Dataset Information

Feasibility of Direct Sputum Molecular Testing for Drug Resistance as Part of Tuberculosis Clinical Trials Eligibility Screening.

ABSTRACT: A rapid diagnosis of drug-resistant tuberculosis (TB) is critical for early initiation of effective therapy. Molecular testing with line probe assays (MTBDRplus and MTBDRsl) on culture isolates has been available for some time and significantly reduces the time to diagnosis of drug resistance. However, routine use of this test directly on sputum is less common. As part of enrollment screening procedures for tuberculosis clinical trials conducted in Hanoi, Vietnam, we evaluated the feasibility and performance of line probe assay (LPA) testing directly on sputum samples from 315 participants with no prior history of TB treatment. Test performance characteristics for the detection of rifampin (RIF) and isoniazid (INH) drug resistance as compared to culture-based drug susceptibility testing (DST) reference standard were calculated. LPA demonstrated high sensitivity and specificity for the diagnosis of drug resistance. Scaling up molecular testing on sputum as part of time-sensitive clinical trial screening procedures in high TB burden settings is feasible and will reduce both time to initiation of appropriate therapy and the risk of late exclusions due to microbiologic ineligibility.

SUBMITTER: Alipanah N

PROVIDER: S-EPMC6627302 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Feasibility of Direct Sputum Molecular Testing for Drug Resistance as Part of Tuberculosis Clinical Trials Eligibility Screening.

Alipanah Narges N Shete Priya B PB Nguyen Hanh H Nguyen Nhung Viet NV Luu Lien L Pham Thuong T Nguyen Hung H Nguyen Phuong P Tran Minh Chi MC Pham Nam N Phan Ha H Phillips Patrick P J PPJ Cattamanchi Adithya A Nahid Payam P

Diagnostics (Basel, Switzerland) 20190530 2

A rapid diagnosis of drug-resistant tuberculosis (TB) is critical for early initiation of effective therapy. Molecular testing with line probe assays (MTBDR<i>plus</i> and MTBDR<i>sl</i>) on culture isolates has been available for some time and significantly reduces the time to diagnosis of drug resistance. However, routine use of this test directly on sputum is less common. As part of enrollment screening procedures for tuberculosis clinical trials conducted in Hanoi, Vietnam, we evaluated the ...[more]

PMID: 31151255

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Project description:BACKGROUND:Web-based methods can be used to collect data from hidden populations, including people who use drugs (PWUD). These methods might be especially advantageous among PWUD in rural areas, where transportation barriers are prevalent, stigma may heighten concerns about confidentiality, and internet access is improving. However, Web-based research with PWUD can be challenging, especially in verifying eligibility. Administering quizzes to verify residential and substance use eligibility could prove valuable in online research among PWUD, yet the utility of this approach is currently unknown. OBJECTIVE:This study describes the implementation of online eligibility quizzes about the local community to verify residence in the target study area along with drug dose, appearance, and price to verify opioid misuse. METHODS:To be eligible, individuals had to live in 1 of 5 eastern Kentucky counties, report using opioids to get high in the past 30 days, and be 18 to 35 years old. Participants recruited from August 2017 to July 2018 were asked questions about their opioid use followed by a quiz about drug dose, appearance, and price to verify substance use eligibility. Residential eligibility was verified with 5-question quizzes assessing knowledge of the county where they reported living. Questions tested knowledge about towns, festivals, and landmarks; local school mascots and colors; and presence of certain retail stores, restaurants, and facilities (eg, jails). A subsample that reported using opioids in the past 24 hours was randomly selected to complete urine drug testing (UDT). Nonparametric tests were performed to explore differences across demographic subgroups. RESULTS:Of the 410 entries assessed for eligibility, 39.3% (161/410) were ineligible as they reported no substance use, being outside the age range, or living outside the study area. Of the remaining 249 who met the eligibility criteria based on age, residency, and opioid misuse, 94.0% (234/249) passed the eligibility quizzes. Among those who passed the heroin quiz, 99.4% (167/168) recognized the image of powdered heroin, 94.6% (159/168) answered the cap size (ie, the purchase unit) question correctly, and 97.0% (163/168) answered the street price question correctly. Among those who passed the drug quiz for prescription opioids, 95% (36/38) answered the dose question correctly, and 82% (31/38) selected the correct image. In a random sample of participants who completed UDT within 3 days of their online screening, 74% (25/34) tested positive for an opioid. CONCLUSIONS:This study demonstrated the utility of using online eligibility screening quizzes to verify opioid misuse and residence. Participants accurately recognized heroin and prescription opioid doses, prices, and images and correctly answered questions about features of their county. Online quizzes to screen and enroll PWUD hold promise for future research as an alternative to more time- and resource-intensive approaches that could offset the advantages of Web-based methods.

Project description:Universal access to drug susceptibility testing for newly diagnosed tuberculosis patients is recommended. Access to culture-based diagnostics remains limited, and targeted molecular assays are vulnerable to emerging resistance mutations. Improved protocols for direct-from-sputum Mycobacterium tuberculosis sequencing would accelerate access to comprehensive drug susceptibility testing and molecular typing. We assessed a thermo-protection buffer-based direct-from-sample M. tuberculosis whole-genome sequencing protocol. We prospectively analyzed 60 acid-fast bacilli smear-positive clinical sputum samples in India and Madagascar. A diversity of semiquantitative smear positivity-level samples were included. Sequencing was performed using Illumina and MinION (monoplex and multiplex) technologies. We measured the impact of bacterial inoculum and sequencing platforms on genomic read depth, drug susceptibility prediction performance, and typing accuracy. M. tuberculosis was identified by direct sputum sequencing in 45/51 samples using Illumina, 34/38 were identified using MinION-monoplex sequencing, and 20/24 were identified using MinION-multiplex sequencing. The fraction of M. tuberculosis reads from MinION sequencing was lower than from Illumina, but monoplexing grade 3+ samples on MinION produced higher read depth than Illumina (P < 0.05) and MinION multiplexing (P < 0.01). No significant differences in sensitivity and specificity of drug susceptibility predictions were seen across sequencing modalities or within each technology when stratified by smear grade. Illumina sequencing from sputum accurately identified 1/8 (rifampin) and 6/12 (isoniazid) resistant samples, compared to 2/3 (rifampin) and 3/6 (isoniazid) accurately identified with Nanopore monoplex. Lineage agreement levels between direct and culture-based sequencing were 85% (MinION-monoplex), 88% (Illumina), and 100% (MinION-multiplex). M. tuberculosis direct-from-sample whole-genome sequencing remains challenging. Improved and affordable sample treatment protocols are needed prior to clinical deployment.

Dataset Information

Feasibility of Direct Sputum Molecular Testing for Drug Resistance as Part of Tuberculosis Clinical Trials Eligibility Screening.

Publications

Feasibility of Direct Sputum Molecular Testing for Drug Resistance as Part of Tuberculosis Clinical Trials Eligibility Screening.

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