Impact of Introducing the Line Probe Assay on Time to Treatment Initiation of MDR-TB in Delhi,India

Setting

National Institute of Tuberculosis and Respiratory Diseases (erstwhile Lala Ram Sarup Institute) in Delhi, India.

Objectives

To evaluate before and after the introduction of the line Probe Assay (LPA) a) the overall time to MDR-TB diagnosis and treatment initiation; b) the step-by-step time lapse at each stage of patient management; and c) the lost to follow-up rates.

Methods

A retrospective cohort analysis was done using data on MDR-TB patients diagnosed during 2009–2012 under Revised National Tuberculosis Control Programme at the institute.

Results

Following the introduction of the LPA in 2011, the overall median time from identification of patients suspected for MDR-TB to the initiation of treatment was reduced from 157 days (IQR 127–200) to 38 days (IQR 30–79). This reduction was attributed mainly to a lower diagnosis time at the laboratory. Lost to follow-up rates were also significantly reduced after introduction of the LPA (12% versus 39% pre-PLA).

Conclusion

Introduction of the LPA was associated with a major reduction in the delay between identification of patients suspected for MDR-TB and initiation of treatment, attributed mainly to a reduction in diagnostic time in the laboratory.     

The Multi-Drug Resistant Tuberculosis Diagnosis and Treatment Cascade in Bangladesh

Objectives

To determine, in areas supported by BRAC, Bangladesh i) the pre-diagnosis and pre-treatment attrition among presumptive and confirmed Multi-Drug Resistant Tuberculosis (MDR-TB) patients and ii) factors associated with attrition.

Methods

This was a retrospective cohort study involving record review. Presumptive MDR-TB patients from peripheral microscopy centres serving 60% of the total population of Bangladesh were included in the study. Attrition and turnaround time for MDR-TB diagnosis by Xpert MTB/RIF and treatment initiation were calculated between July 2012 and June 2014.

Results

Of 836 presumptive MDR-TB patients referred from 398 peripheral microscopy centres, 161 MDR-TB patients were diagnosed. The number of diagnosed MDR-TB patients was less than country estimates of MDR-TB patients (2000 cases) during the study period. Among those referred, pre-diagnosis and pre-treatment attrition was 17% and 21% respectively. Median turnaround time for MDR-TB testing, result receipt and treatment initiation was four, zero and five days respectively. Farmers (RR=2.3, p=0.01) and daily wage laborers (RR=2.1, p=0.04) had twice the risk of having pre-diagnosis attrition. Poor record-keeping and unreliable upkeep of presumptive MDR-TB patient databases were identified as challenges at the peripheral microscopy centres.

Conclusion

There was a low proportion of pre-diagnosis and pre-treatment attrition in patients with presumptive and confirmed MDR-TB under programmatic conditions. However, the recording and reporting system did not detect all presumptive MDR-TB patients, highlighting the need to improve the system in order to prevent morbidity, mortality and transmission of MDR-TB in the community.     

Clinical Benefit of Delamanid (OPC-67683) in the Treatment of Multidrug-Resistant Tuberculosis Patients in China

The cure rates are much lower for multidrug-resistant (MDR) tuberculosis (TB) patients. Delamanid (OPC-67683) has been evaluated in phase-II MDR-TB clinical trials. Herein, we reviewed MDR-TB cases in which treatment regimens, with/without delamanid, were administered. Thirty-eight patients were enrolled; 26 received delamanid-containing regimens (treatment group) while 12 received placebo-containing regimens (control group) for 56 days. Data regarding clinical/radio-microbiological characteristics, drug tolerability, and treatment outcomes were collected. We found that all patients had isolates resistant to a median of 5 (range 2–7) drugs; 24 (92.3 %) patients in treatment group and 11 (91.7 %) in control group had cavities. Culture conversion was obtained in 32 pulmonary TB cases (median 74.5 days). At data censure, 30/38 patients successfully completed therapy with documented negative cultures for at least 18 months before the end of treatment. Two patients (5 consecutive negative cultures) are still on treatment. Six patients had poor outcome (3 failures/2 lost/1 death). In 13 patients, adverse events were observed that included mental disorder, QT interval prolongation, and increased blood cortisol whereas only 3 patients stopped delamanid treatment because of adverse events. It was, therefore, concluded that delamanid was well-tolerated, had low rates of discontinuation, and could be effective for treating MDR-TB.     

Comparing Tuberculosis Diagnostic Yield in Smear/Culture and Xpert? MTB/RIF-Based Algorithms Using a Non-Randomised Stepped-Wedge Design

Setting

Primary health services in Cape Town, South Africa.

Study Aim

To compare tuberculosis (TB) diagnostic yield in an existing smear/culture-based and a newly introduced Xpert^® MTB/RIF-based algorithm.

Methods

TB diagnostic yield (the proportion of presumptive TB cases with a laboratory diagnosis of TB) was assessed using a non-randomised stepped-wedge design as sites transitioned to the Xpert^® based algorithm. We identified the full sequence of sputum tests recorded in the electronic laboratory database for presumptive TB cases from 60 primary health sites during seven one-month time-points, six months apart. Differences in TB yield and temporal trends were estimated using a binomial regression model.

Results

TB yield was 20.9% (95% CI 19.9% to 22.0%) in the smear/culture-based algorithm compared to 17.9% (95%CI 16.4% to 19.5%) in the Xpert^® based algorithm. There was a decline in TB yield over time with a mean risk difference of -0.9% (95% CI -1.2% to -0.6%) (p<0.001) per time-point. When estimates were adjusted for the temporal trend, TB yield was 19.1% (95% CI 17.6% to 20.5%) in the smear/culture-based algorithm compared to 19.3% (95% CI 17.7% to 20.9%) in the Xpert^® based algorithm with a risk difference of 0.3% (95% CI -1.8% to 2.3%) (p = 0.796). Culture tests were undertaken for 35.5% of smear-negative compared to 17.9% of Xpert^® negative low MDR-TB risk cases and for 82.6% of smear-negative compared to 40.5% of Xpert^® negative high MDR-TB risk cases in respective algorithms.

Conclusion

Introduction of an Xpert^® based algorithm did not produce the expected increase in TB diagnostic yield. Studies are required to assess whether improving adherence to the Xpert^® negative algorithm for HIV-infected individuals will increase yield. In light of the high cost of Xpert^®, a review of its role as a screening test for all presumptive TB cases may be warranted.     

Microscopic-Observation Drug-Susceptibility Assay for the Diagnosis of Drug-Resistant Tuberculosis in Harare,Zimbabwe

Introduction

Limited data exist on use of the microscopic-observation drug-susceptibility (MODS) assay among persons suspected of MDR-TB living in high HIV-prevalence settings.

Methods

We retrospectively reviewed available clinical and drug susceptibility data for drug-resistant TB suspects referred for culture and drug-susceptibility testing between April 1, 2011 and March 1, 2012. The diagnostic accuracy of MODS was estimated against a reference standard including Löwenstein-Jensen (LJ) media and manual liquid (BACTEC MGIT) culture. The accuracy of MODS drug-susceptibility testing (DST) was assessed against a reference standard absolute concentration method.

Results

One hundred thirty-eight sputum samples were collected from 99 drug-resistant TB suspects; in addition, six previously cultured MDR isolates were included for assessment of DST accuracy. Among persons with known HIV infection status, 39/59 (66%) were HIV-infected. Eighty-six percent of patients had a history of prior TB treatment, and 80% of individuals were on antituberculous treatment at the time of sample collection. M. tuberculosis was identified by reference standard culture among 34/98 (35%) MDR-TB suspects. Overall MODS sensitivity for M. tuberculosis detection was 85% (95% CI, 69–95%) and specificity was 93% (95% CI, 84–98%); diagnostic accuracy did not significantly differ by HIV infection status. Median time to positivity was significantly shorter for MODS (7 days; IQR 7–15 days) than MGIT (12 days; IQR 6–16 days) or LJ (28 days; IQR 21–35 days; p<0.001). Of 33 specimens with concurrent DST results, sensitivity of the MODS assay for detection of resistance to isoniazid, rifampin, and MDR-TB was 88% (95% CI, 68–97%), 96% (95% CI, 79–100%), and 91% (95% CI, 72–99%), respectively; specificity was 89% (95% CI, 52–100%), 89% (95% CI, 52–100%), and 90% (95% CI, 56–100%), respectively.

Conclusion

In a high HIV-prevalence setting, MODS diagnosed TB and drug-resistant TB with high sensitivity and shorter turnaround time compared with standard culture and DST methods.     

Linkage of Presumptive Multidrug Resistant Tuberculosis (MDR-TB) Patients to Diagnostic and Treatment Services in Cambodia

Setting

National Tuberculosis Programme, Cambodia.

Objective

In a cohort of TB patients, to ascertain the proportion of patients who fulfil the criteria for presumptive MDR-TB, assess whether they underwent investigation for MDR-TB, and the results of the culture and drug susceptibility testing (DST).

Methods

A cross sectional record review of TB patients registered for treatment between July-December 2011.

Results

Of 19,236 TB patients registered, 409 (2%) fulfilled the criteria of presumptive MDR-TB; of these, 187 (46%) were examined for culture. This proportion was higher among relapse, failure, return after default (RAD) and non-converters at 3 months of new smear positive TB patients (>60%) as compared to non-converters at 2 months of new TB cases (<20%). Nearly two thirds (n = 113) of the samples were culture positive; of these, three-fourth (n = 85) grew Mycobacterium tuberculosis complex (MTBc) and one-fourth (n = 28) grew non-tuberculous Mycobacteria. DST results were available for 96% of the MTBc isolates. Overall, 21 patients were diagnosed as MDR-TB (all diagnosed among retreatment TB cases and none from non-converters) and all of them were initiated on MDR-TB treatment.

Conclusion

There is a need to strengthen mechanisms for linking patients with presumptive MDR-TB to culture centers. The policy of testing non-converters for culture and DST needs to be reviewed.     

Outcomes of Multidrug-Resistant Tuberculosis Treatment with Early Initiation of Antiretroviral Therapy for HIV Co-Infected Patients in Lesotho

Background

Although the importance of concurrent treatment for multidrug-resistant tuberculosis (MDR-TB) and HIV co-infection has been increasingly recognized, there have been few studies reporting outcomes of MDR-TB and HIV co-treatment. We report final outcomes of comprehensive, integrated MDR-TB and HIV treatment in Lesotho and examine factors associated with death or treatment failure.

Methods

We reviewed clinical charts of all adult patients who initiated MDR-TB treatment in Lesotho between January 2008 and September 2009. We calculated hazard ratios (HR) and used multivariable Cox proportional hazards regression to identify predictors of poor outcomes.

Results

Of 134 confirmed MDR-TB patients, 83 (62%) were cured or completed treatment, 46 (34%) died, 3 (2%) transferred, 1 (1%) defaulted, and 1 (1%) failed treatment. Treatment outcomes did not differ significantly by HIV status. Among the 94 (70%) patients with HIV co-infection, 53% were already on antiretroviral therapy (ART) before MDR-TB treatment initiation, and 43% started ART a median of 16 days after the start of the MDR-TB regimen. Among HIV co-infected patients who died, those who had not started ART before MDR-TB treatment had a shorter median time to death (80 days vs. 138 days, p = 0.065). In multivariable analysis, predictors of increased hazard of failure or death were low and severely low body mass index (HR 2.75, 95% confidence interval [CI] 1.27–5.93; HR 5.50, 95% CI 2.38–12.69), and a history of working in South Africa (HR 2.37, 95% CI 1.24–4.52).

Conclusions

Favorable outcomes can be achieved in co-infected patients using a community-based treatment model when both MDR-TB and HIV disease are treated concurrently and treatment is initiated promptly.     

Bacteriological follow-up of pulmonary tuberculosis treatment: a study with a simple colorimetric assay

The viability of Mycobacterium tuberculosis (MTB) in serial sputum specimens from persistently smear positive patients was evaluated. The assay was based on oxidation-reduction of Alamar Blue and Malachite Green dyes that change their color in response to MTB growth. A total of 280 sputum specimens from 40 persistently smear positive TB patients and 40 sputa from non-tuberculosis patients were digested, decontaminated and examined microscopically. To check the MTB viability, the sediments from decontaminated samples were inoculated into three culture media: Lowenstein-Jensen (LJ) slants, Alamar Blue and Malachite Green culture tubes. We found that out of 280 smear positive specimens, the LJ culture was positive in 124 (44%). The numbers of correctly identified S+/C+ cases by Alamar Blue and Malachite Green were 118 (95%) and 116 (93%), respectively. The mean time required for reporting the positive signal in Alamar Blue culture tubes was 9 versus 11 days by Malachite Green culture tubes. In the standard LJ culture media the average detection time was 27 days (P < 0.05). The sensitivity of LJ was 99%, Alamar Blue 95% and Malachite Green 93%. The specificity was 100%, 92% and 93%, respectively. The oxidation-reduction method is rapid, sensitive and inexpensive in monitoring the treatment response of patients with pulmonary TB. Thus, using this method can be of paramount importance, particularly in resource-constrained areas.     

Lung cancer patients' journey from first symptom to treatment: Results from a Greek registry

BackgroundTo map the patients’ journey from symptoms onset to treatment initiation for the most frequent histological types of lung cancer in Greece and describe the initial treatment that patients receive.MethodsThe primary data source was a Greek hospital-based registry. Demographic, anthropometric, lifestyle, and diagnostic-related characteristics as well as treatment-related data were extracted from the registry for patients diagnosed with Adenocarcinoma, Squamous and Small Cell Lung Cancer (SCLC). The time intervals from symptoms onset to diagnosis (StD), diagnosis to treatment initiation (DtT), symptoms onset to treatment initiation (StT) and surgery to post–surgery treatment (SRGtT) were estimated.Results231, 120 and 122 patients were diagnosed with Adenocarcinoma, SCLC and Squamous, respectively. The percentage of patients diagnosed at stage III/IV ranged from 75% in Adenocarcinoma to 97.5% in SCLC (p < 0.001). The median (IQR) StD was 52 (28–104) days and no difference was detected across the three histological types (p = 0.301). Cough as first symptom was the only determinant of StD (p = 0.001). The median (IQR) DtT was 23 (13–36) days, with this time interval being shorter among patients with SCLC compared to patients with Adenocarcinoma and Squamous (p < 0.001). The median (IQR) StT was 81 (51–139) days. Almost one third of patients with Adenocarcinoma and Squamous were subjected first to surgery and the median (IQR) SRGtT was 42 (34–55) days.ConclusionsOur results indicate that time interval from symptoms onset to treatment initiation in Greece is substantially prolonged, highlighting the need for strategies to expedite lung cancer diagnosis and access to evidence-based treatment.     

Effectiveness of a Government-Organized and Hospital-Initiated Treatment for Multidrug-Resistant Tuberculosis Patients-A Retrospective Cohort Study

Background

In contrast to the conventional model of hospital-treated and government directly observed treatment (DOT) for multidrug-resistant tuberculosis (MDR-TB) patient care, the Taiwan MDR-TB Consortium (TMTC) was launched in May 2007 with the collaboration of five medical care groups that have provided both care and DOT. This study aimed to determine whether the TMTC provided a better care model for MDR-TB patients than the conventional model.

Methods and Findings

A total of 651 pulmonary MDR-TB patients that were diagnosed nation-wide from January 2000-August 2008 were enrolled. Of those, 290 (45%) MDR-TB patients whose initial sputum sample was taken in January 2007 or later were classified as patients in the TMTC era. All others were classified as patients in the pre-TMTC era. The treatment success rate at 36 months was better in the TMTC era group (82%) than in the pre-TMTC era group (61%) (p<0.001). With multiple logistic regressions, diagnosis in the TMTC era (adjusted odds ratio (aOR) 2.8, 95% confidence interval (CI) 1.9–4.2) was an independent predictor of a higher treatment success rate at 36 months. With the time-dependent proportional hazards method, a higher treatment success rate was still observed in the TMTC era group compared to the pre-TMTC era group (adjusted hazard ratio 6.3, 95% CI 4.2–9.5).

Conclusion

The improved treatment success observed in the TMTC era compared to the pre-TMTC era is encouraging. The detailed TMTC components that contribute the most to the improved outcome will need confirmation in follow-up studies with large numbers of MDR-TB patients.     

Culture conversion among HIV co-infected multidrug-resistant tuberculosis patients in Tugela Ferry, South Africa

Background

Little is known about the time to sputum culture conversion in MDR-TB patients co-infected with HIV, although such patients have, historically, had poor outcomes. We describe culture conversion rates among MDR-TB patients with and without HIV-co-infection in a TB-endemic, high-HIV prevalent, resource-limited setting.

Methods

Patients with culture-proven MDR-TB were treated with a standardized second-line regimen. Sputum cultures were taken monthly and conversion was defined as two negative cultures taken at least one month apart. Time-to-conversion was measured from the day of initiation of MDR-TB therapy. Subjects with HIV received antiretroviral therapy (ART) regardless of CD4 count.

Results

Among 45 MDR-TB patients, 36 (80%) were HIV-co-infected. Overall, 40 (89%) of the 45 patients culture-converted within the first six months and there was no difference in the proportion who converted based on HIV status. Median time-to-conversion was 62 days (IQR 48-111). Among the five patients who did not culture convert, three died, one was transferred to another facility, and one refused further treatment before completing 6 months of therapy. Thus, no patients remained persistently culture-positive at 6 months of therapy.

Conclusions

With concurrent second-line TB and ART medications, MDR-TB/HIV co-infected patients can achieve culture conversion rates and times similar to those reported from HIV-negative patients worldwide. Future studies are needed to examine whether similar cure rates are achieved at the end of MDR-TB treatment and to determine the optimal use and timing of ART in the setting of MDR-TB treatment.     

Quantitative Drug-Susceptibility in Patients Treated for Multidrug-Resistant Tuberculosis in Bangladesh: Implications for Regimen Choice

BackgroundMultidrug-resistant tuberculosis (MDR-TB) treatment in Bangladesh is empiric or based on qualitative drug-susceptibility testing (DST) by comparative growth in culture media with and without a single drug concentration.MethodsAdult patients were enrolled throughout Bangladesh during the period of 2011–2013 at MDR-TB treatment initiation. Quantitative DST by minimum inhibitory concentration (MIC) testing for 12 first and second-line anti-TB drugs was compared to pretreatment clinical characteristics and treatment outcomes. MIC values at or one dilution lower than the resistance breakpoint used for qualitative DST were categorized as borderline susceptible, and MIC values one or two dilutions greater as borderline resistant.ResultsSeventy-four patients were enrolled with a mean age of 35 ±15 years, and 51 (69%) were men. Of the rifampin isolates with MIC >1.0 μg/ml, 12 (19%) were fully susceptible or borderline susceptible to rifabutin (MIC ≤0.5 μg/ml). Amikacin was fully susceptible in 73 isolates (99%), but kanamycin in only 54 (75%) (p<0.001). Ofloxacin was borderline susceptible in 64%, and fully susceptible in only 14 (19%) compared to 60 (81%) of isolates fully susceptible for moxifloxacin (p<0.001). Kanamycin non-susceptibility and receipt of the WHO Category IV regimen trended with interim treatment failure: adjusted odd ratios respectively of 5.4 [95% CI 0.82–36.2] (p = 0.08) and 7.2 [0.64–80.7] (p = 0.11).ConclusionsQuantitative MIC testing could impact MDR-TB regimen choice in Bangladesh. Comparative trials of higher dose or later generation fluoroquinolone, within class change from kanamycin to amikacin, and inclusion of rifabutin appear warranted.     

Direct nitrate reductase assay versus microscopic observation drug susceptibility test for rapid detection of MDR-TB in Uganda

The most common method for detection of drug resistant (DR) TB in resource-limited settings (RLSs) is indirect susceptibility testing on Lowenstein-Jensen medium (LJ) which is very time consuming with results available only after 2-3 months. Effective therapy of DR TB is therefore markedly delayed and patients can transmit resistant strains. Rapid and accurate tests suitable for RLSs in the diagnosis of DR TB are thus highly needed. In this study we compared two direct techniques--Nitrate Reductase Assay (NRA) and Microscopic Observation Drug Susceptibility (MODS) for rapid detection of MDR-TB in a high burden RLS. The sensitivity, specificity, and proportion of interpretable results were studied. Smear positive sputum was collected from 245 consecutive re-treatment TB patients attending a TB clinic in Kampala, Uganda. Samples were processed at the national reference laboratory and tested for susceptibility to rifampicin and isoniazid with direct NRA, direct MODS and the indirect LJ proportion method as reference. A total of 229 specimens were confirmed as M. tuberculosis, of these interpretable results were obtained in 217 (95%) with either the NRA or MODS. Sensitivity, specificity and kappa agreement for MDR-TB diagnosis was 97%, 98% and 0.93 with the NRA; and 87%, 95% and 0.78 with the MODS, respectively. The median time to results was 10, 7 and 64 days with NRA, MODS and the reference technique, respectively. The cost of laboratory supplies per sample was low, around 5 USD, for the rapid tests. The direct NRA and MODS offered rapid detection of resistance almost eight weeks earlier than with the reference method. In the study settings, the direct NRA was highly sensitive and specific. We consider it to have a strong potential for timely detection of MDR-TB in RLS.     

奥拉西坦联合高压氧治疗重度一氧化碳中毒的疗效及对血清LPA、H-FABP及认知功能的影响

目的:探讨奥拉西坦联合高压氧治疗重度一氧化碳中毒的疗效及对血清溶血磷脂酸(LPA)、心型脂肪酸结合蛋白(H-FABP)及认知功能的影响。方法:选择2016年1月-2018年1月我院收治的重度一氧化碳中毒患者90例进行研究,以随机数表法分为观察组(n=48)和对照组(n=42)。对照组给予高压氧治疗,观察组在对照组的基础上加用奥拉西坦治疗。比较两组患者的临床疗效、血清LPA、H-FABP、认知能力、住院时间、迟发性脑病发生率。结果:两组总有效率分别为93.75%、76.19%,差异显著(P0.05);治疗前,两组血清LPA、H-FABP水平无显著性差异;治疗后,两组血清LPA、H-FABP均显著下降,且观察组血清LPA、H-FAB P水平低于对照组,(P0.05);治疗前,两组患者认知功能无显著性差异;治疗后,两组认知功能较治疗前均显著升高(P0.05),且观察组定向力、记忆力、注意力、语言能力水平均明显高于对照组(P0.05);观察组患者住院时间、迟发性脑病发生率均显著低于对照组,差异显著(P0.05)。结论:在重度一氧化碳中毒患者中应用奥拉西坦联合高压氧效果显著,可有效改善患者血清LPA、H-FABP水平及认知功能。     

Epidemiology and Clinical Characteristics of Pediatric Drug-Resistant Tuberculosis in Chongqing,China

To gain insight into the epidemiology of childhood drug resistant tuberculosis (DR-TB) in China that has the second largest burden of TB and the largest number of multidrug resistant (MDR) TB cases in the world, we performed the cross-sectional study to investigate drug resistance of four first-line anti-TB drugs (isoniazid, rifampicin, streptomycin and ethambutol) using Mycobacterium tuberculosis isolates from 196 culture-confirmed pediatric TB cases diagnosed in the Children’s Hospital of Chongqing Medical University, China during 2008–2013. Univariate and multivariate logistic regression analyses were performed to assess the associations between patient demographic and clinical characteristics and DR-and MDR-TB, respectively. Twenty-eight percent (56/196) of the study patients exhibited resistance to at least one of the four first-line anti-TB drugs tested. MDR was found in 4.6% (9/196) of the study patients. More than half (5/9, 55.6%) of the MDR cases were from a single county of Chongqing. A significant association was found between being acid-fast bacilli-smear negative and DR-TB (adjusted OR, 2.33; 95% CI, 1.13–4.80) and between having concurrent thoracic-extrathoracic involvement and MDR-TB (adjusted OR, 9.49; 95% CI, 1.05–85.92), respectively. The findings of this study indicate that the rate of DR is high among pediatric TB patients in Chongqing and suggest an urgent need for studies to identify MDR transmission hotspots in Chongqing, thereby contributing to the control DR- and MDR-TB epidemics in China. The study also generates new insight into the pathogenesis of DR and MDR M. tuberculosis strains and highlights the importance of studying childhood TB to the goal of global TB control.     

Do We Need to Detect Isoniazid Resistance in Addition to Rifampicin Resistance in Diagnostic Tests for Tuberculosis?

Background

Multidrug-resistant tuberculosis (MDR-TB) is resistant to both rifampicin (RIF) and isoniazid (INH). Whereas many TB diagnostics detect RIF-resistance, few detect INH-monoresistance, which is common and may increase risk of acquired MDR-TB. Whether inclusion of INH-resistance in a first-line rapid test for TB would have an important impact on MDR-TB rates remains uncertain.

Methods

We developed a transmission model to evaluate three tests in a population similar to that of India: a rapid molecular test for TB, the same test plus RIF-resistance detection (“TB+RIF”), and detection of RIF and INH-resistance (“TB+RIF/INH”). Our primary outcome was the prevalence of INH-resistant and MDR-TB at ten years.

Results

Compared to the TB test alone and assuming treatment of all diagnosed MDR cases, the TB+RIF test reduced the prevalence of MDR-TB among all TB cases from 5.5% to 3.8% (30.6% reduction, 95% uncertainty range, UR: 17–54%). Despite using liberal assumptions about the impact of INH-monoresistance on treatment outcomes and MDR-TB acquisition, expansion from TB+RIF to TB+RIF/INH lowered this prevalence only from 3.8% to 3.6% further (4% reduction, 95% UR: 3–7%) and INH-monoresistant TB from 15.8% to 15.1% (4% reduction, 95% UR: (-8)-19%).

Conclusion

When added to a rapid test for TB plus RIF-resistance, detection of INH-resistance has minimal impact on transmission of TB, MDR-TB, and INH-monoresistant TB.     

Self-reported risks for multiple-drug resistance among new tuberculosis cases: implications for drug susceptibility screening and treatment

Background

Multiple drug-resistance in new tuberculosis (TB) cases accounts for the majority of all multiple drug-resistant TB (MDR-TB) worldwide. Effective control requires determining which new TB patients should be tested for MDR disease, yet the effectiveness of global screening recommendations of high-risk groups is unknown.

Methods

Sixty MDR-TB cases with no history of previous TB treatment, 80 drug-sensitive TB and 80 community-based controls were recruited in Lima, Peru between August and December, 2008 to investigate whether recommended screening practices identify individuals presenting with MDR-TB. Odd ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression to study the association of potential risk factors with case/control variables.

Results

MDR-TB cases did not differ from drug-sensitive TB and community controls in rates of human immunodeficiency virus infection, reported hospital or prison visits in the 3 years prior to diagnosis. MDR-TB cases were more likely than drug-sensitive TB controls to have had a recent MDR-TB household contact (OR 4.66, (95% CI 1.56–13.87)); however, only 15 cases (28.3%) reported this exposure. In multivariate modeling, recent TB household contact, but not contact with an MDR-TB case, remained predictive of MDR-TB, OR 7.47, (95% CI 1.91–29.3). Living with a partner rather than parents was associated with a lower risk of MDR-TB, OR 0.15, (95% CI 0.04–0.51).

Conclusion

Targeted drug susceptibility testing (DST) linked to reported MDR-TB contact or other high-risk exposures does not identify the majority of new TB cases with MDR disease in Lima where it is endemic. All new TB cases should be screened with DST to identify MDR patients. These findings are likely applicable to other regions with endemic MDR-TB.     

结核分枝杆菌/利福平耐药实时荧光定量核酸扩增检测技术对肺外结核性脓肿的诊断价值分析

摘要 目的：探讨结核分枝杆菌/利福平耐药实时荧光定量核酸扩增检测技术（Xpert MTB/RIF）对肺外结核性脓肿的诊断价值。方法：收集2020年1月至2021年12月无锡市第五人民医院住院的122例高度疑似肺外结核性脓肿患者为研究对象,在超声引导下对脓肿病灶进行针吸穿刺活检,脓液标本分别进行Xpert MTB/RIF检测、结核杆菌脱氧核糖核酸（TB-DNA）检测、MGIT 960培养以及涂片抗酸染色。以临床综合诊断作为参考标准,比较Xpert MTB/RIF检测、TB-DNA检测、MGIT 960培养以及涂片抗酸染色四种方法对肺外结核性脓肿的诊断效能。对比Xpert MTB/RIF检测和MGIT 960药敏试验对利福平的耐药性。观察各类肺外结核性脓肿患者的诊断延迟时间。结果：122例疑似患者中,最终确诊肺外结核性脓肿患者73例,非结核性脓肿者49例。Xpert MTB/RIF检测、MGIT 960培养、TB-DNA检测以及涂片抗酸染色四种方法在肺外结核性脓肿标本中的阳性检出率结果分别为89.04%、20.55%、58.90%、36.99%,四种方法的阳性检出率整体比较差异有统计学意义（P<0.01）,Xpert MTB/RIF检测的阳性检出率明显高于MGIT 960培养、TB-DNA检测以及涂片抗酸染色法,差异均有统计学意义（P<0.05）。以临床综合诊断作为参考标准,Xpert MTB/RIF检测诊断肺外结核性脓肿者的临床诊断价值最高,其敏感度、特异度、阳性预测值、阴性预测值分别为89.04%、100.00%、100.00%、85.96%。Xpert MTB/RIF检测与MGIT 960药敏试验对利福平耐药率之间差异无统计学意义（P>0.05）。肺外结核性脓肿诊断存在明显延迟,尤其以关节结核性脓肿诊断延迟时间最长,平均为103.5天;但在结核性脓胸患者中诊断延迟时间最短,平均为7.6天。结论：与MGIT 960培养、TB-DNA检测以及涂片抗酸染色比较,Xpert MTB/RIF在肺外结核性脓肿中的阳性检出率较高,临床诊断价值最佳,表明其可用作为疑似结核性脓肿患者的快速诊断工具,同时在结核耐药性方面亦可以做到快速筛查。     

Operational challenges in diagnosing multi-drug resistant TB and initiating treatment in Andhra Pradesh, India

Background

Revised National TB Control Programme (RNTCP), Andhra Pradesh, India. There is limited information on whether MDR-TB suspects are identified, undergo diagnostic assessment and are initiated on treatment according to the programme guidelines.

Objectives

To assess i) using the programme definition, the number and proportion of MDR-TB suspects in a large cohort of TB patients on first-line treatment under RNTCP ii) the proportion of these MDR-TB suspects who underwent diagnosis for MDR-TB and iii) the number and proportion of those diagnosed as MDR-TB who were successfully initiated on treatment.

Methods

A retrospective cohort analysis, by reviewing RNTCP records and reports, was conducted in four districts of Andhra Pradesh, India, among patients registered for first line treatment during October 2008 to December 2009.

Results

Among 23,999 TB patients registered for treatment there were 559 (2%) MDR-TB suspects (according to programme definition) of which 307 (55%) underwent diagnosis and amongst these 169 (55%) were found to be MDR-TB. Of the MDR-TB patients, 112 (66%) were successfully initiated on treatment. Amongst those eligible for MDR-TB services, significant proportions are lost during the diagnostic and treatment initiation pathway due to a variety of operational challenges. The programme needs to urgently address these challenges for effective delivery and utilisation of the MDR-TB services.     

Comparison of Three Culture Media for Isolation of Mycobacterium tuberculosis: a 6-Year Study

Among 2,648 specimens positive on culture for Mycobacterium tuberculosis over a 6-year period, 82% grew on Lowenstein-Jensen medium (LJ), 79% on American Trudeau Society (ATS), and 56% on Middlebrook 7H10 (7H10). When these commercial culture media were compared in regard to the number of acid-fast bacilli seen on the original smears, LJ cultures were found to have the highest isolation rates for each smear category, and 7H10 had the lowest rates. Comparing the media from the aspect of number of mycobacterial colonies produced, LJ and ATS had the highest average colony counts, followed by 7H10. These findings were relatively constant over the 6-year period. One possible reason for the low positive rate of 7H10 was the lack of CO(2) enrichment.