Shiming Cheng

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.

Latent tuberculosis infection in rural China: baseline results of a population-based, multicentre, prospective cohort study

BACKGROUND Prophylactic treatment of individuals with latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control in some settings. In China, the prevalence of latent tuberculosis infection, and preventive interventions against this disease, have not been systematically studied. We aimed to assess the prevalence of latent tuberculosis and its associated risk factors in rural populations in China. METHODS Between July 1, and Sept 30, 2013, we undertook a baseline survey of a population-based, multicentre, prospective cohort study of registered residents (≥5 years old) at four study sites in rural China. Eligible participants were identified by door-to-door survey with a household sampling design. We screened participants for active tuberculosis and history of tuberculosis then used a tuberculin skin test and an interferon-γ release assay (QuantiFERON [QFT]) to test for latent infection. We used odds ratios (ORs) and 95% CIs to assess variables associated with positivity of QFT and tuberculin skin tests. FINDINGS 21,022 (90%) of 23,483 eligible participants completed a baseline survey. Age-standardised and sex-standardised rates of skin-test positivity (≥10 mm) ranged from 15% to 42%, and QFT positivity rates ranged from 13% to 20%. Rates of positivity for the tuberculin skin test and the QFT test were low in study participants younger than 20 years and gradually increased with age (p for trend <0·0001). Rates of latent tuberculosis infection were higher for men than women (p<0·0001). Overall agreement between the tuberculin skin test and the QFT test was moderate (81·06%; kappa coefficient 0·485), with skin-test-only positive results associated with the presence of BCG scar, male sex, and ages of 60 years and older, and QFT-only positive results associated with male sex and ages of 60 years and older. INTERPRETATION On the basis of findings showing that the performance of the tuberculin skin test might be affected by various factors including BCG vaccination and age, our results suggest that the prevalence of latent tuberculosis in China might be overestimated by skin tests compared with interferon-γ release assays. FUNDING The National Science and Technology Major Project of China, the Program for Changjiang Scholars and Innovative Research Team in University of China.

Effectiveness of Electronic Reminders to Improve Medication Adherence in Tuberculosis Patients: A Cluster-Randomised Trial.

Background Mobile text messaging and medication monitors (medication monitor boxes) have the potential to improve adherence to tuberculosis (TB) treatment and reduce the need for directly observed treatment (DOT), but to our knowledge they have not been properly evaluated in TB patients. We assessed the effectiveness of text messaging and medication monitors to improve medication adherence in TB patients. Methods and Findings In a pragmatic cluster-randomised trial, 36 districts/counties (each with at least 300 active pulmonary TB patients registered in 2009) within the provinces of Heilongjiang, Jiangsu, Hunan, and Chongqing, China, were randomised using stratification and restriction to one of four case-management approaches in which patients received reminders via text messages, a medication monitor, combined, or neither (control). Patients in the intervention arms received reminders to take their drugs and reminders for monthly follow-up visits, and the managing doctor was recommended to switch patients with adherence problems to more intensive management or DOT. In all arms, patients took medications out of a medication monitor box, which recorded when the box was opened, but the box gave reminders only in the medication monitor and combined arms. Patients were followed up for 6 mo. The primary endpoint was the percentage of patient-months on TB treatment where at least 20% of doses were missed as measured by pill count and failure to open the medication monitor box. Secondary endpoints included additional adherence and standard treatment outcome measures. Interventions were not masked to study staff and patients. From 1 June 2011 to 7 March 2012, 4,292 new pulmonary TB patients were enrolled across the 36 clusters. A total of 119 patients (by arm: 33 control, 33 text messaging, 23 medication monitor, 30 combined) withdrew from the study in the first month because they were reassessed as not having TB by their managing doctor (61 patients) or were switched to a different treatment model because of hospitalisation or travel (58 patients), leaving 4,173 TB patients (by arm: 1,104 control, 1,008 text messaging, 997 medication monitor, 1,064 combined). The cluster geometric mean of the percentage of patient-months on TB treatment where at least 20% of doses were missed was 29.9% in the control arm; in comparison, this percentage was 27.3% in the text messaging arm (adjusted mean ratio [aMR] 0.94, 95% CI 0.71, 1.24), 17.0% in the medication monitor arm (aMR 0.58, 95% CI 0.42, 0.79), and 13.9% in the combined arm (aMR 0.49, 95% CI 0.27, 0.88). Patient loss to follow-up was lower in the text messaging arm than the control arm (aMR 0.42, 95% CI 0.18–0.98). Equipment malfunction or operation error was reported in all study arms. Analyses separating patients with and without medication monitor problems did not change the results. Initiation of intensive management was underutilised. Conclusions This study is the first to our knowledge to utilise a randomised trial design to demonstrate the effectiveness of a medication monitor to improve medication adherence in TB patients. Reminders from medication monitors improved medication adherence in TB patients, but text messaging reminders did not. In a setting such as China where universal use of DOT is not feasible, innovative approaches to support patients in adhering to TB treatment, such as this, are needed. Trial Registration Current Controlled Trials, ISRCTN46846388

Effect of Diagnostic and Treatment Delay on the Risk of Tuberculosis Transmission in Shenzhen, China: An Observational Cohort Study, 1993–2010

Introduction To understand better the risk of tuberculosis transmission with increasing delay in tuberculosis treatment, we undertook a retrospective cohort study in Shenzhen, China. Methods All pulmonary tuberculosis cases in the Shenzhen tuberculosis surveillance database from 1993–2010 were included. Sputum smear positivity and presence of pulmonary cavity were used as proxies for risk of tuberculosis transmission. Results Among 48,441pulmonary tuberculosis cases, 70% presented with symptoms of pulmonary TB, 62% were sputum smear positive, and 21% had a pulmonary cavity on chest x-ray. 95.3% of patients self-presented for evaluation of illness after a median 58 days of delay after symptoms began. The proportion presenting sputum smear positive (p<0.001) and with a pulmonary cavity (p<0.001) increased significantly with increasing duration of delay. Conclusions Delayed diagnosis and treatment of tuberculosis is associated with a significantly increased risk of pulmonary sputum smear positivity and pulmonary cavity. To decrease risk of transmission, treatment delay needs to be reduced further.

Electronic recording and reporting system for tuberculosis in China: experience and opportunities

Tuberculosis (TB) surveillance in China is organized through a nationwide network of about 3200 hospitals and health facilities. In 2005, an electronic Tuberculosis Information Management System (TBIMS) started to be phased in to replace paper recording. The TBIMS collects key information on TB cases notified in TB care facilities, and exchanges real-time data with the Infectious Disease Reporting System, which covers the countrys 37 notifiable diseases. The system is accessible to authorized users at every level of the TB network through a password-protected website. By 2009 the TBIMS achieved nationwide coverage. Completeness of data on patient bacteriological end points improved remarkably over time. Data on about a million active TB cases, including drug-resistant TB, are included each year. The sheer scale of the data handling and the intricate functions that the China TBIMS performs makes it stand apart from the electronic information systems for TB adopted in other countries.

Space-time clustering characteristics of tuberculosis in China, 2005-2011.

Objectives China is one of the 22 tuberculosis (TB) high-burden countries in the world. As TB is a major public health problem in China, spatial analysis could be applied to detect geographic distribution of TB clusters for targeted intervention on TB epidemics. Methods Spatial analysis was applied for detecting TB clusters on county-based TB notification data in the national notifiable infectious disease case reporting surveillance system from 2005 to 2011. Two indicators of TB epidemic were used including new sputum smear-positive (SS+) notification rate and total TB notification rate. Global Moran’s I by ArcGIS was used to assess whether TB clustering and its trend were significant. SaTScan software that used the retrospective space-time analysis and Possion probability model was utilized to identify geographic areas and time period of potential clusters with notification rates on county-level from 2005 to 2011. Results Two indicators of TB notification had presented significant spatial autocorrelation globally each year (p<0.01). Global Moran’s I of total TB notification rate had positive trend as time went by (t=6.87, p<0.01). The most likely clusters of two indicators had similar spatial distribution and size in the south-central regions of China from 2006 to 2008, and the secondary clusters in two regions: northeastern China and western China. Besides, the secondary clusters of total TB notification rate had two more large clustering centers in Inner Mongolia, Gansu and Qinghai provinces and several smaller clusters in Shanxi, Henan, Hebei and Jiangsu provinces. Conclusion The total TB notification cases clustered significantly in some special areas each year and the clusters trended to aggregate with time. The most-likely and secondary clusters that overlapped among two TB indicators had higher TB burden and risks of TB transmission. These were the focused geographic areas where TB control efforts should be prioritized.

The Prevalence and Incidence of Latent Tuberculosis Infection and Its Associated Factors among Village Doctors in China

Background China is a high tuberculosis (TB) burden country. More than half of acute TB cases first seek medical care in village doctors’ clinics or community health centers. Despite being responsible for patient referral and management, village doctors are not systematically evaluated for TB infection or disease. We assessed prevalence and incidence of latent TB infection (LTBI) among village doctors in China. Methods and Findings A longitudinal study was conducted in Inner Mongolia Autonomous Region. We administered a questionnaire on demographics and risk factors for TB exposure and disease; Tuberculin skin testing (TST) and QuantiFERON-TB Gold in-tube assay (QFT-GIT) was conducted at baseline and repeated 12 months later. We used a logistic regression model to calculate adjusted odds ratios (ORs) for risk factors for TST and QFT-GIT prevalence and incidence. At the time of follow up, 19.5% of the 880 participating village doctors had a positive TST and 46.0% had a positive QFT-GIT result. Factors associated with TST prevalence included having a BCG scar (OR = 1.45, 95%CI 1.03–2.04) and smoking (OR = 1.69, 95%CI 1.17–2.44). Risk factors associated with QFT-GIT prevalence included being male (OR = 2.17, 95%CI 1.63–2.89), below college education (OR=1.42, 95%CI 1.01–1.97), and working for ≥25 years as a village doctor (OR = 1.64, 95%CI 1.12–2.39). The annual incidence of LTBI was 11.4% by TST and 19.1% by QFT-GIT. QFT-GIT conversion was associated with spending 15 minutes or more per patient on average (OR = 2.62, 95%CI 1.39–4.97) and having BCG scar (OR = 0.53, 95%CI 0.28–1.00). Conclusions Prevalence and incidence of LTBI among Chinese village doctors is high. TB infection control measures should be strengthened among village doctors and at village healthcare settings.

Annual risk of tuberculosis infection in rural China: a population-based prospective study

Prospective population data on the incidence of tuberculosis (TB) infection has been sparsely reported in the global literature. A population-based prospective study was conducted in rural China to investigate the annual risk of TB infection, and its persistence using serial tuberculin skin tests (TSTs) and an interferon-γ release assay. In total, 13 580 eligible participants from four rural sites, identified as TST negative (<10 mm) or QuantiFERON-TB Gold In-Tube (QFT) (an interferon-γ release assay) negative from a baseline survey, were included in the first years follow-up examination. The annual conversion rate of QFT among the study sites ranged between 2.1% and 4.9% (average 3.1%), and the incidence of TST conversion ranged between 6.0% and 31.1% (average 14.5%). During the second years follow-up, infection persistence was investigated using 390 subjects with QFT conversions. Among them, 49.7% (164 out of 330) were found to be consistently QFT positive. Both the conversion and the persistence of QFT positivity were found to be significantly increased with increasing age. In conclusion, the annual TB infection rate was suggested to be ∼1.5% based on persistent positive results after QFT conversion in rural China. Therefore, infection control among those high-risk populations, including the elderly, should be prioritised for TB control in China. Annual TB infection rate ∼1.5% in rural China, based on persistent positive results after IGRA conversion http://ow.ly/4n95Cw

Combining Domestic and Foreign Investment to Expand Tuberculosis Control in China

Jia and colleagues describe how a combination of increased domestic funding, supplemented by foreign loans and donations since 2002, have led to a dramatic increase in tuberculosis case finding in China.

Tuberculosis control in China: striving for sustainability

www.thelancet.com Vol 379 June 9, 2012 2149 with high HIV infection rates, a large burden of therapeutically destitute patients reside in the community, often in overcrowded single-roomed or informal housing, continue to seek employment, travel for social and other reasons, and are often admitted to local health facilities (not equipped with infection control measures) for acute symptomatic deterioration as the disease worsens. Our own experience is that many patients realise the implications of their disease and want to minimise harm to others, but have no alternatives. Currently, there is no nationwide programme to fund and facilitate infection control within households in South Africa. Even in eastern Europe, an important proportion of these patients have alcohol use disorders or inject drugs, and live outside both the hospital system and traditional homes. The preference in some eastern European countries to redirect, whenever possible, management of these patients to home-care services is promising. A multipronged approach is needed. We believe that there is an urgent need to improve health services supporting XDR tuberculosis treatment and to off er palliative care when appropriate. Thus, integrated models are necessary to tackle this growing problem in diff erent settings, including domiciliary care, community-supported housing, and specialised institutional facilities (if we want to abolish the word “sanatoria”) off ering appropriate care. We all have a common enemy in XDR tuberculosis.