Altmann Sharon, Brandt Curtis R, Murphy Christopher J, Patnaikuni Ravi, Takla Teresa, Toomey Megan, Nesbit Brittany, McIntyre Kimberly, Covert Jill, Dubielzig Richard, Leatherberry Gary, Adkins Elizabeth, Kodihalli Shantha
Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, WI 53706, USA.
J Infect Dis. 2011 Mar 1;203(5):683-90. doi: 10.1093/infdis/jiq103. Epub 2011 Jan 28.
Vaccinia virus keratitis (VACVK) is a complication of smallpox vaccination that can result in blindness. There are no Food and Drug Administration-approved treatments for VACVK, and vaccinia immunoglobulin (VIG) is contraindicated in isolated VACVK. We used a rabbit model of infection to compare several therapeutic options for VACVK.
Rabbit eyes were infected with 10(5) plaque-forming units of the Dryvax strain of vaccinia virus and scored daily for 28 days using a modified MacDonald-Shadduck scoring system. Animals were treated for 10 days after the onset of keratitis with albumin, VIG, prednisolone acetate, trifluridine, or combinations thereof. Ocular viral titers and vaccinia-specific antibody titers were determined by plaque assay and enzyme-linked immunosorbent assay, respectively.
Treatment with intravenous VIG neither exacerbated nor ameliorated VACVK. Topical prednisolone acetate interfered with viral clearance, and ocular disease rebounded in prednisolone-treated groups. The most effective treatment was topical trifluridine alone.
We conclude that (1) VIG did not negatively affect the treatment of isolated keratitis, (2) topical corticosteroids should not be used for treating VACVK, and (3) treatment with topical trifluridine, with or without intravenous VIG, is the preferred therapeutic regimen for treating VACVK.
牛痘病毒性角膜炎(VACVK)是天花疫苗接种的一种并发症,可导致失明。目前尚无美国食品药品监督管理局批准的用于治疗VACVK的疗法,且在孤立性VACVK中禁忌使用牛痘免疫球蛋白(VIG)。我们使用感染兔模型比较了几种治疗VACVK的选择。
兔眼接种10⁵个空斑形成单位的痘苗病毒Dryvax株,使用改良的MacDonald-Shadduck评分系统每日评分,持续28天。角膜炎发作后,动物用白蛋白、VIG、醋酸泼尼松龙、三氟尿苷或其组合治疗10天。分别通过空斑试验和酶联免疫吸附试验测定眼内病毒滴度和牛痘特异性抗体滴度。
静脉注射VIG治疗既未加重也未改善VACVK。局部应用醋酸泼尼松龙干扰病毒清除,醋酸泼尼松龙治疗组的眼部疾病出现反弹。最有效的治疗方法是单独局部应用三氟尿苷。
我们得出以下结论:(1)VIG对孤立性角膜炎的治疗没有负面影响;(2)局部应用皮质类固醇不应用于治疗VACVK;(3)无论是否联合静脉注射VIG,局部应用三氟尿苷治疗是治疗VACVK的首选治疗方案。