"Cidara developed a chemical variant of the drug and attached several copies of it to a piece of an antibody called the Fc fragment"
13th #Meeting of #WHO Expert Working #Group on #Surveillance of #Antiviral Susceptibility of #Influenza Viruses for WHO #GISRS
Source: World Health Organization, Weekly Epidemiological Record: https://www.who.int/publications/journals/weekly-epidemiological-record
{Excerpt, edited}
Executive summary
The WHO Expert Working Group on Surveillance of Influenza Antiviral Susceptibility (AVWG) supports the WHO Global Influenza Surveillance and Response System (GISRS) by providing practical guidance for monitoring the antiviral susceptibility of seasonal and emerging influenza viruses The 13th WHO AVWG meeting was held in hybrid format (faceto-face and virtually) on 13–14 June 2024 in Lyon, France.
Update on susceptibility of seasonal influenza viruses to approved antiviral agents
Between May 2023 and May 2024, WHO collaborating centres (CCs) and participating national influenza centres (NICs) reported that seasonal influenza activity in various regions had resumed to levels before the coronavirus disease 2019 (COVID-19) pandemic. Co-circulation of A(H1N1)pdm09, A(H3N2) and influenza B/Victoria lineage viruses was detected in most regions. Overall, influenza A and B viruses with reduced inhibition (RI) or highly reduced inhibition (HRI) to neuraminidase (NA) inhibitors (NAIs) were detected at low frequency. The most frequently identified substitution associated with RI or HRI by NAIs was NA-H275Y in A(H1N1)pdm09 viruses, which was detected at <2%. Double amino acid substitutions (NA-I223V+ NA-S247N) in A(H1N1)pdm09 viruses (referred to as dual mutant viruses) that resulted in RI by oseltamivir were first detected in May 2023 and spread rapidly to several regions of the world.{1,2} Influenza A and B viruses with amino acid substitutions in the polymerase acidic (PA) protein associated with reduced susceptibility to endonuclease inhibitor (baloxavir) were detected at low frequency. The PA-I38X (including I38T, I38N, I38M and I38V) amino acid substitution being the most frequently reported, but the overall detection frequency has remained low (<2%).
Update on susceptibility of zoonotic and animal influenza viruses to approved antiviral agents
From May 2023 to May 2024, clade 2.3.4.4b A(H5N1) highly pathogenic avian influenza (HPAI) viruses continued to be detected in various regions of the world. Since early 2024, there has been an outbreak of clade 2.3.4.4b A(H5N1) genotype B3.13 viruses in dairy cattle in several states in the United States of America, resulting in sporadic zoonotic infections in humans. In addition, human infection with clade 2.3.2.1c A(H5N1) HPAI has been reported in Cambodia and Viet Nam. WHO CCs, participating NICs and WHO H5 reference laboratories reported antiviral susceptibility testing of A(H5N1) HPAI, low pathogenic avian influenza (LPAI) of various subtypes and swine influenza viruses. Of the clade 2.3.4.4b A(H5N1) HPAI viruses, the NA-T438I substitution, which confers RI by zanamivir and peramivir, was detected at <2% frequency. NA-H275Y, NA-N295S and NA-N295S+NA-T438N associated with RI or HRI by NAIs were also detected among A(H5N1) viruses. NA-T438I has been detected in A(H5N1) viruses isolated from dairy cattle. PA-I38T, PA-A37T and PA-I38M, associated with reduced susceptibility to baloxavir, were detected in A(H5N1) viruses. Most A(H5N1) HPAI viruses remain susceptible to M2 ion channel blockers. Among LPAI, NA-H274Y with HRI by oseltamivir was detected in one A(H8N4) isolate. PA-E199G with reduced susceptibility to baloxavir was detected in one A(H9N2) virus. Overall, animal or zoonotic influenza viruses with reduced susceptibility to NAIs or baloxavir were detected at very low frequencies.
Update of protocols and guidance for GISRS laboratories
Genotypic and/or phenotypic assays can be used to monitor the susceptibility of influenza viruses to NAIs and baloxavir. The WHO AVWG routinely reviews and updates information on NA{3,4} and PA{5} amino acid substitutions associated with reduced susceptibility to NAIs and baloxavir, respectively. Reference virus panels that can be used for NAI and baloxavir susceptibility testing are available for GISRS laboratories at the International Reagent Resource.{6} The WHO AVWG will develop an algorithm for NICs to decide on testing strategies (genotypic versus phenotypic) and methods according to their capacity. Guidance on phenotypic assays for NAI susceptibility testing is provided in a WHO guidance document to NICs, which was updated in 2018.{7} A new phenotypic assay has been developed for testing susceptibility to baloxavir.{8} The protocol will be posted on the WHO website. The WHO-AVWG will also update the WHO guidance document to NICs to include the new phenotypic assay for baloxavir susceptibility testing. In addition, the WHO AVWG will work with the Global Initiative on Sharing All Influenza Data{9} to facilitate identification of NA and PA substitutions in submitted sequences.
Review of external quality assessment programme (EQAP) panels
EQAP was initiated in 2007, and the antiviral panel was introduced in 2013 (panel 12) as an optional component of EQAP to evaluate the ability of NICs to identify influenza viruses with reduced susceptibility to NAIs. Genotypic testing for baloxavir susceptibility was introduced in 2020 (panel 19) for educational purpose (i.e. not scored). Results for the 2023 Global EQAP panel were reported at the 13th WHO AVWG meeting. A total of 178 laboratories participated in the 2023 EQAP; 46 (25.8%) participated in NAI susceptibility testing and 16 (9.0%) in baloxavir susceptibility testing. The results from the Global EQAP antiviral panel are used by members of the WHO AVWG to assess the training requirements of NICs.
Way forward
Two reports, on global antiviral surveillance in 2020-2023 and in 2023–2024, are being prepared for publication. The next WHO AVWG meeting is scheduled for June 2025.
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{1} Leung RC et al. Global emergence of neuraminidase inhibitor-resistant influenza A(H1N1)pdm09 viruses with I223V and S247N mutations: implications for antiviral resistance monitoring. Lancet Microbe. 2024;5(7):627–8. doi:10.1016/S26665247(24)00037-5.
{2} Patel MC et al. Multicountry spread of influenza A(H1N1)pdm09 viruses with reduced oseltamivir inhibition, May 2023-February 2024. Emerg Infect Dis. 2024;30(7):1410–5. doi:10.3201/eid3007.240480.
{3} Summary of neuraminidase (NA) amino acid substitutions associated with reduced inhibition by neuraminidase inhibitors (NAIs). Geneva: World Health Organization; 2023 (https://www.who.int/publications/m/item/summary-of-neuraminidase-(na)-amino-acid-substitutions-associated-with-reduced-inhibition-by-neuraminidase-inhibitors-(nais).
{4} Summary of neuraminidase (NA) amino acid substitutions associated with reduced inhibition by neuraminidase inhibitors (NAIs) among avian influenza viruses of Group 1 and Group 2 NAs. Geneva: World Health Organization; 2024 (https://www. who.int/publications/m/item/summary-of-neuraminidase-(na)-amino-acid-substitutions-associated-with-reduced-inhibition-by-neuraminidase-inhibitors-(nais)among-avian-influenza-viruses-of-group-1-and-group-2-nas).
{5} Summary of polymerase acidic (PA) protein amino acid substitutions analysed for their effects on baloxavir susceptibility. Geneva: World Health Organization; 2024 (https://www.who.int/publications/m/item/summary-of-polymerase-acidic-(pa)-protein-amino-acid-substitutions-analysed-for-their-effects-on-baloxavirsusceptibility).
{6} See https://www.internationalreagentresource.org.
{7} Practical guidance for national influenza centres establishing or implementing neuraminidase inhibitor susceptibility surveillance. Geneva: World Health Organization; 2024 (https://www.who.int/publications/i/item/practical-guidance-for-national-inf luenza-centres-establishing-or-implementing-neuraminidase-inhibitor-susceptibility-surveillance).
{8} Baloxavir susceptibility assessment using influenza replication inhibition neuraminidase-based assay (IRINA). Atlanta (GA): Centers for Disease Control and Prevention; 2023 (https://cdn.who.int/media/docs/default-source/influenza/avwg/ cdc-phenotypic-lp-492rev01d—baloxavir-susceptibility-assessment-using-irina. pdf?sfvrsn=f24254ac_3).
{9} See https://gisaid.org.
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#aH3n2 #aH5n1 #aH9n2 #amantadine #antivirals #AVIANINFLUENZA #baloxavir #birdFlu #drugsResistance #h1n1pdm09 #h5n1 #health #influenza #oseltamivir #science #SEASONALINFLUENZA #updates #WHO #zanamivir
#Antivirals for #PEP of #influenza: a systematic #review and network meta-analysis https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01357-6/fulltext?rss=yes
PEP with #zanamivir, #oseltamivir, #laninamivir, or #baloxavir probably decreases #risk of symptomatic seasonal flu in individuals at high risk for severe disease after exposure to seasonal flu viruses. PEP with zanamivir, oseltamivir, laninamivir, or baloxavir might reduce risk of symptomatic #zoonotic flu after exposure to novel viruses associated with severe disease in infected humans.
#Molecular #surveillance of #influenza A virus in #SaudiArabia: #WGS and metagenomic approaches https://pubmed.ncbi.nlm.nih.gov/38904365/?utm_source=Feedly&utm_medium=rss&utm_campaign=None&utm_content=10ykRO9og5pGdo51l9DEPEpOJ3DVFIn__QK2QPM3dci1C1dEYq&fc=None&ff=20240621125233&v=2.18.0.post9+e462414
One sample containing the #antiviral #resistance-mediating #mutation #S247N toward #oseltamivir and #zanamivir was found.
Outbreaks of influenza A viruses are generally seasonal and cause annual epidemics worldwide. Due to their frequent reassortment and evolution, annual surveillance is of paramount importance to guide vaccine strategies. The aim of this study was to explore the molecular epidemiology of influenza A v …
#h5n1 #birdflu #avianflu #hpai #h5n2 #influence #grippe #flu #press #news
#antivirale #Medikamente #Virostatika geg #Influenza:
#Oseltamivirphosphat (als Generikum od. unter Handelsnamen #Tamiflu)
#Zanamivir ( #Relenza )
#Peramivir ( #Rapivab )
#Baloxavir ( #Xofluza )
Bei bestätigter od. Verdacht auf #Vogelgrippe wird schnellstmögl. Behandlung empfohlen
Tiermodelle & #Beobachtungsstudien deuten auf Nutzen von Virostatika bei mit Vogelgrippe infizierten #Menschen hin
https://www.medscape.com/viewarticle/new-human-cases-avian-flu-anticipated-2024a1000bfg?form=fpf
#Duration of #fever in #children infected with #influenza #H1N1pdm09, #H3N2 or B virus & treated with #baloxavir, #oseltamivir, #laninamivir, or #zanamivir in #Japan during the 2012–13 & 2019–20 seasons, Antiviral Res.: https://www.sciencedirect.com/science/article/pii/S0166354224001475?via%3Dihub
We compared fever duration between baloxavir- & 3 NAIs-treated groups. ...For influenza A, fever duration in baloxavir- & NAIs-treated groups was similar. For influenza B, fever duration was ∼15 h shorter in baloxavir-treated group.
#Antivirals for #PEP of #influenza: a systematic #review and network meta-analysis, MedRxIV, https://www.medrxiv.org/content/10.1101/2024.05.28.24307995v1
Post-exposure #prophylaxis with #zanamivir, #oseltamivir, #laninamivir or #baloxavir might reduce the #risk of symptomatic #zoonotic influenza after exposure to novel influenza A viruses associated with severe disease in infected humans.
Background: To support an update of WHO influenza guidelines, we performed a systematic review and network meta-analysis of the evidence on antiviral drugs for prophylaxis of influenza. Methods: We analyzed randomized controlled trials published as of September 2023 on the efficacy and safety of antivirals compared to another antiviral or placebo, standard care, or no prophylaxis for prevention of symptomatic influenza. Paired reviewers independently screened studies, extracted data and assessed the risk of bias. We used frequentist random effects to perform network meta-analyses and assessed the certainty of evidence using the grading of recommendations assessment, development and evaluation (GRADE) methodology. Findings: We included thirty-three trials of six antivirals (zanamivir, oseltamivir, laninamivir, baloxavir, amantadine, and rimantadine) that enrolled 19096 individuals. Zanamivir, oseltamivir, laninamivir and baloxavir probably achieve important reductions in symptomatic influenza in persons at high risk of severe disease (moderate certainty) when given promptly after exposure to seasonal influenza. These antivirals probably do not achieve important reductions in symptomatic influenza in persons at low risk of severe disease when given promptly after exposure to seasonal influenza (moderate certainty). Zanamivir, oseltamivir, laninamivir and baloxavir might achieve important reductions in symptomatic zoonotic influenza in persons exposed to novel influenza A viruses associated with severe disease in infected humans when given promptly after exposure (low certainty). These antivirals do not result in an important incidence of adverse events related to drugs or serious adverse events, with varying certainty of evidence. Interpretation: Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir or baloxavir probably decreases the risk of symptomatic seasonal influenza in persons at high risk for severe disease after exposure to seasonal influenza viruses. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir or baloxavir might reduce the risk of symptomatic zoonotic influenza after exposure to novel influenza A viruses associated with severe disease in infected humans. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols <https://www.crd.york.ac.uk/prospero/> ### Funding Statement WHO ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: EMBASE, MEDLINE, the Cochrane Central Registry of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Global Health, Epistemonikos and ClincalTrials.gov databases I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data included were derived from publicly available documents cited in the references. Extracted data are available upon request to the corresponding author.
Giuseppe Michieli
David Usharauli
ETIDIoH
Categorical Imperative