Investigation of the role of typhoid toxin in acute typhoid fever in a human challenge model
Investigation of the role of typhoid toxin in acute typhoid fever in a human challenge model
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DOI：
10.1038/s41591-019-0505-4
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发表时间：
2019-07-01
期刊：
影响因子：
82.9
通讯作者：
Pollard, Andrew J.
中科院分区：
文献类型：
--
作者：
Gibani, Malick M.;Jones, Elizabeth;Pollard, Andrew J.
伤寒沙门氏菌是一种人类宿主限制性病原体，每年约有1090万人患伤寒（1）。伤寒毒素被认为在疾病发病机制、慢性感染的建立和人类宿主限制中发挥核心作用（2-6）。然而，它在人类伤寒症中的确切作用尚未完全确定。我们采用随机、双盲的S。伤寒人类攻毒模型（7）。将40名健康志愿者随机（1：1）口服10（4）个菌落形成单位的野生型或同基因伤寒毒素缺失突变株（TN）。伤寒我们观察到伤寒感染率无显著差异（发热≥ 38 ℃ ≥ 12小时和/或S.伤寒菌血症）之间的参与者挑战野生型或TN S。伤寒（15/21（71%）vs 15/19（79%）; P = 0.58）。与野生型相比，用TN菌株激发的参与者的菌血症持续时间显著更长（47.6小时（28.9-97.0）对30.3小时（3.6-49.4）; P
Salmonella Typhi is a human host-restricted pathogen that is responsible for typhoid fever in approximately 10.9 million people annually(1). The typhoid toxin is postulated to have a central role in disease pathogenesis, the establishment of chronic infection and human host restriction(2-6). However, its precise role in typhoid disease in humans is not fully defined. We studied the role of typhoid toxin in acute infection using a randomized, double-blind S. Typhi human challenge model(7). Forty healthy volunteers were randomized (1:1) to oral challenge with 10(4) colony-forming units of wild-type or an isogenic typhoid toxin deletion mutant (TN) of S. Typhi. We observed no significant difference in the rate of typhoid infection (fever >= 38 degrees C for >= 12 h and/or S. Typhi bacteremia) between participants challenged with wild-type or TN S. Typhi (15 out of 21 (71%) versus 15 out of 19 (79%); P = 0.58). The duration of bacteremia was significantly longer in participants challenged with the TN strain compared with wild-type (47.6 hours (28.9-97.0) versus 30.3(3.6-49.4); P