Limei Zhu

Adherence to anti-tuberculosis treatment among pulmonary tuberculosis patients: a qualitative and quantitative study

BackgroundTuberculosis (TB) patients have difficulty following a long-term treatment regimen. Efforts to improve treatment outcomes require better understanding of adherence as a complex behavioral issue and of the particular barriers to and facilitators of patient adherence.MethodsThis study was carried out in Jiangsu Province of China with both quantitative and qualitative approaches. For the quantitative study, 780 sputum-smear positive TB patients consecutively registered since 2006 in 13 counties (districts) were queried with a structured questionnaire. Patients who had missed 10% of their total prescribed doses of TB drugs were deemed as non-adherent. Risks for non-adherence were estimated by computing odds ratios (ORs) and their 95% confidence intervals (95% CIs) using a logistic regression model. We also invited 20 TB patients and 10 local health workers for in-depth interviews. We then used content analysis based on this qualitative study to explore factors associated with non-adherence.ResultsThe proportion of non-adherence among 670 patients was 12.2%. Univariate analysis showed that patients, who were illiterate, divorced/widowed, lacked health insurance and were migrants, were more likely to be non-adherent. The crude ORs(95%CIs) were 2.38(1.37-4.13), 2.42(1.30-4.52), 1.89(1.07-3.32) and 1.98(1.03-3.83), respectively. The risk of non-adherence was lower among patients whose treatment was given under direct observation by village doctors or regular home visits by health workers, with ORs (95% CIs) of 0.19(0.10-0.36) and 0.23(0.10-0.51), respectively. In multivariate analysis, factors associated with non-adherence included illiteracy (OR: 2.42; 95% CI: 1.25-4.67) and direct observation by village doctors (OR: 0.23; 95% CI: 0.11-0.45). The in-depth interviews indicated that financial burdens and extra medical expenditures, adverse drug reactions, and social stigma were additional potential factors accounted for non-adherence.ConclusionMore importance should be given to treatment adherence under the current TB control program. Heavy financial burdens, lack of social support, adverse drug reactions and personal factors are associated with non-adherence. Direct observation and regular home visits by health workers appear to reduce the risk of non-adherence. More patient-centered interventions and greater attention to structural barriers are needed to improve treatment adherence.

Vitamin D receptor gene polymorphisms on the risk of tuberculosis, a meta-analysis of 29 case-control studies.

The relationship of four potentially functional polymorphisms of the vitamin D receptor (VDR) gene, ApaI, BsmI, FokI and TaqI , with tuberculosis susceptibility were considered. The aim of this meta-analysis was to explore the association between the four polymorphisms and tuberculosis risk in different ethnic backgrounds. Eligible case-control studies that were catalogued before April 1st 2013 were enrolled, and the heterogeneity between the studies was evaluated using a χ2 based Q-test. Fixed and random effect models were built to evaluate the association of the four polymorphisms with the risk of tuberculosis, and the association between the four polymorphisms and tuberculosis was expressed as the odds ratio (OR) and 95% confidence interval (CI). Finally, twenty nine qualified studies were enrolled for this meta-analysis that included 6179 tuberculosis cases and 6585 healthy controls. The variant homozygote genotype of the FokI polymorphism was associated with a significantly increased risk of tuberculosis when compared to the heterozygote and wild type homozygote genotypes in the Chinese population (ff vs. Ff+FF: ORrecessive=1.97, 95%CI: 1.32-2.93, P bonferroni=0.0032; heterogeneity test: χ2=0.24, P=0.62). For European subjects, the homozygote and heterozygote genotypes of the BsmI polymorphism were associated with a significantly decreased risk of tuberculosis when compared to the wild type homozygote (bb+Bb vs. BB: ORdominant=0.41, 95%CI, 0.22-0.76, P bonferroni=0.02; heterogeneity test: χ2=2.59, P=0.11). Based on the above results, we conclude that variants of the VDR gene that are homozygous for the FokI polymorphism might be more susceptible to tuberculosis in Chinese. Furthermore, larger sample studies are warranted to confirm the protective effects of BsmI variants on tuberculosis in the Europeans.

The Epidemiology and Geographic Distribution of Nontuberculous Mycobacteria Clinical Isolates from Sputum Samples in the Eastern Region of China

Background Nontuberculous mycobacteria (NTM) have been reported to be increasing worldwide and its geographic distribution differs by region. The aim of this study was to describe the epidemiology and distribution of NTM in the eastern part of China. Methods Sputum samples were collected from 30 surveillance sites for tuberculosis drug resistance test from May 1, 2008 to December 31, 2008. Identification was performed using a biochemical test, multiplex PCR and GenoType Mycobacterium CM/AS assay. Results A total of 1779 smear positive clinical isolates were obtained, of which 60 (3.37%) were NTM. Five species/complex of NTM were identified; M. intracellulare was the predominated species (68.33%), followed by M. abscessus-M. immunogenum (13.33%), Mycobacterium spec. (10.00%), M. Kansasii (6.67%) and M. peregrinum-M. alvei-M. septicum (1.67%). Conclusion M. intracellulare was the main species of NTM in the eastern part of China and clinical physicians should pay more attention to NTM induced pulmonary disease.

Mesenchymal stromal cell treatment prevents H9N2 avian influenza virus-induced acute lung injury in mice

BackgroundThe avian influenza virus (AIV) can cross species barriers and expand its host range from birds to mammals, even humans. Avian influenza is characterized by pronounced activation of the proinflammatory cytokine cascade, which perpetuates the inflammatory response, leading to persistent systemic inflammatory response syndrome and pulmonary infection in animals and humans. There are currently no specific treatment strategies for avian influenza.MethodsWe hypothesized that mesenchymal stromal cells (MSCs) would have beneficial effects in the treatment of H9N2 AIV-induced acute lung injury in mice. Six- to 8-week-old C57BL/6 mice were infected intranasally with 1 × 104 MID50 of A/HONG KONG/2108/2003 [H9N2 (HK)] H9N2 virus to induce acute lung injury. After 30 min, syngeneic MSCs were delivered through the caudal vein. Three days after infection, we measured the survival rate, lung weight, arterial blood gas, and cytokines in both bronchoalveolar lavage fluid (BALF) and serum, and assessed pathological changes to the lungs.ResultsMSC administration significantly palliated H9N2 AIV-induced pulmonary inflammation by reducing chemokines and proinflammatory cytokines levels, as well as reducing inflammatory cell recruit into the lungs. Thus, H9N2 AIV-induced lung injury was markedly alleviated in mice treated with MSCs. Lung histopathology and arterial blood gas analysis were improved in mice with H9N2 AIV-induced lung injury following MSC treatment.ConclusionsMSC treatment significantly reduces H9N2 AIV-induced acute lung injury in mice and is associated with reduced pulmonary inflammation. These results indicate a potential role for MSC therapy in the treatment of clinical avian influenza.

High Latent TB Infection Rate and Associated Risk Factors in the Eastern China of Low TB Incidence

Objectives To disclose the associated risk factors for latent tuberculosis infection (LTBI) and the current situation of LTBI in the eastern China. Methods A cross-sectional study was undertaken to evaluate the LTBI rate and risk factors. Results A total of 5305 subjects were finally included, with the IGRA positive rate of 19.98% (1060/5305). The LTBI rates were increasing with age (ORs were in significance from 6.60 to 20.92). Male gender significantly increased the risk of LTBI by 0.52 fold (OR = 1.52). Both smoking and drinking significantly increased the risk of LTBI (OR = 1.83 and OR = 1.67, respectively). Meanwhile, overweight and close contact with tuberculosis were risk factors for LTBI (OR = 1.36 and OR = 2.38, respectively). However, higher level of education and BCG vaccination lowered the risk of LTBI (OR = 0.16 and OR = 0.39, respectively). The multivariate logistic regression showed that age, male gender, smoking, overweight and close contacting with tuberculosis were risk factors for LTBI, but BCG vaccination was a protective factor for LTBI. Conclusions BCG vaccination exerted protective effect on tuberculosis. However, LTBI rate in the Chinese rural area was critical and subjects above 30 years, male, smoking, overweight and close contact with tuberculosis wound be the targets for LTBI screening and source of tuberculosis.

Genotypes of Mycobacterium tuberculosis isolates in rural China: Using MIRU-VNTR and spoligotyping methods

Abstract Background: The genotypes of Mycobacterium tuberculosis (MTB) have been found to be related to the risk of transmission and the development of drug resistance of this pathogen. Thus, exploring the molecular characteristics of MTB is helpful for understanding and controlling the spread of strains in areas with a high incidence of tuberculosis. Methods: We recruited 512 sputum smear-positive tuberculosis patients from 30 counties from 1 April to 30 June 2010; 503 MTB strains were isolated and 497 were successfully genotyped. We genotyped the strains based on a new 15-locus mycobacterial interspersed repetitive unit–variable number of tandem repeats (MIRU-VNTR) method in combination with spacer-oligonucleotide typing (spoligotyping) technology. Results: Based on spoligotyping, 487 strains displayed known patterns, and 10 were absent from the current global spoligotyping database (SpolDB4). The predominant spoligotypes belonged to the Beijing or Beijing-like family (81.1%). When we used the new 15-locus (MIRU-15) set for the MIRU-VNTR analysis, 388 different patterns were identified, including 46 clusters and 342 unique patterns. The combination of spoligotyping and MIRU-15 demonstrated a high discriminatory power. The proportion of clusters varied significantly between the Beijing and non-Beijing family strains, but no significant association was observed between multidrug resistance and Beijing family strains. Conclusions: The present study demonstrated that the Beijing family strains are the most prevalent in rural China. Spoligotyping in combination with the new MIRU-15 technique is useful for the epidemiological analysis of MTB transmission and could be used as a first-line method for the large-scale genotyping of MTB.

Time to sputum culture conversion and treatment outcome of patients with multidrug-resistant tuberculosis: a prospective cohort study from urban China

Sputum culture plays an important role in monitoring treatment response in patients with multidrug-resistant tuberculosis (MDR-TB), and sputum culture conversion is a clinical tool used to predict therapeutic efficacy [1]. Monthly culture monitoring is essential for earlier detection of treatment failure in patients with MDR-TB. More sensitive signals of nonresponse would further avoid adverse outcomes [2]. The timing of testing for culture conversion has potential as a marker of MDR-TB treatment success http://ow.ly/borO308pPXg

Evaluation of the GenoType(®) MTBDRplus line probe assay on sputum-positive samples in routine settings in China.

BACKGROUND Rapid molecular methods have been recommended for early detection of drug-resistant tuberculosis (TB). OBJECTIVE To evaluate the performance of the GenoType(®) MTBDRplus assay in routine settings in China. METHODS Sputum-positive samples were collected consecutively from 1 April to 31 December 2010. MTBDRplus results were compared to those of conventional drug susceptibility testing (DST). The McNemar χ(2) test and κ coefficient were used to assess performance. RESULTS Of 427 smear-positive sputum samples collected, conventional DST and MTBDTplus confirmed drug resistance in 326. The sensitivities and specificities for MTBDRplus in detecting isoniazid (INH) and rifampicin (RMP) resistance were respectively 76.47%, 95.44%, 85.94% and 93.13%. The McNemar χ(2) test indicated no significant difference between the two methods (P = 0.106 for INH and P = 0.083 for RMP). The κ values for INH, RMP and multidrug resistance were respectively 0.75, 0.75 and 0.70. CONCLUSIONS Although the MTBDRplus assay was moderately concordant with conventional DST in detecting INH and RMP resistance, as a prospective rapid molecular method for MDR-TB detection, potential resistant mutations need to be incorporated to improve the accuracy of detection.

Evaluation of Biochip System in Determining Isoniazid and Rifampicin Resistances of Mycobacterium Tuberculosis in Sputum Samples

Objective To evaluate a biochip system in determining isoniazid and rifampicin resistances of Mycobacterium tuberculosis in sputum samples in a Chinese population. Methods We assembled 907 sputum smeared positive specimens of tuberculosis patients in total. Each sample would be separated into two parts for culture and biochip assay simultaneously. And those cultured positive and having full drug resistance results would be used as reference. The McNemar χ2 test was adopted for evaluating the paired 2×2 table. Results Compared with drug sensitivity test, the agreement rates of the two methods in detecting rifampicin and isoniazid resistances were 93.37% and 94.49%, respectively. The sensitivity and specificity of biochip in detecting isoniazid were 74.31% and 96.92%, respectively. Meanwhile, the sensitivity and specificity for rifampicin were 79.76% and 96.53%, respectively. For multi-drug resistance, the sensitivity and specificity were 64.62% and 97.75%, respectively. Conclusions The biochip system is a rapid and accurate method for drug resistant tuberculosis diagnosis using sputum samples directly, especially for rifampicin resistance detection.

Glycemic Control and the Prevalence of Tuberculosis Infection: A Population-based Observational Study

Background Several cohort studies demonstrate that diabetics are at increased risk for active tuberculosis, and poor glycemic control may exacerbate this risk. A higher prevalence of tuberculosis infection at baseline among diabetics may partially explain these results; however, no population-based studies have investigated this association. Furthermore, whether glycemic control modifies the relationship between diabetes and tuberculosis infection, as it does with active tuberculosis, is unknown. Methods Diabetics were diagnosed through physician evaluation and using 3 laboratory tests including hemoglobin A1C (HbA1C), fasting plasma glucose (FPG), or 2-hour plasma glucose (PG). Tuberculosis infection was diagnosed through tuberculin skin tests, and glycemic control was assessed linearly and categorically using recommended targets. Results Among 4215 participants, the prevalence of tuberculosis infection was 4.1%, 5.5%, and 7.6% in nondiabetic, prediabetic, and diabetic participants (Ptrend = .012). In multivariate analysis, diabetes was associated with tuberculosis infection (adjusted odds ratio [AOR], 1.5; 95% confidence interval [CI], 1.0-2.2). Compared to nondiabetics, diabetics who were undiagnosed (AOR, 2.2 and 1.2 in diagnosed diabetics), FPG >130 mg/dL (AOR, 2.6 and 1.3 in diabetics with FPG ≤130 mg/dL), or not on insulin (AOR, 1.7 and 0.8 in diabetics on insulin) had elevated tuberculosis infection rates. In a linear dose-response analysis, increasing values of FPG (AOR, 1.02 per 1-mg/dL; 95% CI, 1.01-1.03), PG (AOR, 1.02 per 1-mg/dL; 95% CI, 1.01-1.04), and HbA1C (AOR, 1.13 per 1%; 95% CI, 1.04-1.22) all predicted tuberculosis infection. Conclusions Our results suggest glycemic control may modify the relationship between tuberculosis infection and diabetes.