Innate Immune Responses Induced by #H9N2 #Influenza A Virus and #Klebsiella pneumoniae Co-Infection

 

Abstract

Klebsiella pneumoniae infection following H9N2 Influenza A virus (IAV) infection causes severe pneumonia. But the underlying pathogenic mechanisms of H9N2 IAV and K. pneumoniae co-infection are complex and need to be further explored. In this study, the lung transcriptomes of mice with H9N2 IAV and K. pneumoniae co-infection were characterized by transcriptomic profiling. As a result, GO enrichment analysis revealed that the differential genes were primarily involved in the activation of immune responses, cellular components of membranes and extracellular spaces, and defense responses against pathogen infections. According to KEGG enrichment, the differentially expressed genes (DEGs) were concentrated in TLR signaling pathways, RLR signaling pathways, TNF signaling pathways and NLRP3 signaling pathways. Furthermore, in vitro cell models were established to investigate the innate immune responses induced by H9N2 IAV and K. pneumoniae CPS co-stimulation. K. pneumoniae CPS stimulation influenced the cytokine profiles of mink lung epithelial cells infected with H9N2 IAV, worsened cell viability, and aggravated apoptosis, indirectly inhibiting H9N2 IAV replication. The findings demonstrated that K. pneumoniae superinfection modulated the innate immune responses induced by H9N2 IAV infection, contributing to its pathogenesis.

Source: 

Link: https://www.mdpi.com/1999-4915/18/8/900

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#Wastewater Data for Avian #Influenza #H5 (US CDC, August 14 '26)

 

{Excerpt}

(...)

A(H5) detections in the past week

Time Period: August 02, 2026 - August 08, 2026

    -- A(H5) Detection: 5 site(s) (1.2%)

    -- No Detection: 422 site(s) (98.8%)

    -- No samples: 88 site(s)

{Click on Image to Enlarge}

__

(...)

Source: 

Link: https://www.cdc.gov/wastewater/emerging-viruses/h5.html?

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Seasonal #surveillance in #humans in 2026 for #WNV - Weekly Update (ECDC, August 14 '26): 429 cases so far, of which 224 in #Italy

 

{Summary}

Week 33, 2026 | Produced on 14 August 2026 at 06:00, based on data submitted up until and including 13 August 2026.

Current situation

    Since the beginning of the 2026 transmission season, and as at 13 August, 77 areas affected by West Nile virus (WNV) have been identified in nine countries across Europe.

    These areas are located in 

        § Italy (40), 

        § Greece (13), 

        § Romania (12), 

        § France (four), 

        § North Macedonia (three), 

        § Spain (two), 

        § Germany (one), 

        § Kosovo* (one) and 

        § Serbia (one).

    This week, 19 areas are reported as affected for the first time this season. (...)

    The nine countries have reported 429 locally acquired human cases of WNV infection: 

        § Italy has reported 224, 

        § Greece 105, 

        § Spain 42, 

        § North Macedonia 30, 

        § Romania 18, 

        § France six, 

        § Serbia two, 

        § Germany one and 

        § Kosovo* one case.

(...)

Source: 

Link: https://www.ecdc.europa.eu/en/west-nile-fever/surveillance-and-disease-data/disease-data-ecdc

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#Chile - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

The date of last occurrence corresponds to the end date of the most recent event involving backyard birds in Biobío region, involving birds that were not considered poultry as defined by the OIE Terrestrial Code.

Source: 

Link: https://wahis.woah.org/#/in-review/7757

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#Antibody #evasion and receptor binding of #SARS-CoV-2 variants #PQ.16.1.1 and RK.1

 

{Excerpt}

Since its rapid global spread beginning in late 2024, the SARS-CoV-2 variant NB.1.8.1 has progressively displaced older omicron variants, and has established near-total dominance in Asia. More recently, two NB.1.8.1-derived sublineages, PQ.16.1.1 and RK.1, have emerged and expanded substantially, particularly in China and Singapore (...). Specifically, the sublineage PQ.16.1.1 acquired the amino acid substitutions Asp253Gly (within the N-terminal domain), alongside Asn417Thr, Asp420Asn, and Ile478Thr (within the receptor-binding domain) relative to the parental NB.1.8.1 strain (...). Concurrently, the RK.1 sublineage (formally classified as a descendant of the PQ.17.7.2.1 branch) acquired Asp420Asn, His445Pro, and Ile478Thr (...). Furthermore, PQ.16.1.1 has continued to evolve into the SV series sublineages (predominantly SV.2 and SV.2.1), which have maintained all receptor-binding domain mutations, including Asp420Asn, and have subsequently come to dominate the circulating SARS-CoV-2 strains in Singapore (...).

(...)

In summary, the convergent acquisition of the Asp420Asn substitution in NB.1.8.1 sublineages again illustrates a classic SARS-CoV-2 receptor-binding domain evolution trade-off: a sacrifice in hACE2 receptor engagement in exchange for profound, targeted evasion of class 1 neutralising antibodies. (...) Given the increased evasion of class 1 antibodies by these Asp420Asn-carrying sublineages, these variants will likely spread from Asia and begin to prevail in countries where mRNA vaccination is common and populations are enriched with class 1 neutralising antibodies. 

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00429-9/fulltext?rss=yes

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#Vaccine #imprinting drives increased #SARS-CoV-2 #variant infection in #children

 

Abstract

Virus exposure history, particularly first exposure, is believed to shape vaccine efficacy and infection susceptibility; however, evidence for mechanistic links between immune responses in individuals and epidemiological outcome in populations is scarce. Recent co-circulation of SARS-CoV-2 variants XFG and BA.3.2 has revealed a striking enrichment in BA.3.2 cases among children. By combining epidemiological modeling, serology and monoclonal antibody analysis in children and adults, we show the dependence of effective variant-specific antibodies on vaccination history which may explain birth-year influence on differential susceptibility to these co-circulating variants. Ancestral cross-reactive site I antibodies frequently neutralize BA.3.2, but not XFG. By contrast, Omicron type-specific site I/III and III antibodies frequently neutralize XFG but not BA.3.2, revealing a tradeoff in the ability to neutralize these two co-circulating strains. These findings mechanistically link immune history, variant neutralization, antibody repertoire and variant infection risk, and suggest that vaccination regimens in children should prioritize neutralization breadth.

Competing Interest Statement

E.J.W. advises Arpelos Bioscience, Arsenal Biosciences, Coherus, Danger Bio, IpiNovyx, New Limit, Marengo, Pluto Immunotherapeutics Related Sciences, Santa Ana Bio, and Synthekine. E.J.W. is a founder of and holds shares of Coherus, Danger Bio, and Arsenal Biosciences. All other authors declare no competing interests.

Funder Information Declared

National Institute of Allergy and Infectious Diseases, https://ror.org/043z4tv69, 75N93021C00015, U19AI082630, AI105343, AI108545, AI155577, AI149680

National Cancer Institute, 75N91019D00024, 75N91022F00005, 75N91023F00016

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.12.739589v1

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Identification and characterization of #PB2 #mutations associated with #mammalian #adaptation of highly pathogenic #H5N1 avian #influenza viruses

 

Abstract

The highly pathogenic avian influenza virus (HPAIV) subtype H5N1 has been continuously circulating among wild bird populations and domestic poultry. It’s ongoing circulation has led to outbreaks in poultry and U.S. dairy cattle populations, as well as sporadic severe infections in individuals engaged in poultry and dairy farming. These occurrences have raised concerns about the potential evolution of this virus into a pandemic strain. To elucidate the molecular determinants facilitating H5N1 cross-species adaptation and to evaluate its implications for public health, we conducted serials of sequence analysis and specific-site mutations on the viral polymerase subunit PB2 to determine its effect on polymerase activity and viral infectivity. The results showed that three mutations in the PB2 protein (E362G, D441N and M631L) were presented cooperative effects associated with enhanced viral replication in mammalian cells. Compared to the original isolated strain of the 2.3.4.4b clade, A/chicken/NL/FAV-0033/2021, these three mutations were predominantly identified in isolates obtained from cattle and other mammalian hosts between 2021 and 2024. The M631L mutation, identified as the primary determinant of increased polymerase activity in mammalian cells, significantly enhanced the binding affinity of PB2 to ANP32A. The mutation E362G and D441N did not increased polymerase activity and viral replication significantly but enhanced binding affinity of PB2 to ANP32A. The combined mutations with E362G, D441N and M631L resulted in a significantly increased polymerase activity and viral replication in H5N1 virus, and significantly elevated viral loads and aggravated pulmonary pathology in lungs of mice with H5N1 infection. These findings indicate that the PB2-M631L mutation constitutes a crucial molecular marker for the adaptation of H5N1 to mammalian hosts, whereas the E362G and D441N mutations likely function as supportive modulatory factors that optimize this host-adaptation process.

Source: 

Link: https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2026.1867604/full

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False-Reactive Fourth-Generation #HIV #Screening Results Before, During, and After #COVID19 #Pandemic in a High-Prevalence Urban Medical Center

 

Highlights

    • False-reactive HIV screens increased during the COVID-19 pandemic

    • Elevated HIV false-reactive proportions persisted post-pandemic

    • False-reactive HIV screens are predominantly low S/CO values

    • Age, race/ethnicity, and syphilis infection were associated with false-reactive results

    • Unresolved reactive screens reveal gaps in reflex nucleic acid test completion

Abstract

Objective

False-reactive results of the fourth-generation HIV-1/2 antigen/antibody (Ag/Ab) Combo assay trigger additional testing, increased costs, and patient anxiety. Large-scale analyses of false-reactive results spanning the COVID-19 pandemic in high-prevalence communities are lacking. This study aims to investigate the frequency of false-reactive HIV-1/2 Ag/Ab Combo screening results before, during, and after the COVID-19 pandemic and to identify associated patient factors.

Design

We conducted a retrospective study of HIV-1/2 Ag/Ab Combo assays performed from 2019 – 2024 at a tertiary care medical center in Baltimore, MD. False-reactive proportions were compared across pre-pandemic (January – December 2019; n=12,347), pandemic (January 2020 – June 2023, n=33,546), and post-pandemic (July 2023 – December 2024; n=12,238). Associations between false-reactive results and selected patient factors were assessed.

Results

Among 58,131 screens, 1,236 (2.1%) were reactive; 185 were false-reactive, yielding a false-reactive proportion of 15.0% among reactive results. The false-reactive proportion increased from 5% pre-pandemic to 17.9% at the onset of the COVID-19 pandemic and remained near 20% during the pandemic, declining to approximately 14% by 2024 post-pandemic. In multivariable analysis, age >65 or <21, White race, and American Indian/Alaska Native race were associated with higher odds of false-reactive results, whereas coinfection of syphilis was associated with lower odds. Most false-reactive results clustered at low signal-to-cutoff ratio (S/CO) values.

Conclusions

False-reactive HIV Ag/Ab screening results increased during the pandemic and remained elevated afterward. Associated factors analysis and S/CO distributions may help interpretation of questionable reactive screens. Our findings reinforce the importance of reflex HIV nucleic acid testing (NAT) for discordant results.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S138665322600082X?dgcid=rss_sd_all

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Protective Efficacy Evaluation of Various Inactivated #Vaccines Against the Newly Circulated Highly Pathogenic Avian #Influenza Virus #H5N1 of Clade 2.3.4.4b in Pekin #Ducks

 

Abstract

Highly pathogenic avian influenza (HPAI) virus H5N1of clade 2.3.4.4b has emerged as the predominant lineage circulating in poultry flocks worldwide, raising concerns regarding the protective efficacy of currently available commercial vaccines, particularly in domestic ducks, which play an important role in virus maintenance and transmission. Thus, this study evaluated the immunogenicity along with the protective efficacy of four inactivated H5 vaccines against a recently isolated local HPAI-H5N1 (Newvalley-3-H5N1-2024, clade 2.3.4.4b) strain in Pekin ducks in Egypt. A total of 150 seronegative ducks were divided into vaccinated and control groups (10 groups) and vaccinated at 10 days of age. At 31 days of age, the vaccinated and positive control groups were challenged using 106.5 EID50/0.5 mL/duck with the local isolate (Newvalley-3-H5N1-2024) via the oculo-nasal route. The vaccine efficacy was assessed through clinical signs, survival rate, hemagglutination inhibition (HI) antibody titer, tracheal and cloacal viral shedding quantified by real-time RT-PCR, and histopathological examination of trachea, lung, pancreas, and brain tissues. Generally, all ducks vaccinated with the ValleyVac Avian Flu H5 plus and MEFLUVACTM H5 PLUS 8 showed a significantly higher survival rate (100%) at 10 days post-vaccination (DPV) than those in the positive control (66.7% mortality rate). In contrast, ducks exhibited mortality rates ranging from 6.7% in the SERVAC Flu H5N1 group to 13.4% in the Sinder Fluvac group. The ValleyVac Avian Flu H5 plus and MEFLUVAC™ H5 PLUS 8 vaccines induced the highest HI antibody titers at 7, 14, 21, and 28 DPV in both homologous and heterologous AIV antigens, resulting in a significant reduction in viral load among all vaccinated duck groups (p-value < 0.05) comparable to the positive control group. Conversely, the SERVAC Flu H5N1 and Sinder Fluvac vaccines provided partial protection, suboptimal immunogenicity at different time points, and elevated viral shedding. Histopathological findings in ValleyVac Avian Flu H5 plus and MEFLUVAC™ H5 PLUS 8 vaccines exhibited mild tissue alterations following AIV challenge. Marked pathological lesions were observed in the SERVAC Flu H5N1 and Sinder Fluvac vaccinated groups. Among tested vaccines, both ValleyVac Avian Flu H5 plus and MEFLUVACTM H5 PLUS 8 showed the highest level of protective efficacy against the circulating AIV strain compared with other commercial vaccines. This study highlights the need for continuous molecular surveillance, antigenic matching, and regular updating of vaccine seed strains to ensure efficient HPAI control in Egypt.

Source: 

Link: https://www.mdpi.com/1999-4915/18/8/891

____

Seasonal #surveillance in #humans and #animals in 2026 for #WNV, Monthly Report (ECDC, August 12 '26): 245 cases so far

 

August 2026 | Produced on 12 August 2026 at 12:00 based on data submitted up until and including 5 August 2026

Epidemiological summary

Findings from human surveillance

    In 2026, and as at 5 August, seven countries in Europe have reported 245 locally acquired {1} human cases of West Nile Virus (WNV) infection. 

    The earliest and latest date of onset were on 12 May 2026 and 1 August 2026, respectively. 

    Locally acquired cases have been reported by Italy (139 cases), Greece (65, of which four with unknown place of infection), Spain (17 cases), North Macedonia (13 cases), Romania (six cases), France (four cases) and Germany (one case). 

    In Europe, 12 deaths have been reported by Greece (six deaths), Italy (five deaths) and Romania (one death).

    The number of human cases reported so far (245 cases) is below the average for the corresponding period over the past decade (403 cases). 

    However, reporting delays may result in an under-estimation of the current burden, as the 2026 data remain provisional, whereas the ten-year average is based on consolidated data from previous years. 

    In addition, this ten-year average is influenced by several particularly intense WNV transmission seasons, notably in 2018 (1 065 cases reported up to the corresponding week), 2022 (781 cases) and 2024 (654 cases).

    To date, most cases have been reported in Italy (139 cases) and Greece (65 cases). 

    Although the number of cases reported in Italy is lower than during the same period in 2025 (168 cases), it remains the most affected country in Europe in 2026. 

    Greece has reported more cases in 2026 than during the same period in 2025 (65 cases compared with 26 cases). 

    WNV circulation is currently most intense in the Attica NUTS 2 region (48 cases), with Anatoliki Attiki (East Attica, 34 cases) and Voreios Tomeas Athinon (North Athens, seven cases) most affected.

    As at 5 August 2026, locally acquired human cases of WNV infection had been reported in 58 NUTS 3 regions across seven countries. 

    This is higher than at the same point in 2025, when cases were reported in 40 NUTS 3 regions across six countries. 

    However, the geographical spread observed so far in 2026 remains well below the final extent recorded in recent seasons: by the end of 2025, affected regions numbered 160 and in 2024 there were 218. 

    The 2024 season remains the largest WNV season on record in terms of geographical spread.

    This year, six regions reported locally acquired human cases of WNV infection for the first time ever: France in Pyrénées-Orientales (FRJ15); Germany in Rhein-Pfalz-Kreis (DEB3I); Italy in Campobasso (ITF22) and Viterbo (ITI41); North Macedonia in Pelagoniski (MK005) and Vardarski (MK001).

    Similar to previous years, most cases were reported among males aged 65 years and above. 

    Most cases were hospitalised (72%) and presented with neurological symptoms (58%). 

    The proportion hospitalised was lower than the average reported during the previous decade (87%), while the proportion with neurological symptoms was also slightly lower than the historical 10-year average (64%). 

    The case fatality rate was approximately 5%, lower than the average reported during the previous decade (11%). 

    However, this estimate should be interpreted with caution, as clinical outcomes may not yet be known for all reported cases and additional deaths may be recorded as the season progresses and data are consolidated.

    Owing to delays in diagnosis and reporting, and because most WNV infections are asymptomatic or subclinical, the reported case numbers probably underestimate the true number of infections. Seasonal surveillance in humans primarily captures laboratory-confirmed cases, which may further contribute to reporting delays.

Findings from veterinary surveillance

    From the veterinary perspective, 17 WNV outbreaks among equids and 74 outbreaks among birds have been reported in Europe in 2026. 

    The earliest start date of an outbreak among equids and birds was on 30 March 2026 in France and 31 March 2026 in Italy, while the latest onset of an outbreak among equids and birds was, respectively, on 31 July 2026 in Netherlands and 28 July 2026 in Italy. 

    Outbreaks among equids have been reported by France (five outbreaks), Greece (five outbreaks), Italy (five outbreaks), the Netherlands (one outbreak) and Spain (one outbreak). 

    Outbreaks among birds have been reported by Italy (64 outbreaks), France (five outbreaks), Spain (three outbreaks), Austria (one outbreak) and Belgium (one outbreak).

    No information was available on the equid species involved in the outbreaks reported in the Animal Disease Information System (ADIS). 

    The bird species most frequently associated with the reported outbreaks were the common magpie (23) and the hooded crow (20), followed by the carrion crow (5), the common kestrel (5), the Eurasian blackbird (5), the yellow-legged gull (3), Adalbert’s eagle (2), the common wood-pigeon (2), and the little owl (2). 

    Single outbreaks were associated with the common loon, the common raven, the European turtle-dove, the golden eagle, the grey heron, the house sparrow and the northern goshawk.

    The monthly number of WNV outbreaks in equids reported during the first part of 2026 was comparable to the corresponding 10-year monthly average (2016−-2025). 

    However, the number of equid outbreaks in July 2026 remained below the levels observed in July 2018, 2024 and 2025, years characterised by particularly high WNV intensity. 

    In contrast, the number of WNV outbreaks in birds slightly exceeded the corresponding four-year monthly average (2022–2025) in April and May, and was substantially higher in June. 

    This trend reversed in July 2026, when the number of reported outbreaks in birds fell below the four-year average, although it remained higher than in July 2025. However, it should be noted that reporting delays may affect the July numbers, as some outbreaks occurring during that month may be notified in August.

    As at 5 August 2026, outbreaks in birds and/or equids have been reported in 43 NUTS 3 regions across seven countries. This compares with 55 regions (10 countries) during the same period in 2025 and 42 regions (eight countries) in 2024. All seven countries reported WNV outbreaks in birds and/or equids in 2025 and in prior years, reflecting endemic WNV activity in these territories. However, as at 5 August, outbreaks in birds and/or equids were reported to ADIS for the first time in the following six regions: by France in Hauts-de-Seine (FR105) and Seine-et-Marne (FR102); by Belgium in Arr. Namur (BE352), by Greece in Drama (EL514), by Italy in Genova (ITC33) and by the Netherlands in Delf en Westland (NL362).

Patterns across human and veterinary surveillance

    Four countries – France, Greece, Italy, and Spain – reported both human WNV infections and outbreaks in equids and/or birds. 

    As at 5 August, Italy accounted for most of the reported human cases (56.7%) and animal outbreaks (75.8%). 

    Greece reported the second-largest share of human cases (26.5%) but only five equid outbreaks and no bird outbreaks, representing 5.5% of all reported animal outbreaks.

    Differences in the patterns observed across European countries may reflect a combination of ecological, climatic and surveillance-related factors. 

    Favourable climatic conditions and the presence of ecological hotspots, such as wetlands and agricultural areas, may support mosquito vector populations and influence the distribution and behaviour of animal hosts, thereby facilitating WNV circulation. At the same time, differences in WNV surveillance systems across Europe may affect detection and reporting rates.

    The first indication of WNV activity may arise from either human or animal surveillance, depending on local epidemiology, detection capacity and surveillance system sensitivity. Therefore, the absence of reports from one sector should not be interpreted as evidence that WNV is not circulating. 

    In France (Pyrénées-Orientales, FRJ15), Greece (Drama, EL514), and Italy (Genova, ITC33), human cases were reported before, or in the absence of, notified outbreaks in birds or equids. 

    Conversely, in Belgium (Arr. Namur, BE352), France (Hauts-de-Seine, FR105 and Seine-et-Marne, FR102) and the Netherlands (Delft en Westland, NL362), animal detections preceded human cases. 

    Belgium is a relevant example, as WNV was first reported in the country in 2025 through avian surveillance, with no previous detections in humans and animals. In 2026, it has again been identified in birds in a previously unaffected region, highlighting the role of avian surveillance in detecting local virus circulation and geographical spread.

    Active mosquito surveillance is also important for the early detection of WNV circulation. However, results on WNV detection in mosquitoes are not included in this report because they are not legally required to be reported at European level, and the available information is therefore scattered and often project-based.

Seasonal outlook

    Given the favourable weather conditions for WNV transmission in Europe, ECDC and EFSA expect further human cases and outbreaks in equids and birds to be reported in the coming weeks. In previous years, transmission has typically peaked in August and September.

    ECDC and EFSA continue to closely monitor the situation in Europe.

(...)

Source: 

Link: https://www.ecdc.europa.eu/en/infectious-disease-topics/west-nile-virus-infection/surveillance-and-disease-data/monthly-updates

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#Risk #assessment of avian #influenza #H5N5 virus from the first #human case using the #ferret model

 

ABSTRACT

The incursion of Eurasian-origin genotype A6 A(H5N5) virus into North America expanded the genetic diversity among North American highly pathogenic avian influenza viruses and heightened concern about zoonotic risk. Following a fatal human infection with the A(H5N5) virus A/Washington/2148/2025, viral replication was assessed in polarized human bronchial epithelial cells, and pathogenicity, transmissibility in direct contact and respiratory droplet models, and airborne virus shedding were evaluated in ferrets to inform pandemic risk assessment. A(H5N5) displayed robust replication in Calu-3 cells at 33°C and 37°C, showing kinetics and peak titers comparable to those of contemporary genotype B3.13 and D1.1 A(H5N1) viruses. In ferrets, A(H5N5) replicated efficiently in the respiratory tract, disseminated to extrapulmonary tissues, and caused fatal disease in all inoculated animals. Airborne transmission was not observed, and infrequent, low-level detection of virus in air samples paralleled that of A(H5) viruses that are not transmissible via air in ferrets. In a direct contact model, limited transmission was detected within 4 days of exposure, with evidence of lower respiratory tract replication in contact animals. These findings indicate that the A(H5N5) virus has the capacity for robust replication in an airway epithelial cell line and can cause severe systemic infection and mortality in ferrets but has not acquired adaptations for airborne spread in mammals. Collectively, these results underscore heterogeneity among clade 2.3.4.4b A(H5Nx) viruses in North America and the need for genotype-by-genotype evaluation of newly emerged viruses to understand public health risk.

IMPORTANCE

The emergence of Eurasian-origin genotype A6 highly pathogenic avian influenza A(H5N5) virus in North America has increased viral diversity and raised concerns about zoonotic and pandemic risk. In this study, we evaluated the replication kinetics, pathogenesis, and transmission of A/Washington/2148/2025 A(H5N5) virus, which was isolated from the first reported human infection with this influenza virus subtype, using polarized human bronchial epithelial cells and the ferret model. The A(H5N5) virus replicated efficiently in vitro at temperatures representative of the upper and lower respiratory tracts and caused fatal systemic disease in inoculated ferrets. Limited transmission was observed during 4 days of direct contact. Airborne virus detection was infrequent and did not result in airborne transmission. These findings show that A(H5N5) virus can replicate robustly in mammalian cells and cause severe disease but lacks adaptations supporting efficient airborne spread, informing assessment of the pandemic risk posed by genotype A6 influenza viruses.

Source: 

Link: https://journals.asm.org/doi/10.1128/jvi.00856-26

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Protective effect of #H5N8 stockpiled #vaccine against a virus genetically identical to a #human isolate of #bovine #H5N1 #influenza virus

 

Summary

Background

Since early 2024, highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b have caused extensive outbreaks in dairy cattle in the United States, with spillover into mammalian species, including humans. A bovine-derived A(H5N1) virus isolated from a human case retains high pathogenicity and transmissibility in mammalian models, highlighting its pandemic potential. Stockpiled pre-pandemic influenza vaccines are intended to provide early protection before strain-matched vaccines are available; however, their protective efficacy against bovine A(H5N1) viruses has not been directly evaluated in vivo.

Methods

In this study, we assessed the protective efficacy of an AS03-adjuvanted A/Astrakhan/3212/2020 (H5N8) clade 2.3.4.4b-based influenza vaccine stockpiled in Japan using mouse and ferret models. Vaccinated and unvaccinated animals were challenged with a virus genetically identical to a human isolate of bovine A(H5N1) virus. Neutralising antibody responses, viral replication in organs, and survival were evaluated.

Findings

Vaccination with the AS03-adjuvanted A(H5N8)-based stockpiled vaccine induced robust neutralising antibody responses in both animal models, significantly suppressed viral replication, and conferred complete protection against lethal challenge. In contrast, all unvaccinated mice and ferrets succumbed to infection. These findings demonstrate that the AS03-adjuvanted A(H5N8)-based stockpiled vaccine provides strong cross-protective efficacy against bovine A(H5N1) viruses.

Interpretation

An AS03-adjuvanted A(H5N8)-based vaccine stockpiled in Japan could serve as an immediate countermeasure against bovine A(H5N1) viruses during the early phase of a pandemic.

Funding

This work was supported by grants from the Japan Program for Infectious Diseases Research and Infrastructure (JP20wm0125002) and the Japan Initiative for World-leading Vaccine Research and Development Centers (JP223fa627001) from the Japan Agency for Medical Research and Development.

Source: 

Link: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(26)00314-2/fulltext

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Loss-of-function #mutation in #Omicron #variants reduces #spike protein expression and attenuates #SARS-CoV-2 infection

 

Abstract

SARS-CoV-2 Omicron variants emerged in 2022 with >30 novel mutations in the spike alone. While most studies focus on receptor binding domain changes, mutations in the C-terminus of S1 (CTS1), adjacent to the furin cleavage site, have largely been ignored. Here, we examine three Omicron mutations in CTS1: H655Y, N679K, and P681H. Generating a SARS-CoV-2 triple mutant (YKH), we find that the mutant increases spike processing, consistent with prior reports for H655Y/P681H. In addition, the YKH mutant induces attenuated disease, but augments viral loads in male golden Syrian hamsters. Next, we generate a single N679K mutant, finding it reduces viral replication in Calu3 human respiratory cells and induces less disease in male golden Syrian hamsters. Mechanistically, the N679K mutant has increased spike processing but also reduces spike in purified virions; spike decreases are further exacerbated in infected Calu3 cell lysates. Importantly, exogenous spike expression reveals that N679K reduces overall spike protein in the context of the epidemic strain. Although a loss-of-function mutation, transmission competition demonstrates that N679K confers a replication advantage in the upper airway, potentially impacting transmissibility. Together, the data show that N679K reduces overall spike protein during Omicron infection, which has implications for infection, immunity, and transmission.

Source: 

Link: https://www.nature.com/articles/s41467-026-76680-4

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#Bacterial #Infection in #Ebola Virus Disease, #Marburg Virus Disease, #CCHF, and #Lassa Fever

 

Abstract

Background

Concern for bacterial coinfection in patients with high consequence viral infections (HCVIs) has made empiric antibiotic administration the standard of care. However, the incidence, microbiology, and clinical significance of bacterial coinfection in HCVIs remain unclear.

Methods

We conducted a systematic review of case reports, cohort studies, and cross-sectional analyses describing bacterial coinfection in Ebola virus disease (EVD), Marburg virus disease (MVD), Crimean–Congo hemorrhagic fever (CCHF), and Lassa fever (LF). Data were extracted on study design, setting, diagnostic methods, pathogens, antibiotic use, and outcomes.

Results

Thirty publications met inclusion criteria. Bacteremia was most commonly reported among patients with CCHF (n = 46), followed by EVD (n = 16), MVD (n = 16), and LF (n = 2). Of 27 EVD patients treated outside Africa, 7 (26%) had bacterial coinfection. Across HCVIs, bacteremia was detected a median of 11 days after symptom onset (range 0–23) and was associated with features of sepsis. Pathogens included enteric flora, healthcare-associated organisms, opportunistic pathogens, and zoonotic bacteria—most notably Brucella spp. in CCHF. Ceftriaxone was the most common empiric antibiotic but is predicted to have activity against a minority of bloodstream isolates. Mortality among coinfected patients with EVD or MVD was similar to those without bacterial coinfection, whereas coinfected CCHF patients had higher mortality than those without coinfection (15.5%; 95% CI 8.0%–25.9% vs 5.7%; 95% CI 5.1%–6.4%).

Conclusions

Despite being a major concern driving empiric antibiotic use, bacterial coinfection in HCVIs remains poorly described, precluding determination of its incidence or clinical significance. Prospective studies with standardized protocols for bacterial diagnosis and characterization of antimicrobial resistance are needed to guide antimicrobial strategies.

Source: 

Link: https://academic.oup.com/ofid/article/13/8/ofag404/8741539

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Bundibugyo Virus Disease Outbreak in the #DRC, #Uganda & #France - Situation Report 13, Data as of 09 August 2026 (WHO, summary): 4,381 cases & 2,011 deaths in DRC

 

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Event description

Democratic Republic of the Congo

    The Bundibugyo virus disease (BVD) outbreak in the Democratic Republic of the Congo remains in a phase of intense and expanding transmission, with cumulative deaths crossing the grim milestone of 2,000 only 86 days after the outbreak was officially declared on 15 May 2026. 

    Since External Situation Report #12, an additional 579 confirmed cases and 304 confirmed deaths have been reported, bringing the cumulative total to 4,381 confirmed cases and 2,011 confirmed deaths as of 9 August 2026, corresponding to a case fatality ratio of 45.9%. 

    Ituri remains the epicentre, accounting for 85.8% of cumulative cases and 80.6% of cumulative deaths.

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    The epidemic is increasingly characterized by sustained transmission within interconnected geographic clusters alongside continued geographic expansion. 

    

    The Bunia–Rwampara–Mongbwalu–Nizi corridor remains the principal transmission focus, while persistent transmission in North Kivu and  increasing activity in Haut-Uélé indicate spread beyond the original Ituri epicentre. 

    The number of affected health zones increased from 51 in External Situation Report #12 to 53 as of 9 August 2026, with Gombari in Haut-Uélé and  Bafwasende in Tshopo being the most recently affected health zones. 

    Overall, the outbreak now affects 53 of 140 health zones across five provinces.

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    Persistently high mortality continues to highlight gaps in early detection  and timely access to care. 

    

    Community deaths remain frequent, with 34 of 51 reported deaths (66.7%)  occurring outside treatment centres on 9 August 2026.

    Surveillance performance improved, with all 242 validated suspected cases  being investigated on 9 August 2026. 

    Contact follow-up also increased to 86.7%, exceeding 85% for the first  time, although performance remained substantially lower in Haut-Uélé at 57.9%,  partly due to incomplete reporting. 

    Despite these improvements, gaps in alert reporting, contact identification  and follow-up around confirmed cases persist. 

    Treatment capacity also remains under pressure, with several treatment  and transit centres in Ituri saturated, while North Kivu continues to face constraints in referral capacity and Haut-Uélé still lacks a standard Ebola  treatment centre in its six affected health zones.

    Intense transmission is also occurring against a backdrop of increasing  operational and workforce pressures. 

    Challenges related to the timely remuneration of response personnel have  been reported in some affected areas, with potential implications for  workforce motivation and the continuity of response activities, including  community-based interventions and operations at points of entry and points of  control. 

    Community resistance, insecurity and operational incidents continued to  pose challenges to the timely implementation of response activities, including safe  and dignified burials. 

    These pressures are particularly concerning as epidemiological analyses  indicate that transmission is occurring faster than cases are being detected and  isolated, while contact-tracing capacity is increasingly stretched. 

    Despite the absence of further international transmission, the continued high incidence in eastern Democratic Republic  of the Congo poses a substantial risk of cross-border spread, particularly to Uganda and South Sudan through  major population movement corridors. 

    Surveillance at points of entry (PoEs) and points of control (PoCs) continued  along key mobility corridors, although operational constraints persist at  some sites. 

    Continued strengthening of cross-border surveillance, information sharing  and coordination with neighbouring countries remains essential for the early  detection and management of potential cross-border transmission.

Uganda and France

    No new BVD cases have been reported in Uganda. The last confirmed  patient was discharged on 16 July 2026, and all identified contacts subsequently  completed follow-up. As of 9 August 2026, 24 days had elapsed since the last  patient's discharge without a new confirmed case. However, continued high  transmission in neighbouring eastern Democratic Republic of the Congo poses a risk of reintroduction.

    France has reported no secondary transmission following the imported  case detected on 24 June 2026. The patient recovered and was discharged on 4  July 2026 after two consecutive negative polymerase chain (PCR) test results, and all five identified flight contacts completed 21 days of follow-up without  developing symptoms. As of 9 August 2026, 36 days had elapsed since the  patient's discharge without an additional confirmed case being reported in France.

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Situation interpretation

    The BVD outbreak remains uncontrolled, with transmission continuing to  outpace response capacity. Persistent community deaths, geographic expansion  and gaps in contact follow-up indicate continued undetected community transmission, while pressure on treatment facilities, uneven infection  prevention and control capacity, workforce constraints and community resistance continue to challenge response effectiveness. 

    The response should now shift to targeted interruption of transmission in  the main clusters and emerging hotspots, while deepening community leadership  and ownership of the response. This requires empowering trusted local leaders  and community networks to drive active case finding, contact tracing, early care- seeking, and safe and dignified burials, alongside faster case investigation and  isolation and rapid infection prevention and control interventions. Workforce and  payment constraints require urgent resolution, while neighbouring countries  should maintain heightened preparedness given the continued risk of cross-border spread.

Source: 

Link: https://www.afro.who.int/health-topics/ebola-disease

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First detected incursions of avian #influenza #H5N1 clade 2.3.4.4b into mainland #Australia from the Southern Ocean

 

Abstract

High pathogenicity avian influenza H5N1 clade 2.3.4.4b has caused a panzootic of devastating impact to poultry and wildlife globally. The Australian continent and broader Oceania until recently remained the last major region without confirmed detections. Here we report the first H5N1 clade 2.3.4.4b detections from two live seabirds - a brown skua and a southern giant petrel - found on the south coast of Western Australia in June 2026. Virus genome sequencing showed that both viruses were most closely related to H5N1 viruses recently detected on sub-Antarctic islands in the Southern Indian Ocean. In time-calibrated phylogeographic analyses, both viruses sampled in Western Australia clustered with viruses from Heard Island, a sub-Antarctic external territory of Australia. Ancestral location reconstruction also identified Heard Island as the most probable source location, although unsampled intermediate locations cannot be excluded. The two Western Australian detections were estimated to be independent incursions from Heard Island, rather than local transmission on mainland Australia. There was no evidence of reassortment with endemic avian influenza viruses in Australia, and both virus sequences retained key avian-like genetic markers and lacked known substitutions for reduced antiviral susceptibility. These detections revealed a Southern Ocean pathway of recurrent H5N1 incursions into Australia, highlighting the risk of potential establishment on the mainland and the need for heightened surveillance and rapid, nationally-coordinated, virus genomic characterisation.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.08.743700v1

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#Taiwan, #COVID19 #epidemic continues to escalate, citizens urged to get vaccinated (CDC, August 12 '26): PQ.16.1.1 Variant still dominant

 

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    According to data from the Taiwan Centers for Disease Control (CDC), the COVID-19 epidemic in Taiwan is on the rise. 

    In the 31st week (August 2-8), there were 24,645 outpatient and emergency room visits related to COVID-19, a 27.6% increase compared to the previous week (July 26-August 1). 

    Last week (August 4-10), there were 72 new locally transmitted severe cases and 14 new locally transmitted deaths. 

    Since October of last year (2014), there have been a cumulative total of 337 locally transmitted cases of COVID-19 complicated by severe illness, of which 42 have died. 

    The majority of severe cases are among those aged 65 and above (73.9%) and those with a history of chronic diseases (84.0%). 

    89.6% of these cases have not received the COVID-19 vaccine this season. 

    In the past four weeks, the most prevalent variant strain in locally transmitted cases has been PQ.16.1.1.

    The CDC explained that the global positivity rate is on the rise, particularly in Europe and Africa, while the Western Pacific region remains at a plateau. 

    The COVID-19 outbreaks are rising in China, Thailand, South Korea, and the United States; Japan is experiencing a relatively high point with fluctuating outbreaks, while Hong Kong's outbreak is declining; the most prevalent variants globally recently are NB.1.8.1, XFG, and JN.1.

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Source: 

Link: https://www.cdc.gov.tw/Bulletin/Detail/rKEajQHrBk-SYtJSD4SB5w?typeid=9

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Effectiveness of #Oseltamivir in Hospitalized #Children With Laboratory-Confirmed #Influenza, 2014-2023

 

Key Points

    ° Question: 

        § Does oseltamivir treatment reduce risk of intensive care unit (ICU) admission and hospital length of stay among pediatric patients hospitalized with influenza?

    ° Findings:  

        § Using a cohort study from a population-based surveillance network in 13 states across 8 influenza seasons, oseltamivir treatment was found to decrease both the likelihood of ICU admission and hospital length of stay among pediatric patients hospitalized with laboratory-confirmed influenza.

    ° Meaning:  

        § These findings support the current national recommendations from the American Academy of Pediatrics, US Centers for Disease Control and Prevention, and Infectious Diseases Society of America that recommend antiviral treatment for children hospitalized with laboratory-confirmed influenza.

Abstract

Importance  

National organizations recommend antiviral treatment for hospitalized children with influenza; however, use in this setting has recently declined. Studies of oseltamivir effectiveness in children are limited by misclassification bias, unknown symptom onset date, and incomplete capture of antiviral use prior to admission.

Objective  

To assess the association between oseltamivir receipt and intensive care unit (ICU) admission and hospital length of stay (LOS) among pediatric influenza-associated hospitalizations.

Design, Setting, and Participants  

This cohort study used data that were obtained from the Influenza Hospitalization Surveillance Network (FluSurv-NET), which conducts US population-based surveillance for laboratory-confirmed influenza hospitalizations for all ages across 13 states. The study data include seasons 2014 to 2015 through 2022 to 2023, excluding 2020 to 2021. Participants included children aged younger than 18 years who were hospitalized with laboratory-confirmed influenza and for whom a respiratory symptom onset date was available. These data were analyzed from October 2024 through May 2026.

Exposures  

Oseltamivir receipt as a time-dependent exposure.

Main Outcome(s) and Measure(s)  

The primary outcome was time from symptom onset to ICU admission. Secondary outcome was time from admission to discharge (LOS). Adjusted Cox proportional hazard models (aHR) with oseltamivir receipt as a time-dependent exposure were used.

Results  

After exclusions, 6044 influenza cases were included in the primary ICU analysis, of whom 4240 (70.2%) received oseltamivir, and 7103 cases were included in the secondary LOS analysis, of whom 5746 (80.9%) received oseltamivir. In the ICU analysis, the median (IQR) age was 3 (1-7) years, 3382 (56%) were male and 3721 (44%) were female, and 2937 (49%) had 1 or more medical comorbidity—the most common of which was asthma in 1547 children (26%). In adjusted models, compared with untreated children, oseltamivir treatment reduced the hazard of ICU admission (aHR, 0.69; 95% CI, 0.60-0.80) and shortened LOS (analyzed as hazard of hospital discharge; aHR, 1.13; 95% CI, 1.06-1.21).

Conclusions and Relevance  

In this cohort of children hospitalized with influenza, oseltamivir treatment was significantly associated with a reduced risk of ICU admission by 31% and decreased hospital LOS. These findings demonstrate the benefits of oseltamivir receipt and support current national recommendations for oseltamivir treatment as soon as possible in children hospitalized with suspected or laboratory-confirmed influenza.

Source: 

Link: https://jamanetwork.com/journals/jamapediatrics/fullarticle/2852671

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