Implementation of the GenoType® MTBDRplus Assay in a Laboratory in Manila, Philippines: An Analysis of the Effect on Time to Diagnostic Results and Treatment Initiation Open Access

Abstract

Implementation of the GenoType® MTBDR plus Assay in a Laboratory in Manila, Philippines:

An Analysis of the Effect on Time to Diagnostic Results and Treatment Initiation

Background: The steady rise in multidrug resistant tuberculosis (MDR TB) cases
challenges global TB control efforts and strains national TB control programs. However,
despite the increase, few patients are tested for drug susceptibility and enrolled in
treatment regimens. Accurate and timely diagnosis of MDR TB is critical in mitigating its
spread, but conventional tests (such as culture or sputum smear microscopy) are slow and
do not provide drug susceptibility testing (DST). The WHO recommends that line probe
assays (LPAs) be used for rapid TB detection and DST.
Methods: The GenoType® MTBDR plus LPA was implemented into routine TB testing
in a mycobacteriology laboratory in Manila, Philippines. Patient enrollment was divided
into validation (culture-based testing) and demonstration (LPA testing) phases and
patients were tested for presence of TB and resistance to RIF and INH. Performance
characteristics were calculated for LPA versus the gold-standard culture-based methods.
Time from specimen collection to availability of diagnostic results and to treatment
initiation were compared between the two phases. The association between patient
characteristics and the two outcomes were also examined.
Results: The performance characteristics for detection of RIF-resistance, INH-resistance,
and MDR TB status decreased from the validation to the demonstration phase. Although
the time from sample collection to availability of diagnostic results was significantly
shorter for the demonstration phase (p<0.0001), there was no significant difference for
time to treatment initiation between the two phases (p=0.09).
Conclusion: This study suggests that the MTBDR plus assay may serve as a suitable and
rapid test for public health practice that may reduce the waiting period for diagnostic
results. However, appropriate and timely treatment depends on factors other than
diagnostics, and TB control programs should be prepared to manage changes associated
with the introduction a rapid diagnostic test.

Table of Contents

TABLE OF CONTENTS

BACKGROUND…………………………………………………………….......................…………….1

METHODS

Data Source……………………………………………………………..........................…………..5
Performance Characteristics……………………………………....................…………………6
Survival Analyses……………………………………………………………..........................……7

RESULTS

Performance Characteristics……………………………………….....................………………8
Survival Analyses……………………………………………………….............................………9

DISCUSSION……………………………………………………………………........................………11

CONCLUSION………………………………………………………………………........................…..15

REFERENCES………………………………………………………………….........................………..16

TABLES AND FIGURES

Figure 1. Flow diagram depicting number of patients at various stages of the
study, including their separation in validation and demonstration phase……….....19

Table 1. Patient characteristics of those who were enrolled into the study and
had valid laboratory test results, separated in validation and demonstration
phase accordingly………………………………………………………..….......................…...….20

Table 2. Performance characteristics for LPA testing versus gold standard
culture based methods (either liquid or solid media), separated by validation
and demonstration phase……………………………………….....................……………...……21

Figure 2. Kaplan-Meier curves evaluating the difference in time to availability
of diagnostic results for validation (culture-based testing) versus demonstration
phase (LPA testing)……………………………………………........................………………...…22

Figure 3. Kaplan-Meier curves evaluating the difference in time to treatment for
validation (culture-based testing) versus demonstration phase (LPA testing).....23

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Health Sciences, Epidemiology
Keyword	MTBDRplus TB line probe assay TB treatment MDR-TB TB diagnostics multidrug resistant tuberculosis tuberculosis
Committee Chair / Thesis Advisor	Goodman, Michael, Emory University
Committee Members	Alexander, Heather, CDC
Partnering Agencies	CDC

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