Drug susceptibility testing using molecular techniques can enhance tuberculosis diagnosis

Thomas C Victor,Paul D Van Helden,Rabia Johnson,Judit N Nagy,Douglas Young ,John Wain ,M Bosman ,Robin M Warren ,A M Jordaan

doi:10.3855/jidc.320

Abstract

Sputum samples were collected from tuberculosis patients in a high tuberculosis incidence area in the Western Cape, South Africa. The aim of this study was to evaluate the performance and time to diagnosis of a genotypic drug susceptibility testing method. During June 2000 and November 2003, a total of 1,540 samples were sent for drug susceptibility testing (DST) to the national health laboratory services, and of those, a phenotypic DST result was obtained for 1,373 samples whereas a genotypic DST result was obtained for 1,301 of 1,540 samples. Performance-based calculations were done on 1,244 samples for which both a phenotypic and genotypic DST result was available. The reproducibility of the genotypic and phenotypic DST methods was 97% and 95%, respectively. The sensitivity and specificity of the genotypic DST method was 68% and 99% for Isoniazid and 87% and 99% for Rifampicin, respectively. Smear gradation was found to influence the performance of the genotypic DST method. The genotypic DST method gave accurate DST results for 75% of the samples within 20 days (range, 15-25), whereas the phenotypic DST results were only available for 75% of the samples after 38 days (range, 26-115) (p<0.001). This study showed that the genotypic DST could improve tuberculosis control by rapid diagnosis of drug resistant tuberculosis. This finding may have important implications for the control of drug resistant tuberculosis as it may reduce the chance for further transmission events.

Highlights

In resource poor countries, the World HealthOrganization (WHO) guidelines recommend the diagnosis of tuberculosis (TB) by smear microscopy in all new TB cases and smear microscopy, culture and drug susceptibility testing (DST) in re-treatment cases [1]
The reproducibility of the routine phenotypic DST method was 95% when the DST results of sequential follow-up samples were compared
It is well known that DST for some drugs is difficult due to technical reasons and these results are not always accurate [14,15]

Summary

Introduction

The World HealthOrganization (WHO) guidelines recommend the diagnosis of tuberculosis (TB) by smear microscopy in all new TB cases and smear microscopy, culture and drug susceptibility testing (DST) in re-treatment cases [1]. Routine phenotypic DST methods are culture based and are initially done to detect isoniazid (INH) and rifampicin (RIF) resistance. DST usually takes between 3 to 6 weeks, resulting in long diagnostic delays These delays are further exacerbated in new cases with primary drug resistance, given that DST is only initiated after 2 to 3 months of first line therapy. Conclusion: This study showed that the genotypic DST could improve tuberculosis control by rapid diagnosis of drug resistant tuberculosis. This finding may have important implications for the control of drug resistant tuberculosis as it may reduce the chance for further transmission events.

Objectives

Methods

Results

Conclusion