Prolonged Influenza Virus Infection during Lymphocytopenia and Frequent Detection of Drug-Resistant Viruses
Prolonged Influenza Virus Infection during Lymphocytopenia and Frequent Detection of Drug-Resistant Viruses
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DOI：
10.1086/598684
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发表时间：
2009-05-15
影响因子：
6.4
通讯作者：
Kroes, Aloys C. M.
中科院分区：
文献类型：
--
作者：
Gooskens, Jairo;Jonges, Marcel;Kroes, Aloys C. M.
导致人类流感病毒长期呼吸道感染、决定其临床影响和耐药病毒发展的因素尚不清楚。在 3 年期间，在 8 名免疫功能低下患者中观察到症状性流感病毒排泄时间≥ 2 周，并发现与发病时淋巴细胞减少症（8 名患者中的 8 名）的相关性高于粒细胞减少症（8 名患者中的 2 名）或单核细胞减少症（8 名患者中的 2 名）。 8 名患者中有 6 名 (75%) 出现流感下呼吸道感染（10 次发作），接受奥司他韦治疗与临床改善显着相关（8 次发作中的 8 次对比 2 次未治疗发作中的 0 次；P = .02）。病毒完全清除与淋巴细胞重建密切相关 (P = .04)，但在奥司他韦治疗后的前 2 周内从未观察到。符合耐药性分析条件的 3 名患者中，有 2 名 (67%) 出现了神经氨酸酶抑制剂耐药性流感病毒。总之，流感病毒长期感染与淋巴细胞减少、流感下呼吸道感染以及抗病毒治疗期间频繁产生耐药性有关。在奥司他韦治疗期间观察到流感下呼吸道感染的临床改善，但病毒的完全清除取决于淋巴细胞的重建，无论是否接受抗病毒药物。
The factors that cause prolonged human influenza virus respiratory tract infection and determine its clinical impact and the development of drug-resistant viruses are unclear. During a 3-year period, symptomatic influenza virus excretion for >= 2 weeks was observed among 8 immunocompromised patients and found to be associated with lymphocytopenia at onset (8 of 8 patients) more often than with granulocytopenia (2 of 8 patients) or monocytopenia (2 of 8 patients). Six (75%) of 8 patients developed influenza lower respiratory tract infection (10 episodes), and receipt of oseltamivir treatment was significantly associated with clinical improvement (8 of 8 episodes vs. 0 of 2 untreated episodes; P = .02). Complete viral clearance was strongly correlated with lymphocyte reconstitution (P = .04) but was never observed during the first 2 weeks after oseltamivir treatment. Neuraminidase inhibitor-resistant influenza viruses emerged in 2 (67%) of 3 patients eligible for resistance analysis. In conclusion, prolonged influenza virus infection was associated with lymphocytopenia, influenza lower respiratory tract infection, and frequent development of drug resistance during antiviral therapy. Clinical improvement in influenza lower respiratory tract infection is observed during oseltamivir treatment, but complete viral clearance is dependent on lymphocyte reconstitution, irrespective of receipt of antiviral medication.