Development of oseltamivir and zanamivir resistance in influenza A(H1N1)pdm09 virus, Denmark, 2014.

This study reveals the selection of antiviral resistance mutations in influenza A(H1N1)pdm09 virus in an immunocompromised patient during a 6-month period. The patient was treated with two courses of oseltamivir (5 days and 2 months, respectively), with the first course starting at symptom onset, and subsequently zanamivir (2 months and 10 days, respectively). Respiratory samples were investigated by Sanger and next generation sequencing (NGS) and, for NGS data, low-frequency-variant-detection analysis was performed. Neuraminidase-inhibition tests were conducted for samples isolated in Madin-Darby canine kidney cells. In a sample collected 15 days after the end of the first treatment with oseltamivir (Day 20 post-symptom onset), oseltamivir resistance was detected (mutation H275Y with 60.3% frequency by NGS). Day 149 when the patient had almost completed the second zanamivir treatment, mixes of the following resistance mutations were detected; H275Y(65.1%), I223R(9.2%), and E119G(89.6%), accompanied by additional mutations, showing a more complex viral population in the long-term treated patient. Two samples obtained on Day 151 from bronchoalveolar lavage (BAL) and nasopharyngeal swab, respectively, showed different mutation profiles, with a higher frequency of antiviral resistance mutations in BAL. The results emphasise the importance of timely antiviral resistance testing both for treatment of individual patients as well as for preventive measures to control the development...
Source: Euro Surveill - Category: Infectious Diseases Authors: Tags: Euro Surveill Source Type: research

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ConclusionThese results suggested that IFN-γ plays an important role in acute lung injury induced by severe influenza A(H1N1)pdm09 infection, and monoclonal antibodies against IFN-γ could be useful as a potential therapeutic remedy for future influenza pandemics.
Source: Journal of Microbiology, Immunology and Infection - Category: Microbiology Source Type: research
Current challenges: from the path of "original antigenic sin" towards the development of universal flu vaccines. Int Rev Immunol. 2019 Nov 09;:1-16 Authors: Biswas A, Chakrabarti AK, Dutta S Abstract Annual flu led by influenza viruses is contemplated to be one of the foremost global health challenges due to its rapid spread leading to the life-threatening epidemic or pandemic. An enormous number of people die due to flu and its associated intricacies every year. Annual vaccination is considered to be the gold standard strategy to protect the individual from acquiring infection and further de...
Source: International Reviews of Immunology - Category: Allergy & Immunology Tags: Int Rev Immunol Source Type: research
Tuberculosis (TB) has now surpassed HIV as the leading infectious cause of death, and treatment success rates are declining. Multidrug-resistant TB, extensively drug-resistant TB, and even totally drug-resistant TB threaten to further destabilize disease control efforts. The second wave in TB drug development, which includes the diarylquinoline, bedaquiline, and the nitroimidazoles delamanid and pretomanid, may offer options for simpler, shorter, and potentially all-oral regimens to treat drug-resistant TB. The “third wave” of TB drug development includes numerous promising compounds, including less toxic versi...
Source: Clinics in Chest Medicine - Category: Respiratory Medicine Authors: Source Type: research
Vancomycin-resistant enterococci are troublesome pathogens in clinical settings because of few treatment options. A VanA/VanM-type vancomycin-resistant Enterococcus faecium clinical isolate was identified in Japan. This strain, named AA708, harbored five plasmids, one of which migrated during agarose gel electrophoresis without S1 nuclease treatment, which is indicative of a linear topology. We named this plasmid pELF1. Whole genome sequencing (WGS) analysis of the AA708 strain revealed that the complete sequence of pELF1 was 143,316 bp long and harbored both the vanA and vanM gene clusters. Furthermore, mfold analysis and...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
AbstractThe aim was to develop a predictive model of infection by multidrug-resistant microorganisms (MDRO). A national, retrospective cohort study was carried out including all patients attended for an infectious disease in 54 Spanish Emergency Departments (ED), in whom a microbiological isolation was available from a culture obtained during their attention in the ED. A MDRO infection prediction model was created in a derivation cohort using backward logistic regression. Those variables significant atp 21 points). Findings were similar in the validation cohort. Several patient-specific factors were independently associate...
Source: European Journal of Clinical Microbiology and Infectious Diseases - Category: Microbiology Source Type: research
Based on discussions with various folk at scientific and industry conferences earlier this year, regarding whether or not our rejuvenation research, development, and advocacy community is challenging to approach and understand as an outsider, I recently put together an introductory document for entrepreneurs entitled How to Start a Biotech Company in the Longevity Industry (PDF). Given my experiences, it is primarily aimed at entrepreneurs with previous experience in other industries, who are now interested in helping to treat aging as a medical condition and there by greatly improve the human condition. The young...
Source: Fight Aging! - Category: Research Authors: Tags: Activism, Advocacy and Education Source Type: blogs
(CNN) — From climate change to superbugs, the World Health Organization has laid out 10 big threats to our global health in 2019. And unless these threats get addressed, millions of lives will be in jeopardy. Here’s a snapshot of 10 urgent health issues, according to the United Nations’ public health agency: Not vaccinating when you can One of the most controversial recent health topics in the US is now an international concern. “Vaccine hesitancy — the reluctance or refusal to vaccinate despite the availability of vaccines — threatens to reverse progress made in tackling vaccine-prevent...
Source: WBZ-TV - Breaking News, Weather and Sports for Boston, Worcester and New Hampshire - Category: Consumer Health News Authors: Tags: Health News CNN Local TV Source Type: news
This study reveals the selection of antiviral resistance mutations in influenza A(H1N1)pdm09 virus in an immunocompromised patient during a 6-month period. The patient was treated with two courses of oseltamivir (5 days and 2 months, respectively), with the first course starting at symptom onset, and subsequently zanamivir (2 months and 10 days, respectively). Respiratory samples were investigated by Sanger and next generation sequencing (NGS) and, for NGS data, low-frequency-variant-detection analysis was performed. Neuraminidase-inhibition tests were conducted for samples isolated in Madin-Darby canine kidney cells. In a...
Source: Eurosurveillance - Category: Infectious Diseases Source Type: research
In conclusion, the E119D NA mutation that could emerge in A(H1N1)pdm09 viruses during zanamivir therapy has a significant impact on viral fitness and such mutant is unlikely to be highly transmissible.
Source: Antiviral Therapy - Category: Virology Source Type: research
In this study, the viral fitness of the recombinant wild-type (WT), E119D and E119D/H275Y A(H1N1)pdm09 viruses was evaluated in vitro and in experimentally-infected C57BL/6 mice and guinea pigs. In replication kinetics experiments, viral titers obtained with the E119D and E119D/H275Y recombinants were up to 2- and 4-log lower compared to the WT virus in MDCK and ST6GalI-MDCK cells, respectively. Enzymatic studies revealed that the E119D mutation significantly decreased the surface NA activity. In experimentally-infected mice, a 50% mortality rate was recorded in the group infected with the WT recombinant virus whereas no m...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research
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