The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling.
The Global Burden of Latent Tuberculosis Infection: A Re-estimation Using Mathematical Modelling.
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全球潜伏性结核感染负担：基于数学模型的重新估算
DOI：
10.1371/journal.pmed.1002152
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发表时间：
2016-10
期刊：
影响因子：
15.8
通讯作者：
Dodd PJ
中科院分区：
文献类型：
--
作者：
Houben RM;Dodd PJ
目前对占世界人口“三分之一”的潜在结核病感染(LTBI)造成的全球负担的估计已接近20岁。鉴于控制长期结核病感染作为《到2050年消灭结核病战略》的一部分的重要性、人口学和科学认识的变化以及结核病控制方面的进展，必须重新评估长期结核病感染的全球负担。我们构建了1934至2014年间各国感染风险(ARI)的趋势，使用LTBI调查(1950年至2011年的131项调查)对ARI的直接估计，以及根据世界卫生组织(WHO)对1990年至2014年涂阳结核病患病率的估计计算出的ARI的间接估计。使用高斯过程回归生成没有数据的国别年的ARI，并表示不确定性。将估计的ARI时间序列应用于每个国家的人口学，以计算感染、最近感染(在两年内感染)和最近感染异烟肼(INH)耐药菌株的人数和比例。由此产生的估计数按世卫组织区域汇总。我们估计了现有感染对2035年和2050年结核病发病率的贡献。2014年，LTBI的全球负担为23.0%(95%不确定区间[UI]：20.4%-26.4%)，总计约17亿人。世卫组织东南亚、西太平洋和非洲地区的患病率最高，约占LTBI患者的80%。最近感染的流行率为全球人口的0.8%(95%UI：0.7%-0.9%)，相当于5550万(95%UI：4820万-6380万)目前处于结核病高危状态的人，其中10.9%(95%UI：10.2%-11.8%)对异烟肼耐药。假设从2015年起不再有新的感染，单是目前的长期结核病感染，预计在2035年将在该地区每年产生16.5/10万人/年的结核病发病率，2050年将产生8.3/10万/年的结核病发病率。局限性包括直接ARI数据的数量和方法的异质性，以及关于LTBI潜在清除的证据有限。我们估计，2014年全球约有17亿人潜伏感染结核分枝杆菌(M.tb)，略低于全球人口的四分之一。如果要实现2050年消除结核病的目标，迫切需要投资于新的工具，以改善对有发展成疾病风险的长期结核病患者的诊断和治疗，以解决这一潜在的储蓄者问题。在这项数学模型研究中，Rein Houben和他的同事提供了对全球潜在结核病感染的最新估计，以及该宿主对消除结核病目标的影响。处理潜在的结核病感染者是实现消除结核病的关键。目前的估计是，全球“三分之一”的人口感染了结核病，这一估计被广泛引用，但近20年来一直没有正式估计。人口统计学的变化、结核病负担的大小和分布，以及新的科学见解和新数据的可获得性，意味着需要重新估计。我们在1934年至2014年期间生成了年度感染风险，并将其应用于国家层面的人口模型，尽可能量化不确定性。我们估计，2014年约有17亿人感染了LTBI；略低于全球人口的四分之一。如果不加以解决，目前的长期结核病负担本身就可能阻碍实现全球消除结核病的目标。要使长期结核病控制取得成功，就需要对长期结核病采取积极的方法。研究和开发应侧重于开发更好的工具，以确定将从长期脑损伤治疗中受益的个人。来自新的基于人群的LTBI流行率研究的更多经验数据将加强估计。
The existing estimate of the global burden of latent TB infection (LTBI) as “one-third” of the world population is nearly 20 y old. Given the importance of controlling LTBI as part of the End TB Strategy for eliminating TB by 2050, changes in demography and scientific understanding, and progress in TB control, it is important to re-assess the global burden of LTBI. We constructed trends in annual risk in infection (ARI) for countries between 1934 and 2014 using a combination of direct estimates of ARI from LTBI surveys (131 surveys from 1950 to 2011) and indirect estimates of ARI calculated from World Health Organisation (WHO) estimates of smear positive TB prevalence from 1990 to 2014. Gaussian process regression was used to generate ARIs for country-years without data and to represent uncertainty. Estimated ARI time-series were applied to the demography in each country to calculate the number and proportions of individuals infected, recently infected (infected within 2 y), and recently infected with isoniazid (INH)-resistant strains. Resulting estimates were aggregated by WHO region. We estimated the contribution of existing infections to TB incidence in 2035 and 2050. In 2014, the global burden of LTBI was 23.0% (95% uncertainty interval [UI]: 20.4%–26.4%), amounting to approximately 1.7 billion people. WHO South-East Asia, Western-Pacific, and Africa regions had the highest prevalence and accounted for around 80% of those with LTBI. Prevalence of recent infection was 0.8% (95% UI: 0.7%–0.9%) of the global population, amounting to 55.5 (95% UI: 48.2–63.8) million individuals currently at high risk of TB disease, of which 10.9% (95% UI:10.2%–11.8%) was isoniazid-resistant. Current LTBI alone, assuming no additional infections from 2015 onwards, would be expected to generate TB incidences in the region of 16.5 per 100,000 per year in 2035 and 8.3 per 100,000 per year in 2050. Limitations included the quantity and methodological heterogeneity of direct ARI data, and limited evidence to inform on potential clearance of LTBI. We estimate that approximately 1.7 billion individuals were latently infected with Mycobacterium tuberculosis (M.tb) globally in 2014, just under a quarter of the global population. Investment in new tools to improve diagnosis and treatment of those with LTBI at risk of progressing to disease is urgently needed to address this latent reservoir if the 2050 target of eliminating TB is to be reached. In this mathematical modelling study, Rein Houben and colleagues provide updated estimates of latent tuberculosis infection worldwide and its implications of this reservoir with respect to goals for eliminating tuberculosis. Addressing the latent TB infection reservoir is critical to achieving TB elimination. The current estimate that “one-third” of the global population is infected with tuberculosis is widely cited but has not been formally estimated for nearly 20 y. Changes in demography, the size and distribution of TB burden, as well as new scientific insights and the availability of new data mean a re-estimation is needed. We generated an annual risk of infection between 1934 and 2014 and applied this to a country-level demographic model, quantifying uncertainty wherever possible. We estimated that approximately 1.7 billion individuals were infected with LTBI in 2014; just under a quarter of the global population. If left unaddressed, the current LTBI burden alone will likely prevent achieving the global TB targets for TB elimination. For long-term TB control to be successful, an aggressive approach to LTBI is needed. Research and development should focus on developing better tools to identify individuals who will benefit from LTBI treatment. Estimates would be strengthened by additional empirical data from new population-based studies of LTBI prevalence.