Targeted next-generation sequencing of sputum for diagnosis of drug-resistant TB: results of a national survey in Democratic Republic of the Congo
Targeted next-generation sequencing of sputum for diagnosis of drug-resistant TB: results of a national survey in Democratic Republic of the Congo
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DOI：
10.1038/s41598-020-67479-4
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发表时间：
2020-07-01
影响因子：
4.6
通讯作者：
Dean, Anna S.
中科院分区：
文献类型：
--
作者：
Kayomo, Michel Kaswa;Mbula, Vital Nkake;Dean, Anna S.
结核病 (TB) 患者的耐药性监测对于预防抗菌药物耐药性的传播至关重要。刚果民主共和国（DR Congo）被世界卫生组织（WHO）列为结核病和耐多药结核病（MDR-TB）高负担国家，但没有全国代表性的耐药数据。 2016-2017 年，使用创新的分子方法在全国 11 个省的 108 个显微镜检查中心对结核病患者进行了全国调查。痰样本采集自 1,545 名新患者和 163 名既往治疗患者。这些均通过 Xpert MTB/RIF 检测进行测试，然后直接对痰进行靶向下一代测序。利福平耐药率较低，新治患者中利福平耐药率为 1.8% (95% CI: 1.0-3.2)，既往治疗患者中利福平耐药率为 17.3% (95% CI: 11.9-24.4)。对吡嗪酰胺、氟喹诺酮类药物和二线注射剂的耐药性也较低。利福平敏感患者中异烟肼耐药率较高，新治患者为 6.6% (95% CI: 4.4-9.8)，既往治疗患者为 8.7% (95%: 3.2-21.2)。诊断和治疗异烟肼耐药患者仍然是一个挑战，因为目前的国家诊断算法会错过许多患者，该算法是通过 Xpert MTB/RIF 检测利福平耐药性驱动的。这是第一项直接对痰液进行靶向测序的全国性调查。它可以为其他尚未具备快速标本运输网络或进行培养能力的环境提供概念验证。
The surveillance of drug resistance among tuberculosis (TB) patients is central to preventing the spread of antimicrobial resistance. The Democratic Republic of the Congo (DR Congo) is classified by the World Health Organization (WHO) as a country with a high burden of TB and multidrug-resistant TB (MDR-TB), but there are no nationally representative data on drug resistance. In 2016-2017, a national survey of TB patients was conducted in 108 microscopy centres across all 11 provinces of the country using innovative molecular approaches. Sputum samples were collected from 1,545 new and 163 previously treated patients. These were tested by the Xpert MTB/RIF assay, followed by targeted next-generation sequencing performed directly on sputum. The prevalence of rifampicin resistance was low, at 1.8% (95% CI: 1.0-3.2) among new and 17.3% (95% CI: 11.9-24.4) among previously treated patients. Resistance to pyrazinamide, fluoroquinolones and second-line injectables was also low. The prevalence of resistance to isoniazid among rifampicin-susceptible patients was higher, at 6.6% (95% CI: 4.4-9.8) among new and 8.7% (95% : 3.2-21.2) among previously treated patients. Diagnosing and treating isoniazid-resistant patients remains a challenge, given that many will be missed by the current national diagnostic algorithm that is driven by detecting rifampicin resistance by Xpert MTB/RIF. This is the first nationwide survey incorporating targeted sequencing directly on sputum. It serves as a proof-of-concept for other settings that do yet have rapid specimen transport networks or capacity to conduct culture.