Lee Sangun, Harwood Melanie, Girouard Don, Meyers Marvin J, Campbell Mary A, Beamer Gillian, Tzipori Saul
Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts, United States of America.
Center for World Health and Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, United States of America.
PLoS One. 2017 Oct 3;12(10):e0185906. doi: 10.1371/journal.pone.0185906. eCollection 2017.
Recent reports highlighting the global significance of cryptosporidiosis among children, have renewed efforts to develop control measures. We have optimized the gnotobiotic piglet model of acute diarrhea to evaluate azithromycin (AZR), nitazoxanide (NTZ), or treatment with both against Cryptosporidium hominis, the species responsible for most human cases. Piglets, animals reproducibly clinically susceptible to C. hominis, when inoculated with 106 oocysts, developed acute diarrhea with oocyst excretion in feces within 3 days. Ten day-treatment with recommended doses for children, commencing at onset of diarrhea, showed that treatment with AZR or NTZ relieved symptoms early in the treatment compared with untreated animals. Piglets treated with AZR exhibited no reduction of oocyst excretion whereas treatment with NTZ significantly reduced oocyst shedding early, increasing however after 5 days. While treatment with AZR+NTZ led to considerable symptomatic improvement, it had a modest effect on reducing mucosal injury, and did not completely eliminate oocyst excretion. Doubling the dose of AZR and/or NTZ did not improve the clinical outcome, confirming clinical observations that NTZ is only partially effective in reducing duration of diarrhea in children. This investigation confirms the gnotobiotic piglet as a useful tool for drug evaluation for the treatment of cryptosporidiosis in children.
近期报告强调了隐孢子虫病在全球儿童中的重要性，这促使人们重新努力制定控制措施。我们优化了急性腹泻无菌仔猪模型，以评估阿奇霉素（AZR）、硝唑尼特（NTZ）或两者联合使用对人隐孢子虫的治疗效果，人隐孢子虫是导致大多数人类病例的病原体。仔猪是对人隐孢子虫具有临床易感性的动物，接种106个卵囊后，3天内出现急性腹泻并伴有粪便中卵囊排出。从腹泻开始时起，用儿童推荐剂量进行为期10天的治疗，结果显示，与未治疗的动物相比，使用AZR或NTZ治疗可在治疗早期缓解症状。用AZR治疗的仔猪卵囊排出量没有减少，而用NTZ治疗可在早期显著减少卵囊排出，但在5天后又有所增加。虽然AZR+NTZ联合治疗可显著改善症状，但对减轻黏膜损伤的作用不大，也不能完全消除卵囊排出。将AZR和/或NTZ的剂量加倍并没有改善临床疗效，这证实了临床观察结果，即NTZ在缩短儿童腹泻持续时间方面仅部分有效。这项研究证实了无菌仔猪是评估治疗儿童隐孢子虫病药物的有用工具。
