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Chinese Scientists Discover Drug Resistant Mutations in Severe Cases of H7N9 Infected Individuals

Recently, Chinese scientists published their research results on the Lancet. The study shows that H7N9 infected patients with severe outcomes have been identified antiviral resistance mutations. The project was initiated by the Shanghai Public Health Clinical Centre (SPHCC), China. Dr. HAO Pei from Pathogen Diagnostic Technology research and development Centre, Institut Pasteur of Shanghai, Chinese Academy of Sciences, is the first co-author and contributed to the data analysis using high-throughput sequencing.

They studied 14 patients with A/H7N9 disease admitted to SPHCC from April 4th to 20th, 2013. 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.

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, which needs to be closely monitored and considered in pandemic preparedness planning.

Prof. WEN Yumei, the Chief of Shanghai H7N9 Prevention and Control Group, confirmed that the use of antiviral treatment (neuraminidase inhibitors) is suitable to most patients. So that treatment is suggested once the patient is diagnosed, and detection of the viral load and resistance mutation in the gene locus is essential in the patient specimen, so as to improve the efficacy of the treatment. At the same time, scientists need to speed up new drug development.

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