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Abstract Background Under a changing climate, the joint effects of temperature and relative humidity on tuberculosis (TB) are poorly understood. To address this research gap, we conducted a time-series study to explore the joint effects of temperature and relative humidity on TB incidence in China, considering potential modifiers. Methods Weekly data on TB cases and meteorological factors in 22 cities across mainland China between 2011 and 2020 were collected. The proxy indicator for the combined exposure levels of temperature and relative humidity, Humidex, was calculated. First, a quasi-Poisson regression with the distributed lag non-linear model (DLNM) was constructed to examine the city-specific associations between humidex and TB incidence. Second, a multivariate meta-regression model was used to pool the city-specific effect estimates, and to explore the potential effect modifiers. Results A total of 849,676 TB cases occurred in the 22 cities between 2011 and 2020. Overall, a conspicuous J-shaped relationship between humidex and TB incidence was discerned. Specifically, a decrease in humidex was positively correlated with an increased risk of TB incidence, with a maximum relative risk (RR) of 1.40 (95% CI: 1.11–1.76). The elevated RR of TB incidence associated with low humidex (5th humidex) appeared on week 3 and could persist until week 13, with a peak at approximately week 5 (RR: 1.03, 95% CI: 1.01–1.05). The effects of low humidex on TB incidence vary by Natural Growth Rate (NGR) levels. Conclusion A J-shaped exposure-response association existed between humidex and TB incidence in China. Humidex may act as a better predictor to forecast TB incidence compared to temperature and relative humidity alone, especially in regions with higher NGRs.

BackgroundThe COVID-19 pandemic has disrupted the diagnosis, treatment, and care for tuberculosis (TB). Delays in seeking TB care may result in increased community transmission and unfavorable treatment outcomes. We sought to understand the influence of the COVID-19 pandemic on the proportion of patients with TB who delayed seeking the diagnosis and care for TB and explore the reasons for their postponement.MethodsWe surveyed a representative sample of outpatients treated for pulmonary TB from June to November 2020 using an anonymous standardized questionnaire. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CIs) of factors associated with the postponement of TB care. We used routinely collected surveillance data to assess trends of TB reports before and after the emergence of COVID-19 (2017–2019 vs. 2020–2022) in Tianjin, China.ResultsAmong 358 participants who were diagnosed with pulmonary TB during the COVID-19 response, 61 (17%) postponed seeking TB diagnosis due to COVID-19, with 39 (64%) citing fear as the primary reason. Female sex (aOR:2.0; 95% CI: 1.1–3.7), previous antituberculosis treatment (aOR:3.2; 95%CI: 1.4–7.6), and TB diagnosis during the first-level response (aOR = 3.2, 1.7–6.2) were associated with the postponement. Among all 518 participants receiving antituberculosis treatment, 57 (11%) had postponed their regular healthcare visits due to COVID-19, 175 (34%) received no treatment supervision, and 32 (6%) experienced treatment interruption. Compared to 2017–2019, reported pulmonary TB declined by 36.8% during the first-level response to COVID-19, 23.5% during the second-level response, 14% during the third-level response in 2020, and 4.3% in 2021.ConclusionThe COVID-19 response reduced the number of people who sought and received diagnosis, treatment, and care for TB in Tianjin, China. Integrative programs to ensure access and continuity of TB services should be considered and dual testing for SARS-CoV-2 and M. tuberculosis may facilitate finding cases.

Abstract Background Bacteriological confirmation (BC) proportion among notified pulmonary TB patients in China is among the lowest in the world. This study was to understand the yield of BC using different testing strategies and patient-level factors associated with BC among pulmonary TB patients in Tianjin, China during 2017–2018. Methods A retrospective study was conducted, enrolling pulmonary TB patients reported to National TB Information Management System (TBIMS) in Tianjin during 2017–2018. BC was defined as a positive result by any of the followings: smear microscopy, culture, or nucleic acid amplification test. Individual characteristics were compared between patients with positive and negative bacteriological results using contingency tables and χ2 test. Multivariable logistic regression was applied to analyze factors associated with BC, calculating adjusted odds ratios (aOR) and 95% confidence intervals (CI) (α = 0.05). Results Of 6364 reported patients, 4181 (65.7%) were bacteriologically confirmed. Positivity proportion was 43.1% (2746/6364) for smear microscopy, 57.7% (3380/5853) for culture, 61.7% (1608/2605) for Xpert® MTB/RIF assay (Xpert) and 73.4% (1824/2484) for combination of the three. The unemployed (aOR = 1.5, 95% CI: 1.0–2.2) and farmers (aOR = 1.7, 95% CI: 1.1–2.8) compared with students; diagnosis by inpatient hospitals compared with TB clinics (aOR = 3.4, 95% CI: 2.6–4.4); having symptoms for ≥2 weeks (aOR = 1.4, 95% CI: 1.1–1.8); cough (aOR = 2.2, 95% CI: 1.8–2.8); blood sputum (aOR = 1.5, 95% CI: 1.0–2.2); cavitation on chest X-ray (aOR = 3.3, 95% CI: 2.5–4.3); bilateral lung lobes affected (aOR = 1.7, 95% CI: 1.4–2.2) were factors associated with BC. Conclusions Combination test was an effective way to improve BC among pulmonary TB patients. Being unemployed, farmers, having prolonged symptoms, and more severe in TB condition were factors associated with BC. We recommend combination of tests to improve BC for pulmonary TB patients, especially who are in early stage of the disease or with conditions tend to be bacteriologically negative.

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.

Objective To investigate the cost-effectiveness of a comprehensive programme for drug-resistant tuberculosis launched in four sites in China in 2011. Methods In 2011-2012, we reviewed the records of 172 patients with drug- resistant tuberculosis who enrolled in the comprehensive programme and we collected relevant administrative data from hospitals and China's public health agency. For comparison, we examined a cohort of 81 patients who were treated for drug-resistant tuberculosis in 2006-2009. We performed a cost-effectiveness analysis, from a societal perspective, that included probabilistic uncertainty. We measured early treatment outcomes based on three-month culture results and modelled longer-term outcomes to facilitate estimation of the comprehensive programme's cost per disability-adjusted life- year (DALY) averted. Findings The comprehensive programme cost 8837 United States dollars (US$) per patient treated. Low enrolment rates meant that some fixed costs were higher, per patient, than expected. Although the comprehensive programme appeared 30 times more costly than the previous one, it resulted in greater health benefits. The comprehensive programme, which cost US$ 639 (95% credible interval: 112 to 1322) per DALY averted, satisfied the World Health Organization's criterion for a very cost-effective intervention. Conclusion The comprehensive programme, which included rapid screening, standardized care and financial protection, improved individual outcomes for MDR tuberculosis in a cost-effective manner. To support post-2015 global heath targets, the comprehensive programme should be expanded to non-residents and other areas of China. [TEXT NOT REPRODUCIBLE IN ASCII] Objectif Etudier le rapport cout-efficacite d'un programme global de lutte contre la tuberculose pharmacoresistante lance en 2011 dans quatre regions chinoises. Methodes En 2011-2012, nous avons analyse les dossiers de 172 patients atteints de tuberculose pharmacoresistante qui s'etaient inscrits a ce programme global et nous avons collecte des donnees administratives pertinentes aupres de differents hopitaux et de l'agence de sante publique chinoise. A titre de comparaison, nous avons examine une cohorte de 81 patients soignes pour une tuberculose pharmacoresistante entre 2006 et 2009. Nous avons realise une analyse cout-efficacite, sur le plan societal, qui incluait une Incertitude probabiliste. Nous avons mesure les resultats du traitement precoce en fonction de resultats de culture sur trois mois et modelise les resultats a long terme pourfaciliter l'estimation du cout du programme global par annee de vie corrigee du facteur incapacite (AVCI) evitee. Resultats Le programme global coute 8837 dollars des Etats-Unis (US$) par patient soigne. Le faible taux d'inscription signifiait que certains couts fixes par patient etaient plus importants que prevu. Bien que ce programme global se soit revele 30 fois plus cher que le precedent, il a debouche surdes avantages accrus en matiere de sante. Le programme global, qui coute 639 US$ (intervalle de credibilite a 95 %: 112 a 1322) par AVCI evitee, satisfait au critere de l'Organisation mondiale de la Sante definissant une Intervention tres rentable. Conclusion Le programme global, qui Incluait un depistage rapide, des soins standardises et une protection financiere, a ameliore les resultats des patients atteints de tuberculose multiresistante en limitant les depenses. Afin de soutenir les objectifs mondiaux pour l'apres-2015 en matiere de sante, le programme global devrait etre elargi aux nonresidents et a d'autres regions de Chine. [TEXT NOT REPRODUCIBLE IN ASCII] Objetivo Investigar la costoeficacia de un programa integral para la tuberculosis farmacorresistente lanzado en cuatro localizaciones de China en 2011. Metodos En 2011-2012, se revisaron los informes de 172 pacientes con tuberculosis farmacorresistente que se habian inscrito en el programa Integral y se recogieron datos administrativos relevantes de hospitales y la agenda de salud publica de China. Como termino de comparacion, se examino un cohorte de 81 pacientes que habian sido tratados para la tuberculosis farmacorresistente en 2006-2009. Se llevo a cabo un analisis de costoeficacia desde una perspectiva societaria que incluia la incertidumbre probabilistlca. Se midieron los resultados de los tratamientos tempranos basados en los resultados de un cultivo de tres meses y se modelaron resultados a largo plazo para facilitar la estimacion del coste del programa integral de anos de vida en funcion de la discapacidad (AVAD) evitada. Resultados El programa integral costo 8.837 dolares estadounidenses (USD) por paciente tratado. Las bajas tasas de inscripcion significaban que algunos de los costes fijos eran mayores por paciente que lo esperado. A pesar de que el programa integral parecia 30 veces mas costoso que el anterior, tuvo como resultado unos mejores beneficios para la salud. El programa integral, que costo 639 USD (Intervalo de credibilidad del 95%: de 112 a 1.322) por AVAD evitado, satisfizo el criterio de la Organizacion Mundial de la Salud en cuanto a Intervenciones muy costoefectivas. Conclusion El programa integral, que incluia un examen rapido, cuidados estandar y proteccion financiera, mejoro los resultados individuales de la tuberculosis multirresistente (MR) de una manera costoefectiva. Para apoyar los objetivos de salud globales posteriores a 2015, el programa integral deberia expandirse a no residentes y otras areas de China., Introduction China has more than halved tuberculosis prevalence and mortality since 1990, from 215 cases and 19 deaths per 100 000 population to 108 cases and 4 deaths per 100 [...]

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

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. [ABSTRACT FROM AUTHOR]

Tuberculosis is a disease of poverty that claims the lives of over a million people annually. (1) Globally, tuberculosis is concentrated in low- to middle-income countries. The five countries--Brazil, the [...]

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. [ABSTRACT FROM AUTHOR]

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, AUC0-8, 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 AUC0-8 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 AUC08 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. [ABSTRACT FROM AUTHOR]

Background: In response to the COVID-19 epidemic, China implemented a series of interventions that impacted tuberculosis (TB) control in the country., Methods: Based on routine surveillance data and questionnaires, the study analyzed TB notification, follow-up examinations, and treatment outcomes. The data were split into three phases in relation to outbreak, lockdown and reopen when the nationwide COVID-19 response started in 2020: control (11 weeks prior), intensive (11 weeks during and immediately after), and regular (4 additional weeks). Data from 2017-2019 were used as baseline., Findings: The notified number of TB patients decreased sharply in the 1 st week of the intensive period but took significantly longer to rebound in 2020 compared with baseline. The percentages of TB patients undergoing sputum examination within one week after 2 months treatment and full treatment course in the intensive period were most affected and decreased by 8% in comparison with control period. 75•2% (221/294) of counties reallocated CDC and primary health care workers to fight the COVID-19 epidemic, 26•9% (725/2694) of TB patients had postponed or missed their follow-up examinations due to travel restrictions and fear of contracting COVID-19., Interpretation: In the short term, the COVID-19 epidemic mostly affected TB notification and follow-up examinations in China, which may lead to a surge of demand for TB services in the near future. To cope with this future challenge, an emergency response mechanism for TB should be established., Funding: National Health Commission of China-Bill & Melinda Gates Foundation TB Collaboration project (OPP1137180)., Competing Interests: The authors have no competing interests., (© 2020 The Authors. Published by Elsevier Ltd.)