Table of Content

10 June 2008, Volume 30 Issue 6

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Effective treatment of tuberculosis in mice with nanoparticulated streptomycin

Lu Yu,Zhao Weijie,Zheng Meiqin,et al.

Chinese Journal of Antituberculosis. 2008, 30(6):  502-505. 

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Objective To investigate the antituberculosis efficacy of newly developed nanoparticulate forms of streptomycin（SM） for parenteral administration in comparison with conventional preparation "streptomycin sulfate for injections".Methods SPF female BALB/c mice were infected with M.tuberculosis（H₃₇Rv,ATCC27294,10⁷CFU/mouse,iv）.Infected mice were treated ip as follows: Untreated（saline）,5 times per week;SM sulfate USP,200 mg/kg,5 times per week（positive control）;SM sulfate USP,100 mg/kg,twice weekly（comparative control）;SM-NP BSA,100 mg/kg,twice weekly;SM-NP CRM,100 mg/kg,twice weekly.SM formulations were administered ip for 28 days.Four mice from each group were assessed for CFU count and organ weights on days 14,28 and 56.Results All animals survived in NP-SM CRM group,received 800 mg cumulative dose of SM,while survival rate for positive control（SM USP,cumulative 4000 mg） was 92%,and for comparative control（SM USP,total 800 mg） was 58%.Bacterial count in lungs and spleen were significantly lower（2.53 orders of magnitude） in NP groups.Conclusions The activity of Streptomycin,incorporated into biodegradable NP,was significantly improved in comparison to a conventional formulation using an acute murine tuberculosis infection model.It resulted in an 80% decrease of total dose of SM with an increased survival rate.

Rapid detection for capreomycin resistance in clinical isolates of Mycobacterium tuberculosis by phage amplified biological assay

Lin Jianxiong,Wang Dongmin,Peng Dongdong,et al.

Chinese Journal of Antituberculosis. 2008, 30(6):  506-509. 

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Objective To develop a rapid method to detect Mycobacterium tuberculosis(MTB) resistance to capreomycin by phage biologic amplification,and evaluate its application value.Methods Using Absolute concentration method as control,112 MTB isolates were detected their resistance to capreomycin.If the result is inconsistent,its capreomycin MIC was determined using Bactec MGIT 960.Test condition is as follow: 10^-3mg/ml MTB inoculation,capreomycin concentration 5μg/ml,incubate at 37℃ for 24 hours.Results Of 112 MTB isolates,91 were capreomycin-sensitive and 21 were capreomycin-resistance by phage biologic amplification assay;92 were capreomycin-sensitive and 20 were capreomycin-resistance by the Absolute concentration method.Comparing the Results between these two methods,89 capreomycin-sensitive and 18 capreomycin-resistance isolates were consistent.Of 5 isolates with inconsistent results,the Results from phage biologic amplification assay in 3 isolates were consistent with that from MICs.Using the Absolute concentration method as control,the sensitivity,specificity,positive predictive value,negative predictive value,and diagnostic accuracy of detection of capreomycin resistance by phage biologic amplification assay were 90%(18/20),96.7%(89/92),85.7%(18/21),97.8%(89/91),and 95.5%(107/112),respectively.Conclusions It is sensitive,specific,simple and quick to detect the capreomycin resistance in MTB by phage biologic amplification assay,which needs 2 days and do not require special equipments.

Immunotherapeutic effects of IFN-γ combined with M.vaccae vaccine on mice model with tuberculosis

Li Dan,Du Debing,Qiu Shaoqin,et al.

Chinese Journal of Antituberculosis. 2008, 30(6):  510-514. 

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Objective To study the immunotherapeutic effects and its mechanism of IFN-γ combined with M.vaccae vaccine on mice model with tuberculosis.Methods Sixty BALB/c mice were randomly divided into 5 groups: normal group,tuberculosis model group,IFN-γ group,M.vaccae vaccine group,the IFN-γ+ M.vaccae vaccine group.Each group included 12 mice.Forty-eight mice was infected by the tail vein with 1×10⁶CFU of M.tuberculosis H₃₇Rv strain,and treated intraperitoneally with the saline,IFN-γ,IFN-γ combined with M.vaccae vaccine at 10 days after infection.Six mice each group were sacrificed at 6 weeks after infection.The body weights of the mice and the weights of lungs and spleens from the mice were measured.The lungs and spleens of the mice were taken,determined the CFU,and observed histopathologic changes.The level of IFN-γ and IL-4 in the blood were detected with ELISA method.The expression of IFN-γ mRNA and IL-4 mRNA in lungs were detected by RT-PCR method.The survival times in the other 30 mice were evaluated in 60 days.Results The pathological changes of lungs in the three treatment groups were localized,while those in tuberculosis model group were extensive.All of mice died in tuberculosis model group,none of mice died in the normal group and the IFN-γ+ M.vaccae vaccine group,only one mice died in IFN-γ group and M.vaccae vaccine group.At 6 weeks after infection,compared with tuberculosis model group,the CFUs in lungs and spleens were significantly decreased in IFN-γ groups(7.12±0.51) and(6.42±0.48) and in M.vaccae vaccine groups(6.31±0.47) and(6.07±0.39),particularly in the IFN-γ+ M.vaccae vaccine group(2.67±0.36) and(2.12±0.33)(P<0.05).The level of IFN-γ in the blood and the expression of IFN-γ mRNA in lung tissue of mice in tuberculosis model group(162±46) pg/ml and(0.18±0.06) were lower than that in normal group((521±198) pg/ml and(0.98±0.13))(P<0.01),and IFN-γ groups(402±134) pg/ml and(0.66±0.08),M.vaccae vaccine groups(416±153) pg/ml and(0.68±0.09) and IFN-γ+ M.vaccae vaccine group(493±145) pg/ml,(0.81±0.11) were higher than that in tuberculosis model group(P<0.05).The level of IL-4 in the blood and the expression of IL-4 mRNA in lung tissue in tuberculosis model group((102±24.8) pg/ml and(1.46±0.25))were higher than that in normal group((56.2±14.5) pg/ml and(0.04±0.01))(P<0.01),and IFN-γ groups((73.5±15.3) pg/ml and(0.63±0.12)),M.vaccae vaccine groups(71.3±14.6) pg/ml and(0.59±0.13) and IFN-γ+ M.vaccae vaccine group(60.8±12.7) pg/ml and(0.28±0.03) were lower than that in tuberculosis model group(P<0.05).Conclusions IFN-γ combined with M.vaccae vaccine could improve host defence against the infection of Mycobacterium tuberculosis,and reduce mycobacterial growth during tuberculosis,and might be associated with a decrease in inflammation in lung and spleen tissue by activating the Th1 response,and inhibiting the Th2 response,and they have cooperative effect.

The change and the clinical significance of Th1/Th2 cells in patients with tuberculous meningitis

Cai Qingshan,Cai Long,Li Fujian,et al.

Chinese Journal of Antituberculosis. 2008, 30(6):  515-519. 

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Objective To study the distributive characteristics of CD4⁺T helper subtypeⅠandⅡ(Th1/Th2) and Th1-type cytokine(IFN-γ) and Th2-type cytokine(IL-4) in the peripheral blood and the cerebrospinal fluid in patients with tuberculous meningitis,and to gain insight into the poss-ible role of the local and the systemic Th1/Th2 cell-mediated immune response in the pathogenesis of tuberculous meningitis.Methods The ratio of Th1/Th2 cells in the peripheral blood and the cerebrospinal fluid from patients with tuberculous meningitis at the begining and at the three months of chemotherapy was determined by Flow Cytometry,and the concentrations of IFN-γ,IL-4 in the serum and the cerebrospinal fluid of patients with tuberculous meningitis were measured with cytometric bead array(CBA).30 health controls were determined the ratio of Th1/Th2 cells and the concentrations of cytokine in the sera.Results(1) The ratio of Th1/Th2 cells in peripheral blood and the concentrations of IFN-γ,IL-4 in the sera were 3.8%±0.9%,2.03%±1.51%,29.05 ng/L,55.05 ng/L respectively in group tuberculous meningitis at the begining of chemotherapy,4.0%±0.8%,1.6%±1.1%,30.60 ng/L,52.70 ng/L respectively in group tuberculous meningitis at the three months of chemotherapy,6.3%±2.6%,1.7%±0.6%,65.95 ng/L,50.30 ng/L in group healthy.For the ratio of Th1 and the concentrations of IFN-γ in the blood of group tuberculous meningitis were lower than those in group healthy control(P<0.05).There were no statistical differences between the beginning and three months after chemotherapy in group tuberculous meningitis(P>0.05).(2) The ratio of Th1 cells in the cerebrospinal fluid from 25 patients with tuberculous meningitis at the begining and the three months of chemotherapy were 8.4%±4.6%,7.1%±4.4%,respectively.(3) The concentrations of IFN-γ in the cerebrospinal fluid from 30 patients with tuberculous meningitis at the begining and the three months of chemotherapy were 176.45 ng/L、75.50 ng/L,respectively.Conclusions The level of Th1 cells in the peripheral blood from group tuberculous meningitis was lower than that in group healthy control.Th1 response in the cerebrospinal fluid from the patients with tuberculous meningitis at the begining of chemotherapy was higher than that at the three months of chemotherapy.

Mid-term evaluation report on the world bank loaned/DFID granted TB control project in Xinjiang Uygur Autonomous Region

Wu Weidong,Yang Taihua,Li Yuehua,et al.

Chinese Journal of Antituberculosis. 2008, 30(6):  520-523. 

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Objective To evaluation the implementation of the World Bank Loan/DFID granted TB Control Project in Xinjiang Uygur Autonomous Region,and to provide scientific data and evidence for adjusting Mid-term project plan.Methods According to the forms on the Mid-term evaluation of MOH,The annual surveillance data and other materials in 96 counties of Xinjiang from 2002—2005 were collected,summarized and analyzed.Results The project was fully carried out in 96 counties in Xinjiang Uygur Autonomous Region,and the DOTS cover rate is 100%,The registration rate of smear-positive of TB patients have increased from 52/100000 to 89/100000 from 2002 to 2005,the treatment and management of infectious TB patients for free of charge were above 98%,the cure rates of smear-positive of TB is 95%,the cure rates of re-treatment TB patients achieved over 90%,Conclusions The implementation of the World Bank Loan/DFID granted TB Control Project in Xinjiang Uygur Autonomous Region has reached the Mid-term goals of the TB control project and the stage goals of China TB control plan.Evaluation shows,it is necessary to do much more efforts on TB control work in Xinjiang,in order to achieve the goal of NTP.

Operational research on increasing TB case detection through intensive referral and tracing in Hunan province

Bai Liqiong¹,Yang Hualin,Jian Xuewu,et al.

Chinese Journal of Antituberculosis. 2008, 30(6):  524-527. 

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Objective To explore a feasible approach to increase case detection of tuberculosis through intensive referral and tracing of TB suspects and patients between hospital and TB dispensary.Methods An operational research was conducted in 3 cities and 38 jurisdiction counties sampled by non-probability,and a strategic referral and tracing system between hospitals/clinics and TB dispensary was developed upon the local situation in Hunan province of China.One-year monitoring of referral,tracing and diagnosis of TB suspects and cases data was used to assess the outcomes of the project implementation.Comparisons of the case detection and notification of new smear-positive tuberculosis were made between the project year and the previous year,project areas and non-project areas.Results Among 126 public general hospitals/clinics in 38 project counties,124 hospitals referred a mean of 10 TB suspects and cases to TB dispensary monthly.Comparing with the previous year,the initial consultation rate of TB suspects increased 102.1%;the referral of TB suspects from hospitals/clinics to TB dispensary increased 5 times a total of 10596 new smear-positive PTB cases were identified and the notification of new smear positive PTB increased by 112.9% from 27.12/100000 in the previous year to 57.71/100000 in the project year,a significantly higher than non-project area,whose notification was 38.77/100000.Conclusions Intensive referral and tracing of TB suspects and patients between hospital and TB dispensary is a feasible and effective approach to increase case detection.Strengthening administrative intervention and incentive mechanism are essential to achieve the project objectives.

Clinical study on treatment of multi-drug resistance cavitary pulmonary tuberculosis with drug gel

Chen Zhi,Liang Jianqin,Wang Jinhe,et al.

Chinese Journal of Antituberculosis. 2008, 30(6):  528-531. 

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Objective To evaluate the clinical outcome and safety of the treatment of multi-drug resistance cavitary pulmonary tuberculosis with drug gel by fiberbronchoscope.Methods 204 patients of cavitary pulmonary tuberculosis were included in the study.108 patients of them treated with drug gel by fiberbronchoscope and anti-tuberculosis treatment were classified into the experiment group.96 patients treated anti-tuberculosis treatment were classified into the control group.20 mg of the gel used in the experiment group contains pasiniazid 600 mg,streptomycin 1000mg,pyrazinamide 500mg and L-ofloxacin 400mg.Sputum negative conversion rate,tuberculose focus treatment effective power,tuberculous cavity treatment effective power,complication and adverse reaction of all patients at the 6th,12th and 18th month post-treatment were observed.Results Sputum negative conversion rate in the experiment group were 51.9%,79.6% and 88.9% at the 6th,12th and 18th month post-treatment respectively,which were higher than those in the control group.Tuberculose focus treatment effective power in the experiment group were 52.8%,81.5% and 90.7%,tuberculous cavity treatment effective power were 50.9%,79.6% and 89.8% at the 6th,12th and 18th month post-treatment respectively,which were higher than those in the control group too.Complication and adverse reaction of patients in the two groups had no significant difference.Conclusions The clinical outcome and safety of the treatment of multi-drug resistance cavitary pulmonary tuberculosis with drug gel by fiberbronchoscope are better than those of the routine anti-tuberculosis treatment.

Analysis of pulmonary tuberculosis cases reported and referred from general hospital from 2005 to 2007

Fan Yueling

Chinese Journal of Antituberculosis. 2008, 30(6):  532-534. 

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Objective To provide the evidence for enhancing PPM-DOTS and maintaining sustainable development for TB control.By analysing the role of general hosipitals in TB care finding.Methods Shanxi Monthly report on TB case-finding from 2005 to 2007 and Shanxi Monthly report on TB suspect reporting and referring TB suspect from general hospital and being traced by TB control unit were collected and analyzed.Results The rate of referred from general hospital and cases arrived in TB dispensary were 34.2%、35.6% and 39.2% respectively;the rate of traced cases by TB dispensary were 65.6%、82.4% and 91.7% respectively;the rate of arrived in TB dispensary were 65.9%、68.3% and 71% respectively;the rate of total arrived in TB dispensary were 62.7%、71.8% and 78.8% respectively from 2005 to 2007.24.4% of TB cases and suspected referred from general hospital and arrived in TB dispensary were smear positive cases.31.9% of cases and suspected traced and arrived in TB dispensary were diagnosed smear positive.Conclusions The rate of referred from general hospital and cases arrived in TB dispensary were all increasing from 2005 to 2007;the rate of traced cases by TB dispensary;the rate of arrived in TB dispensary and the rate of total arrived in TB dispensary increased too from 2005 to 2007;the case finding proportion through referring and tracing increased every year from 2005 to 2007.The role of generals hospital in TB case finding is important and PPM-DOTS should be enhanced.

Clinical analysis of 132 active pulmonary tuberculosis in hospitalized patients in a general hospital

Wang Baozeng,Qiu Xiaojian

Chinese Journal of Antituberculosis. 2008, 30(6):  536-540. 

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Objective In order to investigate the reasons for management delay and to obtain better identification to untypical tuberculosis,a retrospective study was carried out in a general hospital to assess the onset,diagnosis and treatment of active tuberculosis in hospitalized patients.Methods From Jan 2002 to Dec 2006,the data of 132 patients with active pulmonary tuberculosis who were hospitalized in Beijing Tiantan hospital were analyzed,include clinical symptoms,auxiliary examinations,diagnosis,and managements,etc.Results 29 patients(22%) were admitted in hospital as other diseases at out-patient clinic,mostly including pneumonia,bellows shadow and lung Abscess.103 patients(78%) were admitted as other diseases but discovered combination with active tuberculosis,mostly including chronic obstructive pulmonary diseases and pleurisy.The elders,migrate workers and peasants from other area accounted for the big proportion of the total population.The common clinical symptoms included fever(43.9%),cough(37.1%),low appetite(21.2%),wheeze(19.7%),headache(11.4%),breath holding(10.6%),chest pain(10.6%),hemoptysis(9.1%) and debility(8.3%).There were 11 patients with merely pulmonary tuberculosis,and 121 combination with other diseases,mostly including cerebrovascular disease,malnutrition,chronic obstructive pulmonary diseases and diabetes.51 patients had more than two kinds of diseases.There were 21 patients with extrapulmonary tuberculosis,mostly including tuberculous meningitis,intracranial tuberculosis and intestinal tuberculosis.89 patients were diagnosed identified pulmonary tuberculosis by CT,while 14 patients conceivable,Final diagnosis ratio was 86.4% by CT.Sputum smear examination were not be performed before admission.82 patients(62.1%) had sputum smear after admission,among which 31(37.8%) were positive.Conclusions Clinical physicians at out-patient clinic in general hospital must keep an alert dealing with pulmonary tuberculosis patients by sputum smear and chest CT for early identification.