Gurarie D, Zimmerman P A, King C H
Department of Mathematics, 220 Yost Hall, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-7058, USA.
J Theor Biol. 2006 May 21;240(2):185-99. doi: 10.1016/j.jtbi.2005.09.015. Epub 2005 Nov 2.
Our increasing appreciation of the high prevalence of mixed-species Plasmodium infection in malaria-endemic regions has resulted in controversy regarding the likely mechanism(s) of regulation for mixed parasite burden within an individual human host. In the present study, we examined dynamic models of Plasmodium spp. regulation by fever and by non-specific (NS) and species-specific (SS) immunity (including the influence of their variable time-delays, duration, and efficacy) in order to assess the likely role of these factors in regulating detectable parasitemia and clinical disease. Our models suggest that in order to observe the irregular waves of fever and parasitemia that are often found in multiply infected subjects, there must be a differential SS immune effect (beyond the regulatory effects of the species-transcendent density-dependent factors previously posited to control mixed-species parasitemia), and time-dependent variation in immunity to the dominant species. By implementation of individual SS immune controls of non-permanent duration, the resulting multi-dimensional model can be viewed as multiple single-species oscillators coupled via a NS species-transcendent controller. This extended model exhibits the essential patterns of long-term mixed infections. Although this 'circuit-immunity' model gives only a qualitative estimate of the complex web of participating agents and reaction pathways, it provides a starting point for future studies of the specific and NS within-host mechanisms that regulate mixed-species malaria infection.
我们对疟疾流行地区混合物种疟原虫感染高患病率的认识不断提高，引发了关于个体人类宿主内混合寄生虫负担可能的调控机制的争议。在本研究中，我们研究了疟原虫物种的动态模型，通过发热以及非特异性（NS）和物种特异性（SS）免疫（包括它们可变的时间延迟、持续时间和效力的影响）来进行调控，以评估这些因素在调节可检测到的寄生虫血症和临床疾病中可能发挥的作用。我们的模型表明，为了观察到多重感染个体中经常出现的发热和寄生虫血症的不规则波动，必须存在差异的SS免疫效应（除了先前假定用于控制混合物种寄生虫血症的超越物种的密度依赖性因素的调节作用之外），以及对优势物种免疫的时间依赖性变化。通过实施非永久性持续时间的个体SS免疫控制，由此产生的多维模型可以被视为通过NS物种超越控制器耦合的多个单物种振荡器。这个扩展模型展示了长期混合感染的基本模式。尽管这个“回路免疫”模型仅对参与因素和反应途径的复杂网络进行了定性估计，但它为未来研究调节混合物种疟疾感染的特异性和宿主内NS机制提供了一个起点。
