The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China.

BACKGROUND: Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. METHODS: We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027-2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. RESULTS: By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69-72) and 72% (UI: 70-74), and the PSI vaccine by 31% (UI: 30-32) and 44% (UI: 42-47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8-1.1) and 1.1 million (UI: 0.9-1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. CONCLUSIONS: Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

Tuberculosis prevalence in China, 1990-2010; a longitudinal analysis of national survey data.

BACKGROUND: China scaled up a tuberculosis control programme (based on the directly observed treatment, short-course [DOTS] strategy) to cover half the population during the 1990s, and to the entire population after 2000. We assessed the effect of the programme. METHODS: In this longitudinal analysis, we compared data from three national tuberculosis prevalence surveys done in 1990, 2000, and 2010. The 2010 survey screened 252,940 eligible individuals aged 15 years and older at 176 investigation points, chosen by stratified random sampling from all 31 mainland provinces. All individuals had chest radiographs taken. Those with abnormal radiographs, persistent cough, or both, were classified as having suspected tuberculosis. Tuberculosis was diagnosed by chest radiograph, sputum-smear microscopy, and culture. Trained staff interviewed each patient with tuberculosis. The 1990 and 2000 surveys were reanalysed and compared with the 2010 survey. FINDINGS: From 1990 to 2010, the prevalence of smear-positive tuberculosis decreased from 170 cases (95% CI 166-174) to 59 cases (49-72) per 100,000 population. During the 1990s, smear-positive prevalence fell only in the provinces with the DOTS programme; after 2000, prevalence decreased in all provinces. The percentage reduction in smear-positive prevalence was greater for the decade after 2000 than the decade before (57% vs 19%; p<0.0001). 70% of the total reduction in smear-positive prevalence (78 of 111 cases per 100,000 population) occurred after 2000. Of these cases, 68 (87%) were in known cases-ie, cases diagnosed with tuberculosis before the survey. Of the known cases, the proportion treated by the public health system (using the DOTS strategy) increased from 59 (15%) of 370 cases in 2000 to 79 (66%) of 123 cases in 2010, contributing to reduced proportions of treatment default (from 163 [43%] of 370 cases to 35 [22%] of 123 cases) and retreatment cases (from 312 [84%] of 374 cases to 48 [31%] of 137 cases; both p<0.0001). INTERPRETATION: In 20 years, China more than halved its tuberculosis prevalence. Marked improvement in tuberculosis treatment, driven by a major shift in treatment from hospitals to the public health centres (that implemented the DOTS strategy) was largely responsible for this epidemiological effect. FUNDING: Chinese Ministry of Health.

Tuberculosis control in China: use of modelling to develop targets and policies.

It is unclear if current programmes in China can achieve the post-2015 global targets for tuberculosis - 50% reduction in incidence and a 75% reduction in mortality by 2025. Chinese policy-makers need to maintain the recent decline in the prevalence of tuberculosis, while revising control policies to cope with an epidemic of drug-resistant tuberculosis and the effects of ongoing health reform. Health reforms are expected to shift patients from tuberculosis dispensaries to designated hospitals. We developed a mathematical model of tuberculosis control in China to help set appropriate targets and prioritize interventions that might be implemented in the next 10 years. This model indicates that, even under the most optimistic scenario - improved treatment in tuberculosis dispensaries, introduction of a new effective regimen for the treatment of drug-susceptible tuberculosis and optimal care of cases of multidrug-resistant tuberculosis - the current global targets for tuberculosis are unlikely to be reached. However, reductions in the incidence of multidrug-resistant tuberculosis should be feasible. We conclude that a shift of patients from tuberculosis dispensaries to designated hospitals is likely to hamper efforts at tuberculosis control if cure rates in the designated hospitals cannot be maintained at a high level. Our results can inform the planning of tuberculosis control in China.

Il est difficile de savoir si les programmes actuellement menés en Chine permettront d'atteindre les objectifs mondiaux pour l'après-2015 concernant la tuberculose, qui consistent à réduire l'incidence de 50% et la mortalité de 75% d'ici à 2025. Les dirigeants chinois doivent confirmer le récent déclin de la prévalence de la tuberculose, mais aussi revoir les politiques de lutte pour faire face à une épidémie de tuberculose pharmacorésistante et les effets de l'actuelle réforme de la santé. La réforme de la santé est censée prévoir le transfert des patients traités dans des dispensaires antituberculeux vers des hôpitaux expressément désignés. Nous avons élaboré un modèle mathématique de lutte contre la tuberculose en Chine qui aide à définir les objectifs appropriés et à hiérarchiser les interventions qui pourraient être réalisées au cours des dix prochaines années. Ce modèle indique que même dans le scénario le plus optimiste ­ amélioration du traitement dans les dispensaires antituberculeux, introduction d'un nouveau schéma thérapeutique efficace pour le traitement de la tuberculose sensible et traitement optimal des cas de tuberculose multirésistante ­, il paraît difficile d'atteindre les objectifs mondiaux actuels pour la tuberculose. Néanmoins, il devrait être possible de réduire l'incidence de la tuberculose multirésistante. Nous en concluons que le transfert des patients traités dans des dispensaires antituberculeux vers des hôpitaux expressément désignés est susceptible d'entraver les efforts de lutte contre la tuberculose s'il est impossible de maintenir des taux de guérison élevés dans ces hôpitaux. Nos résultats peuvent servir de base à la planification de la lutte contre la tuberculose en Chine.

No está claro si los programas actuales en China pueden alcanzar los objetivos globales para la tuberculosis después de 2015, una reducción del 50% de la incidencia y una reducción del 75% de la mortalidad de aquí a 2025. Los responsables políticos de China necesitan mantener el reciente descenso en la prevalencia de la tuberculosis, al mismo tiempo que revisan las políticas de control para hacer frente a una epidemia de tuberculosis farmacorresistente y los efectos en la reforma sanitaria en curso. Se espera que las reformas sanitarias trasladen los pacientes de los dispensarios para tuberculosis a los hospitales designados. Se ha desarrollado un modelo matemático de control de la tuberculosis en China para ayudar a establecer los objetivos apropiados y priorizar las intervenciones que podrían implementarse en los próximos diez años. Este modelo indica que, incluso en el escenario más optimista (una mejora del tratamiento en los dispensarios para tuberculosis, la introducción de un nuevo y efectivo régimen para el tratamiento de la tuberculosis farmacosensible y la atención óptima en casos de la tuberculosis farmacorresistente), es muy poco probable que se cumplan los objetivos actuales globales para la tuberculosis. Sin embargo, las reducciones en la incidencia de la tuberculosis farmacorresistente deberían ser factibles. Se concluye que es posible que un cambio de los pacientes de los dispensarios para tuberculosis a los hospitales designados obstaculice los esfuerzos de un control para la tuberculosis si las tasas de cura en los hospitales designados no pueden mantenerse en un nivel alto. Nuestros resultados pueden dar información sobre la planificación del control de la tuberculosis en China.

[A study on the cooperation between centers for disease control and special tuberculosis hospitals for treatment and management of multi-drug resistant tuberculosis].

OBJECTIVE: To improve the effectiveness of case detection and treatment of multi-drug resistant tuberculosis (MDR-TB) by implementing a mechanism of cooperation between hospitals and centers for disease control (CDC). METHODS: Since 1 March 2010, a new mechanism of cooperation between hospitals and CDCs had been established in 5 cities including Daqing, Quzhou, Puyang, Tianjin and Wanzhou in China. Data of MDR-TB case-detection, treatment and economic burdens before the intervention (January 1, 2006-June 30, 2009) and after the intervention (March 1, 2010-February 29, 2012) were collected. Then all data were analyzed by statistical method. RESULTS: After the intervention, samples from 68.4% (5 287/7 733) of smear-positive TB patients in the study regions underwent TB drug-resistant testing, and the number of the detected MDR-TB cases were 9.8 times that prior to the intervention. 93.1% (108/116) of the patients incorporated into the treatment of MDR-TB received the standardized initial chemotherapy program, and the number was 7 times that before the intervention. The referral rates after hospital discharge raised from 0% before the intervention to 92.8% after (90/97) the intervention; and 85.7% (83/97) of the patients received treatment and management by CDC. When the 6-month injection ended, MDR-TB patients still under treatment after the intervention were 84.5% (82/97), and those whose sputum culture became negative were 56.7% (55/97). The proportion of patients with self-paid and with catastrophic expenditures after the intervention were reduced to 18.0% (1 678/9 324) and 44.7% (17/38) respectively, as compared to 75.4% (7 659/10 158) and 76.7% (23/30) respectively before the intervention. CONCLUSION: To establish a well-performed Hospital-CDC cooperation mechanism could promote the performance of MDR-TB case detection and treatment.

The Impact of COVID-19 Epidemic on Tuberculosis Reports Among Students - Guizhou Province, China, 2020.

What is already known about this topic?: In 2020, the implementation of non-medical interventions during the coronavirus disease 2019 (COVID-19) epidemic has created a negative impact on tuberculosis (TB) control. It is unclear if the prevalence of TB among students in Guizhou Province was also affected. What is added by this report?: Among TB cases, the proportion of student TB patients was 19.91% in the back-to-school period in 2020, which was higher than the 13.37% registered in 2017-2019, but this decreased in the COVID-19 pandemic period. The time interval between symptom onset and care-seeking of the student TB patients was the shortest in the back-to-school and physical check-up periods. What are the implications for public health practice?: TB active screening was effective for timely detection and diagnosis of TB among students, which could prevent TB outbreaks in schools.

Development and Application of a Multidrug-Resistant Tuberculosis Case Management System - Yunnan Province, China, 2017-2020.

Introduction: Treatment and case management of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge in tuberculosis (TB) control and prevention. This pilot study aims to apply and test a new electronic information system in order to help bolster case management of MDR-TB. Methods: The MDR-TB Case Management System (CMS) was developed and piloted in the Yunnan Tuberculosis Clinical Center (TCC) in 2017. Next, 5 sites in Yunnan were randomly selected and sampled as pilots in 2018. The real-time regular follow-up rate (RFUR) was calculated for pilot sites. Loss to follow-up (LTFU) rates of MDR-TB treatment cohorts between pilot and non-pilot sites were compared by a chi-square test. LTFU for MDR-TB treatment cohorts was then assessed by univariate and multivariate binary logistic regression. Results: The average regular follow-up rate was 90.7% in TCC and 73.7% in five other pilot sites of Yunnan Province respectively. The average LTFU rate for pilot sites (9.0%) was lower than non-pilot sites (20.6%, P<0.01). The risk of LTFU during MDR-TB treatment reduced 61.7% in CMS pilot cases (adjusted odds ratio: 0.38, 95% confidence interval: 0.23-0.60) compared with non-pilot cases. Conclusions: As a significant supplement to the Tuberculosis Information Management System, the CMS strengthened the collection, analysis, and utilization of strategic information for MDR-TB cases. The system improved case management by embedding it as a tool of the Comprehensive Supportive Care service model.

Characteristics of rifampicin-resistant tuberculosis detection in China, 2015-2019.

BACKGROUND: The very high burden of rifampicin resistance tuberculosis (RR-TB) and the very low detection of RR-TB cases are a major challenge that China has been facing. This study analyzed the characteristics of RR-TB detection in China after the change of RR-TB detection strategy since 2015, aiming to provide reference and evidence for the development of more precise national drug resistance tuberculosis prevention and control policy. METHODS: We extracted data related to rifampicin resistance screening from the national Tuberculosis Information Management System (TBIMS) from 2015 to 2019, and used descriptive research methods to analyze the screening rate of presumptive RR-TB, the number and duration of RR-TB patients detected and drug resistance testing methods in each year. Chi-square test was used to compare the differences in component ratio or rate between years, and Kruskal Wallis test was used to compare the differences in median days for detection of RR-TB patients in each year. RESULTS: A total of 68,200 RR-TB cases were detected during 2015-2019, of which 48.1% were new cases. The number and detection rate of RR-TB cases increased year by year, from 10 019 and 14.3% in 2015 to 18 623 and 28.7% in 2019, respectively. Of the bacteriologically confirmed TB cases, 81.9% were tested for RR in 2019, a considerable increase from 29.5% in 2015. In 2019, only 41.0% of RR-TB cases had fluoroquinolones (FQs) susceptibility testing performed, and this proportion has been declining year by year since 2016. The proportion of application of rapid molecular tools increased from 24.0% in 2015 to 67.1% in 2019, and the median days to obtain RR results was significantly shortened. In 2019, 76.0% of RR-TB cases were diagnosed as presumptive RR-TB in county-level hospitals. CONCLUSIONS: After China modified the RR-TB detection strategy, the screening rate of RR and the number of RR-TB cases increased significantly. The RR testing methods now predominantly utilize rapid molecular tools. However, comprehensive measures should be implemented to close the gap in the detection of RR-TB cases. It is imperative to take FQs susceptibility testing seriously and effectively strengthen the laboratory capacity of county-level hospitals.

Epidemiological Characteristics of Rifampicin-Resistant Tuberculosis in Students - China, 2015-2019.

What is already known about this topic? The number of students with tuberculosis (TB) has been increasing since 2015. However, the prevalence of rifampicin-resistant tuberculosis (RR-TB) among student population is unclear. What is added by the report? The number of students with RR-TB has significantly increased from 2015 to 2019, especially in the western region of China. The majority of patients were college students. Students with RR-TB were mainly new patients. What are the implications for public health practice? The following measures are recommended: strengthening TB surveillance in schools, promoting the application of convenient and rapid molecular drug susceptibility testing tools, and actively carrying out drug resistance screening and follow ups for cohabiting children of adult RR-TB patients.

Practical Experiences of Delivering Multidrug-Resistant Tuberculosis Comprehensive Supportive Care Services in China.

What is already known about this topic? The World Health Organization consolidated guidelines on recommend care for tuberculosis (TB) and support for multidrug-resistant TB (MDR-TB) patients. But guidelines have not provided detailed guidance or tools for health services providers to implement comprehensive patient care. What is added by this report? China CDC and the United States Agency for International Development-funded Control and Prevention of MDR-TB program introduced a differentiated and personalized comprehensive and supportive care services (CSC) to improve treatment adherence. What are the implications for public health practice? The CSC model helps MDR-TB patients complete treatment and improve treatment success rates, and scaling up the program and implementation in other parts of the country is worth consideration.

Impact of the gate-keeping policies of China's primary healthcare model on the future burden of tuberculosis in China: a protocol for a mathematical modelling study.

INTRODUCTION: In the past three decades, China has made great strides in the prevention and treatment of tuberculosis (TB). However, the TB burden remains high. In 2019, China accounted for 8.4% of global incident cases of TB, the third highest in the world, with a higher prevalence in rural areas. The Healthy China 2030 highlights the gate-keeping role of primary healthcare (PHC). However, the impact of PHC reforms on the future TB burden is unclear. We propose to use mathematical models to project and evaluate the impacts of different gate-keeping policies. METHODS AND ANALYSIS: We will develop a deterministic, population-level, compartmental model to capture the dynamics of TB transmission within adult rural population. The model will incorporate seven main TB statuses, and each compartment will be subdivided by service providers. The parameters involving preference for healthcare seeking will be collected using discrete choice experiment (DCE) method. We will solve the deterministic model numerically over a 20-year (2021-2040) timeframe and predict the TB prevalence, incidence and cumulative new infections under the status quo or various policy scenarios. We will also conduct an analysis following standard protocols to calculate the average cost-effectiveness for each policy scenario relative to the status quo. A numerical calibration analysis against the available published TB prevalence data will be performed using a Bayesian approach. ETHICS AND DISSEMINATION: Most of the data or parameters in the model will be obtained based on secondary data (eg, published literature and an open-access data set). The DCE survey has been reviewed and approved by the Ethics Committee of the School of Public Health, Sun Yat-sen University. The approval number is SYSU [2019]140. Results of the study will be disseminated through peer-reviewed journals, media and conference presentations.

Is knowledge retained by healthcare providers after training? A pragmatic evaluation of drug-resistant tuberculosis management in China.

OBJECTIVES: Considering the urgent need of training to improve standardised management of drug-resistant infectious disease and the lack of evidence on the impact of training, this study evaluates whether training participants' knowledge on multidrug-resistant tuberculosis (MDR-TB) is improved immediately and a year after training. SETTING AND PARTICIPANTS: The study involved 91 MDR-TB healthcare providers (HCPs), including clinical doctors, nurses and CDC staff, who attended a new MDR-TB HCP training programme in Liaoning and Jiangxi provinces, China. MAIN OUTCOME MEASURES: A phone-based assessment of participants' long-term retention of knowledge about MDR-TB management was conducted in July 2017, approximately 1 year after training. The proportion of correct responses in the long-term knowledge assessment was compared with a pretraining test and an immediate post-training test using a χ2 test. Factors influencing participants' performance in the long-term knowledge assessment were analysed using linear regression. RESULTS: Across both provinces, knowledge of definitions of drug-resistant TB, standardised MDR-TB case detection protocols and laboratory diagnosis was improved 1 year after the training by 14.5% (p=0.037), 32.4% (p<0.001) and 31% (p<0.001) relative to pretraining. However, compared with immediately after training, the knowledge of the three topics declined by 26.5% (p=0.003), 19.8% (p=0.018) and 52.7% (p<0.001) respectively in Jiangxi, while no significant decline was observed in Liaoning. Additionally, we found that obtaining a higher score in the long-term knowledge assessment was associated with longer years of clinical experience (coefficient=0.51; 95 CI% 0.02 to 0.99; p=0.041) and attending training in Liaoning (coefficient=0.50; 95% CI 0.14 to 0.85; p=0.007). CONCLUSION: Our study, the first to assess knowledge retention of MDR-TB HCPs 1 year after training, showed an overall positive long-term impact of lecture-style group training on participants' knowledge. Knowledge decline 1 year after training was observed in one province, Jiangxi, and this may be partly addressed by targeted support to HCPs with fewer years of clinical experience.

Attrition and delays before treatment initiation among patients with MDR-TB in China (2006-13): Magnitude and risk factors.

BACKGROUND: China's national tuberculosis programme does not have cohort wise information regarding attrition and delays in the multidrug resistant tuberculosis (MDR-TB) diagnosis and treatment pathway. OBJECTIVE: Under the Global Fund programmatic management of drug-resistant TB (2006-13), we assessed the attrition and delay in the pathway and the factors associated. METHODS: Cohort study involving secondary programme data. All patients identified as presumptive MDR-TB (defined as i) previously treated TB patients which included recurrent TB, return after loss to follow up, treatment after failure and ii) new TB patients that were non-converters at three months of treatment or in close contact with a known MDR-TB patient) during October 2006 to June 2013 were eligible for phenotypic drug susceptibility testing (DST). Pre-diagnosis attrition (presumptive MDR-TB not undergoing culture and DST) and pre-treatment attrition (confirmed MDR-TB patients not initiated on treatment) was calculated. Diagnosis delay was the time interval from DST eligibility to DST result, treatment initiation delay was fom DST result to treatment initiation and total delay was from DST eligbility to treatment initiation. Factors associated with attrition and delay were identified using log binomial regression and linear regression, respectively. RESULTS: Of 78 564 presumptive MDR-TB patients, 2 470 (3.1%) underwent pre-diagnosis attrition. Of 9 283 MDR-TB patients, 3 361 (36.2%) underwent pre-treatment attrition. Median(IQR) diagnosis delay was 84 (64, 114) days; treatment initation delay was 23(6,68) days and total delay was 117(77,187) days. Long diagnosis delay was an independent predictor of pre-treatment attrition in a dose response relationship. While pre-treatment attrition was less likely among presumptive criterion 'previously treated' and with increasing time period, it was more likey among elderly and in east and west region. While the diagnosis delay increased with time period, treatment initiation delay and total delay reduced with time period. Short diagnosis delay was associated with west region, smear negative patients and presumptive criterion 'treatment after lost to follow up'. Short treatment initiation delay was associatied with east and west regions while long treatment initiation delay was associated with elderly and presumptive criterion 'recurrent TB'. Total delay predictors were similar to treatment initiation delay. In addition, short total delay was associated with presumptive criterion 'treatment after failure'. CONCLUSION: The diagnosis and treatment delay were long and the pre-treatment attrition was considerable high. Long diagnosis delay is likely to predict pre-treatment attrition.

Clinical outcome of multidrug-resistant tuberculosis patients receiving standardized second-line treatment regimen in China.

OBJECTIVES: The aim of this study was to retrospectively analyze the clinical outcome and the risk factors associated with poor outcome of MDR-TB patients receiving standardized second-line treatment regimen in China. METHODS: Between January 2008 and December 2010, a total of 12,100 clinical diagnosed TB cases at high risk of drug-resistant TB (DR-TB) were enrolled in this study. Routine follow-up tests were conducted every month during the 6-month intensive phase, and every two months during the 18-month continuation phase. RESULTS: On the basis of phenotypical drug susceptibility test (DST) results, 2322 MDR-TB patients were confirmed, of which 1542 further received standardized second-line anti-TB regimen. The treatment success rate was 47.6% (734/1542): 688 patients (44.6%) were cured and 46 (3.0%) completed treatment. The percentage of cases with favorable outcome in previously untreated patients (57.6%) was significantly higher than that in treatment-experienced patients (46.1%, OR: 1.58, 95% CI: 1.17-2.14). In addition, a significant lower percentage of male MDR-TB cases with favorable outcome (45.8%) was observed using female MDR-TB cases as a reference (52.0%, OR: 1.31, 95% CI: 1.03-1.60). The proportion of MDR-TB cases with favorable outcome was significantly decreased in older age groups. CONCLUSIONS: In conclusion, our data demonstrate that less than half of these patients receiving standardized second-line treatment regimen meet the definition of successful treatment during a 3-year period in China. More attention should be paid to the MDR-TB population at high-risk of poor clinical outcome, including male, elderly age, and those who have received prior treatment.

[Analysis of the cost of public health service items in four centers for disease control and prevention in county level in China].

OBJECTIVE: To analyze the unreasonable part of full cost of the public health service items in county level. METHODS: On basis of typical survey in 2005, 18 questionnaires were released and the response rate was 100%. The whole cost and ladder apportionment of expense methods were employed to account the full cost of items including practice items, items required by government and nationwide items required by government provided by 4 centers for disease control and prevention in county level. RESULTS: It was found that 28.4% - 54.9% nationwide items required by government had not been provided, but 2.8% - 10.2% items being not required by government had been provided. Furthermore the frequency of the items required by government was not up to par from 8 topmost to 2 bottommost on average every year. The efficiency was not high because of lacking in the vehicle for work, and 33.3% - 43.6% shortage of equipments for laboratory, and 18.1% - 45.8% logistic staff and technicians only 2/3 time of the whole year had a full workload. All the above resulted in the bias from the standard cost of items required by government. CONCLUSION: For compensating the cost of items reasonable and accurate by government, a kind standard cost of the items according to the government request should be established.

Comparing yield and relative costs of WHO TB screening algorithms in selected risk groups among people aged 65 years and over in China, 2013.

OBJECTIVE: To calculate the yield and cost per diagnosed tuberculosis (TB) case for three World Health Organization screening algorithms and one using the Chinese National TB program (NTP) TB suspect definitions, using data from a TB prevalence survey of people aged 65 years and over in China, 2013. METHODS: This was an analytic study using data from the above survey. Risk groups were defined and the prevalence of new TB cases in each group calculated. Costs of each screening component were used to give indicative costs per case detected. Yield, number needed to screen (NNS) and cost per case were used to assess the algorithms. FINDINGS: The prevalence survey identified 172 new TB cases in 34,250 participants. Prevalence varied greatly in different groups, from 131/100,000 to 4651/ 100,000. Two groups were chosen to compare the algorithms. The medium-risk group (living in a rural area: men, or previous TB case, or close contact or a BMI <18.5, or tobacco user) had appreciably higher cost per case (USD 221, 298 and 963) in the three algorithms than the high-risk group (all previous TB cases, all close contacts). (USD 72, 108 and 309) but detected two to four times more TB cases in the population. Using a Chest x-ray as the initial screening tool in the medium risk group cost the most (USD 963), and detected 67% of all the new cases. Using the NTP definition of TB suspects made little difference. CONCLUSIONS: To "End TB", many more TB cases have to be identified. Screening only the highest risk groups identified under 14% of the undetected cases,. To "End TB", medium risk groups will need to be screened. Using a CXR for initial screening results in a much higher yield, at what should be an acceptable cost.

The Global Fund in China: Multidrug-resistant tuberculosis nationwide programmatic scale-up and challenges to transition to full country ownership.

China has the world's second largest burden of multidrug-resistant tuberculosis (MDR-TB; resistance to at least isoniazid and rifampicin), with an estimated 57,000 cases (range, 48,000-67,000) among notified pulmonary TB patients in 2015. During October 1, 2006-June 30, 2014, China expanded MDR-TB care through a partnership with the Global Fund to Fight AIDS, Tuberculosis, and Malaria (Global Fund). We analyzed data on site expansion, patient enrolment, treatment outcomes, cost per patient, and overall programme expenditure. China expanded MDR-TB diagnostic and treatment services from 2 prefectures in 2006 to 92 prefectures, covering 921 of the country's 3,000 counties by June 2014. A total of 130,910 patients were tested for MDR-TB, resulting in 13,744 laboratory-confirmed cases, and 9,183 patients started on MDR-TB treatment. Treatment success was 48.4% (2011 cohort). The partnership between China and the Global Fund resulted in enormous gains. However, changes to health system TB delivery and financing coincided with the completion of the Global Fund Programme, and could potentially impact TB and MDR-TB control. Transition to full country financial ownership is proving difficult, with a decline in enrollment and insufficient financial coverage. Given needed improvement to the current treatment success rates, these factors jeopardise investments made for MDR-TB control and care. China now has a chance to cement its status in TB control by strengthening future financing and ensuring ongoing commitment to quality service delivery.

Effect of a comprehensive programme to provide universal access to care for sputum-smear-positive multidrug-resistant tuberculosis in China: a before-and-after study.

BACKGROUND: China has a quarter of all patients with multidrug-resistant tuberculosis (MDRTB) worldwide, but less than 5% are in quality treatment programmes. In a before-and-after study we aimed to assess the effect of a comprehensive programme to provide universal access to diagnosis, treatment, and follow-up for MDRTB in four Chinese cities (population 18 million). METHODS: We designated city-level hospitals in each city to diagnose and treat MDRTB. All patients with smear-positive pulmonary tuberculosis diagnosed in Center for Disease Control (CDC) clinics and hospitals were tested for MDRTB with molecular and conventional drug susceptibility tests. Patients were treated with a 24 month treatment package for MDRTB based on WHO guidelines. Outpatients were referred to the CDC for directly observed therapy. We capped total treatment package cost at US$4644. Insurance reimbursement and project subsidies limited patients' expenses to 10% of charges for services within the package. We compared data from a 12 month programme period (2011) to those from a retrospective survey of all patients with MDRTB diagnosed in the same cities during a baseline period (2006-09). FINDINGS: 243 patients were diagnosed with MDRTB or rifampicin-resistant tuberculosis during the 12 month programme period compared with 92 patients (equivalent to 24 per year) during the baseline period. 172 (71%) of 243 individuals were enrolled in the programme. Time from specimen collection for resistance testing to treatment initiation decreased by 90% (from median 139 days [IQR 69-207] to 14 days [10-21]), the proportion of patients who started on appropriate drug regimen increased 2·7 times (from nine [35%] of 26 patients treated to 166 [97%] of 172), and follow-up by the CDC after initial hospitalisation increased 24 times (from one [4%] of 23 patients to 163 [99%] of 164 patients). 6 months after starting treatment, the proportion of patients remaining on treatment increased ten times (from two [8%] of 26 patients to 137 [80%] of 172), and 116 (67%) of 172 patients in the programme period had negative cultures or clinical-radiographic improvement. Patients' expenses for hospital admission after MDRTB diagnosis decreased by 78% (from $796 to $174), reducing the ratio of patients' expenses to annual household income from 17·6% to 3·5% (p<0·0001 for all comparisons between baseline and programme periods). However, 36 (15%) patients did not start or had to discontinue treatment in the programme period because of financial difficulties. INTERPRETATION: This comprehensive programme substantially increased access to diagnosis, quality treatment, and affordable treatment for MDRTB. The programme could help China to achieve universal access to MDRTB care but greater financial risk protection for patients is needed. FUNDING: Bill & Melinda Gates Foundation.