Prolonged Influenza Virus Shedding and Emergence of Antiviral Resistance in Immunocompromised Patients and Ferrets

被引：88

作者：

van der Vries, Erhard ^{[1
]}

Stittelaar, Koert J. ^{[2
]}

van Amerongen, Geert ^{[2
]}

Kroeze, Edwin J. B. Veldhuis ^{[2
]}

de Waal, Leon ^{[2
]}

Fraaij, Pieter L. A. ^{[1
,3
]}

Meesters, Roland J. ^{[4
]}

Luider, Theo M. ^{[4
]}

van der Nagel, Bart ^{[5
]}

Koch, Birgit ^{[5
]}

Vulto, Arnold G. ^{[5
]}

Schutten, Martin ^{[1
]}

Osterhaus, Albert D. M. E. ^{[1
,2
]}

机构：

[1] ErasmusMC, Dept Virol, Rotterdam, Netherlands

[2] Viroclin Biosci BV, Rotterdam, Netherlands

[3] ErasmusMC Sophia, Dept Paediat, Rotterdam, Netherlands

[4] ErasmusMC, Dept Neurol, Rotterdam, Netherlands

[5] ErasmusMC, Dept Hosp Pharm, Rotterdam, Netherlands

来源：

PLOS PATHOGENS | 2013年 / 9卷 / 05期

关键词：

ORGAN TRANSPLANT RECIPIENTS; A H1N1 VIRUS; STEM-CELL TRANSPLANTATION; OSELTAMIVIR-RESISTANT; NEURAMINIDASE INHIBITORS; UNITED-STATES; INTRAVENOUS ZANAMIVIR; MEDICAL PROGRESS; SINGLE-CENTER; ILL PATIENTS;

D O I：

10.1371/journal.ppat.1003343

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Immunocompromised individuals tend to suffer from influenza longer with more serious complications than otherwise healthy patients. Little is known about the impact of prolonged infection and the efficacy of antiviral therapy in these patients. Among all 189 influenza A virus infected immunocompromised patients admitted to ErasmusMC, 71 were hospitalized, since the start of the 2009 H1N1 pandemic. We identified 11 (15%) cases with prolonged 2009 pandemic virus replication (longer than 14 days), despite antiviral therapy. In 5 out of these 11 (45%) cases oseltamivir resistant H275Y viruses emerged. Given the inherent difficulties in studying antiviral efficacy in immunocompromised patients, we have infected immunocompromised ferrets with either wild-type, or oseltamivir-resistant (H275Y) 2009 pandemic virus. All ferrets showed prolonged virus shedding. In wild-type virus infected animals treated with oseltamivir, H275Y resistant variants emerged within a week after infection. Unexpectedly, oseltamivir therapy still proved to be partially protective in animals infected with resistant virus. Immunocompromised ferrets offer an attractive alternative to study efficacy of novel antiviral therapies.

引用

页数：11

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