Modeling the emergence of the 'hot zones': tuberculosis and the amplification dynamics of drug resistance
Modeling the emergence of the 'hot zones': tuberculosis and the amplification dynamics of drug resistance
复制标题
DOI：
10.1038/nm1102
复制
发表时间：
2004-10-01
期刊：
影响因子：
82.9
通讯作者：
Chou, T
中科院分区：
文献类型：
--
作者：
Blower, SM;Chou, T
“热点地区”是耐多药结核病流行率（或发病率）超过5%的地区。我们提出了一个新的数学模型（放大器模型），跟踪多个（前MDR，MDR和后MDR）耐药结核分枝杆菌菌株的出现和演变。我们重建可能的演变轨迹，在过去的三十年中产生的热点区域，并确定关键的因果因素。结果与世界卫生组织（世卫组织）最近报告的数据一致。我们的分析产生了三个重要的见解。首先，矛盾的是，我们发现，成功减少野生型泛敏感菌株的程序的区域往往演变成热区。第二，即使MDR菌株的适应性（因此传染性）比野生型泛敏感菌株低得多，也会出现一些热区。第三，MDR水平受病例发现率、治愈率和扩增概率的影响。为了有效控制热点地区的耐多药结核病，世界卫生组织必须明确一个目标，以最大限度地减少扩增概率。
`Hot zones' are areas that have >5% prevalence (or incidence) of multidrug-resistant tuberculosis (MDRTB). We present a new mathematical model (the amplifier model) that tracks the emergence and evolution of multiple (pre-MDR, MDR and post-MDR) strains of drug-resistant Mycobacterium tuberculosis. We reconstruct possible evolutionary trajectories that generated hot zones over the past three decades, and identify the key causal factors. Results are consistent with recently reported World Health Organization (WHO) data. Our analyses yield three important insights. First, paradoxically we found that areas with programs that successfully reduced wild-type pansensitive strains often evolved into hot zones. Second, some hot zones emerged even when MDR strains were substantially less fit (and thus less transmissible) than wild-type pansensitive strains. Third, levels of MDR are driven by case-finding rates, cure rates and amplification probabilities. To effectively control MDRTB in the hot zones, it is essential that the WHO specify a goal for minimizing the amplification probability.