A hierarchical model for analyzing multisite individual-level disease surveillance data from multiple systems.

Passive surveillance systems are widely used to monitor diseases occurrence over wide spatial areas due to their cost-effectiveness and integration into broadly distributed healthcare systems. However, such systems are generally associated with imperfect ascertainment of disease cases and with heterogeneous capture probabilities arising from factors such as differential access to care. Augmenting passive surveillance systems with other surveillance efforts provides a way to estimate the true number of incident cases. We develop a hierarchical modeling framework for analyzing data from multiple surveillance systems that allows for individual-level covariate-dependent heterogeneous capture probabilities, and borrows information across surveillance sites to improve estimation of the true number of incident cases. Inference is carried out via a two-stage Bayesian procedure. Simulation studies illustrated superior performance of the proposed approach with respect to bias, root mean square error, and coverage compared to a model that does not borrow information across sites. We applied the proposed model to data from three surveillance systems reporting pulmonary tuberculosis (PTB) cases in a major center of ongoing transmission in China. The analysis yielded bias-corrected estimates of PTB cases from the passive system and led to the identification of risk factors associated with PTB rates, as well as factors influencing the operating characteristics of the implemented surveillance systems.

Assessing the influencing factors of out-of-pocket costs on tuberculosis in Sichuan Province: a cross-sectional study.

BACKGROUND: Although diagnosis and treatment services for tuberculosis (TB) are provided free of charge in most countries, direct non-medical and indirect costs due to absenteeism, also place a significant burden on patients and their families. Sichuan Province has the second highest incidence of TB in China, with an incidence of approximately 100 cases per 100 000 people. However, there are limited research on out-of-pocket expenditure (OOPE) and its influencing factors in TB patients in Sichuan Province. METHODS: A retrospective cross-sectional study was conducted on TB patients in designated medical institutions for TB in Sichuan Province from 2017-2021. A face-to-face questionnaire was conducted to obtain the information related to hospitalization of patients, and the multi-level regression model was used to analyse the factors that influence OOPE and total out-of-pocket expenditure (TOOPE) of TB patients. RESULTS: A total of 2644 patients were investigated, and 74.24% of TB patients and their families experienced catastrophic total costs due to TB. The median total cost was 9223.37 CNY (1429.98 USD), in which the median direct and indirect costs of TB patients were 10185.00 CNY (1579.07 USD) and 2400.00 CNY (372.09 USD), respectively, and indirect costs contributed to 43% of total costs. The median OOPE and TOOPE costs were 6024.00 CNY (933.95 USD) and 11890.50 CNY (1843.49 USD), respectively. OOPE and TOOPE had common influencing factors including whether the patient's family had four or more members, a history of hospitalization, combination with other types of TB, the number of visits before diagnosis, and co-occurrence with chronic disease. CONCLUSIONS: The OOPE and TOOPE for TB patients and their families in Sichuan Province are still heavy. In the long run, it is necessary to strengthen education and awareness campaigns on TB related knowledge, disseminate basic medical knowledge to the public, improve healthcare-seeking behavior, and enhance the healthcare infrastructure to improve the accuracy of TB diagnosis and reduce the significant OOPE and TOOPE faced by TB patients and their families in Sichuan Province.

Prenatal and early-life exposure to the Great Chinese Famine increased the risk of tuberculosis in adulthood across two generations.

Global food security is a major driver of population health, and food system collapse may have complex and long-lasting effects on health outcomes. We examined the effect of prenatal exposure to the Great Chinese Famine (1958-1962)-the largest famine in human history-on pulmonary tuberculosis (PTB) across consecutive generations in a major center of ongoing transmission in China. We analyzed >1 million PTB cases diagnosed between 2005 and 2018 in Sichuan Province using age-period-cohort analysis and mixed-effects metaregression to estimate the effect of the famine on PTB risk in the directly affected birth cohort (F1) and their likely offspring (F2). The analysis was repeated on certain sexually transmitted and blood-borne infections (STBBI) to explore potential mechanisms of the intergenerational effects. A substantial burden of active PTB in the exposed F1 cohort and their offspring was attributable to the Great Chinese Famine, with more than 12,000 famine-attributable active PTB cases (>1.23% of all cases reported between 2005 and 2018). An interquartile range increase in famine intensity resulted in a 6.53% (95% confidence interval [CI]: 1.19-12.14%) increase in the ratio of observed to expected incidence rate (incidence rate ratio, IRR) in the absence of famine in F1, and an 8.32% (95% CI: 0.59-16.6%) increase in F2 IRR. Increased risk of STBBI was also observed in F2. Prenatal and early-life exposure to malnutrition may increase the risk of active PTB in the exposed generation and their offspring, with the intergenerational effect potentially due to both within-household transmission and increases in host susceptibility.

Spatio-temporal analysis of socio-economic characteristics for pulmonary tuberculosis in Sichuan province of China, 2006-2015.

BACKGROUND: The disease burden caused by pulmonary tuberculosis (TB) in Sichuan province still persisted at a high level, and large spatial variances were presented across regional distribution disparities. The socio-economic factors were suspected to affect the population of TB notification, we aimed to describe TB case notification rate (CNR) and identify which factors influence TB epidemic are necessary for the prevention and control of the disease in Sichuan province. METHODS: A retrospective cross-sectional study and an ecological spatial analysis was conducted to quantify the presence and location of spatial clusters of TB by the Moran's I index and examined these patterns with socio-economic risk factors by hierarchical Bayesian spatio-temporal model. RESULTS: A total of 630,009 pulmonary TB cases were notified from 2006 to 2015 in 181 counties of Sichuan province. The CNR decreased year by year since 2007, from 88.70 to 61.37 per 100,000 persons. The spatial heterogeneities of CNR were observed during the study periods. Global Moran's I index varied from 0.23 to 0.44 with all P-value < 0.001. The Bayesian spatio-temporal model with parametric spatio-temporal interactions was chosen as the best model according to the minimum of Deviance Information Criterion (DIC)(19,379.01), and in which the quadratic form of time was taken. The proportion of age group and education year were all associated with CNR after adjusting the spatial effect, temporal effect and spatio-temporal interactions. TB CNR increased by 10.2% [95% credible interval (CI): 6.7-13.7%] for every 1-standard-deviation increase in proportion of age group and decreased by 23% (95% CI: 13.7-32.7%) for every 1-standard-deviation increase in education year. CONCLUSIONS: There were spatial clusters of TB notification rate in Sichuan province from 2006 to 2015, and heavy TB burden was mainly attributed to aging and low socioeconomic status including poor education. Thus, it is more important to pay more attention to the elderly population and improve socioeconomic status including promoting education level in Sichuan province to reduce the TB burden.

Evidence for heterogeneity in China's progress against pulmonary tuberculosis: uneven reductions in a major center of ongoing transmission, 2005-2017.

BACKGROUND: China contributed 8.9% of all incident cases of tuberculosis globally in 2017, and understanding the spatiotemporal distribution of pulmonary tuberculosis (PTB) in major transmission foci in the country is critical to ongoing efforts to improve population health. METHODS: We estimated annual PTB notification rates and their spatiotemporal distributions in Sichuan province, a major center of ongoing transmission, from 2005 to 2017. Time series decomposition was used to obtain trend components from the monthly incidence rate time series. Spatiotemporal cluster analyses were conducted to detect spatiotemporal clusters of PTB at the county level. RESULTS: From 2005 to 2017, 976,873 cases of active PTB and 388,739 cases of smear-positive PTB were reported in Sichuan Province, China. During this period, the overall reported incidence rate of active PTB decreased steadily at a rate of decrease (3.77 cases per 100,000 per year, 95% confidence interval (CI): 3.28-4.31) that was slightly faster than the national average rate of decrease (3.14 cases per 100,000 per year, 95% CI: 2.61-3.67). Although reported PTB incidence decreased significantly in most regions of the province, incidence was observed to be increasing in some counties with high HIV incidence and ethnic minority populations. Active and smear-positive PTB case reports exhibited seasonality, peaking in March and April, with apparent links to social dynamics and climatological factors. CONCLUSIONS: While PTB incidence rates decreased strikingly in the study area over the past decade, improvements have not been equally distributed. Additional surveillance and control efforts should be guided by the seasonal-trend and spatiotemporal cluster analyses presented here, focusing on areas with increasing incidence rates, and updated to reflect the latest information from real-time reporting.

Predictors of death among TB/HIV co-infected patients on tuberculosis treatment in Sichuan, China: A retrospective cohort study.

Mycobacterium tuberculosis is the most common opportunistic infection among patients with human immunodeficiency virus (HIV) infection, and it is also the leading cause of death, causing approximately one-third of acquired immune deficiency syndrome deaths worldwide. China is on the World Health Organization's global list of 30 high-tuberculosis (TB) burden countries. The objective of this study was to evaluate the mortality rate, survival probabilities, and factors associated with death among patients with TB/HIV co-infection undergoing TB treatment in Sichuan, China. A retrospective cohort study was conducted using the Chinese National TB Surveillance System data of TB/HIV co-infected patients enrolled in TB treatment from January 2020 to December 2020. We calculated the mortality rate and survival probabilities using the Kaplan-Meier estimator, and a Cox proportional hazard model was conducted to identify independent risk factors for TB/HIV co-infection mortality. Hazard ratios and their respective 95% confidence intervals were also reported in this study. Of 828 TB/HIV co-infected patients, 44 (5.31%) died during TB treatment, and the crude mortality rate was 7.76 per 1000 person-months. More than half of the deaths (n = 23) occurred in the first 3 months of TB treatment. Overall survival probabilities were 97.20%, 95.16%, and 91.75% at 3rd, 6th, and 12th month respectively. The independent risk factors for mortality among TB/HIV co-infected patients were having extra-pulmonary TB and pulmonary TB co-infection, history of antiretroviral therapy interruption, and baseline cluster of differentiation 4 T-lymphocyte counts <200 cells/µL at the time of HIV diagnosis. Antiretroviral therapy is important for the survival of TB/HIV co-infected patients, and it is recommended to help prolong life by restoring immune function and preventing extra-pulmonary TB.

Drug Resistance of Mycobacterium tuberculosis Based on Whole-Genome Sequencing in the Yi Ethnic Group, Sichuan Province, China.

This study investigated drug-resistant tuberculosis (DR-TB) in the Yi ethnic group. The study was designed to identify risk factors for DR-TB and its relationship with HIV/AIDS. To establish the resistance to antituberculosis drugs, whole-genome sequencing (WGS) was performed using culture-positive Mycobacterium tuberculosis samples collected from people of the Yi ethnic group from March 2019 to March 2021. Baseline characteristics were obtained from China's tuberculosis surveillance system. A total of 116 M. tuberculosis strains were included in the final analysis. Lineage 2.2 (75.86%) was the dominant sublineage, followed by lineage 4.5 (18.97%) and lineage 4.4 (5.17%). The rates of rifampicin-resistant (RR-TB), multidrug-resistant (MDR-TB), and preextensively drug-resistant TB (pre-XDR-TB) were 18.97%, 10.34%, and 6.03%, respectively. Drug-resistant strains were not found in the elderly (age ≥ 65 years). The proportions of RR/MDR-TB and pre-XDR-TB cases among re-treatment patients were higher than those among new patients (χ 2 = 12.155, P = 0.003; χ 2 = 22.495, P = 0.001, respectively). The pre-XDR-TB case proportions were higher among female patients than among males and higher among referred patients (χ 2 = 5.456, P = 0.032; χ 2 = 15.134, P = 0.002, respectively). The rates of RR/MDR-TB and pre-XDR-TB did not differ appreciably among groups with different HIV infection statuses nor lineage populations. DR-TB poses a serious challenge to the Yi ethnic group. Re-treatment patients, women, and referred patients were at high risk of MDR/RR-TB or pre-XDR-TB while HIV and lineage 2 had negligible association with drug resistance. Whole-genome sequencing should be used to guide the design of treatment regimens and to tailor public interventions.

Treatment outcome and its associated factors among HIV-MTB co-infected patients in Sichuan, China: A retrospective study.

Human immunodeficiency virus (HIV)-Mycobacterium tuberculosis (MTB) co-infection has become a pressing global public health problem. Although tuberculosis (TB) is both treatable and curable, it has been exacerbated by the HIV/acquired immune deficiency syndrome (AIDS) epidemic. HIV-MTB co-infected patients have a variety of disease-specific, and treatment-related factors that can adversely affect their treatment outcomes. This study was conducted to assess the outcomes of TB treatment and its associated factors among HIV-MTB co-infected patients in Sichuan, Southwest China. A retrospective study was performed on HIV-MTB co-infected patients who were diagnosed and registered in TB designated hospitals in Sichuan from January 1, 2016, to December 31, 2020. Data were collected from patients' electronic medical records regarding their demographic, clinical, and social support information, and categorical data, such as sex, were reported using numbers and percentages. χ2 and t-tests were conducted to compare groups in relation to different levels of medical institutions. A binary logistic regression model was used to identify the factors associated with unsuccessful TB treatment outcomes. For logistic regression analysis performed using an α of 0.05, odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated for various risk factors. A total of 3677 registered HIV-MTB co-infected patients were enrolled. After adjusting for other variables, male, advanced age, receiving TB treatment at the municipal medical institution, being diagnosed with external pulmonary TB, referral or tracing, being sputum smear positive, not initiating antiretroviral therapy (ART) and not using fixed-dose combinations were the main risk factors for treatment failure of HIV-MTB co-infected patients in Sichuan province. Sex, age, hospital level, patient source, other diagnostic factors (e.g., sputum smear results, anatomical site of TB), and factors of therapeutic schemes (e.g., antiretroviral therapy, fixed-dose combinations) may serve as risk factors to estimate the likely treatment outcome of HIV-TB co-infection.

A spatial hierarchical model for integrating and bias-correcting data from passive and active disease surveillance systems.

Disease surveillance data are important for monitoring disease burden and occurrence, and for informing a wide range of efforts to improve population health. Surveillance for infectious diseases may be conducted passively, relying on reports from healthcare facilities, or actively, involving surveys of the population at risk. Passive surveillance typically provides wide spatial coverage, but is subject to biases arising from differences in care-seeking behavior, diagnostic practices, and under-reporting. Active surveillance minimizes these biases, but is typically constrained to small areas and subpopulations due to resource limitations. Methods based on linkage of individual records between passive and active surveillance datasets provide a means to estimate and correct for the biases of each system, leveraging the size and coverage of passive surveillance and the quality of data in active surveillance. We develop a spatial Bayesian hierarchical model for bias-correcting data from both systems to yield an improved estimate of disease measures after adjusting for under-ascertainment. We apply the framework to data from a passive and an active surveillance system for pulmonary tuberculosis (PTB) in Sichuan, China, and estimate the average sensitivity of the active surveillance system at 70% (95% credible interval: 62%, 78%), and the passive system at 30% (95% CI: 24%, 35%). Passive surveillance sensitivity exhibited considerable spatial variability, and was positively associated with a site's gross domestic product per capita. Bias-corrected estimates of county-level PTB prevalence in the province in 2010 identified regions in the southeast with the highest PTB burden, yielding different geographic priorities than previous reports.

Access to Bacteriologic-Based Diagnosis in Smear Positive Retreatment Tuberculosis Patients in Rural China: A Cross-Sectional Study in Three Geographic Varied Provinces.

OBJECTIVE: To determine factors influencing the utilization and accessibility to bacteriologic-based tuberculosis (TB) diagnosis among sputum smear positive (SS+) retreatment TB patients, and to develop strategies for improving the case detection rate of MDR-TB in rural China. STUDY DESIGN AND SETTING: A cross-sectional study of SS+ TB retreatment patients was conducted in eight counties from three provinces with different implementation period and strategy of MDR-TB program in China. Demographic and socioeconomic parameters were collected by self-reporting questionnaires. Sputum samples were collected and cultured by the laboratory of county-designated TB clinics and delivered to prefectural Centers for Disease Prevention and Control (CDC) labs for DST with 4 first-line anti-TB drugs. RESULTS: Among the 196 SS+ retreatment patients, 61.22% received culture tests during current treatment. Patients from more developed regions (OR = 24.0 and 3.6, 95% CI: 8.6-67.3 and 1.1-11.6), with better socio-economic status (OR = 3. 8, 95% CI: 1.3-10.7), who had multiple previous anti-TB treatments (OR = 5.0, 95% CI: 1.6-15.9), and who failed in the most recent anti-TB treatment (OR = 2.6, 95% CI: 1.0-6.4) were more likely to receive culture tests. The percentage of isolates resistant to any of first-line anti-TB drugs and MDR-TB were 50.0% (95% CI: 39.8%-60.2%) and 30.4% (95% CI: 21.0%-39.8%) respectively. CONCLUSIONS: Retreatment SS+ TB patients, high risk MDR-TB population, had poor utilization of access to bacteriologic-based TB diagnosis, which is far from optimal. The next step of anti-TB strategy should be focused on how to make bacteriological-based diagnosis cheaper, safer and more maneuverable, and how to assure the DST-guided treatment for these high-risk TB patients.

Prevalence and predictors of HIV among Chinese tuberculosis patients by provider-initiated HIV testing and counselling (PITC): a multisite study in South Central of China.

BACKGROUND: Tuberculosis (TB) and HIV are two worldwide public health concerns. Co-infection of these two diseases has been considered to be a major obstacle for the global efforts in reaching the goals for the prevention of HIV and TB. METHOD: A comprehensive cross-sectional study was conducted to recruit TB patients in three provinces (Guangxi, Henan and Sichuan) of China between April 1 and September 30, 2010. RESULTS: A total of 1,032 consenting TB patients attended this survey during the study period. Among the participants, 3.30% were HIV positive; about one quarter had opportunistic infections. Nearly half of the participants were 50 years or older, the majority were male and about one third were from minority ethnic groups. After adjusting for site, gender and areas of residence (using the partial/selective Model 1), former commercial plasma donors (adjusted OR [aOR] = 33.71) and injecting drug users(aOR = 15.86) were found to have significantly higher risk of being HIV-positivity. In addition, having extramarital sexual relationship (aOR = 307.16), being engaged in commercial sex (aOR = 252.37), suffering from opportunistic infections in the past six months (aOR = 2.79), losing 10% or more of the body weight in the past six months (aOR = 5.90) and having abnormal chest X-ray findings (aOR = 20.40) were all significantly associated with HIV seropositivity (each p<0.05). CONCLUSIONS: HIV prevalence among TB patients was high in the study areas of China. To control the dual epidemic, intervention strategies targeting socio-demographic and behavioral factors associated with higher risk of TB-HIV co-infection are urgently called for.