Trauer James M, Denholm Justin T, McBryde Emma S
Burnet Institute, 89 Commercial Road, Melbourne 3004, Australia; Victorian Infectious Diseases Service at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia; Department of Medicine (Royal Melbourne Hospital/Western Hospital), University of Melbourne, Victoria 3010, Australia.
Victorian Infectious Diseases Service at the Peter Doherty Institute for Infection and Immunity, Victoria 3010, Australia; Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia.
J Theor Biol. 2014 Oct 7;358:74-84. doi: 10.1016/j.jtbi.2014.05.023. Epub 2014 May 27.
We present a mathematical model to simulate tuberculosis (TB) transmission in highly endemic regions of the Asia-Pacific, where epidemiology does not appear to be primarily driven by HIV-coinfection. The ten-compartment deterministic model captures many of the observed phenomena important to disease dynamics, including partial and temporary vaccine efficacy, declining risk of active disease following infection, the possibility of reinfection both during the infection latent period and after treatment, multidrug resistant TB (MDR-TB) and de novo resistance during treatment. We found that the model could not be calibrated to the estimated incidence rate without allowing for reinfection during latency, and that even in the presence of a moderate fitness cost and a lower value of R0, MDR-TB becomes the dominant strain at equilibrium. Of the modifiable programmatic parameters, the rate of detection and treatment commencement was the most important determinant of disease rates with each respective strain, while vaccination rates were less important. Improved treatment of drug-susceptible TB did not result in decreased rates of MDR-TB through prevention of de novo resistance, but rather resulted in a modest increase in MDR-TB through strain replacement. This was due to the considerably greater relative contribution of community transmission to MDR-TB incidence, by comparison to de novo amplification of resistance in previously susceptible strains.
我们提出了一个数学模型,用于模拟亚太地区结核病(TB)高流行地区的传播情况,在这些地区,流行病学似乎并非主要由艾滋病毒合并感染驱动。这个十房室确定性模型捕捉了许多对疾病动态至关重要的观察到的现象,包括部分和暂时的疫苗效力、感染后活动性疾病风险的下降、在感染潜伏期和治疗后再次感染的可能性、耐多药结核病(MDR-TB)以及治疗期间的新发耐药性。我们发现,如果不考虑潜伏期的再次感染,该模型无法校准到估计的发病率,而且即使存在适度的适应性代价和较低的R0值,耐多药结核病在平衡状态下也会成为主要菌株。在可修改的规划参数中,检测和开始治疗的速率是每种菌株疾病发生率的最重要决定因素,而疫苗接种率则不太重要。改善对药物敏感结核病的治疗并不会通过预防新发耐药性而导致耐多药结核病发病率下降,反而会通过菌株替代导致耐多药结核病略有增加。这是因为与先前敏感菌株中耐药性的新发扩增相比,社区传播对耐多药结核病发病率的相对贡献要大得多。