Michael Edwin, Singh Brajendra K
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA.
BMC Med. 2016 Jan 28;14:14. doi: 10.1186/s12916-016-0557-y.
The current WHO-led initiative to eradicate the macroparasitic disease, lymphatic filariasis (LF), based on single-dose annual mass drug administration (MDA) represents one of the largest health programs devised to reduce the burden of tropical diseases. However, despite the advances made in instituting large-scale MDA programs in affected countries, a challenge to meeting the goal of global eradication is the heterogeneous transmission of LF across endemic regions, and the impact that such complexity may have on the effort required to interrupt transmission in all socioecological settings.
Here, we apply a Bayesian computer simulation procedure to fit transmission models of LF to field data assembled from 18 sites across the major LF endemic regions of Africa, Asia and Papua New Guinea, reflecting different ecological and vector characteristics, to investigate the impacts and implications of transmission heterogeneity and complexity on filarial infection dynamics, system robustness and control.
We find firstly that LF elimination thresholds varied significantly between the 18 study communities owing to site variations in transmission and initial ecological parameters. We highlight how this variation in thresholds lead to the need for applying variable durations of interventions across endemic communities for achieving LF elimination; however, a major new result is the finding that filarial population responses to interventions ultimately reflect outcomes of interplays between dynamics and the biological architectures and processes that generate robustness/fragility trade-offs in parasite transmission. Intervention simulations carried out in this study further show how understanding these factors is also key to the design of options that would effectively eliminate LF from all settings. In this regard, we find how including vector control into MDA programs may not only offer a countermeasure that will reliably increase system fragility globally across all settings and hence provide a control option robust to differential locality-specific transmission dynamics, but by simultaneously reducing transmission regime variability also permit more reliable macroscopic predictions of intervention effects.
Our results imply that a new approach, combining adaptive modelling of parasite transmission with the use of biological robustness as a design principle, is required if we are to both enhance understanding of complex parasitic infections and delineate options to facilitate their elimination effectively.
目前由世界卫生组织主导的根除大型寄生虫病——淋巴丝虫病(LF)的倡议,基于单剂量年度群体药物给药(MDA),这是为减轻热带疾病负担而设计的最大型卫生项目之一。然而,尽管在受影响国家实施大规模MDA项目方面取得了进展,但实现全球根除目标面临的一个挑战是,LF在流行地区的传播具有异质性,以及这种复杂性可能对在所有社会生态环境中阻断传播所需的努力产生的影响。
在此,我们应用贝叶斯计算机模拟程序,将LF传播模型与从非洲、亚洲和巴布亚新几内亚主要LF流行地区的18个地点收集的现场数据进行拟合,这些地点反映了不同的生态和媒介特征,以研究传播异质性和复杂性对丝虫感染动态、系统稳健性和控制的影响及意义。
我们首先发现,由于传播和初始生态参数的地点差异,18个研究社区之间的LF消除阈值差异显著。我们强调了这种阈值差异如何导致需要在流行社区应用不同时长的干预措施来实现LF消除;然而,一个主要的新发现是,丝虫种群对干预措施的反应最终反映了动态过程与在寄生虫传播中产生稳健性/脆弱性权衡的生物学结构和过程之间相互作用的结果。本研究中进行的干预模拟进一步表明,理解这些因素也是设计能够在所有环境中有效消除LF的方案的关键。在这方面,我们发现将媒介控制纳入MDA项目不仅可以提供一种对策,可靠地增加全球所有环境中的系统脆弱性,从而提供一种对不同地点特定传播动态具有稳健性的控制选项,而且通过同时降低传播模式的变异性,还能更可靠地对干预效果进行宏观预测。
我们的结果表明,如果我们既要加强对复杂寄生虫感染的理解,又要确定有效促进其消除的方案,就需要一种新方法,即将寄生虫传播的适应性建模与将生物学稳健性作为设计原则相结合。