, they would have to bear full premium in keeping the insurance. Only 20% of patients without insurance coverage returned to work on hospital discharge, which is lower than the group covered by NRCMS (25%).
The same observation was reflected by out-of-pocket expenses. When monthly expenditure went above USD150, over 39% of patients chose to return to work despite the suggested home isolation care. This is true for patients under all kinds of insurance except NRCMS. The reason behind this could be the cost of keeping the insurance coverage. Premium for NRCMS is only USD4.5 / year which is way below any other insurance premium included in this study.
In combating this problem, the government could consider full medical coverage for MDR-TB patients, through special TB protection and registration programs, to enable expenses to be credited directly to the government, or an appointed agent. This can simplify the application and reimbursement process made on a per visit basis, and sooth patient’s fundamental financial difficulty.
4.3 Problems faced during treatment and possible solutions
Although WHO had downregulated the importance of second-line injections in 2018, it was still widely used in many MDR-TB regimens in China in 2017[32, 33]. When new drugs are unavailable, clinicians will resort to injection to construct part of an effective regimen. The pain and uncomfortable experience with injection discouraged most patients from adhering to treatment. And deficient regimen and insufficient treatment are among the main causes which led to more drug resistance and treatment failure[34, 35].
Furthermore, most anti-MDR-TB drugs have obvious toxic side effects which cause treatment adherence failure. A 62-year-old female MDR-TB patient in our study has stopped treatment on her own several times. Her current drug sensitivity test turned out to be XDR-TB.
In addition, most MDR-TB patients suffer from severe psychological stress[36, 37]. Worrisome thoughts included their illness being difficult to cure and the fear of spreading the disease to their family and friends. At the same time, they also worried about being isolated and alienated by their friends and family.
Providing care providers with free TB drugs and patients with new and effective oral medications, counselling service, and organizing patient groups to share experience will help them get the emotional support they need to complete treatment. This in turn would reduce disease spreading and minimize drug-resistance TB to be further developed.
There were some limitations in our study. Firstly, the participants were only from 3 cities therefore are not representative of all MDR-TB patients. The lack of control groups hindered comparisons with other population groups. Secondly, some patients refused to be interviewed or lost contact, which may have contributed to a loss of important relevant information and caused selection bias leading to underestimation of the difficulties the overall MDR-TB patients are facing. Thirdly, the study had not measured the risk of disease transmission from these patients who were currently on TB treatment, therefore no conclusions can be drawn on the relationship between airborne risk and infection risk spread by the said patients in the current study.
In summary, poverty and TB control has long been proved to have an inverse correlation. Tackling the problem must start from the root cause to alleviate caseload, all the way up to follow-up management of patients to minimize transmission and disease progression. Funding, free effective new oral medicine, providing patient-centred support and performance-linked incentives together could make a major step towards treatment success for TB.