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Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance

Identifieur interne : 001B54 ( PascalFrancis/Curation ); précédent : 001B53; suivant : 001B55

Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance

Auteurs : YUNWEN HU [République populaire de Chine] ; SHUIHUA LU [République populaire de Chine] ; ZHIGANG SONG [République populaire de Chine] ; WEI WANG [République populaire de Chine] ; PEI HAO [République populaire de Chine] ; JIANHUA LI [République populaire de Chine] ; XIAONAN ZHANG [République populaire de Chine] ; Hui-Ling Yen [Hong Kong] ; BISHENG SHI [République populaire de Chine] ; TAO LI [République populaire de Chine] ; WENCAI GUAN [République populaire de Chine] ; LEI XU [République populaire de Chine] ; YI LIU [République populaire de Chine] ; SEN WANG [République populaire de Chine] ; XIAOLING ZHANG [République populaire de Chine] ; DI TIAN [République populaire de Chine] ; ZHAOQIN ZHU [République populaire de Chine] ; JING HE [République populaire de Chine] ; KAI HUANG [République populaire de Chine] ; HUIJIE CHEN [République populaire de Chine] ; LULU ZHENG [République populaire de Chine] ; XUAN LI [République populaire de Chine] ; JIE PING [République populaire de Chine] ; BIN KANG [République populaire de Chine] ; XIUHONG XI [République populaire de Chine] ; LIJUN ZHA [République populaire de Chine] ; YIXUE LI [République populaire de Chine] ; ZHIYONG ZHANG [République populaire de Chine] ; Malik Peiris [Hong Kong] ; ZHENGHONG YUAN [République populaire de Chine]

Source :

RBID : Pascal:13-0220415

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English descriptors

Abstract

Background On March 30, a novel influenza A subtype H7N9 virus (A/H7N9) was detected in patients with severe respiratory disease in eastern China. Virological factors associated with a poor clinical outcome for this virus remain unclear. We quantified the viral load and analysed antiviral resistance mutations in specimens from patients with A/H7N9. Methods We studied 14 patients with A/H7N9 disease admitted to the Shanghai Public Health Clinical Centre (SPHCC), China, between April 4, and April 20, 2013, who were given antiviral treatment (oseltamivir or peramivir) for less than 2 days before admission. We investigated the viral load in throat, stool, serum, and urine specimens obtained sequentially from these patients. We also sequenced viral RNA from these specimens to study the mutations associated with resistance to neuraminidase inhibitors and their association with disease outcome. Findings All patients developed pneumonia, seven of them required mechanical ventilation, and three of them further deteriorated to become dependent on extracorporeal membrane oxygenation (ECMO), two of whom died. Antiviral treatment was associated with a reduction of viral load in throat swab specimens in 11 surviving patients. Three patients with persistently high viral load in the throat in spite of antiviral therapy became ECMO dependent. An Arg292Lys mutation in the virus neuraminidase (NA) gene known to confer resistance to both zanamivir and oseltamivir was identified in two of these patients, both also received corticosteroid treatment. In one of them, wild-type sequence Arg292 was noted 2 days after start of antiviral treatment, and the resistant mutant Lys292 dominated 9 days after start of treatment. Interpretation Reduction of viral load following antiviral treatment correlated with improved outcome. Emergence of NA Arg292Lys mutation in two patients who also received corticosteroid treatment led to treatment failure and a poor clinical outcome. The emergence of antiviral resistance in A/H7N9 viruses, especially in patients receiving corticosteroid therapy, is concerning, needs to be closely monitored, and considered in pandemic preparedness planning. Funding National Megaprojects of China for Infectious Diseases, Shanghai Municipal Health and Family Planning Commission, the National Key Basic Research Program of China, Ministry of Science and Technology, and National Natural Science Foundation of China.
pA  
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Pascal:13-0220415

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<title xml:lang="en" level="a">Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance</title>
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<name sortKey="Yunwen Hu" sort="Yunwen Hu" uniqKey="Yunwen Hu" last="Yunwen Hu">YUNWEN HU</name>
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<name sortKey="Xiuhong Xi" sort="Xiuhong Xi" uniqKey="Xiuhong Xi" last="Xiuhong Xi">XIUHONG XI</name>
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<s1>Department of Infectious Diseases, Shanghai Public Health Clinical Center</s1>
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<name sortKey="Zhiyong Zhang" sort="Zhiyong Zhang" uniqKey="Zhiyong Zhang" last="Zhiyong Zhang">ZHIYONG ZHANG</name>
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<s1>State Key Laboratory of Emerging Infectious Disease, School of Public Health, University of Hong Kong</s1>
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<name sortKey="Zhenghong Yuan" sort="Zhenghong Yuan" uniqKey="Zhenghong Yuan" last="Zhenghong Yuan">ZHENGHONG YUAN</name>
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<term>Influenza A virus</term>
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<div type="abstract" xml:lang="en">Background On March 30, a novel influenza A subtype H7N9 virus (A/H7N9) was detected in patients with severe respiratory disease in eastern China. Virological factors associated with a poor clinical outcome for this virus remain unclear. We quantified the viral load and analysed antiviral resistance mutations in specimens from patients with A/H7N9. Methods We studied 14 patients with A/H7N9 disease admitted to the Shanghai Public Health Clinical Centre (SPHCC), China, between April 4, and April 20, 2013, who were given antiviral treatment (oseltamivir or peramivir) for less than 2 days before admission. We investigated the viral load in throat, stool, serum, and urine specimens obtained sequentially from these patients. We also sequenced viral RNA from these specimens to study the mutations associated with resistance to neuraminidase inhibitors and their association with disease outcome. Findings All patients developed pneumonia, seven of them required mechanical ventilation, and three of them further deteriorated to become dependent on extracorporeal membrane oxygenation (ECMO), two of whom died. Antiviral treatment was associated with a reduction of viral load in throat swab specimens in 11 surviving patients. Three patients with persistently high viral load in the throat in spite of antiviral therapy became ECMO dependent. An Arg292Lys mutation in the virus neuraminidase (NA) gene known to confer resistance to both zanamivir and oseltamivir was identified in two of these patients, both also received corticosteroid treatment. In one of them, wild-type sequence Arg292 was noted 2 days after start of antiviral treatment, and the resistant mutant Lys292 dominated 9 days after start of treatment. Interpretation Reduction of viral load following antiviral treatment correlated with improved outcome. Emergence of NA Arg292Lys mutation in two patients who also received corticosteroid treatment led to treatment failure and a poor clinical outcome. The emergence of antiviral resistance in A/H7N9 viruses, especially in patients receiving corticosteroid therapy, is concerning, needs to be closely monitored, and considered in pandemic preparedness planning. Funding National Megaprojects of China for Infectious Diseases, Shanghai Municipal Health and Family Planning Commission, the National Key Basic Research Program of China, Ministry of Science and Technology, and National Natural Science Foundation of China.</div>
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<s0>Background On March 30, a novel influenza A subtype H7N9 virus (A/H7N9) was detected in patients with severe respiratory disease in eastern China. Virological factors associated with a poor clinical outcome for this virus remain unclear. We quantified the viral load and analysed antiviral resistance mutations in specimens from patients with A/H7N9. Methods We studied 14 patients with A/H7N9 disease admitted to the Shanghai Public Health Clinical Centre (SPHCC), China, between April 4, and April 20, 2013, who were given antiviral treatment (oseltamivir or peramivir) for less than 2 days before admission. We investigated the viral load in throat, stool, serum, and urine specimens obtained sequentially from these patients. We also sequenced viral RNA from these specimens to study the mutations associated with resistance to neuraminidase inhibitors and their association with disease outcome. Findings All patients developed pneumonia, seven of them required mechanical ventilation, and three of them further deteriorated to become dependent on extracorporeal membrane oxygenation (ECMO), two of whom died. Antiviral treatment was associated with a reduction of viral load in throat swab specimens in 11 surviving patients. Three patients with persistently high viral load in the throat in spite of antiviral therapy became ECMO dependent. An Arg292Lys mutation in the virus neuraminidase (NA) gene known to confer resistance to both zanamivir and oseltamivir was identified in two of these patients, both also received corticosteroid treatment. In one of them, wild-type sequence Arg292 was noted 2 days after start of antiviral treatment, and the resistant mutant Lys292 dominated 9 days after start of treatment. Interpretation Reduction of viral load following antiviral treatment correlated with improved outcome. Emergence of NA Arg292Lys mutation in two patients who also received corticosteroid treatment led to treatment failure and a poor clinical outcome. The emergence of antiviral resistance in A/H7N9 viruses, especially in patients receiving corticosteroid therapy, is concerning, needs to be closely monitored, and considered in pandemic preparedness planning. Funding National Megaprojects of China for Infectious Diseases, Shanghai Municipal Health and Family Planning Commission, the National Key Basic Research Program of China, Ministry of Science and Technology, and National Natural Science Foundation of China.</s0>
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<s2>NW</s2>
<s5>08</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA">
<s0>Influenza A virus</s0>
<s2>NW</s2>
<s5>08</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE">
<s0>Charge virale</s0>
<s5>09</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG">
<s0>Viral load</s0>
<s5>09</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA">
<s0>Carga vírica</s0>
<s5>09</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE">
<s0>Emergence</s0>
<s5>11</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG">
<s0>Emergence</s0>
<s5>11</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA">
<s0>Emergencia</s0>
<s5>11</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE">
<s0>Epidémiologie</s0>
<s5>12</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG">
<s0>Epidemiology</s0>
<s5>12</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA">
<s0>Epidemiología</s0>
<s5>12</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE">
<s0>Antiviral</s0>
<s5>17</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG">
<s0>Antiviral</s0>
<s5>17</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA">
<s0>Antiviral</s0>
<s5>17</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE">
<s0>Résistance</s0>
<s5>18</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG">
<s0>Resistance</s0>
<s5>18</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA">
<s0>Resistencia</s0>
<s5>18</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE">
<s0>Médecine</s0>
<s5>19</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG">
<s0>Medicine</s0>
<s5>19</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA">
<s0>Medicina</s0>
<s5>19</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE">
<s0>Influenzavirus A</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG">
<s0>Influenzavirus A</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA">
<s0>Influenzavirus A</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE">
<s0>Orthomyxoviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG">
<s0>Orthomyxoviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA">
<s0>Orthomyxoviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fN21>
<s1>203</s1>
</fN21>
<fN44 i1="01">
<s1>OTO</s1>
</fN44>
<fN82>
<s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
</record>

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