Rifampicin-resistant Tuberculosis Cases Research Articles

Five-year tuberculosis trends analysis in eight districts of Mwanza region, Tanzania; (2017-2021).

In Tanzania like other developing countries, TB detection is hindered by totally missed, late notification, and delayed diagnosis of active cases. Apart from having TB control strategies and interventions to detect patients and put them on treatment to cut down the chain of transmission, TB remains a health concern. Limited data exist on the burden and trends of tuberculosis in Mwanza, which includes fishing communities and living conditions that are associated with high TB transmission like overcrowding. This study aimed to determine tuberculosis trends in the Mwanza region of Tanzania for five years, from 2017 to 2021. We extracted routine TB diagnostic data from 2017 to 2021 from eight districts of the Mwanza region of Tanzania from the electronic TB database. Data were captured in Microsoft Office Excel 2007 with district TB and leprosy coordinators and then imported into STATA 13 (Stata Corp LLC, College Station, TX, USA) for analysis. We estimated the TB case detection rate per 100,000 population. A total of 6,414 laboratory-confirmed tuberculosis cases were detected in eight districts of the Mwanza region in Tanzania from 2017 to 2021. The average tuberculosis detection rate in five years was 34.7 per 100,000 population. Overall, the TB detection rate was two times higher in people without HIV (30.5) compared to those infected with HIV; 13.4 per 100,000 population. Of the 15 rifampicin-resistant TB cases detected in the year 2018, 66.7% (10/15) were HIV-negative compared to 33.3% (5/15) infected with HIV. The TB case detection rate decreased in Mwanza region from 43.9 in 2017 to 21.4 per 100,000 population in 2021. Other parameters were missing in the database, which indicates remarkable gaps in the established database to monitor TB management in the region. The program may consider investigating and improving the documentation of information necessary to attain its goals.

Rifampicin Resistant Tuberculosis Among Presumptive Pulmonary Tuberculosis in Province Referral Hospital, Indonesia: Dynamic Cases of a 7-Year Report.

Indonesia has the second highest tuberculosis (TB) cases globally. This study aimed to determine the sociodemographic factors associated with TB and rifampicin-resistant tuberculosis (RR-TB) cases among presumptive pulmonary TB patients in Aceh Referral Hospital. Study Design: A retrospective cross-sectional study. A retrospective cross-sectional review of presumptive pulmonary TB patients having a sputum test at the clinical microbiology laboratory was conducted from January 2015 to December 2021. Patient characteristics and drug susceptibility data were abstracted from the hospital information system of TB (SITB) and analyzed by univariate and bivariate analysis. The Mycobacterium tuberculosis (MTB) was detected in 32.8% sample (1,521/4,637). Of the TB-confirmed cases, 14.1% (215/1,521) were resistant to rifampicin (RR-TB). Most of them were male patients (71.63%), were in the age range of 35-54 years (48.7%), lived in rural areas of the country (56.3%), and were previously TB-treated cases (65.5%). Overall, 35-44-year-old patients (adjusted odds ratio [AOR]=2.11, 95% CI=1.25, 3.5, P<0.05) were more likely to have RR-TB compared to>65-year-old patients. Gender and residence were not associated with RR-TB (P>0.05). Case detection decreased in pandemic conditions (19.5% in 2019 to 13.9% and 7.91% in 2020 and 2021, respectively). The findings revealed the dynamic cases and sociodemographic factors of TB and RR-TB in a province referral hospital in Indonesia for 7 years. The cases of TB and RR-TB among presumptive TB patients were 32.8% and 14.1%, respectively. The cases were found to be more noticeable in males, adults (45-54 years old), and patients residing in rural areas.

Impact of line probe assay-based molecular testing on individualized treatment in patients with rifampicin-resistant tuberculosis: data from the prospective INNOVA4TB cohort study in Ukraine.

Ukraine remains a high World Health Organization priority country for drug-resistant tuberculosis (TB). Rifampicin-resistant TB (RR-TB) has a more protracted, more complicated, and more expensive treatment. In 2021, Ukraine reported 4025 RR-TB cases - 5.4 times more (751) than all 30 European Union/ European Economic Area countries together. The objective of the study was to determine the diagnostic accuracy of line probe assay (LPA), AID Autoimmun Diagnostika GmbH, for detecting resistance to anti-TB drugs and its clinical application for selecting treatment regimens. A prospective observational cohort study. From May 2019 to June 2020, we consecutively enrolled patients with active TB hospitalized at the Regional Phthisiopulmonology Center (Vinnytsia, Ukraine), aged between 18 and 82 years. The LPA was performed in the Genetic Research Laboratory at National Pirogov Memorial Medical University, Vinnytsia, Ukraine. A total of 84 clinical specimens and 97 culture isolates from 126 TB patients were tested during the study. Accuracy (95% confidence interval) of LPA for clinical samples in comparison with phenotypic drug susceptibility test (DST) was 80.1 (68.5-89.0) for isoniazid (H), 74.7 (62.4-84.6) for rifampicin (R), 74.4 (62.5-84.1) for ethambutol, 71.4 (41.9-91.6) for streptomycin, 84.6 (62.4-96.5) for prothionamide/ethionamide, and 84.6 (73.6-92.3) for levofloxacin (Lfx), respectively. We found a significantly higher sensitivity of LPA for H, R, and Lfx for the culture isolates compared to clinical specimens (p < 0.05). LPA detected different mutations in 6 out of 17 (35.5%) patients susceptible to R by Xpert. A shorter treatment regimen with an injectable agent demonstrated a low suitability rate of 5% (8/156) in a cohort of RR-TB patients from Ukraine. Initial LPA testing accurately identifies resistance to anti-TB drugs and facilitates the selection of an appropriate treatment regimen, minimizing exposure to empirical therapy.

Household drug-resistant TB contact tracing in Tajikistan.

BACKGROUND: Tajikistan has a high burden of rifampicin-resistant TB (RR-TB), with 2,700 new cases estimated for 2021 (28/100,000 population). TB is spread among household members through close interaction and children exposed through household contact progress to disease rapidly and frequently.METHODS: We retrospectively analysed programmatic data from household contact tracing in Dushanbe over 50 months. We calculated person-years of follow-up, contact tracing yield, number needed to screen (NNS) and number needed to test (NNT) to find one new case, and time to diagnosis.RESULTS: We screened 6,654 household contacts of 830 RR-TB index cases; 47 new RR-TB cases were detected, 43 in Year 1 and 4 in Years 2 or 3. Ten were aged <5 years; 46/47 had TB symptoms, 34/45 had chest radiographs consistent with TB, 11/35 were Xpert Ultra-positive, 29/32 were tuberculin skin test-positive and 28/47 had positive TB culture and phenotypic drug susceptibility results. The NNS to find one RR-TB case was 141.57 and the NNT was 34.49. The yields for different types of contacts were as follows: 0.7% for screened contacts, 2.9% for tested contacts, 17.0% for symptomatic contacts and 12.1% for symptomatic contacts aged below 5 years.CONCLUSION: RR-TB household contact tracing was feasible and productive in Tajikistan, a low middle-income country with an inefficient healthcare delivery system.

Isoniazid Resistance Level and Associated Resistance Conferring-mutations in Rifampicin Resistant Mycobacterium tuberculosis

Background: Multidrug resistant tuberculosis (MDR-TB) is a global public health problem causing treatment failure. Rifampicin (RIF) resistance has been used as a surrogate marker for MDR-TB diagnosis, but level of isoniazid (INH) resistance and associated resistance conferring mutations for INH in rifampicin-resistant TB cases are little known. Objective: The objective of this study was to determine level of isoniazid resistance and associated resistance conferring mutations in rifampicin resistant Mycobacterium tuberculosis (MTB) in sputum samples. Methods: A total 53 RIF resistant MTB isolates in sputum, detected by Xpert-MTB RIF assay were enrolled in the study. Culture positive samples were tested by BACTEC MGIT 960 system and level of isoniazid resistance was determined, defined as minimum inhibitory concentration of INH of &gt;0.4 µg/mL and 0.1-0.4 µg/mL as high level and low level INH resistance respectively. Distribution of mutation in katG (codon 315) and inhA promoter (-5, -8, -15 and -16) genes by Real-time PCR among the different degrees of INH resistance was investigated. Results: Among the growth positive isolates, 68.8% of the resistant isolates had high level INH resistance, where katG was found to be the prominent mutation, with or without combined with inhA mutation. Positive predictive value (PPV) of katG mutation was 84.6% in detecting a high level of INH resistance. Low level resistance was present in 31.3% isolates, conferring mutation in inhA and katG in equal percentage (40%), but no detectable mutations were found in 20% low level INH resistant MTB isolates. The PPV of inhA mutation was 33.3% in detection low level resistance. Conclusion: Most of the INH resistant isolates conferred high level resistance and were associated with katG mutation. Evaluation of level INH resistance before using high dose INH will help to avoid dose dependent toxicity and to determine an appropriate treatment regimen. Bangladesh Medical Res Counc Bull 2023; 49(2): 120-125

Analysis of Xpert MTB/RIF results in retested patients with very low initial bacterial loads: A retrospective study in China

The Xpert MTB/RIF (Xpert) assay has been widely used to diagnose suspected active tuberculosis (TB) and rifampicin-resistant TB cases. Despite its excellent performance record, false-positive Xpert rifampicin (RIF) resistance results are obtained for specimens with extremely low bacterial loads. We aimed to study the feasibility of repeat Xpert testing as a strategy for reducing the odds of obtaining false-positive results when testing paucibacillary TB patients. We enrolled previously tested TB patients with very low initial bacterial loads from May 2016 to February 2022 for Xpert retesting. A total of 251 TB patients were retested using the Xpert assay. RIF resistance was noted in 65 (25.9 %) patients when tested by Xpert at initial diagnosis. Only 107 (42.6 %) of 251 patients tested positive for MTB when retested via Xpert. The majority (98.6 %) of RIF-susceptible cases were still susceptible to RIF when retested. Initial Xpert testing yielded 35 positive results for MTB in the RIF-resistant group, of whom 25 (71.4 %) still exhibited RIF resistance when retested. All culture-positive MTB isolates in the RIF-susceptible group were also RIF-susceptible by phenotypic DST. In the RIF-resistant group, 10 of 14 culture-positive MTB isolates exhibited RIF resistance, of which 4 isolates were deemed RIF-susceptible by phenotypic DST. The proportion of double mutations within the MTB rpoB RRDR sequence, as detected by hybridization of Xpert D and E probes, was significantly higher in the RIF-susceptible group than in the RIF-susceptible group. Our results demonstrated that initial RIF-susceptible results were more accurate than RIF-resistant results. Additionally, patients with double mutations that delayed probe D/E hybridization were more likely to have false-positive Xpert results. Our findings emphasize that repeat Xpert MTB/RIF testing is necessary for TB patients with extremely low bacterial loads who are at high risk for RIF-resistant TB.

High proportion of RR-TB and mutations conferring RR outside of the RRDR of the rpoB gene detected in GeneXpert MTB/RIF assay positive pulmonary tuberculosis cases, in Addis Ababa, Ethiopia.

Globally, TB is the leading cause of infectious disease morbidity and mortality with many diagnostic uncertainties. Access to affordable and rapid diagnostics remained a major challenge for many developing countries which bear the greatest burden of TB delaying the initiation time to treatment. This study aimed to assess the GeneXpert MTBRIF assay probe utility for the detection of pulmonary TB and Rifampicin-resistant TB cases in Addis Ababa, Ethiopia. A cross-sectional study was performed from October 2019 to July 2020 in Saint Peter TB Specialized Hospital in Addis Ababa metropolitan area, Ethiopia. This study enrolled 216 clinically suspected new presumptive pulmonary TB cases confirmed by GeneXpert MTB/RIF Assay. Sociodemographic and clinical characteristics were captured using a structured tool. Data were entered in Microsoft Excel 2019, checked for inconsistency, cleaned promptly, and exported to IBM SPSS Statistics for Windows, Version 26.0. Armonk, N.Y: IBM Corp, the USA for analysis. Descriptive analysis and binary and multivariate logistics regression were performed and all statistical significance was determined at a 95% confidence level. The majority of the study participants, 55.1% [119/216] were males aged 6-80 years. The prevalence of RR MTB was 11.11% [24/216]. A higher proportion of RR TB was found in female patients [54.2%, 13/24], in patients in the age group of 30-50 years [45.8%, 11/24], in married individuals [62.5%, 15/24], in persons whose residence is urban [79.2%, 19/24], in persons who had a previous history of TB symptoms [100%, 24/24], in persons who had a history of contact with active and LTBI [33.3%, 8/24], and in persons who had a history of HIV and IDUs [41.7%, 10/24]. Occupation (AOR 22.868, 95% CI 1.655-316.022, p = 0.019), history of previous PTB+ (AOR 4.222, 95% CI 1.020-17.47, p = 0.047), and history of HIV and IDUs (AOR 4.733, 95% CI 1.416-15.819, p = 0.012) were independent predictors associated with RR-TB emergence. The commonest mutation 62.5% [15/24] was found in probe E (codons 529-533) region. There was no mutation associated with probe A (codons 507-511), probe B (codons 511-518), and probe C (codons 518-523) regions, as well as no combination of missed probes, was revealed. However, 12.5% [3/24] of RR TB patients were found without unidentified missed probe types detected outside of the RRDR. The delta Ct max was >4.0 and the highest proportion of 35.6% [77/216] RR TB was detected in samples of medium DNA load. The proportion of RR-TB we observed in this study was high. Similarly, a higher proportion of RR TB was detected outside of the RRDR. Moreover, a significant number of the GeneXpert MTB/RIF Assay probes were identified as unhybridized and this critical observation would mean that most of the probes had no or minimal utility in this geographical region. This calls for further studies to uncover mutation in the rpoB gene conferring RR and reshape TB triage and definite diagnostic algorithm in Ethiopia.

Trends of Xpert MTB/RIF in the diagnosis of Mycobacterium tuberculosis and rifampicin resistance in Southwest Nigeria: A 4-year retrospective study

Objectives: In recent years, there has been an increased uptake of Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) for the diagnosis of tuberculosis (TB), with added benefits for detecting rifampicin-resistant TB (RR-TB). We set out to determine the trends in notification of MTB and RR-TB over 4 years in a tertiary hospital in Southwest Nigeria. Materials and Methods: This is a retrospective analysis of single early morning sputum/gastric washing sample for presumed TB in a tertiary health center between January 2016 and December 2019. Xpert MTB/RIF was used to detect (MTB) and RR-TB. Results: The mean age of the 4625 presumptive TB patients was 43.4 (18.8) years, with the majority aged 31–45 (30.6%). Males totaled 2247 (49.6%). Human immunodeficiency virus (HIV) coinfection was found in 756 (16.7%) of them. Using the Xpert MTB/RIF assay, the overall MTB notification was 12.9% (584/4526) and was associated with HIV status, P &lt; 0.001. MTB notification trends increased from 5.6% in 2016 to 23.8% in 2019, P &lt; 0.001. The overall yield of RR-TB was 7.5%. The proportion of RR-TB from TB cases declined from 28% in 2016 to 4.6% in 2019. Forty-two of the 44 cases of the RR-TB (42/572; 7.3%, [95% CI: 5.31, 9.75]) were new cases, with TB treatment failure and relapse cases accounting for 10.1% (2/11; 10.1%, [95% CI: 0.35, 42.5]) of all RR-TB cases (P &lt; 0.01). RR-TB was associated with being older than 45 years (adjusted odds ratio = 2.046, [95% CI: 1.046, 4.004]). HIV infection status and gender had no effect on RR-TB status. Conclusion: This study found an increase in MTB detection with Xpert MTB/RIF utilization. Ages &gt;45 years have 2–4-fold increased risk of developing RR-TB and should be targeted for drug resistance prevention.

Distribution and frequency of common mutations in rpoB gene of Mycobacterium tuberculosis detected by Xpert MTB/RIF and identification of residential areas of rifampicin resistant-TB cases: A first retrospective study from Mizoram, Northeast India

Rifampicin resistance (RR) is a surrogate marker of multidrug-resistant tuberculosis. The aim of this study is to determine the frequency of the commonly mutated probes for rpoB gene and locate the residential areas of the Rifampicin Resistant-TB (RR-TB) patients in a high endemic zone of Northeast India. Archived data of 13,454 Xpert MTB/RIF reports were evaluated retrospectively between 2014 and 2021. Socio-demographic and available clinical information were reviewed and analyzed for RR-TB cases only. Logistic Regression was used to analyze the parameters with respect to probe types. P-value≤0.05 was considered to be statistically significant. 2,894 patients had Mycobacterium tuberculosis infection out of which 460 were RR-TB, which was most prevalent among 25-34years. The most common mutation occurred in probe A (25.9%) followed by E (23.5%), D (9.8%), B (2.6%) and the least in C (0.2%). High prevalence (34.3%) of probe mutation combinations were also found: probes AB (0.4%), AD (32.8%), AE (0.4%), DE (0.2%) and ADE (0.4%). Seventeen patients (3.7%) were found without any missing probes. RR-TB patients were mostly located in Aizawl North -III, South -II and East -II constituencies. This study provides genetic pattern of drug resistance accountable for RR over the past years in Mizoram which will help local clinicians in the initiation of correct treatment. Also, our findings provide a baseline data on the magnitude of RR-TB within the state and identification of the residential areas can help local health authorities in planning surveillance programs to control the spread of RR-TB.

Comparison of tests done, and tuberculosis cases detected by Xpert® MTB/RIF and Xpert® MTB/RIF-Ultra in Uganda.

Uganda introduced Xpert® MTB/RIF assay into its TB diagnostic algorithm in January 2012. In July 2018, this assay was replaced with Xpert® MTB/RIF Ultra assay. We set out to compare the tests done and tuberculosis cases detected by Xpert® MTB/RIF and Xpert® MTB/RIF Ultra assay in Uganda. This was a before and after study, with the tests done and TB cases detected between Jan-June 2019 when using Xpert® MTB/RIF Ultra assay compared to those done between Jan-June 2018 while using Xpert® MTB/RIF assay. This data was analyzed using Stata version 13, it was summarized into measures of central tendency and the comparison between Xpert® MTB/RIF Ultra and Xpert® MTB/RIF was explored using a two-sided T-test which was considered significant if p <0.05. One hundred and twelve (112) GeneXpert sites out of a possible 239 were included in the study. 128,476 (M: 1147.11, SD: 842.88) tests were performed with Xpert® MTB/RIF Ultra assay, with 9693 drug-susceptible TB (DS-TB) cases detected (M: 86.54, SD: 62.12) and 144 (M: 1.28, SD: 3.42) Rifampicin Resistant TB cases (RR-TB). Whilst 107, 890 (M: 963.30, SD: 842.88) tests were performed with Xpert® MTB/RIF assay between, 8807 (M: 78.63, SD: 53.29) DS-TB cases were detected, and 147 (M: 1.31, SD: 2.39) RR-TB cases. The Number Need to Test (NNT) to get one TB case was 12 for Xpert® MTB/RIF and 13 for Xpert ®MTB/RIF Ultra. On comparing the two assays in terms of test performance (p = 0.75) and case detection both susceptible TB (p = 0.31) and RR-TB (p = 0.95) were not found statistically significant. This study found no significant difference in test performance and overall detection of DS-TB and RR-TB when using Xpert® MTB/RIF Ultra and Xpert® MTB/RIF assays. The health systems approach should be used to elucidate all the probable potential of Xpert® MTB/RIF Ultra.

Evaluation of the resistance of Mycobacterium tuberculosis to rifampicin at the regional hospital center of Maradi, Niger Republic.

According to the World Health Organization (WHO) data, 600,000 cases of rifampicin-resistant tuberculosis (TB) have been reported worldwide, including 490,000 cases of multidrug-resistant TB. Thus, through the present study, we proposed to evaluate the resistance of Mycobacterium tuberculosis to rifampicin in the regional hospital of Maradi. Our study involved 887 sputum samples that were GeneXpert tested from January 2016 to December 2020. These data were collected from the laboratory records of the Maradi Regional Hospital and analyzed with SPSS and Excel 2013 software. In total, more than half of the patients were male, i.e., a sex ratio of 3.03. The average age was 41 years. The rate of detection of M. tuberculosis by GeneXpert was 42% and the frequency of resistance to rifampicin was 20%. However, treatment failure and relapse were associated with this monoresistance in 53.95% and 30.26% of cases, respectively. The present study shows a fairly high prevalence of rifampicin resistance in the Maradi region, corresponding to twice the WHO threshold. The vast majority of these cases presented either a therapeutic failure or a relapse. Urgent and effective actions must be taken to significantly reduce the rates of treatment failure and relapse to decrease the rate of monoresistance and thus avoid the emergence of multidrug-resistant strains.

Investigation of 3-year inpatient TB cases in Zunyi, China: Increased TB burden but improved bacteriological diagnosis.

BackgroundAs one of the top three high tuberculosis (TB) burden countries, China is a country where the overall TB incidence continues to decline. However, due to its large population and area, the increased TB burden exists in regional areas.MethodsThis retrospective study analyzed local inpatient pulmonary TB cases in the Affiliated Hospital of Zunyi Medical University (AHZMU) from January 2016 to December 2018 in a high TB incidence and economically-less-developed area of China. Four methods, acid-fast bacilli stain, culture, Xpert and LAMP, were used to detect Mycobacterium tuberculosis (M.tb), while proportional method and Xpert were used to identify rifampicin-resistant TB (RR-TB). Case number, treatment history, M.tb confirmed TB and rifampicin resistant proportion were analyzed to investigate the local TB epidemic.ResultsTotal 3,910 local inpatient cases with pulmonary TB were admitted to AHZMU during this study period. The annual numbers of total TB cases increased 26.4% (from 1,173 to 1,483), while new cases increased 29.6% (from 936 to 1,213) and RR-TB cases increased 2.7 times (from 31 to 84). Meanwhile, the percentage of previously treated cases declined from 20.2 to 18.2% and the M.tb confirmed TB proportion increased from 34.7 to 49.7%.ConclusionThe elevated M.tb confirmed TB proportion and the declined percentage of previously treated cases indicated the improved TB diagnosis and treatment of AHZMU. However, the increasing number of total TB cases, new and RR-TB cases showed an upward trend and increased TB burden in a relatively underdeveloped area of China.

The global impact of household contact management for children on multidrug-resistant and rifampicin-resistant tuberculosis cases, deaths, and health-system costs in 2019: a modelling study

SummaryBackgroundEstimates suggest that at least 30 000 children develop multidrug-resistant or rifampicin-resistant tuberculosis each year. Despite household contact management (HCM) being widely recommended, it is rarely done.MethodsWe used mathematical modelling to evaluate the potential country-level and global effects and cost-effectiveness of multidrug-resistant or rifampicin-resistant tuberculosis HCM for children younger than 15 years who are living with a person with newly diagnosed multidrug-resistant or rifampicin-resistant tuberculosis. We compared a baseline of no HCM with several HCM strategies and tuberculosis preventive therapy regimens, calculating the effect on multidrug-resistant or rifampicin-resistant tuberculosis cases, deaths, and health-system costs. All HCM strategies involved the screening of children for prevalent tuberculosis disease but with tuberculosis preventive therapy either not given or targeted dependent on age, HIV status, and result of tuberculin skin test. We evaluated the use of fluoroquinolones (ie, levofloxacin and moxifloxacin), delamanid, and bedaquiline as tuberculosis preventive therapy.FindingsCompared with a baseline without HCM, HCM for all adults diagnosed with multidrug-resistant or rifampicin-resistant tuberculosis in 2019 would have entailed screening 227 000 children (95% uncertainty interval [UI]: 205 000–252 000) younger than 15 years globally, and averted 2350 tuberculosis deaths (1940–2790), costing an additional US$63 million (74–95 million). If all the children within the household who had been in contact with the person with multidrug-resistant or rifampicin-resistant tuberculosis received tuberculosis preventive therapy with levofloxacin, 5620 incident tuberculosis cases (95% UI 4540–6890) and an additional 1240 deaths (970–1540) would have been prevented. Incremental cost-effectiveness ratios were lower than half of per-capita gross domestic product for most interventions in most countries. Targeting only children younger than 5 years and those living with HIV reduced the number of incident cases and deaths averted, but improved cost-effectiveness. Tuberculosis preventive therapy with delamanid increased the effect, in terms of reduced incidence and mortality, compared with levofloxacin.InterpretationHCM for patients with multidrug-resistant or rifampicin-resistant tuberculosis is cost-effective in most settings and could avert a substantial proportion of multidrug-resistant or rifampicin-resistant tuberculosis cases and deaths in children globally.FundingUK Medical Research Council.

Management of rifampicin-resistant TB: programme indicators and care cascade analysis in South Africa.

BACKGROUND: Xpert® MTB/RIF was expected to revolutionise the management of rifampicin-resistant TB (RR-TB) by enabling rapid and decentralised diagnosis of rifampicin (RIF) resistance.METHODS: We performed a care cascade analysis for a cohort of RR-TB patients managed under programmatic conditions. Cumulative incidences of time to completion of the RR-TB care cascade steps were estimated, reasons for delay or attrition from the cascade investigated and WHO programme indicators for monitoring of RR-TB programmes calculated.RESULTS: Of 502 patients diagnosed with RR-TB using Xpert, 64% initiated multidrug-resistant TB (MDR-TB) treatment immediately, 20% after some first-line treatment, 16% never initiated MDR-TB treatment, mainly because of death (44%) or loss to follow-up (26%) soon after diagnosis. A supplementary sputum sample was collected within 14 days of treatment in 58.8% of cases. Only 63% of RR-TB cases were assessed for isoniazid resistance, and only 65% of MDR-TB cases were evaluated for pre-XDR-TB (extensively drug-resistant TB). Treatment was individualised in 57% of pre-XDR and 68% of XDR-TB patients. Only 8% completed the entire RR-TB care cascade as intended.CONCLUSION: Fidelity to the RR-TB algorithm was poor, with substantial losses at each step of the cascade, highlighting the fact that implementation of novel technologies needs to be accompanied by health system strengthening to maximise impact.

Mutational Frequencies in Mycobacterial rpoB gene using GeneXpert/MTB Rif Assay in Rifampicin Resistant patients at a tertiary care setting in Urban Sindh, Pakistan: Analysis from a Five-Year Period.

Objectives:To assess the mutational frequencies in Mycobacterial rpoB gene using GeneXpert/MTB Rif Assay in rifampicin resistant patients during 2013-2017 at a tertiary care setting in Urban Sindh, Pakistan.Methods:This Retrospective Descriptive Cross-Sectional Study was conducted at the TB laboratories, Ojha Institute of Chest Diseases, Dow University of Health Sciences. The record of 713 positive cases of Rifampicin Resistant Tuberculosis from January 2013 to December 2017 were analysed. These were diagnosed using GeneXpert® that detects mutations in the 81 base pair region of rpoB gene with the help of five molecular probes A, B, C, D and E. All invalid and extra pulmonary samples were excluded.Results:In total, 713 cases were found to be rifampicin resistant during the five-year period, among which 374 (52.45%) were males while 339 (47.55%) were females. Among the five standard probes A, B, C, D and E, 97.48% of the cases had a single mutation. Among these, mutations in Probe E (66.48%) were the most common, followed by Probe B (14.3%) and Probe D (11.08%). Only 13 cases (1.82%) of double mutations and five cases (0.7%) of triple mutations were detected.Conclusion:The rpoB gene Probe E region 529-533 appears the most potent site for a mutation and development of rifampicin resistance in the rpoB gene in Mycobacterium tuberculosis, that encodes the β-subunit of RNA polymerase. The most affected age-group in both males and females is 19-45 Years.

PP400 Cost-Effectiveness Analysis Of Adding Bedaquiline To Drug Regimens For Multidrug-Resistant Tuberculosis Treatment In China

IntroductionAccording to the World Health Organization, there were approximately 0.5 million new cases of rifampicin-resistant tuberculosis in 2018, of which 78 percent were multidrug-resistant tuberculosis (MDR-TB), and China has one of the largest shares of the global burden (14%). In recent years, the Chinese government has made progress in TB control and prevention, but for MDR-TB, treatment options are still limited and expensive, and novel drugs are not always available. This research aims to evaluate the cost-effectiveness of adding bedaquiline to a background regimen (BR) of drugs for MDR-TB treatment in China, and to provide evidence for government to improve public health policies.MethodsA cohort-based Markov model was developed to evaluate the incremental cost-effectiveness ratio (ICER) of bedaquiline plus BR (BBR) versus BR alone in MDR-TB treatment, over a 10-year time horizon. Data were sourced from a phase II clinical trial, real-world data in China, published literature, and expert opinion. Outcomes were evaluated in quality-adjusted life years (QALYs) and life-years gained (LYG). The discount rate was 3.5%. Probabilistic and deterministic sensitivity analyses were conducted.ResultsThe discounted costs per person for BBR was CNY 135,706 [USD 19,172], compared with CNY 92,465 [USD 13,063] for BR. The discounted utility per person for BBR was also higher than that for BR (3.943 QALYs versus 3.193 QALYs). The ICER of BBR was CNY 58,096 [USD 8,208]/QALY, which was lower than the willingness-to-pay threshold of CNY 212,676 [USD 30,046] (three-times the gross domestic product per capita). Therefore, BBR was considered to be cost-effective. The sensitivity analysis confirmed the robustness of the results. BBR remained cost-effective in the sensitivity analysis, with a 77.2 percent probability of being cost-effective versus BR.ConclusionsIn China, bedaquiline is not included in the National Reimbursement Medicine List, which results in a heavy financial burden for MDR-TB patients. From this study, BBR was cost-effective by significantly reducing time to sputum culture conversion and increasing QALYs and LYGs, which offset the higher drug costs.

Predictive analysis of the situation of tuberculosis in the world based on the results of the annual WHO report

Background. A statistical analysis published in the WHO report for 2019 showed that almost 10.0 million people (about 9.0-11.1 million) fell ill with tuberculosis (TB) worldwide in 2018. The purpose of a systematic examination and analysis of the WHO report is to summarize the achievements and study of complex issues in overcoming tuberculosis in the world at the present stage, that need more attention, more scrutiny, or a change in approach to addressing specific challenges towards achieving the strategic global goals for eradicating this infection.&#x0D; Materials and methods. We used test access to such full – text and abstract databases: a single package of the information database EBSCO; the largest abstract and citation database of peer-reviewed literature Scopus; Google Scholar; MEDLINE with Full Text; MEDLINE Complete; Dyna Med Plus; EBSCO eBooks Clinical Collection; Web of Science Core Collection WoS (CC); SCIE (Science Citation Index Expanded); SSCI (Social Science Citation Index); AHCI (Artand Humanities Citation Index).&#x0D; Results and discussion. By geography, most TB cases in 2018 were reported in the WHO regions: Southeast Asia – 44 %, African – 24 % and Western Pacific – 18 %. Lower percentages were recorded in the Eastern Mediterranean (8 %), America (3 %) and Europe (3 %). Eight countries account for two – thirds of the world’s total TB cases: India (27 %), China (9 %), Indonesia (8 %), Philippines (6 %), Pakistan (6 %), Nigeria (4 %), Bangladesh (4 %) and South Africa (3 %). These and 22 other countries on the WHO list of 30 high tuberculosis countries account for 87 % of TB worldwide. Multidrugresistant tuberculosis (MDRTB) continues to be a public health threat worldwide. In 2018, about half a million new cases of rifampicin-resistant tuberculosis were reported (of which 78 % had multidrug-resistant tuberculosis). The three countries with the largest share of the global MRTB burden are India (27 %), China (14%) and the Russian Federation (9 %). Globally, 3.4 % of new cases of tuberculosis and 18% of previously treated cases are tuberculosis with extensively resistance or rifampicin-resistant (MDR/RR-TB), with the highest rates of detection (&gt;50 % in previously detected cases) in the countries of the former Soviet Union.&#x0D; Conclusion. The epidemic situation in TB in the world and Ukraine remains complex and at this stage has certain peculiarities, and the prognosis for its overcoming shortly is rather doubtful. There is a tendency to reduce the incidence of tuberculosis, but several complex and controversial issues have been outlined for the eradication of this infectious disease by WHO’s End TB strategy.

Comparing diagnostic accuracy of CB-NAAT and ZN staining in diagnosis of Pulmonary and Extra-pulmonary Tuberculosis cases at tertiary care teaching hospital of north India.

Background: Continuing the fight to eradicate tuberculosis from India, which has 24 per cent of the world’s total number of TB cases, is a big challenge for the country to achieve its goal of being TB free by 2025. Keeping in view limitation of culture and smear microscopy, a rapid, accurate, point-of-care diagnostic test that is affordable and can be readily implemented is urgently needed. In recent years, cartridge based nucleic acid amplification test (CBNAAT) has been recommended by World Health Organization as a rapid diagnostic test for detection of tuberculosis and rifampicin resistance. In our study we have tried to analyse whether this has proved as a first critical step in controlling tuberculosis. Aim : In this study, we retrospectively compared results for diagnosis of suspected pulmonary and Extrapulmonary tuberculosis cases, from September 2017 to January 2018 for Ziehl-Neelsen (ZN) and GeneXpert (Xpert® MTB/Rif assay) taking culture as gold standard, in the Department of Microbiology DRPGMC&H Kangra at Tanda. Methods: Performance of Xpert was compared to acid-fast microscopic examination using Ziehl-Neelsen (ZN) stain in patients with culture-confirmed tuberculosis. Results:: Out of total 914 specimens of clinically suspected patients of tuberculosis of all age groups ,683(75%) were pulmonary specimens and231(25%)were extrapulmonary .For pulmonary samples, the sensitivity and specificity for CBNAAT samples were 82.3% and 98.5% while that for sputum smear were 63.7% and 99.3%% respectively. For extrapulmonary samples, the sensitivity and specificity for CBNAAT samples were 85.7% and 93.5% respectively; while that for sputum smear were 60.7% and 100% respectively. Conclusion: Although the development of the Xpert MTB/RIF assay is undoubtedly a landmark event in a high TB burden country like India as this test will help in rapid diagnosis of smear-negative and rifampicin resistant TB cases, which were earlier a challenge for the TB control programmes Key Words: Tuberculosis (TB) Cartridge based nucleic acid amplification test (CBNAAT) Rifampicin (RIF),Mycobacterium tuberculosis(MTB),Ziehl Neelsen(ZN)

Drug-resistant tuberculosis diagnosis since Xpert® MTB/RIF introduction in Papua New Guinea, 2012-2017.

Xpert® MTB/RIF was introduced in Papua New Guinea in 2012 for the diagnosis of tuberculosis (TB) and of rifampicin-resistant TB (RR-TB), a marker of multi-drug-resistant TB (MDR-TB). To assess the concordance of Xpert with phenotypic drug susceptibility testing (DST) performed at the supranational reference laboratory and to describe the patterns of drug-resistant TB observed. This was a retrospective descriptive study of laboratory data collected from April 2012 to December 2017. In 69 months, 1408 specimens with Xpert results were sent for mycobacterial culture and DST; Mycobacterium tuberculosis was cultured from 63% (884/1408) and DST was completed in 99.4%. The concordance between Xpert and culture for M. tuberculosis detection was 98.6%. Of 760 RR-TB cases, 98.7% were detected using Xpert; 98.5% of 620 MDR-TB cases were identified using phenotypic DST. Phenotypic resistance to second-line drugs was detected in 59.4% (522/879) of specimens tested, including 29 with fluoroquinolone resistance; the majority were from the National Capital District and Daru Island. The high concordance between phenotypic DST and Xpert in identifying RR-TB cases supports the scale-up of initial Xpert testing in settings with high rates of drug resistance. However, rapid DST in addition to the detection of RR-TB is required.

Is rifampin resistance a reliable predictive marker of multidrug-resistant tuberculosis in China: A meta-analysis of findings

Systematic review of multidrug-resistant tuberculosis (MDR-TB) prevalence among rifampicin (RIF)-resistant tuberculosis (RR-TB) patients in 34 provinces of China was conducted to correlate RIF resistance with concurrent isoniazid (INH) resistance. Database searches (PubMed, Embase, China National Knowledge Infrastructure, Chinese Scientific Journal, Wanfang), identified drug resistance surveillance studies conducted between January 1, 2000 and June 30, 2018. Of 1554 records, random-effects meta-analysis of 34 studies of adequate methodological quality yielded 108,366 TB cases for MDR-TB prevalence analysis of RR-TB cases. MDR-TB prevalence among RR-TB cases varied from 57% (Xinjiang; 95% CI 47%, 67%) to 95% (Taiwan; 95% CI 92%, 98%), for a pooled national rate of 77% (95% CI 75%, 80%). Subgroup and meta-regression analyses revealed greater MDR-TB prevalence in previously treated versus new RR-TB cases (P < 0.001), with no significant differences of regional initial drug resistance rates or sampling methods. Regional MDR-TB prevalence among RR-TB cases was lowest (69%) in the Northeast Region (95% CI 65%, 73%) and highest (90%) in Hong Kong, Macao and Taiwan (95% CI 81%, 98%). In China, ∼77% of RR-TB cases are MDR-TB. Thus, RIF resistance cannot effectively predict MDR-TB. Highly variable RR-TB prevalence across China warrants improved TB management.