Detection of Second Line Drug Resistance among Drug Resistant Mycobacterium Tuberculosis Isolates in Botswana.

Tuelo Mogashoa,Botshelo Kgwaadira,Brigitta Derendinger,Lucy Mupfumi,Ishmael Kasvosve,Robin M Warren,Thato Iketleng,Serej D Ley,Thusoyaone T Tsholofelo,Goabaone Rankgoane-Pono,Elizabeth M Streicher,Sikhulile Moyo,Margaret Mokomane,Simani Gaseitsiwe,Pinkie Melamu

doi:10.3390/pathogens8040208

Abstract

The emergence and transmission of multidrug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis (M.tb) strains is a threat to global tuberculosis (TB) control. The early detection of drug resistance is critical for patient management. The aim of this study was to determine the proportion of isolates with additional second-line resistance among rifampicin and isoniazid resistant and MDR-TB isolates. A total of 66 M.tb isolates received at the National Tuberculosis Reference Laboratory between March 2012 and October 2013 with resistance to isoniazid, rifampicin or both were analyzed in this study. The genotypes of the M.tb isolates were determined by spoligotyping and second-line drug susceptibility testing was done using the Hain Genotype MTBDRsl line probe assay version 2.0. The treatment outcomes were defined according to the Botswana national and World Health Organization (WHO) guidelines. Of the 57 isolates analyzed, 33 (58%) were MDR-TB, 4 (7%) were additionally resistant to flouroquinolones and 3 (5%) were resistant to both fluoroquinolones and second-line injectable drugs. The most common fluoroquinolone resistance-conferring mutation detected was gyrA A90V. All XDR-TB cases remained smear or culture positive throughout the treatment. Our study findings indicate the importance of monitoring drug resistant TB cases to ensure rapid detection of second-line drug resistance.

Highlights

In 2017, 10 million people fell ill with tuberculosis (TB) and 1.6 million people died of TB [1].In the same year, an increase in cases of rifampicin monoresistant and multidrug resistant TB (MDR-TB defined as TB that is resistant to rifampicin and isoniazid) from 490,000 in 2016 to 558,000 in 2017 was observed [1]
The clinical treatment outcome data was obtained from the Botswana National Tuberculosis Program (BNTP) patient database
Among the 57 drug resistant isolates, the first and second-line drug susceptibility testing (DST) results showed that 19% of the cases were resistant to rifampicin only, 11% were resistant to isoniazid only, 58% were resistant to both isoniazid and rifampicin (MDR), 7% of the MDR isolates showed additional resistance to flouroquinolones while 5% of the MDR isolates were resistant to flouroquinolones and SLIDS (XDR)

Summary

Introduction

An increase in cases of rifampicin monoresistant and multidrug resistant TB (MDR-TB defined as TB that is resistant to rifampicin and isoniazid) from 490,000 in 2016 to 558,000 in 2017 was observed [1]. The increasing numbers of rifampicin and MDR-TB cases poses a risk to TB control programs throughout the world [2]. The standardized World Health Organization (WHO) MDR-TB treatment regimen recommends the use of second-line injectable drugs (SLIDs) in combination with flouroquinolones as part of the standardized MDR-TB treatment regimen [2]. The resistance to a fluoroquinolone and a SLID negatively impacts treatment outcome and has been defined as extensively drug resistant TB (XDR-TB) [5,6,7]. MDR-TB in combination with resistance to either a fluoroquinolone or a SLID has been termed Pre-XDR-TB

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