Xin-Xu Li

Seasonal variations in notification of active tuberculosis cases in China, 2005-2012.

Background Although seasonal variation in tuberculosis (TB) incidence has been described in many countries, it remains unknown in China. Methods A time series decomposition analysis (X-12-ARIMA) was performed to examine the seasonal variation in active TB cases nationwide from 2005 through 2012 in China. Seasonal amplitude was calculated for the evaluation of TB seasonal variation. Results A total of 7.78 million active TB cases were reported over a period of 8 years. A spring peak (April) was observed with seasonal amplitude of 46.3%, compared with the winter trough (February). Most cases in provinces with subtropical and tropical monsoon climate showed lower amplitudes than those in temperate continental, plateau and mountain climate regions. The magnitude of seasonality varied inversely with annual average temperature, r (95% CI) = -0.71 (-0.79, -0.61). The seasonal amplitudes were 56.7, 60.5, 40.6, 46.4 and 50.9% for patients aged ≤14, 15–24, 25–44, 45–64, and ≥65 years, respectively. Students demonstrated greater seasonal amplitude than peasants, migrant workers and workers (115.3% vs. 43.5, 41.6 and 48.1%). Patients with pulmonary TB had lower amplitude compared to patients with pleural and other extra-pulmonary TB (EPTB) (45.9% vs. 52.0 and 56.3%). Relapse cases with sputum smear positive TB (SS+ TB) had significantly higher seasonal amplitude compared to new cases with sputum smear positive TB (52.2% vs. 41.6%). Conclusions TB is a seasonal disease in China. The peak and trough of TB transmission actually are in winter and in autumn respectively after factors of delay are removed. Higher amplitudes of TB seasonality are more likely to happen in temperate continental, plateau and mountain climate regions and regions with lower annual average temperature, and young person, students, patients with EPTB and relapse cases with SS+ TB are more likely to be affected by TB seasonality.

Exploration of ecological factors related to the spatial heterogeneity of tuberculosis prevalence in P. R. China

Background The current prevalence of tuberculosis (TB) in the Peoples Republic of China (P. R. China) demonstrates geographical heterogeneities, which show that the TB prevalence in the remote areas of Western China is more serious than that in the coastal plain of Eastern China. Although a lot of ecological studies have been applied in the exploration on the regional difference of disease risks, there is still a paucity of ecological studies on TB prevalence in P. R. China. Objective To understand the underlying factors contributing to the regional inequity of TB burden in P. R. China by using an ecological approach and, thus, aiming to provide a basis to eliminate the TB spatial heterogeneity in the near future. Design Latent ecological variables were identified by using exploratory factor analysis from data obtained from four sources, i.e. the databases of the National TB Control Programme (2001–2010) in P. R. China, the China Health Statistical Yearbook during 2002–2011, the China Statistical Yearbook during 2002–2011, and the provincial government websites in 2013. Partial least squares path modelling was chosen to construct the structural equation model to evaluate the relationship between TB prevalence and ecological variables. Furthermore, a geographically weighted regression model was used to explore the local spatial heterogeneity in the relationships. Results The latent ecological variables in terms of ‘TB prevalence’, ‘TB investment’, ‘TB service’, ‘health investment’, ‘health level’, ‘economic level’, ‘air quality’, ‘climatic factor’ and ‘geographic factor’ were identified. With the exception of TB service and health levels, other ecological factors had explicit and significant impacts on TB prevalence to varying degrees. Additionally, each ecological factor had different impacts on TB prevalence in different regions significantly. Conclusion Ecological factors that were found predictive of TB prevalence in P. R. China are essential to take into account in the formulation of locally comprehensive strategies and interventions aiming to tailor the TB control and prevention programme into local settings in each ecozone.

Intestinal Parasite Co-infection among Pulmonary Tuberculosis Cases without Human Immunodeficiency Virus Infection in a Rural County in China

Epidemiologic studies of co-infection with tuberculosis (TB) and intestinal parasites in humans have not been extensively investigated in China. A cross-section study was conducted in a rural county of Henan Province, China. Pulmonary TB (PTB) case-patients receiving treatment for infection with Mycobacterium tuberculosis and healthy controls matched for geographic area, age, and sex were surveyed by using questionnaires. Fecal and blood specimens were collected for detection of intestinal parasites, routine blood examination, and infection with human immunodeficiency virus. The chi-square test was used for univariate analysis and multivariate logistic regression models were used to adjust for potential confounding factors. A total of 369 persons with PTB and 366 healthy controls were included; all participants were negative for human immunodeficiency virus. The overall prevalence of intestinal parasites in persons with PTB was 14.9%, including intestinal protozoa (7.9%) and helminthes (7.6%). The infection spectrum of intestinal parasites was Entamoeba spp. (1.4%), Blastocystis hominis (6.2%), Trichomonas hominis (0.3%), Clonorchis sinensis (0.3%), Ascaris lumbricoides (0.5%), Trichuris trichiura (2.2%), and hookworm (4.6%). The prevalence of intestinal parasites showed no significant difference between persons with PTB and healthy controls after adjusting for potential confounding factors. There was no factor that affected infection rates for intestinal parasites between the two groups. Infection with intestinal parasites of persons with PTB was associated with female sex (adjusted odds ratio [AOR] = 2.05, 95% confidence interval [CI] = 1.01-4.17), body mass index ≤ 19 (AOR = 3.02, 95% CI = 1.47-6.20), and anemia (AOR = 2.43, 95% CI = 1.17-5.03). Infection of healthy controls was only associated with an annual labor time in farmlands > 2 months (AOR = 4.50, 95% CI = 2.03-10.00). In addition, there was no significant trend between rates of infection with intestinal parasites and duration of receiving treatment for infection with M. tuberculosis in persons with PTB. The prevalence of intestinal parasites was not higher in persons with PTB, and there was no evidence that PTB increased susceptibility to intestinal parasites in this study. However, for patients with PTB, women and patients with comorbidities were more likely to be infected with intestinal parasites.

Predictors on Delay of Initial Health-Seeking in New Pulmonary Tuberculosis Cases among Migrants Population in East China

Objectives To determine the length of delay in initial health-seeking in new pulmonary tuberculosis (PTB) cases among migrant population in the eastern part of China, and factors associated with it. Methods A cross-sectional study was conducted using a structured questionnaire in six counties in Shanghai, Guangdong and Jiangsu from May to October, 2008, to estimate the extent and factors responsible for delayed initial health-seeking of the new PTB cases. The interval between self-reported onset of TB symptoms and date of first attendance at any medical institution was determined. More than the median duration was defined as delayed health-seeking. Results A total of 323 new migrant PTB patients participated in the study. Only 6.5% had medical insurance. The median and mean durations to initial health-seeking were respectively 10 and 31 days. There was no significant association between socio-demographic factors and delayed initial health-seeking. Average monthly working days >24 (AOR, 1.61; 95% CI, 1.03–2.51), and hemoptysis or bloody sputum (AOR, 0.48; 95% CI, 0.28–0.85) were significantly associated with delayed initial health-seeking. Conclusions Interventions to improve health seeking behavior among the migrant population in China must focus on strengthening their labor, medical security and health education.

Spatial variations of pulmonary tuberculosis prevalence co-impacted by socio-economic and geographic factors in People's Republic of China, 2010.

BackgroundThe report of the fifth national tuberculosis (TB) epidemiological survey in P. R. China, 2010, roughly showed that pulmonary TB (PTB) prevalence was higher in western China than in central and eastern China. However, accurately estimating the continuous spatial variations of PTB prevalence and clearly understanding factors impacting on spatial variations of PTB prevalence are important for allocating limited resources of national TB programme (NTP) in P. R. China.MethodsUsing ArcGIS Geostatistical Wizard (ESRI, Redlands, CA), an evaluation was performed to decide that which kriging and cokriging methods along with different combinations of types of detrending, semivariogram models, anisotropy and covariables (socio-economic and geographic factors) can accurately construct spatial distribution surface of PTB prevalence using statistic data sampled from the fifth national TB epidemiological survey in P. R. China, 2010, and then the evaluation results were used to explore factors of spatial variations.ResultsThe global cokriging with socio-economic and geographic factors as covariables proved to be the best geostatistical methods for accurately estimating spatial distribution surface of PTB prevalence. The final continuous surfaces of PTB prevalence distribution demonstrated that PTB prevalence were lower in Beijing, Tianjin, Shanghai and southeastern coast China, higher in western and southwestern China, and crossed between low and high in central China.ConclusionsThe predicted continuous surface perspicuously illustrated the spatial variations of PTB prevalence that were co-impacted by socio-economic and geographic factors, which can be used to better allocate the always limited resources of NTP in P. R. China.

Prevalence and risk factors of intestinal protozoan and helminth infections among pulmonary tuberculosis patients without HIV infection in a rural county in P. R. China.

Although co-infection of tuberculosis (TB) and intestinal parasites, including protozoa and helminths, in humans has been widely studied globally, very little of this phenomenon is known in China. Therefore, a cross-sectional study was conducted in a rural county of China to investigate such co-infections. Patients with pulmonary TB (PTB) undergoing anti-Mycobacterium tuberculosis (anti-MTB) treatment were surveyed by questionnaires, and their feces and blood specimens were collected for detection of intestinal protozoa and helminths, routine blood examination and HIV detection. The χ(2) test and multivariate logistic regression model were used to identify risk factors. A total of 369 patients with PTB were included and all of them were HIV negative. Overall, only 7.3% of participants were infected with intestinal protozoa, among which prevalence of Blastocystis hominis, Entamoeba spp. and Trichomonas hominis were 6.0%, 1.1% and 0.3%, respectively; 7.0% were infected with intestinal helminths, among which prevalence of hookworm, Trichuris trichiura, Ascaris lumbricoides and Clonorchis sinensis were 4.3%, 1.9%, 0.5% and 0.3%, respectively; and 0.5% were simultaneously infected with intestinal protozoa and helminths. Among patients with PTB, body mass index (BMI)≤18 (OR=3.30, 95% CI=1.44-7.54) and raised poultry or livestock (e.g., chicken, duck, pig) (OR=3.96, 95% CI=1.32-11.89) were significantly associated with harboring intestinal protozoan infection, while BMI≤18 (OR=3.32, 95% CI=1.39-7.91), anemia (OR=3.40, 95% CI=1.44-8.02) and laboring barefoot in farmlands (OR=4.54, 95% CI=1.88-10.92) were significantly associated with having intestinal helminth infection. Additionally, there was no significant relationship between duration of anti-MTB treatment and infection rates of intestinal parasites including protozoa and helminths. Therefore, preventing malnutrition, avoiding unprotected contact with reservoirs of protozoa, and improving health education for good hygiene habits, particularly wearing shoes while outdoors, are beneficial in the prevention of intestinal protozoan and helminth infection among patients with PTB.

Spatial-temporal analysis of pulmonary tuberculosis in the northeast of the Yunnan province, People’s Republic of China

BackgroundThe number of pulmonary tuberculosis (PTB) cases in China ranks third in the world. A continuous increase in cases has recently been recorded in Zhaotong prefecture-level city, which is located in the northeastern part of Yunnan province. This study explored the space-time dynamics of PTB cases in Zhaotong to provide useful information that will help guide policymakers to formulate effective regional prevention and control strategies.MethodsThe data on PTB cases were extracted from the nationwide tuberculosis online registration system. Time series and spatial cluster analyses were applied to detect PTB temporal trends and spatial patterns at the town level between 2011 and 2015 in Zhaotong. Three indicators of PTB treatment registration history were used: initial treatment registration rate, re-treatment registration rate, and total PTB registration rate.ResultsSeasonal trends were detected with an apparent symptom onset peak during the winter season and a registration peak during the spring season. A most likely cluster and six secondary clusters were identified for the total PTB registration rate, one most likely cluster and five secondary clusters for the initial treatment registration rate, and one most likely cluster for the re-treatment registration rate. The most likely cluster of the three indicators had a similar spatial distribution and size in Zhenxiong County, which is characterised by a poor socio-economic level and the largest population in Yunnan.ConclusionThis study identified temporal and spatial distribution of PTB in a high PTB burden area using existing health data. The results of the study provide useful information on the prevailing epidemiological situation of PTB in Zhaotong and could be used to develop strategies for more effective PTB control at the town level. The cluster that overlapped the three PTB indicators falls within the geographic areas where PTB control efforts should be prioritised.

Usability of a Medication Event Reminder Monitor System (MERM) by Providers and Patients to Improve Adherence in the Management of Tuberculosis

Poor initiation and implementation and premature discontinuation of anti-tuberculous therapy, all forms of nonadherence, are major reasons for treatment failure, the development of drug-resistant tuberculosis, and transmission to other non-infected individuals. Directly Observed Therapy (DOT) has been the worldwide standard, but implementation of DOT is burdensome for providers and patients, especially in resource-limited settings, where most of the burden of active TB is located. Among the alternatives to DOT is electronic monitoring (EM) of drug dosing histories. Here we report a usability study of a newly-designed, modular electronic monitor product, called the MERM (Medication Event and Reminder Monitor), that is compatible with TB medication formats and supply chains in resource-limited settings. This study, done in a rural setting in China, showed that the use of the MERM for EM of TB medications was associated with a high degree of user performance, acceptability, and satisfaction among both TB patients and medical staff. Based on these data, EM is becoming the standard of care for drug-susceptible TB patients in China and scaled implementations in several other countries with high TB burden have begun. In addition, the MERM is being used in MDR-TB patients and in clinical trials involving patients with TB/HIV and latent TB.

Association between Multidrug-Resistant Tuberculosis and Risk Factors in China: Applying Partial Least Squares Path Modeling

Background Multidrug-resistant tuberculosis (MDR-TB) resulting from various factors has raised serious public health concerns worldwide. Identifying the ecological risk factors associated with MDR-TB is critical to its prevention and control. This study aimed to explore the association between the development of MDR-TB and the risk factors at the group-level (ecological risk factors) in China. Methods Data on MDR-TB in 120 counties were obtained from the National Tuberculosis Information Management System, and data on risk-factor variables were extracted from the Health Statistical Yearbook, provincial databases, and the meteorological bureau of each province (municipality). Partial Least Square Path Modeling was used to detect the associations. Results The median proportion of MDR-TB in new TB cases was 3.96% (range, 0–39.39%). Six latent factors were extracted from the ecological risk factors, which explained 27.60% of the total variance overall in the prevalence of MDR-TB. Based on the results of PLS-PM, TB prevention, health resources, health services, TB treatment, TB detection, geography and climate factors were all associated with the risk of MDR-TB, but socioeconomic factors were not significant. Conclusions The development of MDR-TB was influenced by TB prevention, health resources, health services, TB treatment, TB detection, geography and climate factors. Such information may help us to establish appropriate public health intervention strategies to prevent and control MDR-TB and yield benefits to the entire public health system in China.

Profiling B and T cell immune responses to co-infection of Mycobacterium tuberculosis and hookworm in humans.

BackgroundHumoral and cellular immune responses play protective roles against Mycobacterium tuberculosis (MTB) infection. However, hookworm infection decreases the immune response to hookworm and bystander antigens. Currently, immune responses to co-infection of MTB and hookworm are still unknown, although co-infection has been one of the public health problems in co-endemic areas of pulmonary tuberculosis (PTB) and hookworm disease. Therefore, it is essential to evaluate B and T cell immune responses to the co-infection.MethodsSeventeen PTB cases co-infected with hookworm, 26 PTB cases, 15 patients with hookworm infection, and 24 healthy controls without PTB or hookworm infection were enrolled in the study. Expressions of CD3, CD4, CD8, CD10, CD19, CD20, CD21, CD25, CD27, CD38, FoxP3, and PD-1 were assessed on B and T cell subsets using multicolor flow cytometry.ResultsFor the B cell (CD19+) subsets, naïve B cells (CD10−CD27−CD21+CD20+), plasma cells (CD10−CD27+CD21−CD20−), and tissue-like memory B cells (CD10−CD27−CD21−CD20+) had higher proportions, whilst resting memory B cells (CD10−CD27+CD21+CD20+) had lower proportions in the group co-infected with MTB and hookworm as compared to other groups. Frequencies of activated memory B cells (CD10−CD27+CD21−CD20+) did not differ among the four groups. For the T cell (CD3+) subsets, frequencies of regulatory T cells (CD4+CD25+Foxp3+) and exhausted CD4+ and CD8+ T cells (CD4+PD-1+ and CD8+PD-1+) were higher, and frequencies of activated CD4+ and CD8+ T cells (CD4+CD38+ and CD8+CD38+) were lower in the co-infected group as compared to the other groups.ConclusionThe change patterns of the cell profile of circulating lymphocytes were indentified in human co-infection of MTB and hookworm, which might indicate that the humoral and cellular immune responses are more suppressed.