دانلود رایگان مقاله آنالیز ژنوتیپ و فنوتیپ ویروس آنفولانزای ایزوله شده

عنوان فارسی
آنالیز ژنوتیپ و فنوتیپ ویروس های آنفولانزا ایزوله شده از بزرگسالان طی فاز دوم مطالعات زانامیویر داخل وریدی در افراد بستری
عنوان انگلیسی
Phenotypic and genotypic analysis of influenza viruses isolated from adult subjects during a phase II study of intravenous zanamivir in hospitalised subjects
صفحات مقاله فارسی
0
صفحات مقاله انگلیسی
9
سال انتشار
2016
نشریه
الزویر - Elsevier
فرمت مقاله انگلیسی
PDF
کد محصول
E1095
رشته های مرتبط با این مقاله
پزشکی
گرایش های مرتبط با این مقاله
ویروس شناسی پزشکی
مجله
تحقیقات ضد ویروس - Antiviral Research
دانشگاه
گلاکسو، استیونج، بریتانیا
کلمات کلیدی
آنفلوانزا، زانامیویر داخل وریدی، حساسیت ضد ویروس
۰.۰ (بدون امتیاز)
امتیاز دهید
چکیده

Abstract


Intravenous zanamivir (IVZ) is a neuraminidase (NA) inhibitor (NAI) under investigation for the treatment of subjects hospitalised with influenza. The study included 130 symptomatic, hospitalised adults with influenza. Subjects received IVZ for 5e10 days. Viruses were cultured and analysed for susceptibility to zanamivir. Mean IC50s (n ¼ 50) (±SD) for influenza A/H1N1pdm09, A/H3N2 and influenza B were 0.20 ± 0.06, 0.26 ± 0.07 and 1.61 ± 0.35 nM, respectively, and are comparable to data observed for sensitive isolates. A total of 185 NA and 180 haemagglutinin (HA) sequences were obtained from 123 subjects; the majority did not contain resistance substitutions. Four influenza A/H1N1pdm09 viruses from four subjects harboured NA resistance substitutions: three, Y155H, D199G and S247N, were present at Day 1 before IVZ exposure and the fourth, E119D/E, was detected at Post Treatment þ5 Days but was not present at 5 other timepoints. Five subjects harboured virus with treatment-emergent NA substitutions not associated with resistance; N63D, V83A, W190C, M269K (A/H1N1pdm09) and R210K (A/H3N2). Viruses from fifteen subjects harboured HA resistance substitutions, (A/H1N1pdm09) one emerged during treatment: S162N (Day 5). Five viruses harboured treatment-emergent HA substitutions (A/ H1N1pdm09) not associated with resistance: E81K, V108L, S164D, D168N and S185N. 10/92 subjects with A/H1N1pdm09 harboured a D222 HA substitution, which has been associated with increased virulence. The emergent substitutions are not associated with resistance but may have arisen due to selection pressure during IVZ treatment or by chance. In this study, there was evidence for resistance selection in a post treatment sample but the resistant variant did not persist in later visit samples.

نتیجه گیری

4.5. Summary


Development of resistance is a key factor in reducing the efficacy of antivirals and is of particular concern during treatment of immunocompromised patients. In this study, a significant number of subjects were immunocompromised and there was evidence for resistance selection in a post treatment sample but the resistant variant did not persist in later visit samples. IVZ may be considered as a treatment option for hospitalised patients with influenza particularly when oseltamivir resistant virus is present or suspected.


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