This is the first time to analyze the characteristics of RR-TB case detection at the level of PMDT after 2015, especially after implementation of the national 13th five year TB Program in 2016 in China.
Our analysis indicated that the RR screening rate and the number of RR-TB cases detection have increased significantly from 2015 to 2020. In 2019, the screening rate of RR in all bacteriologically confirmed TB cases reached 81.9%, exceeding the global level of 61%  and has become a routine work of the National TB Program (NTP). Delay in the diagnosis of RR-TB is one of the important reasons for the death, loss and inappropriate treatment for RR-TB cases [22–24], as well as increases in the risk of drug resistance spreading in the community. The median days for RR-TB cases to obtain RR results have been significantly reduced to 15 days in 2019, which is lower than 26 days in South Korea . Shanghai, China, a metropolis with a population of 30 million, the diagnosis time has been as short as 9 days .
The main reason for the above changes is that after the national drug resistant cases detection policy was modified, in order to achieve the national 13th Five-Year TB Program targets, the governments at all levels strengthened their commitment, especially near the end of the 13th Five-Year TB Program. This was done by increasing the capabilities of laboratories in weak areas and the aggressive scale up of the use of rapid molecular DST tools. From 2015 to 2018, the Chinese government has invested a total of about 260 million CNY to support economically underdeveloped areas such as the central and western regions to equip rapid molecular diagnostic tools . Furthermore, China central government provided funds for transportation costs of the county-level sputum specimens and strains and raised funds from various sources to provide free screening costs for presumptive RR-TB cases. These comprehensive measures improved the detection of RR-TB. Although the RR screening rate among high-risk groups has not yet reached the target of the 13th Five-Year TB Program, it will be achievable given the right strategic focus complemented by sustained leadership and adequate resources in 2020.
Our analysis also revealed that the source of presumptive RR-TB cases has changed in 2015–2019. More and more presumptive RR-TB cases are diagnosed in county-level hospitals, and the proportion is as high as 76.0% in 2019. The main reason for this trend is that the 13th Five-Year TB Program called for improving TB graded diagnosis and treatment services in order to strengthen the integration of TB prevention and treatment and make more rational use of medical resources . By enhancing the capacity building of county-level TB designated hospitals and the differentiation of medical insurance reimbursement to guide patients visiting hospitals in their jurisdiction to improve the accessibility of health care. The finding is of significance to China’s future deployment of PMDT. Although the diagnosis of drug-resistant TB is set at the prefecture level, it is necessary to include county-level rapid rifampicin susceptibility testing so that RR cases can receive appropriate treatment early and can reduce the spread of drug resistance. And only by improving the TB diagnosis capabilities of county-level hospitals can “missing RR-TB cases” be reduced.
Our analysis also found some issues about which to be concerned. First, the proportion of new RR-TB cases has reached 54.8% in 2019. New RR-TB cases represent primary rifampicin resistance, suggesting that we need to pay attention to the spread of drug-resistant tuberculosis. Some studies in China have shown the transmission of multidrug-resistant tuberculosis [28, 29]. Our analysis results also indicate that the potential risk of community transmission of RR-TB in China is relatively high in recent years. China currently has no legislation on isolation treatment or travel restrictions for infectious RR-TB cases. It is imperative that China explores the possibility of legislation to manage infectious RR-TB in the future.
A second key concern is the still low detection rate of RR-TB cases. 2019 was the year with the largest number of cases diagnosed, but only 28% of RR-TB patients estimated by WHO were detected. This suggests that more than 70% of RR-TB cases were being missed. The main reasons are firstly that the rate of bacteriologically confirmed TB cases in China was low. It was 47% in 2019, which is lower than the global rate of 57% . Secondly, 5% of prefectures cannot carry out DST nationwide and 17% of the prefectures have just gained the ability for DST in 2018–2019. The likelihood of insufficient personnel capacity and experience will affect the patient's diagnosis. Thirdly, there are limitations on current drug- resistance diagnostic algorithms regarding utilization of the Xpert. Xpert is just a tool for the diagnosis of RR in bacteriologically confirmed TB in China and isn’t used in the diagnosis of signs or symptoms of TB as recommended by the WHO to maximize the detection of TB and RR-TB cases . Xpert is still an expensive tool for China because the number of people with presumptive TB symptoms in China is enormous (about 3 million people per year).
A third issue relates to the FQs susceptibility testing. Contrary to the increasing RR screening rate, FQs testing proportion has been declining year by year from 2016 and only 41.0% of RR-TB cases were tested for FQs susceptibility in 2019, which was far lower than 71% globally , and was lower than 44% in South Africa . According to WHO's good susceptibility testing coverage standards, although China's RR screening rate has exceeded 80%, due to the low FQs susceptibility testing rate, China has not yet reached good testing coverage . The main reason for the low proportion of FQs susceptibility testing is that the FQs screening rate is not a target indicator of the 13th Five-Year TB Program. Despite FQs susceptibility was tested, the result was not registered in the TBIMS in time. In addition, similar to the reason for the lower RR-TB detection, the DST capability of some newly implemented PMDT prefectures, especially second-line drug susceptibility testing, still need to be improved. Apart from the above two reasons, since FQs susceptibility testing is not free currently, this will also lead to a lower proportion of FQ testing.
FQ is the backbone of RR treatment regimens and FQs resistance is associated with poor treatment outcomes. WHO recommended that, before initiating treatment for RR-TB cases, it is necessary to carry out susceptibility testing for FQs, preferably by rapid assay .The resistance rate of FQs among RR-TB patients in China is 27.4% , which is higher than the global average of 21% . This implies that at least 1/4 of RR-TB cases enrolled for treatment that have not undergone FQs susceptibility testing will have a risk of poor treatment outcomes. China has introduced the short-course chemotherapy regimen recommended by the WHO for 9–12 months. The key eligible criterion for using the short-term regimen is that the patient is not resistant to FQs. Therefore, in order to enable patients to apply appropriate chemotherapy regimens to ensure the patient's therapeutic effect, it is imperative to conduct FQs susceptibility testing for RR-TB patients.
There are some limitations in our study. We used data from the TBIMS. The registration system only classifies the RR testing as “fast” and “traditional”, and it is not yet possible to distinguish whether the FQs susceptibility testing is “molecular” or “traditional”. If we need to understand the current ability of FQs rapid molecular DST in China, a special investigation needs to be conducted. In addition, the current system is unable to obtain data about whether the results of RR are directly diagnosed at the county level or by transporting specimens to prefectures for diagnosis. This data is meaningful for the national budget for the delivery of sputum specimens and the layout of rifampicin resistance testing institutions.