CYP2E1, GSTM1 and GSTT1 genetic polymorphisms and susceptibility to antituberculosis drug-induced hepatotoxicity: a nested case-control study.

WHAT IS KNOWN AND OBJECTIVE: The pathogenic mechanism of antituberculosis drug-induced hepatotoxicity (ATDH) is thought to involve drug-metabolizing enzymes including N-acetyl transferase2 (NAT2), cytochrome P4502E1 (CYP2E1) and glutathione S-transferase (GST) M1, T1. The associations between genetic polymorphisms of those genes and ATDH have been reported but with inconsistent results. Moreover, most studies were hospital-based retrospective studies and not prospective. We aimed to investigate possible associations of CYP2E1, GSTM1 and GSTT1 genetic polymorphisms with ATDH using a more robust case-control study nested in a population-based prospective antituberculosis treatment cohort. METHODS: A total of 4304 patients with smear-positive tuberculosis (TB) who received standard short-course chemotherapy were monitored for 6-9 months. Incidence density sampling method was adopted to select controls and 4 : 1 matched with each ATDH cases by age (± 5 years), sex, treatment history, disease severity and drug dosage. The CYP2E1, GSTM1 and GSTT1 polymorphisms were genotyped using PCR-RFLP and multiplex PCR methods. Conditional logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI), as well as corresponding P-values. RESULTS AND DISCUSSION: A total of 89 ATDH cases and 356 controls were included in this study. There was no statistically significant association between CYP2E1 RsaI c1/c1 genotype or DraI C/C genotype and ATDH (OR = 0·99, 95% CI:0·62-1·59; OR = 1·13, 95% CI: 0·40-3·20, respectively) compared with CYP2E1 RsaI c1/c2 or c2/c2 genotypes or DraI D/D genotype, or between GSTM1/GSTT1 null genotypes and ATDH (OR = 1·22, 95% CI: 0·76-1·96; OR = 0·96, 95% CI: 0·60-1·52, respectively) compared with non-null genotypes. WHAT IS NEW AND CONCLUSION: This is the first study of the involvement of CYP2E1, GSTM1 and GSTT1 genetic polymorphisms in ATDH using a nested case-control population-based prospective cohort design. We could not confirm positive associations of genetic polymorphisms of CYP2E1 RsaI, CYP2E1 DraI, GSTM1 null and GSTT1 null with ATDH reported by various groups, in our Chinese TB population.

The impact of migrants on the epidemiology of tuberculosis in Beijing, China.

SETTING: Tuberculosis (TB) services in the Municipality of Beijing, China. OBJECTIVE: To evaluate the impact of migrants on the epidemiology and management of TB in Beijing. DESIGN: Comparison of information on permanent residents and migrants from routine reports of TB cases registered in Beijing from 1993 to 2005. RESULTS: From 1993 to 2005, there was a steady rise in the proportion of migrants among TB cases notified in Beijing, from approximately one in 10 cases to one in three cases. The results of treatment in migrant cases of TB over the period 1997-2004 were unsatisfactory. The proportion of cases cured among permanent residents was 90.6%, compared with only 37.0% of cases among migrants. CONCLUSION: Migrants pose a challenge to TB services in Beijing. Special attention must be given to them by the National Tuberculosis Programme to address these challenges.

The impact of directly-observed treatment on the epidemiology of tuberculosis in Beijing.

SETTING: Fully supervised chemotherapy, or directly observed treatment (DOT), for newly detected smear-positive cases in Beijing, has been successfully implemented for two decades. OBJECTIVE: To evaluate the progress made in tuberculosis control, and in particular to evaluate the impact of DOT on tuberculosis epidemiology in Beijing. DESIGN: Epidemiological parameters on tuberculosis, consisting of mortality, prevalence, notification rate, tuberculous meningitis in children and initial drug resistance rate, were collected and analysed. Their trends were evaluated and compared with DOT implemented for new smear-positive cases in Beijing from 1978 to 1996. RESULTS: The coverage of DOT for new smear-positive pulmonary tuberculosis cases has increased from 10% in 1978 to more than 90% since 1990. Since DOT was introduced in 1978, mortality from tuberculosis has declined by an average of more than 7% per year. The reduction rate of 17.2%, and the rates of chronic cases and tuberculous meningitis in children decreased dramatically. The rate of newly registered smear-positive cases decreased from 18.9/100000 in 1986 to 7.3/100000 in 1996, giving an average annual reduction rate of 9.1 during this period. Initial resistance to isoniazid and streptomycin decreased from respectively 13.9% and 12.3% in 1978-1979 to 4.2% and 5.8% by 1996. The level of multidrug resistance was low and stable, at 0.8% in 1996. CONCLUSION: The experience of the Beijing tuberculosis control programme convincingly demonstrates that it is possible to improve the epidemiological situation rapidly in a low-income country, at very low cost and in a manner that is self-sufficient and sustainable.

[Mass photofluorography in early detection of peripheral lung cancer].

During 5 consecutive years of 100 mm photofluorography, 21 cases of primary lung cancer were discovered among 211,881 checked subjects in 54 factories in the suburbs of Beijing. Detection rate was 9.9/100,000. In the male smokers 40 years old or over, who comprised 13.7% of all examined with a detection rate of 55.0/100,000. Among the 21 cases, peripheral cancer was 61.9%, in which 38.4% were stage I 69.2% were treated by surgical resection, much higher than that of the central type. It may be concluded that photofluorography in mass screening has a certain value in early detection of the peripheral lung cancer and the male smokers 40 years or over should be examined as a priority group.

Trend of initial drug resistance of tubercle bacilli isolated from new patients with pulmonary tuberculosis and its correlation with the tuberculosis programme in Beijing.

SETTING: The tuberculosis control programme of Beijing. OBJECTIVE: To observe the trend of initial drug resistance of tubercle bacilli and to try to correlate it with the Beijing tuberculosis control programme. DESIGN: Susceptibility testing of randomly collected isolates of positive sputum culture from new patients with pulmonary tuberculosis without a history of prior antituberculosis therapy, in 1962 and continuously since 1978. Collection of treatment data from the Beijing tuberculosis control programme. RESULTS: The trend of initial drug resistance in Beijing began to decline in 1978. The Beijing tuberculosis treatment programme has been very successful, resulting in rapid reduction of prevalence of smear-positive cases. CONCLUSION: It appears that the trend of initial drug resistance correlates with progress made in the implementation of the successful tuberculosis programme in Beijing. It is recommended that continuous observation of initial drug resistance be one of the indices of tuberculosis surveillance.

The prevalence of asthma and asthma-like symptoms among adults in rural Beijing, China.

No data have been reported on the prevalence of asthma in rural areas of China. The objective of the present study was to determine the prevalence of asthma-like symptoms, reported asthma and reported asthma attacks in rural Beijing, China, and to compare the prevalence in 20-44-yr-old participants with those reported for Canada and the European Community Respiratory Health Survey (ECRHS). For a cross-sectional survey, 30 villages were randomly selected in the counties of Shunyi and Tongxian, 50 km north and east respectively of the city of Beijing and within the municipality of Beijing. The International Union Against Tuberculosis and Lung Disease questionnaire on bronchial symptoms translated into Chinese was completed by village doctors for each individual of >15 yrs. The survey was completed by 22,561 individuals, representing 98% of the eligible population. The prevalence of asthma-like symptoms and reported asthma attacks was higher in females than in males and increased with age. Smoking significantly increased the prevalence of symptoms; the effect in females was greater than in males. Among the 20-44-yr-olds, the prevalence of reported asthma attacks in the previous 12 months was 0.67% in rural Beijing, very much lower than that reported in ECRHS centres (3.1%), urban Canada (6.9%) and semirural Canada (5.1%), after adjusting for age and sex. The prevalence of asthma-like symptoms was also very low in rural Beijing compared with ECRHS centres and Canada. It is concluded that the prevalence of asthma-like symptoms and reported asthma was low in rural China compared with other countries, consistent with reports of the relative scarcity of asthma in farms and the "hygiene hypothesis".

Risk of tuberculosis infection and tuberculous meningitis after discontinuation of Bacillus Calmette-Guerin in Beijing.

In Beijing, the notification rate of smear-positive tuberculosis (TB) has been below 20 per 100,000 since 1986, and continues to decline. To accurately measure the risk of TB infection in a population in which the results of tuberculin skin testing were not confounded by vaccination with Bacillus Calmette-Guerin (BCG), BCG vaccination at birth was discontinued from 1988 in Shun-yi County. In 1995, the prevalence of TB infection among 12,836 primary school children aged 6 to 7 yr and without BCG scars was 1.4%, giving an estimated annual risk of infection of 0.19% (95% confidence interval: 0.16 to 0.22%). The prevalence of TB infection in children aged 5 to 9 yr in Beijing in 1950 was 46%. The number of cases of tuberculous meningitis did not increase after discontinuation of BCG. We conclude that discontinuation of BCG had no detectable harmful effects, and that control of TB in Beijing has markedly reduced the prevalence of TB infection since 1950.