[Influences of intervention on the abilities of detecting pulmonary tuberculosis cases in general hospitals].

OBJECTIVE: To explore the influences of intervention on the abilities of detecting pulmonary tuberculosis cases in general hospitals. METHODS: We selected 6 general hospitals at 3 different levels (A, B, and C). The intervened group included hospitals A1, B1, and C1, and the non-intervened group included hospitals A2, B2, and C2. The results after intervention were compared. RESULTS: The report rate of pulmonary tuberculosis, sputum positive rate of reported cases, and sputum check rate of reported cases were significantly higher in hospital A1 than grouping hospital A2 (P = 0.000, P = 0.045, and P = 0.017, respectively). The report rate and sputum examination rate of reported cases were significantly higher in hospital B1 than grouping hospital B2 (P = 0.000, P = 0.024, respectively). The report rate and sputum examination rate of reported cases were significantly lower in hospital C1 than grouping hospital C2 (P = 0.000, P = 0.001, respectively). In hospital A1, the report rate, sputum positive rate of reported cases, and sputum check rate of reported cases were not significantly different before and after intervention (P = 0.182, P = 0.116, and P = 0.583, respectively). In hospital B1, the report rate were significantly different before and after intervention (P = 0.004), while the sputum positive rate of reported cases and sputum check rate of reported cases were not significantly different (P = 0.909, P = 0.052, respectively). In hospital C1, the report rate was significantly higher after intervention (P = 0.025). In hospital C2, the sputum check rate significantly increased (P = 0.000). CONCLUSIONS: Intervention influences the hospitals abilities to detect pulmonary tuberculosis cases. However, more optimized and long-term intervention mechanism should be established to increase case detection rate of pulmonary tuberculosis.

[Study on the efficacy and safety of short-term treatment including fluoroquinolones anti-tuberculosis drugs for rifampicin resistant pulmonary tuberculosis].

OBJECTIVE: To evaluate the efficacy and safety of short-term treatment including fluoroquinolones anti-tuberculosis drugs for rifampicin resistant pulmonary tuberculosis (TB) in those areas carrying out the 'TB control project'. METHODS: TB cases involved in this study were from TB drug resistance surveillance in Heilongjiang province, Zhejiang province and Shenzhen city from 2004 to 2006. TB cases with rifampicin resistant were randomly divided into the treatment group (including fluoroquinolones anti-tuberculosis drugs group) and the control group (re-treatment regimen group). The treatment group was treated with 3RFT AM Ofx Pto PAS-INH/5RFT Ofx Pto PAS-INH while the control group was treated with 3 H3R3Z3E3S3/5 H3R3E3. Efficacy of short-term treatment was analyzed by per-protocol analysis (PP analysis) and intention-to-treat analysis (ITT analysis) while drug adverse reactions was also observed. RESULTS: (1) 154 patients with rifampicin resistant pulmonary tuberculosis were recruited among them, 25 (16.2%) were only resistant to rifampicin, 114 (74.0%) to MDR-TB and 15 (9.8%) to others (resistant R+S, resistant R+E and resistant R+E+S). 114 TB cases completed the full course of treatment,with 71 in the treatment group and 43 in the control group. (2) Sputum negative conversion rate of the treatment group and the control group were 78.9% and 65.1% (chi2CMH = 4.558, P = 0.011) respectively, by per-protocol analysis. Sputum negative conversion rate of the treatment group and the control group were 65.9% and 40.6% (chi2CMH = 0.272, P = 0.001) respectively, by intention-to-treat analysis. The sputum negative conversion rate of the treatment group was higher than in the control group when treating rifampicin resistant pulmonary tuberculosis and MDR-TB patients. (3) Three patients withdrew in each of the two groups because of adverse effects to the drugs. Rates of adverse reaction to drugs appeared to be 23.9% (17/71) and 18.6% (8/43) in the treatment and in the control groups, with no statistically significant difference between the two groups. CONCLUSION: The efficacy of treatment including fluoroquinolones anti-tuberculosis drugs group seemed better than the re-treatment regimen group in treating patients with rifampicin resistant pulmonary tuberculosis and those MDR-TB patients.

[Purification of the heparin-binding haemagglutinin adhesin of Mycobacterium tuberculosis and its application in diagnosis of tuberculosis].

OBJECTIVE: To investigate the application of heparin-binding haemagglutinin adhesin (HBHA) in tuberculosis (TB) diagnosis. METHODS: We prepared native HBHA from cultivated Mycobacterium Bovis Calmetta Guerin (BCG) in Suton liquid medium. After BCG grew to the stationary status, native HBHA was acquired by specific CL-6B chromatography column binding heparin. At the same time, we cloned hbhA gene from Mycobacterium tuberculosis into PET-32alpha (+) expression vector. Recombinant HBHA from E. coli was obtained. Based on the native HBHA and recombinant HBHA, we chose 4 groups of pulmonary TB, extra-pulmonary TB, PPD (-) and PPD (+) healthy control with 47 in each group and conducted ELISA from serum for specific HBHA antibody level. At last we calculated the sensitivity and specificity in TB diagnosis by detection of anti-HBHA antibody level. RESULTS: The native HBHA could be diluted and purified with the PBS containing the 375 mmol/L NaCl by specific CL-6B chromatography column binding heparin; There was no significant difference in experimental result based on the natural and recombinant HBHA protein, also no difference between PPD (-) and PPD (+) healthy control groups. Serum antibody level by ELISA could distinguish pulmonary TB and ertra-pulmonary TB (t = 12.224, P< 0.05). The antibody level of the TB groups (pulmonary TB and ertra-pulmonary TB) was higher than the healthy control groups [PPD (+) and PPD (-) healthy control] (t =25.909, P<0.05). CONCLUSION: Both recombinant and native HBHA can be used as immunological diagnosis in TB. It can be used in TB and especially extra-pulmonary TB diagnosis.

[Effects of two treatment regimens for drug-resistant tuberculosis in tuberculosis control project areas: a comparative study].

OBJECTIVES: To search for an ideal therapeutic regimen for multidrug resistant tuberculosis conforming to the situation of China. METHODS: One hundred and fifty-four patients with rifampin-resistant tuberculosis, 114 multi-drug resistant (MDR-TB) and 40 resistant to other drugs, in Heilongjiang, Zhejiang, and Shenzhen, 107 males and 47 females, aged 39 (19-77), were randomly divided into 2 groups: 85 patients in the group of drug-resistant regimen, 3RFT AM Ofx Pto PAS-INH/5RFT Ofx Pto PAS-INH regimen, including rifapentine (RFT), amikacin (Am), ofloxacin (Ofx), protionamide (Pto), para-aminosalicylic acid-isoniazid (PAS-INH) for 3 months and then RFT, Ofx, Pto, and PAS-INH for 5 months, and 69 in the retreatment regimen group undergoing 3 H3R3Z3E3S3/5 H3R3E3, including isoniazid (H), rifampin (R), pyrazinamide (Z), ethambutol (E), and streptomycin (S) for 3 months and then H, R, and E for 5 months. Sputum smear was checked and the sputum smear conversion rate was calculated as an effective treatment indicator 3, 6, and 8 months later. RESULTS: One hundred and fourteen of the 154 patients were treated for a good 8 months. The sputum smear conversion rate 8 months after treatment of the drug-resistant regimen group was 65.9% (56/85), significantly higher than that of the retreatment regimen group [40.6% (28/69), chi2 = 9.834, P = 0.002]. Eighty-five of the 114 MDR-TB patients had been treated for a good 8 months with a sputum smear conversion rate of 61.8% (42/68), significantly higher than that of the retreatment regimen group [39.1% (18/46), chi2 = 5.638, P = 0.018]. Sputum smear conversion at the end of the 8th month was related to age, course of disease, therapeutic regimen, and the type of drug-resistance (all P < 0.05). The side-effect rate of the drug-resistant regimen group was 23.9% (17/71), higher than that of the retreatment regimen group [18.6% (8/43)], but not significantly (chi2 = 0.446, P = 0.504). CONCLUSION: The drug-resistant regimen recommended above is more effective than the retreatment regimen and should be considered in the areas where the WHO guideline fails to be followed or drug sensitivity test (DST) cannot be conducted and adjusted according to the results of DST and treatment.

[Improved case finding by using sputum examination in pulmonary tuberculosis suspects with clinical symptoms].

OBJECTIVE: To investigate more effective methods in case finding of tuberculosis (TB). METHODS: Sputum examination for TB suspects was applied on the basis of traditional chest X-ray screening. TB suspects with cough more than 3 weeks were subjected to a sputum examination firstly. The case finding rate of X-ray screening alone and in combination with sputum examination for TB suspects were compared. RESULTS: Nine hundred new cases of active pulmonary TB were detected by application of sputum examination to TB suspects, among which 73 more cases were found than X-ray screening alone, and the case detection rate increased 8.8% (73/827). Among the 900 new cases, 30 more cases were found than that of X-ray screening alone in 262 smear positive cases, and the case detection rate increased 12.9%. Three hundred sixty cases were culture positive, among which 63 more cases were found than X-ray screening alone, the case detection rate increased 21.2% (63/297). Among the cases detected by X-ray screening alone, the smear positive rate was 28.1% (232/827), and the culture positive rate was 35.9% (297/827). However, among the cases detected by sputum examination, 29.1% (262/900) was smear positive, and 40.0% (360/900) was culture positive. Among the 73 more cases of active pulmonary TB found by using sputum examination in TB suspects, both the smear positive and the culture positive rates were higher, 41.1% (30/70) and 86.3% (63/73) respectively, as compared to those of cases found by X-ray screening (28.1% and 35.9% respectively). CONCLUSION: Sputum examination in individuals with symptoms suggestive of pulmonary TB could find out more cases with active disease (21.2%) than chest X-ray screening alone.

[Study of the disease burden of patients with drug-resistant and drug-sensitive tuberculosis in Guangdong and Zhejiang provinces].

OBJECTIVE: To investigate the disease burden of drug-resistant and drug-sensitive tuberculosis (TB) patients in Guangdong and Zhejiang provinces. METHODS: Three hundred and two patients with TB, who had been involved in the project for drug resistance surveillance and completed the full course of treatment, were enrolled for this study. The proportion method for drug susceptibility was used. The method of disability adjusted life year (DALY) was applied to assess the disease burden of TB patients. RESULTS: The average DALYs of initial cases with drug-sensitive and drug-resistant TB, and retreated cases with drug-sensitive and drug-resistant TB, were 0.26, 0.68, 0.49, and 1.04, respectively. The average DALY loss of drug-resistant TB patients was 0.86 and that of drug-sensitive TB patients was 0.44. CONCLUSIONS: The values of DALY for initial and retreated cases with drug-resistant TB were 2 times higher than those for patients with drug-sensitive TB, indicating the higher disease burden in drug-resistant TB patients. Therefore, to reduce the disease burden of patients with drug-resistant TB, standardized protocols must be applied in the treatment of TB.

[Study of the expression profile of immunogenesis associated genes in tuberculosis by microarray].

OBJECTIVE: To explore the difference of gene expression profile in tuberculosis patients. METHODS: mRNA levels of pleural fluid and peripheral blood mononuclear cells (PBMC) in tuberculous pleurisy and lung cancer patients were compared by cDNA microarray. Paired mRNAs from fluid specimens of tuberculosis and lung cancer cases were labeled with different fluorochromes during cDNA probe synthesis in a reverse-transcription reaction. The signal intensity of each spot was measured by laser scanner and gene expression was quantified as the tubercle-to-normal fluorescence ratio (T:N ratio). The gene was defined as over expression when the T:N ratio was greater than 2.0 and under expression when the ratio was less than 0.5. RESULTS: Among 626 immunogenesis associated genes there were 53 differences, of which 31 (tnf-alpha, ig-lambda, il-17, il-17r, hla-dp, lcp1, tcralpha, tcrbeta, hsp75, cxcr4, fyb, hla-g, hla-a, il18bp, il-2r, lt-beta, il-8, ip-10, mcp-1, il-12, il-12r, il-10, canx, irf2, ifn-gamma, tlr, il-1, il-7, tlr, lsp-1, il-14)were higher and 22 (il-4, il-18, il-15, ifg-1, scya14, ablim, peci, ppid, hsf 2, actg2, maoa, ttid, gatm, tgfb3, insr, thbd, trap1, tcrgamma, tcrdelta, il-13r, il-11, igf1, a2m)were lower in tuberculous pleurisy than those in the control. CONCLUSIONS: The immunogenesis of tuberculosis involves multi-genetic expression changes, such as tnf-alpha, il-17, il-12, tcralpha, tcrbeta, hsp75, cxcr4, il-4, il-18, il-15 etc., the expression profile of which changed dramatically. The results provide new insight for understanding of the pathogenic mechanisms of tuberculosis and exploring new therapeutic strategies.

[In vitro study on cross resistance of rifampin and rifapentine for Mycobacterium tuberculosis].

OBJECTIVE: To study the bactericidal effect of rifapentine and its cross-resistance with rifampin for Mycobacterium tuberculosis and to determine the critical concentration of rifapentine for laboratory drug susceptibility test and therefore to provide the laboratory data for using rifapentine in the treatment of tuberculosis, particularly rifampin resistant tuberculosis. METHODS: We detected the minimal inhibitory concentrations (MICs) of rifampin and rifapentine to H(37) Rv and isolated strains of rifampin susceptible and resistant Mycobacterium tuberculosis by using Middlebrook 7H9, Sauton and Lowenstein-Jensen media. RESULTS: The MICs of rifampin were > or = 0.32 microg/ml for 80% of the 19 rifampin susceptible strains on Middlebrook 7H9 and the MICs of rifapentine ranged from 0.02 microg/ml to 0.32 microg/ml for most of the strains (84%). The MICs of rifapentine were 2 - 4 times lower than those of rifampin to H(37) Rv and most clinical isolates. The rifapentine susceptible isolates were mostly separated from resistant strains at MICs 5-10 microg/ml. CONCLUSIONS: Our results demonstrate the cross resistance of rifampin and rifapentine and the stronger bactericidal potency of rifapentine than rifampin. Some rifampin resistant strains still show susceptibility to rifapentine, which suggests rifapentine may be effective in the treatment of rifampin resistant tuberculosis. Our results also determined a critical resistant concentration of rifapentine for routine drug susceptibility test.

[The epidemic of childhood tuberculosis in China].

OBJECTIVE: To analyze the epidemic situation of children Tuberculosis (TB) in China. METHODS: To sum up the data of four times national TB epidemic survey from 1979 to 2000, and analyze the epidemic situation of children whose age were between 0 and 14. RESULTS: The TB prevalence rates in children were 8.8%, 9.6%, 7.5% and 9.0% in 1979, 1984/85, 1990, 2000. The active pulmonary TB (PTB) prevalence rates in children were 241.7/100 000 172.1/100 000, 91.8/100 000 in 1979, 1990 and 2000, the bacteriological positive PTB prevalence rates were 12.7/100 000, 12.3/100 000 in 1990 and 2000, the smear positive PTB prevalence rates were 7.5/100 000, 7.5/100 000 and 6.7/100 000 in 1979, 1990 and 2000; It was estimated there were 26.08 million children who were infected by microbacterial TB, 266 thousands children active PTB cases, 36 thousands children bacteriological positive PTB cases and 19 thousands children smear positive PTB cases in 2000 according to the data of the national population survey. the rates were 4.5%, 5.9%, 1.8%, 1.3% when comparing them to the all patients. the ratio of children TB prevalence rates between city and country were 1.8, 1.8, 1.7 and 1.2 in the four survey. CONCLUSIONS: The TB prevalence rates in children had not obvious decrease from 1979 to 2000 were not allowed to optimize to the epidemic of children TB. The bacteriological negative PTB had a bigger. The difference of children TB prevelance between city and country reduced gradually. The quantity of sample and other factors influenced the forecast value of PPD to disease, so it would be a trend of using the routine surveillance to replace the national epidemic survey. BCG still would be the an important content in our national TB control before the emergence of the new and more efficient vaccine.

[Molecular epidemical characteristics of Mycobacterium tuberculosis strains from the nationwide random survey for the epidemiology of tuberculosis in China, 2000].

OBJECTIVE: To explore the epidemical distribution characteristics of Mycobacterium tuberculosis isolated from China. METHODS: The M. tuberculosis strains were gained by multi-stratified grouping random sampling method from the nationwide random survey for the epidemiology of tuberculosis in China, 2000, and analyzed by IS6110-based RFLP and DR-based Spoligotyping DNA fingerprinting. These fingerprinting patterns were transferred into digital data and compared each other, and clustered by Gel compar4.1 Software. The clustering values in different TB patients were compared by chi(2) test and the risk factors for recent transmission were calculated by Odd Ratios. RESULTS: Two hundreds and four of 402 M. tuberculosis strains from this survey were determined to be "Beijing Genotype" M. Tuberculosis strain by DNA fingerprinting analysis. Three clusters M. tuberculosis strains sharing identical fingerprint pattern were found, including one cluster belong to a same family. There were significant difference between female and male, and younger (< 40 years old) and elder (>or= 40 years old) (P < 0.05). Odds Ratio 1 showed youth [1.68 95% CI (1.01 - 2.80)] and male [2.04 95% CI (1.07 - 3.96)], but Odds Ratio 2 showed youth [0.3 95% CI (0.2 - 0.44)] and male [4.96 95% CI (2.77 - 9.00)]. CONCLUSION: M. tuberculosis strains of Beijing Genotype are prevailing in China at present. Male and elder were shown to be significant risk factors for recent transmission. The infection source of M. tuberculosis could be traced by DNA fingerprinting.

[Forecast about number of patients with pulmonary tuberculosis 2001 - 2010].

OBJECTIVE: To forecast the number of patients with pulmonary tuberculosis in 2010. METHODS: A mathematical model was established based on the nationwide epidemiological survey on tuberculosis conducted in 2000 so as to forecast the numbers of patients with pulmonary tuberculosis in 2000s. RESULTS: (1) The number of patients with pulmonary tuberculosis would be a little more than that in 2000, with the pulmonary tuberculosis case detection rate rho of 0.26 being adopted. (2) The number of patients with pulmonary tuberculosis would be smaller than that in 2000, with the pulmonary tuberculosis case detection rate rho of 0.30 being adopted. (3) If the current intervention strategy manages to keep the pulmonary tuberculosis case detection rate at the level of 0.35, the decline in number of patients with pulmonary tuberculosis will approach the goal set by the national program that the number of patients with pulmonary tuberculosis be decreased by 50%. CONCLUSION: The goal set by the national program can be achieved only when the pulmonary tuberculosis case detection rate reaches 0.35.

[DNA fingerprinting of Mycobacterium tuberculosis strains from Beijing, Guangdong and Ningxia].

OBJECTIVE: To explore the epidemic distribution of Mycobacterium tuberculosis isolates from Beijing, Guangdong and Ningxia, and to determine M. tuberculosis strains of the "Beijing Family". METHODS: Two hundred and six IS6110 DNA fingerprinting patterns of M. tuberculosis strains from three provinces (city) were transferred to digital data, compared with the world M. tuberculosis DNA fingerprinting database, and then clustered by Gel compare 4.1 software. The clustering values in different patients with tuberculosis were compared by chi(2) test. Risk factors for recent transmission were calculated using odd ratios. RESULTS: No M. tuberculosis strains were found the same as those of DNA fingerprint database. 56.8% (117/206) fingerprinting patterns of M. tuberculosis shared by least two-thirds of the IS6110 fragments and their Spoligotyping fingerprinting patterns were consistent with those of M.tuberculosis strains of the "Beijing Family". There were significant differences between female and male, different age groups (< 42 years old) and older (>or= 42 years old) (P < 0.05). Odd ratio was 5.06 in the group younger than 42 years old (95% CI: 1.00 - 34.34) and was 4.43 (95% CI: 0.94 - 28.76) in males. CONCLUSION: M. tuberculosis strains of "Beijing Family" were popular in Beijing, Guangdong and Ningxia. Men and younger age group (< 42) were shown to be infected by identical strains more often than women and older aged which might play an important role in the recent transmission of tuberculosis in these areas. IS6110 DNA fingerprinting of M. tuberculosis could be used to trace the source of tuberculosis infection.

Sample survey of drug-resistant tuberculosis in Henan, China, 1996.

BACKGROUND: There is little reliable data on the global drug resistance to tuberculosis (TB) as most of the existing data is based upon biased samples, is not standardized or was obtained using poor techniques. For this reason, the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) developed a global project on anti-TB drug resistance surveillance (DRS) in 1994. China joined this project in 1995 and the province of Henan was selected as the first site for collection of representative samples to survey the prevalence of drug-resistant TB. METHODOLOGY: Standard drug susceptibility testing by the proportion method against streptomycin (S), isoniazid (H), rifampicin (R), and ethambutol (E) was performed with Mycobacterium tuberculosis isolated from 916 new cases and 456 previously treated cases. Treatment outcome of these patients has been evaluated according to the regimens and drug susceptibility patterns. RESULTS: Drug resistance among new cases to any drug was found to be 43.0% and any resistance: S, 32.5%; H, 31.0%; R, 20.7%; and E, 10.3%. Drug resistance among previously treated cases to any drug was 68.2% and any resistance: S, 52.2%; H, 49.3%; R, 48.3%; and E, 20.4%. The cure rate for new cases was 43.3% and 29.4% for previously treated cases. The poor cure rate resulted mainly from a high defaulter rate. CONCLUSION: Drug-resistant TB was found to be highly prevalent in Henan and the cure rate remained poor. The results strongly indicated that Henan should take immediate action to improve the cure rate of patients through expansion of the introduction of the directly observed treatment short-course strategy.