Efficacy and Safety of Combined Bedaquiline and Delamanid Use among Patients with Multidrug-Resistant Tuberculosis in Beijing,China

Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients.Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM.Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups.Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.

Assessment of the Indirect Cost of Drug Resistant Tuberculosis Treatment to Patients in a High Burden, Low Income Setting in Mozambique

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.

Analysis of The Correlation Between inhA Gene Mutation and Resistance to Protionamide in Drug-Resistant Mycobacterium Tuberculosis

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.

Mutation Characteristics of inhA and katG Genes in Isoniazid-Resistant Mycobacterium Tuberculosis Patients in Xinjiang

Objective:To analyze the mutation characteristics of inhA and katG genes in isoniazid-resistant Mycobacterium tuberculosis in Xinjiang.Methods:The katG and inhA in 148 strains of isoniazid-resistant Mycobacterium tuberculosis were amplified through fluorescence quantitative PCR,and the amplified products were sequenced and compared.Results:The inhA gene mutation rate of 148 strains of isoniazid-resistant mycobacterium tuberculosis was 13.51%(20/148),among which the inhA gene mutation rate among patients of Han,Uygur,and Kazakh ethnicity were 15.87%,13.21%,and 17.65%,respectively.There was no significant difference in the inhA mutation rate among nationalities(c^(2)=2.897,P>0.05).The mutation rate of the katG gene was 84.46%(125/148),among which the mutation rates of patients of Han,Uyghur,and Kazak ethnicities were 82.54%,84.91%,and 76.47%,respectively.The Hui and other ethnic groups were all affected by the katG gene mutation.There was no significant difference in the mutation rate of the katG gene among different ethnicities(c^(2)=3.772,P>0.05).The mutation rates of the inhA gene in southern Xinjiang,northern Xinjiang,and other provinces were 18.60%,9.28%,and 37.50%,respectively.The mutation rates of the inhA gene in different regions were statistically different(c^(2)=6.381,P<0.05).There was no significant difference in the inhA mutation rate between patients from southern and northern Xinjiang(c^(2)=2.214,P>0.05)and between southern Xinjiang and other provinces(c^(2)=1.424,P>0.05).However,the mutation rate of the inhA gene in patients from other provinces was higher than that in northern Xinjiang(c^(2)=5.539,P<0.05).The mutation rates of the katG gene in southern Xinjiang,northern Xinjiang,and other provinces were 81.40%,87.63%,and 62.50%,respectively.There was no significant difference in the mutation rates of the katG gene among different regions(c^(2)=3.989,P>0.05).Conclusion:katG gene mutation was predominant in isoniazid-resistant tuberculosis patients in Xinjiang Uygur Autonomous Region,and inhA and katG gene mutation were no different among different ethnic groups.

Inferring Mycobacterium Tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China

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.

Immune formulation-assisted conventional therapy on anti-infective effectness of multidrug-resistant Mycobacterium tuberculosis infection mice

Objective:To study the effect of immune formulation-assisted conventional therapy on antiinfective ability of multidrug-resistant Mycobacterium tuberculous infection mice.Methods:BALB/c mice were used as experimental animals,multidrug-resistant Mycobacterium tuberculosis infection models were built,randomly divided into model group,moxifloxacin group,thymopentin group and combined treatment group and given corresponding drug intervention,and then colony numbers in the spleen and lung,T lymphocyte subset contents and programmed death-1(PD-1) expression levels in peripheral blood were detected.Results:Colony numbers in lung and spleen of moxifloxacin group and thymopentin group were significantly lower than those of model group and colony numbers in lung and spleen of combined treatment group were significantly lower than those of moxifloxacin group and thymopentin group:contents of CD3^+CD4^+T cells,Thl and Thl7 in peripheral blood of moxifloxacin group and thymopentin group were higher than dtose of model group,and contents of CD3^+CD8^+T cells.Th2 and Treg were lower than those of model group;contents of CD3^+CD4^+T cells.Th 1 and Th 17 in peripheral blood of combined treatment group were higher than those of moxifloxacin group and thymopentin group,and contents of CD3^+CD8^+T cells.Th2 and Treg were lower than those of moxifloxacin group and thymopentin group:PD-I expression levels on T lymphocyte,B lymphocyte and monocyte surface in peripheral blood of moxifloxacin group and thymopentin group were lower than those of model group,and PD-I expression levels on T lymphocyte.B lymphocyte and monocyte surface in peripheral blood of combined treatment group were lower than those of moxifloxacin group and thymopentin group.Conclusions:Immune formulation thymopentin can enhance the anti-infective ability of multidrug-resistant Mycobacterium tuberculosis infection mice,decrease bacterial load in lung and spleen,and enhance immune function.

Prevalence and Risk Factors of Primary Drug-Resistant Tuberculosis in China

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.

Rapid Detection of rpoB Gene Mutations in Rif-resistant M.tuberculosis Isolates by Oligonucleotide Microarray

Objective To detect the specific mutations in rpoB gene of Mycobacterium tuberculosis by oligonucleotide microarray. Methods Four wild-type and 8 mutant probes were used to detect rifampin resistant strains. Target DNA of M. tuberculosis was amplified by PCR, hybridized and scanned. Direct sequencing was performed to verify the results of oligonucleotide microarray Results Of the 102 rifampin-resistant strains 98 （96.1%） had mutations in the rpoB genes. Conclusion Oligonucleotide microarray with mutation-specific probes is a reliable and useful tool for the rapid and accurate diagnosis of rifampin resistance in M. tuberculosis isolates.

Drug Resistance Pattern in Pulmonary Tuberculosis Patients and Risk Factors Associated with Multi-Drug Resistant Tuberculosis

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.

Clinical Study of Drug-resistant Pulmonary Tuberculosis Treated by Combination of Anti-Tuberculosis Chemicals and Compound Astragalus Capsule(复方黄芪胶囊)

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.

Drug-Induced Hypothyroidism during Anti-Tuberculosis Treatment of Multidrug-Resistant Tuberculosis: Notes from the Field

We followed 188 euthyroidic persons undergoing treatment for multidrug resistant tuberculosis (MDR-TB) in the state of Karnataka, India to determine the incidence of hypothyroidism during anti-tuberculosis treatment. Overall, among MDR-TB patients with valid thyroid stimulating hormone (TSH) values, about 23% developed hypothyroidism (TSH value ≥10 mIU/ml) during anti-tuberculosis treatment;the majority (74%) occurring after 3 months of treatment. Among 133 patients who received a regimen that contained ethionamide, 42 (32%) developed hypothyroidism. Among 17 patients that received a regimen that contained para-aminosalicylate sodium, 6 (35%) developed hypothyroidism. Among 9 HIV positive patients on antiretroviral treatment, 4 (44%) developed hypothyroidism. These results differ from previously reported 4% incidence of hypothyroidism amongst patients who passively reported thyroidal symptoms during treatment, suggesting routine serologic monitoring of TSH throughout the course of treatment for MDR-TB is warranted.

Natural Remedies against Multi-Drug Resistant <i>Mycobacterium tuberculosis</i>

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.

Random amplified polymorphic DNA analysis of Mycobacterium tuberculosis isolates resistant to Isoniazid in Indonesia

Background: M. tuberculosisis the most important etiological factor of tuberculosis. One of the factors that make TB hard to eradicate is the emergence of M. tuberculosisdrug resistance. Drug resistance in M. tuberculosisis attributed primarily to the accumulation of mutations in the drug target gene. Objectives: to analyze profile of Random Amplified Polymorphic DNA (RAPD) in M. tuberculosisisolates resistant to Isoniazid and found RAPD marker. Methods: seven Isoniazid resistant isolate of M. tuberculosisfrom Ma kassar, Indonesia strain were analyzed by RAPD method using primers OPN 02, OPN 09, OPN 20, BG 65, N 9, that amplification fragment DNA than as molecular marker. Results: The results of the present study showed high degree of polymerphism in theM.tuberculosisstrains in the population, and found that specific DNA fragment at Isoniazid resistant isolates using primer N 9 is 1450 bp as a marker. Conclusion: This study gives information about RAPD marker of M. tuberculosis strain to Isoniazid resistant.

Molecular Characterization of Drug-Resistant Beijing Family Isolates of Mycobacterium Tuberculosis from Tianjin,China

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.

Early efficacy of individual regimens containing bedaquiline in patients with drug resistant tuberculosis

Objective:To evaluate early efficacy of sputum conversion within 6 months of individual regimens containing bedaquiline in patients with drug resistant tuberculosis.Methods:We conducted a retrospective study among patients with drug resistant tuberculosis who were receiving individual regimens containing bedaquiline.The primary outcome was sputum conversion of both smear and culture within 6 months of treatment.We used medical records of drug resistant tuberculosis patients from January 2020 to December 2021.The study was conducted at Dr.Soetomo Hospital,Indonesia from August to October 2022.Results:In this study,44 eligible drug resistant tuberculosis patients were initiated on regimens containing bedaquiline.There were 52.3%males and the median age was 45.5 years.The rates of previous treatment(70.5%)and lung cavity(36.4%)were high.The most common companion drugs included clofazimine,cycloserine,levofloxacin,and linezolid.Sputum smear and culture conversion was seen in 79.4%and 82.1%at the 2nd month,respectively.More than 97%patients had smear and culture conversion at the end of 6 months.Conclusions:Among drug resistant tuberculosis patients,individual regimens containing bedaquiline were associated with high rates of smear and culture conversion at the end of 6 months.Early efficacy of regimens containing bedaquiline can be used to predict cure rate at the end of treatment.

Treatment outcomes and adverse drug reactions among patients with drug-resistant tuberculosis receiving all-oral,long-term regimens:First record viewing report from Pakistan

Objective:To assess the effectiveness and adverse drug reactions of all-oral regimens for patients with multidrug-resistant tuberculosis.Methods:This retrospective study was conducted at 10 Programmatic Management of Drug Resistant Tuberculosis sites in Punjab province of Pakistan.Patients receiving treatment for drug resistant tuberculosis from July 2019 to December 2020 with at least interim result i.e.6th month culture conversion or final outcomes(cured,complete,lost to follow-up,failure,death)available,were included in the study.Data was extracted from electronic data management system.For the reporting and management of adverse drug events,active tuberculosis drug safety monitoring and management was implemented across all sites.All the data was analyzed using SPSS version 22.Results:Out of 947 drug resistant tuberculosis patients included in this study,579(68%)of the patients had final outcomes available.Of these,384(67.9%)successfully completed their treatment.Out of 368(32%)patients who had their interim results available,all had their 6th month culture negative.Combining new medications was thought to result in serious adverse outcomes such as QT prolongation.However,this study did not record any severe adverse events among patients.Conclusions:All-oral regimens formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with traditional injectable treatment.

Risk Factors for Multidrug-Resistant Tuberculosis and Characteristics of Cases: A Case-Control Study of Patients Attending ALERT General Hospital in Addis Ababa, Ethiopia

Background:Tuberculosis remains a major public-health problem in the world, despite several efforts to improve case identification and treatment. Particularly multidrug-resistant tuberculosis is becoming a major threat to tuberculosis control programs in Ethiopia which seriously threatens the control and prevention efforts and is associated with both high death rates and treatment costs. Methods: A case-control study was conducted to assess risk factors and characteristics of MDR-TB cases at ALERT Hospital, Addis Ababa, Ethiopia, where cases were 167 MDR-TB patients, while controls were newly diagnosed and bacteriologically confirmed pulmonary TB cases of similar number, who were matched by sex and age of 5-years interval. Results: The socio-demographic characteristics of the participants indicated that majority (53.3%) were males and 46.7% females;a little over half of cases (55.1%) were in the age group 26 - 45 years, whereas 46.7% of controls were in this age group. According to the multivariable logistic regression analysis, previous history of hospital admission was the only factor that was identified as predictor which increased risk to develop MDR-TB by almost twenty times (AOR = 19.5;95% CI: 9.17 - 41.62) and P-value of <0.05. All other studied factor such as being unemployed, family size, having member of household member with TB, and history of visiting hospital in past 12 months etc., didn’t show any statistically significant association. Conclusion: The study identified previous history of hospital admission as independent predictors for the occurrence of MDR-TB, while other studied variables didn’t show any strong association. The findings added to the pool of knowledge emphasizing the need for instituting strong infection control practice at health care facilities to prevent nosocomial transmission of MDR-TB.

Rapid Detection of Rifampin-resistant Clinical Isolates of Mycobacterium tuberculosis by Reverse Dot Blot Hybridization

Objective A PCR-reverse dot blot hybridization （RDBH） assay was developed for rapid detection of rpoB gene mutations in ＇hot mutation region＇ of Mycobacterium tuberculosis （M. tuberculosis）. Methods 12 oligonucleotide probes based on the wild-type and mutant genotype rpoB sequences of M. tuberculosis were designed to screen the most frequent wild-type and mutant genotypes for diagnosing RIF resistance. 300 M. tuberculosis clinical isolates were detected by RDBH, conventional drug-susceptibility testing （DST） and DNA sequencing to evaluate the RDBH assay. Results The sensitivity and specificity of the RDBH assay were 91.2% （165/181） and 98.3% （117/119）, respectively, as compared to DST. When compared with DNA sequencing, the accuracy, positive predictive value （PPV） and negative predictive value （NPV） of the RDBH assay were 97.7% （293/300）, 98.2% （164/167）, and 97.0% （129/133）, respectively. Furthermore, the results indicated that the most common mutations were in codons 531 （48.6%）, 526 （25.4%）, 516 （8.8%）, and 511 （6.6%）, and the combinative mutation rate was 15 （8.3%）. One and two strains of insertion and deletion were found among all strains, respectively. Conclusion Our findings demonstrate that the RDBH assay is a rapid, simple and sensitive method for diagnosing RIF-resistant tuberculosis.

Multidrug-Resistant Tuberculosis in the Democratic Republic of Congo: Analysis of Continuous Surveillance Data from 2007 to 2016

Background: For countries with limited resources such as the Democratic Republic of the Congo (DRC), the diagnosis of Multidrug-resistant tuberculosis (MDR-TB) is still insufficient. The MDR-TB identification is done primarily among at-risk groups. The knowledge of the true extent of the MDR-TB remains a major challenge. This study tries to determine the proportion of MDR-TB in each group of presumptive MDR-TB patients and to identify some associated factors. Methods: This is an analysis of the DRC surveillance between 2007 and 2016. The proportions were expressed in Percentage. The logistic regression permits to identify the associated factors with the RR-/MDR-TB with adjusted Odds-ratio and 95% CI. Significance defined as p ≤ 0.05. Results: Overall, 83% (5407/6512) of the MDR-TB presumptive cases had each a TB test. 86.5% (4676/5407) had each a culture and drug sensitive testing (DST) on solid medium, and 24.3% (1312/5407) had performed an Xpert MTB/RIF test. The proportion of those with at least one first-line drug resistance was 59.3% [95% CI 57.2 - 61.4] among which 50.1%, [95% CI 47.9 - 52.3] for the isoniazid, 45.6% [95% CI 43.4 - 47.8] for the rifampicin, 49.9% [95% CI 47.8 - 52.1] for ethambutol and 35.8% [95% CI 33.7 - 37.9] for streptomycin. The confirmation of MDR-TB was 42.8% [95% CI 38.4 - 47.8]. Combining both tests, the proportion of RR-/MDR-TB was 49.6% [95% CI 47.9 - 51.4] for all presumptives. This proportion was 60.0% for failures, 40.7% for relapses and 34.7% for defaulters. Associated factors with the diagnosis of MDR-TB were: aged less than 35 years;prior treatment failure;defaulters;the delay between the collection of sputum and the test completion. Conclusion: The proportion of RR-/MDR-TB among the presumptives has been higher than those estimated generally. The National tuberculosis programme (NTP) should improve patient follow-up to reduce TB treatment failures and defaulting. Moreover, while increasing the use of molecular tests, they should reduce sample delivery times when they use culture and DST concomitantly.

Detecting katG Drug Resistant Genetic Mutation among pneumoconiosis patients complicated with tuberculosis in Mycobacterium tuberculosis L-forms by PCR-SSCP

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.