The Allometry of Host-Pathogen Interactions

BackgroundUnderstanding the mechanisms that control rates of disease progression in humans and other species is an important area of research relevant to epidemiology and to translating studies in small laboratory animals to humans. Body size and metabolic rate influence a great number of biological rates and times. We hypothesize that body size and metabolic rate affect rates of pathogenesis, specifically the times between infection and first symptoms or death.
Methods and Principal FindingsWe conducted a literature search to find estimates of the time from infection to first symptoms (tS) and to death (tD) for five pathogens infecting a variety of bird and mammal hosts. A broad sampling of diseases (1 bacterial, 1 prion, 3 viruses) indicates that pathogenesis is controlled by the scaling of host metabolism. We find that the time for symptoms to appear is a constant fraction of time to death in all but one disease. Our findings also predict that many population-level attributes of disease dynamics are likely to be expressed as dimensionless quantities that are independent of host body size.
Conclusions and SignificanceOur results show that much variability in host pathogenesis can be described by simple power functions consistent with the scaling of host metabolic rate. Assessing how disease progression is controlled by geometric relationships will be important for future research. To our knowledge this is the first study to report the allometric scaling of host/pathogen interactions.

研究背景：阐明调控人类及其他物种疾病进展速率的内在机制，是流行病学（epidemiology）领域的重要研究方向，同时也可为小型实验动物研究向人类临床研究的转化提供关键理论支撑。机体体型与代谢速率会对众多生物学速率与时间进程产生广泛影响。本研究提出假说：机体体型与代谢速率会影响发病进程的速率，具体体现为病原体（pathogen）感染宿主（host）至首次出现症状，或直至宿主死亡的时间间隔。

研究方法与主要结果：我们通过系统性文献检索，收集了5种分别感染多种鸟类与哺乳类宿主的病原体的相关数据，即病原体从感染宿主至首次出现症状（tS）、直至宿主死亡（tD）的时间估算值。本次开展的广泛疾病采样涵盖1种细菌、1种朊病毒（prion）、3种病毒，分析结果显示，发病进程受宿主代谢的异速缩放（allometric scaling）规律调控。我们发现，除1种疾病外，其余所有疾病中，宿主出现症状的时长均为其至死亡时长的固定比例。本研究结果同时预测，疾病动态的诸多种群层面属性，大概率可表示为与宿主体型无关的无量纲量（dimensionless quantities）。

研究结论与意义：本研究结果表明，宿主发病进程中的诸多差异，可通过与宿主代谢缩放规律相符的简单幂函数（power functions）进行描述。探究疾病进展如何受几何关系调控，将是未来相关研究的重要方向。据我们所知，本研究首次报道了宿主-病原体相互作用的异速缩放规律。