ETIDIOH - NEW

 Public Domain. Source: WikiArt,  https://www.wikiart.org/en/titian/pesaros-madonna-1526 _____

Abstract SARS-CoV-2 main protease, Mpro , is responsible for processing the viral polyproteins into individual proteins, including the protease itself. Mpro is a key target of anti-COVID-19 therapeutics such as nirmatrelvir (the active component of Paxlovid). Resistance mutants identified clinically and in viral passage assays contain a combination of active site mutations (e.g., E166V, E166A, L167F), which reduce inhibitor binding and enzymatic activity, and non-active site mutations (e.g., P252L, T21I, L50F), which restore the fitness of viral replication. To probe the role of the non-active site mutations in fitness rescue, here we use an Mpro triple mutant (L50F/E166A/L167F) that confers nirmatrelvir drug resistance with a viral fitness level similar to the wild-type. By comparing peptide and full-length Mpro protein as substrates, we demonstrate that the binding of Mpro substrate involves more than residues in the active site. Particularly, L50F and other non-active site mutations...

Abstract Background The International Health Regulations (2005) (IHR), requires that States Parties develop their capacities to detect, assess, and respond to public health threats and report to the World Health Assembly through the States Parties Annual Report (SPAR). The National Pandemic Preparedness and Response Plans (PPRP) contribute to countries capacities however there are some discrepancies between both tools. To identify gaps and define priority actions to strengthen pandemic plans, we assessed the concordance between national pandemic preparedness and response plans for respiratory pathogens against the pandemic checklist published in 2023 and the SPAR. Methods In this retrospective, semi-quantitative study , conducted in August 2024, we reviewed the most recent respiratory pandemic plans for 35 PAHO member states and assessed their concordance with (1) actionable guidelines in the World Health Organization pandemic checklist and (2) IHR (2005) core capacities using the late...

Abstract H1N1 influenza viruses are responsible for both seasonal and pandemic influenza . The continual antigenic shift and drift of these viruses highlight the urgent need for a universal influenza vaccine to elicit broadly neutralizing antibodies (bnAbs). Identification and characterization of bnAbs elicited in natural infection and immunization to influenza virus hemagglutinin (HA) can provide insights for development of a universal influenza vaccine. Here, we structurally and biophysically characterize four antibodies that bind to a conserved region on the HA membrane-proximal region known as the anchor epitope. Despite some diversity in their VH and VK genes, the antibodies interact with the HA through germline-encoded residues in HCDR2 and LCDR3. Somatic mutations on HCDR3 also contribute hydrophobic interactions with the conserved HA epitope. This convergent binding mode provides extensive neutralization breadth against H1N1 viruses and suggests possible countermeasures against...

Situation at a glance On 30 January 2025, the Ministry of Health of Uganda declared an outbreak of Sudan virus disease (SVD) following confirmation from three national reference laboratories.  The case presented with signs and symptoms between 20 and 21 January and died on 29 January at the National Referral Hospital in Kampala.  As of 30 January 2025, 45 contacts have been identified , including 34 healthcare workers and 11 family members.  Sudan virus disease belongs to the same family as Ebola virus disease. It is caused by Sudan virus (SUDV). It is a severe disease with high case fatality from 41% to 70% in past outbreaks.  In the absence of licensed vaccines and therapeutics for the prevention and treatment of SVD, the risk of potential serious public health impact is high.  Early supportive patient care and treatment may increase the chance of survival from severe disease. Description of the situation On 30 January 2025, the Ministry of Health of Uganda de...

  Antiviral Res WU Q, Wu H, Hu Y, Zheng X, et al Immune evasion of Omicron variants JN.1, KP.2, and KP.3 to the polyclonal and monoclonal antibodies from COVID-19 convalescents and vaccine recipients. Antiviral Res. 2025 Jan 24:106092. doi: 10.1016/j.antiviral.2025.106092. PubMed           Abstract available Infect Control Hosp Epidemiol HANKINS RJ, Handke L, Fey PD, Cavalieri RJ, et al Prospective, crossover, comparative study of two methods of chlorhexidine bathing. Infect Control Hosp Epidemiol. 2025 Jan 30:1-6. doi: 10.1017/ice.2024. PubMed           Abstract available PISCHEL L, Aguolu OG, Ahmed N, Campbell MM, et al Social mixing patterns of United States healthcare personnel at a quaternary health center: a prospective observational study. Infect Control Hosp Epidemiol. 2025 Jan 30:1-9. doi: 10.1017/ice.2024. PubMed           Abstract availab...

  Biochemistry (Mosc) KOROLEVA ON, Kuzmina NV, Tolstova AP, Dubrovin EV, et al Effect of C- and N-Terminal Polyhistidine Tags on Aggregation of Influenza A Virus Nuclear Export Protein. Biochemistry (Mosc). 2024;89:2238-2251. PubMed           Abstract available BMC Pediatr ZHANG P, Xin M, Bai Y, Ren X, et al Severe central nervous system injury in 9 children with COVID-19. BMC Pediatr. 2025;25:63. PubMed           Abstract available Epidemiol Infect BEDNARSKA NG, Smith S, Bardsley M, Loveridge P, et al Trends in general practitioner consultations for hand foot and mouth disease in England between 2017 and 2022. Epidemiol Infect. 2025;153:e22. PubMed           Abstract available J Virol KIRKPATRICK ROUBIDOUX E, Meliopoulos V, Livingston B, Brigleb PH, et al Intraductal infection with H5N1 clade 2.3.4.4b influenza virus. J Virol. 2025 Jan 31:e0192724....

ABSTRACT Reassortant highly pathogenic avian influenza A(H5N2) clade 2.3.4.4.b viruses were detected from ducks and environmental samples in Egypt , June 2024. Genomic and phylogenetic analyses revealed a novel genotype produced by the reassortment of an A( H5N1 ) clade 2.3.3.4b virus with an A( H9N2 ) G1-like virus. Monitoring the spread of this virus is important. Source: Emerging Microbes and Infections,  https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2455601#abstract _____

Abstract Following reports of HPAI H5N1 infections of dairy cattle in the United States (US) in March 2024, we established a Pan-Canadian Milk network to monitor retail milk in Canada. Milk samples from across Canada that had previously tested negative for influenza A virus (IAV) RNA were tested for the presence of anti-IAV nucleoprotein (NP) antibodies , as an indicator of past infection of dairy cattle. None of the 109 milk samples tested had evidence of anti-IAV NP antibodies. This is consistent with previous findings from our academic group as well as others including federal testing initiatives that have not found any IAV RNA in milk. Although not surprising given that no cases of H5N1 in cattle have been reported in Canada to date, this work further supports that the extensive outbreak in dairy cattle in the US has not extended northward into Canada, and the integrity of the Canadian milk supply remains intact. Source: MedRxIV,  https://www.medrxiv.org/content/10.1101/2025.01...

LETTER In March 2024, highly pathogenic avian influenza (HPAI) H5N1 of the clade 2.3.4.4b was detected in dairy cows in Texas and has since been detected in several other U.S. states (1). Virus has been detected within cow’s milk , indicating that the mammary epithelium may support viral replication (2). Virus has also been detected on milking machines , leading to a hypothesis that influenza is spreading through fomites from udder to udder instead of the intranasal route (3, 4). There have been studies using cows to better understand mammary infections; however, the cow model is costly and limited (1, 5). We sought to establish a model for intramammary infections of H5N1 and H1N1 influenza virus in mice . (...) Source: Journal of Virology,  https://journals.asm.org/doi/full/10.1128/jvi.01927-24?af=R _____

{Excerpt} Time Period: January 19 - January 25, 2025 -- H5 Detection : 33 sites ( 10.1% ) -- No Detection : 295 sites ( 89.9% ) -- No samples in last week : 61 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/bird-flu/h5-monitoring/index.html _____

The laboratory diagnosed type H5 on Thursday, January 23 in one of the sick birds that was sampled in the framework of passive surveillance , on January 24 all birds were culled, on January 29 the laboratory confirmed the detection of Neuraminidase 1 and identification of hemagglutinin genes found in the cleavage site of avian influenza virus type A lineage Goose/Guangdong (Gs/GD) subtype H5, clade 2.3.4.4. highly pathogenic. Out of the 408 backyard birds, one died and two became sick in Chiriquí Region. Source: WOAH,  https://wahis.woah.org/#/in-review/6225 ____

A  foie gras goose holding in Heves Region. Source: WOAH,  https://wahis.woah.org/#/in-review/6227 _____

 A breeding goose holding in Pest Region. Source: WOAH,  https://wahis.woah.org/#/in-review/6228 _____

 A wild Eurasian Jackdaw in Lounais-Suomen aluehallintovirasto Region. Source: WOAH,  https://wahis.woah.org/#/in-review/6229 _____

Abstract In April 2024, the Instituto Nacional de Enfermedades Respiratorias of Mexico City identified a case of unsubtypeable Influenza A in a 58-year-old immunocompromised patient with renal failure due to diabetic nephropathy and bacterial peritonitis. Through sequencing the M, NS, NA, NP, and HA complete segments, we identified an H5N2 influenza virus with identity of 99% with avian influenza A(H5N2) from Texcoco, Mexico, in 2024. This case is the first reported with direct evidence of human infection caused by the H5N2 influenza virus; the relationship of the virus with the severity of his condition remains unknown. Source: Viruses,  https://www.mdpi.com/1999-4915/17/2/205 _____

Summary Background DR Congo has the highest global burden of mpox , a disease caused by infection with the monkeypox virus . The incidence has risen since 1980, but recent analyses of epidemiological trends are lacking. We aimed to describe trends in suspected and confirmed mpox cases in DR Congo using epidemiological and laboratory mpox surveillance data collected from 2010 to 2023, and provide insights that can better inform the targeting and monitoring of control strategies. Methods We analysed aggregated national epidemiological surveillance data and individual-level laboratory data from 2010 to 2023. We calculated incidence based on suspected cases, case-fatality ratios, and percentage of laboratory-confirmed cases and assessed geospatial trends. Demographic and seasonal trends were investigated using generalised additive mixed models. Findings Between Jan 1, 2010, and Dec 31, 2023, a total of 60 967 suspected cases and 1798 suspected deaths from mpox were reported in DR Congo ( c...

Summary Highly pathogenic avian influenza has spilled into many mammals, most notably cows and poultry, with several dozen human breakthrough infections. Zoonotic crossovers , with hemagglutinins mutated to enhance viral ability to use human α2-6-linked sialic acid receptors versus avian α2-3-linked ones, highlight the pandemic risk . To gain insight into these crossovers, we determined the cryoelectron microscopy (cryo-EM) structure of the hemagglutinin from the zoonotic H5N1 A/Texas/37/2024 strain (clade 2.3.4.4b) in complex with a previously reported neutralizing antibody . Surprisingly, we found that the receptor-binding site of this H5N1 hemagglutinin was already occupied by an α2-3-linked sialic acid and that this glycan emanated from asparagine N169 of a neighboring protomer on hemagglutinin itself. This structure thus highlights recognition by influenza hemagglutinin of an “auto”-α2-3-linked sialic acid from N169, an N-linked glycan conserved in 95% of H5 strains, and adds “aut...

Abstract Influenza virus pandemics and seasonal epidemics have claimed countless lives. Recurrent zoonotic spillovers of influenza viruses with pandemic potential underscore the need for effective countermeasures . In this study, we show that pre-exposure prophylaxis with broadly neutralizing antibody (bnAb) MEDI8852 is highly effective in protecting cynomolgus macaques from severe disease caused by aerosolized highly pathogenic avian influenza H5N1 virus infection. Protection was antibody dose–dependent yet independent of Fc-mediated effector functions at the dose tested. Macaques receiving MEDI8852 at 10 milligrams per kilogram or higher had negligible impairment of respiratory function after infection, whereas control animals were not protected from severe disease and fatality. Given the breadth of MEDI8852 and other bnAbs, we anticipate that protection from unforeseen pandemic influenza A viruses is achievable. Source: Science,  https://www.science.org/doi/10.1126/science.ado64...

Abstract In late 2023 an H5N1 lineage of high pathogenicity avian influenza virus (HPAIV) began circulating in American dairy cattle.  Concerningly, high titres of virus were detected in cows’ milk , raising the concern that milk could be a route of human infection . Cows’ milk is typically pasteurised to render it safe for human consumption, but the effectiveness of pasteurisation on influenza viruses in milk was uncertain . To assess this, here we evaluate heat inactivation in milk for a panel of different influenza viruses. This includes human and avian influenza A viruses (IAVs), an influenza D virus that naturally infects cattle, and recombinant IAVs carrying contemporary avian or bovine H5N1 glycoproteins . At pasteurisation temperatures of 63 °C and 72 °C , we find that viral infectivity is rapidly lost and becomes undetectable before the times recommended for pasteurisation ( 30 minutes and 15 seconds, respectively ). We then show that an H5N1 HPAIV in milk is effectively i...