Benefits of using multiple first-line therapies against malaria
Benefits of using multiple first-line therapies against malaria
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DOI：
10.1073/pnas.0804628105
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发表时间：
2008-09-16
影响因子：
11.1
通讯作者：
Laxminarayan, Ramanan
中科院分区：
文献类型：
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作者：
Boni, Maciej F.;Smith, David L.;Laxminarayan, Ramanan
尽管有许多治疗疟疾的药物和疗法，但许多国家的国家政策建议对大多数临床疟疾病例使用单一一线疗法。为了评估这是否是对整个人群的最佳策略，我们设计了疟疾的进化流行病学模型框架，并比较了抗性进化背景下不同治疗策略的益处。我们的结果表明，在人群范围内使用多种一线疗法（MFT）来对抗疟疾，比使用单一疗法或循环疗法（无论是按照固定的循环时间表还是在耐药水平或治疗失败过高时轮换疗法）产生更好的临床结果。 MFT 策略还可以延迟耐药菌株（表型）的出现并减缓其固定，并且它们允许更大比例的人群得到治疗，而无需牺牲未来对因高耐药水平而可能无法治疗的病例的治疗。早期的论文指出，与 MFT 策略相比，循环策略的缺点是创造的环境变化较小，从而使寄生虫更容易进化出耐药性。在这里，我们说明了寄生虫生态学的第二个特征，它损害了循环政策的表现，即循环政策比 MFT 政策更快地降低了寄生虫种群的平均适应度，从而使新的抗性类型更容易入侵和传播。使用多种一线疗法对抗疟疾的临床益处表明，MFT 政策应在疟疾消除和控制计划中发挥关键作用。
Despite the availability of many drugs and therapies to treat malaria, many countries' national policies recommend using a single first-line therapy for most clinical malaria cases. To assess whether this is the best strategy for the population as a whole, we designed an evolutionary-epidemiological modeling framework for malaria and compared the benefits of different treatment strategies in the context of resistance evolution. Our results show that the population-wide use of multiple first-line therapies (MFT) against malaria yields a better clinical outcome than using a single therapy or a cycling strategy where therapies are rotated, either on a fixed cycling schedule or when resistance levels or treatment failure become too high. MFT strategies also delay the emergence and slow the fixation of resistant strains (phenotypes), and they allow a larger fraction of the population to be treated without trading off future treatment of cases that may be untreatable because of high resistance levels. Earlier papers have noted that cycling strategies have the disadvantage of creating a less temporally variable environment than MFT strategies, making resistance evolution easier for the parasite. Here, we illustrate a second feature of parasite ecology that impairs the performance of cycling policies, namely, that cycling policies degrade the mean fitness of the parasite population more quickly than MFT policies, making it easier for new resistant types to invade and spread. The clinical benefits of using multiple first-line therapies against malaria suggest that MFT policies should play a key role in malaria elimination and control programs.