Dubois A, Berg D E, Fiala N, Heman-Ackah L M, Perez-Perez G I, Blaser M J
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA.
J Gastroenterol. 1998 Feb;33(1):18-22. doi: 10.1007/pl00009961.
Rhesus monkeys raised in colonies tend to become naturally infected by Helicobacter pylori early in life. Earlier attempts to cure H. pylori infection with a 10-day triple therapy (metronidazole, amoxicillin, and peptobismol) were only partially (60%) successful, probably because of preexisting metronidazole resistance. This study was carried out to determine the efficacy of an alternative clarithromycin-omeprazole-based therapy for curing H. pylori infection in Rhesus monkeys (Macaca mulatta), and to examine histologic and serologic correlates of curing. Five monkeys were endoscoped under ketamine anesthesia. Histology and culture of gastric biopsies and serologic tests demonstrated that they were H. pylori-positive. Two animals had not received prior anti-H. pylori treatment, while three other animals had failed triple therapy and carried metronidazole-resistant H. pylori strains. Quadruple therapy with omeprazole, clarithromycin, amoxicillin, and bismuth subsalicylate was given for 10 days to these five animals. All five animals were cured of the infection, and remained H. pylori-free, based on histology and culture at regular intervals for the 5 months posttherapy during which they were followed. Gastritis scores and anti-H. pylori IgG levels decreased in each animal during this period to levels characteristic of uninfected animals. These results indicate that an omeprazole-clarithromycin-based regimen can cure H. pylori infection in Rhesus monkeys, with resolution of abnormal histology and serologic responses. They suggest that this preclinical animal model is useful for testing new anti-H. pylori therapies.
群居饲养的恒河猴在幼年时往往会自然感染幽门螺杆菌。早期尝试用为期10天的三联疗法(甲硝唑、阿莫西林和胃必治)治疗幽门螺杆菌感染,仅取得了部分(60%)成功,这可能是由于预先存在甲硝唑耐药性。本研究旨在确定一种基于克拉霉素 - 奥美拉唑的替代疗法治疗恒河猴(猕猴)幽门螺杆菌感染的疗效,并检查治愈的组织学和血清学相关性。五只猴子在氯胺酮麻醉下接受了内镜检查。胃活检的组织学和培养以及血清学检测表明它们幽门螺杆菌呈阳性。两只动物此前未接受过抗幽门螺杆菌治疗,而另外三只动物三联疗法失败且携带耐甲硝唑的幽门螺杆菌菌株。对这五只动物给予奥美拉唑、克拉霉素、阿莫西林和次水杨酸铋的四联疗法,为期10天。在治疗后的5个月随访期间,定期进行组织学和培养检查,结果显示所有五只动物的感染均被治愈,且未再感染幽门螺杆菌。在此期间,每只动物的胃炎评分和抗幽门螺杆菌IgG水平均降至未感染动物的特征水平。这些结果表明,基于奥美拉唑 - 克拉霉素的治疗方案可以治愈恒河猴的幽门螺杆菌感染,并使异常的组织学和血清学反应恢复正常。它们表明这种临床前动物模型可用于测试新的抗幽门螺杆菌疗法。