Assessing the #susceptibility of highly pathogenic #avian #influenza #H5N1 viruses to #oseltamivir using embryonated chicken #eggs (Indian J Med Res., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Indian J Med Res. 2019 Nov;150(5):486-491. doi: 10.4103/ijmr.IJMR_845_18.

Assessing the susceptibility of highly pathogenic avian influenza H5N1 viruses to oseltamivir using embryonated chicken eggs.

Tare DS1, Kode SS1, Hurt AC2, Pawar SD3.

Author information: 1 Avian Influenza Group, ICMR-National Institute of Virology-Microbial Containment Complex, Pune, Maharashtra, India. 2 WHO Collaborating Centre for Reference & Research on Influenza (VIDRL), Peter Doherty Institute for Infection & Immunity, Melbourne VIC 3000, Australia. 3 ICMR-National Institute of Virology-Mumbai Unit, Mumbai, Maharashtra, India.

 

Abstract

BACKGROUND & OBJECTIVES:

The susceptibility of influenza viruses to neuraminidase inhibitors (NAIs) is studied using enzyme-based assays, sequence analysis and in vitro and in vivo studies. Oseltamivir carboxylate (OC) is the active prodrug of the NAI oseltamivir. There is lack of information on the use of embryonated chicken eggs for studying susceptibility of highly pathogenic avian influenza (HPAI) H5N1 viruses to antiviral drugs. The aim of the present study was to assess the use of 10 day old embryonated chicken eggs for studying antiviral susceptibility of HPAI H5N1 viruses.

METHODS:

Two HPAI H5N1 viruses isolated from India were used in the study. Fluorescence-based NAI assay was performed to determine antiviral susceptibility of these viruses. In ovo antiviral assays were carried out using 10 day old embryonated chicken eggs. The virus dilutions were incubated with 14 μg/ml of OC and inoculated in the allantoic cavity. In the eggs, 50 per cent egg infectious dose (EID50) titres as well as mortality were quantitated.

RESULTS:

The two viruses used were susceptible to OC in the NAI assay. It was found that there was a significant drop in EID50titres; however, no significant protection from mortality after OC treatment was observed.

INTERPRETATION & CONCLUSIONS:

By measuring viral titres, the egg model was suitable to study the susceptibility of HPAI viruses to antiviral drugs along with NAI assay. The present study highlights the use of eggs as a model to study susceptibility of HPAI viruses to OC.

KEYWORDS: Antivirals – embryonated chicken eggs – H5N1 – highly pathogenic avian influenza – oseltamivir

PMID: 31939392 DOI: 10.4103/ijmr.IJMR_845_18

Keywords: Antivirals; Drugs resistance; Avian Influenza; H5N1; Animal models.

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Evaluating the effects of #oseltamivir phosphate on #platelet counts: a retrospective review (Platelets, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Platelets. 2020 Jan 13:1-5. doi: 10.1080/09537104.2020.1714576. [Epub ahead of print]

Evaluating the effects of oseltamivir phosphate on platelet counts: a retrospective review.

Shaim H1, McCaffrey P1, Trieu JA2, DeAnda A3, Yates SG1.

Author information: 1 Department of Pathology, Division of Transfusion Medicine, University of Texas Medical Branch, Galveston, TX, USA. 2 Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA. 3 Department of Surgery, Division of Cardiothoracic Surgery, University of Texas Medical Branch, Galveston, TX, USA.

 

Abstract

Desialylation of platelets results in platelet clearance by the Ashwell-Morrell Receptors (AMR) found on hepatocytes. Studies suggest that oseltamivir phosphate inhibits human sialidases, enzymes responsible for desialylation, extending the lifespan of circulating platelets. We thus evaluated, the effects of oseltamivir on platelet count (PC) following treatment. Of the 385 patients evaluated for influenza, 283 (73.5%) were influenza-infected. Of the 283 infected patients, 241 (85.2%) received oseltamivir (I + O+) while 42 patients did not (I + O-). One hundred two non-infected patients received oseltamivir (I-O+). The two groups receiving oseltamivir (I + O+, I-O+), demonstrated a statistically greater increase in the PC (57.53 ± 93.81, p = .013 and 50.79 ± 70.59, p = .023, respectively) relative to the group that did not (18.45 ± 89.33 × 109/L). The observed increase in PC was statistically similar (p = .61) in both groups receiving oseltamivir (I + O+, I-O+), suggesting that this effect is independent of influenza. Comparing clinical characteristics between responders and non-responders to oseltamivir treatment showed that only duration of oseltamivir treatment (AOR = 1.30, 95% CI 1.05-1.61, p = .015) was associated with a positive PC response. Our findings suggest a correlation between oseltamivir treatment and an increase in PCs. Future studies assessing the possible uses of oseltamivir in medical conditions characterized by diminished or defective thrombopoiesis are warranted.

KEYWORDS: Ashwell-Morell Receptor; glycans; oseltamivir; thrombocytopenia

PMID: 31931672 DOI: 10.1080/09537104.2020.1714576

Keywords: Antivirals; Oseltamivir; Platelets; Hematology.

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Early Administration of #Oseltamivir Within 48 Hours After Onset of Flulike Symptoms Can Reduce the #Risk of Influenza B Virus-Associated #Pneumonia in Hospitalized #Pediatric Patients with Influenza B Virus Infection (Pediatr Infect Dis J., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Pediatr Infect Dis J. 2020 Feb;39(2):e20-e22. doi: 10.1097/INF.0000000000002528.

Early Administration of Oseltamivir Within 48 Hours After Onset of Flulike Symptoms Can Reduce the Risk of Influenza B Virus-Associated Pneumonia in Hospitalized Pediatric Patients with Influenza B Virus Infection.

Dai Z1, Zhang L, Yu Q, Liu L, Yang M, Fan K.

Author information: 1 From the Department of Accident and Emergency, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

 

Abstract

We conducted a retrospective study to identify the risk factors for pneumonia in hospitalized pediatric patients with influenza B infection. Receiving oseltamivir within the first 48 hours of onset and frequent cough was respectively considered as a protective factor and a risk factor for the influenza B virus-associated pneumonia in hospitalized pediatric patients. Early administration of oseltamivir can reduce the risk of influenza B virus-associated pneumonia.

PMID: 31929434 DOI: 10.1097/INF.0000000000002528

Keywords: Seasonal Influenza; Influenza B; Antivirals; Oseltamivir; Pneumonia; Pediatrics.

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#Influenza A/ #H4N2 #mallard #infection experiments further indicate #zanamivir as less prone to induce #environmental #resistance development than #oseltamivir (J Gen Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Gen Virol. 2019 Dec 19. doi: 10.1099/jgv.0.001369. [Epub ahead of print]

Influenza A/H4N2 mallard infection experiments further indicate zanamivir as less prone to induce environmental resistance development than oseltamivir.

Tepper V1,2, Nykvist M2, Gillman A3, Skog E3, Wille M4,2, Lindström HS5, Tang C6, Lindberg RH6, Lundkvist Å2, Järhult JD3.

Author information: 1 Institute of Environmental Engineering, ETH Zürich, Switzerland. 2 Zoonosis Science Center, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. 3 Zoonosis Science Center, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 4 Present address: WHO Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. 5 Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, Umeå University, Umeå, Sweden. 6 Department of Chemistry, Umeå University, Umeå, Sweden.

 

Abstract

Neuraminidase inhibitors (NAIs) are the gold standard treatment for influenza A virus (IAV). Oseltamivir is mostly used, followed by zanamivir (ZA). NAIs are not readily degraded in conventional wastewater treatment plants and can be detected in aquatic environments. Waterfowl are natural IAV hosts and replicating IAVs could thus be exposed to NAIs in the environment and develop resistance. Avian IAVs form the genetic basis for new human IAVs, and a resistant IAV with pandemic potential poses a serious public health threat, as NAIs constitute a pandemic preparedness cornerstone. Resistance development in waterfowl IAVs exposed to NAIs in the water environment has previously been investigated in an in vivo mallard model and resistance development was demonstrated in several avian IAVs after the exposure of infected ducks to oseltamivir, and in an H1N1 IAV after exposure to ZA. The N1 and N2 types of IAVs have different characteristics and resistance mutations, and so the present study investigated the exposure of an N2-type IAV (H4N2) in infected mallards to 1, 10 and 100 µg l-1 of ZA in the water environment. Two neuraminidase substitutions emerged, H274N (ZA IC50 increased 5.5-fold) and E119G (ZA IC50 increased 110-fold) at 10 and 100 µg l-1 of ZA, respectively. Reversion towards wild-type was observed for both substitutions in experiments with removed drug pressure, indicating reduced fitness of both resistant viruses. These results corroborate previous findings that the development of resistance to ZA in the environment seems less likely to occur than the development of resistance to oseltamivir, adding information that is useful in planning for prudent drug use and pandemic preparedness.

KEYWORDS: H4N2; LPAI; antiviral resistance; avian influenza; drug residues; environment; influenza A; neuraminidase inhibitor; pandemic preparedness; zanamivir

PMID: 31855133 DOI: 10.1099/jgv.0.001369

Keywords: Avian Influenza; Antivirals; Drugs Resistance; H1N1pdm09; H4N2; Wild Birds.

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#Baloxavir marboxil #treatment of nude mice infected with #influenza A virus (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Baloxavir marboxil treatment of nude mice infected with influenza A virus

Maki Kiso, Seiya Yamayoshi, Jurika Murakami, Yoshihiro Kawaoka

The Journal of Infectious Diseases, jiz665, https://doi.org/10.1093/infdis/jiz665

Published: 14 December 2019

 

Abstract

Immunocompromised patients infected with influenza virus require prolonged treatment with neuraminidase inhibitors, because these patients are not able to eradicate the virus from the respiratory tract, leading to the emergence of drug-resistant mutant viruses. Here, we examined the efficacy of baloxavir marboxil in nude mice, which are immunologically deficient. Daily treatment with a suboptimal dose of baloxavir marboxil increased the survival time of the virus-infected nude mice but did not clear the virus from their respiratory organs, resulting in gradual body weight loss after termination of treatment. Despite the prolonged baloxavir marboxil treatment, few resistant mutants were detected.

influenza, baloxavir marboxil, drug resistance, immunocompromised

Issue Section: Brief Report

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Keywords: Antivirals; Drugs Resistance; Influenza A; Oseltamivir; Baloxavir; Animal models.

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#Neuraminidase #inhibitors for #ILI in primary care (Lancet, summary)

[Source: The Lancet, full page: (LINK). Summary, edited.]

Neuraminidase inhibitors for influenza-like illness in primary care

Nelson Lee, Michael Ison

Published: December 12, 2019 / DOI: https://doi.org/10.1016/S0140-6736(19)33097-1

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Primary care physicians have an important role in managing most of the influenza cases during seasonal epidemics. Symptomatic treatment and antibiotics are commonly prescribed due to undifferentiated manifestations of acute respiratory infections. Neuraminidase inhibitor treatment is recommended in outpatients if they have severe symptoms or are at risk for complications and present within 2 days of illness. 1
However, global use of neuraminidase inhibitor treatment is low. 2
Concerns about the modest benefits and side-effects of neuraminidase inhibitors and inaccessibility to rapid, sensitive influenza diagnostics might have reduced broader use of this treatment.

(…)

Keywords: Seasonal Influenza; Antivirals; Oseltamivir.

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#Oseltamivir plus usual care versus usual care for #influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial (Lancet, abstract)

[Source: The Lancet, full page: (LINK). Abstract, edited.]

Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial

Prof Christopher C Butler, FMedSci, Alike W van der Velden, PhD, Emily Bongard, PhD, Benjamin R Saville, PhD, Jane Holmes, PhD, Prof Samuel Coenen, PhD, Johanna Cook, MSc, Prof Nick A Francis, PhD, Prof Roger J Lewis, PhD, Prof Maciek Godycki-Cwirko, PhD, Carl Llor, PhD, Prof Sławomir Chlabicz, PhD, Prof Christos Lionis, PhD, Prof Bohumil Seifert, PhD, Pär-Daniel Sundvall, PhD, Annelies Colliers, MSc, Rune Aabenhus, PhD, Prof Lars Bjerrum, PhD, Nicolay Jonassen Harbin, MD, Prof Morten Lindbæk, PhD, Dominik Glinz, PhD, Heiner C Bucher, MD, Bernadett Kovács, MSc, Ruta Radzeviciene Jurgute, MD, Pia Touboul Lundgren, MD, Prof Paul Little, PhD, Prof Andrew W Murphy, PhD, An De Sutter, PhD, Prof Peter Openshaw, FMedSci, Prof Menno D de Jong, PhD, Jason T Connor, PhD, Veerle Matheeussen, PhD, Margareta Ieven, PhD, Prof Herman Goossens, PhD, Prof Theo J Verheij, PhD

Published: December 12, 2019 / DOI: https://doi.org/10.1016/S0140-6736(19)32982-4

 

Summary

Background

Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups.

Methods

We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921.

Findings

Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1·29, 95% Bayesian credible interval [BCrI] 1·20–1·39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1·13 to 1·72. The estimated absolute mean benefit from oseltamivir was 1·02 days (95% [BCrI] 0·74–1·31) overall, and in the prespecified subgroups, ranged from 0·70 (95% BCrI 0·30–1·20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3·20 (95% BCrI 1·00–5·50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group.

Interpretation

Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2–3 days sooner.

Funding

European Commission’s Seventh Framework Programme.

Keywords: Seasonal Influenza; Antivirals; Oseltamivir.

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