Presumptive Multidrug-resistant Tuberculosis Research Articles

Factors associated with tuberculosis drug resistance among presumptive multidrug resistance tuberculosis patients identified in a DRTB surveillance study in western Kenya

Multidrug-resistant tuberculosis (MDR-TB) is caused by M. tuberculosis (Mtb) with resistance to the first-line anti-TB medicines isoniazid (INH) and rifampicin (RIF). In Western Kenya, there is reported low prevalence of drug resistant strains among HIV tuberculosis patients, creating a need to determine factors associated with drug resistance patterns among presumptive MDR-TB patients. To determine factors associated with drug resistance patterns among presumptive MDR-TB patients in western Kenya. Three hundred and ninety (390) sputum sample isolates from among presumptive multidrug TB patients, were analyzed for TB drug resistance as per Ministry of Health (MoH) TB program diagnostic algorithm. Frequency and percentages were used to summarize categorical data while median and interquartile range (IQR) were used for continuous data. Multivariable logistic regression was carried out to identify factors associated with TB drug resistance. Out of 390 participants enrolled, 302/390 (77.4 %) were males, with a median age of 34 years. The HIV-infected were 118/390 (30.3 %). Samples included 322 (82.6 %) from presumptive patients, while 68/390 (17.4 %) were either lost to follow-up patients, failures to first-line treatment or newly diagnosed cases. A total of 64/390 (16.4 %) of the isolates had at least some form of drug resistance. Out of 390, 14/390 (3.6 %) had MDR, 12 (3.1 %) were RIF mono-resistance, 34 (8.7 %) had INH, while 4 (1 %) had ethambutol resistance. The category of previously treated patients (those who received or are currently on TB treatment) had a 70 % reduced likelihood of resistance (aOR: 0.30; 95 % CI: 0.13–0.70). In contrast, older age was associated with an increased likelihood of resistance to INH and RIF, with an adjusted odds ratio of 1.04 per year (95 % CI: 1.00–1.08). Prompt MDR-TB diagnosis is essential for appropriate patient care, management, and disease prevention and control. We recommend active surveillance on drug resistant TB in these regions to detect drug resistance patterns for rapid disease management.

Pre-diagnosis and pre-treatment attritions among presumptive MDR/RR-TB patients in Chonburi province, Thailand, 2015-2017

The low detection rate of multidrug-resistant tuberculosis (MDR-TB) is one of the major obstacles to TB control in Thailand. Thus, this study aimed to assess pre-diagnosis and pre-treatment attrition rates among patients suspected of having MDR-TB, identify factors related to pre-diagnosis attrition, and determine the turnaround times (TAT) of diagnosis and treatment pathway. A retrospective cohort analysis was conducted using a record review. Among 972 presumptive MDR-TB patients, only 354 (36.4%) underwent drug-susceptibility testing (DST). Multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) was found in 32 patients, consisting of 26 (81.2%) males and 6 (18.8%) females. Pre-diagnosis and pre-treatment attrition rates were 63.58 % and 28.1%, respectively. Furthermore, the median (interquartile range [IQR]) turnaround time for MDR-TB testing was seven days (IQR 0-62 days), and the median time to the start of MDR-TB treatment was 20 days (IQR 2-38 days). Meanwhile, the factors associated with pre-diagnosis attrition were migrants, presumptive TB cases presenting at secondary-level hospitals, TB patients identified from hospitals outside the Ministry of Public Health, and extrapulmonary TB cases. The results of this research demonstrated that only one-third of patients at risk of MDR-TB underwent DST. Therefore, it is essential for healthcare workers at all levels to be educated and trained to identify patients that are eligible for DST. In addition, other interventions such as the decentralization of laboratory services and MDR-TB treatment to secondary-care district hospitals are also urgently needed.

Prevalence and Drug Susceptibility of Non-tuberculous mycobacteria Among Presumptive MDR-TB Patients Admitted at KIDH in Kilimanjaro, Tanzania

Background The reports on Non-tuberculous mycobacteria (NTM) pulmonary infections associated with multidrug-resistant tuberculosis are increasing worldwide. Despite a significant increase in knowledge about NTM infections, they present a diagnostic and therapeutic challenge in resource-limited settings. This study aimed to determine the prevalence and drug susceptibility of NTM among presumptive multidrug-resistant tuberculosis patients in Tanzania. Materials and Methods A cross-sectional study was conducted from April to October 2021 on presumptive Multidrugresistant tuberculosis patients admitted at KIDH in Kilimanjaro. All isolated mycobacterial growth was characterized into MTBC and NTM and finally tested for susceptibility on the firstline anti-tuberculosis drugs. The data were analyzed using Stata version 16 (Stata Corp, College Station, TX, USA), and presented using frequency and tables. A p-value less ≤ 0.05 was considered statistically significant. Results The study population included 160 presumptive MDR-TB patients and 75% were males, NTM infections were found in 14 (8.75 %). In 17 patients that were HIV positive, 13 were infected by NTM, the Mycobacterium avium complex was the most frequently isolated NTM (9/14 patients, 64.3 %). Almost all isolates of NTM were resistant to majority of the first-line anti TB drugs. Conclusion Findings from this study indicate that HIV infected individuals who were regarded as presumptive MDR-TB patients are at high risk of NTM infections. High proportion of NTM isolates were MAC, which included M. avium and M. in tracellulare. Additionally, NTM isolates showed to be resistant to majority of the recommended first-line anti-TB drugs used in the country indicating challenging treatment outcome

Laboratory Cost Analysis of Conventional and Newer Molecular Tests for Diagnosis of Presumptive Multidrug-Resistant Tuberculosis Patients.

Introduction:Tuberculosis (TB) remains a deadliest infectious disease. Lack of rapid test with low cost is one of the important challenges to eradicate the TB. The objective of the study was to analyze the laboratory costs of conventional and newer molecular tests, for diagnosis of presumptive multidrug-resistant TB (MDR-TB) patients.Methods:A detailed laboratory cost of various conventional tests (Ziehl − Neelsen [ZN] microscopy, light-emitting diode-fluorescent microscopy [LED-FM], culture and drug susceptibility testing [DST] using solid Lowenstein–Jensen media and liquid media [BACTEC MGIT 960]) was compared with rapid methods (GenoType MTBDRplus line probe assay [LPA] and GeneXpert MTB/RIF assay). Laboratory cost was also calculated in terms of cost per TB and MDR-TB case detected by using different diagnostic scenarios.Results:Cost per test for ZN microscopy, LED-FM, LPA, GeneXpert MTB/RIF assay, solid culture plus DST, liquid culture plus DST was found as $2.5 (INR 156.8), $2.0 (INR128.9), $18.6 (INR1210), $13.8 (INR 895.2), $21.5 (INR 1396.6), and $29.1 (INR 1888.2), respectively. The laboratory cost for detecting TB and MDR-TB by diagnostic scenarios involving molecular DST was found to be less as compared to involving only conventional liquid culture-based test.Conclusions:The implementation of rapid molecular tests with selective use of liquid culture-based DST may be less in cost as compared to the use of culture-based DST alone, at high burden reference TB laboratory.

Correlation of inhA mutations and ethionamide susceptibility: Experience from national reference center for tuberculosis.

Background:Detection of ethionamide (ETH) resistance is crucial as it is part of antitubercular regime. It is crucial to examine the role of inhA gene mutations as a surrogate marker for the detection of ETH resistance, in the Indian context. The present retrospective study was designed with this objective.Subjects and Methods:The study was conducted in National Reference Laboratory within the tertiary care institute from January 1, 2018, to June 30, 2019, over 18 months duration. A total of 6612 sputum samples from presumptive multidrug-resistant tuberculosis (TB) patients were received from four districts of Delhi, outdoor and inpatients. Line probe assay (LPA) was performed for smear-positive or culture-positive samples for Mycobacterium tuberculosis. All isolates found to be INH resistant by LPA were cultured and phenotypic susceptibility to ETH was conducted for selected isolates as per the guidelines.Results:A total of 246 isolates were analyzed, for which phenotypic susceptibility to ETH and mutations in inhA were available. ETH resistance was detected among 87/108 (80.5%) isolates with inhA mutation. Sensitivity and specificity of inhA mutation for detection of ETH resistance were 80.5% and 83.8%, respectively. No inhA mutation was detected in 29/116 (25%) ETH-resistant isolates in our study, whereas ETH was found to be phenotypically susceptible in spite of the presence of inhA mutation among 21/130 (16.1%) isolates.Conclusions:Mutations in inhA gene in LPA predict ETH resistance with fairly good sensitivity and specificity. However, it is imperative to perform phenotypic detection of ETH resistance at proper concentration, in addition to detecting inhA mutation.

English

Multi Drug Resistant Tuberculosis (MDR-TB) is a public health challenge, which itself remains a global public health problem. Its impact is worsened by co-infection with Human immunodeficiency virus (HIV). In order to institute successful TB control strategies, factors for development of MDR-TB must be understood. This study aimed to identify and describe clinical and demographic determinants for development of MDR-TB among TB patients. This was a cross sectional, hospital-based study conducted between April 2017 and December 2019 involving 428 presumptive MDR-TB patients. Specimens were subjected to GeneXpert MTB/RIF assay, microscopy and Line probe assay for diagnosis of MDR-TB. A questionnaire was used to collect demographic information from patients. The odds of having MDR-TB among patients who were cigarette smokers were four-times compared to non-smoking patients (aOR=3.94; 95%CI: 1.845-8.428, p<0.001). Alcohol abuse increased the chances of having MDR-TB by ten times (aOR=9.98: 95%CI; 2.414-41.267, p=0.001). Being HIV positive strongly increased the likelihood of having MDR-TB (aOR=2266.0: 95% CI; 407.5-2599.8, p<0.001). Compared to treatment failure, relapse and non-adherence were found to be strong predictors for MDR-TB (aOR=64.22: (95% CI; 12.786-322.507) p=0.001), and (aOR=37.44: (95% CI; 3.895-359.836, p=0.002), respectively. HIV infection, TB relapse, history of irregular treatment, cigarette smoking, alcohol abuse, and treatment failure (return) is factors development of MDR-TB. Integrated TB/HIV control programs that will include the establishment of strong diagnostic and drug delivery systems, patient management, and TB resistance surveillance systems are recommended. Key words: Tuberculosis, multi drug resistant tuberculosis (MDR-TB), HIV, M. tuberculosis, adherence; relapse.

Multidrug-resistant tuberculosis surveillance and cascade of care in Madagascar: a five-year (2012\u20132017) retrospective study

BackgroundIn Madagascar, the multidrug-resistant tuberculosis (MDR-TB) surveillance programme was launched in late 2012 wherein previously treated TB cases and symptomatic MDR-TB contacts (hereafter called presumptive MDR-TB cases) undergo drug susceptibility testing. This retrospective review had per aim to provide an update on the national MDR-TB epidemiology, assess and enhance programmatic performance and assess Madagascar’s MDR-TB cascade of care.MethodsFor 2012–2017, national TB control programme notification, clinical management data and reference laboratory data were gathered. The development and coverage of the surveillance programme, the MDR-TB epidemiology and programmatic performance indicators were assessed using descriptive, logistic and spatial statistical analyses. Data for 2017 was further used to map Madagascar’s TB and MDR-TB cascade of care.ResultsThe geographical coverage and diagnostic and referral capacities of the MDR-TB surveillance programme were gradually expanded whereas regional variations persist with regard to coverage, referral rates and sample referral delays. Overall, the rate of MDR-TB among presumptive MDR-TB cases remained relatively stable, ranging between 3.9% in 2013 and 4.4% in 2017. Most MDR-TB patients were lost in the second gap of the cascade pertaining to MDR-TB cases reaching diagnostic centres but failing to be accurately diagnosed (59.0%). This poor success in diagnosis of MDR-TB is due to both the current use of low-sensitivity smear microscopy as a first-line diagnostic assay for TB and the limited access to any form of drug susceptibility testing. Presumptive MDR-TB patients’ sample referral took a mean delay of 28 days before testing. Seventy-five percent of diagnosed MDR-TB patients were appropriately initiated on treatment, and 33% reached long-term recurrence-free survival.ConclusionsAn expansion of the coverage and strengthening of MDR-TB diagnostic and management capacities are indicated across all regions of Madagascar. With current limitations, the surveillance programme data is likely to underestimate the true MDR-TB burden in the country and an updated national MDR-TB prevalence survey is warranted. In absence of multiple drivers of an MDR-TB epidemic, including high MDR-TB rates, high HIV infection rates and inter-country migration, Madagascar is in a favourable starting position for MDR-TB control and elimination.

Pretreatment Out-of-Pocket Expenses for Presumptive Multidrug-Resistant Tuberculosis Patients, India, 2016-2017.

In India, under the National Tuberculosis Elimination Programme, the government provides free treatment for multidrug-resistant tuberculosis; however, many patients seek care elsewhere, which is costly. To determine those out-of-pocket expenses, we interviewed 40 presumptive patients and found that they spent more than their median annual income before registering for the government program.

Prevalence of Multidrug Resistant &amp;lt;i&amp;gt;Mycobacterium tuberculosis&amp;lt;/i&amp;gt; among Tuberculosis Patients Admitted to Adama Hospital Medical College, Adama, Ethiopia: A Retrospective Study

Multidrug resistant tuberculosis (MDR-TB) is an emerging challenge for TB control programs globally. Ethiopia ranks 7th among the world’s 22 high TB burden countries. According to report of WHO (2017), TB is one of the leading infectious causes of death in Ethiopia claiming the life of more than 30 thousand people annually. The surge of MDR-TB has been compounding the problem further. Facility-based MDR-TB researches have not been generated in equal pace with community-based ones. The aim of this study was to assess the prevalence of MDR-TB using clinical records of MDR-TB patients in Adama Hospital Medical College (AHMC) from 2014 to 2018. All clinical data of MDR-TB from 2014-2018 was collected from AHMC TB department. Socio-demographic and risk factor data were collected from patients using semi-structured questionnaire. Data were analyzed using Microsoft excel and SPSS version 20. Out of a total 2332 TB suspected cases admitted to AHMC from 2014 to 2018, 175 (7.5%) were confirmed MDR-TB cases or confirmed Rifampicin resistant cases. In particular, 97 (4.2%) presented presumptive MDR-TB alone and 78 (3.3%) showed confirmed Rifampicin resistance alone. Comparison among age groups showed the highest prevalence for 24 - 44 years with 1.8% and 1.5% confirmed MDR-TB and Rifampicin resistance. The overall prevalence of MDR-TB was moderate indicating for possible rise of the problem due to course of time. Further study combining both community and health facility based is recommended to highlight the need to make useful strategies for testing, surveillance and effective clinical management of MDR-TB cases.

Prevalence and Factors Associated with Multidrug-Resistant Tuberculosis (MDR-TB) among Presumptive MDR-TB Patients in Tigray Region, Northern Ethiopia.

Background Tuberculosis (TB) is one of the major public health problems. There are alarming reports of increasing multidrug-resistant tuberculosis (MTR-TB) from various parts of the globe, including Ethiopia. This study was designed to determine the prevalence and factors associated with MDR-TB among presumptive MDR-TB cases in Tigray Regional State, Ethiopia. Methods A cross-sectional study was conducted in Tigray Regional State from 2015 to 2016. Two hundred sputum samples were collected, transported, processed using 2% N-acetyl-L-cysteine-sodium hydroxide, and cultured in LJ medium. Besides, the microscopic examination was performed after ZN staining. Moreover, drug susceptibility test was done using molecular line probe assay. Descriptive statistics and binary and multivariable logistic regression were done. A statistical test was regarded as significant when the P value was <0.05. Results The prevalence of MDR-TB was found to be 18.5%. About one-fourth (26.5%) of the study participants had sputum smear positive for acid-fast bacilli (AFB). TB culture was positive in 37% of the samples, and rifampicin mono-resistant cases accounted for 3.5% of the presumptive MDR-TB cases. Three (1.5%) were new MDR-TB cases, while the rest had been treated previously for TB. Most (63.5%) of the MDR-TB cases were from 15 to 44 years of age. Age was associated with MDR-TB with a crude odds ratio of 1.06 (CI: 1.02–1.10) and adjusted odds ratio of 1.06 (CI: 1.00–1.11). Conclusions The prevalence of MDR-TB was found to be high. Preventive measures should be taken to prevent the transmission of MDR-TB in the community.

Magnitude and reasons for pre-diagnosis attrition among presumptive multi-drug resistant tuberculosis patients in Bago Region, Myanmar: A mixed methods study

In Myanmar, Rifampicin resistant tuberculosis (RR-TB, a proxy for Multi-drug resistant TB) case detection is very low. Our study objectives were to assess the proportion of eligible TB patients who had not undergone RR-TB testing (Xpert-MTB/Rif tests) in Bago Region, Myanmar and to understand the reasons and solutions for non-testing. We conducted a mixed-methods study involving analysis of routinely collected programme data followed by key informant interviews (KIIs) with 32 health care providers. From October 2016 to March 2017, of the 2,331 eligible patients, 1,066 (46%) had not undergone Xpert-MTB/Rif testing. Patients from townships without Xpert-MTB/Rif testing facilities, new TB patients, patients whose HIV status was negative or unknown and extra pulmonary TB patients were less likely to undergo Xpert-MTB/Rif testing. From the health care providers’ perspective, the most common reasons for non-testing were: (a) lack of awareness of the eligibility criteria; (b) difficulties in collecting sputum and transportation from eligible patients to the testing sites. We conclude that nearly half of eligible patients were not tested for RR-TB. Training of health care providers about the latest eligibility criteria and improvement in sputum collection and transportation systems particularly for townships without Xpert-MTB/Rif testing facilities are required to improve RR-TB testing.

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.

Has the utilisation of Xpert® MTB/RIF in Manicaland Province, Zimbabwe, improved with new guidance on whom to test?

Setting: Manicaland Province, Zimbabwe. Objectives: To compare the utilisation and results of deploying Xpert® MTB/RIF in 13 (one provincial, six district and six rural) hospitals between January and June 2016, when Xpert was recommended only for those with presumptive multidrug-resistant tuberculosis (MDR-TB) and coinfection with human immunodeficiency virus (HIV), and between January and June 2017, when Xpert was recommended for all presumptive TB patients. Design: This was a cross-sectional study. Results: Xpert assays averaged 759 monthly in 2016 and 1430 monthly in 2017 (88% increase). Utilisation of Xpert averaged 22% monthly in 2016 and 42% in 2017 (88% increase). In 2017, utilisation of Xpert was significantly higher in provincial (82%) than in district (51%) and rural (26%) hospitals (P < 0.001). The proportion of successful assays that detected TB decreased significantly from 13% in 2016 to 7% in 2017 (a 46% decrease, P < 0.001); this phenomenon was observed in all types of hospital. The proportion of persons detected with rifampicin-resistant TB was similar between hospitals (4% in 2016 and 3% in 2017). The proportion of registered TB cases with bacteriological confirmation increased from 48% in 2016 to 53% in 2017 (P = 0.04). Conclusion: Xpert use in all presumptive TB patients led to a significant increase in assay numbers and utilisation of Xpert instruments, resulting in more bacteriological confirmation of cases.

Delay before drug susceptibility testing among patients with presumptive multidrug-resistant tuberculosis in Gujarat, India.

Reducing delay in the diagnosis of multidrug-resistant tuberculosis (MDR-TB) by performing genotypic drug susceptibility testing (DST) among eligible patients as early as possible can improve clinical presentation and treatment outcomes and reduce transmission. We aimed to determine the delay from being eligible for DST to performing DST and factors associated with the delay. This was a retrospective cohort study involving record review among presumptive MDR-TB patients who underwent genotypic DST from five selected districts in the state of Gujarat, India (2014). Specimens were couriered from the designated microscopy centres (DMCs) to two designated genotypic DST facilities located outside the districts. Of 2212 patients, the median duration from eligibility to the specimen being sent, from the specimen being sent to DST and from eligibility to DST was 3, 5 and 8 d, respectively. Patients from DMCs in teaching hospitals and with presumptive MDR-TB criteria 'follow-up smear positive' and 'TB-human immunodeficiency virus co-infection' had a significantly higher risk of delay between eligibility and testing (≥8 d). The delay in the specimen being sent after eligibility contributed to high delays in these subgroups. The districts were doing well in implementing timely DST among presumptive MDR-TB patients. However, there is room for improvement in reducing the delays in the sending of specimens among certain patient subgroups.

Provider reported barriers and solutions to improve testing among tuberculosis patients 'eligible for drug susceptibility test': A qualitative study from programmatic setting in India.

BackgroundIn a study conducted in Bhopal district (a setting with facility for molecular drug susceptibility testing (DST)) located in central India in 2014–15, we found high levels of pre-diagnosis attrition among patients with presumptive multi drug-resistant tuberculosis (MDR-TB)–meaning TB patients who were eligible for DST, were not being tested.ObjectivesIn this study, we explored the health care provider perspectives into barriers and suggested solutions for improving DST.MethodsThis was a descriptive qualitative study. One to one interviews (n = 10) and focus group discussions (n = 2) with experienced key informants involved in programmatic management of DR-TB were conducted in April 2017. Manual descriptive thematic analysis was performed.ResultsThe key barriers reported were a) lack of or delay in identification of patients eligible for DST because of using treatment register as the source for identifying patients b) lack of assured specimen transport after patient identification and c) lack of tracking. Extra pulmonary TB patients were not getting identified as eligible for DST. Solutions suggested by the health care providers were i) generation of unique identifier at identification in designated microscopy center (DMC), immediate intimation of unique identifier to district and regular monitoring by senior TB laboratory and senior treatment supervisors of patients eligible for DST that were missed; ii) documentation of unique identifier at each step of cascade; iii) use of human carriers/couriers to transport specimen from DMCs especially in rural areas; and iv) routine entry of all presumptive extra-pulmonary TB specimen, as far as possible, in DMC laboratory register.ConclusionLack of assured specimen transport and lack of accountability for tracking patient after identification and referral were the key barriers. The identification of patients eligible for DST among microbiologically confirmed TB at the time of diagnosis and among clinically confirmed TB at the time of treatment initiation is the key. Use of unique identifier at identification and its use to ensure cohort wise tracking has to be complemented with specimen transport support and prompt feedback to the DMC. The study has implications to improve detection of MDR-TB among diagnosed/notified TB patients.

Low pre-diagnosis attrition but high pre-treatment attrition among patients with MDR-TB: An operational research from Chennai, India

BackgroundWorldwide, there’s concern over high pre-diagnosis and pre-treatment attritions or delays in Multidrug resistant tuberculosis (MDR-TB) diagnosis and treatment pathway (DTP). We conducted this operational research among patients with presumptive MDR-TB in north and central Chennai, India to determine attrition and turnaround times (TAT) at various steps of DTP and factors associated with attrition. MethodsStudy was conducted in Revised National Tuberculosis Control Programme setting. It was a retrospective cohort study involving record review of all patients with presumptive MDR-TB (eligible for DST) in 2014. ResultsOf 628 eligible for DST, 557 (88%) underwent DST and 74 (13%) patients were diagnosed as having MDR-TB. Pre-diagnosis and pre-treatment attrition was 11% (71/628) and 38% (28/74) respectively. TAT [median (IQR)] to test from eligibility for DST and initiate DR-TB treatment from diagnosis were 14 (9,27) and 18 (13,36) days respectively. Patients with smear negative TB and detected in first quarter of 2014 were less likely to undergo DST. Patients in first quarter of 2014 had significantly lower risk of pre-treatment attrition. ConclusionThere was high uptake of DST. However, urgent attention is required to reduce pre-treatment attrition, improve TAT to test from eligibility for DST and improve DST among patients with smear-negative TB.

Frequency of multi-drug resistance and mutations in Mycobacterium tuberculosis isolates from Punjab state of India

Data regarding prevalence of multi-drug resistant tuberculosis (MDR-TB) and associated common mutations is scarce from Punjab region. The study was designed to determine rate of MDR-TB among presumptive MDR-TB from Punjab and mutation patterns using GenoType MTBDRplus assay. Total of 812 consecutive sputum samples were received from January 2012 to July 2013, from 14 districts of Punjab at the National Reference Laboratory at New Delhi for diagnosis of MDR-TB as hand holding activity. Presumptive MDR-TB patients were identified on basis of criterion B defined by the programme. Smear positive and negatives patients were found to be 636/798 (79.7%) and 162/ 798 (20.3%) respectively. Total of 606 GenoType MTBDRplus tests were conducted and mutations in rpoB, kat G and inhA genes analyzed. Total of 94/606 (15.5%), 43/606 (7.1%) and 40/606 (6.6%) were found to be RIF and INH resistant, mono-RIF resistant and 40/606 (6.6%) mono-INH resistant respectively. Commonest known mutation for RIF in rpoB gene and INH in kat G gene was S531L (80/ 137; 58.4%) and S315T1 (119/134; 88.8%) respectively. Mutations in inhA were found in 21/134 (15.7%) strains. Average turn-around time (TAT) for dispatch of result toPunjab was 4.6days. Prevalence of RIF resistance in Punjab was found to be 22.6%. Common mutations for RIF and INH were similar to that in other regions of country. GenoType MTBDRplus was found to be useful assay for rapid detection of MDR-TB, responsible for determining better management of MDR-TB patients under the programme.

Frequency of multi-drug resistance and mutations in Mycobacterium tuberculosis isolates from Punjab state of India

Data regarding prevalence of multi-drug resistant tuberculosis (MDR-TB) and associated common mutations is scarce from Punjab region. The study was designed to determine rate of MDR-TB among presumptive MDR-TB from Punjab and mutation patterns using GenoType MTBDRplus assay. Total of 812 consecutive sputum samples were received from January 2012 to July 2013, from 14 districts of Punjab at the National Reference Laboratory at New Delhi for diagnosis of MDR-TB as hand holding activity. Presumptive MDR-TB patients were identified on basis of criterion B defined by the programme. Smear positive and negatives patients were found to be 636/798 (79.7%) and 162/ 798 (20.3%) respectively. Total of 606 GenoType MTBDRplus tests were conducted and mutations in rpoB, kat G and inhA genes analyzed. Total of 94/606 (15.5%), 43/606 (7.1%) and 40/606 (6.6%) were found to be RIF and INH resistant, mono-RIF resistant and 40/606 (6.6%) mono-INH resistant respectively. Commonest known mutation for RIF in rpoB gene and INH in kat G gene was S531L (80/ 137; 58.4%) and S315T1 (119/134; 88.8%) respectively. Mutations in inhA were found in 21/134 (15.7%) strains. Average turn-around time (TAT) for dispatch of result toPunjab was 4.6 days. Prevalence of RIF resistance in Punjab was found to be 22.6%. Common mutations for RIF and INH were similar to that in other regions of country. GenoType MTBDRplus was found to be useful assay for rapid detection of MDR-TB, responsible for determining better management of MDR-TB patients under the programme.

MDR-TB in Puducherry, India: reduction in attrition and turnaround time in the diagnosis and treatment pathway.

Setting: A mixed-methods operational research (OR) study was conducted to examine the diagnosis and treatment pathway of patients with presumptive multidrug-resistant tuberculosis (MDR-TB) during 2012-2013 under the national TB programme in Puducherry, India. High pre-diagnosis and pre-treatment attrition and the reasons for these were identified. The recommendations from this OR were implemented and we planned to assess systematically whether there were any improvements. Objectives: Among patients with presumptive MDR-TB (July-December 2014), 1) to determine pre-diagnosis and pre-treatment attrition, 2) to determine factors associated with pre-diagnosis attrition, 3) to determine the turnaround time (TAT) from eligibility to testing and from diagnosis to treatment initiation, and 4) to compare these findings with those of the previous study (2012-2013). Design: This was a retrospective cohort study based on record review. Results: Compared to the previous study, there was a decrease in pre-diagnosis attrition from 45% to 24% (P < 0.001), in pre-treatment attrition from 29% to 0% (P = 0.18), in the TAT from eligibility to testing from a median of 11 days to 10 days (P = 0.89) and in the TAT from diagnosis to treatment initiation from a median of 38 days to 19 days (P = 0.04). There is further scope for reducing pre-diagnosis attrition by addressing the high risk of patients with human immunodeficiency virus and TB co-infection or those with extra-pulmonary TB not undergoing drug susceptibility testing. Conclusion: The implementation of findings from OR resulted in improved programme outcomes.

More than half of presumptive multidrug-resistant cases referred to a tuberculosis referral laboratory in the Tigray region of Ethiopia are multidrug resistant

Objective/background: Generating epidemiological data on multidrug-resistant tuberculosis (MDR-TB) is essential to assess the magnitude and trends of anti-TB drug resistance. This study determined the prevalence of MDR-TB among presumptive MDR cases referred to a TB referral laboratory in the Tigray region of Ethiopia. Methods: A retrospective cross-sectional study was conducted on 262 culture-positive presumptive MDR-TB samples submitted to the Tigray Regional Research Laboratory for MDR testing between January 2013 and August 2014. Relevant data were recorded using a structured recording format. Results: Out of 262 Mycobacterium tuberculosis isolates, 143 (54.6%) were MDR, 28 (10.7%) were resistant to rifampicin only, and 19 (7.3%) were resistant to isoniazid only. The prevalence of MDR-TB among newly infected cases was 66.7% (8/12) and that among previously treated cases was 54.1% (97/179). Of the variables tested, being a male was found to be associated with the development of MDR-TB (p=.003). Conclusion: More than half of the presumptive MDR cases referred to the Tigray Regional Research Laboratory were MDR. The prevalence was high in both newly infected and previously treated cases. Hence, re-enforcing the TB prevention methods, and strengthening the directly observed treatment short-course (DOTS) strategy and the capacity of laboratories to undertake drug susceptibility testing (DST) in the region are imperative in order to curb the emergence and transmission of MDR-TB.