CDC

2018年,248例基本上淋巴腺鼠疫were reported around theworld从两个国家（马达加斯加和刚果民主共和国）的98％（Madagascar和民主共和国） - 十年来跌至90％，并且从大流行音乐中哭泣，将世界上的人口摧毁直到19岁以下^钍世纪。

So, why should one bother to conduct clinical trials of treatments for plague? Especially since they are so challenging that none has been completed successfully so far?

正是因为没有临床试验的硬证据 - 我们想要的强大测试为了感到自信，某种治疗是安全有效的 - 目前存在的任何药物和方案都存在于目前推荐和正在使用的任何药物。因为瘟疫没有消失。

A number of drugs are approved for use for plague by the United States Food and Drug Administration (FDA) based on the so-called ‘animal rule’, which applies to situations whereby human studies are not feasible and experimental data are used instead. Some of these drugs have long been in use, and physicians feel generally comfortable using them.

然而，存在几种不同的方案，有些具有显着的缺点。许多国家严重依赖于氨基糖苷类，如链霉素（自20世纪40年代后期以来使用）和庆大霉素，治疗瘟疫。虽然有效，氨基糖苷类对患者表现出高毒性，并且需要繁重的肾和听觉测试，其中许多低收入国家的卫生设施都没有能够进行。Streptomycinin particular has poor global availability and, coupled with high prices and administration via injection only, it is becoming less of a viable option in poorly resourced settings. Because of these safety concerns some countries use doxycycline, which is however bacteriostatic and only for oral intake, therefore not adapted for more severe forms of plague. Both aminoglycosides and tetracyclines are contraindicated in pregnancy.

存在的其他选项确实存在患者负担和卫生系统资源的负担。例如，环丙沙星为链霉素和庆大霉素显示出相同或优异的治疗效果非人类研究;它可以口服或通过注射施用，允许在临床适当时切换给药路线的能力;它不需要大量监测。

有一些试图测试方案临床上但是，现场条件（瘟疫主要发生在偏远农村地区）和内部骚乱已联系完成它们。还存在其他挑战：没有综合试验方法和商定的核心结果组，以评估治疗效果。

That’s why, in response to a growing need for more robust and comprehensive evidence supporting the effectiveness of all available treatment regimens, the University of Oxford, Institut Pasteur de Madagascar, Centre Hospitalier Universitaire Joseph Raseta Befelatanana and Centre d’Infectiologie Charles Mérieux, have teamed up to organize a randomized clinical trial in Madagascar in which patients will receive either the country’s first-line treatment (streptomycin followed by ciprofloxacin) or the third-line treatment (ciprofloxacin alone). The trial is titled “An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY)” and the protocol has recently been published.

由于全球瘟疫案例的分布现在主要在低收入国家，我们尤为重要的是，我们将证据基础扩展到更安全的方案，更容易遵守，可用于低资源健康环境。我们的目标是确定基于施用环丙沙星的方案，单独施用CiProfloxacin可以成为一线治疗并满足这种全球健康需求。但这种治疗在所有环境中也是有价值的。

我们不要忘记耶尔西尼亚瘟疫- 导致瘟疫的细菌 - 存在于世界各地的跳蚤和啮齿动物中，并且在包括美国和中国在内的高收入国家和低收入国家定期出现零星案件。

我们不要忘记耶尔西尼亚瘟疫– the bacterium causing plague – is present in fleas and rodents all over the world, and that sporadic cases occur regularly in high-, middle- and low-income countries alike, including theUSA和中国。在案例在更高的数量更加定期看出，瘟疫已经证明它仍然存在流行潜力：2017年，Madagascarreported an urban outbreak of pneumonic plague that resulted in 1878 cases across two of its primary urban areas. On the other hand, plague has the potential to arise in locations where it has not been reported in humans for years or even decades, as was the case inLibya直到2009年，没有检测到25年的瘟疫情况。最后，在2020年8月，California报告了第一个案例在5年内的血管瘟疫，赫尔德曼被困扰着中国，一个十几岁的男孩从泡瘟都死亡Mongolia。

Plague is a zoonotic disease of epidemic potential with an active reservoir in many countries, including advanced economies, and the ability to lay dormant for long periods of time. Contact between humans and wildlife is increasing, risking more frequent zoonotic spillover and more human cases. Before we reach the next plague epidemic and questions arise over which treatment option is best, we must test. And epidemic or not, we must obtain the evidence we need in order to improve care and improve outcomes for patients in all healthcare settings for a disease that has quite literally ‘plagued’ humanity for five millennia.