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https://www.readbyqxmd.com/read/29745939/antiviral-treatment-of-childhood-influenza-an-update
#1
Amaran Moodley, John S Bradley, David W Kimberlin
PURPOSE OF REVIEW: Influenza virus can cause severe or life-threatening infection in children. This review provides an update on antiviral medications available to treat and prevent influenza in both healthy children and children with underlying medical conditions, and recommendations on their appropriate use in the outpatient and inpatient settings. RECENT FINDINGS: Despite the significant morbidity and mortality associated with influenza infection, a large number of children hospitalized with influenza do not receive specific antiviral treatment with a neuraminidase inhibitor...
June 2018: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29674164/impact-of-r152k-and-r368k-neuraminidase-catalytic-substitutions-on-in-vitro-properties-and-virulence-of-recombinant-a-h1n1-pdm09-viruses
#2
Véronique Tu, Yacine Abed, Clément Fage, Mariana Baz, Guy Boivin
Neuraminidase (NA) mutations conferring resistance to NA inhibitors (NAIs) are expected to occur at framework or catalytic residues of the NA enzyme. Numerous clinical and in vitro reports already described NAI-resistant A(H1N1)pdm09 variants harboring various framework NA substitutions. By contrast, variants with NA catalytic changes remain poorly documented. Herein, we investigated the effect of R152K and R368K NA catalytic mutations on the NA enzyme properties, in vitro replicative capacity and virulence of A(H1N1)pdm09 recombinant viruses...
April 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29673121/trends-of-neuraminidase-inhibitors-use-in-children-with-influenza-related-respiratory-infections
#3
Kazuhiro Uda, Yusuke Okubo, Kensuke Shoji, Isao Miyairi, Naho Morisaki, Nobuaki Michihata, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga
BACKGROUND: Neuraminidase inhibitors are recommended for children hospitalized with influenza-related respiratory infections, and oseltamivir is the first choice of treatment in most situations. However, little is known regarding the recent trend in using neuraminidase inhibitors and their difference in health economy. The aim of this study was to reveal recent trends in neuraminidase inhibitor use and compare hospitalization costs across different treatment regimens. METHODS: We retrospectively obtained the hospital discharge records of inpatients under 18 years of age with a diagnosis of influenza-related respiratory infections using a national inpatient database in Japan...
April 19, 2018: Pediatric Pulmonology
https://www.readbyqxmd.com/read/29601892/susceptibility-of-brazilian-influenza-a-h1n1-pdm09-viruses-to-neuraminidase-inhibitors-in-the-2014-2016-seasons-identification-of-strains-bearing-mutations-associated-with-reduced-inhibition-profile
#4
Aline R Matos, Paola C Resende, Milene D Miranda, Cristiana C Garcia, Braulia C Caetano, Jonathan C O Lopes, Maria C Debur, Ana L F Cury, Lucas A Vianna, Magliones C Lima, Marcelo Schirmer, Larissa Gubareva, Aeron C Hurt, David W Brown, Marilda M Siqueira
Neuraminidase inhibitors (NAIs) are the main class of antivirals currently used for the treatment of influenza infections. As influenza viruses are constantly evolving, drug-resistance can emerge resulting in reduced effectiveness of treatment. This study evaluated the presence of molecular markers associated with NAI susceptibility in 724 influenza A(H1N1)pdm09 positive samples from Brazilian surveillance system from the 2014-2016 seasons, including 76 isolates tested for oseltamivir (OST) susceptibility and 23 isolates also tested for zanamivir, peramivir and laninamivir susceptibility...
March 27, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29574145/identification-of-indonesian-clade-2-1-highly-pathogenic-influenza-a-h5n1-viruses-with-n294s-and-s246n-neuraminidase-substitutions-which-further-reduce-oseltamivir-susceptibility
#5
Jennifer L McKimm-Breschkin, Susan Barrett, Frank Y K Wong, Pudjiatmoko, Muhammad Azhar, Paul Selleck, Kelly R Davies, Nining Hartaningsih, James McGrane
We have tested the in vitro susceptibility to the neuraminidase (NA) inhibitors of 96 highly pathogenic clade 2.1 A(H5N1) viruses from Indonesia, isolated between 2008 and 2011. HPAI virus samples obtained through the Influenza Virus Monitoring (IVM) surveillance program in Indonesia were tested for susceptibility to oseltamivir and zanamivir. The NAs of four viruses were identified as extreme outliers to oseltamivir, based on statistical analysis by box plots, with IC50 values ranging from 46-62 nM. The NAs of two of these viruses from Sumatra and Aceh, had an N294S substitution, while one virus from Sulawesi had an S246N NA substitution...
March 21, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29493493/an-i436n-substitution-confers-resistance-of-influenza-a-h1n1-pdm09-viruses-to-multiple-neuraminidase-inhibitors-without-affecting-viral-fitness
#6
Jin Jung Kwon, Won-Suk Choi, Ju Hwan Jeong, Eun-Ha Kim, Ok-Jun Lee, Sun-Woo Yoon, Jungwon Hwang, Richard J Webby, Elena A Govorkova, Young Ki Choi, Yun Hee Baek, Min-Suk Song
The resistance of influenza viruses to neuraminidase (NA) inhibitors (NAIs; i.e. oseltamivir, zanamivir, peramivir and laninamivir) can be associated with several NA substitutions, with differing effects on viral fitness. To identify novel molecular markers conferring multi-NAI resistance, the NA gene of oseltamivir-resistant (H275Y, N1 numbering) 2009 pandemic influenza [A(H1N1)pdm09] virus was enriched with random mutations. This randomly mutated viral library was propagated in Madin-Darby canine kidney (MDCK) cells under zanamivir pressure and gave rise to additional changes within NA, including an I436N substitution located outside the NA enzyme active site...
March 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29487035/clinical-effectiveness-of-four-neuraminidase-inhibitors-oseltamivir-zanamivir-laninamivir-and-peramivir-for-children-with-influenza-a-and-b-in-the-2014-2015-to-2016-2017-influenza-seasons-in-japan
#7
Nobuhisa Ishiguro, Naoko Koseki, Miki Kaiho, Tadashi Ariga, Hideaki Kikuta, Koji Oba, Takehiro Togashi, Keisuke Morita, Akira Inagawa, Akiko Okamura, Shigeru Yamazaki, Satoru Shida, Mutsuko Konno, Nobuaki Kawamura, Akihito Ishizaka, Kimihiko Takada, Keiji Tsubakihara, Naoko Nagano, Mutsuo Shibata, Hideto Furuyama, Yoshihiro Matsuzono, Akemi Koike, Mari Murashita, Yoshio Hatae, Hideki Arioka, Tatsuru Yamanaka, Toru Watanabe, Yuuichi Tabata, Yoshihiro Kumita, Kyosuke Hazama, Yasushi Akutsu, Hayato Aoyagi, Chie Tobise, Katsuki Azuma, Kohichi Yasoshima, Yoko Sawada, Kazuyuki Uetsuji, Akira Tsuchida, Akira Tsuchiyama, Kazue Yasuda, Yasuhisa Odagawa, Mikio Yoshioka
The clinical effectiveness of four neuraminidase inhibitors (NAIs) (oseltamivir, zanamivir, laninamivir, and peramivir) for children aged 0 months to 18 years with influenza A and B were investigated in the 2014-2015 to 2016-2017 influenza seasons in Japan. A total of 1207 patients (747 with influenza A and 460 with influenza B) were enrolled. The Cox proportional-hazards model using all of the patients showed that the duration of fever after administration of the first dose of the NAI was shorter in older patients (hazard ratio = 1...
June 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29372885/immune-response-after-a-single-intravenous-peramivir-administration-in-children-with-influenza
#8
Masatoki Sato, Koichi Hashimoto, Yukihiko Kawasaki, Mitsuaki Hosoya
BACKGROUND: Immune response after intravenous peramivir administration, which is approved for children with influenza infection in Japan, is unclear. METHODS: Kinetics of viral load and serum cytokine levels before and after peramivir therapy were analysed in 17 and 8 hospitalized children infected with influenza A and B, respectively. Additionally, haemagglutination inhibition (HI) titre was measured. The first day of hospital admission was defined as day 0. RESULTS: Serum interleukin (IL)-6 levels in influenza-A-infected children significantly decreased after peramivir administration, unlike in those with influenza B where a decrease on day 1 was followed by an increase on day 2...
January 26, 2018: Antiviral Therapy
https://www.readbyqxmd.com/read/29324342/peramivir-conjugates-as-orally-available-agents-against-influenza-h275y-mutant
#9
Peng-Cheng Wang, Din-Chi Chiu, Jia-Tsrong Jan, Wen-I Huang, Yin-Chen Tseng, Ting-Ting Li, Ting-Jen Cheng, Keng-Chang Tsai, Jim-Min Fang
Peramivir is an efficacious neuraminidase (NA) inhibitor for treatment of influenza by intravenous administration. However, the efficacy of peramivir toward the H275Y mutant is appreciably reduced. To address this drawback, conjugation of peramivir with caffeic acid is devised in this study to enhance the binding affinity with neuraminidases. The C2-OH group of peramivir is elaborated to link with caffeate derivatives, giving the desired conjugates 8 and 9 that possess potent NA inhibitory activity against both wild-type and H275Y viruses with the IC50 values in nanomolar range...
February 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29321438/vogt-koyanagi-harada-disease-associated-with-influenza-a-virus-infection-a-case-report
#10
Nozomu Yoshino, Ai Kawamura, Akira Ishii, Katsuyuki Yoshida, Tamami Watanabe, Takeshi Yamashita, Takahiko Fukuchi, Fumihiko Toyoda, Akihiko Kakehashi, Hitoshi Sugawara
We herein report a case of a 31-year-old Japanese man who simultaneously had a positive influenza A virus antigen test result and Vogt-Koyanagi-Harada disease (VKHD), demonstrated by both diffuse multiple early hyperfluorescent points on fluorescein fundus photography and serous retinal detachments on optical coherence tomography. He had meningitis. It was difficult to determine whether the main cause of meningitis was influenza A or VKHD. After initial treatment with peramivir for influenza A and then methylprednisolone pulse with subsequent corticosteroid therapy for VKHD, his symptoms improved gradually...
January 11, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29284320/clinical-and-virologic-effects-of-four-neuraminidase-inhibitors-in-influenza-a-virus-infected-children-aged-4-12-years-an-open-label-randomized-study-in-japan
#11
Nobuo Hirotsu, Yutaka Saisho, Takahiro Hasegawa, Takao Shishido
BACKGROUND: Neuraminidase inhibitors (NAIs) reduce influenza symptoms but clear evidence of relationships between viral titer reduction and symptom alleviation is lacking. This open-label, randomized study evaluated differences in viral dynamics between NAIs, and relationships between viral dynamics and influenza symptoms (trial registration number: UMIN000012670). METHODS: Patients (n = 123) aged 4-12 years with influenza A virus infection were randomized to intravenous peramivir, oral oseltamivir, inhaled zanamivir, or inhaled laninamivir...
February 2018: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/29273435/severe-abnormal-behavior-incidence-after-administration-of-neuraminidase-inhibitors-using-the-national-database-of-medical-claims
#12
Yuuki Nakamura, Tamie Sugawara, Yasushi Ohkusa, Kiyosu Taniguchi, Chiaki Miyazaki, Mariko Momoi, Nobuhiko Okabe
An earlier study using the number of abnormal behaviors reported to the study group as the numerator and the number of influenza patient prescribed each neuraminidase inhibitor (NI) estimated by respective pharmaceutical companies found no significant difference among incidence rates of the most severe abnormal behaviors by type of NI throughout Japan. However, the dataset for the denominator used in that earlier study was the estimated number of prescriptions. In the present study, to compare the incidence rates of abnormal behavior more precisely among influenza patients administered several sorts of NI or administered no NI, we used data obtained from the National Database of Electronic Medical Claims (NDBEMC) as the denominator to reach a definitive conclusion...
March 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29159346/peramivir-analogues-bearing-hydrophilic-side-chains-exhibit-higher-activities-against-h275y-mutant-than-wild-type-influenza-virus
#13
Din-Chi Chiu, Tzu-Chen Lin, Wen-I Huang, Ting-Jen Cheng, Keng-Chang Tsai, Jim-Min Fang
Peramivir is an effective anti-influenza drug in the clinical treatment of influenza, but its efficacy toward the H275Y mutant is reduced. The previously reported cocrystal structures of inhibitors in the mutant neuraminidase (NA) suggest that the hydrophobic side chain should be at the origin of reduced binding affinity. In contrast, zanamivir having a hydrophilic glycerol side chain still possesses high affinity toward the H275Y NA. We thus designed five peramivir analogues (5-9) carrying hydrophilic glycol or glycerol side chains, and evaluated their roles in anti-influenza activity, especially for the H275Y mutant...
November 29, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29082897/peramivir-susceptibilities-of-recombinant-influenza-a-and-b-variants-selected-with-various-neuraminidase-inhibitors
#14
Clément Fage, Véronique Tu, Julie Carbonneau, Yacine Abed, Guy Boivin
BACKGROUND: Peramivir is a parenteral neuraminidase inhibitor (NAI) approved for treating influenza infections in a few countries. We determined peramivir susceptibilities of several uncharacterized influenza A and B neuraminidase (NA) and haemagglutinin (HA) mutants selected with different NAIs. METHODS: Recombinant wild-type (WT) and mutant NA proteins were expressed in 293T cells and susceptibility to peramivir, oseltamivir and zanamivir was determined by NA inhibition assay using the MUNANA substrate...
2017: Antiviral Therapy
https://www.readbyqxmd.com/read/29063410/discovery-of-potent-neuraminidase-inhibitors-using-a-combination-of-pharmacophore-based-virtual-screening-and-molecular-simulation-approach
#15
Rohini K, Shanthi V
Neuraminidase (NA), a surface protein, facilitates the release of nascent virus and thus spreads infection. It has been renowned as a potential drug target for influenza A virus infection. The drugs such as oseltamivir, zanamivir, peramivir, and laninamivir are approved for the treatment of influenza infection. Additionally, investigational drugs namely MK2206, tamiphosphor, crenatoside, and dehydroepiandrosterone (DHEA) are also available for the treatment. However, recent outbreaks of highly pathogenic and drug-resistant influenza A strains highlighted the need to discover novel NA inhibitor...
October 23, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/29046464/screening-for-neuraminidase-inhibitor-resistance-markers-among-avian-influenza-viruses-of-the-n4-n5-n6-and-n8-neuraminidase-subtypes
#16
Won-Suk Choi, Ju Hwan Jeong, Jin Jung Kwon, Su Jeong Ahn, Khristine Kaith S Lloren, Hyeok-Il Kwon, Hee Bok Chae, Jungwon Hwang, Myung Hee Kim, Chul-Joong Kim, Richard J Webby, Elena A Govorkova, Young Ki Choi, Yun Hee Baek, Min-Suk Song
Several subtypes of avian influenza viruses (AIVs) are emerging as novel human pathogens, and the frequency of related infections has increased in recent years. Although neuraminidase (NA) inhibitors (NAIs) are the only class of antiviral drugs available for therapeutic intervention for AIV-infected patients, studies on NAI resistance among AIVs have been limited, and markers of resistance are poorly understood. Previously, we identified unique NAI resistance substitutions in AIVs of the N3, N7, and N9 NA subtypes...
January 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/28976569/hplc-ms-ms-analysis-of-peramivir-in-rat-plasma-elimination-of-matrix-effect-using-the-phospholipid-removal-solid-phase-extraction-method
#17
Mingdao Lei, Wei Gan, Yongbing Sun
A simple HPLC-MS/MS method has been developed for the determination of peramivir in rat plasma in the present study. The analytes were separated on a C18 column (50 × 2.1 mm, 1.7 μm) and a triple-quadrupole mass spectrometer equipped with an electrospray ionization source was applied for the detection. A phospholipid-free cartridge solid-phase extraction was used to pretreat the plasma and eliminate the endogenous phospholipid. The in-source collision-induced dissociation approach showed that this pretreatment could result in negligible ion suppression from the extracted sample and could produce cleaner samples when compared with the protein precipitation...
March 2018: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28934455/drug-susceptibility-evaluation-of-an-influenza-a-h7n9-virus-by-analyzing-recombinant-neuraminidase-proteins
#18
Larisa V Gubareva, Katrina Sleeman, Zhu Guo, Hua Yang, Erin Hodges, Charles T Davis, Tatiana Baranovich, James Stevens
Background: Neuraminidase (NA) inhibitors are the recommended antiviral medications for influenza treatment. However, their therapeutic efficacy can be compromised by NA changes that emerge naturally and/or following antiviral treatment. Knowledge of which molecular changes confer drug resistance of influenza A(H7N9) viruses (group 2NA) remains sparse. Methods: Fourteen amino acid substitutions were introduced into the NA of A/Shanghai/2/2013(H7N9). Recombinant N9 (recN9) proteins were expressed in a baculovirus system in insect cells and tested using the Centers for Disease Control and Prevention standardized NA inhibition (NI) assay with oseltamivir, zanamivir, peramivir, and laninamivir...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28869418/a-meta-analysis-of-laninamivir-octanoate-for-treatment-and-prophylaxis-of-influenza
#19
Masayoshi Higashiguchi, Tomoshige Matsumoto, Takashi Fujii
BACKGROUND: Laninamivir octanoate is a recently developed inhaled neuraminidase inhibitor for treating influenza virus infection. We performed meta-analyses to clarify the efficacy of laninamivir octanoate on influenza treatment and prevention. METHODS: MEDLINE and CENTRAL were searched to identify eligible studies. The log median time to event ratios (logMRs) and log odds ratios (logORs) were combined with meta-analysis. RESULTS: Nine studies in treatment settings and three studies in prophylaxis settings were eligible for this meta-analysis...
September 4, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28802866/global-update-on-the-susceptibility-of-human-influenza-viruses-to-neuraminidase-inhibitors-2015-2016
#20
Larisa V Gubareva, Terry G Besselaar, Rod S Daniels, Alicia Fry, Vicki Gregory, Weijuan Huang, Aeron C Hurt, Patricia A Jorquera, Angie Lackenby, Sook-Kwan Leang, Janice Lo, Dmitriy Pereyaslov, Helena Rebelo-de-Andrade, Marilda M Siqueira, Emi Takashita, Takato Odagiri, Dayan Wang, Wenqing Zhang, Adam Meijer
Four World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza (WHO CCs) assessed antiviral susceptibility of 14,330 influenza A and B viruses collected by WHO-recognized National Influenza Centres (NICs) between May 2015 and May 2016. Neuraminidase (NA) inhibition assay was used to determine 50% inhibitory concentration (IC50 ) data for NA inhibitors (NAIs) oseltamivir, zanamivir, peramivir and laninamivir...
October 2017: Antiviral Research
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