Modeling the role of bacteriophage in the control of cholera outbreaks
Modeling the role of bacteriophage in the control of cholera outbreaks
复制标题
DOI：
10.1073/pnas.0600166103
复制
发表时间：
2006-03-21
影响因子：
11.1
通讯作者：
Levin, BR
中科院分区：
文献类型：
--
作者：
Jensen, MA;Faruque, SM;Levin, BR
霍乱是一种水媒传染病，继续困扰着发展中国家。个体通过饮用来自被霍乱弧菌的毒性菌株污染的水库的水而被感染。对孟加拉国达卡霍乱暴发的流行病学和环境观察表明，霍乱弧菌特异性裂解噬菌体可能通过杀死水库和受感染个体中存在的细菌来限制霍乱暴发的严重程度。为了量化这一想法并产生可检验的假设，我们分析了一个数学模型，该模型将霍乱的流行病学与细菌和噬菌体的种群动力学相结合。在生物学上合理的条件下，我们发现噬菌体可以减轻霍乱疫情。如果噬菌体捕食在爆发前限制了细菌密度，那么噬菌体密度的短暂减少可以破坏这种限制，随后的细菌生长可以引发霍乱爆发。爆发的严重程度取决于宿主中剩余噬菌体的密度。如果爆发是由细菌密度上升引发的，噬菌体的引入可以降低爆发的严重程度并促进其下降。在这两种情况下，噬菌体效应的大小主要取决于弧菌生长和噬菌体死亡率;比率越低，效应越大。我们的分析还表明，环境水库中的细菌是高度传染性的，或者大多数受害者摄入了被环境水污染的食物或饮用水中的细菌，这些食物或饮用水携带很少的可行的霍乱弧菌。我们的理论结果作出了一些经验检验的预测。
Cholera is a waterborne diarrheal disease that continues to plague the developing world. individuals become infected by consuming water from reservoirs contaminated by virulent strains of the bacterium Vibrio cholerae. Epidemiological and environmental observations of a cholera outbreak in Dhaka, Bangladesh, suggest that lytic bacteriophage specific for V. cholerae may limit the severity of cholera outbreaks by killing bacteria present in the reservoir and in infected individuals. To quantify this idea and generate testable hypotheses, we analyzed a mathematical model that combines the epidemiology of cholera with the population dynamics of the bacteria and phage. Under biologically reasonable conditions, we found that vibriophage can ameliorate cholera outbreaks. If phage predation limits bacterial density before an outbreak, a transient reduction in phage density can disrupt that limitation, and subsequent bacterial growth can initiate a cholera outbreak. The severity of the outbreak depends on the density of phage remaining in the reservoir. If the outbreak is initiated instead by a rise in bacterial density, the introduction of phage can reduce the severity of the outbreak and promote its decline. In both situations, the magnitude of the phage effect depends mainly on vibrio growth and phage mortality rates; the lower the rates, the greater the effect. Our analysis also suggests that either bacteria in the environmental reservoir are hyperinfectious or most victims ingest bacteria amplified in food or drinking water contaminated by environmental water carrying few viable V. cholerae. Our theoretical results make a number of empirically testable predictions.