Successful Treatment of Parainfluenza Virus Respiratory Tract Infection With DAS181 in 4 Immunocompromised Children.
Successful Treatment of Parainfluenza Virus Respiratory Tract Infection With DAS181 in 4 Immunocompromised Children.
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DOI：
10.1093/jpids/piu039
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发表时间：
2015-06
影响因子：
3.2
通讯作者：
Englund JA
中科院分区：
文献类型：
--
作者：
Waghmare A;Wagner T;Andrews R;Smith S;Kuypers J;Boeckh M;Moss R;Englund JA
副流感病毒（PIV）是一种常见的儿科病原体，与免疫功能低下（IC）宿主的显著发病率相关。DAS 181是一种新型唾液酸酶融合蛋白抑制剂，似乎在体外和体内均可有效对抗PIV;尚未评价其在IC儿童中的使用。使用定量逆转录聚合酶链反应诊断患者PIV感染。DAS 181是在紧急研究新药申请中获得的，通过气雾剂室或雾化器给药。每天评估患者的临床状况和不良结局。确定了4例在呼吸道标本中检出PIV的儿童造血细胞移植（HCT）患者，并使用DAS 181进行治疗。患者1和2分别在同种异体移植后9个月和2天通过支气管肺泡灌洗诊断为PIV下呼吸道感染（LRTI）。在鼻拭子PIV诊断时，患者3在计划的自体HCT之前接受化疗。患者4在HCT后2天通过鼻洗液诊断为PIV。患者1-3具有与LRTI一致的临床症状和胸部影像学。吸入DAS 181给药5-10天。所有4例患者均耐受治疗。在治疗开始时需要吸氧的所有患者中观察到需氧量和呼吸频率的临床改善。所有患者的病毒载量在治疗1周内下降，并且在患者3的治疗第3天变得不可检测。DAS 181用于治疗4例患有PIV疾病的严重IC儿科患者。药物耐受性良好。在所有病例中均观察到治疗开始后病毒载量和症状的改善。本报告支持在PIV感染的IC患者中进行的前瞻性随机研究。
Parainfluenza virus (PIV), a common pediatric pathogen, is associated with significant morbidity in immunocompromised (IC) hosts. DAS181, a novel sialidase fusion protein inhibitor, seems to be effective against PIV in vitro and in vivo; its use in IC children has not been evaluated. Patients were diagnosed with PIV infection using a quantitative reverse transcription-polymerase chain reaction. DAS181 was obtained under emergency investigational new drug applications and was administered via aerosol chamber or nebulizer. Patients were assessed daily for their clinical condition and adverse outcomes. Four pediatric hematopoietic cell transplantation (HCT) patients with PIV detected in respiratory specimens were identified and treated with DAS 181. Patients 1 and 2 were diagnosed with PIV lower respiratory tract infection (LRTI) by bronchoalveolar lavage at 9 months and 2 days after allogeneic transplantation, respectively. Patient 3 was on chemotherapy prior to planned autologous HCT at time of PIV diagnosis from a nasal swab. Patient 4 was diagnosed with PIV via nasal wash 2 days after HCT. Patients 1–3 had clinical symptoms and chest imaging consistent with LRTI. Inhaled DAS181 was administered for 5–10 days. All 4 patients tolerated therapy well. Clinical improvement in oxygen requirement and respiratory rate was observed in all patients who required oxygen at therapy initiation. Viral load decreased in all patients within 1 week of therapy and became undetectable by day 3 of therapy in patient 3. DAS181 was used to treat 4 severely IC pediatric patients with PIV disease. The drug was well tolerated. Improvement in both viral loads and symptoms after initiation of therapy was observed in all cases. This report supports prospective, randomized studies in IC patients with PIV infection.