Spatial Heterogeneity of Extensively Drug Resistant-Tuberculosis in Western Cape Province, South Africa

Tuberculosis (TB) remains a leading global infectious disease killer. 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 and a fluoroquinolone, with efforts urgently needed to improve response. 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 clear geographic hotspots within RR-TB high burden areas. We also found hotspots in both percentage and count of amikacin-resistant and ofloxacin-resistant TB. The spatial distribution of percentage ofloxacin-resistant TB hotspots is 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 and improve outcomes may need to be targeted within spatial locations with RR-TB. Further research is required to understand underlying drivers of XDR-TB transmission in these locations.

结核病（Tuberculosis, TB）仍是全球范围内引发传染病相关死亡的主要病因之一。广泛耐药结核病（Extensively Drug-Resistant TB, XDR-TB）患者的治疗结局尤其不佳，直至近期，XDR-TB被定义为同时对氨基糖苷类与氟喹诺酮类药物耐药的利福平耐药结核病（Rifampicin-Resistant TB, RR-TB），目前亟需采取措施以改善此类患者的治疗应答效果。
本研究采用2012年至2015年间南非西开普省的实验室结核病检测数据，识别XDR-TB与XDR前体结核病（pre-XDR-TB，即对任意一种二线药物耐药的利福平耐药结核病）的空间聚集热点区域。研究人员绘制了全省及开普敦市内，利福平耐药结核病患者中罹患XDR-TB、pre-XDR-TB的占比与病例数分布，以及阿米卡星耐药结核病、氧氟沙星耐药结核病的相关数据。
研究结果显示，pre-XDR-TB的占比以及XDR-TB/pre-XDR-TB的病例数在利福平耐药结核病高负担区域内呈现高度异质性，且存在明确的地理聚集热点；同时，阿米卡星耐药与氧氟沙星耐药结核病的占比及病例数也存在聚集热点区域。氧氟沙星耐药结核病占比的空间分布与XDR-TB聚集热点区域高度相似，这提示氟喹诺酮类药物耐药通常是继发额外耐药性的第一步。
本研究表明，用于降低XDR-TB发病率并改善其治疗结局的干预措施，需针对利福平耐药结核病高发的空间区域开展精准部署。未来仍需开展进一步研究，以阐明此类区域内XDR-TB传播的潜在驱动因素。