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

Narges Alipanah^{1

2

3}, Priya B Shete^{4

5}, Hanh Nguyen⁶, Nhung Viet Nguyen^{7

8}, Lien Luu⁹, Thuong Pham¹⁰, Hung Nguyen^{11

12}, Phuong Nguyen¹³, Minh Chi Tran¹⁴, Nam Pham^{15

16}, Ha Phan^{17

18}, Patrick P J Phillips^{19

20}, Adithya Cattamanchi^{21

22}, Payam Nahid^{23

24

25}

Affiliations

¹ Santa Clara Valley Medical Center, San Jose, CA 95128, USA. narges.alipanah@ucsf.edu.
² UCSF Center for Tuberculosis, San Francisco, CA 94110, USA. narges.alipanah@ucsf.edu.
³ University of California, San Francisco, CA 94143, USA. narges.alipanah@ucsf.edu.
⁴ UCSF Center for Tuberculosis, San Francisco, CA 94110, USA. Priya.Shete@ucsf.edu.
⁵ University of California, San Francisco, CA 94143, USA. Priya.Shete@ucsf.edu.
⁶ Vietnam National Tuberculosis Programme/UCSF Research Collaboration, Hanoi, Vietnam. hanh202000@gmail.com.
⁷ Vietnam National Tuberculosis Programme/UCSF Research Collaboration, Hanoi, Vietnam. vietnhung@yahoo.com.
⁸ National Reference Laboratory, National Lung Hospital, Hanoi, Vietnam. vietnhung@yahoo.com.
⁹ Hanoi Lung Hospital, Hanoi, Vietnam. honglien38@gmail.com.
¹⁰ Hanoi Lung Hospital, Hanoi, Vietnam. drthuongbvphn@gmail.com.
¹¹ Vietnam National Tuberculosis Programme/UCSF Research Collaboration, Hanoi, Vietnam. hungmtb75@gmail.com.
¹² National Reference Laboratory, National Lung Hospital, Hanoi, Vietnam. hungmtb75@gmail.com.
¹³ National Reference Laboratory, National Lung Hospital, Hanoi, Vietnam. phuong125a@gmail.com.
¹⁴ Stanford Healthcare ValleyCare, Pleasanton, CA 94588, USA. minhchi.tran@gmail.com.
¹⁵ Vietnam National Tuberculosis Programme/UCSF Research Collaboration, Hanoi, Vietnam. thanhnam.bvphn@gmail.com.
¹⁶ Hanoi Lung Hospital, Hanoi, Vietnam. thanhnam.bvphn@gmail.com.
¹⁷ University of California, San Francisco, CA 94143, USA. steinriver@yahoo.com.
¹⁸ Vietnam National Tuberculosis Programme/UCSF Research Collaboration, Hanoi, Vietnam. steinriver@yahoo.com.
¹⁹ UCSF Center for Tuberculosis, San Francisco, CA 94110, USA. Patrick.Phillips@ucsf.edu.
²⁰ University of California, San Francisco, CA 94143, USA. Patrick.Phillips@ucsf.edu.
²¹ UCSF Center for Tuberculosis, San Francisco, CA 94110, USA. Adithya.Cattamanchi@ucsf.edu.
²² University of California, San Francisco, CA 94143, USA. Adithya.Cattamanchi@ucsf.edu.
²³ UCSF Center for Tuberculosis, San Francisco, CA 94110, USA. pnahid@ucsf.edu.
²⁴ University of California, San Francisco, CA 94143, USA. pnahid@ucsf.edu.
²⁵ Vietnam National Tuberculosis Programme/UCSF Research Collaboration, Hanoi, Vietnam. pnahid@ucsf.edu.

PMID: 31151255
PMCID: PMC6627302
DOI: 10.3390/diagnostics9020056

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

Narges Alipanah et al. Diagnostics (Basel). 2019.

. 2019 May 30;9(2):56.

doi: 10.3390/diagnostics9020056.

Authors

Affiliations

¹ Santa Clara Valley Medical Center, San Jose, CA 95128, USA. narges.alipanah@ucsf.edu.
² UCSF Center for Tuberculosis, San Francisco, CA 94110, USA. narges.alipanah@ucsf.edu.
³ University of California, San Francisco, CA 94143, USA. narges.alipanah@ucsf.edu.
⁴ UCSF Center for Tuberculosis, San Francisco, CA 94110, USA. Priya.Shete@ucsf.edu.
⁵ University of California, San Francisco, CA 94143, USA. Priya.Shete@ucsf.edu.
⁶ Vietnam National Tuberculosis Programme/UCSF Research Collaboration, Hanoi, Vietnam. hanh202000@gmail.com.
⁷ Vietnam National Tuberculosis Programme/UCSF Research Collaboration, Hanoi, Vietnam. vietnhung@yahoo.com.
⁸ National Reference Laboratory, National Lung Hospital, Hanoi, Vietnam. vietnhung@yahoo.com.
⁹ Hanoi Lung Hospital, Hanoi, Vietnam. honglien38@gmail.com.
¹⁰ Hanoi Lung Hospital, Hanoi, Vietnam. drthuongbvphn@gmail.com.
¹¹ Vietnam National Tuberculosis Programme/UCSF Research Collaboration, Hanoi, Vietnam. hungmtb75@gmail.com.
¹² National Reference Laboratory, National Lung Hospital, Hanoi, Vietnam. hungmtb75@gmail.com.
¹³ National Reference Laboratory, National Lung Hospital, Hanoi, Vietnam. phuong125a@gmail.com.
¹⁴ Stanford Healthcare ValleyCare, Pleasanton, CA 94588, USA. minhchi.tran@gmail.com.
¹⁵ Vietnam National Tuberculosis Programme/UCSF Research Collaboration, Hanoi, Vietnam. thanhnam.bvphn@gmail.com.
¹⁶ Hanoi Lung Hospital, Hanoi, Vietnam. thanhnam.bvphn@gmail.com.
¹⁷ University of California, San Francisco, CA 94143, USA. steinriver@yahoo.com.
¹⁸ Vietnam National Tuberculosis Programme/UCSF Research Collaboration, Hanoi, Vietnam. steinriver@yahoo.com.
¹⁹ UCSF Center for Tuberculosis, San Francisco, CA 94110, USA. Patrick.Phillips@ucsf.edu.
²⁰ University of California, San Francisco, CA 94143, USA. Patrick.Phillips@ucsf.edu.
²¹ UCSF Center for Tuberculosis, San Francisco, CA 94110, USA. Adithya.Cattamanchi@ucsf.edu.
²² University of California, San Francisco, CA 94143, USA. Adithya.Cattamanchi@ucsf.edu.
²³ UCSF Center for Tuberculosis, San Francisco, CA 94110, USA. pnahid@ucsf.edu.
²⁴ University of California, San Francisco, CA 94143, USA. pnahid@ucsf.edu.
²⁵ Vietnam National Tuberculosis Programme/UCSF Research Collaboration, Hanoi, Vietnam. pnahid@ucsf.edu.

PMID: 31151255
PMCID: PMC6627302
DOI: 10.3390/diagnostics9020056

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.

Keywords: DR-TB; Hain test; MTBDRplus; MTBDRsl; clinical trials; diagnostics; line probe assay; molecular testing; tuberculosis.

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Conflict of interest statement

The authors declare no conflict of interest.

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

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

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Abstract

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