Spatial heterogeneity of extensively drug resistant-tuberculosis in Western Cape Province, South Africa

Abstract

Tuberculosis (TB) remains a leading infectious disease killer globally. Treatment outcomes are especially poor among people with extensively drug-resistant (XDR) TB, until recently defined as rifampicin-resistant (RR) TB with resistance to an aminoglycoside (amikacin) and a fluoroquinolone (ofloxacin). We used laboratory TB test results from Western Cape province, South Africa between 2012 and 2015 to identify XDR-TB and pre-XDR-TB (RR-TB with resistance to one second-line drug) spatial hotspots. We mapped the percentage and count of individuals with RR-TB that had XDR-TB and pre-XDR-TB across the province and in Cape Town, as well as amikacin-resistant and ofloxacin-resistant TB. We found the percentage of pre-XDR-TB and the count of XDR-TB/pre-XDR-TB highly heterogeneous with geographic hotspots within RR-TB high burden areas, and found hotspots in both percentage and count of amikacin-resistant and ofloxacin-resistant TB. The spatial distribution of percentage ofloxacin-resistant TB hotspots was similar to XDR-TB hotspots, suggesting that fluoroquinolone-resistace is often the first step to additional resistance. Our work shows that interventions used to reduce XDR-TB incidence may need to be targeted within spatial locations of RR-TB, and further research is required to understand underlying drivers of XDR-TB transmission in these locations.

Integrating Molecular Diagnostics and GIS Mapping: A Multidisciplinary Approach to Understanding Tuberculosis Disease Dynamics in South Africa Using Xpert MTB/RIF

“…Past studies also found that mutations in the region of the rpoB gene represented by probes E and D were the most common [39,40]. The Western Cape province had the highest detection rate of RR Mtb with probe E, followed by parts of KwaZulu Natal and Mpumalanga, areas where previous studies have reported high levels of drug-resistant Mtb [41][42][43][44]. The KwaZulu Natal and Mpumalanga provinces border Swaziland, which previously reported the unreliability of Xpert in identifying the rpoB 1491F mutation [45].…”