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.

Cost-Effectiveness Analysis of Combined Chemotherapy Regimen Containing Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis in China

Objective This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline(BR)and the conventional treatment regimen(CR,not containing Bedaquiline)for the treatment of adults with multidrug-resistant tuberculosis(MDR-TB)in China.Methods A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years.The model parameter data were synthesized from the literature,the national TB surveillance information system,and consultation with experts.The incremental cost-effectiveness ratio(ICER)of BR vs.CR was determined.Results BR(vs.CR)had a higher sputum culture conversion rate and cure rate and prevented many premature deaths(decreased by 12.8%),thereby obtaining more quality-adjusted life years(QALYs)(increased by 2.31 years).The per capita cost in BR was as high as 138,000 yuan,roughly double that of CR.The ICER for BR was 33,700 yuan/QALY,which was lower than China's 1×per capita Gross Domestic Product(GDP)in 2020(72,400 yuan).Conclusion BR is shown to be cost effective.When the unit price of Bedaquiline reaches or falls below57.21 yuan per unit,BR is expected to be the dominant strategy in China over CR.

Sensorineural Hearing Loss in Multidrug-Resistant Tuberculosis Patients in Kinshasa (Democratic Republic of Congo): Prospective Cohort Study of Therapeutic Regimen with Aminoglycoside versus Bedaquiline

Context: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem in developing countries such as the Democratic Republic of Congo (DRC), which continues to face the emergence of MDR-TB cases. Because of the ototoxic effects of AGs, the World Health Organization (WHO) has recommended the introduction of the bedaquiline regimen. However, very few data are available regarding the susceptibility of bedaquiline to induce hearing loss, hence the present study set out to compare the AG-based regimen and the bedaquiline-based regimen in the occurrence of hearing loss in MDR-TB patients. Methods: This is a prospective multicenter cohort study that included 335 MDR-TB patients, performed in Kinshasa (DRC) during the period from January 2020 to January 2021. Sociodemographic, clinical, biological and audiometric data were analyzed using Stata 17. Repeated-measures analysis of variance was used to compare changes in the degree of hearing loss over time between the two groups of patients on AG and bedaquiline regimens. The double-difference method was estimated using regression with fixed-effects. A p value < 0.05 was considered the threshold for statistical significance. Results: The degree of hearing loss was similar between the two groups at the first month [AGs (28 dB) vs BDQ (30 dB);p = 0.298]. At six months, the mean degree of hearing loss was significantly greater in the aminoglycoside regimen group [AGs (60.5 dB) vs BDQ (44 dB);p < 0.001]. The double difference was significant, with a greater increase in hearing loss in the AGs group (diff-in-diff 18.3;p < 0.001). After adjustment for age and serum albumin, the group receiving the AG-based regimen had a 2-point greater worsening than those with bedaquiline at the sixth month (diff-in-diff 19.8;p Conclusion: Hearing loss is frequent with both treatment regimens, but more marked with the Aminoglycoside-based regimen. Thus, bedaquiline should also benefit for audiometric monitoring in future MDR-TB patients.

Determinants of the Sensorineural Hearing Loss in Patients with Multidrug-Resistant Tuberculosis in Kinshasa (Democratic Republic of the Congo): A Prospective Cohort Study

Background: The onset of the hearing loss is a major challenge during the treatment of multidrug-resistant tuberculosis (MDR-TB). Aminoglycoside-based regimens, to a lesser extent based on bedaquiline, induce ototoxic sensorineural hearing loss. Research on risk factors is essential to enable high-risk individuals to benefit from preventive measures in settings with limited resources. Objective: This study aimed to assess the determinants of the hearing loss in patients with MDR-TB. Methods: This prospective multicenter cohort study included 337 patients with MDR-TB. It was performed in Kinshasa (Democratic Republic of the Congo) between January 2020 and January 2021. Sociodemographic, clinical, biological, therapeutic, and audiometric data were exported and analyzed using Stata 17 and MedCalc. The fixed-effect linear regression panel model was used to assess the degree of the hearing loss over time according to the following covariates: therapeutic regimen (aminoglycosides, bedaquiline, or alternate), stage of chronic kidney disease (CKD), age at inclusion, body mass index, serum albumin level, HIV status, alcohol intake, hypertension, and hemoglobin level. The Hausman test was used to select between fixed- and random-effect estimators. The threshold for statistical significance was set at p Result: A total of 236 patients (70%) received an aminoglycoside-based regimen, 61 (18%) received a bedaquiline-based regimen, and 40 (12%) received aminoglycosides relayed by bedaquiline. The frequency of the hearing loss increased from 62% to 96.3% within six months for all therapeutic regimens. The Hearing loss worsened, with moderate (72.4%) and profound (16%) deafness being predominant. An Exposure to the treatment for more than one month (β coeff: 27.695, Se: 0.793, p β coeff: 6.102, Se: 1.779, p β coeff: 5.610, Se: 1.682, p = 0.001), and an eGFR β coeff: 6.730, Se: 2.70, p = 0.013) were the independent risk factors associated with the hearing loss in patients with MDR-TB. Conclusions: The Hearing loss was more prevalent and worsened during the treatment of the patients with MDR-TB. An Exposure for more than one month, AG-based regimens, advanced age, hypoalbuminemia, and CKD have emerged as the main determinants of the worsening of the hearing loss.

Serum IL-1β and IL-18 correlate with ESR and CRP in multidrug-resistant tuberculosis patients

Dear Editor： The emergence of multidrug-resistant tuberculosis （MDR-TB） is bringing new challenges. MDR-TB is caused by Mycobacterium tuberculosis （M. tuberculosis） that is resistant to isoniazid and rifampicin, with or with- out resistance to other anti-tuberculosis drugs. Approximately 450,000 people developed MDR-TB worldwide in 2012 and an estimated 170,000 people died from the disease. Bacterial burden is not strictly corre- lated with disease progression, and several hallmarks of severe tuberculosis suggest that insufficiently controlled inflammation plays an important role in pathogenesis.

Case of bronchoesophageal fistula with gastric perforation due to multidrug-resistant tuberculosis

Gastric perforation and tuberculous bronchoesophageal fistula(TBEF) are very rare complications of extrapulmonary tuberculosis(TB). We present a case of pulmonary TB with TBEF and gastric perforation caused by a multidrug-resistant tuberculosis strain in a nonacquired immune deficiency syndrome male patient.The patient underwent total gastrectomy with Rouxen-Y end-to-side esophagojejunostomy and feeding jejunostomy during intravenous treatment with anti-TB medication, and esophageal reconstruction with colonic interposition and jejunocolostomy were performed successfully after a full course of anti-TB medication.Though recent therapies for TBEF have favored medication, patients with severe stenosis or perforation require surgery and medication with anti-TB drugs basedupon adequate culture and drug susceptibility testing.

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.

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.

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.

Screening outcomes of household contacts of multidrug-resistant tuberculosis patients in Peshawar,Pakistan

Objective:To assess the profile of TB/multidrug-resistant TB(MDR-TB) among household contacts of MDR-TB patients.Methods:Close contacts of MDR-TB patients were traced in the cross-sectional study.Different clinical,radiological and bacteriological were performed to rule out the evidence of TB/MDR-TB.Results:Between January 2012 and December 2012,a total of 200 index MDR-TB patients were initiated on MDR-TB treatment,out of which home visit and contacts screening were conducted for 154 index cases.Of 610 contacts who could be studied,41(17.4%) were diagnosed with MDR-TB and 10(4.2%) had TB.The most common symptoms observed were cough,chest pain and fever.Conclusions:The high incidence of MDR-TB among close contacts emphasize the need for effective contact screening programme of index MDR-TB cases in order to cut the chain of transmission of this disease.

Multidrug-Resistant Tuberculosis Disease in North-Kivu Province, Democratic Republic of Congo

Introduction: The emergency of Mycobacterium tuberculosis resistant to the first line drug reduced access possibility to second line drugs for appropriate treatment and required for urgent action especially in le Democratic Republic of Congo (DRC), which counts among the highest tuberculosis (TB) burden countries in Africa. Objective: To present prevalence and describe multidrug-resistant tuberculosis cases in North-Kivu Province identified by using Genexpert technology. Methods: We conducted an observational prospective study on multidrug-resistant tuberculosis (MDR-TB) cases in North-Kivu Province, DRC from 2017 to 2018. All cases of MDR-TB identified by Genexpert MTB/ RIB were included in this series. Result: Of 15,544 tuberculosis cases registered during the study period, 19 cases of MDR-TB were identified. 57.9% was male, 89.5% was retreatment cases and 5.3% was coinfection HIV/TB cases. Conclusion: This new molecular technology diagnostic facilitates multidrug-resistance tuberculosis detection and improves the reporting of data lack.

Identification, Synthesis, Isolation and Spectral Characterization of Multidrug-Resistant Tuberculosis (MDR-TB) Related Substances

Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.

Cost of treatment support for multidrug-resistant tuberculosis using patient-centred approaches in Ethiopia: a model-based method

Background Patient and health system costs for treating multidrug-resistant tuberculosis (MDR-TB) remain high even after treatment duration was shortened. Many patients do not finish treatment, contributing to increased transmission and antimicrobial resistance. A restructure of health services, that is more patient-centred has the potential to reduce costs and increase trust and patient satisfaction. The aim of the study is to investigate how costs would change in the delivery of MDR-TB care in Ethiopia under patient-centred and hybrid approaches compared to the current standard-of-care.Methods We used published data, collected from 2017 to 2020 as part of the Standard Treatment Regimen of Anti-Tuberculosis Drugs for Patients with MDR-TB (STREAM) trial, to populate a discrete event simulation (DES) model. The model was developed to represent the key characteristics of patients’ clinical pathways following each of the three treatment delivery strategies. To the pathways of 1000 patients generated by the DES model we applied relevant patient cost data derived from the STREAM trial. Costs are calculated for treating patients using a 9-month MDR-TB treatment and are presented in 2021 United States dollars (USD).Results The patient-centred and hybrid strategies are less costly than the standard-of-care, from both a health system (by USD 219 for patient-centred and USD 276 for the hybrid strategy) and patient perspective when patients do not have a guardian (by USD 389 for patient-centred and USD 152 for the hybrid strategy). Changes in indirect costs, staff costs, transport costs, inpatient stay costs or changes in directly-observed-treatment frequency or hospitalisation duration for standard-of-care did not change our results.Conclusion Our findings show that patient-centred and hybrid strategies for delivering MDR-TB treatment cost less than standard-of-care and provide critical evidence that there is scope for such strategies to be implemented in routine care. These results should be used inform country-level decisions on how MDR-TB is delivered and also the design of future implementation trials.

Characterization of Mutations in Genes Related to Rifampicin and Isoniazid Resistance in Multidrug-resistant Mycobacterium tuberculosis Strains from Hangzhou,China

Tuberculosis(TB),caused by the Mycobacterium tuberculosis complex(MTBC),is the 13^(th)leading cause of death and the second leading cause of infectious killer after COVID-19(above HIV and AIDS),according to the World Health Organization's 2022 Global TB Report.In 2021,10.6 million people were diagnosed with a new episode of TB and 1.6 million people died as a result.

Treatment outcomes for multidrug-resistant tuberculosis under DOTS-Plus:a systematic review and meta-analysis of published studies

Background:Anti-tuberculosis drug resistance is a major public health problem that threatens the progress made in tuberculosis care and control worldwide.Treatment success rates of multidrug-resistant tuberculosis(MDR-TB)is a key issue that cannot be ignored.There is a paucity of evidence that assessed studies on the treatment of MDR-TB,which focus on the effectiveness of the directly observed treatment,short-course(DOTS)-Plus program.Therefore,it is crucial to assess and summarize the overall treatment outcomes for MDR-TB patients enrolled in the DOTS-Plus program in recent years.The purpose of this study was to thus assess and summarize the available evidence for MDR-TB treatment outcomes under DOTS-Plus.Methods:A systematic review and meta-analysis of published literature was conducted.Original studies were identified using the databases MEDLINE®/PubMed®,Hinari,and Google Scholar.Heterogeneity across studies was assessed using the Cochran’s Q test and I2 statistic.Pooled estimates of treatment outcomes were computed using the random effect model.Results:Based on the 14 observational studies included in the meta-analysis,it was determined that 5047 patients reported treatment outcomes.Of these,the pooled prevalence,63.5%(95%CI:58.4-68.5%)successfully completed full treatment(cured or treatment completed)with a pooled cure rate of 55.6%,whereas 12.6%(95%CI:9.0-16.2%)of the patients died,14.2%(95%CI:11.6-16.8%)defaulted from therapy,and 7.6%(95%CI:5.6-9.7%)failed therapy.Overall 35.4%(95%CI:30-40.8%)of patients had unsuccessful treatment outcomes.An unsatisfactorily high percentage 43%(95%CI:32-54%)of unsuccessful treatment outcomes was observed among patients who were enrolled in standardized treatment regimens.Conclusion:This study revealed that patients with MDR-TB exhibited a very low treatment success rate compared to the World Health Organization 2015 target of at least 75 to 90%.The high default rate observed by conducting this literature review could possibly explain the spread of the MDR-TB strain in various populations.A better treatment success rate was observed among patients in individualized treatment regimens than in standardized ones.Conducting further individual-based meta-analysis is recommended to identify potential factors for defaulting treatment using large-scale and multi-center studies.

Primary gastroduodenal tuberculosis presenting as gastric outlet obstruction:A case report and review of literature

BACKGROUND Mycobacterium tuberculosis(TB)is the causative agent of TB,a chronic granulo-matous illness.This disease is prevalent in low-income countries,posing a significant global health challenge.Gastrointestinal TB is one of the three forms.The disease can mimic other intra-abdominal conditions,leading to delayed diagnosis owing to the absence of specific symptoms.While gastric outlet obs-truction(GOO)remains a frequent complication,its incidence has declined with the advent of proton pump inhibitors and Helicobacter pylori eradication therapy.Gastroduodenal TB can cause upper gastrointestinal hemorrhage,obstruction,and malignancy-like tumors.CASE SUMMARY A 23-year-old male presented with recurrent epigastric pain,distension,nausea,vomiting,and weight loss,prompting a referral to a gastroenterologist clinic.Endoscopic examination revealed distorted gastric mucosa and signs of chronic inflammation.However,treatment was interrupted,possibly owing to vomiting or comorbidities such as human immunodeficiency virus infection or diabetes.Subsequent surgical intervention revealed a dilated stomach and diffuse thickening of the duodenal wall.Resection revealed gastric wall effacement with TB.CONCLUSION Primary gastric TB is rare,frequently leading to GOO.Given its rarity,suspicions should be promptly raised when encountering relevant symptoms,often requiring surgical intervention for diagnosis and treatment.

Rising challenge of multidrug-resistant tuberculosis in China:a predictive study using Markov modeling

Background:Multidrug-resistant tuberculosis(MDR-TB)is on the rise in China.This study used a dynamic Markov model to predict the longitudinal trends of MDR-TB in China by 2050 and to assess the effects of alternative control measures.Methods:Eight states of tuberculosis transmission were set up in the Markov model using a hypothetical cohort of 100000 people.The prevalence of MDR-TB and bacteriologically confirmed drug-susceptible tuberculosis(DS-TB+)were simulated and MDR-TB was stratified into whether the disease was treated with the recommended regimen or not.Results:Without any intervention changes to current conditions,the prevalence of DS-TB+was projected to decline 67.7%by 2050,decreasing to 20 per 100000 people,whereas that of MDR-TB was expected to triple to 58/100000.Furthermore,86.2%of the MDR-TB cases would be left untreated by the year of 2050.In the case where MDR-TB detection rate reaches 50%or 70%at 5%per year,the decline in prevalence of MDR-TB would be 25.9 and 36.2%respectively.In the case where treatment coverage was improved to 70%or 100%at 5%per year,MDR-TB prevalence in 2050 would decrease by 13.8 and 24.1%,respectively.If both detection rate and treatment coverage reach 70%,the prevalence of MDR-TB by 2050 would be reduced to 28/100000 by a 51.7%reduction.Conclusions:MDR-TB,especially untreated MDR-TB,would rise rapidly under China’s current MDR-TB control strategies.Interventions designed to promote effective detection and treatment of MDR-TB are imperative in the fights against MDR-TB epidemics.

Trends in burden of multidrug-resistant tuberculosis in countries,regions,and worldwide from 1990 to 2017:results from the Global Burden of Disease study

Background:Antituberculosis-drug resistance is an important public health issue,and its epidemiological patterns has dramatically changed in recent decades.This study aimed to estimate the trends of multidrug-resistant tuberculosis(MDR-TB),which can be used to inform health strategies.Methods:Data were collected from the Global Burden of Disease study 2017.The estimated annual percentage changes(EAPCs)were calculated to assess the trends of MDR-TB burden at global,regional,and national level from 1990 to 2017 using the linear regression model.

Multidrug-resistant tuberculosis transmission among middle school students in Zhejiang Province,China

Background:Despite significant advancements in the treatment and diagnosis of tuberculosis(TB)over the past decade,drug-resistant TB remains an increasing threat to public health.TB outbreaks are most commonly reported in schools considering the delay in TB diagnosis,sustained contact,and overcrowding observed in schools.This report describes multidrug-resistant TB(MDR-TB)transmission in a school in Zhejiang Province.We aimed to raise awareness regarding MDR-TB transmission among students.Case presentation:The index patient was a 16-year-old girl in the second year of junior middle school in Zhejiang Province,China,who had been experiencing persistent cough and expectoration for 37 days since 1 March 2014.She tested positive for smear pulmonary and extrapulmonary TB on 8 April 2014 and was subsequently diagnosed with MDR-TB on 1 May 2014.However,the patient was resistant to isoniazid,rifampicin,ethambutol,and streptomycin.Thus,she was suspended from school for anti-TB treatment.All 54 students who were in close contact with the index patient in the same class were screened,and 5 tested positive on the tuberculin skin test.Their exposure time to the index patient was approximately 37 days.Three classmates were subsequently diagnosed with MDR-TB,with similar resistance profiles nearly two years later.Their average discovery delay was 55 days.These three classmates were also suspended from school for anti-TB treatment.During the treatment period,four students visited the local TB-designated hospital for further consultation every month and were followed up once a month by the local community health service center until they were completely cured.Conclusions:Discovery delay for an index patient played a primary role in MDR-TB transmission inside the school.To immediately detect TB,morning examinations in schools should be performed.TB trackers and case managers should work closely with public health workers and physicians in cases of TB outbreaks or transmissions involving students.Moreover,individuals who are in close contact with MDR-TB patients should undergo careful clinical follow-up for at least two years.Implementing a joint examination strategy to ensure early detection,diagnosis,and treatment of MDR-TB transmission is recommended.

Multidrug-resistant Tuberculosis Burden among the New Tuberculosis Patients in Zhejiang Province： An Observational Study, 2009-2013

Background：Screening on multidrug-resistant tuberculosis （MDR-TB） has been limited to the serious TB subpopulations excluding the new TB patients.This study aimed to examine MDR-TB burden among the new TB patients.Methods：We conducted a study in Zhejiang Province during 2009-2013 to screen for MDR-TB patients among the low MDR-TB risk patients and five subpopulations of high MDR-TB risk patients.The number,prevalence,and trend of MDR-TB were compared while the logistic regression model was used to examine risk factors related to MDR-TB.Results：A total of 200 and 791 MDR-TB cases were,respectively,identified from the 9830 new TB cases and 2372 high-risk suspects who took MDR-TB screening from 2009 to 2013.The MDR-TB rates went down in both of the new TB patients and five MDR-TB high-risk groups over the study time,but the percentage of MDR-TB patients identified from the new TB patients in all diagnosed MDR-TB cases kept stable from 28.3% in 2011 to 27.0% in 2012 to 26.0% in 2013.Conclusions：The study indicated that MDR-TB burden among new TB patients was high,thus screening for MDR-TB among the new TB patients should be recommended in China as well as in the similar situation worldwide.