Ministry of Health and Sanitation, Sierra Leone; Rey Juan Carlos University and Hospital Universitario Fundación Alcorcon, Madrid, Spain; National Tuberculosis Programme, Sierra Leone.
Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine, London, UK.
Lancet Glob Health. 2022 Apr;10(4):e543-e554. doi: 10.1016/S2214-109X(22)00004-3.
Multidrug-resistant tuberculosis (MDR-TB) is a global health emergency. We aimed to evaluate treatment outcomes among people with MDR-TB in Sierra Leone and investigate social and health factors associated with adverse treatment outcomes.
This national, retrospective cohort study recruited all people notified with MDR-TB to the Sierra Leone National TB Programme, admitted to Lakka hospital (Lakka, Western Area Rural District, Freetown, Sierra Leone) between April, 2017, and September, 2019. Participants were followed up to May, 2021. People who were eligible but had no social or health data available, or were subsequently found to have been misdiagnosed, were excluded from participation. MDR-TB treatment was with the 2017 WHO-recommended short (9-11 month) or long (18-24 month) aminoglycoside-containing regimens. Multivariable logistic regression models examined associations of programmatic social and health data with WHO-defined adverse treatment outcomes (death, treatment failure, loss to follow-up).
Of 370 notified MDR-TB cases, 365 (99%) were eligible for study participation (five participants were excluded due to lack of social or health data or misdiagnosis). Treatment was started by 341 (93%) of 365 participants (317 received the short regimen, 24 received the long regimen, and 24 received no treatment). Median age was 35 years (IQR 26-45), 263 (72%) of 365 were male and 102 (28%) were female, 71 (19%) were HIV-positive, and 127 (35%) were severely underweight (body-mass index <16·5 kg/m). Overall, 267 (73%) of 365 participants had treatment success, 95 (26%) had an adverse outcome, and three (1%) were still on treatment in May, 2021. Age 45-64 years (adjusted odds ratio [aOR] 2·4, 95% CI 1·2-5·0), severe underweight (aOR 4·2, 1·9-9·3), untreated HIV (aOR 10, 2·6-40·0), chronic lung disease (aOR 2·0, 1·0-4·2), previously unsuccessful drug-sensitive tuberculosis retreatment (aOR 4·3, 1·0-19), and a long regimen (aOR 6·5, 2·3-18·0) were associated with adverse outcomes. A sensitivity analysis showed that prothionamide resistance (aOR 3·1, 95% CI 1·5-10·0) and aminoglycoside-related complete deafness (aOR 6·6, 1·3-35) were independently associated with adverse outcomes.
MDR-TB treatment success in Sierra Leone approached WHO targets and the short regimen was associated with higher success. The social and health factors associated with adverse outcomes in this study suggest a role for integrated tuberculosis, HIV, and non-communicable disease services alongside nutritional and socioeconomic support for people with MDR-TB and emphasise the urgent need to scale up coverage of all-oral aminoglycoside-sparing regimens.
Wellcome Trust, Joint Global Health Trials.
耐多药结核病(MDR-TB)是全球卫生紧急情况。我们旨在评估塞拉利昂耐多药结核病患者的治疗结果,并调查与不良治疗结果相关的社会和健康因素。
这项全国性的回顾性队列研究招募了所有向塞拉利昂国家结核病规划报告的耐多药结核病患者,并于 2017 年 4 月至 2019 年 9 月入住 Lakka 医院(Lakka,西部农村地区,弗里敦,塞拉利昂)。参与者随访至 2021 年 5 月。有资格但没有社会或健康数据,或随后发现被误诊的人被排除在参与之外。MDR-TB 治疗采用了 2017 年世卫组织推荐的含有短(9-11 个月)或长(18-24 个月)氨基糖苷类药物的方案。多变量逻辑回归模型研究了方案社会和健康数据与世卫组织定义的不良治疗结果(死亡、治疗失败、失访)之间的关联。
在 370 例报告的耐多药结核病病例中,365 例(99%)符合研究参与条件(由于缺乏社会或健康数据或误诊,有 5 名参与者被排除在外)。365 名参与者中有 341 名(93%)开始治疗(317 名接受短疗程,24 名接受长疗程,24 名未接受治疗)。中位年龄为 35 岁(IQR 26-45),365 名患者中 263 名(72%)为男性,102 名(28%)为女性,71 名(19%)为 HIV 阳性,127 名(35%)为严重消瘦(体重指数<16.5kg/m2)。总体而言,365 名参与者中有 267 名(73%)治疗成功,95 名(26%)出现不良结果,3 名(1%)在 2021 年 5 月仍在治疗中。年龄 45-64 岁(调整后的优势比[aOR]2.4,95%CI 1.2-5.0)、严重消瘦(aOR 4.2,1.9-9.3)、未治疗的 HIV(aOR 10,2.6-40.0)、慢性肺部疾病(aOR 2.0,1.0-4.2)、先前不成功的药物敏感结核病复治(aOR 4.3,1.0-19)和长疗程(aOR 6.5,2.3-18.0)与不良结果相关。敏感性分析显示,吡嗪酰胺耐药(aOR 3.1,95%CI 1.5-10.0)和氨基糖苷类相关完全耳聋(aOR 6.6,1.3-35)与不良结果独立相关。
塞拉利昂的耐多药结核病治疗成功率接近世卫组织的目标,短疗程与更高的成功率相关。这项研究中与不良治疗结果相关的社会和健康因素表明,结核病、艾滋病毒和非传染性疾病服务的整合,以及耐多药结核病患者的营养和社会经济支持,发挥了作用,并强调迫切需要扩大所有口服氨基糖苷类药物节省方案的覆盖面。
威康信托基金会,全球结核病联合临床试验。