Risk of death during acute infection is accelerating across diverse host-pathogen systems and consistent with multiple models of host-pathogen interaction.

IF 3.7 2区 生物学 Q2 MICROBIOLOGY
mSphere Pub Date : 2025-05-27 Epub Date: 2025-04-28 DOI:10.1128/msphere.00953-24
Tim O'Sullivan, Canan Karakoç, Kristofer Wollein Waldetoft, Sam P Brown
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引用次数: 0

Abstract

Infectious diseases remain a major cause of global mortality, yet basic questions concerning the relationship between within-host processes governing pathogen burden (pathogen replication, immune responses) and population-scale (epidemiological) patterns of mortality remain obscure. We use a structured literature review to leverage the extensive biomedical data generated by controlled host infections to address the epidemiological question of whether infection-induced mortality is constant, accelerating, or follows some other pattern of change and to infer the within-host mechanistic basis of this pattern. We show that across diverse lethal infection models, the risk of death increases approximately exponentially in time since infection, in a manner phenomenologically similar to the dynamics of all-cause death. We further show that this pattern of accelerating risk is consistent with multiple alternate mechanisms of pathogen growth and host-pathogen interaction, underlining the limitations of current experimental approaches to connect within-host processes to epidemiological patterns. We review critical experimental questions that our work highlights, requiring additional non-invasive data on pathogen burden throughout the course of infection.IMPORTANCEHere, we ask a simple question: what are the dynamics of pathogen-induced death? Death is a central phenotype in both biomedical and epidemiological infectious disease biology, yet very little work has attempted to link the biomedical focus on pathogen dynamics within a host and the epidemiological focus on populations of infected hosts. To systematically characterize the dynamics of death in controlled animal infections, we analyzed 209 data sets spanning diverse lethal animal infection models. Across experimental models, we find robust support for an accelerating risk of death since the time of infection, contrasting with conventional epidemiological models that assume a constant elevated risk of death. Using math models, we show that multiple processes of growth and virulence are consistent with accelerating risk of death, and we end with a discussion of critical experiments to resolve how within-host biomedical processes map onto epidemiological patterns of disease.

在不同的宿主-病原体系统中,急性感染期间的死亡风险正在加速,这与宿主-病原体相互作用的多种模型一致。
传染病仍然是全球死亡的一个主要原因,但有关控制病原体负担的宿主内部过程(病原体复制、免疫反应)与人口规模(流行病学)死亡模式之间关系的基本问题仍然不清楚。我们使用结构化的文献综述来利用由受控宿主感染产生的广泛生物医学数据来解决流行病学问题,即感染引起的死亡率是恒定的、加速的还是遵循其他变化模式,并推断这种模式的宿主内部机制基础。我们表明,在不同的致命感染模型中,死亡风险随着时间的推移呈指数增长,在现象上类似于全因死亡的动态。我们进一步表明,这种加速风险的模式与病原体生长和宿主-病原体相互作用的多种替代机制是一致的,强调了当前将宿主内过程与流行病学模式联系起来的实验方法的局限性。我们回顾了我们工作强调的关键实验问题,需要在整个感染过程中提供额外的非侵入性病原体负担数据。在这里,我们提出一个简单的问题:病原体诱导死亡的动力学是什么?死亡是生物医学和流行病学传染病生物学的中心表型,但很少有工作试图将生物医学关注宿主内病原体动力学和流行病学关注受感染宿主种群联系起来。为了系统地描述受控动物感染的死亡动态,我们分析了209个数据集,涵盖了不同的致命动物感染模型。在实验模型中,我们发现自感染以来死亡风险加速的有力支持,与假设死亡风险持续升高的传统流行病学模型形成鲜明对比。使用数学模型,我们表明生长和毒力的多个过程与加速死亡的风险是一致的,我们以关键实验的讨论结束,以解决宿主内生物医学过程如何映射到疾病的流行病学模式。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
mSphere
mSphere Immunology and Microbiology-Microbiology
CiteScore
8.50
自引率
2.10%
发文量
192
审稿时长
11 weeks
期刊介绍: mSphere™ is a multi-disciplinary open-access journal that will focus on rapid publication of fundamental contributions to our understanding of microbiology. Its scope will reflect the immense range of fields within the microbial sciences, creating new opportunities for researchers to share findings that are transforming our understanding of human health and disease, ecosystems, neuroscience, agriculture, energy production, climate change, evolution, biogeochemical cycling, and food and drug production. Submissions will be encouraged of all high-quality work that makes fundamental contributions to our understanding of microbiology. mSphere™ will provide streamlined decisions, while carrying on ASM''s tradition for rigorous peer review.
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