Summary 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.
Summary 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.
Abstract Background Fixed-dose combination (FDC) formulations for the treatment of tuberculosis are now being recommended by the World Health Organization and used worldwide for reducing the risk of ...emerging drug resistance. China also plans that the FDC coverage will be achieved 100% in 2015 in every county in the country. However, the quality of FDCs with respect to variable bioavailability is a major issue. Objectives This study was conducted in healthy Chinese subjects to compare the bioavailability of rifampicin, isoniazid, ethambutol, and pyrazinamide from a 4-drug FDC formulation versus that of the separate formulations. Methods The study was designed as randomized, single-dose, 2-treatment, 2-period crossover trial with a washout period of 1 week. Blood samples were collected at 0 (baseline), 10, 20, and 40 minutes and at 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose. Plasma concentrations of the 4 drugs were measured by using a rapid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated by using noncompartmental methods. Bioequivalence was determined if the 90% CIs of the log-transformed test/reference ratios AUC0–24 , AUC0–∞ , and Cmax were within the predetermined range of 80% to 125%. Tolerability was assessed by using clinical parameters and subject reports. Results A total of 18 male subjects (mean SD age, 36.4 10.6 years) were enrolled and completed the study. In the case of rifampicin, the 90% CIs for the log-transformed ratios of Cmax , AUC0–24 , and AUC0–∞ were 81.8 to 100.9, 89.5 to 100.2, and 87.1 to 98.0, respectively. For ethambutol, these values were 84.7 to 105.7, 93.5 to 105.1, and 92.1 to 105.4. For pyrazinamide, these values were 83.3 to 93.9, 95.8 to 101.4, and 97.0 to 104.1. For isoniazid, the 90% CIs for the log-transformed ratios of AUC0–24 , and AUC0∞ were 83.5 to 94.6 and 83.4 to 94.4. However, the point estimates for Cmax (62.2–86.7) were outside the limit for bioequivalence. No adverse events were observed during the study. Conclusions The findings from this single-dose study in healthy Chinese male volunteers suggest that the combined formulation was bioequivalent to separate formulations of rifampicin, ethambutol, and pyrazinamide at the same dose levels. However, isoniazid was not bioequivalent based on Cmax values. Both formulations were well tolerated. Chinese Clinical Trials registration number: ChiCTR-TTRCC-12002451.
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