Objective: To investigate the characteristics of katG and inhA gene mutations in multidrug-resistant tuberculosis (MDR-TB), pre-extensively drug-resistant tuberculosis (preXDR-TB), and their correlation with resistanc...Objective: To investigate the characteristics of katG and inhA gene mutations in multidrug-resistant tuberculosis (MDR-TB), pre-extensively drug-resistant tuberculosis (preXDR-TB), and their correlation with resistance to protionamide (Pto). Methods: A total of 229 patients with MDR-TB and pre-XDR-TB diagnosed in the Eighth Affiliated Hospital of Xinjiang Medical University from January 2020 to February 2024 were selected to analyze the characteristics of katG and inhA mutations in MTB clinical isolates and their correlation with Pto resistance. Results: The mutation rate of katG (with or without inhA mutation) was 85.2%. The mutation rates in MDR-TB and pre-XDR-TB were 87.4% (125/143) and 81.4% (70/86), respectively. The mutation rate of inhA (including katG mutation) was 14.8% (34/229), which was 12.6% (18/143) and 18.6% (16/86) in MDR-TB and pre-XDR-MTB, respectively. There was no difference in mutation (P > 0.05). Conclusion: The total resistance rate to Pto in 229 strains was 8.7% (20/229), which was 8.4% (12/143) and 9.3% (8/86) in MDR-TB and pre-XDR-TB, respectively. Among the inhA mutant strains, 13 were resistant to the Pto phenotype, and the resistance rate was 65% (13/20). In MDR-TB and pre-XDR-TB strains resistant to Pto, inhA gene mutations occurred in 66.7% (6/9) and 63.6% (7/11), respectively. The resistance rates of MDR-MTB and pre-XDR-TB strains without inhA gene mutation to Pto were 2.4% (3/125) and 5.7% (4/70), respectively.展开更多
Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its asso...Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its associated cost and side effects. The objective of this study was to assess the drug resistance pattern and assess risk factor associated with MDR-TB among pulmonary tuberculosis patients attending National Tuberculosis Center. Methodology: The comparative cross sectional study was conducted at National Tuberculosis Center during August 2015 to February 2015. Early morning sputum samples were collected from pulmonary tuberculosis suspected patients and subjected to Ziehl-Neelsen staining and fluorochrome staining and culture on Lowenstein-Jensen (LJ) medium. Drug Susceptibility test was performed on culture positive isolates by using proportion method. Univariate and multivariate analysis was computed to assess the risk factors of MDR-TB. Results: Out of 223 sputum samples, 105 were fluorochrome staining positive, 85 were ZN staining positive and 102 were culture positive. Out of 102 culture positive isolates, 37.2% were resistance to any four anti-TB drugs. 11 (28.9%) were initial drug resistance and 28 (43.7%) were acquired drug resistance. The overall prevalence of MDR-TB was 11.7%, of which 2 (5.3%) were initial MDR-TB and 10 (15.6%) were acquired MDR-TB. Univariate and multivariate analysis showed female were significantly associated (P = 0.05) with MDR-TB. Conclusion: Drug resistance TB particularly MDR-TB is high. The most common resistance pattern observed in this study was resistance to both isoniazid and rifampicin. Female were found to be associated with MDR-TB. Thus, early diagnosis of TB and provision of culture and DST are crucial in order to combat the threat of DR-TB.展开更多
Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of th...Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.展开更多
Introduction: Tuberculosis is closely linked to poverty, with patients facing significant indirect treatment costs. Treating drug-resistant tuberculosis further increases these expenses. Notably, there is a lack of pu...Introduction: Tuberculosis is closely linked to poverty, with patients facing significant indirect treatment costs. Treating drug-resistant tuberculosis further increases these expenses. Notably, there is a lack of published data on the indirect costs incurred by patients with drug-resistant tuberculosis in Mozambique. Objective: To assess the indirect costs, income reduction, and work productivity incurred by patients undergoing diagnosis and treatment for Drug-Resistant Tuberculosis (DRTB) in Mozambique during their TB treatment. Methods: As part of a comprehensive mixed-methods study conducted from January 2021 to April 2023, this research utilized a descriptive cross-sectional approach, incorporating both quantitative and qualitative methods. The primary goal was to evaluate the costs incurred by the national health system due to drug-resistant TB. Additionally, to explore the indirect costs experienced by patients and their families during treatment, semi-structured interviews were conducted with 27 individuals who had been undergoing treatment for over six months. Results: All survey participants unanimously reported a significant decline in labour productivity, with 70.3% experiencing a reduction in their monthly income. Before falling ill, the majority of respondents (33.3%) earned up to $76.92 monthly, representing the minimum earnings range, while 29.2% had a monthly income above $230.77, the maximum earnings range. Among those who experienced income loss, the majority (22.2%) reported a decrease of up to $76.92 per month, and 18.5% cited a loss exceeding $230.77 per month. Notably, patients with Drug-Resistant Tuberculosis (DRTB) have not incurred the direct costs of the disease, as these are covered by the government. Conclusion: The financial burden of treating Drug-Resistant Tuberculosis (DRTB), along with the income reduction it causes, is substantial. Implementing a patient-centred, multidisciplinary, and multisector approach, coupled with strong psychosocial support, can significantly reduce the catastrophic costs DRTB patients incur.展开更多
Background/objective: A nationwide survey on the resistance to first line anti-tuberculosis (anti-TB) drugs was conducted in Ghana from 2007-2008 by Noguchi Memorial Institute for Medical Research in collaboration wit...Background/objective: A nationwide survey on the resistance to first line anti-tuberculosis (anti-TB) drugs was conducted in Ghana from 2007-2008 by Noguchi Memorial Institute for Medical Research in collaboration with the National Tuberculosis Control Programme. We aimed to characterize mycobacterial species causing pulmonary tuberculosis (PTB) and determine the resistance pattern to first line anti-TB drugs among newly diagnosed and previously treated PTB patients in Ghana. Methods: Two sputum samples from consented new smear positive PTB patients who had never been treated for TB or had been on anti-TB treatment for less than a month and patients who had been treated for TB previously for more than a month in selected diagnostic centres nationwide were collected for culture, identification and drug susceptibility test. Culture positive isolates were tested against streptomycin (S), isoniazid (H), rifampicin (R) and ethambutol (E) using the simplified proportion method and line probe assay (LPA). The LPA was performed in mid-2017. Results: Among 410 samples, 345 positive cultures were obtained and identified as Mycobacterium tuberculosis complex (MTBC). Of the 345 isolates, 133 were further differentiated by GenoType MTBC®as M. tuberculosis, 126 (94.7%) and M. africanum 7 (5.3%). The overall drug resistance patterns were as follows: 43/345 (12.5%), 6/345 (1.7%), 9/345 (2.6%) and 71/345 (20.6%) were resistant to H, R, E and S respectively and 5/345 (1.4%) were multi-drug resistant (MDR). Conclusion: The results indicate high levels of resistance to S and H among new and previously treated TB patients. We recommend adequate surveillance systems including periodic national anti-TB drug resistance surveys.展开更多
Tuberculosis(TB)is a chronic infectious disease caused by Mycobacterium Tuberculosis(MTB).It is the second largest single cause of death besides novel coronavirus pneumonia.Along with the abuse of antibiotics and exte...Tuberculosis(TB)is a chronic infectious disease caused by Mycobacterium Tuberculosis(MTB).It is the second largest single cause of death besides novel coronavirus pneumonia.Along with the abuse of antibiotics and extensive use of anti-tuberculosis drugs,multidrug-resistant(MDR)TB,drug-resistant(XDR)TB and totally drug-resistant(TDR)TB became obstacles to the tuberculosis eradication worldwide.According to the World Health Organization(WHO)statistics,China is not only a high burden tuberculosis country in the world,but also a country with a serious epidemic of MDR.Traditional drugs fail to meet the needs of tuberculosis control.Therefore,it is urgent to find new targets of anti-tuberculosis drugs and develop new anti-tuberculosis drugs.Hence,this paper systematically summarizes the mechanism of traditional and newly developed anti-tuberculosis drugs,in which stressing the research progress of drug resistance mechanisms.This work provides us with new insights of new anti-tuberculosis drug developments,and may contribute to a reduction in the harm that tuberculosis brings to society.展开更多
Objective To investigate the prevalence of primary drug-resistant tuberculosis(TB) and associated risk factors in China. We also explored factors contributing to the transmission of multidrug-resistant tuberculosis...Objective To investigate the prevalence of primary drug-resistant tuberculosis(TB) and associated risk factors in China. We also explored factors contributing to the transmission of multidrug-resistant tuberculosis(MDR-TB). Methods A total of 2794 representative, Mycobacterium tuberculosis isolates from treatment-naive patients were subjected to drug susceptibility testing, and risk factors for drug-resistant TB were analyzed. We also analyzed MDR-TB strain sublineages, drug-resistance-conferring mutations, and risk factors associated with clustered primary MDR strains. Results Among 2794 Mycobacterium tuberculosis isolates from treatment-naive patients, the prevalence of any resistance to first-line drugs was 33.2% and the prevalence of MDR-TB was 5.7%. We did not find any risk factors significantly associated with resistance to first-line drugs. The 93 primary MDR-TB isolates were classified into six sublineages, of which, 75(80.6%) isolates were the RD105-deleted Beijing lineage. The largest sublineage included 65(69.9%) isolates with concurrent deletions of RD105, RD207, and RD181. Twenty-nine(31.2%) primary MDR strains grouped in clusters; MDR isolates in clusters were more likely to have S531 L rpoB mutation. Conclusion This study indicates that primary drug-resistant TB and MDR-TB strains are prevalent in China, and multiple measures should be taken to address drug-resistant TB.展开更多
The prognosis of patients with previously treated tuberculosis (TB) was suggested to be dependent on whether the initial treatment was in compliance with the established guidelines. The aim of this retrospective multi...The prognosis of patients with previously treated tuberculosis (TB) was suggested to be dependent on whether the initial treatment was in compliance with the established guidelines. The aim of this retrospective multicenter study was to determine the proportion of new TB patients who received standard doses of rifampicin in multiple provinces of China, and the relationship between low doses of rifampicin and frequency of rifampicin-resistance as well as treatment outcomes. A total of 713 new TB patients were treated with either once-daily dose of bulk anti-TB drugs (group I) or every other day combination blister packs of anti-TB drugs containing rifampicin (group II) at more than 30 TB treatment centers/hospitals in China. Treatment history, therapeutic doses of rifampicin, and information about patients were extracted from their medical records and analyzed, and rifampicin-resistance of isolates collected from patients following the treatment as well as treatment outcomes were compared between two treatment groups. Among 522 patients in treatment group I, 154 (29.5%) received standard and 363 (69.5%) received low doses of rifampicin;238 (45.6%) isolates were rifampicin-resistant, and 243 (46.6%) were successfully treated. Among 191 patients in treatment group II, 175 (91.6%) received standard and 15 (7.9%) received low doses of rifampicin;72 (37.7%) isolates were rifampicin-resistant, and 105 (55%) were successfully treated. When patients who received low doses of rifampicin were compared to others within the same treatment group, increased rates for rifampicin-resistance and treatment failure were observed. Results from this study showed that most new TB patients in treatment group I (69.5%) received low doses of rifampicin, and their treatment outcomes were worse than those in treatment group II, indicating that low doses of rifampicin used for the initial treatment of new TB patients were correlated to increased frequency of rifampicin-resistance and poorer treatment outcomes.展开更多
Objective:To determine the patterns of resistance to first line anti-tuberculosis(TB)drugs among a collection of Mycobacterium tuberculosis(MTB)isolates from 5 provinces of Iran.Methods:A total of the 6 426 clinical s...Objective:To determine the patterns of resistance to first line anti-tuberculosis(TB)drugs among a collection of Mycobacterium tuberculosis(MTB)isolates from 5 provinces of Iran.Methods:A total of the 6 426 clinical specimens from patients suspected of active TB were collected from March 2010 to June 2012.All specimens were subjected for microscopy and culture tests in the TB centers of studies provinces.Drug susceptibility testing to the first line anti-TB drugs for culture positive MTB was performed on Lwenstein-Jensen(LJ)medium using proportion method.Results:Of 6 426 clinical specimens,261 were culture positive for mycobacteria,of which 252 were MTB and 9 were MOTT(mycobacteria other than tuberculosis).Of 252 MTB isolates.211(83.7%)were pan-susceptible and 41(16.3%)were resistant to at least one drug.Resistance was most common to streptomycin.30 isolates(12.0%),followed by isoniuzid,20isolates(8.0%),rifampin,15 isolates(6.0%)and ethambutol,14 isolates(5.5%).Sixteen(6.3%)MTB isolates were MDR.A clear evidence of heterogeneity amongst the 5 provinces in the proportions with resistance to one or more drugs was observed[χ~2=12.209(4 degrees of freedom),P values=0.015 9].Conclusions:The prevalence of drug resistance in this study area underscoring the need for further enforcement of TB control strategies in the Iran.Drug susceptibility testing for all TB cases to provide optimal treatment,establishing advanced diagnostic facilities for rapid detection of MDR-TB and continuous monitoring of drug resistance are recommended for prevention and control of drug-resistant TB.展开更多
Background: We aim to determine the proportions and patterns of resistance to first-line drugs: isoniazid (H), rifampicin (R), ethambutol (E) and streptomycin (S) among pulmonary tuberculosis patients. Methods: Strain...Background: We aim to determine the proportions and patterns of resistance to first-line drugs: isoniazid (H), rifampicin (R), ethambutol (E) and streptomycin (S) among pulmonary tuberculosis patients. Methods: Strains were obtained from 1584 culture positive pulmonary tuberculosis patients. All specimens were inoculated into L?wenstein-Jensen media (LJ) and TK selective;drug susceptibility tests (DST) were performed for first-line drugs. Results: Multidrug resistant (MDR) were detected in 146 (9.2%) isolates. Three hundred (18.9%) isolates were resistant to H;220 (13.9%) to R;168 (10.6%) to S;137 (8.6%) to E. Any drug resistance was detected in 442 (27.9%) isolates. MDR rate was higher in male patients than females (P = 0.006). MDR rates were different according to the age groups (P = 0.02). The highest rate was in 35 - 44 years and the lowest rate was in 15 - 24 years. Conclusions: We found an association between middle age and male gender and MDR tuberculosis.展开更多
Tuberculosis (TB) is one of the major causes of morbidity and mortality worldwide. In India, nearly 1.8 million new cases of TB are reported annually, which accounts for a fifth of new cases in the world—greater than...Tuberculosis (TB) is one of the major causes of morbidity and mortality worldwide. In India, nearly 1.8 million new cases of TB are reported annually, which accounts for a fifth of new cases in the world—greater than in any other country. Anti-tubercular drugs (ATDs) have been used for decades, and widespread resistance to them is a very serious public health concern in any part of the world. Aim of this study was to determine the prevalence of Rifampicin (the first line Anti-TB drug) resistance among both pulmonary and extra-pulmonary samples tested positive for Mycobacterium tuberculosis and thereby predict the prevalence of Multi-drug resistant (MDR) tuberculosis in Kolkata and its Suburban regions. All 331 randomly collected clinical samples (both Pulmonary and Extra Pulmonary) were initially screened by Zeihl-Neelsen AFB staining followed by culture on BacT/Alert 3D system and on Lowenstein-Jensen medium and the positive samples were subjected to detection of Mycobacterium tuberculosis complex (MTBC) and simultaneous analysis of Rifampicin resistance by Xpert MTB/RIF assay. Out of the 51 (15.40%) culture positive samples, 13.7% of pulmonary samples and 9.09% of extra-pulmonary samples were Rifampicin resistant. The prevalence of Rifampicin resistant TB in our study is high and the possible reasons can be mixing of new as well as retreatment cases and smaller sample size but, yet it can help Government and public health regulatory bodies to formulate adequate strategies to fight against drug resistant tuberculosis, especially in this part of the world.展开更多
Introduction: Recently rapid development of drug resistant TB, particularly MDR TB (Multi Drug Resistant TB) and XDRTB (Extensively Drug-Resistant TB) possess a major threat to control of tuberculosis globally. I...Introduction: Recently rapid development of drug resistant TB, particularly MDR TB (Multi Drug Resistant TB) and XDRTB (Extensively Drug-Resistant TB) possess a major threat to control of tuberculosis globally. Information on the extent of MDR-TB from Kenya is largely limited due to several factors. Monitoring of development of resistance is a vital tool in providing critical information for effective planning for TB control and in management of patients infected with TB. Methods: Cross-sectional with cluster design. Results: A total of 2,171 participants recruited into the study from 50 selected clusters. Prevalence of rifampicin resistance for new cases was 1.3% [95% CI, 0.8-2.0] and INH resistance was 5.5% [95% CI, 4.5-6.7]. MDR TB was found in 0.67% of new cases and 2.1% amongst previously treated TB cases. Discussion: Resistance to isoniazid in Kenya has been on the decline due to introduction of rifampicin in combined therapy. There was increase of MDR TB among new cases by 24% and decline in previously treated cases due to lethal impact of HIV. Conclusions: Although drug resistance TB is a growing problem in Kenya, resistance to isoniazid and rifampicin MDR TB is less than previously estimated. The country should continue to monitor drug resistance and ensure effective use of anti TB medicines.展开更多
Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse eff...Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.展开更多
To study the characteristics of drug-resistant genetic mutation of rpoB on coal workers' pneumoconiosis complicated with L-form of Mycobacterium tuberculosis. Methods: A total of 42 clinical isolated strains of Myco...To study the characteristics of drug-resistant genetic mutation of rpoB on coal workers' pneumoconiosis complicated with L-form of Mycobacterium tuberculosis. Methods: A total of 42 clinical isolated strains of Mycobacterium tuberculosis L-forms were collected, including 31 drug-resistant strains. Their genomes DNA were extracted, the target genes were amplified by PCR, and the hot regions in the rpoB gene were analyzed by automated DNA sequenator. Results: No mutation of rpoB gene was identified in 11 rifampicin-sensitive strains while conformation changes were found in 31 rifampicin-resistant strains. The mutation rate was 93.55% (29/31) in resistant strains, mainly concentrated in codon 531 (51.6%, 16/31) and 526 (32.26%, 10/31). Base substitutions happened, including 27 unit point mutation and 2 two point mutation. The mutation of codon 516 that new found wasn't reported by internal and overseas scholars. Conclusion: The substitution of highly conserved amino acids encoded by rpoB gene results in the molecular mechanism responsible for rifampicin resistance in Mycobacterium tuberculosis L-forms. It also proves that rpoB gene is diversiform.展开更多
Objective:To study the relationship between mutation in the katG gene and drug resistance of INH in Mycobacterium tuberculosis L-forms among patients of pneumoconiosis complicated with pulmonary tuberculosis, and to ...Objective:To study the relationship between mutation in the katG gene and drug resistance of INH in Mycobacterium tuberculosis L-forms among patients of pneumoconiosis complicated with pulmonary tuberculosis, and to explore the clinical application of PCR-SSCP. Methods: A total of 52 clinical isolated strains of Mycobacterium tuberculosis L-forms were collected. Mutation in the katG genes was detected by PCR-SSCP and traditional antimicrobial susceptibility test (AST). Results: The results by AST showed that there were 40 persisters in 52 clinical isolated strains. The drug resistant rate was 76.92%(40/52), and the gene mutation rate of katG was 57.70%(30/52)by PCR-SSCP, the difference was no quite significance (X^2 = 2.8507, P 〉 0.05). The coincidence rate of two methods was 75.00% (30/40). Conclusion: The detectionrate of katG resistant strains in Mycobacterium tuberculosis L-forms was high by PCR-SSCP. The combined application of PCR-SSCP and traditional antimicrobial susceptibility test can improve the detecting rate.展开更多
Introduction: More than half of patients with central nervous system tuberculosis (CNS TB) die or are left with severe neurological deficits despite receiving anti-TB treatment. Aims of the study: This study examined ...Introduction: More than half of patients with central nervous system tuberculosis (CNS TB) die or are left with severe neurological deficits despite receiving anti-TB treatment. Aims of the study: This study examined risk factors associated with poor response to initial treatment with four anti-TB drug regimens or three drug regimens with steroids as adjuvant therapy. Methods: This study analyzed medical records from two tertiary hospitals in Busan, Korea, between January 2009 and March 2012. The subjects were non-human immunodeficiency virus (HIV)-infected patients aged ≥16 years with clinical CNS TB. The subjects were divided into two groups according to response to treatment. Results: In totally, 52 patients with CNS TB were included. Of these, 14 (26%) and 38 (73%) showed poor and good responses, respectively. Of the patients with poor response, nine had stage III disease (64.3%) according to the British Medical Research Council (BMRC) staging system. A significantly higher proportion was seen in the good response group (p < 0.05). Patients with positive cerebrospinal fluid (CSF) acid-fast bacillus (AFB) culture, positive sputum AFB culture, positive CSF TB polymerase chain reaction (PCR) results, and brain tuberculoma had poorer responses (p < 0.05). Multivariate analysis to determine risk factors associated with poor response to anti-TB therapy revealed that a poor response was associated with stage III clinical signs upon diagnosis (odds ratio [OR] 32.122;95% confidence interval [CI] 2.221 - 464.605), positive sputum AFB culture (OR 13.624;95% CI 1.066 - 174.149), and tuberculoma on brain images (OR 45.714;95% CI 1.893 - 1104.018). Conclusions: The results demonstrate the importance of identifying the severity of CNS TB and promptly administering anti-TB drugs. It is necessary to perform drug susceptibility testing for anti-TB drugs. Further studies are needed to confirm the correlations between risk factors associated with poor response and anti-TB drug resistance and the other risk factors.展开更多
Objective: To study the relationship between drug resistant genetic mutation and drug resistance in Mycobacterium tuberculosis L-form, discuss the internal relationship between drug resistances and drug-resistant rel...Objective: To study the relationship between drug resistant genetic mutation and drug resistance in Mycobacterium tuberculosis L-form, discuss the internal relationship between drug resistances and drug-resistant related genes and explore the value of PCR- SSCP to clinical application. Methods: A total of 52 clinically isolated strains of tuberculosis L-form were collected among 97 pneumoconiosis patients complicated with tuberculosis. The gene mutations of katG, rpoB and rpsL were detected by PCR-SSCP, and the results were compared with those analyzed by traditional antimicrobial susceptibility test(AST). Results: The gene muta- tion rates of katG, rpoB and rpsL by PCR-SSCP were respectively 57.70% (30/52), 65.38% (32/52) and 40.38% (21/52). The rate of reversion was 78.85%(41/52) and the result of drag-resistant genes was invariable. The results of AST showed that there were 40 (76.92%) multi-drug resistant strains in 52 clinically isolated strains. The number for three-drug resistant strain was 21 (40.38%) and that of two-drug resistant was 19(36.54%), but only 12(23.08%) strains were one drug resistant. The rate of total drug-resistance was 100%, but there were 15 strains of allied mutation of three genes, 16 of two mutations and 6 of only one by PCR-SSCP. The coincidences were respectively 71.43%, 84.12% and 50.00%. Then there was no significant difference between the allied mutations of multi-drug resistant gene and the mutations of only one drug resistant gene (P 〉 0.05). Conclusion: PCR-SSCP technique has a higher sensibility and specificity to detect the genes of katG, rpoB and rpsL in tuberculosis L-form among pneumoconiosis complicated with tuberculosis,and the detecting rate of two drug resistant strains and three drug resistant strains was higher. The combined application of PCR-SSCP and AST has advantages at earlier diagnosis and guidance of clinical medications.展开更多
Objective: To observe and evaluate the therapeutic effect of anti-tuberculosis (anti-TB) chemicals and Compound Astragalus Capsule (CAC) in combinedly treating drug resistant pulmonary tuberculosis (DR-TB). Methods: N...Objective: To observe and evaluate the therapeutic effect of anti-tuberculosis (anti-TB) chemicals and Compound Astragalus Capsule (CAC) in combinedly treating drug resistant pulmonary tuberculosis (DR-TB). Methods: Ninety-two patients with DR-TB were equally randomized into the treated group (treated with combination therapy) and the control group (treated with anti-TB chemicals alone). The therapeutic course for both groups was 18 months. Therapeutic effects between the two groups were compared at the end of the therapeutic course. Sputum bacterial negative rate, focal absorption effective rate, cavity closing rate, 10-day symptom improving rate, the incidence of adverse reaction and 2-year bacteriological recurrence rate between the two groups were compared. Results: In the treated group, the sputum bacterial negative conversion rate was 84. 8% , focal absorption effective rate 91. 3% , cavity closing rate 58. 7% and 10-day symptom improving rate 54. 4% , while in the control group, the corresponding rates were 65.2% , 73. 9 % , 37.0% and 26.1 % , respectively. Comparison between the groups showed significant difference in all the parameters (P<0.05, P<0.05, P<0.05 and P<0.01). The incidence of adverse reaction and 2-year bacteriological recurrence rate in the treated group were 23. 9% and 2.6% respectively, while those in the control group 50. 0% and 16. 7% , which were higher than the former group with significant difference ( P<0. 01 and P<0. 05, respectively). Conclusion: The therapeutic effect of combined treatment with anti-TB and CAC is superior to that of treatment with anti-TB chemicals alone, and the Chinese herbal medicine showed an adverse reaction alleviating effect, which provides a new therapy for DR-TB, and therefore, it is worth spreading in clinical practice.展开更多
Objective Tuberculosis remains a severe public health issue, and the Beijing family of mycobacterium tuberculosis (M. tuberculosis) is widespread in East Asia, especially in some areas in China, like Beijing and Tia...Objective Tuberculosis remains a severe public health issue, and the Beijing family of mycobacterium tuberculosis (M. tuberculosis) is widespread in East Asia, especially in some areas in China, like Beijing and Tianjin. This study aimed at determining the mutation patterns of drug-resistant Beijing strains of M. tuberculosis isolated from Tianjin, China. Methods A total of 822 M. tuberculosis isolates were screened for drug resistance by an absolute concentration method and the genotype was identified by PCR. 169 drug-resistant isolates of the Beijing family were analyzed for the potential mutations in the rpoB, katG, inhA promoter region and in rpsL, rrs and embB genes, which are associated with resistance to rifampin (RFP), isoniazid (INH), streptomycin (SM) and ethambutol (EMB) respectively by PCR and DNA sequencing. Results Fifty-eight out of 63 RFP-resistant isolates were found to carry the mutations within the 81-bp RFP resistance determining region (RRDR) of the rpoB gene and the most frequent mutations occurred at codon 531 (44.4%), 526 (28.6%), and 516 (7.9%) respectively. 16 mutation pattems affecting 12 different codons around the RRDR of rpoB were found. Of 116 INH-resistant isolates, 56 (48.3%) had the mutation of katG 315 (AGC→ACC) (Ser→Thr), 3 (2.6%) carried S315N (AGC→AAC) and 27 (16.0%) had the mutation of inhA-15A→T. 84 out of 122 SM-resistant isolates (68.9%) displayed mutations at the codons 43 or 88 with AAG→AGG (Lys→Arg) of the rpsL gene and 22 (18.0%) with the mutations at positions 513A→C, 516C→T or 905 A→G in the rrs gene. Of 34 EMB-resistant isolates, 6 had mutation with M306V (ATG→GTG), 3 with M306I (ATG→ATT), 1 with M306I (ATG→ATA), 1 with D328Y (GAT→TAT), 1 with V348L (GTC→CTC), and 1 with G406S (GGC→AGC) in the embB gene. Conelusion These novel findings extended our understanding of resistance-related mutations in the Beijing strains of M. tuberculosis and may provide a scientific basis for development of new strategies for diagnosis and control of tuberculosis in China and other countries where Beijing strains are prevalent.展开更多
Tuberculosis (TB), caused by Mycobacterium tuberculosis is an infectious deadly disease and the treatment of which is one of the most severe challenges at the global level. Currently more than 20 chemical medications ...Tuberculosis (TB), caused by Mycobacterium tuberculosis is an infectious deadly disease and the treatment of which is one of the most severe challenges at the global level. Currently more than 20 chemical medications are described for the treatment of TB. Regardless of availability of several drugs to treat TB, the causative agent, M. tuberculosis is nowadays getting resistant toward the conventional drugs and leading to conditions known as Multidrug-resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). This situation has terrified the global health community and raised a demand for new anti-tuberculosis drugs. Medicinal plants have been used to cure different common as well as lethal diseases by ancient civilizations due to its virtue of variety of chemical compounds which may have some important remedial properties. The aim of the present review is to focus the anti-tubercular medicinal plants native to India as well as the plants effective against MDR or XDR-TB across the globe. In the present review, we have addressed 25 medicinal plants for TB and 16 plants effective against MDR-TB testified from India and 23 herbal plants described for MDR-TB across the world during 2011-2015. These herbal plants can serve as promising candidates for developing novel medications to combat multidrug resistant M. tuberculosis.展开更多
基金Study on the Correlation Between inhA Gene Mutation of Multidrug-Resistant MTB and Resistance to Protionamide (Project number: 2022013)。
文摘Objective: To investigate the characteristics of katG and inhA gene mutations in multidrug-resistant tuberculosis (MDR-TB), pre-extensively drug-resistant tuberculosis (preXDR-TB), and their correlation with resistance to protionamide (Pto). Methods: A total of 229 patients with MDR-TB and pre-XDR-TB diagnosed in the Eighth Affiliated Hospital of Xinjiang Medical University from January 2020 to February 2024 were selected to analyze the characteristics of katG and inhA mutations in MTB clinical isolates and their correlation with Pto resistance. Results: The mutation rate of katG (with or without inhA mutation) was 85.2%. The mutation rates in MDR-TB and pre-XDR-TB were 87.4% (125/143) and 81.4% (70/86), respectively. The mutation rate of inhA (including katG mutation) was 14.8% (34/229), which was 12.6% (18/143) and 18.6% (16/86) in MDR-TB and pre-XDR-MTB, respectively. There was no difference in mutation (P > 0.05). Conclusion: The total resistance rate to Pto in 229 strains was 8.7% (20/229), which was 8.4% (12/143) and 9.3% (8/86) in MDR-TB and pre-XDR-TB, respectively. Among the inhA mutant strains, 13 were resistant to the Pto phenotype, and the resistance rate was 65% (13/20). In MDR-TB and pre-XDR-TB strains resistant to Pto, inhA gene mutations occurred in 66.7% (6/9) and 63.6% (7/11), respectively. The resistance rates of MDR-MTB and pre-XDR-TB strains without inhA gene mutation to Pto were 2.4% (3/125) and 5.7% (4/70), respectively.
文摘Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its associated cost and side effects. The objective of this study was to assess the drug resistance pattern and assess risk factor associated with MDR-TB among pulmonary tuberculosis patients attending National Tuberculosis Center. Methodology: The comparative cross sectional study was conducted at National Tuberculosis Center during August 2015 to February 2015. Early morning sputum samples were collected from pulmonary tuberculosis suspected patients and subjected to Ziehl-Neelsen staining and fluorochrome staining and culture on Lowenstein-Jensen (LJ) medium. Drug Susceptibility test was performed on culture positive isolates by using proportion method. Univariate and multivariate analysis was computed to assess the risk factors of MDR-TB. Results: Out of 223 sputum samples, 105 were fluorochrome staining positive, 85 were ZN staining positive and 102 were culture positive. Out of 102 culture positive isolates, 37.2% were resistance to any four anti-TB drugs. 11 (28.9%) were initial drug resistance and 28 (43.7%) were acquired drug resistance. The overall prevalence of MDR-TB was 11.7%, of which 2 (5.3%) were initial MDR-TB and 10 (15.6%) were acquired MDR-TB. Univariate and multivariate analysis showed female were significantly associated (P = 0.05) with MDR-TB. Conclusion: Drug resistance TB particularly MDR-TB is high. The most common resistance pattern observed in this study was resistance to both isoniazid and rifampicin. Female were found to be associated with MDR-TB. Thus, early diagnosis of TB and provision of culture and DST are crucial in order to combat the threat of DR-TB.
基金funded by the National Key R&D Program of China [2022YFC2305200]Natural Science Foundation of Xinjiang Uygur Autonomous Region [2021A01D145 and 2022D01A115]Applied Technology Research and Development Programing Project of Kashgar Prefecture [KS2021031 and KS2021034]。
文摘Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.
文摘Introduction: Tuberculosis is closely linked to poverty, with patients facing significant indirect treatment costs. Treating drug-resistant tuberculosis further increases these expenses. Notably, there is a lack of published data on the indirect costs incurred by patients with drug-resistant tuberculosis in Mozambique. Objective: To assess the indirect costs, income reduction, and work productivity incurred by patients undergoing diagnosis and treatment for Drug-Resistant Tuberculosis (DRTB) in Mozambique during their TB treatment. Methods: As part of a comprehensive mixed-methods study conducted from January 2021 to April 2023, this research utilized a descriptive cross-sectional approach, incorporating both quantitative and qualitative methods. The primary goal was to evaluate the costs incurred by the national health system due to drug-resistant TB. Additionally, to explore the indirect costs experienced by patients and their families during treatment, semi-structured interviews were conducted with 27 individuals who had been undergoing treatment for over six months. Results: All survey participants unanimously reported a significant decline in labour productivity, with 70.3% experiencing a reduction in their monthly income. Before falling ill, the majority of respondents (33.3%) earned up to $76.92 monthly, representing the minimum earnings range, while 29.2% had a monthly income above $230.77, the maximum earnings range. Among those who experienced income loss, the majority (22.2%) reported a decrease of up to $76.92 per month, and 18.5% cited a loss exceeding $230.77 per month. Notably, patients with Drug-Resistant Tuberculosis (DRTB) have not incurred the direct costs of the disease, as these are covered by the government. Conclusion: The financial burden of treating Drug-Resistant Tuberculosis (DRTB), along with the income reduction it causes, is substantial. Implementing a patient-centred, multidisciplinary, and multisector approach, coupled with strong psychosocial support, can significantly reduce the catastrophic costs DRTB patients incur.
文摘Background/objective: A nationwide survey on the resistance to first line anti-tuberculosis (anti-TB) drugs was conducted in Ghana from 2007-2008 by Noguchi Memorial Institute for Medical Research in collaboration with the National Tuberculosis Control Programme. We aimed to characterize mycobacterial species causing pulmonary tuberculosis (PTB) and determine the resistance pattern to first line anti-TB drugs among newly diagnosed and previously treated PTB patients in Ghana. Methods: Two sputum samples from consented new smear positive PTB patients who had never been treated for TB or had been on anti-TB treatment for less than a month and patients who had been treated for TB previously for more than a month in selected diagnostic centres nationwide were collected for culture, identification and drug susceptibility test. Culture positive isolates were tested against streptomycin (S), isoniazid (H), rifampicin (R) and ethambutol (E) using the simplified proportion method and line probe assay (LPA). The LPA was performed in mid-2017. Results: Among 410 samples, 345 positive cultures were obtained and identified as Mycobacterium tuberculosis complex (MTBC). Of the 345 isolates, 133 were further differentiated by GenoType MTBC®as M. tuberculosis, 126 (94.7%) and M. africanum 7 (5.3%). The overall drug resistance patterns were as follows: 43/345 (12.5%), 6/345 (1.7%), 9/345 (2.6%) and 71/345 (20.6%) were resistant to H, R, E and S respectively and 5/345 (1.4%) were multi-drug resistant (MDR). Conclusion: The results indicate high levels of resistance to S and H among new and previously treated TB patients. We recommend adequate surveillance systems including periodic national anti-TB drug resistance surveys.
基金Fundamental Research Program of Shanxi province(No.202103021223339,20210302124435)Shanxi Scholarship Council of China(No.2022-175)+1 种基金Fundamental Research Program of Shanxi Datong University(No.2019Q2,2019Q4)Doctoral Scientific Research Foundation of Shanxi Datong University(No.2018-B-13,2018-B-28)。
文摘Tuberculosis(TB)is a chronic infectious disease caused by Mycobacterium Tuberculosis(MTB).It is the second largest single cause of death besides novel coronavirus pneumonia.Along with the abuse of antibiotics and extensive use of anti-tuberculosis drugs,multidrug-resistant(MDR)TB,drug-resistant(XDR)TB and totally drug-resistant(TDR)TB became obstacles to the tuberculosis eradication worldwide.According to the World Health Organization(WHO)statistics,China is not only a high burden tuberculosis country in the world,but also a country with a serious epidemic of MDR.Traditional drugs fail to meet the needs of tuberculosis control.Therefore,it is urgent to find new targets of anti-tuberculosis drugs and develop new anti-tuberculosis drugs.Hence,this paper systematically summarizes the mechanism of traditional and newly developed anti-tuberculosis drugs,in which stressing the research progress of drug resistance mechanisms.This work provides us with new insights of new anti-tuberculosis drug developments,and may contribute to a reduction in the harm that tuberculosis brings to society.
基金supported by a research grant from the National Science & Technology Major Project (2014ZX10003001001) and (2014ZX10003002)
文摘Objective To investigate the prevalence of primary drug-resistant tuberculosis(TB) and associated risk factors in China. We also explored factors contributing to the transmission of multidrug-resistant tuberculosis(MDR-TB). Methods A total of 2794 representative, Mycobacterium tuberculosis isolates from treatment-naive patients were subjected to drug susceptibility testing, and risk factors for drug-resistant TB were analyzed. We also analyzed MDR-TB strain sublineages, drug-resistance-conferring mutations, and risk factors associated with clustered primary MDR strains. Results Among 2794 Mycobacterium tuberculosis isolates from treatment-naive patients, the prevalence of any resistance to first-line drugs was 33.2% and the prevalence of MDR-TB was 5.7%. We did not find any risk factors significantly associated with resistance to first-line drugs. The 93 primary MDR-TB isolates were classified into six sublineages, of which, 75(80.6%) isolates were the RD105-deleted Beijing lineage. The largest sublineage included 65(69.9%) isolates with concurrent deletions of RD105, RD207, and RD181. Twenty-nine(31.2%) primary MDR strains grouped in clusters; MDR isolates in clusters were more likely to have S531 L rpoB mutation. Conclusion This study indicates that primary drug-resistant TB and MDR-TB strains are prevalent in China, and multiple measures should be taken to address drug-resistant TB.
文摘The prognosis of patients with previously treated tuberculosis (TB) was suggested to be dependent on whether the initial treatment was in compliance with the established guidelines. The aim of this retrospective multicenter study was to determine the proportion of new TB patients who received standard doses of rifampicin in multiple provinces of China, and the relationship between low doses of rifampicin and frequency of rifampicin-resistance as well as treatment outcomes. A total of 713 new TB patients were treated with either once-daily dose of bulk anti-TB drugs (group I) or every other day combination blister packs of anti-TB drugs containing rifampicin (group II) at more than 30 TB treatment centers/hospitals in China. Treatment history, therapeutic doses of rifampicin, and information about patients were extracted from their medical records and analyzed, and rifampicin-resistance of isolates collected from patients following the treatment as well as treatment outcomes were compared between two treatment groups. Among 522 patients in treatment group I, 154 (29.5%) received standard and 363 (69.5%) received low doses of rifampicin;238 (45.6%) isolates were rifampicin-resistant, and 243 (46.6%) were successfully treated. Among 191 patients in treatment group II, 175 (91.6%) received standard and 15 (7.9%) received low doses of rifampicin;72 (37.7%) isolates were rifampicin-resistant, and 105 (55%) were successfully treated. When patients who received low doses of rifampicin were compared to others within the same treatment group, increased rates for rifampicin-resistance and treatment failure were observed. Results from this study showed that most new TB patients in treatment group I (69.5%) received low doses of rifampicin, and their treatment outcomes were worse than those in treatment group II, indicating that low doses of rifampicin used for the initial treatment of new TB patients were correlated to increased frequency of rifampicin-resistance and poorer treatment outcomes.
基金supported by project No.17108 from Tehran University of Medical Sciences
文摘Objective:To determine the patterns of resistance to first line anti-tuberculosis(TB)drugs among a collection of Mycobacterium tuberculosis(MTB)isolates from 5 provinces of Iran.Methods:A total of the 6 426 clinical specimens from patients suspected of active TB were collected from March 2010 to June 2012.All specimens were subjected for microscopy and culture tests in the TB centers of studies provinces.Drug susceptibility testing to the first line anti-TB drugs for culture positive MTB was performed on Lwenstein-Jensen(LJ)medium using proportion method.Results:Of 6 426 clinical specimens,261 were culture positive for mycobacteria,of which 252 were MTB and 9 were MOTT(mycobacteria other than tuberculosis).Of 252 MTB isolates.211(83.7%)were pan-susceptible and 41(16.3%)were resistant to at least one drug.Resistance was most common to streptomycin.30 isolates(12.0%),followed by isoniuzid,20isolates(8.0%),rifampin,15 isolates(6.0%)and ethambutol,14 isolates(5.5%).Sixteen(6.3%)MTB isolates were MDR.A clear evidence of heterogeneity amongst the 5 provinces in the proportions with resistance to one or more drugs was observed[χ~2=12.209(4 degrees of freedom),P values=0.015 9].Conclusions:The prevalence of drug resistance in this study area underscoring the need for further enforcement of TB control strategies in the Iran.Drug susceptibility testing for all TB cases to provide optimal treatment,establishing advanced diagnostic facilities for rapid detection of MDR-TB and continuous monitoring of drug resistance are recommended for prevention and control of drug-resistant TB.
文摘Background: We aim to determine the proportions and patterns of resistance to first-line drugs: isoniazid (H), rifampicin (R), ethambutol (E) and streptomycin (S) among pulmonary tuberculosis patients. Methods: Strains were obtained from 1584 culture positive pulmonary tuberculosis patients. All specimens were inoculated into L?wenstein-Jensen media (LJ) and TK selective;drug susceptibility tests (DST) were performed for first-line drugs. Results: Multidrug resistant (MDR) were detected in 146 (9.2%) isolates. Three hundred (18.9%) isolates were resistant to H;220 (13.9%) to R;168 (10.6%) to S;137 (8.6%) to E. Any drug resistance was detected in 442 (27.9%) isolates. MDR rate was higher in male patients than females (P = 0.006). MDR rates were different according to the age groups (P = 0.02). The highest rate was in 35 - 44 years and the lowest rate was in 15 - 24 years. Conclusions: We found an association between middle age and male gender and MDR tuberculosis.
文摘Tuberculosis (TB) is one of the major causes of morbidity and mortality worldwide. In India, nearly 1.8 million new cases of TB are reported annually, which accounts for a fifth of new cases in the world—greater than in any other country. Anti-tubercular drugs (ATDs) have been used for decades, and widespread resistance to them is a very serious public health concern in any part of the world. Aim of this study was to determine the prevalence of Rifampicin (the first line Anti-TB drug) resistance among both pulmonary and extra-pulmonary samples tested positive for Mycobacterium tuberculosis and thereby predict the prevalence of Multi-drug resistant (MDR) tuberculosis in Kolkata and its Suburban regions. All 331 randomly collected clinical samples (both Pulmonary and Extra Pulmonary) were initially screened by Zeihl-Neelsen AFB staining followed by culture on BacT/Alert 3D system and on Lowenstein-Jensen medium and the positive samples were subjected to detection of Mycobacterium tuberculosis complex (MTBC) and simultaneous analysis of Rifampicin resistance by Xpert MTB/RIF assay. Out of the 51 (15.40%) culture positive samples, 13.7% of pulmonary samples and 9.09% of extra-pulmonary samples were Rifampicin resistant. The prevalence of Rifampicin resistant TB in our study is high and the possible reasons can be mixing of new as well as retreatment cases and smaller sample size but, yet it can help Government and public health regulatory bodies to formulate adequate strategies to fight against drug resistant tuberculosis, especially in this part of the world.
文摘Introduction: Recently rapid development of drug resistant TB, particularly MDR TB (Multi Drug Resistant TB) and XDRTB (Extensively Drug-Resistant TB) possess a major threat to control of tuberculosis globally. Information on the extent of MDR-TB from Kenya is largely limited due to several factors. Monitoring of development of resistance is a vital tool in providing critical information for effective planning for TB control and in management of patients infected with TB. Methods: Cross-sectional with cluster design. Results: A total of 2,171 participants recruited into the study from 50 selected clusters. Prevalence of rifampicin resistance for new cases was 1.3% [95% CI, 0.8-2.0] and INH resistance was 5.5% [95% CI, 4.5-6.7]. MDR TB was found in 0.67% of new cases and 2.1% amongst previously treated TB cases. Discussion: Resistance to isoniazid in Kenya has been on the decline due to introduction of rifampicin in combined therapy. There was increase of MDR TB among new cases by 24% and decline in previously treated cases due to lethal impact of HIV. Conclusions: Although drug resistance TB is a growing problem in Kenya, resistance to isoniazid and rifampicin MDR TB is less than previously estimated. The country should continue to monitor drug resistance and ensure effective use of anti TB medicines.
文摘Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.
基金Supported by the Natural Science Foundation of Universities of Anhui Province (KJ2008A152)the Natural Science Foundation of the Committee of Education of Anhui Province (2005KJ238)
文摘To study the characteristics of drug-resistant genetic mutation of rpoB on coal workers' pneumoconiosis complicated with L-form of Mycobacterium tuberculosis. Methods: A total of 42 clinical isolated strains of Mycobacterium tuberculosis L-forms were collected, including 31 drug-resistant strains. Their genomes DNA were extracted, the target genes were amplified by PCR, and the hot regions in the rpoB gene were analyzed by automated DNA sequenator. Results: No mutation of rpoB gene was identified in 11 rifampicin-sensitive strains while conformation changes were found in 31 rifampicin-resistant strains. The mutation rate was 93.55% (29/31) in resistant strains, mainly concentrated in codon 531 (51.6%, 16/31) and 526 (32.26%, 10/31). Base substitutions happened, including 27 unit point mutation and 2 two point mutation. The mutation of codon 516 that new found wasn't reported by internal and overseas scholars. Conclusion: The substitution of highly conserved amino acids encoded by rpoB gene results in the molecular mechanism responsible for rifampicin resistance in Mycobacterium tuberculosis L-forms. It also proves that rpoB gene is diversiform.
基金National Science Foundation Youth fund of Anhui University of Science & Technology(200537)
文摘Objective:To study the relationship between mutation in the katG gene and drug resistance of INH in Mycobacterium tuberculosis L-forms among patients of pneumoconiosis complicated with pulmonary tuberculosis, and to explore the clinical application of PCR-SSCP. Methods: A total of 52 clinical isolated strains of Mycobacterium tuberculosis L-forms were collected. Mutation in the katG genes was detected by PCR-SSCP and traditional antimicrobial susceptibility test (AST). Results: The results by AST showed that there were 40 persisters in 52 clinical isolated strains. The drug resistant rate was 76.92%(40/52), and the gene mutation rate of katG was 57.70%(30/52)by PCR-SSCP, the difference was no quite significance (X^2 = 2.8507, P 〉 0.05). The coincidence rate of two methods was 75.00% (30/40). Conclusion: The detectionrate of katG resistant strains in Mycobacterium tuberculosis L-forms was high by PCR-SSCP. The combined application of PCR-SSCP and traditional antimicrobial susceptibility test can improve the detecting rate.
文摘Introduction: More than half of patients with central nervous system tuberculosis (CNS TB) die or are left with severe neurological deficits despite receiving anti-TB treatment. Aims of the study: This study examined risk factors associated with poor response to initial treatment with four anti-TB drug regimens or three drug regimens with steroids as adjuvant therapy. Methods: This study analyzed medical records from two tertiary hospitals in Busan, Korea, between January 2009 and March 2012. The subjects were non-human immunodeficiency virus (HIV)-infected patients aged ≥16 years with clinical CNS TB. The subjects were divided into two groups according to response to treatment. Results: In totally, 52 patients with CNS TB were included. Of these, 14 (26%) and 38 (73%) showed poor and good responses, respectively. Of the patients with poor response, nine had stage III disease (64.3%) according to the British Medical Research Council (BMRC) staging system. A significantly higher proportion was seen in the good response group (p < 0.05). Patients with positive cerebrospinal fluid (CSF) acid-fast bacillus (AFB) culture, positive sputum AFB culture, positive CSF TB polymerase chain reaction (PCR) results, and brain tuberculoma had poorer responses (p < 0.05). Multivariate analysis to determine risk factors associated with poor response to anti-TB therapy revealed that a poor response was associated with stage III clinical signs upon diagnosis (odds ratio [OR] 32.122;95% confidence interval [CI] 2.221 - 464.605), positive sputum AFB culture (OR 13.624;95% CI 1.066 - 174.149), and tuberculoma on brain images (OR 45.714;95% CI 1.893 - 1104.018). Conclusions: The results demonstrate the importance of identifying the severity of CNS TB and promptly administering anti-TB drugs. It is necessary to perform drug susceptibility testing for anti-TB drugs. Further studies are needed to confirm the correlations between risk factors associated with poor response and anti-TB drug resistance and the other risk factors.
基金This work was supported by the Youth Natural Science Foundation of Anhui University of Science & Technology(200537)
文摘Objective: To study the relationship between drug resistant genetic mutation and drug resistance in Mycobacterium tuberculosis L-form, discuss the internal relationship between drug resistances and drug-resistant related genes and explore the value of PCR- SSCP to clinical application. Methods: A total of 52 clinically isolated strains of tuberculosis L-form were collected among 97 pneumoconiosis patients complicated with tuberculosis. The gene mutations of katG, rpoB and rpsL were detected by PCR-SSCP, and the results were compared with those analyzed by traditional antimicrobial susceptibility test(AST). Results: The gene muta- tion rates of katG, rpoB and rpsL by PCR-SSCP were respectively 57.70% (30/52), 65.38% (32/52) and 40.38% (21/52). The rate of reversion was 78.85%(41/52) and the result of drag-resistant genes was invariable. The results of AST showed that there were 40 (76.92%) multi-drug resistant strains in 52 clinically isolated strains. The number for three-drug resistant strain was 21 (40.38%) and that of two-drug resistant was 19(36.54%), but only 12(23.08%) strains were one drug resistant. The rate of total drug-resistance was 100%, but there were 15 strains of allied mutation of three genes, 16 of two mutations and 6 of only one by PCR-SSCP. The coincidences were respectively 71.43%, 84.12% and 50.00%. Then there was no significant difference between the allied mutations of multi-drug resistant gene and the mutations of only one drug resistant gene (P 〉 0.05). Conclusion: PCR-SSCP technique has a higher sensibility and specificity to detect the genes of katG, rpoB and rpsL in tuberculosis L-form among pneumoconiosis complicated with tuberculosis,and the detecting rate of two drug resistant strains and three drug resistant strains was higher. The combined application of PCR-SSCP and AST has advantages at earlier diagnosis and guidance of clinical medications.
文摘Objective: To observe and evaluate the therapeutic effect of anti-tuberculosis (anti-TB) chemicals and Compound Astragalus Capsule (CAC) in combinedly treating drug resistant pulmonary tuberculosis (DR-TB). Methods: Ninety-two patients with DR-TB were equally randomized into the treated group (treated with combination therapy) and the control group (treated with anti-TB chemicals alone). The therapeutic course for both groups was 18 months. Therapeutic effects between the two groups were compared at the end of the therapeutic course. Sputum bacterial negative rate, focal absorption effective rate, cavity closing rate, 10-day symptom improving rate, the incidence of adverse reaction and 2-year bacteriological recurrence rate between the two groups were compared. Results: In the treated group, the sputum bacterial negative conversion rate was 84. 8% , focal absorption effective rate 91. 3% , cavity closing rate 58. 7% and 10-day symptom improving rate 54. 4% , while in the control group, the corresponding rates were 65.2% , 73. 9 % , 37.0% and 26.1 % , respectively. Comparison between the groups showed significant difference in all the parameters (P<0.05, P<0.05, P<0.05 and P<0.01). The incidence of adverse reaction and 2-year bacteriological recurrence rate in the treated group were 23. 9% and 2.6% respectively, while those in the control group 50. 0% and 16. 7% , which were higher than the former group with significant difference ( P<0. 01 and P<0. 05, respectively). Conclusion: The therapeutic effect of combined treatment with anti-TB and CAC is superior to that of treatment with anti-TB chemicals alone, and the Chinese herbal medicine showed an adverse reaction alleviating effect, which provides a new therapy for DR-TB, and therefore, it is worth spreading in clinical practice.
基金supported by National Science Key Grant(2008ZX10003-009).
文摘Objective Tuberculosis remains a severe public health issue, and the Beijing family of mycobacterium tuberculosis (M. tuberculosis) is widespread in East Asia, especially in some areas in China, like Beijing and Tianjin. This study aimed at determining the mutation patterns of drug-resistant Beijing strains of M. tuberculosis isolated from Tianjin, China. Methods A total of 822 M. tuberculosis isolates were screened for drug resistance by an absolute concentration method and the genotype was identified by PCR. 169 drug-resistant isolates of the Beijing family were analyzed for the potential mutations in the rpoB, katG, inhA promoter region and in rpsL, rrs and embB genes, which are associated with resistance to rifampin (RFP), isoniazid (INH), streptomycin (SM) and ethambutol (EMB) respectively by PCR and DNA sequencing. Results Fifty-eight out of 63 RFP-resistant isolates were found to carry the mutations within the 81-bp RFP resistance determining region (RRDR) of the rpoB gene and the most frequent mutations occurred at codon 531 (44.4%), 526 (28.6%), and 516 (7.9%) respectively. 16 mutation pattems affecting 12 different codons around the RRDR of rpoB were found. Of 116 INH-resistant isolates, 56 (48.3%) had the mutation of katG 315 (AGC→ACC) (Ser→Thr), 3 (2.6%) carried S315N (AGC→AAC) and 27 (16.0%) had the mutation of inhA-15A→T. 84 out of 122 SM-resistant isolates (68.9%) displayed mutations at the codons 43 or 88 with AAG→AGG (Lys→Arg) of the rpsL gene and 22 (18.0%) with the mutations at positions 513A→C, 516C→T or 905 A→G in the rrs gene. Of 34 EMB-resistant isolates, 6 had mutation with M306V (ATG→GTG), 3 with M306I (ATG→ATT), 1 with M306I (ATG→ATA), 1 with D328Y (GAT→TAT), 1 with V348L (GTC→CTC), and 1 with G406S (GGC→AGC) in the embB gene. Conelusion These novel findings extended our understanding of resistance-related mutations in the Beijing strains of M. tuberculosis and may provide a scientific basis for development of new strategies for diagnosis and control of tuberculosis in China and other countries where Beijing strains are prevalent.
文摘Tuberculosis (TB), caused by Mycobacterium tuberculosis is an infectious deadly disease and the treatment of which is one of the most severe challenges at the global level. Currently more than 20 chemical medications are described for the treatment of TB. Regardless of availability of several drugs to treat TB, the causative agent, M. tuberculosis is nowadays getting resistant toward the conventional drugs and leading to conditions known as Multidrug-resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). This situation has terrified the global health community and raised a demand for new anti-tuberculosis drugs. Medicinal plants have been used to cure different common as well as lethal diseases by ancient civilizations due to its virtue of variety of chemical compounds which may have some important remedial properties. The aim of the present review is to focus the anti-tubercular medicinal plants native to India as well as the plants effective against MDR or XDR-TB across the globe. In the present review, we have addressed 25 medicinal plants for TB and 16 plants effective against MDR-TB testified from India and 23 herbal plants described for MDR-TB across the world during 2011-2015. These herbal plants can serve as promising candidates for developing novel medications to combat multidrug resistant M. tuberculosis.