Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK; Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, UK; TB Modelling Group, TB Centre, London School of Hygiene & Tropical Medicine, London, UK.
Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK; Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, UK; TB Modelling Group, TB Centre, London School of Hygiene & Tropical Medicine, London, UK.
Lancet Infect Dis. 2019 Aug;19(8):903-912. doi: 10.1016/S1473-3099(19)30307-X. Epub 2019 Jul 4.
To end the global tuberculosis epidemic, latent tuberculosis infection needs to be addressed. All standard treatments for latent tuberculosis contain drugs to which multidrug-resistant (MDR) Mycobacterium tuberculosis is resistant. We aimed to estimate the global burden of multidrug-resistant latent tuberculosis infection to inform tuberculosis elimination policy.
By fitting a flexible statistical model to tuberculosis drug resistance surveillance and survey data collated by WHO, we estimated national trends in the proportion of new tuberculosis cases that were caused by MDR strains. We used these data as a proxy for the proportion of new infections caused by MDR M tuberculosis and multiplied trends in annual risk of infection from previous estimates of the burden of latent tuberculosis to generate trends in the annual risk of infection with MDR M tuberculosis. These estimates were used in a cohort model to estimate changes in the global and national prevalence of latent infection with MDR M tuberculosis. We also estimated recent infection levels (ie, in 2013 and 2014) and made predictions for the future burden of MDR tuberculosis in 2035 and 2050.
19·1 million (95% uncertainty interval [UI] 16·4 million-21·7 million) people were latently infected with MDR tuberculosis in 2014-a global prevalence of 0·3% (95% UI 0·2-0·3). MDR strains accounted for 1·2% (95% UI 1·0-1·4) of the total latent tuberculosis burden overall, but for 2·9% (95% UI 2·6-3·1) of the burden among children younger than 15 years (risk ratio for those younger than 15 years vs those aged 15 years or older 2·65 [95% UI 2·11-3·25]). Recent latent infection with MDR M tuberculosis meant that 1·9 million (95% UI 1·7 million-2·3 million) people globally were at high risk of active MDR tuberculosis in 2015.
We estimate that three in every 1000 people globally carry latent MDR tuberculosis infection, and prevalence is around ten times higher among those younger than 15 years. If current trends continue, the proportion of latent tuberculosis caused by MDR strains will increase, which will pose serious challenges for management of latent tuberculosis-a cornerstone of tuberculosis elimination strategies.
UK Medical Research Council, Bill & Melinda Gates Foundation, and European Research Council.
为了终结全球结核病流行，需要解决潜伏性结核感染问题。所有标准的潜伏性结核治疗方案都包含了对耐多药（MDR）结核分枝杆菌耐药的药物。本研究旨在估计全球耐多药潜伏性结核感染的负担，为结核病消除政策提供依据。
我们通过拟合世界卫生组织收集的结核药物耐药监测和调查数据的灵活统计模型，估计了新结核病例中由 MDR 菌株引起的比例的国家趋势。我们将这些数据用作由 MDR 结核分枝杆菌引起的新感染比例的替代指标，并将感染风险的年度趋势乘以先前潜伏性结核负担的估计值，从而生成 MDR 结核分枝杆菌感染风险的年度趋势。这些估计值被用于队列模型，以估计全球和国家耐多药潜伏性结核感染的变化。我们还估计了最近的感染水平（即 2013 年和 2014 年），并对 2035 年和 2050 年 MDR 结核的未来负担进行了预测。
2014 年，全球有 1910 万人（95%置信区间 [95%UI]：1640 万至 2170 万）感染了耐多药潜伏性结核——全球流行率为 0.3%（95%UI：0.2 至 0.3）。MDR 菌株占全部潜伏性结核负担的 1.2%（95%UI：1.0 至 1.4），但在 15 岁以下儿童中占 2.9%（95%UI：2.6 至 3.1）（与 15 岁以上者相比，风险比为 2.65[95%UI：2.11 至 3.25]）。最近感染耐多药 M 结核意味着全球有 190 万人（95%UI：170 万至 230 万）在 2015 年有发生耐多药结核的高风险。
我们估计，全球每 1000 人中就有 3 人感染耐多药潜伏性结核，而在 15 岁以下人群中，这一比例约为 10 倍。如果目前的趋势继续下去，由 MDR 菌株引起的潜伏性结核比例将会增加，这将对潜伏性结核的管理构成严重挑战——这是结核病消除策略的基石。
英国医学研究理事会、比尔和梅琳达·盖茨基金会以及欧洲研究理事会。
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