Challenge model for Helicobacter pylori infection in human volunteers
Challenge model for Helicobacter pylori infection in human volunteers
复制标题
DOI：
10.1136/gut.2003.037499
复制
发表时间：
2004-09-01
期刊：
影响因子：
24.5
通讯作者：
Monath, TP
中科院分区：
文献类型：
--
作者：
Graham, DY;Opekun, AR;Monath, TP
背景：评估幽门螺杆菌疫苗候选物需要可靠的攻毒模型。
方法：使用从一名轻度胃炎患者身上获取的一种cag致病岛阴性、OipA阳性、对多种抗生素敏感的幽门螺杆菌菌株（贝勒菌株100）对志愿者进行攻毒。志愿者在睡前服用40毫克法莫替丁，并在次日早晨服用含10⁴ - 10¹⁰菌落形成单位（cfu）幽门螺杆菌的牛肉汤。通过碳 - 13尿素呼气试验（C - 13 - UBT）、培养和组织学检查确认感染。在攻毒后4周或12周给予根除治疗，并通过至少两次独立的尿素呼气试验以及培养和组织学检查确认根除情况。
结果：20名受试者（9名女性和11名男性；年龄23 - 33岁）接受了幽门螺杆菌攻毒。18人（90%）被感染。出现轻度至中度消化不良症状，在第9天至第12天达到高峰，然后缓解。一名受试者的呕吐物中含有的幽门螺杆菌每毫升超过10³个活菌。攻毒后两周，胃组织学检查显示典型的慢性幽门螺杆菌性胃炎，伴有强烈的急性和慢性炎症。幽门螺杆菌的密度（通过每活检组织的菌落形成单位评估）同样与攻毒剂量无关。未发现最小感染剂量。攻毒后两周，胃黏膜白细胞介素8水平增加了20多倍。
结论：攻毒可靠地导致了幽门螺杆菌感染。尽管缺乏cag致病岛，但感染与典型的幽门螺杆菌性胃炎相关，伴有胃黏膜中强烈的多形核细胞浸润和白细胞介素8的诱导。实验性幽门螺杆菌感染是评估疫苗候选物的可行方法之一。
Background: A reliable challenge model is needed to evaluate Helicobacter pylori vaccine candidates.Methods: A cag pathogenicity island negative, OipA positive, multiple antibiotic susceptible strain of H pylori obtained from an individual with mild gastritis (Baylor strain 100) was used to challenge volunteers. Volunteers received 40 mg of famotidine at bedtime and 10(4)-10(10) cfu of H pylori in beef broth the next morning. Infection was confirmed by C-13 urea breath test (C-13-UBT), culture, and histology. Eradication therapy was given four or 12 weeks post challenge and eradication was confirmed by at least two separate UBTs, as well as culture and histology.Results: Twenty subjects (nine women and 11 men; aged 23-33 years) received a H pylori challenge. Eighteen (90%) became infected. Mild to moderate dyspeptic symptoms occurred, peaked between days 9 and 12, and resolved. Vomitus from one subject contained >10(3) viable/ml H pylori. By two weeks post challenge gastric histology showed typical chronic H pylori gastritis with intense acute and chronic inflammation. The density of H pylori (as assessed by cfu/biopsy) was similarly independent of the challenge dose. A minimal infectious dose was not found. Gastric mucosal interleukin 8 levels increased more than 20-fold by two weeks after the challenge.Conclusion: Challenge reliably resulted in H pylori infection. Infection was associated with typical H pylori gastritis with intense polymorphonuclear cell infiltration and interleukin 8 induction in gastric mucosa, despite absence of the cag pathogenicity island. Experimental H pylori infection is one of the viable approaches to evaluate vaccine candidates.