Associations of residential greenness exposure and ambient air pollutants with newly-diagnosed drug-resistant tuberculosis cases.

Growing evidence has found the health protective effects of greenness exposure on tuberculosis (TB) and the impact of ambient air pollutants on TB drug-resistance. However, it remains unclear whether residential greenness is also beneficial to reduce TB drug-resistance, and whether air pollution modify the greenness-TB resistance relationship. We enrolled 5006 newly-diagnosed TB patients from Shandong, China, during 2014 to 2021. Normalized Difference Vegetation Index (NDVI) in 250 m and 500 m buffer around individuals' residential zone was used to assess greenness exposure. All patients were divided by quartiles of NDVI250-m and NDVI500-m (from low to high: Q1, Q2, Q3, Q4) respectively. Six logistic regression models (NDVI, NDVI + PM2.5/PM10/SO2/NO2/O3) were used to estimate the association of NDVI and TB drug-resistance when adjusting different air pollutants or not. All models were adjusted for age, gender, body mass index, complications, smoking, drinking, population density, nighttime light index, road density. Compared with participants in NDVI250-m Q1 and NDVI500-m Q1, other groups had lower rates of MDR-TB, PDR-TB, RFP-resistance, SM-resistance, RFP + SM resistance, INH + RFP + EMB + SM resistance. NDVI500-m reduced the risk of multidrug resistant tuberculosis (MDR-TB) and the adjusted odds ratio (aOR, 95% confidence interval, CI) compared with NDVI500-m Q1 were 0.736 (0.547-0.991) in NDVI + PM10 model, 0.733 (0.544-0.986) in NDVI + PM2.5 model, 0.735(0.546-0.99) in NDVI + SO2 model, 0.736 (0.546-0.991) in NDVI + NO2 model, respectively, P < 0.05. NDVI500-m contributed to a decreased risk of streptomycin (SM)-resistance. The aOR of rifampicin (RFP) + SM resistance were 0.132 (NDVI250-m, Q4 vs Q1, 95% CI: 0.03-0.578), 0.199 (NDVI500-m, Q3 vs. Q1, 95% CI: 0.057-0.688) and 0.264 (NDVI500-m, Q4 vs. Q1, 95% CI: 0.087-0.799). The adjusted ORs (Q2 vs. Q1, 95% CI) of isoniazid (INH) + RFP + ethambutol (EMB) + SM resistance in 500 m buffer were 0.276 (0.119-0.639) in NDVI model, 0.279 (0.11-0.705) in NDVI + PM10 model, 0.281 (0.111-0.713) in NDVI + PM2.5 model, 0.279 (0.11-0.709) in NDVI + SO2 model, 0.296 (0.117-0.754) in NDVI + NO2 model, 0.294 (0.116-0.748) in NDVI + O3 model, respectively. The study showed, for the first time, that residential greenness exposure in 500 m buffer is beneficial for reducing newly-diagnosed DR-TB (including PDR-RB, MDR-TB, MR-TB), and ambient air pollutants may partially mediate this association.

Transmission dynamics and phylogeography of Mycobacterium tuberculosis in China based on whole-genome phylogenetic analysis.

OBJECTIVES: This study aimed to describe the lineage-specific transmissibility and epidemiological migration of Mycobacterium tuberculosis in China. METHODS: We curated a large set of whole-genome sequences from 3204 M. tuberculosis isolates, including thousands of newly sequenced genomes, and applied a series of metrics to compare the transmissibility of M. tuberculosis strains between lineages and sublineages. The countrywide transmission patterns of major lineages were explored. RESULTS: We found that lineage 2 (L2) was the most prevalent lineage in China (85.7%), with the major sublineage 2.2.1 (80.9%), followed by lineage 4 (L4) (13.8%), which comprises major sublineages 4.2 (1.5%), 4.4 (6.2%) and 4.5 (5.8%). We showed evidence for frequent cross-regional spread and large cluster formation of L2.2.1 strains, whereas L4 strains were relatively geographically restricted in China. Next, we applied a series of genomic indices to evaluate M. tuberculosis strain transmissibility and uncovered higher transmissibility of L2.2.1 compared with the L2.2.2 and L4 sublineages. Phylogeographic analysis showed that southern, eastern, and northern China were highly connected regions for countrywide L2.2.1 strain spread. CONCLUSIONS: The present study provides insights into the different transmission and migration patterns of the major M. tuberculosis lineages in China and highlights that transmissible L2.2.1 is a threat to tuberculosis control.

Genomic analysis of lineage-specific transmission of multidrug resistance tuberculosis in China.

OBJECTIVES: We investigated the genetic diversities and lineage-specific transmission dynamics of multidrug-resistant tuberculosis (MDR-TB), with the goal of determining the potential factors driving the MDR epidemics in China. METHODS: We curated a large nationwide Mycobacterium tuberculosis (M. tuberculosis) whole genome sequence data set, including 1313 MDR strains. We reconstructed the phylogeny and mapped the transmission networks of MDR-TB across China using Bayesian inference. To identify drug-resistance variants linked to enhanced transmissibility, we employed ordinary least-squares (OLS) regression analysis. RESULT: The majority of MDR-TB strains in China belong to lineage 2.2.1. Transmission chain analysis has indicated that the repeated and frequent transmission of L2.2.1 plays a central role in the establishment of MDR epidemic in China, but no occurrence of a large predominant MDR outbreak was detected. Using OLS regression, the most common single nucleotide polymorphisms (SNPs) associated with resistance to isoniazid (katG_p.Ser315Thr and katG_p.Ser315Asn) and rifampicin (rpoB_p.Ser450Leu, rpoB_p.His445Tyr, rpoB_p.His445Arg, rpoB_p.His445Asp, and rpoB_p.His445Asn) were more likely to be found in L2 clustered strains. Several putative compensatory mutations in rpoA, rpoC, and katG were significantly associated with clustering. The eastern, central, and southern regions of China had a high level of connectivity for the migration of L2 MDR strains throughout the country. The skyline plot showed distinct population size expansion dynamics for MDR-TB lineages in China. CONCLUSION: MDR-TB epidemic in China is predominantly driven by the spread of highly transmissible Beijing strains. A range of drug-resistance mutations of L2 MDR-TB strains displayed minimal fitness costs and may facilitate their transmission.

Impact of alcohol drinking and tobacco smoking on the drug-resistance of newly diagnosed tuberculosis: a retrospective cohort study in Shandong, China, during 2004-2020.

OBJECTIVES: To investigate the independent and collective impact of alcohol drinking and tobacco smoking on the drug-resistance of newly diagnosed tuberculosis (TB). DESIGN: This was a retrospective cohort study. SETTING: Shandong, China. PARTICIPANTS: Patients with newly diagnosed TB from 1 January 2004 to 31 December 2020 were collected. Exclusive criteria: retreated cases; extrapulmonary tuberculosis; without information on drug susceptibility testing results, smoking or drinking habits; bacteriological identification as non-tuberculous mycobacteria. PRIMARY AND SECONDARY OUTCOME MEASURES: Patients were classified into four groups including smokers only (G1), drinker only (G2), smoker +drinker (G3), non-smoker +non-drinker group (G0). We described the drug-resistant profiles, clinical factors and calculated the ORs of different drug-resistance among G1, G2, G3, compared with G0 through univariate and multivariate logistics regression models. RESULTS: Of the 7996 TB cases enrolled, the proportions of G1, G2, G3 and G0 were 8.25%, 3.89%, 16.46% and 71.40%, respectively. The rates of drug-resistant (DR)-TB, mono-resistant TB, multidrug resistant (MDR)-TB, polydrug resistant TB in G1, G2, G3 and G0 were 19.24%/16.4%/17.33%/19.08%, 11.52%/8.68%/10.94%/11.63%, 3.03%/2.57%/2.96%/3.66% and 4.70%/4.82%/3.34%/ 4.08%, respectively. G3 had a higher risk of MDR1: isoniazid +rifampin (adjusted OR (aOR)=1.91, 95% CI: 1.036 to 3.532), but had a lower risk of DR-TB (aOR=0.84, 95% CI: 0.71 to 0.99), rifampin-related resistance (aOR=0.68, 95% CI: 0.49 to 0.93), streptomycin-related resistance (aOR=0.82, 95% CI: 0.68 to 0.99), ethambutol-related resistance (aOR=0.57, 95% CI: 0.34 to 0.95), MDR3: isoniazid +rifampin+streptomycin (aOR=0.41, 95% CI: 0.19 to 0.85), any isoniazid +streptomycin resistance (aOR=0.85, 95% CI: 0.71 to 1.00). However, there were no significant differences between G1 and G0, G2 and G0 in all drug-resistant subtypes. Those patients with cavity had a higher risk of DR-TB among G3 (OR=1.35, 95% CI: 1.01 to 1.81). CONCLUSION: Although we did not found an independent impact of alcohol drinking or tobacco smoking on TB drug-resistance, respectively, these two habits had a combined effect on TB drug-resistance.

Association between body mass index and newly diagnosed drug-resistant pulmonary tuberculosis in Shandong, China from 2004 to 2019.

BACKGROUND: Drug-resistant tuberculosis (DR-TB), obesity, and malnutrition are growing public health problems in the world. However, little has discussed the impact of different BMI status on the emergence of TB drug resistance. We aimed to explore the drug-resistant profiles of DR-TB and its clinical predictors among underweight, overweight or obesity population. METHODS: 8957 newly diagnosed TB cases with drug susceptibility results and BMI data in Shandong China, from 2004 to 2019 were enrolled. Multivariable and univariable logistic regression models were applied to investigate the impact of BMI on different drug-resistance. Clinical predicators and drug-resistant profiles of DR-TB among obesity, underweight, normal TB group were also described. RESULTS: Among 8957 TB cases, 6417 (71.64%) were normal weight, 2121 (23.68%) were underweight, 373 (4.16%) were overweight, and 46 (0.51%) were obese. The proportion of drug resistance and co-morbidity among normal weight, underweight, overweight, obese TB groups were 18.86%/18.25%/20.38%/23.91% (DR-TB), 11.19%/11.74%/9.65%/17.39% (mono-resistant tuberculosis, MR-TB), 3.41%/3.06%/5.36%/0.00% (multidrug resistant tuberculosis, MDR-TB), 4.21%/3.39%/5.36%/6.52% (polydrug resistant tuberculosis, PDR-TB), 10.57%/8.44%/19.57%/23.91% (co-morbidity), respectively. Compared with normal weight group, underweight were associated with lower risk of streptomycin-related resistance (OR 0.844, 95% CI 0.726-0.982), but contributed to a higher risk of MR-TB (isoniazid) (odds ratio (OR) 1.347, 95% CI 1.049-1.730; adjusted OR (aOR) 1.31, 95% CI 1.017-1.686), P < 0.05. In addition, overweight were positively associated with MDR-TB (OR 1.603, 95% CI 1.002-2.566; aOR 1.639, 95% CI 1.02-2.633), isoniazid + rifampicin + streptomycin resistance (OR 1.948, 95% confidence interval (CI): 1.061-3.577; aOR 2.113, 95% CI 1.141-3.912), Any isoniazid + streptomycin resistance (OR 1.472, 95% CI 1.013-2.14; aOR 1.483, 95% CI 1.017-2.164), P < 0.05. CONCLUSIONS: The higher risk of MDR-TB, isoniazid + rifampicin + streptomycin resistance, Any isoniazid + streptomycin resistance, and co-morbidity among overweight population implies that routine screening for drug sensitivity and more attention on co-morbidity among overweight TB cases may be necessary. In addition, underweight TB cases have a higher risk of isoniazid resistance. Our study suggests that an in-depth study of the interaction between host metabolic activity and infection of DR-TB may contribute more to novel treatment options or preventive measures, and accelerate the implementation of the STOP TB strategy.

Drug-Resistant Tuberculosis Among Children: A Systematic Review and Meta-Analysis.

Background: Drug-resistant tuberculosis (DR-TB), especially multidrug-resistant tuberculosis (MDR-TB) is a public health threat. Little is known about estimates of different profiles and rates of DR-TB among children globally. Methods: We did a systematic review and meta-analysis of observational studies reporting DR-TB among children by searching Embase, PubMed, and Scopus databases from January 1, 2000 to October 1, 2020. Publications reporting more than 60 children with bacteriological confirmed tuberculosis and phenotypical drug susceptibility testing (DST) results were included. Pooled proportions of MDR-TB and sub-analysis by age subgroups, regions, economical levels were performed. Results: We identified 4,063 studies, of which 37 were included. Of 23,652 pediatric TB patients, the proportions of DR-TB, MDR-TB, mono-resistant TB, polydrug resistant TB, extensively drug-resistant TB were 13.59% (1,964/14,453), 3.72% (881/23,652), 6.07% (529/8,719), 1.61% (119/7,361), 0.44% (30/6,763), respectively. The pooled proportion of MDR-TB among 23,652 children of 37 studies was 3.7% (95% CI, 3.5-4.0%). Rate of MDR-TB was much lower in high-income countries (1.8%) than that in lower-middle-income countries (6.3%) and upper-middle-income countries (7.3%). More specifically, the rates of MDR-TB were 1.7% in USA, 1.7% in UK, 2.9% in India, 6.0% in South Africa, 9.8% in China, respectively. Conclusions: The burden of DR-TB remains high in children, and there are potential associations between rates of pediatric MDR-TB and national economical levels. More interventions on child TB cases in low-income countries may be urgently needed in future.

Ambient air pollutants, diabetes and risk of newly diagnosed drug-resistant tuberculosis.

BACKGROUND: Drug-resistant tuberculosis (DR-TB), diabetes and exposure to air pollution are thought to be important threat to human health, but no studies have explored the effects of ambient air pollutants on DR-TB when adjusting diabetes status so far. METHODS: We performed a study among 3759 newly diagnosed TB cases with drug-susceptibility testing results, diabetes status, and individual air pollution data in Shandong from 2015 to 2019. Generalized linear mixed models (GLMM) including three models (Model 1: without covariates, Model 2: adjusted by diabetes status only, Model 3: with all covariates) were applied. RESULTS: Of 3759 TB patients enrolled, 716 (19.05%) were DR-TB, and 333 (8.86%) had diabetes. High exposure to O3 was associated with an increased risk of RFP-resistance (Model 2 or 3: odds ratio (OR) = 1.008, 95% confidence intervals (CI): 1.002-1.014), ethambutol-resistance (Model 3: OR = 1.015, 95%CI: 1.004-1.027) and any rifampicin+streptomycin resistance (Model 1,2,3: OR = 1.01, 95%CI: 1.002-1.018) at 90 days. In contrast, NO2 was associated with a reduced risk of DR-TB (Model 3: OR = 0.99, 95%CI: 0.981-0.999) and multidrug-resistant TB (MDR-TB) (Model 3: OR = 0.977, 95%CI: 0.96-0.994) at 360 days. Additionally, SO2 (Model 1, 2, 3: OR = 0.987, 95%CI: 0.977-0.998) showed a protective effect on MDR-TB at 90 days. PM2.5 (90 days, Model 2: OR = 0.991, 95%CI: 0.983-0.999), PM10 (360 days, Model 2: OR = 0.992, 95%CI: 0.985-0.999) had protective effects on any RFP+SM resistance. CONCLUSIONS: O3 contributed to an elevated risk of TB resistance but PM2.5, PM10, SO2, NO2 showed an inverse effect. Air pollutants may affect the development of drug resistance among TB cases by adjusting the status of diabetes.

Drug resistance of previously treated tuberculosis patients with diabetes mellitus in Shandong, China.

BACKGROUND: Although the association between diabetes mellitus (DM) and tuberculosis (TB) has been well-documented for centuries, evidence of the link between diabetes and drug resistance among previously treated TB patients remains limited and inconsistent. METHODS: An observational study was performed that involved 1791 retreated TB-no DM patients (refers to TB cases without diabetes) and 93 retreated TB-DM patients (refers to TB cases with diabetes) in Shandong, China from 2004 to 2017. Baseline data including demographic and clinical characteristics, drug susceptibility test (DST) results, and diabetes status were collected. Categorical baseline characteristics were compared by Fisher's exact or Pearson Chi-square test. Univariable analysis and multivariable logistic models were used to estimate the association between diabetes and different drug resistance profiles. RESULTS: Retreated TB-DM patients have a higher rate of drug resistance than TB-no DM patients (34.41% vs 25.00%, P < 0.01). Diabetes co-morbidity was significantly associated with any drug-resistant tuberculosis (DR-TB, odds ratio (OR):1.56, 95% confidence interval (CI): 1.01-2.43), multidrug resistant tuberculosis (MDR-TB, OR: 2.48, 95%CI:1.39-4.41; adjusted OR (aOR):2.94, 95%CI:1.57-5.48), isoniazid-related resistance (OR:1.71, 95%CI:1.04-2.81), rifampin-related resistance (OR:2.56, 0.54, 95%CI: 1.54-4.26; aOR:2.69, 95%CI:1.524-4.74), isoniazid + rifampin resistance (OR: 3.55, 95%CI:1.33-9.44; aOR:4.13, 95%CI:1.46-11.66), any resistance to isoniazid + streptomycin (OR:2.34, 95%CI:1.41-3.89; aOR:2.22, 95%CI:1.26-3.94), and any resistance to rifampin + isoniazid (OR:2.48, 95%CI:1.39-4.41; aOR:2.94, 95%CI: 1.57-5.48), compared with pan susceptible TB cases, P < 0.05. CONCLUSIONS: The risk of acquired drug resistance increased significantly among retreated TB-DM patients compared with retreated TB-no DM patients, underlining the necessity of more interventions during the clinical management of TB-DM cases.

Primary drug resistance of mycobacterium tuberculosis in Shandong, China, 2004-2018.

BACKGROUND: Primary drug-resistant tuberculosis (DR-TB) has contributed to a significant health and economic burden on a global scale, especially in China. we sought to estimate epidemiological characteristics of primary DR-TB in China from 2004 to 2018. METHODS: Eleven thousand four hundred sixty-seven newly diagnosed and 1981 retreated TB cases with drug susceptibility data were included. Chi-Square test for trends, linear regression, a joinpoint regression model and temporal trend in proportions of the different resistance patterns were carried out. RESULTS: The proportion of primary DR-TB and mono-resistant TB (MR-TB) in China had reduced by more than 12% since 2004, and were 21.38%, 13.35% in 2018 respectively. Among primary DR-TB cases (2173,18.95%), the percentage of multiresistant TB (MDR-TB, from 5.41 to 17.46%), male (from 77.03 to 84.13%), cavity (from 13.51 to 43.92%), rifampicin(RFP)-resistant TB (from 8.11 to 26.98%), streptomycin(SM)-resistant TB (from 50.00 to 71.43%) increased significantly (P < 0.05). On the contrary, the proportion of female, non-cavity, isoniazide(INH)-resistant TB (from 55.41 to 48.15%) and MR-TB (from 82.43 to 62.43%) decreased significant (P < 0.05). The primary drug resistance rate among female, cavity, smoking, drinking, 15 to 44 year-old TB subgroups increased by 0.16, 6.24, 20.95, 158.85, 31.49%, respectively. The percentage of primary DR-TB, RFP-resistant TB dropped significantly during 2004-2007 in Joinpoint regression model. CONCLUSION: The total rate of drug resistance among new TB cases showed a downward trend in Shandong, China, from 2004 to 2018. Primary drug resistance patterns were shifting from female, non-cavity, INH-resistant TB, and MR-TB groups to male, cavity, RFP/SM-resistant TB, and MDR-TB groups. Considering the rising drug resistance rate among some special population, future control of primary DR-TB in China may require an increased focus on female, cavity, smoking, drinking, or 15 to 44 year-old TB subgroups.

Primary drug resistance among tuberculosis patients with diabetes mellitus: a retrospective study among 7223 cases in China.

BACKGROUND: Given the high burden of tuberculosis (TB) and diabetes mellitus (DM) in China and the worse outcome of TB-DM cases (refers to TB patients with diabetes), and drug-resistant tuberculosis cases (DR-TB), it is of great significance to explore the association between diabetes and primary DR-TB for TB elimination target in China. We assessed the clinical characteristics, drug-resistance profile, and increased risk of resistance among TB-DM patients across China from 2004 to 2017. METHOD: 7223 cases with drug-susceptibility data were collected from Shandong, China. Categorical baseline characteristics of new TB cases were compared by DM status using Fisher's exact or Pearson Chi-square test. Univariable analysis and multivariable logistic models were used to estimate the association between diabetes and different drug-resistance profiles and the risk factors of primary drug resistance among TB-DM cases. RESULT: Of 7223 newly diagnosed TB patients, 426 (5.90%) were TB-DM cases. TB-DM csaes were more likely to be older，accompanied by higher body mass index (BMI) and hypertension than TB-no DM cases (refers to TB patients without diabetes). The rates of DR-TB (21.83% vs 16.96%), polydrug resistant TB (PDR-TB, 6.10% vs 3.80%), isoniazid (INH)+streptomycin (SM)-resistant TB (4.93% vs 3.13%), and SM-resistant TB (16.20% vs 11.7%) among TB-DM group were higher than TB-no DM group, P<0.05. DM was significantly associated with any DR-TB (adjusted (aOR):1.30; 95% CI, 1.02-1.65), SM-related resistance (aOR: 1.43; 95% CI, 1.08-1.88), PDR-TB (OR: 1.57; 95% CI, 1.04-2.36; aOR: 1.59; 95% CI, 1.04-2.44), compared with pan-susceptible TB patients (P<0.05). CONCLUSION: Our study indicated that TB-DM groups had a higher proportion of drug resistance than TB groups, and diabetes was identified as a risk factor of total DR, PDR, SM resistance and INH+SM resistance among newly diagnosed TB cases. Good management of diabetes and TB infection screening program among DM patients might be necessary for improving TB control in China.

Drug-Resistant Tuberculosis among Children, China, 2006-2015.

Microbial drug resistance has become a major public health concern worldwide. To acquire epidemiologic data on drug-resistant tuberculosis (DR TB) among children, a major cause of illness and death for this population, we conducted a retrospective study of 2006-2015 data from 36 TB prevention and control institutions in Shandong Province, China. A total of 14,223 new TB cases, among which children (<18 years of age) accounted for only 5.5%, were caused by culture-confirmed Mycobacterium tuberculosis. Among children with TB, 18.9% had DR TB and 6.9% had multidrug-resistant TB. Over the past decade, the percentage of DR TB; multidrug-resistant TB; and overall first-line drug resistance for isoniazid, rifampin, ethambutol, and streptomycin among children increased significantly (at least 12%). Understanding the long-term trends of DR TB among children can shed light on the performance of TB control programs, thereby contributing to global TB control.

Trends and characteristics of drug-resistant tuberculosis in rural Shandong, China.

OBJECTIVES: The aim of this study was to describe the secular trends in drug-resistant tuberculosis (DR-TB) and to identify unique characteristics of multidrug-resistant tuberculosis (MDR-TB) in rural China. METHODS: A retrospective study was conducted using TB data collected from 36 TB prevention and control institutions serving rural populations in Shandong Province, China, for the period 2006-2015. RESULTS: Approximately 8.3% of patients suffered from MDR-TB, among whom 70% were newly treated patients; this rate increased by 1.3% annually during the 10-year study period. An increase in the percentage of overall first-line drug resistance against isoniazid, rifampicin, ethambutol, and streptomycin was confirmed (p<0.05). The percentage of MDR-TB in new and previously treated cases increased at yearly rates of 9.9% and 11.1%, respectively. MDR-TB patients were more likely to be female (odds ratio (OR) 1.58, 95% confidence interval (CI) 1.32-1.89), smokers (OR 1.75, 95% CI 1.47-2.07), to have had recent TB contact (OR 1.58, 95% CI 1.04-2.42), or to have been retreated (OR 2.89, 95% CI 2.46-3.41). CONCLUSIONS: Increasing MDR-TB and rates of primary MDR-TB characterize DR-TB cases in rural China. Persistent efforts need to be made among MDR-TB patients in future TB control strategies.

Epidemiological Trends of Drug-Resistant Tuberculosis in China From 2007 to 2014: A Retrospective Study.

The emergence and spread of drug-resistant tuberculosis (DR-TB) has become the major concern in global TB control nowadays due to its limited therapy options and high mortality. A comprehensive evaluation for the epidemiological trends of DR-TB in mainland China, of which TB incidences remain high, is essential but lacking. This study aimed to describe the trends of DR-TB overtime, especially multidrug-resistant TB (MDR-TB); and to identify unique characteristics of MDR-TB cases compared with drug-susceptible TB cases in Mainland China. We retrospectively analyzed surveillance data collected from 36 TB prevention and control institutions in Shandong Province, China over an 8-year period. Unique characteristics of MDR-TB were identified; Chi-square test for trends and linear regression were used to assess the changes in proportions of different resistance patterns overtime. The overall MDR rate was 6.2% in our sample population. There were no statistically significant changes in the percentage of drug-susceptible, isoniazid (INH) resistance, ethambutol (EMB) resistance, streptomycin (SM) resistance, and MDR TB during our study period except that the overall rifampin (RFP) resistance and rifampin monoresistance (RMR) increased at a yearly rate of 0.2% and 0.1%, respectively. Among those with known treatment histories, a higher MDR rate of 8.7% was observed, in which 53.9% were primary MDR-TB patients, and this rate was increasing at a yearly rate of 4.1% over our study period. MDR-TB patients were more likely to be female (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.05-1.34), aged 25 to 44 years (OR, 1.67; 95%CI, 1.45-1.93), retreated (OR, 11.95; 95%CI, 9.68-14.76), having prior TB contact (OR, 1.89; 95%CI, 1.19-2.78) and having cavity (OR, 1.57; 95%CI 1.36-1.81), or bilateral disease (OR, 1.45; 95%CI 1.19-1.76) on chest radiology. Persistent high levels of MDR-TB, increasing rates of primary MDR-TB and RMR characterize DR-TB cases in mainland China; community-acquired drug resistance may be one of the most modifiable factors in future TB control strategies.

[Epidemic status of drug-resistant Mycobacterium tuberculosis in Shandong province, China].

OBJECTIVE: To analyze the present epidemic status of drug-resistant Mycobacterium tuberculosis (MTB) in Shandong Province of China, as compared with findings of survey for drug-resistant MTB in 1997, and therefore to provide valuable data for making the current control policy of drug-resistant MTB. METHODS: From October 2004 to December 2011, the culture positive sputum samples of all 5916 new registered sputum smear-positive TB patients at the county-level TB dispensaries were tested for drug susceptibility. Finally 5542 cases with test results were included in the analysis. Of the total cases, 4198 were male and 1344 were female. The age range of the patients were 15 to 92 years old and the average age was (51 ± 20) years old, among whom, 1304 were ≤ 29 years old, 2106 were from 30 to 59 years old and 2132 were ≥ 60 years old. Of all the cases, 4332 (78.2%) only received initial treatment and 1210 (21.8%) received retreatment. The SPSS 13.0 was used for statistical analysis and χ(2) test was used to compare category, gender, and age groups of patients. RESULTS: The total drug resistance (TDR) rate was 19.4% (1075/5542), which was lower than 23.4% (288/1229) in 1997 in Shandong Province (χ(2) = 10.193, P < 0.01). The rates of single drug resistance (SDR), multidrug resistance (MDR) and poly-drug resistance (PDR) were 11.3% (629/5542), 3.7% (203/5542) and 4.4% (243/5542), respectively. The TDR rate in patients with initial treatment was 19.0% (822/4332), and 62.7% (515/822) of which was SDR. The TDR rate of patients with retreatment was 20.9% (253/1210), and 54.9% (139/253) of which tended to be MDR or PDR. Among TDR patients, those with initial treatment accounted for 76.5% (822/1075) and SDR patients accounted for 58.5% (629/1075). The MDR rate of patients with initial treatment was 2.9% (124/4332) and the rate of patients with retreatment was 6.5% (79/1210), the differences being significant (χ(2) = 36.032, P < 0.01). The TDR rate, initial TDR rate, and retreatment TDR rate in males were 19.9% (834/4198), 19.5% (641/3287), and 21.2% (193/911), respectively, as compared to 17.9% (241/1344), 17.3% (181/1045), and 20.1% (60/299) in females, the differences being not significant (χ(2) = 0.170-2.452, P > 0.05). CONCLUSIONS: The drug-resistant TB control work in Shandong Province has made great achievements in recent years. However, patients with initial treatment were more likely to have drug-resistant MTB. Therefore the future control work should focus on early detection, effective treatment and management to control the spread of drug-resistant MTB.

[Application of mycobacterial interspersed repetitive units in typing Mycobacterium tuberculosis in Shandong].

OBJECTIVE: To evaluate the application of mycobacterial interspersed repetitive units (MIRU) in typing Mycobacterium tuberculosis in Shandong. METHOD: 826 strains of M. tuberculosis from laboratories of 12 county tuberculosis dispensaries in Shandong were cultured and typed by MIRU genotyping in the KICID laboratory. RESULTS: The 826 strains were typed to 201 distinct MIRU patterns, and 123 isolates were unique, 703 strains were grouped into 1 of 78 different MIRU clusters, and the MIRU genotype of the largest cluster was 223325173533. Among the clustered strains, 18 patients had an epidemiological history of contact. The Hunter-Gaston discriminatory index was 0.90. The allelic diversity of the sample was calculated for each other of the MIRU loci, and showed that MIRU26 had 10 alleles and was highly discriminative, while other five MIRU loci (MIRU31, 10, 39, 40, 4) were moderately discriminative. The reproducibility of the MIRU method was 100%. It took about RMB yen50 to genotype one strain. CONCLUSIONS: MIRU genotyping is a reproducible, fast, simple, and relatively cheap method. But because the isolates of 223325173533 genotype are predominant (30.89% of the isolates) in Shandong Province, it needs a second method IS6110 RFLP or by adding other more discriminative variable-number tandem repeat (VNTR) loci to improve the discriminative power.

[The short-term and long-term treatment outcomes in patients with pulmonary tuberculosis positive for drug-resistant and sensitive strains].

OBJECTIVES: To analyze the treatment outcomes in patients with smear positive tuberculosis, and to compare the difference in treatment response among patients infected with drug-sensitive and drug-resistant strains. METHODS: From 1998 to 2000, seven hundred and seventy-seven patients with primary smear-positive tuberculosis, which were from 30 surveillance sites, were followed for two years to monitor their treatment outcomes. RESULTS: At the completion of the 6 months' therapy, the overall rate of treatment failure was 1.8%, 2.6% for the drug-resistant cases and 1.6% for the drug-sensitive cases. Six-month follow-up showed a positive conversion rate of 2.7% in all the cases, 8.5% and 1.2% (P < 0.005) in the drug-resistant and the drug-sensitive cases respectively. One year follow-up showed that the positive conversion rate was 2.6% in all the cases, 6.9% and 1.6% (P < 0.005) in the drug-resistant and the drug-sensitive cases, respectively. Two-year follow-up showed an overall positive conversion rate of 1.3%, 1.0% and 1.3% in the drug-resistant and the drug-sensitive cases, respectively. Of the 152 drug-resistant cases, the rate of treatment failure was 2.6% at the completion of 6 months' therapy, but in cases with MDR-TB the rate was 10.3%. Six-month follow-up showed an overall positive conversion rate of 8.5%, but the rate reached 37.0% in cases with MDR-TB. One-year and two-year follow-up showed that the positive conversion rates were 6.9% and 1.0% respectively in all the drug-resistant cases, but 6.3% and 6.7% respectively in the MDR cases. CONCLUSIONS: Under the guidelines of the National Tuberculosis Program (NTP), the 2H(3)R(3)S(3)Z(3)/4H(3)R(3) regimen for primary smear-positive pulmonary TB was effective. But the cure rate was lower and the positive conversion rate higher in patients with MDR-TB.