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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#US #CDC A(#H5N1) #Birdflu Response #Update, November 18, 2024

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/spotlights/h5n1-response-11152024.html

{Excerpts}

Situation Update
November 18, 2024 – CDC continues to respond to the public health challenge posed by a multistate outbreak of avian influenza A(H5N1) virus, or "H5N1 bird flu," in dairy cows, poultry and other animals in the United States. CDC is working in collaboration with the U.S. Department of Agriculture (USDA), the Food and Drug Administration (FDA), Administration for Strategic Preparedness and Response (ASPR), state public health and animal health officials, and other partners using a One Health approach.

Since April 2024, CDC, working with state public health departments, has confirmed avian influenza A(H5) virus infections in 52 people in the United States. Twenty-one of these cases were associated with exposure to avian influenza A(H5N1) virus -infected poultry and 30 were associated with exposure to infected dairy cows [A][B]. The source of the exposure in one case, which was reported by Missouri on September 6, could not be determined.

The 52 cases include 26 cases among dairy farm workers in California, five of which were confirmed by CDC on November 13 and 14, and one additional case in a poultry farm worker in Oregon. This is the first human case of H5N1 bird flu reported in Oregon. All recent cases have occurred in workers on affected farms. All available data so far suggest sporadic instances of animal-to-human spread. These farm workers all described mild symptoms, many with eye redness or discharge (conjunctivitis). Some workers who tested positive in Washington reported some mild upper respiratory symptoms. None of the workers were hospitalized.

CDC is aware of the human case of H5N1 bird flu reported in Canada and is in communication with the Public Health Agency of Canada (PHAC), which has confirmed that the case was caused by an H5N1 virus that is different than those causing outbreaks in dairy cows and other animals in the United States. More information about the case in Canada and ongoing epidemiological investigation is available in a statement from PHAC. Updated case counts for the United States, including by state and source of exposure, are recorded in a table on CDC’s website. To date, person-to-person spread of H5 bird flu has not been identified in the United States. CDC believes the immediate risk to the general public from H5 bird flu remains low, but people with exposure to infected animals are at higher risk of infection.

On the animal health side, since March 2024, USDA has confirmed infected cattle in 505 dairy herds in 15 U.S. states. The number of affected herds continues to grow nationally, with almost all new infections identified in herds in California. USDA reports that, since April 2024, there have been H5 detections in 50 commercial poultry flocks and 38 backyard flocks, for a total of 25.61 million birds affected.

Among other activities reported in previous spotlights and ongoing, recent highlights of CDC’s response to this include:

Laboratory Update
To date, CDC has confirmed 11 human cases of H5 bird flu in poultry farm workers in Washington. Genetic sequencing of influenza virus from clinical specimens from these cases showed no changes in the hemagglutinin (HA) associated with increased infectivity or transmissibility among people. However, in influenza specimens from three of these H5 cases, CDC identified a change, NA-S247N, that may slightly reduce susceptibility to the neuraminidase inhibitor oseltamivir in laboratory tests. NA-S247N has been detected sporadically in seasonal influenza viruses and has rarely been found in A(H5N1) viruses. Historically, two H5N1 viruses with the NA-S247N change have been tested for susceptibility to oseltamivir: an A(H5N1) virus collected from a chicken in Laos in 2008 (A/chicken/Laos/13/2008; PMID: 20016036) and a clade 2.3.4.4b H5N1 virus collected from a dolphin in Florida in 2022 (A/dolphin/Florida/2022; PMID: 37494978 and PMID: 38637646). These laboratory studies found either mildly reduced or reduced inhibition by oseltamivir, with results well below what has been reported for oseltamivir resistance of other influenza viruses. It is important to note that this change is not spreading in H5 viruses. Additionally, this change is not expected to have an impact on the ability of influenza viruses to replicate or spread more easily. While NA-S247N may slightly reduce antiviral susceptibility in laboratory testing, that is NOT the same as resistance. Results of laboratory studies demonstrating mildly reduced or reduced inhibition by oseltamivir may not indicate reduced effectiveness of antiviral treatment of a patient with H5N1 virus infection. NA-S247N is unlikely to have a meaningful impact on the clinical benefit of oseltamivir, which is the currently recommended antiviral for treatment for H5 bird flu. CDC continues to recommend oseltamivir for treatment of patients with H5N1 and for post-exposure prophylaxis of close contacts of confirmed H5N1 patients and those with higher risk exposures to animals infected with H5N1 viruses.

Due to low viral RNA concentrations in clinical specimens from these three cases and unsuccessful attempts to isolate virus in culture, multiple sequencing attempts were required to generate data sufficient to meet CDC quality thresholds for posting of partial NA sequences.

CDC also identified a different change in the polymerase acidic (PA) protein of a virus collected from a recently confirmed human case of H5N1 bird flu in California (A/California/150/2024). This change, PA-I38M, is associated with decreased susceptibility to the influenza antiviral medication baloxavir marboxil and has been sporadically detected in a small number of avian influenza viruses. Baloxavir is not currently recommended for treatment or post-exposure prophylaxis of H5N1 virus infection. As indicated above, oseltamivir is the recommended antiviral treatment for H5N1 bird flu. No H5N1 patients in the U.S. have received baloxavir treatment for H5N1. There are no available data on baloxavir treatment of H5N1 patients worldwide. And the optimal dosing and duration of baloxavir for treatment or post-exposure prophylaxis of H5N1 virus infection in humans are unknown.

Influenza genetic sequence data from these and other recently confirmed cases of H5 bird flu in humans have been posted in GISAID and GenBank. Additional laboratory investigations are ongoing and planned at CDC to better understand the implications of these changes in the context of the currently spreading H5 viruses. In summary, although these particular changes have not been detected widely and are not spreading among dairy cattle or birds, these findings underscore the importance of ongoing surveillance and testing to analyze H5 viruses for any changes that could potentially impact their susceptibility to flu antiviral medications.

Surveillance Update
As noted above, CDC has so far confirmed 11 cases in Washington state and 26 cases in California.

CDC continues to support states that are monitoring people with exposure to cows, birds, or other domestic or wild animals infected, or potentially infected, with avian influenza A(H5N1) virus. To date, more than 7,300 people have been monitored as a result of their exposure to infected or potentially infected animals, and at least 380 people who have developed flu-like symptoms, including conjunctivitis, have been tested as part of this targeted, situation-specific testing. More information on monitoring can be found at Symptom Monitoring Among Persons Exposed to HPAI.

In addition, since February 25, 2024, more than 60,000 specimens have been tested for avian influenza A(H5) virus or other novel influenza viruses at public health labs. One of the specimens, collected as a part of routine surveillance, was identified as presumptive positive for avian influenza A(H5) virus and was confirmed as H5N1 bird flu positive by CDC.

CDC also continues to monitor flu surveillance data using CDC’s 2024-2025 influenza surveillance strategy, especially in areas where avian influenza A(H5N1) viruses have been detected in dairy cows or other animals, for any unusual trends, including in flu-like illness, conjunctivitis, or influenza virus activity. Overall, for the most recent week of data, CDC flu surveillance systems show no indicators of unusual flu activity in people.

(…)

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#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, Nov. 16 ’24)

1. ZHANG W, Lin X, Li ZY, Zhang LJ, et al
   Novel intercellular spread mode of respiratory syncytial virus contributes to neutralization escape.
   Antiviral Res. 2024;231:106023.
   PubMed         Abstract available
2. LO CW, Kariv O, Hao C, Gammeltoft KA, et al
   Replication Capacity and Susceptibility of Nirmatrelvir-Resistant Mutants to Next-Generation Mpro Inhibitors in a SARS-CoV-2 Replicon System.
   Antiviral Res. 2024 Oct 16:106022. doi: 10.1016/j.antiviral.2024.106022.
   PubMed         Abstract available
3. VAN DER HORST D, Carter-Timofte ME, Danneels A, Silva da Costa L, et al
   Large-scale deep learning identifies the antiviral potential of PKI-179 and MTI-31 against coronaviruses.
   Antiviral Res. 2024;231:106012.
   PubMed         Abstract available
4. HERRMANN A, Gege C, Wangen C, Wagner S, et al
   Orally Bioavailable RORgamma/DHODH Dual Host-Targeting Small Molecules with Broad-Spectrum Antiviral Activity.
   Antiviral Res. 2024 Sep 19:106008. doi: 10.1016/j.antiviral.2024.106008.
   PubMed         Abstract available
5. ZHANG K, Yang XM, Sun H, Cheng ZS, et al
   Modulating apoptosis as a novel therapeutic strategy against Respiratory Syncytial Virus infection: insights from Rotenone.
   Antiviral Res. 2024;231:106007.
   PubMed         Abstract available
6. KUMAR P, Zhang X, Shaha R, Kschischo M, et al
   Identification of antibody-resistant SARS-CoV-2 mutants via N4-Hydroxycytidine mutagenesis.
   Antiviral Res. 2024;231:106006.
   PubMed         Abstract available
7. DO TND, Abdelnabi R, Boda B, Constant S, et al
   The triple combination of Remdesivir (GS-441524), Molnupiravir and Ribavirin is highly efficient in inhibiting coronavirus replication in human nasal airway epithelial cell cultures and in a hamster infection model.
   Antiviral Res. 2024 Sep 3:105994. doi: 10.1016/j.antiviral.2024.105994.
   PubMed         Abstract available
8. RICHTER M, Khrenova M, Kazakova E, Riabova O, et al
   Dynamic features of virus protein 1 and substitutions in the 3-phenyl ring determine the potency and broad-spectrum activity of capsid-binding pyrazolo[3,4-d]pyrimidines against rhinoviruses.
   Antiviral Res. 2024;231:105993.
   PubMed         Abstract available
9. LEE P, Kim J, Oh H, Kim CU, et al
   Coronavirus Nucleocapsid-based Vaccine Provides Partial Protection against Hetero-species Coronavirus in Murine Models.
   Antiviral Res. 2024 Aug 22:105991. doi: 10.1016/j.antiviral.2024.105991.
   PubMed         Abstract available

   Biochem Biophys Res Commun

10. ZHAN Y, Li M, Gong R
    Protein mimics of fusion core from SARS-CoV-1 can inhibit SARS-CoV-2 entry.
    Biochem Biophys Res Commun. 2024;736:150857.
    PubMed         Abstract available
11. UCHIKUBO-KAMO T, Ishimoto N, Umezawa H, Hirohama M, et al
    Structural insights into Influenza A virus RNA polymerase PB1 binding to nuclear import host factor RanBP5.
    Biochem Biophys Res Commun. 2024;739:150952.
    PubMed         Abstract available

    Epidemiol Infect

12. GANDINI S, Conly J, Spencer EA, Evans D, et al
    Oro-faecal transmission of SARS-CoV-2: A systematic review of studies employing viral culture from gastrointestinal and other potential oro-faecal sources and evidence for transmission to humans.
    Epidemiol Infect. 2024;152:e138.
    PubMed         Abstract available
13. MAO S, Gu D, Wang D, Li P, et al
    Prevalence and prognosis of tinnitus in post-COVID-19 patients: a cross-sectional survey.
    Epidemiol Infect. 2024;152:e137.
    PubMed         Abstract available

    J Infect Dis

14. COHEN C, du Plessis M, Martinson N, Moyes J, et al
    A potential platform for future vaccine trials identifies high incidence of symptomatic and asymptomatic influenza infection among children aged 6-23 months in South Africa.
    J Infect Dis. 2024 Nov 14:jiae550. doi: 10.1093.
    PubMed         Abstract available

    J Virol

15. LI C, Culhane MR, Schroeder DC, Cheeran MC-J, et al
    Quantifying the impact of vaccination on transmission and diversity of influenza A variants in pigs.
    J Virol. 2024 Nov 12:e0124524. doi: 10.1128/jvi.01245.
    PubMed         Abstract available
16. POWELL JD, Thomas MN, Anderson TK, Zeller MA, et al
    2018-2019 human seasonal H3N2 influenza A virus spillovers into swine with demonstrated virus transmission in pigs were not sustained in the pig population.
    J Virol. 2024 Nov 11:e0008724. doi: 10.1128/jvi.00087.
    PubMed         Abstract available

    MMWR Morb Mortal Wkly Rep

17. MELLIS AM, Coyle J, Marshall KE, Frutos AM, et al
    Serologic Evidence of Recent Infection with Highly Pathogenic Avian Influenza A(H5) Virus Among Dairy Workers – Michigan and Colorado, June-August 2024.
    MMWR Morb Mortal Wkly Rep. 2024;73:1004-1009.
    PubMed         Abstract available
18. MARSHALL KE, Drehoff CC, Alden N, Montoya S, et al
    Personal Protective Equipment Use by Dairy Farmworkers Exposed to Cows Infected with Highly Pathogenic Avian Influenza A(H5N1) Viruses – Colorado, 2024.
    MMWR Morb Mortal Wkly Rep. 2024;73:999-1003.
    PubMed         Abstract available
19. FRUTOS AM, Ahmad HM, Ujamaa D, O’Halloran AC, et al
    Underutilization of Influenza Antiviral Treatment Among Children and Adolescents at Higher Risk for Influenza-Associated Complications – United States, 2023-2024.
    MMWR Morb Mortal Wkly Rep. 2024;73:1022-1029.
    PubMed         Abstract available
20. LEFFERTS B, Bressler S, Keck JW, Desnoyers C, et al
    Nirsevimab Effectiveness Against Medically Attended Respiratory Syncytial Virus Illness and Hospitalization Among Alaska Native Children – Yukon-Kuskokwim Delta Region, Alaska, October 2023-June 2024.
    MMWR Morb Mortal Wkly Rep. 2024;73:1015-1021.
    PubMed         Abstract available
21. MINTA AA, Ferrari M, Antoni S, Lambert B, et al
    Progress Toward Measles Elimination – Worldwide, 2000-2023.
    MMWR Morb Mortal Wkly Rep. 2024;73:1036-1042.
    PubMed         Abstract available

    PLoS Biol

22. DADONAITE B, Ahn JJ, Ort JT, Yu J, et al
    Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance.
    PLoS Biol. 2024;22:e3002916.
    PubMed         Abstract available
23. HAY JA, Zhu H, Jiang CQ, Kwok KO, et al
    Reconstructed influenza A/H3N2 infection histories reveal variation in incidence and antibody dynamics over the life course.
    PLoS Biol. 2024;22:e3002864.
    PubMed         Abstract available

    PLoS One

24. ZHOU Y, Jin L, Lai X, Li Y, et al
    Adverse events associated with oseltamivir and baloxavir marboxil in against influenza virus therapy: A pharmacovigilance study using the FAERS database.
    PLoS One. 2024;19:e0308998.
    PubMed         Abstract available
25. GARZON DIAZ K, Villamil Duarte A, Velasco Forero S, Herrera Jacobo S, et al
    Post-pandemic face-to-face learning environments for undergraduate students: A scoping review protocol.
    PLoS One. 2024;19:e0309932.
    PubMed         Abstract available
26. LEITNER SM
    Working from home and mental well-being at different stages of the COVID-19 pandemic.
    PLoS One. 2024;19:e0312299.
    PubMed         Abstract available
27. WANG SB, Hanson JL
    Childhood socioeconomic position relates to adult decision-making: Evidence from a large cross-cultural investigation.
    PLoS One. 2024;19:e0310972.
    PubMed         Abstract available
28. AHMED S, Raza B, Hussain L, Sadiq T, et al
    Enhancing multiclass COVID-19 prediction with ESN-MDFS: Extreme smart network using mean dropout feature selection technique.
    PLoS One. 2024;19:e0310011.
    PubMed         Abstract available
29. CAROLIN A, Yan K, Bishop CR, Tang B, et al
    Tracking inflammation resolution signatures in lungs after SARS-CoV-2 omicron BA.1 infection of K18-hACE2 mice.
    PLoS One. 2024;19:e0302344.
    PubMed         Abstract available
30. VIVES-RODRIGUEZ AL, Marin A, Schiloski KA, Hajos GP, et al
    Impact of remote social interaction during the COVID-19 pandemic on the cognitive and psychological status of older adults with and without cognitive impairment: A randomized controlled study.
    PLoS One. 2024;19:e0311792.
    PubMed         Abstract available
31. COUGHENOUR C, Chien LC, Labus B, Gakh M, et al
    Shifting employment and perceptions of household responsibilities during early stages of the COVID-19 pandemic in Nevada, USA.
    PLoS One. 2024;19:e0309906.
    PubMed         Abstract available
32. STOCKL KM, Tucker J, Beaubrun A, Certa JM, et al
    Real-world use of multiplex point-of-care molecular testing or laboratory-based molecular testing for influenza-like illness in a 2021 to 2022 US outpatient sample.
    PLoS One. 2024;19:e0313660.
    PubMed         Abstract available
33. LI Y, Kong D, Ding Y, Wang J, et al
    The potential impact of COVID-19 vaccination on patients with immune thrombocytopenic purpura: A protocol for systematic review and meta-analysis.
    PLoS One. 2024;19:e0308546.
    PubMed         Abstract available
34. TANAKA R, Tamao K, Ono M, Yamayoshi S, et al
    In vitro one-pot construction of influenza viral genomes for virus particle synthesis based on reverse genetics system.
    PLoS One. 2024;19:e0312776.
    PubMed         Abstract available
35. FEATHER J, Liverpool S, Allen E, Owen M, et al
    Locating the evidence for children and young people social prescribing: Where to start? A scoping review protocol.
    PLoS One. 2024;19:e0310644.
    PubMed         Abstract available
36. TANG F, Yang W, Wu W, Yao Y, et al
    Comparative analysis of state-level policy responses in global health governance: A scoping review using COVID-19 as a case.
    PLoS One. 2024;19:e0313430.
    PubMed         Abstract available
37. KNEDLIKOVA L, Dedkova L, Kolar S, Ceska K, et al
    The impact of the COVID-19 pandemic on stress and coping in parents of children with Autism Spectrum Disorder.
    PLoS One. 2024;19:e0313426.
    PubMed         Abstract available
38. EZEZIKA O, Kotsaftis TS, Amponsah-Dacosta E, Demi S, et al
    A protocol for modeling the factors influencing the deployment of the COVID-19 vaccine across African countries.
    PLoS One. 2024;19:e0311800.
    PubMed         Abstract available
39. XIAO J, Liu B, Matsika J, Wu R, et al
    Evaluating male sexual function and reproductive health during Omicron outbreak in China.
    PLoS One. 2024;19:e0310145.
    PubMed         Abstract available
40. PARK HR, Lee SY, Moon HJ, Kim JH, et al
    Longitudinal changes in sleep and sleep-related symptoms among Korean adults between 2010 to 2022, including the COVID-19 pandemic period.
    PLoS One. 2024;19:e0311600.
    PubMed         Abstract available
41. CHEWASKULYONG B, Satjaritanun P, Ketpueak T, Suksombooncharoen T, et al
    Neutralizing antibodies and safety of a COVID-19 vaccine against SARS-CoV-2 wild-type and Omicron variants in solid cancer patients.
    PLoS One. 2024;19:e0310781.
    PubMed         Abstract available
42. SHUKLA I, Wilmers CC
    Waste reduction decreases rat activity from peri-urban environment.
    PLoS One. 2024;19:e0308917.
    PubMed         Abstract available
43. AMER A, Ayoub A, Brousseau E, Auger N, et al
    Risk of severe influenza infection in women with a history of pregnancy complications: A longitudinal cohort study.
    PLoS One. 2024;19:e0313653.
    PubMed         Abstract available
44. MIYAKITA K, Sato F, Nakano K
    Performance evaluation of virtually deployed road networks for inter-drone communications.
    PLoS One. 2024;19:e0313400.
    PubMed         Abstract available
45. HOFFSTADT HE, Verhoef MJ, Akkermans A, van der Steen JT, et al
    “Are you listening?”: Experiences shared online by family caregivers of patients in the palliative phase during the Covid-19-pandemic.
    PLoS One. 2024;19:e0310624.
    PubMed         Abstract available
46. LI X, Han J, Lin H
    The effects of psychological flexibility and night shifts on mental health and well-being in nurses.
    PLoS One. 2024;19:e0313634.
    PubMed         Abstract available
47. KENNEDY L, Hirdes JP, Heckman G, Searle SD, et al
    The effect of the COVID-19 pandemic on delirium incidence in Ontario long-term care homes: A retrospective cohort study.
    PLoS One. 2024;19:e0311098.
    PubMed         Abstract available
48. GAO W, Yang S
    Higher-order moments spillovers among energy, carbon and tourism markets: Time- and frequency-domain evidence.
    PLoS One. 2024;19:e0313002.
    PubMed         Abstract available
49. SIX S, Israel D, Bilsen J, Kharagjitsing A, et al
    Insights into cultural and compliance challenges in type 2 diabetes care: A qualitative study of Moroccan and Belgian patients in Belgium.
    PLoS One. 2024;19:e0310800.
    PubMed         Abstract available
50. CHAIR SY, Kilpatrick K, Heffernan C, Hays SM, et al
    Impact of the COVID-19 pandemic on clinical care and patient-focused outcomes of advanced nursing practice: A cross-sectional study.
    PLoS One. 2024;19:e0313751.
    PubMed         Abstract available

    Proc Natl Acad Sci U S A

51. IYANIWURA SA, Ribeiro RM, Zitzmann C, Phan T, et al
    The kinetics of SARS-CoV-2 infection based on a human challenge study.
    Proc Natl Acad Sci U S A. 2024;121:e2406303121.
    PubMed         Abstract available
52. NGUYEN MH, Palfy G, Fogeron ML, Ninot Pedrosa M, et al
    Analysis of the structure and interactions of the SARS-CoV-2 ORF7b accessory protein.
    Proc Natl Acad Sci U S A. 2024;121:e2407731121.
    PubMed         Abstract available

    Vaccine

53. IRALA S, Hamid S, Penayo E, Michel F, et al
    COVID-19 vaccine effectiveness against hospitalizations in Paraguay, May 2021-April 2022: A test-negative design.
    Vaccine. 2023 Sep 14:S0264-410X(23)01069-1. doi: 10.1016/j.vaccine.2023.
    PubMed         Abstract available
54. LEWIS NM, Harker EJ, Leis A, Zhu Y, et al
    Assessment and mitigation of bias in influenza and COVID-19 vaccine effectiveness analyses – IVY Network, September 1, 2022-March 30, 2023.
    Vaccine. 2024;43.
    PubMed         Abstract available
55. KOUASSI KS, Chisupa E, Clarke A, Massenon I, et al
    Pandemic-related resilience in HPV vaccination programmes – Perspectives from selected countries in Africa on what it will take to vaccinate 90 % of girls by 2030.
    Vaccine. 2024;42 Suppl 2:S33-S36.
    PubMed         Abstract available

    Virology

56. NOWAK R, Gazecka M, Hoffmann M, Kierzek R, et al
    TMPRSS2-specific antisense oligonucleotides inhibit host cell entry of emerging viruses.
    Virology. 2024;600:110218.
    PubMed         Abstract available
57. OO A, Chen Z, Cao D, Cho YJ, et al
    Biochemical simulation of mutation synthesis and repair during SARS-CoV-2 RNA polymerization.
    Virology. 2024;600:110255.
    PubMed         Abstract available
58. WANG C, Zhang Y, Yang C, Ren W, et al
    Receptor binding mechanism and immune evasion capacity of SARS-CoV-2 BQ.1.1 lineage.
    Virology. 2024;600:110241.
    PubMed         Abstract available
59. WANG M, Valadez-Ingersoll M, Gilmore TD
    Control of nuclear localization of the nucleocapsid protein of SARS-CoV-2.
    Virology. 2024;600:110232.
    PubMed         Abstract available

Adverse #events associated with #oseltamivir and #baloxavir marboxil in against #influenza virus #therapy: A #pharmacovigilance study using the FAERS database

Source: PLoS One, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0308998

Abstract
Background
Influenza virus is a widespread pathogen that poses significant health risks to humans. Oseltamivir and Baloxavir Marboxil are commonly utilized medications for both treating and preventing influenza infections. Despite their widespread use, there remains a need to thoroughly investigate their safety profiles and potential adverse reactions.

Objective
This study aims to comprehensively analyze the adverse events associated with oseltamivir and baloxavir marboxil in real-world clinical settings, with the goal of assessing their safety and potential risks in the management of influenza virus infections.

Methods
We conducted a retrospective analysis utilizing data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database, spanning from the first quarter of 2004 to the third quarter of 2023. The analysis encompassed examination of drug utilization patterns, types of adverse events reported, patient demographics, and other pertinent factors.

Results
From the first quarter of 2004 to the third quarter of 2023, FAERS collected over 17,035,521 adverse event reports (AE reports). Among these reports, there were 38,384 reports associated with oseltamivir, and 3,364 reports associated with baloxavir marboxil. Oseltamivir and Baloxavir Marboxil were primarily used for the treatment of influenza virus infections, accounting for 62.43% and 67.49% of their total usage, respectively. The main adverse reactions reported for oseltamivir were vomiting (case reports = 1402) followed by confusional state (case reports = 353), while for baloxavir marboxil, adverse reactions mainly centered around off-label use (case reports = 378) and intentional product use issues (case reports = 278). In terms of systemic adverse reactions, oseltamivir primarily affected psychiatric disorders (n = 45), whereas baloxavir marboxil mainly impacted the gastrointestinal system (n = 7). Additionally, regarding adverse reactions in pregnant women, the occurrence of normal newborns was a significant signal for oseltamivir, suggesting a certain level of safety during maternal use. Conversely, reports of adverse reactions such as respiratory arrest were documented for baloxavir marboxil, while no such reports were associated with oseltamivir.

Conclusion
This study provides a comprehensive analysis of the adverse reactions observed with the clinical use of oseltamivir and baloxavir marboxil, revealing the safety and risks associated with these two drugs in the treatment and prevention of influenza virus infections. Firstly, although both drugs are used for influenza treatment, they exhibit different types of adverse reactions. Oseltamivir predominantly affects the psychiatric system, while baloxavir marboxil primarily impacts the gastrointestinal system. Additionally, oseltamivir demonstrates a certain level of safety for use in pregnant women, while reports of adverse reactions such as respiratory arrest are associated with baloxavir marboxil. Despite the clinical significance of this study, limitations exist due to the voluntary nature of data reporting, which may lead to reporting biases and incomplete information. Future research could employ more rigorous prospective study designs, integrating clinical trials and epidemiological studies, to more accurately assess the safety risks of oseltamivir and baloxavir marboxil.

____

Source: US Centers for Disease Control and Prevention, edited, https://www.cdc.gov/media/releases/2024/t1107-mmwr-telebriefing.html

Please Note: This transcript is not edited and may contain errors.

Operator – 00:00

Welcome and thank you for standing by. At this time, all participants are in a listen only mode until the question and answer session of today's conference. At that time, you may press star one on your phone to ask a question. I would like to inform all parties that today's conference is being recorded. If you have any objections, you may disconnect at this time, I would now like to turn the conference over to Benjamin Haynes, thank you, maybe again.

Moderator – 00:23

Thank you Courtney, and thank you all for joining us today as we release a new MMWR and updated CDC guidance on the H5N1 bird flu outbreaks. We're joined today by Dr. Demetre C. Daskalakis, Director of the National Center for Immunization and Respiratory Diseases and CDC Principal Deputy Director, Dr. Nirav Shah, I'd like to remind everybody that this briefing is embargoed until 1pm Eastern, when our MMWR goes live on the CDC website. I'll now turn the call over to Dr Daskalakis.

Dr. Demetre C. Daskalakis – 00:58

Thank you and good morning everyone. I will first provide an update on H5 cases in the United States. Then we'll share some findings that are being published in an MMWR later today. 

So first, the situation overview. 

To date, there have been 46 human cases of H5 in the US, in 2024 25 cases were due to the ongoing outbreak in dairy cows. 20, which of which are 21, of which are in California. 20 cases are due to poultry depopulation, including the 11 recent cases from Washington State. Additionally, there is one case in Missouri with no known animal or animal product exposure. 

CDC continues to assess the risk to the general population is low. 

Efforts to protect people with exposure to animals or animal products affected by H5 continues to be a key focus of our public health activities. I'd like to now share the results of an important study focused on workers that will be published in the Morbidity and Mortality Weekly Report later today, or MMWR. 

So this is the Michigan Colorado dairy worker survey, CDC, coordinated with state health departments in Michigan and Colorado to conduct an anonymized serosurvey among dairy workers exposed to dairy cows infected with H5N1 influenza A. So as a reminder, a serosurvey is a collection and testing of blood from a defined population. 

In this case, dairy farm workers to estimate the prevalence of antibodies against an infectious pathogen, in this case, H5N1, as an indicator of possible exposure prevalence or immunity. 

The purpose of the serosurvey was to expand our understanding of the extent of infections among exposed dairy farm worker workers, how these infections related to symptoms experienced by participants, and what activities or actions were associated with infection. 

Blood samples were collected from June to August 2024 from 115 people who worked on dairy farms in Michigan and Colorado with cows that were confirmed positive for H5 virus. 

35 of the people included in this serosurvey had results previously reported earlier this summer, and as a reminder, there were dairy farm workers from Michigan and all tested negative for H5N1 antibodies. 

80 additional people were recruited in Michigan and Colorado to increase the sample size of the serosurvey and provide more robust results. 

Samples were collected 15 to 90 days after H5N1 virus was identified in cows on the farm. Along with getting their blood drawn, individuals were interviewed to learn more about what they did on the farm, what protective measures they took, and whether they had been sick since cows on their farms had been diagnosed with H5N1 or quarantine. 

All samples were tested for antibodies against the H5N1 virus isolated from the first human case this year in Texas. And we also tested samples against a seasonal H1N1, virus as a positive control. 

So on to the results, eight of the 115 samples, that's 7% were seropositive against HPAI, or highly pathogenic avian influenza. The 2.3.4.4b A clade that we see circulating among dairy cows using two different antibody tests to be considered antibody or seropositive, both tests had to be positive using accepted criteria. 

Another lab protocol was also performed to remove seasonal influenza antibodies and to rule out that the positive H5N1 tests were due to cross reactivity related to these commonly circulated viruses. 

On to the specific results, 8 of the 115 people tested positive for H5N1 antibodies using this protocol of the seropositive individuals, four remembered having symptoms, mostly conjunctivitis. The other four did not among these four people, illnesses began prior to or shortly after identification of infected herds, more details of who was who had positive results. All eight were Spanish speakers. All eight reported milking cows or cleaning the milking parlor, supporting these as higher risk activities, none wore respiratory protection, and less than half were eye protection, highlighting the need for better tools to support worker protection. Only one person reported they worked with infected cows, despite the fact that they were working with cows on farms with known infection. 

One important limitation to the survey data is that the interviews were conducted on an average 49 days after the first exposure to infected cows with some workers interviewed up to 90 days after their first exposure. That makes recall of minor symptoms potentially difficult. 

Nevertheless, these data help us better understand the potential for infection with mild or no symptoms, as well as highlighting interventions that may help workers reduce their risk of exposure and infection with H5N1.

I’ll now hand the mic over to Dr. Shah, who will go into more details about actions that CDC is taking to further mitigate risk to people who work with animals and animal products potentially affected by H5N1 Dr Shah.

Dr. Nirav Shah – 06:05

Thank you, Dr Daskalakis, and good morning everyone. This is Nirav Shah from CDC, and I'm going to be discussing the steps that CDC is taking in light of the serology results that Dr Daskalakis just outlined. The purpose of these actions is to keep workers safe, to limit the transmission of H5N1 to humans and reduce the possibility of the virus changing right now. 

There are two principal ways that people in the United States are being infected with H5N1 via exposure to infected poultry during culling events, and via exposure to infected dairy cows during the milking process. What we are announcing today is an intensification of recommendations to focus on the highest exposure tasks in poultry and dairy operations, ultimately to reduce the risk of infection. 

We're doing so in three areas. 

Number one, expanding our recommendation for who should be tested for H5N1. 

Number two, a new recommendation for use of Tamiflu for exposed, asymptomatic workers. 

And then number three, focusing our PPE guidance for workers based on their risk of exposure coupled with additional training activities. 

So let's start with testing the serology data that Dr Daskalakis outlined show that there may be individuals who were infected with H5 but who do not recall having symptoms. That means that we in public health need to cast a wider net in terms of who is offered a test so that we can identify, treat and isolate those individuals. Now, previously, as part of an outbreak investigation, we focused on workers who were exposed and who had symptoms. 

Going forward, CDC is expanding our testing recommendation to include workers who were exposed and who do not have symptoms, particularly those workers who were exposed without having worn proper PPE. Again, we're expanding our recommendation to include workers who were exposed and who do not have symptoms, particularly those who were not wearing appropriate PPE. 

The purpose of this expansion, informed by the new serology data, is to actively identify exposed workers with H5, even if their symptoms are so mild as to be unnoticeable, so that those two that those workers too, can be offered treatment and isolation. This active case finding reduces the likelihood that a mild infection could turn into a severe infection, or that the infection spreads to anyone else. 

Simply put, the less room we give this virus to run, the fewer chances it has to cause harm or to change. And the best way to limit the virus's room to run is to test, identify, treat and isolate as many cases as possible in humans and as quickly as possible. 

Second, let's turn to our new recommendation for medication for exposed asymptomatic workers. A key part of our strategy is to offer treatment with Tamiflu to workers who were exposed and who show symptoms that are consistent with H5N1 infection, but in light of the data that Dr Daskalakis outlined, which showed again, the existence of individuals with mild or even no symptoms that they can remember, CDC now recommends offering Tamiflu to asymptomatic workers who had a high risk exposure to H5N1 animals without having worn adequate PPE. 

Again, we are expanding the scope of who CDC recommends Tamiflu for to include now workers who are asymptomatic, who had a high risk exposure to an H5N1 infected animal without having worn adequate PPE. 

So what's at high risk exposure? Well, that could include an unprotected splash in the face with raw cow milk or on the poultry setting, something that might have happened during a depopulation or culling event where the individual was not wearing appropriate PPE. 

Just as with our expanded testing recommendation, more widespread use of Tamiflu achieves several goals. Chief among them is to protect workers. It reduces the likelihood of an asymptomatic case being symptomatic because they're receiving Tamiflu, and thus, it lowers the risk and the chances of onward transmission to close contacts, and then the third thing is our focus on PPE guidance to farms and workers based on their risk level. 

CDC continues to focus on primary prevention strategies like PPE for workers with potential occupational exposures to animals or to animal products that are infected by H5 in light of the serology data. CDC is updating our PPE recommendations for workers based on their risk of workplace exposure going forward. 

CDC PPE recommendations will prioritize what PPE a farm worker should wear based on our data indicating which farm tasks present the highest risk for H5N1, exposure and infection, for example, culling operations or working in the milking parlor with sick or infected animals, simply put, the higher risk activities will call for more PPE use. 

CDC has developed additional resources to support training workers on PPE use and to explain its role in preventing H5N1 from animals infecting humans. 

CDC will continue to evaluate this situation and will update our guidance as needed. To close, what we've discussed today is an example of CDC using data to drive action. We will continue working with trusted partners to reach farm workers and their employers to communicate these prevention strategies as widely as possible. And then finally, before we open it up to questions, we will, we anticipate publishing a spotlight today that contains these updated recommendations. With that, we'll turn it over back to our team for questions.

Moderator 12:34

Thank you. Dr. Shah. We are now ready to open up for questions.

Operator – 12:39

Thank you. We will now begin the question and answer session. If you would like to ask a question, please press star one. If you need to withdraw your question, press star two. Again to ask a question, please press star one. Our first question comes from Brenda Goodman from CNN.

Brenda Goodman – CNN – 12:58

Thank you so much for taking my question and congratulations on these studies, because I know you had some significant headwinds to get them done. I have a question about the eight workers, are they counted as cases now? Or will they be counted as cases in the human case count? And then I was curious. You gave an update at the beginning. Dr Daskalakis about how many human cases of H5 were associated with poultry depopulations this year. Why do you think we're so many seeing so many more human infections with poultry depopulation because we've had age five in poultry before, and I think we only had one case prior this year.

Dr. Demetre C. Daskalakis – 13:38

Great. Thank you for those questions. So on the first question, these retrospective serologies are not going to be reported as cases, so they are really looking retrospectively, helping us learn, but they're not going to be called cases. On the second question, I think there are a lot of reasons why we could potentially be seeing more human disease related to or human infections related to the culling operations. 

One is there's more H5, so that's probably one of the most important. Like both in wild birds as well as in poultry, we're seeing a significant increase, and the more the sort of H5 community viral load is high in animals, the more likely it is that humans will be exposed. 

I think the second is also that we, I think, have raised a lot of attention to carefully screening individuals with H5 exposure for even mild symptoms. So there could be that as well. 

In terms of other characteristics of the virus, we are not seeing any changes with the virus that would indicate ease of transmission. But given sort of our current environment, the sort of increasing experience with age five and one really creating strategies to better protect workers based on this data is, I think, the right thing to do at this time.

Operator – 15:00

Our next question comes from Megan Molteni from STAT

Megan Molteni from STAT – 15:06

Thanks for taking my question. I was wondering if you could clarify something that you said about only one of the persons who tested positive for antibodies reporting having worked with known infected cows, and it sounded like you were saying that that meant there was a need for more additional education. But could it also be that these animals that they're working with are asymptomatic, and so, you know, they're going through the milking parlors and they're not getting separated out into quarantine? Can you talk a bit about what we know about asymptomatic disease in the animal.

Dr. Demetre C. Daskalakis – 15:41

Great. Thank you. So. So I think that you put the nail on the head that this is really about about education and also self-assessment of risk, which I think is an important piece of both why one would wear post, why one would wear appropriate PPE as well as pursue post exposure prophylaxis. So these were farms with known infected cows, and so it was really about the fact that they didn't have the awareness that they had any sick cows that they were working with, even though they were in environments where sick cows were known. So it really speaks to the importance of more on farm training around H5 as well as ways to protect from H5

Megan Molteni from STAT – 16:22

Okay, thank you. Can you also just, very quickly, are there any more serology studies planned in other states, like thinking about California, given the number of herds we see there now.

Dr. Demetre C. Daskalakis – 16:33

Thank you for that question. So we are currently working, and I think we've, we've put this up on one of our prior spotlights on a serology study, a serosurvey, that is that was conducted it physically in Ohio, because there was a large convention of bovine practitioners, and so we about 150 of them provided blood samples as well as survey data. And we will update on those once they become available.

Operator – 17:04

Our next question comes from Josh Nathan-Kazis from Barrons.

Josh Nathan-Kazis from Barrons – 17:08

Sorry. Thank you so much. Two quick questions. One, I wonder if you could have some context. I mean, how unexpected is it that there would be asymptomatic HVAC cases? That's something that's been seen before elsewhere. How much of a surprise of the finding and separately I saw in the MMWR says that 40% of the workers reported feeling ill while H5 was on their farm, although only a fraction of those actually had serological evidence of infection. I wonder, if you just talk about what might be going on there and why so many of the workers said they felt sick, even if their blood tests didn't say they were sick.

Dr. Demetre C. Daskalakis – 17:46

Thank you. So on the first question, I think that the only way to sort of take out surprises by doing the studies, which is why it's important that we have that information. 

But I think given the mildness of the symptoms that many people are presenting with, it's not a surprise that some people wouldn't recall symptoms up to 90 days after their exposure. 

So again, though not surprising, it actually is approximately in line with other serosurveys that have been conducted that focused on, on, again, this specific clade of H5N1, so a study that happened in workers, 2223 showed about 4.6% were seropositive, and about 14% as you recall from a pre print that UT Galveston Galveston put out in early 2024 also showed asymptomatic individuals with infection. 

So again, not surprising, but in line with some of the other data. 

Now, question two, not every respiratory symptom is related to H5N1. And so we've actually seen in other environments that there is several other viruses that could explain respiratory symptoms. 

So in this circumstance, though there was not serology done for other respiratory symptoms, that likelihood is that the illnesses that they that they experienced, were not caused by H5N1 based on our testing criteria. Over,

Dr. Nirav Shah – 19:13

Hey Josh, this is Nirav. One other point you noted, or you framed some of these results as asymptomatic, the structure of the survey itself doesn't demonstrate whether these individuals were asymptomatic or whether they just couldn't remember having had symptoms. 

And so the most we can say is that they can't remember having had symptoms. Some of them may have had mild symptoms that, again, were unmemorable. Some of them may have been indeed asymptomatic. The data that we have does not allow us to determine which of those it was, and so for that reason, we're not characterizing these as asymptomatic. All we can say is that they don't recall having had symptoms.

Operator – 19:55

Our next question comes from Erica Edwards.

Erica Edwards – 20:00

Hey, thanks so much. I appreciate the opportunity. And a couple questions. One is about the severity of H5N1 illness in people. I mean, obviously previous estimates from other areas of the world have quoted mortality rate of at least 50% I'm curious what you're learning about from studying the H5N1 infections here in the US that I think would be quite mild. What's different here? And then, if I also could ask, could you talk about any work that's being done to develop rapid tests, H5N1? Thank you.

Dr. Demetre C. Daskalakis – 20:32

Thanks for that question. So on, the severity, again, what we've been seeing in the United States is extremely mild symptoms. 

So again, ranging from moderate to mild conjunctivitis, and some people also experiencing mild respiratory symptoms, and also some with constitutional symptoms, like there have been some folks with beavers. 

So, you know, I think that there are a couple of hypotheses, which is all that we can really provide as to why there's a difference in severity. 

One, you know though, though H, all, H, 5n, ones are not built the same. So these are actually potentially different genotypes. So we know that there's sort of different clades and genotypes circulating. 

So what we have in the US at this point has only caused mild illness. 

Also, there could be issues related to the populations that are exposed to the virus, as well as to the magnitude of the exposure. So again, all hypotheses. So we don't have a very clear answer, but from the perspective of what we're seeing in the US, everything has been mild.

Dr. Nirav Shah – 21:40

And then this is Nirav on your latter question around rapid tests. So CDC has been working very closely with our colleagues at NIH particularly their rad X program, to evaluate some of the rapid diagnostic tests that are already available on the market, to determine whether those tests are capable of detecting H5 These are tests that can already detect influenza A, influenza B, sometimes even COVID in general. 

But the question is, can they detect H5 the current circulating version of H5 as part of their overall diagnostic approach? And CDC has been collaborating with our NIH colleagues to try to understand the utility of those tests. We don't have a timeline on when those data will be available, but I know that work is underway right now. 

Separately, we've been working with diagnostics companies to determine what types of additional rapid tests might be useful in the marketplace to try to move or shorten the duration between becoming symptomatic or exposed and then being able to have access to testing. Clearly rapid test still an important niche there, so we're very much in favor of them. We've just got to make sure that they are capable of serving that purpose.

Dr. Demetre C. Daskalakis – 22:48

Just one other thing to add is CDC will also be working with with a couple of states, to do a testing pilot where we're actually assessing a near point of care, or point of care test against lab based testing for H5, so that will also help elucidate some point of care strategies or or self-testing that may help in the future.

Operator – 23:15

Our next question comes from Washington Post.

Washington Post – 23:21

Hi. Thanks for taking this call. Two questions. One, you mentioned one of the justifications for these precautionary measures being preventing onward spread, but we've also been hearing there's no evidence of human to human transmission. So does this new data create any concerns that some of these dairy workers may have been spreading the virus among each other, and then the second one is now that we have an incoming administration that's promised mass deportations. Are you worried about about a cooperation with these, investing with these investigate public health investigations in the future? Would you get the same kind of cooperation that you did with with workers, if there's a potential, if there's mass deportations looming, great

Dr. Nirav Shah – 24:07

This is Nirav as to the former question, I'm glad you raised that for avoidance of doubt and for clarity, there is nothing that we've seen in the new serology data that gives rise to a concern about person to person transmission. So to your point that you made about, why are we going this extra step with additional testing and Tamiflu to further in that regard? And the answer is to drive that risk down as low as possible. This is fundamentally a respiratory virus, and although we have not seen changes to the virus that would suggest the capacity for it to spread from person to person. 

We want to keep that risk as low as where it is right now, one of the best ways to do that is to identify individuals who have been exposed through greater testing and provide them with Tamiflu to drive down the levels of virus in their body, which, again. Helps us keep that low risk as low as possible. As to your latter question, we're not commenting on anything related to transition or an incoming administration. We're focused today on the serology data and the CDC actions therein. Thanks,

Moderator – 25:15

Cortney. We have time for two more questions, please.

Operator – 25:19

Our next question comes from Youri Benadjalud from ABC News.

Youri Benadjalud from ABC News – 25:22

Thanks for taking my question. This data seems to support that there are a lot of cases that are potentially being undercounted, and there's only 46 confirmed by the CDC so far. How many cases in across forums, in the US, do you think that could actually be out there? And then I'll have a follow up, please.

Dr. Nirav Shah – 25:43

Thanks Yuri. Our data suggests that there in any outbreak situation, we know that there are individuals who may have been exposed, may have been infected, who are not part of the count. This is what serology data helps us get a better retrospective understanding of we still need more data to better characterize that so we can't speculate today on how many unidentified cases that there might be. We've always known that that's a possibility. What these data really help us understand is that some of those workers may have had such mild symptoms, such that they may not recall having been ill, and thus we need to identify those individuals and make sure they've got medication, as I said, in connection with the prior question, to drive their risk of getting ill as far as possible down, as well as to reduce the likelihood of spread. But better characterizing right now, how much of the iceberg is above the water versus below the water. It's not something we have enough data on quite yet.

Operator – 26:43

Our last question was from Kai Kuperschmid from Himes Magazine.

Kai Kuperschmid from Himes Magazine – 26:51

Thanks for taking my question. So I wanted to ask a little bit about the timeline. Here you said the the samples were taken, I think June to August. It's November now, and just in general, I mean, it's taken a long time to get this kind of data. I know a lot of people have been waiting for it. Can you describe a little bit why it took this long, and what the hurdles are to do this, also to do it in other places, possibly. Thanks guys.

Dr. Demetre C. Daskalakis – 27:14

So I think a lot of the timeline is really around just sort of the standard procedures for serology for H5. So the first is again, we had to sort of gather the specimens. They had to come to CDC. And then the subsequent pieces are that these 115 specimens had to be run in our BSL, three labs that, as increasing data emerged, the cross reactivity with seasonal flu became something that we needed to be addressing in the testing. We then had to develop additional protocols to do the adsorption for seasonal flu, then run the absorption and then rerun the tests again. So this was released, really at a good time and a good timeline, given the complexity of non-routine laboratory testing that was needed to be able to characterize these individuals. Thanks for your question.

Moderator – 28:10

I’d like to thank you all for joining us today. If we did not get to your question, or if you have follow up questions, please feel free to call the main CDC press office at 404-639-3286 or you can email media@cdc.gov Thank you for joining us, and this will conclude our call.

That concludes today’s conference. Thank you for participating. You may disconnect at this time.

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