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国家层面的结核病流行病学:自限性过程与艾滋病病毒的影响

Tuberculosis Epidemiology at the Country Scale: Self-Limiting Process and the HIV Effects.

作者信息

Krsulovic Felipe Augusto Maurin, Lima Mauricio

机构信息

Pontificia Universidad Católica de Chile, Santiago, Chile.

出版信息

PLoS One. 2016 Apr 19;11(4):e0153710. doi: 10.1371/journal.pone.0153710. eCollection 2016.

Abstract

BACKGROUND

The global spread of the human immunodeficiency virus (HIV) is the main hypothesis behind tuberculosis (TB) positive trends in the last decades, according to modeling studies and World Health Organization Reports (WHO). On one hand, TB (WHO) reports do not explicitly consider a modeling approach, but cover country and global TB trends. On the other hand, modeling studies usually do not cover the scale of WHO reports, because of the amount of parameters estimated to describe TB natural history. Here we combined these two principal sources of TB studies covering TB High Burden Countries (HBCs) dynamics. Our main goals were: (i) to detect the endogenous component of TB dynamics since 1974 for TB HBCs; and (ii) to explore the HIV exogenous effects on TB models`parameters.

METHODS AND FINDINGS

We explored the relationship between the TB per capita population rate of change (RI) and the infectious class size following an endogenous/exogenous framework. RI can be affected by intra-population processes (i.e. competition, predation) and exogenous variables like HIV. We found that TB dynamics had always a strong endogenous component, represented by a negative correlation between TB population size and RI, which was captured by the discrete logistic model. Moreover, we explored the HIV exogenous effects on TB models`parameters. We found that overall the TB+HIV logistic model was more parsimonious than TB model alone, principally in the African region. Our results showed that HIV affected principally TB carrying capacity, as expected by the known HIV effects on TB natural-history. We also tested if DOTS (Directly Observed Treatment Short-Course Strategy), poverty levels and BCG (Bacillus Calmette-Guérin) coverage explained the models´ residuals variances, but they did not.

CONCLUSIONS

Since 1974, TB dynamics were categorized in distinct chronological domains, with different dynamics but nearly the same underlying mechanism: a negative relationship between RI and infected class size (i.e. self-limiting). In the last decades, not only HIV spread represented a new TB chronological domain, but it also has been pushing TB carrying capacity (K) to higher levels. TB has a complex natural-history and imposes real challenges to model its dynamics. Yet, we were able to explore and reveal the main drivers of TB dynamics for HBCs since 1974, through a simple approach. Based on our results, we suggest that the endogenous view should be considered as a plausible hypothesis to model and explain TB dynamics and that future World Health Organization reports could include the endogenous/exogenous framework as a supplement to help to decipher the main drivers of TB dynamics and other diseases.

摘要

背景

根据模型研究和世界卫生组织报告(WHO),人类免疫缺陷病毒(HIV)的全球传播是过去几十年结核病(TB)呈阳性趋势背后的主要假设。一方面,结核病(WHO)报告没有明确考虑建模方法,而是涵盖国家和全球结核病趋势。另一方面,由于估计用于描述结核病自然史的参数数量众多,模型研究通常没有涵盖WHO报告的规模。在这里,我们结合了这两种涵盖结核病高负担国家(HBCs)动态的主要结核病研究来源。我们的主要目标是:(i)检测自1974年以来结核病高负担国家结核病动态的内源性组成部分;(ii)探索HIV对结核病模型参数的外源性影响。

方法和结果

我们在内源性/外源性框架下探索了人均结核病变化率(RI)与感染类大小之间的关系。RI可能受到种群内部过程(即竞争、捕食)和HIV等外源性变量的影响。我们发现结核病动态始终具有强大的内源性组成部分,表现为结核病种群规模与RI之间的负相关,离散逻辑模型捕捉到了这种相关性。此外,我们探索了HIV对结核病模型参数的外源性影响。我们发现总体而言,结核病合并HIV逻辑模型比单独的结核病模型更简洁,主要在非洲地区。我们的结果表明,正如已知的HIV对结核病自然史的影响所预期的那样,HIV主要影响结核病的承载能力。我们还测试了直接观察短程治疗策略(DOTS)、贫困水平和卡介苗(BCG)覆盖率是否能解释模型的残差方差,但它们不能。

结论

自1974年以来,结核病动态被分类在不同的时间域中,具有不同的动态但几乎相同的潜在机制:RI与感染类大小之间的负相关关系(即自我限制)。在过去几十年中,不仅HIV传播代表了一个新的结核病时间域,而且它还一直在将结核病承载能力(K)推向更高水平。结核病有复杂的自然史,对其动态建模提出了实际挑战。然而,我们能够通过一种简单的方法探索并揭示自1974年以来结核病高负担国家结核病动态的主要驱动因素。基于我们的结果,我们建议内源性观点应被视为建模和解释结核病动态的一个合理假设,并且未来世界卫生组织的报告可以将内源性/外源性框架作为补充纳入,以帮助解读结核病动态和其他疾病的主要驱动因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd1a/4836699/562a36f3165f/pone.0153710.g001.jpg

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