Highly Pathogenic Avian #Influenza A(#H5N1) Virus #Infections in #Humans

Abstract

Background

Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States, with sporadic human cases. We describe characteristics of human A(H5N1) cases identified from March through October 2024 in the United States.

Methods

We analyzed data from persons with laboratory-confirmed A(H5N1) virus infection using a standardized case-report form linked to laboratory results from the Centers for Disease Control and Prevention influenza A/H5 subtyping kit.

Results

Of 46 case patients, 20 were exposed to infected poultry, 25 were exposed to infected or presumably infected dairy cows, and 1 had no identified exposure; that patient was hospitalized with nonrespiratory symptoms, and A(H5N1) virus infection was detected through routine surveillance. Among the 45 case patients with animal exposures, the median age was 34 years, and all had mild A(H5N1) illness; none were hospitalized, and none died. A total of 42 patients (93%) had conjunctivitis, 22 (49%) had fever, and 16 (36%) had respiratory symptoms; 15 (33%) had conjunctivitis only. The median duration of illness among 16 patients with available data was 4 days (range, 1 to 8). Most patients (87%) received oseltamivir; oseltamivir was started a median of 2 days after symptom onset. No additional cases were identified among the 97 household contacts of case patients with animal exposures. The types of personal protective equipment (PPE) that were most commonly used by workers exposed to infected animals were gloves (71%), eye protection (60%), and face masks (47%).

Conclusions

In the cases identified to date, A(H5N1) viruses generally caused mild illness, mostly conjunctivitis, of short duration, predominantly in U.S. adults exposed to infected animals; most patients received prompt antiviral treatment. No evidence of human-to-human A(H5N1) transmission was identified. PPE use among occupationally exposed persons was suboptimal, which suggests that additional strategies are needed to reduce exposure risk. (Funded by the Centers for Disease Control and Prevention.)

Source: New England Journal of Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2414610

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#Critical #Illness in an #Adolescent with #Influenza A(#H5N1) Virus #Infection

To the Editor:

Highly pathogenic avian influenza A(H5N1) viruses are circulating among wild birds and poultry in British Columbia, Canada.1 These viruses are also recognized to cause illness in humans. Here, we report a case of critical illness caused by influenza A(H5N1) virus infection in British Columbia.

On November 4, 2024, a 13-year-old girl with a history of mild asthma and an elevated body-mass index (the weight in kilograms divided by the square of the height in meters) of greater than 35 presented to an emergency department in British Columbia with a 2-day history of conjunctivitis in both eyes and a 1-day history of fever. She was discharged home without treatment, but cough, vomiting, and diarrhea then developed, and she returned to the emergency department on November 7 in respiratory distress with hemodynamic instability. On November 8, she was transferred, while receiving bilevel positive airway pressure, to the pediatric intensive care unit at British Columbia Children’s Hospital with respiratory failure, pneumonia in the left lower lobe, acute kidney injury, thrombocytopenia, and leukopenia (...). A nasopharyngeal swab obtained at admission was positive for influenza A but negative for A(H1) and A(H3) by the BioFire Respiratory Panel 2.1 assay (BioFire Diagnostics). Reflex testing of the specimen with the Xpert Xpress CoV-2/Flu/RSV plus assay (Cepheid) revealed an influenza A cycle threshold (Ct) value of 27.1. This finding indicates a relatively high viral load for which subtyping would be expected; the lack of subtype identification suggested infection with a novel influenza A virus. Oseltamivir treatment was started on November 8 (Table S2), and the use of eye protection, N95 respirators, and other precautions against droplet, contact, and airborne transmission were implemented.

A reverse-transcriptase–polymerase-chain-reaction (RT-PCR) test specific for influenza A(H5)2 was positive on the day of admission. The patient had signs of respiratory deterioration — chest radiographs were consistent with progression to acute respiratory distress syndrome (...) — which prompted tracheal intubation and initiation of venovenous extracorporeal membrane oxygenation (ECMO) on November 9. Continuous renal replacement therapy was initiated on November 10. Combination antiviral treatment with amantadine (initiated on November 9) and baloxavir (initiated on November 11) was added to ongoing treatment with oseltamivir. Bacterial cultures of blood (samples obtained at admission) and endotracheal aspirate (obtained after intubation) yielded no growth.

Because of concern for cytokine-mediated hemodynamic instability, plasma exchange was performed daily from November 14 through November 16. Serial influenza A–specific RT-PCR tests showed increasing Ct values, which suggested a decline in the viral RNA load in serum and a decline in viral RNA in upper- and lower-respiratory specimens shortly after the initiation of antiviral treatment, with the first negative RT-PCR result for serum obtained on November 16 (...). It is notable that lower-respiratory specimens consistently yielded lower Ct values than upper-respiratory specimens, a finding that suggested higher viral levels in the lower-respiratory tract (...).

Influenza A(H5N1) virus was cultured from respiratory specimens obtained between November 8 and November 12 but not from subsequent respiratory specimens or from any serum specimens (...). No evidence of reduced susceptibility to any of the three antiviral agents used in treatment was observed in serial respiratory specimens by either genomic analysis or phenotypic testing with the NA-Star influenza neuraminidase inhibitor resistance detection kit (ThermoFisher Scientific) (...). The patient’s respiratory status improved, ECMO was discontinued on November 22, and the patient’s trachea was extubated on November 28.

The viral genome sequence obtained from a tracheal-aspirate specimen collected on November 9 (8 days after the onset of symptoms) was reconstructed as described previously.3 The virus was typed as clade 2.3.4.4b, genotype D1.1,4 most closely related to viruses detected in wild birds in British Columbia around the same time (...). Markers of adaptation to humans were detected in the tracheal-aspirate specimen collected on November 9: the E627K mutation was detected (52% allele frequency) in the polymerase basic 2 (PB2) gene product, and analysis of the H5 hemagglutinin (HA) gene yielded ambiguous calls in the codons for amino acid residues E186 (E190 according to H3 mature HA numbering) — 28% allele frequency for E186D — and Q222 (Q226 according to H3 mature HA numbering) — 35% allele frequency for Q222H. The mutations in the H5 HA gene have previously been shown to increase binding to α2-6–linked sialic acids, which act as receptors that facilitate viral entry into cells in the human respiratory tract and enable viral replication.5

Highly pathogenic avian influenza A(H5N1) virus infection acquired in North America can cause severe human illness. Evidence for changes to HA that may increase binding to human airway receptors is worrisome.

Agatha N. Jassem, Ph.D., British Columbia Centre for Disease Control, Vancouver, BC, Canada; Ashley Roberts, M.D., British Columbia Children’s Hospital, Vancouver, BC, Canada; John Tyson, Ph.D., James E.A. Zlosnik, Ph.D., Shannon L. Russell, Ph.D., British Columbia Centre for Disease Control, Vancouver, BC, Canada; Jessica M. Caleta, M.Sc., Public Health Agency of Canada, Winnipeg, MB, Canada; Eric J. Eckbo, M.D., British Columbia Centre for Disease Control, Vancouver, BC, Canada; Ruimin Gao, Ph.D., Taeyo Chestley, Ph.D., Public Health Agency of Canada, Winnipeg, MB, Canada; Jennifer Grant, M.D., British Columbia Centre for Disease Control, Vancouver, BC, Canada; Timothy M. Uyeki, M.D., M.P.H., Centers for Disease Control and Prevention, Atlanta, GA; Natalie A. Prystajecky, Ph.D., British Columbia Centre for Disease Control, Vancouver, BC, Canada; Chelsea G. Himsworth, D.V.M., Ph.D., British Columbia Ministry of Agriculture and Food, Abbotsford, BC, Canada; Elspeth MacBain, M.D., British Columbia Children’s Hospital, Vancouver, BC, Canada; Charlene Ranadheera, Ph.D., Public Health Agency of Canada, Winnipeg, MB, Canada; Lynne Li, M.D., British Columbia Children’s Hospital, Vancouver, BC, Canada; Linda M.N. Hoang, M.D., British Columbia Centre for Disease Control, Vancouver, BC, Canada; Nathalie Bastien, Ph.D., Public Health Agency of Canada, Winnipeg, MB, Canada; David M. Goldfarb, M.D., British Columbia Children’s Hospital, Vancouver, BC, Canada.

Source: New England Journal of Medicine, https://www.nejm.org/doi/full/10.1056/NEJMc2415890

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Immunogenicity of inactivated #H5 avian #influenza #vaccine used in commercial laying #pullet in #Tehran province

Abstract

Highly pathogenic avian influenza (HPAI) is a viral disease caused by some H5 and H7 subtypes of influenza virus type A in most species of birds, especially poultry. HPAI viruses are amongst the most challenging viruses that threaten both human and animal health. Consequently, various strategies such as the use of vaccines have been proposed to control the disease. After a catastrophic pandemic and the failure of conventional methods (elimination and extermination) in Iran, multiple vaccines has been used to control the disease. This study investigates the immunogenicity of two recombinant inactivated commercial vaccines of H5N1 and H5N3 subtypes in laying pullet flocks in Tehran Province, Iran. From 32 halls in 6 breeding units of laying pullets, 3200 sera and 800 tracheal and cloacal swabs were collected. After collecting the samples, Serum neutralisation (SN) and hemagglutination inhibition (HI) tests were conducted on sera to determine the serum titers of H5 specific antibody obtained from vaccine inoculation in three steps: before, after first vaccination and after the second vaccination (booster). SN and HI tests were carried out by the alpha and beta methods on the pooled samples by the vaccine type (as antigen for HI and SN), and the results were compared. The PCR was performed on the tracheal and cloacal swab samples to possibly detect the HA (H5)virus in the studied flocks. The HI test results showed that both vaccines had a Serum antibody titre above 5 (log2) after two vaccination rounds, indicating a desirable immunogenic response. The SN test results also showed a neutralisation index above 104.5 for both vaccines, indicating more than 50% reduction in antigenicity of the virus. The PCR results were negative. This study was the first investigation of immunogenicity following two-time vaccination against H5 subtype vaccines in Iranian poultry flocks, indicated suitable antibody titer against the influenza virus in vaccinated flocks.

Source: Archives of Razi Institute, https://archrazi.areeo.ac.ir/article_130878.html

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Spatio-temporal #dynamics and #risk cluster #analysis of highly pathogenic avian #influenza (#H5N1) in #poultry: Advancing #outbreak #management through customized regional strategies in #Egypt

ABSTRACT 

Background: 

Highly pathogenic avian influenza (HPAI) (H5N1) has been endemic in Egypt for almost two decades, profoundly impacting both the poultry industry and public health. Egypt stands as a prominent epicenter for HPAI H5N1 outbreaks in Africa, marked by the highest number of positive human cases. Despite continuous governmental efforts, prior research underscored the inadequacy of strategies in controlling the virus spread. 

Aim: 

This study identified spatiotemporal patterns and high-risk clusters of HPAI H5N1 outbreaks at the subdistrict level. 

Methods: 

This study involved trial tracking of HPAI H5N1 endemicity dynamics, enabling tailored interventions at a regional level based on robust epidemiological investigations to address the persistent challenge of HPAI H5N1 in Egypt. This study illuminated spatiotemporal outbreak dynamics, with specific attention on Menofia governorate. 

Results: 

Despite the region’s early poultry impacts, initial outbreaks did not originate from Menofia in studied epidemic waves (EWs). Outbreak risk spatial distribution displayed an escalating pattern at the northern border, followed by risk reduction through the sixth EW. The predominant hot spot region was localized within rural districts, particularly villages, while urbanization coincided with lower outbreak density. Observed smoothed densities revealed epidemic propagation within urban centers, preceding its transition to new areas and establishing direct connections with neighboring cities. Primary cluster prognostication was plausible, occurring in regions previously hosting elevated relative risk clusters during preceding EWs. Identification of enduring pinpoint clusters, persistent for extended durations, indicated close contact dynamics and localized viral circulation within populations. 

Conclusion: 

This study highlights the significance of customized regional interventions based on the rigorous epidemiological framework. This approach is pivotal in the profound comprehension of endemicity dynamics, efficiently limits geographical infection spread, and contains outbreaks within delineated areas.

Source: Open Veterinary Journal, https://doi.org/10.5455/OVJ.2024.v14.i11.20

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A Potent #Pandemic Avian #Influenza Virus #Vaccine Based on a 4th Generation Fully Deleted #Adenoviral #Vector

Abstract

The GreVac system was developed as a fast and flexible plug-and-play vaccine platform based on an architecture of fully deleted (fd) helper virus-independent (hi) adenoviral (Ad) vectors. The present study established the potency of the GreVac technology. It demonstrated that the GreFluVie5 vaccine fully protected mice against lethal challenges with the A/Vietnam/1203/2004 (H5N1) pandemic avian influenza virus. The GreFluVie5 vector delivered a transgene expression cassette for the H5 hemagglutinin and N1 neuramidase influenza genes. Its fd Ad genome was carried in a capsid of the human serotype 5 (Ad5). The efficacies of three different doses and three different administration routes were compared in the mouse model. The vaccine fully protected animals against viral challenges with the wild-type A/Vietnam/1203/2004 virus, whose replication in the recipients' lungs was terminated. It induced strong immune responses. The present experiments also revealed that the intra muscular (i.m.) delivery route of GreFluVie5 was more efficient than sub cutaneous (s.c.) or intra nasal (i.n.) ones. Based on the results of this trial and GreVac's intrinsic versatility and fast development time, we believe that this platform is ideally suited to swiftly deliver powerful vaccines to infectious diseases with high eruption potentials.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.30.630761v1

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#France - High pathogenicity avian #influenza #H5 viruses (#poultry) (Inf. with) - Immediate notification

 Two poultry farms in Normandie Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6127

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#Albania - High pathogenicity avian #influenza #H5N1 viruses (poultry) (Inf. with) - Immediate notification

 Backyard poultry in Tiranë Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6130

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

 A wild bird in Brandenburg Region. 

Source: WOAH, https://wahis.woah.org/#/in-review/6133

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A low pathogenic avian #influenza A/Mallard/South Korea/KNU2019-34/2019 (#H1N1) virus has the potential to increase the #mammalian #pathogenicity

Abstract

Influenza, a highly contagious respiratory infectious disease caused by an influenza virus, is a threat to public health worldwide. Avian influenza viruses (AIVs) have the potential to cause the next pandemic by crossing the species barrier through mutation of viral genome. Here, we investigated the pathogenicity of AIVs obtained from South Korea and Mongolia during 2018–2019 by measuring viral titers in the lungs and extrapulmonary organs of mouse models. In addition, we assessed the pathogenicity of AIVs in ferret models. Moreover, we compared the ability of viruses to replicate in mammalian cells, as well as the receptor-binding preferences of AIV isolates. Genetic analyses were finally performed to identify the genetic relationships and amino acid substitutions between viral proteins during mammalian adaptation. Of the 24 AIV isolates tested, A/Mallard/South Korea/KNU2019-34/2019 (KNU19-34; H1N1) caused severe bodyweight loss and high mortality in mice. The virus replicated in the lungs, kidneys, and heart. Importantly, KNU19-34-infected ferrets showed high viral loads in both nasal washes and lungs. KNU19-34 replicated rapidly in A549 and bound preferentially to human like α2,6-linked sialic acids rather than to avian-like α2,3-linked sialic acids, similar to the pandemic A/California/04/2009 (H1N1) strain. Gene segments of KNU19-34 were distributed in Egypt and Asia lineages from 2015 to 2018, and the virus had several amino acid substitutions compared to H1N1 AIV isolates that were non-pathogenic in mice. Collectively, the data suggest that KNU19-34 has zoonotic potential and the possibility of new mutations responsible for mammalian adaptation.

Source: Virologica Sinica, https://www.sciencedirect.com/science/article/pii/S1995820X24002062?via%3Dihub

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LC-MS/MS characterization of #SOBERANA®02, a #RBD - #tetanus toxoid conjugate #vaccine against #SARS-CoV-2

Abstract

SOBERANA-02 is a safe and effective conjugate vaccine against SARS-CoV-2, produced using the maleimide-thiol chemistry. In this vaccine, the Cys538 in the recombinant receptor binding domain (RBD) of SARS-CoV-2 is linked, through a thiosuccinimide linker, to lysine residues of tetanus toxoid (TT) preparation. LC-MS/MS analysis revealed that TT is a complex mixture of proteins, similar to other TTs where the detoxified tetanus neurotoxin (d-TeNT) has been shown to be the most abundant protein (30-56%), regardless the quantification method used. The fifteen most abundant proteins account for approximately 78% of the total proteins. LC-MS/MS analysis of the activation process showed that 102 out of 107 lysine residues in the d-TeNT incorporated a maleimide group. In contrast, when tryptic peptides isolated by Ni2+-NTA affinity chromatography, were analyzed by LC-MS/MS, only 22 Lys residues in the d-TeNT were cross-linked to the RBD C-terminal tryptic peptide (538CVNF541-HHHHHH), probably due to steric hindrance. Twelve and eighteen conjugation sites were assigned based on the identification of linear peptides carrying a conjugated lysine residues (K(+1454.58 Da) or K(+1472.59 Da)) and cross-linked peptides with stabilized linker forms, respectively. Eight conjugation sites were coincidently assigned by both strategies. The assignment of the conjugation sites was manually validated by observed regularities (z equal or higher to 3+, XIC, immonium ions, specific linker fragment ions) not considered by the identification software (PEAKS, Kojak and pLink2). The RBD was also conjugated, but to a lesser extent, to ten other low abundance carrier proteins. To our knowledge, this work is the first report of conjugation site assignment in a TT-based conjugate vaccine.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.27.630511v1?rss=1

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Enhanced #RNA #replication and #pathogenesis in recent #SARS-CoV-2 #variants harboring the L260F mutation in NSP6

Abstract

The COVID-19 pandemic has been driven by SARS-CoV-2 variants with enhanced transmission and immune escape. Apart from extensive evolution in the Spike protein, non-Spike mutations are accumulating across the entire viral genome and their functional impact is not well understood. To address the contribution of these mutations, we reconstructed genomes of recent Omicron variants with disabled Spike expression (replicons) to systematically compare their RNA replication capabilities independently from Spike. We also used a single reference replicon and complemented it with various Omicron variant Spike proteins to quantify viral entry capabilities in single-round infection assays. Viral entry and RNA replication were negatively correlated, suggesting that as variants evolve reduced entry functions under growing immune pressure on Spike, RNA replication increases as a compensatory mechanism. We identified multiple mutations across the viral genome that enhanced viral RNA replication. NSP6 emerged as a hotspot with a distinct L260F mutation independently arising in the BQ.1.1 and XBB.1.16 variants. Using mutant and revertant NSP6 viral clones, the L260F mutation was validated to enhance viral replication in cells and increase pathogenesis in mice. Notably, this mutation enhanced host lipid droplet consumption by NSP6 without impacting its known ER-zippering function or double-membrane vesicle morphology. Collectively, a systematic analysis of RNA replication of recent Omicron variants defined NSP6 key role in viral RNA replication that provides insight into evolutionary trajectories of recent variants with possible therapeutic implications.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.30.628795v1?rss=1

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#USA, #Oregon: State ends year with highest #pertussis case count since 1950

As Oregon sweeps past the 1,100 cases mark, health officials remind everyone that vaccination against whooping cough is best way to prevent transmission

PORTLAND, Ore.—Oregon swept past the 1,100 mark for the number of pertussis cases it’s seen during 2024, beating its 2012 record of 910 cases in a single year—and making the need for people to stay up to date with their vaccinations all the more urgent.

As of Monday, Dec. 30, Oregon Health Authority registered 1,105 cases of pertussis—also known as whooping cough—during 2024. There were 44 outbreaks, although the majority of cases were sporadic individual or household-related cases and not associated with outbreaks. The 2024 count represents the highest number of pertussis cases reported in Oregon in a single year since 1950, when 1,420 cases were reported.

Since 2003, eight Oregonians with pertussis have died. Five were younger than 4 months old, and there have been three deaths in adults – one in 2023 and two in 2024.

While Oregon didn’t beat its 74-year record for most cases in a year, 1,105 is still an extremely high number for a vaccine-preventable disease, said Paul Cieslak, M.D., medical director for communicable diseases and immunizations at OHA’s Public Health Division. It’s also a stark reminder of how quickly the bacterial infection can spread and cause illness, particularly among people who are under- or unvaccinated.

“The pertussis vaccine is a public health success story in terms of its effectiveness in reducing severe illness and deaths from the disease—particularly among infants,” Cieslak said.

According to data from the epidemiologists in Oregon Public Health Division’s Acute and Communicable Disease Prevention Section, the median age of the 2024 cases is 12; 7.2% of cases are less than a year old, 80% are 18 or younger and 50% are female. About half of the cases are up to date with pertussis vaccines.

Lane County has reported the highest number of pertussis cases this year with 315. Rounding out the top five counties are Multnomah, 235 cases; Clackamas, 135; Washington, 119; and Marion, 75.

Pertussis case counts vary considerably from year to year, routinely reaching triple digits. However, during the COVID-19 pandemic, restrictions such as masking requirements and school closures were in effect, which kept annual case counts low, Cieslak said. Vaccination rates also slipped.

“People were less motivated to get vaccinated against pertussis when there was less concern they would be exposed to the infection in the first place,” he said.

But with pertussis activity so high this year, there are more opportunities for people to be exposed, Cieslak noted. Those who are unvaccinated or too young to be vaccinated, such as infants, are at the highest risk from infection, with babies most likely to be hospitalized with pertussis.

But there are ways to protect vulnerable individuals. Pregnant people can protect their young babies by getting the Tdap vaccine—which protects against tetanus, diphtheria and pertussis—at 27–36 weeks’ gestation. Mothers will make antibodies and pass them to their babies across the placenta, protecting them from the moment of birth. It is recommended during each pregnancy.

“In recent years, about two-thirds of pregnant Oregonians have been getting vaccinated during pregnancy,” Cieslak said. “However, only 11 of the mothers of the 80 infant cases this year had documentation of having gotten the recommended shot.”

Vaccination against pertussis is routinely recommended for infants, children, adolescents and adults. Children should receive the DTaP vaccine against diphtheria, tetanus and pertussis at 2, 4, 6 and 15 to 18 months old, and again at age 4 to kindergarten age. All persons 10 years old and older should receive a single dose of Tdap.

“Additionally, when pertussis strikes a household in which an infant or pregnant person lives, we recommend all members of the household receive a course of antibiotics effective against Bordetella pertussis—typically, a five-day course of azithromycin,” Cieslak said.

Source: Department of Health, https://content.govdelivery.com/accounts/ORHA/bulletins/3c9f333

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#Risk #assessment of 2024 #cattle #H5N1 using age-stratified #serosurveillance data

ABSTRACT

The highly pathogenic avian influenza virus A(H5N1) clade 2.3.4.4b has caused a human outbreak in North America since March 2024. Here, we conducted a serosurveillance study to determine the risk of A(H5N1) clade 2.3.4.4b (2024 cattle H5N1) to general population. In the initial screening of 180 serum specimens encompassing all age groups, 2.2% (4/180) had detectable neutralizing antibody (nAb) titers against 2024 cattle H5N1, with all collected from older adults aged ≥60 years old. Further screening showed that 5.0% (15/300) of adults aged ≥70 years old had detectable nAb titers against the 2024 cattle H5N1. All serum specimens with nAb titer of ≥40 had detectable HI titer, and there was a positive correlation between nAb titer and HA binding (r=0.3311, 95% confidence interval 0.2264 to 0.4283; P<0.0001). The nAb titer against seasonal H1N1 virus was 3.9-fold higher for patients with detectable H5N1 nAb than those without (geometric mean titer: 108.5 [95% CI 56.3-209.1] vs 27.9 [95% CI 21.0-37.0], P=0.0039), but there was no statistically significant difference between H5N1 and H3N2 nAb titer. There was no difference in demographics, comorbidities and clinical frailty scores between individuals with detectable H5N1 nAb and those without. Our findings suggest that most individuals lack nAb response against 2024 cattle H5N1 and there is an urgency to develop and evaluate H5N1 vaccine or prophylactic monoclonal antibodies. Immune imprinting may be responsible for the cross neutralization between H5N1 and H1N1 among older adults.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2024.12.23.24319580v1

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#Origin, spread, and interspecies #transmission of a dominant #genotype of BJ/94 #lineage #H9N2 avian #influenza viruses with increased #threat

Abstract

The H9N2 subtype of avian influenza viruses (AIVs) is widely prevalent in poultry and wild birds globally, with occasional transmission to humans. In comparison to other H9N2 lineages, the BJ/94 lineage has raised more public health concerns; however, its evolutionary dynamics and transmission patterns remain poorly understood. In this study, we demonstrate that over three decades (1994–2023), BJ/94 lineage has undergone substantial expansion in its geographical distribution, interspecies transmission, and viral reassortment with other AIV subtypes, increasing associated public health risks. These changes were primarily driven by the emergence of a dominant genotype G57. In the first decade, G57 emerged in East China and rapidly adapted to chickens and spread across China. Since 2013, the G57 genotype has expanded beyond China into eight other countries and reassorted with various AIV subtypes to form new zoonotic reassortants. Chickens have played a key role in the generation and circulation of the G57 viruses, with ducks and other poultry species likely assuming an increasingly importantly role. Over the past decade, G57 has been more frequently detected in wild birds, mammals, and humans. Additionally, Vietnam has emerged as a new hotspot for the international spread of G57. Our results suggest that the BJ/94 lineage H9N2 virus may continue to overcome geographical and species barriers, with potentially more severe consequences.

Source: Virus Evolution, https://academic.oup.com/ve/article/10/1/veae106/7919252

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#Germany - High pathogenicity avian #influenza #H5 viruses (#poultry) (Inf. with) - Immediate notification

 A poultry farm in Bayern Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6131

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High Pathogenicity Avian #Influenza Virus (HPAIV) #H5N1 clade 2.3.4.4b recovered from a kelp #gull (Larus dominicanus) in the South Shetland Islands, #Antarctica

Abstract

Whole-genome analysis of the earliest-detected High Pathogenicity Avian Influenza Virus (HPAIV) H5N1 clade 2.3.4.4b detected in Hannah Point, Antarctica (January 2024) reveals close relatedness to strains that circulated in pinnipeds and seabirds along the Atlantic coast of South America during the second half of 2023.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.29.630510v1?rss=1

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Dona Antonia de Ipenarrieta y Galdos and her Son, Diego Velazquez (c.1631)

 

Credits: Public Domain.

Source: WikiArt, https://www.wikiart.org/en/diego-velazquez/dona-antonia-de-ipenarrieta-y-galdos-and-her-son

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The #PA-X #host shutoff site 100 V exerts a contrary effect on viral #fitness of the highly pathogenic #H7N9 #influenza A virus in mice and chickens

ABSTRACT

Several viruses, including influenza A virus (IAV), encode viral factors to hijack cellular RNA biogenesis processes to direct the degradation of host mRNAs, termed “host shutoff.” Host shutoff enables viruses to simultaneously reduce antiviral responses and provides preferential access for viral mRNAs to cellular translation machinery. IAV PA-X is one of these factors that selectively shuts off the global host genes. However, the specific role of PA-X host shutoff activity in viral fitness of IAV remains poorly understood. Herein, we successfully mapped PA-X 100 V as a novel site important for host shutoff of the H7N9 and H5N1 viruses. By analysing the polymorphism of this residue in various subtype viruses, we found that PA-X 100 was highly variable in H7N9 viruses. Structural analysis revealed that 100 V was generally close to the PA-X endonuclease active site, which may account for its host shutoff activity. By generating the corresponding mutant viruses derived from the parental H7N9 virus and the PA-X-deficient H7N9 virus, we determined that PA-X 100 V significantly enhanced viral fitness in mice while diminishing viral virulence in chickens. Mechanistically, PA-X 100 V significantly increased viral polymerase activity and viral replication in mammalian cells. Furthermore, PA-X 100 V highly blunted the global host response in 293T cells, particularly restraining genes involved in energy metabolism and inflammatory response. Collectively, our data provided information about the intricate role of the PA-X host shutoff site in regulating the viral fitness of the H7N9 influenza virus, which furthers our understanding of the complicated pathogenesis of the influenza A virus.

Source: Virulence, https://www.tandfonline.com/doi/full/10.1080/21505594.2024.2445238

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#USA, Snow #Geese Test Presumptive Positive for Avian #H5 #Influenza; #Delaware #poultry producers encouraged to take precautions

 {Excerpt}

DOVER, Del. (Dec. 28, 2024) – The Delaware Department of Natural Resources and Environmental Control (DNREC) and the Delaware Department of Agriculture (DDA) announced today that laboratory testing conducted by the University of Delaware’s Allen Laboratory, part of the National Animal Health Laboratory Network, has returned presumptive positive findings of H5 avian influenza in sick and dead snow geese collected on December 27, 2024, in coastal Sussex County. 

In response to the findings, the state of Delaware has established a Joint Information Center with DNREC, DDA, the Delaware Division of Public Health (DPH) and the Delaware Emergency Management Agency (DEMA).

The detections mark the Delmarva region’s most recent confirmation of H5 avian influenza in wild birds since May 2022, when the virus was found through wildlife surveillance in black vultures in Harford County, Md. Avian influenza is known to be carried by wild birds, especially waterfowl, raptors, and vultures.

Avian influenza is a highly contagious airborne respiratory virus that spreads quickly among birds through nasal and eye secretions and manure. Snow geese, which are waterfowl, are known to migrate from the Arctic and form large flocks in Delaware each winter. Due to close contact with thousands of other snow geese while feeding and roosting, they can get sick and die. It is unknown when or where the snow geese may have acquired the virus given their highly migratory nature and association with other waterfowl and waterbirds throughout the Atlantic Flyway through which they travel into Delaware and more southern states.

People should not touch or handle injured, sick, or dead birds. Special attention should be paid to keep pets and children away from these wild birds and bird droppings.

Even with the ongoing detections of HPAI in wild birds, poultry, and dairy cattle in North America, continuing testing of people who are in close contact with infected animals indicates a low risk to the general public’s health. The H5N1 virus has infected very few people and has not been documented to be transmitted between people. The proper handling and cooking of all poultry and eggs to an internal temperature of 165°F is recommended as a general food safety precaution.

(...)

Source: Department of Health, https://news.delaware.gov/2024/12/28/snow-geese-test-presumptive-positive-for-avian-influenza-delaware-poultry-producers-encouraged-to-take-precautions/

_____

Molecular #Evolution of the #H5 and #H7 Highly Pathogenic Avian #Influenza Virus #Haemagglutinin Cleavage Site Motif

ABSTRACT

Avian influenza viruses are ubiquitous in the Anatinae subfamily of aquatic birds and occasionally spill over to poultry. Infection with low pathogenicity avian influenza viruses generally leads to subclinical or mild clinical disease. In contrast, highly pathogenic avian influenza viruses emerge from low pathogenic forms and can cause severe disease associated with extraordinarily high mortality rates. Here, we describe the natural history of avian influenza virus, with a focus on H5Nx and H7Nx subtypes, and the emergence of highly pathogenic forms; we review the biology of AIV; we examine cleavage of haemagglutinin by host cell enzymes with a particular emphasis on the biochemical properties of the proprotein convertases, and trypsin and trypsin-like proteases; we describe mechanisms implicated in the functional evolution of the haemagglutinin cleavage site motif that leads to emergence of HPAIVs; and finally, we discuss the diversity of H5 and H7 haemagglutinin cleavage site sequence motifs. It is crucial to understand the molecular attributes that drive the emergence and evolution of HPAIVs with pandemic potential to inform risk assessments and mitigate the threat of HPAIVs to poultry and human populations.

Source: Reviews in Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/rmv.70012

_____

#Coronavirus Disease Research #References (by AMEDEO, December 28 2024)

 

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   Int J Infect Dis

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    Radiology

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   Inhibitors of dihydroorotate dehydrogenase synergize with the broad antiviral activity of 4'-fluorouridine.
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   Epidemiol Infect

3. SUTER J, Devos I, Matthes KL, Staub K, et al
   The health and demographic impacts of the "Russian flu" pandemic in Switzerland in 1889/1890 and in the years thereafter.
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   PubMed         Abstract available
   
   

   
   JAMA

4. ANDERER S
   CDC Calls Attention to Underuse of Antiviral Treatment in Higher-Risk Youth With Influenza.
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   PubMed        
   
   

   
   PLoS Comput Biol

5. CALMON L, Colosi E, Bassignana G, Barrat A, et al
   Preserving friendships in school contacts: An algorithm to construct synthetic temporal networks for epidemic modelling.
   PLoS Comput Biol. 2024;20:e1012661.
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   PLoS One

6. BAGALA I, Namuganga JF, Nayebare P, Cuu G, et al
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7. ZHANG Y, Guo X, Su Y
   Spatiotemporal dynamic and regional differences of public attention to vaccination: An empirical study in China.
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8. KIM S, Aum T, Lee DG
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9. OPOKU-BOATENG YN, Opoku-Asante E, Lagarde M, Nketiah-Amponsah E, et al
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19. WANG J, Tonnies T, Brinks R
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20. FRAIHA ALS, da Silva Santos BSA, Aguilar NR, Gallinari GC, et al
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21. WERTHNER Q, Faehrmann L, Och K, Bragazzi NL, et al
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Virological and #antigenic characteristics of #SARS-CoV-2 #variants #LF721, #NP1, and #LP81

Abstract

XEC and KP.3.1.1 have surpassed KP.3 to become the globally dominant lineages due to their unique NTD mutations. However, several emerging JN.1 sublineages, such as LF.7.2.1, MC.10.1, NP.1, and, especially, LP.8.1, have demonstrated superior growth advantages compared to XEC. It is critical to access the virological and antigenic characteristics of these emerging SARS-CoV-2 variants. Here, we found that LF.7.2.1 is significantly more immune invasive than XEC, primarily due to the A475V mutation, which enabled the evasion of Class 1 neutralizing antibodies. However, LF.7.2.1's weak ACE2 binding affinity substantially impaired its fitness. Likewise, MC.10.1 and NP.1 exhibited strong antibody immune evasion due to the A435S mutation, but their limited ACE2 engagement efficiency restricted their growth advantage, suggesting that A435S may regulate the Spike conformation, similar to the NTD glycosylation mutations found in KP.3.1.1 and XEC. Most importantly, we found that LP.8.1 showed comparable humoral immune evasion to XEC but demonstrated much increased ACE2 engagement efficiency, supporting its rapid growth. These findings highlight the trade-off between immune evasion and ACE2 engagement efficiency in SARS-CoV-2 evolution, and underscore the importance of monitoring LP.8.1 These findings highlight the trade-off between immune evasion and ACE2 engagement efficiency in SARS-CoV-2 evolution, and underscore the importance of monitoring LP.8.1 and its descend lineages.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.27.630350v1?rss=1

_____

#USA, Confirmed #H5N1 #influenza #human case summary during 2024 #outbreak, by state and exposure source {as of Dec. 27 '24: 1 new case, total = 66}

 {Excerpt}

Exposure Source

[State - Exposure Associated with Commercial Agriculture and Related Operations: Dairy Herds (Cattle), Poultry Farms and Culling Operations - Other Animal Exposure† - Exposure Source Unknown‡ - State Total]

1) California - 36 - 0 - 0 - 1 - 37 {+1}

2) Colorado - 1 - 9 - 0 - 0 - 10

3) Iowa - 0 - 1 - 0 - 0 - 1

4) Louisiana - 0 - 0 - 1 - 0 - 1

5) Michigan - 2 - 0 - 0 - 0 - 2

6) Missouri - 0 - 0 - 0 - 1 - 1

7) Oregon - 0 - 1 - 0 - 0 - 1

8) Texas - 1 - 0 - 0 - 0 - 1

9) Washington - 0 - 11 - 0 - 0 - 11

10) Wisconsin - 0 - 1 - 0 - 0 - 1

-- Source Total - 40 - 23 - 1 - 2 - 66 {+1}

NOTE: One additional case was previously detected in a poultry worker in Colorado in 2022.

{†} Exposure was related to other animals such as backyard flocks, wild birds, or other mammals

{‡} Exposure source was not able to be identified

Probable human case summary during the 2024 outbreak, by state and exposure source {Seven Cases}

When a case tests positive for H5 at a public health laboratory but testing at CDC is not able to confirm H5 infection, per Council of State and Territorial Epidemiologists (CSTE) guidance, a case is reported as probable.

-- Probable cases with commercial poultry exposure (e.g., poultry farms or culling operations):

- Washington (3)

- Arizona (2)

-- Probable cases with commercial dairy (cattle) exposure:

- California (1)

-- Probable cases with exposure source unknown:

- Delaware (1)

Confirmed and probable cases are typically updated by 5 PM EST on Mondays (for cases confirmed by CDC on Friday, Saturday, or Sunday), Wednesdays (for cases confirmed by CDC on Monday or Tuesday), and Fridays (for cases confirmed by CDC on Wednesday and Thursday). Affected states may report cases more frequently.

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/situation-summary/?CDC_AAref_Val=https://www.cdc.gov/flu/avianflu/avian-flu-summary.htm

_____

Acute #respiratory #infections complicated by #malaria (previously undiagnosed disease) - #DRC

{Excerpts}

27 December 2024

Situation at a glance

This is an update to the Disease Outbreak News on Undiagnosed disease in the Democratic Republic of the Congo published on 8 December 2024 (now named acute respiratory infections complicated by malaria). 

It includes updated epidemiological investigation information and preliminary laboratory results. 

On 29 November, an alert was raised by local health zone authorities of Panzi health zone in Kwango province after an increase in deaths, particularly among children under five years of age, following febrile illness. 

Enhanced epidemiological surveillance was rapidly implemented, which in the absence of a clear diagnosis was based on the detection of syndromic cases of febrile illnesses with cough, body weakness, with one of a number of other symptoms compatible with acute respiratory and febrile illnesses. 

This resulted in a rapid increase in the number of cases meeting the definition, with a total of 891 cases reported as of 16 December. 

However, the weekly number of reported deaths (48 deaths reported over the period) has remained relatively stable. 

As of 16 December, laboratory results from a total of 430 samples indicated positive results for malaria, common respiratory viruses (Influenza A (H1N1, pdm09), rhinoviruses, SARS-COV-2, Human coronaviruses, parainfluenza viruses, and Human Adenovirus). 

While further laboratory tests are ongoing, together these findings suggest that a combination of common and seasonal viral respiratory infections and falciparum malaria, compounded by acute malnutrition led to an increase in severe infections and deaths, disproportionally affecting children under five years of age. 

Multidisciplinary rapid response teams have been deployed to investigate the event and strengthen the response. 

Efforts are ongoing to address the health needs in Panzi health zone. 

Enhanced surveillance in the community and within health facilities continues. 

The teams have also been providing support for diagnosis, the treatment of patients as well as with risk communication and community engagement. 

This event highlights the severe burden from common infectious diseases (acute respiratory infections and malaria) in a context of vulnerable populations facing food insecurity. It emphasizes the need to strengthen access to health care and address underlying causes of vulnerability, particularly malnutrition, given the worsening food insecurity.

Description of the situation

Since the last Disease Outbreak News on this event was published on 8 December 2024, 485 additional suspected cases and 17 additional deaths have been reported from Panzi health zone in Kwango Province, Democratic Republic of the Congo, across 25 out of the 30 health areas in Panzi. These cases were identified as a result of enhanced surveillance put in place following the report of deaths in the context of febrile illness with acute respiratory symptoms and anaemia, first reported on 29 November. While the number of reported cases was not deemed particularly unusual in a context of high burden of pneumonia, malaria and acute respiratory infections, particularly at the start of the rainy season, it is the increase in the number of deaths that triggered the alert on 29 November.

In the absence of diagnosis, a broad surveillance case definition was used, with the resulting case numbers reflecting the detection of any febrile illness occurring in Panzi and thus representing a range of diseases and clinical syndromes. The case definition includes: any person living in the Panzi health zone from September 2024 to date, presenting with fever, cough, body weakness, runny nose, with or without one of the following symptoms and signs: chills, headache, difficulty breathing, malnutrition, body aches. This was done to better understand the epidemiology and characteristics of deaths and to collect a range of clinical samples for laboratory testing.

Between 24 October and 16 December 2024, 48 deaths and a total of 891 cases across 25/30 health areas of Panzi health zone met the case definition. Children under five years of age are disproportionally affected, representing 47% of all cases and 54% of all deaths, while they represent around 18% of the population, likely reflecting the vulnerability of young children to severe disease and death in this context. The main symptoms associated with death include difficulty in breathing, anaemia, and signs of acute malnutrition.

A total of 430 samples including blood samples, oropharyngeal and nasopharyngeal swabs, urine and breastmilk samples were collected from suspected cases in Panzi health zone and transported to the laboratory at the INRB. 

Out of 88 rapid diagnostics tests for malaria performed in the field, 55 (62%) samples tested positive. In addition, out of 26 samples analyzed by PCR BioFire Global Fever Panel test (which tests 18 different pathogens including some of the viral hemorrhagic fevers), 17 (65%) samples tested positive for Plasmodium falciparum.  In addition, a total of 89 samples were tested at INRB Respiratory Disease Surveillance Laboratory. Of the 89 samples, 64 samples were positive for common respiratory viruses including Influenza A (H1N1, pdm09) (n=25), rhinoviruses (n=18), SARS-COV-2 (n=15), Human coronaviruses (n=3), parainfluenza viruses (n=2), and Human adenovirus (n=1).

Other laboratory tests on the collected samples, including virological and bacterial analysis, are still ongoing. The ongoing investigations and preliminary laboratory findings suggest that a combination of common viral respiratory infections and falciparum malaria, compounded by acute malnutrition led to an increase in severe infections and deaths.

Enhanced surveillance will continue, alongside response activities. The number of weekly reported suspected cases has remained steady with the exception of an increase in epidemiological week 50 (week ending 15 December 2024, Figure 1). While this may partly reflect an increase in transmission of respiratory viruses and malaria with the rainy season, it is driven by an increase in surveillance and case finding following the deployment of the rapid response teams. Notably, the increase in cases is not matched with a comparable increase in deaths.

(...)

There are proportionally more cases reported among females (58%, 514/889), particularly among adults (66% female, 173/262). While data is lacking to better understand this difference, it may stem from contact patterns of respiratory virus transmission within households, particularly a close interaction between mothers and children during acute respiratory illnesses. 

(...)

The affected area experienced deterioration in food security in recent months, with increasing levels of acute malnutrition. Between July and December 2024, which coincides with a drop in acute malnutrition, Kwango province was in Integrated Food Security Phase Classification (IPC) Acute Malnutrition (AMN) Phase 3 (Serious). Between January and June 2025, an increase in cases of malnutrition is projected in the province with a significant deterioration in the nutritional situation expected, moving to IPC AMN Phase 4 (Critical). Between July 2024 and June 2025, nearly 4.5 million children aged 6 to 59 months in the DRC are facing or expected to face acute malnutrition, including approximately 1.4 million cases of severe acute malnutrition and 3.1 million cases of moderate acute malnutrition. It is also estimated that 3.7 million pregnant and breastfeeding women are facing or expected to face acute malnutrition over the same period.[1]

Severe acute malnutrition is a life-threatening condition that requires medical treatment. In addition, disease and malnutrition combine to worsen each other. The area has low routine vaccination coverage. There is also very limited access to diagnostics and quality case management, and a lack of supplies and transportation, shortage of health staff in the area, as well as financial and geographical barriers to access to health care. Increasing malaria trends are expected with the start of the rainy season, however, malaria control measures in the area are very limited. Together, these factors may increase the severity of malaria, and common respiratory infections.

Overall, this event highlights the severe burden from common infectious diseases (acute respiratory infections and malaria) in a context of vulnerable populations facing food insecurity and emphasizes the need to strengthen access and quality of health care.

Public health response

1. Leadership and coordination:

Daily coordination meetings are being held at the national level, with provincial teams actively participating in ongoing planning and response.

National rapid response team (RRT) composed of experts from Ministry of Health (MoH), INRB and WHO deployed from Kinshasa on 7 December and arrived in Panzi on 10 December. Following the departure of the national team, a joint MoH-Africa CDC rapid response team has been deployed with support from WHO.

2. Surveillance:

A case definition has been developed based on clinical symptoms observed, guiding surveillance and reporting efforts.  

Active case search is continuing in health facilities and the community. 

Data collection is ongoing, focusing on preparing a line list and detailed epidemiological analysis.  

Community deaths are being investigated to better understand the context of deaths and vulnerability factors.

WHO is deploying a senior epidemiologist and a data manager to support the ongoing surveillance activities and improve data collection.

3. Case Management:

Provincial and national RRTs, including WHO, UNICEF and Médecins Sans Frontières, have been deployed to the affected areas and are strengthening case management in health facilities as well as providing medical supplies including medication. The teams carried medication and medical equipment to support case management and prevent more deaths.

Efforts are underway to strengthen the capacity of healthcare providers to ensure the best possible care for patients. 

Six oxygen concentrators are being installed at the Panzi General Referral Hospital and three hotspot health centers to support patient care.

4. Laboratory:

Laboratory equipment was transported to collect samples from cases and send samples for testing at the INRB in Kinshasa. Additionally, RDTs for malaria and COVID-19 have been provided to assist in diagnosis. 

Laboratory reagents have been procured to continue facilitating the ongoing testing at INRB.

5. Risk communication and community engagement:

Key messages were developed to enhance public awareness and encourage general preventive behaviors. These messages are being disseminated through community engagement, with sensitization campaigns underway. 

6. Infection prevention and control:

Infection prevention and control measures are being reinforced. Health workers have been briefed on key practices, including the proper use of masks, hand washing, and gloves, to reduce the risk of transmission of respiratory and other pathogens. 

7. Logistics

Logistical support is being provided for effective case management, including the transportation of samples to INRB Kinshasa for laboratory testing. Health facilities and hospitals in the most affected health areas are being supplied with appropriate medications and sampling kits to support the response. 

Medical kits for malaria, IPC kits, blood transfusion kits as well as additional medical supplies to support treatment efforts have been provided.

A mobile internet kit is being deployed to address some of the telecommunication challenges in the affected health zone. 

WHO risk assessment

Symptoms such as fever, cough, headache, and body aches have been observed since 24 October, primarily through health worker reports, and an uptick in deaths was observed in epi week 47, which triggered the signal. Since the alert was reported, there has not been any significant increase in reported deaths.

The epidemiological information together with the early laboratory result indicate an event triggered by an increase in acute respiratory virus cases associated with malaria, with a background of a worsening of the nutritional situation in Panzi, disproportionally affecting young children. 

The WHO African Region accounts for about 94% of all malaria cases and 95% of deaths globally (World Malaria Report 2024). Children under five account for about 76% of all malaria deaths in the Region. Over half of these deaths occurred in four countries: Nigeria (30.9%), the Democratic Republic of the Congo (11.3%), Niger (5.9%) and United Republic of Tanzania (4.3%). Support is being provided for laboratory diagnosis and strengthening case management including the treatment of malaria cases with appropriate medication.

An increase in common respiratory viruses and malaria is expected at this time of year in Panzi with the rainy season, however it is the increase in deaths that triggered the initial signal. There has been an increase in influenza and SARS-CoV-2 activity reported from Kinshasa through sentinel sites since mid-October. WHO and UNICEF estimates of national immunization coverage for 2023 show DTP3 and PCV3 coverage at 60% and 59%, respectively, however, no data is currently available for the affected health zone, leading to uncertainties about vaccine-derived population immunity.

The Integrated Food Security Phase Classification (IPC) for acute food insecurity levels in Kwango province increased from IPC 1 (acceptable) in April 2024 to IPC 3 (Crisis Level) in September 2024. This suggests a significant phase of increase in food insecurity and risk of severe acute malnutrition. In Addition, the IPC acute malnutrition classification currently classifies Panzi health zone as IPC acute malnutrition phase 3 (serious), projected to move to phase 4 (critical) from January 2025.

While mortality from common infectious diseases is expected to increase as transmission increases, this event highlights that mortality from known and expected infectious diseases can be high in a context of vulnerability and malnutrition, emphasizing the need to strengthen malaria control, clinical management, improve access to care and reduce the prevalence of malnutrition.

Gaps in case management have also been identified. Stock-outs of medications for treating common diseases frequently occur, and care is not provided free of charge, which could limit access to treatment for vulnerable populations and increase severity and mortality of known and treatable infections.

The affected area’s remoteness and logistical barriers, including a two-day or longer road journey from Kinshasa due to the rainy season affecting the roads and limited telecommunication network coverage across the health areas, have hampered the rapid deployment of response teams and resources. Furthermore, there is no functional laboratory in the health zone or province, requiring the collection and shipment of samples to Kinshasa for analysis. This has delayed diagnosis and can continue to impact the ongoing response efforts. 

Insecurity in the region adds another layer of complexity to the response. The potential for attacks by armed groups poses a direct risk to response teams and communities, which could further disrupt the response. 

Based on the above rationale, the overall public health risk level to the affected communities is assessed as high, and requires an integrated public health approach to reduce mortality from infections, improve nutritional status and strengthen malaria control, among others.

At the national level, the risk is considered low due to the localized nature of the event and that it is caused by a range of illnesses whose severity is compounded by the vulnerability of the population in the local context. However, many other areas of DRC are seeing increasing levels of malnutrition, and what has been witnessed in Panzi could also happen elsewhere in the country.

As such, efforts need to continue to prevent similar situation in other vulnerable parts of the country.  At the regional and global levels, the risk remains low at this time.  

WHO advice

To reduce the impact of the ongoing event in the Panzi health zone, WHO advises the following measures:  

-- Strengthening coordination mechanisms at all levels—national, provincial, zonal, and local—is critical for a unified response. Enhanced communication infrastructure, such as satellite phones, is required to overcome the limited network coverage in affected areas.

-- Improving surveillance efforts is a priority to better understand disease trends and mortality. Active case searches should continue in both health facilities and communities, with a particular focus on areas reporting deaths and family clusters. Community-based surveillance must be strengthened to ensure early case detection and rapid response.

-- Careful characterization of the clinical syndrome and outcomes and an improved case definition based on the information collected will be necessary to understand the situation. In particular, data which clarify possibility of coinfection and multiple pathologies, and uncertainties in outcomes among vulnerable groups should be collected. The WHO has established the Global Clinical Platform to provide rapid turnaround of structured data analysis using anonymized case records; its use is recommended in the detailed capture of patient syndromes and outcomes. 

-- Effective case management requires ensuring an adequate supply of essential medications, access to oxygen therapy, and training of healthcare workers including basic emergency and critical care to support treatment and prevent more deaths. RDTs for malaria should be distributed to facilitate early diagnosis and prompt treatment. Long-term laboratory capacity strengthening, and decentralization will be important in provision of diagnostic capability in the affected health zone and detect cause of deaths early.  

-- Infection prevention and control measures must be reinforced across all health facilities. Healthcare workers should receive training on best practices, including the proper use of personal protective equipment such as masks and gloves, as well as strict hand hygiene protocols. These measures will reduce transmission risks within health facilities and improve the safety of healthcare delivery.  

-- The role and added value of the health sector during food crises is crucial to prevent, reduce and reverse the causal relationship between poor nutrition, disease and death – before, during and after the onset of severe food shortages. As needs and vulnerabilities during food crises are complex, interlinked and multidimensional, intersectoral coordination and collaboration, especially between the health, nutrition, water, sanitation and hygiene (WASH) and food security clusters, should be stepped up as part of the overall humanitarian response. Data collection and analysis should be strengthened to inform the overall response.

-- Risk communication and community engagement are essential to raising public awareness. Targeted messages should be disseminated to educate the public on respiratory illness symptoms, preventive measures, and the importance of seeking care early. Community leaders must be engaged to build trust and encourage adherence to public health guidance. Addressing misinformation and fears within the community is critical to ensuring effective collaboration in the response.  

-- Logistical and security challenges also require attention. Strengthening logistical support for the deployment of teams and supplies will ensure timely access to affected areas. Contingency plans should be developed to address potential insecurity posed by armed groups, safeguarding response personnel and maintaining continuity in response activities.  

(...)

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON547

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#USA, Novel #Influenza A #H5N1 Virus: Five New Cases reported in Week 51/2024 {3 in #California, 1 in #Wisconsin, 1 in #Iowa}

{Excerpts}

-- Five confirmed cases of influenza A(H5) were reported to CDC this week. 

-- To date, human-to-human transmission of influenza A(H5) virus has not been identified in the United States.

Three of these cases were reported by the California Department of Public Health. The cases occurred in workers aged ≥18 years at commercial dairy cattle farms in an area where highly pathogenic avian influenza (HPAI) A(H5N1) viruses had been detected in cows. The individuals had mild symptoms, which they reported to local health department officials. There have now been 37 total confirmed cases and one probable case in California during the 2024-2025 influenza season.

One case was reported by the Wisconsin Department of Health. This case occurred in an individual aged ≥18 years who worked at a poultry facility where HPAI A(H5N1) virus had been identified in birds. This individual developed respiratory symptoms during Week 50. Specimens were collected from the individual and initially tested at the state public health laboratories using the CDC influenza A(H5) assay before being sent to CDC for further testing. Influenza A(H5) virus was confirmed at CDC. This is the first influenza A(H5) case in Wisconsin.

One case was reported by the Iowa Department of Health and Human Services. This case occurred in an individual aged ≥18 years who worked at a poultry facility where HPAI A(H5N1) virus had been identified in birds. This individual developed conjunctivitis and respiratory symptoms during Week 50. Specimens were collected from the individual and initially tested at the State Hygienic Laboratory at the University of Iowa using the CDC influenza A(H5) assay before being sent to CDC for further testing. Influenza A(H5) virus was confirmed at CDC. This is the first influenza A(H5) case in Iowa.

Notification to WHO of the cases reported by the Wisconsin and Iowa departments of health was initiated per International Health Regulations (IHR). More information regarding IHR can be found at http://www.who.int/topics/international_health_regulations/en/. 

No additional notification to WHO of the cases exposed to dairy cows in California is required per International Health Regulations (IHR).

The CSTE position statement, which includes updated case definitions for confirmed, probable, and suspected cases is available at http://www.cste.org/resource/resmgr/position_statements_files_2023/24-ID-09_Novel_Influenza_A.pdf

An up-to-date human case summary during the 2024 outbreak by state and exposure source is available at www.cdc.gov/bird-flu/situation-summary/index.html

Information about avian influenza is available at https://www.cdc.gov/flu/avianflu/index.htm.

Interim recommendations for Prevention, Monitoring, and Public Health Investigations are available at https://www.cdc.gov/bird-flu/prevention/hpai-interim-recommendations.html.

The latest case reports on avian influenza outbreaks in wild birds, commercial poultry, backyard or hobbyist flocks, and mammals in the United States are available from the USDA at https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/animal-disease-information/avian/avian-influenza/2022-hpai.

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/fluview/surveillance/2024-week-51.html

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Highly Pathogenic Avian #Influenza Contributes to the #Population Decline of the Peregrine #Falcon (Falco peregrinus) in the #Netherlands

Abstract

Highly pathogenic avian influenza (HPAI) epizootics have caused repeated mass mortality events among wild birds. The effect of the infection is potentially detrimental for a variety of bird species, including the Peregrine Falcon (Falco peregrinus). The numbers of wintering and breeding Peregrine Falcons in the Netherlands have recently declined. We investigated the changes in population trends in relation to HPAI H5 virus outbreaks. For this purpose, we analyzed variations in annual numbers of wintering and breeding birds, the virology of reported dead birds, and the presence of the HPAI H5 virus in unhatched eggs. We showed that significant mortalities of Peregrine Falcons had occurred in 2016–2017 and 2020–2023, years of major HPAI H5 virus outbreaks. In particular, the highest rates of bird mortality and HPAI virus infection were reported in 2023. In this year, over 80% (28/32) of the tested birds were positive for HPAI H5 virus. No HPAI H5 virus was present in the eggs. Based on these findings, we concluded that HPAI represents a serious threat to the Peregrine Falcon population in the Netherlands, and, in combination with anthropogenic factors, may contribute to the decline of this species. Targeted HPAI surveillance and disease mitigation measures are necessary for the conservation of this species.

Source: Viruses, https://www.mdpi.com/1999-4915/17/1/24

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#USA, #Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater (Dec. 27 '24)

{Excerpt}

Time Period: December 15 - December 21, 2024

-- H5 Detection: 52 sites (17.4%)

-- No Detection:  246 sites (82.6%)

-- No samples in last week:  87 sites

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/h5-monitoring/index.html

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Evidence of an emerging triple- #reassortant #H3N3 avian #influenza virus in #China

Abstract

The H3 subtype of avian influenza virus (AIV) stands out as one of the most prevalent subtypes, posing a significant threat to public health. In this study, a novel triple-reassortant H3N3 AIV designated A/chicken/China/16/2023 (H3N3), was isolated from a sick chicken in northern China. The complete genome of the isolate was determined using next-generation sequencing, and the AIV-like particles were confirmed via transmission electron microscopy. Subsequent phylogenetic analyses revealed that HA and NA genes of the H3N3 isolate clustered within the Eurasian lineage of AIVs, exhibiting the closest genetic relationship with other H3N3 AIVs identified in China during 2023. Interestingly, the HA and NA genes of the nove H3N3 isolate were originated from H3N8 and H10N3 AIVs, respectively, and the six internal genes originated from prevalent H9N2 AIVs. These findings indicated the novel H3N3 isolate possesses a complex genetic constellation, likely arising from multiple reassortment events involving H3N8, H9N2, and H10N3 subtype influenza viruses. Additionally, the presence of Q226 and T228 in the HA protein suggests the H3N3 virus preferentially binds to α-2,3-linked sialic acid receptors. The HA cleavage site motif (PEKQTR/GIF) and the absence of E627K and D701N mutations in PB2 protein classify the virus as a characteristic low pathogenicity AIV. However, several mutations in internal genes raise concerns about potential increases in viral resistance, virulence, and transmission in mammalian hosts. Overall, this study provides valuable insights into the molecular and genetic characterization of the emerging triple-reassortant H3N3 AIVs, and continued surveillance of domestic poultry is essential for monitoring the H3N3 subtype evolution and potential spread.

Source: BMC Genomics, https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-024-11152-x

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The #evolution of #hemagglutinin-158 and #neuraminidase-88 #glycosylation sites modulates antigenicity and #pathogenicity of clade 2.3.2.1 #H5N1 avian #influenza viruses

Abstract

Clade 2.3.2.1 of the H5N1 avian influenza virus (AIV) evolved into several subclades. However, the effect of glycosylation on the biological characteristics of hemagglutinin (HA) and/or neuraminidase (NA) from H5N1 AIVs remains unclear. Here, we determined that the global prevalence of clade 2.3.2.1 H5N1 AIVs with deglycosylated residue 158 on HA (HA158-) and glycosylated residue 88 on NA (NA88+) were predominant via multiple sequence analysis. The deglycosylation of residue on NA 88 (NA88-) was observed in clade 2.3.2.1a (new) and clade 2.3.2.1e H5N1 AIVs. Interestingly, NA88- was coupled with the acquisition of 158 glycosylation sites on HA (HA158+) in clade 2.3.2.1e H5N1 AIVs from China, and clade 2.3.2.1a (new) H5N1 AIVs exhibiting the HA158-NA88- pattern were predominant in Bangladesh. Meanwhile, the temporal distribution of strain HA158+ NA88- was highly consistent with the implementation of Re-6 vaccine in China. The recombinant H5N1 AIVs constructed using a reverse genetic system showed that the acquisition of the HA158 glycosylation site facilitated viral evasion from Re-6 antisera, and the virus lacking glycosylation sites at HA158 and NA88 resulted in reduced NA activity, replication in mammalian cells, and pathogenicity in both chickens and mice compared to that of the viruses with alternative glycosylation patterns. Therefore, the acquisition of HA158+ in clade 2.3.2.1e H5N1 AIVs enables evasion of Re-6 vaccination pressure, and the virulence of clade 2.3.2.1 H5N1 AIVs is modulated by the absence of glycosylation sites at HA158 and NA88. Our finding highlighted the importance of epidemiological surveillance and timely updating vaccines of H5 AIVs.

Source: Veterinary Microbiology, https://www.sciencedirect.com/science/article/abs/pii/S0378113524003559?via%3Dihub

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#DRC, #Kwango province affected by #influenza {A #H1N1} virus in #Panzi health zone

The flu caused by the Influenza virus, associated with malaria on a ground of malnutrition, is the unknown disease that has been decimating the population in the health zone of Panzi, in the province of Kwango, for more than a month.

This is what the diagnosis made by the INRB reveals after in-depth analyses. 

The governor of Kwango province, Willy Bitwisila, officially declared on Wednesday night, December 5, this epidemic which has caused around thirty deaths and more than 400 cases in this part of the Kasongolunda territory.

"This is the epidemic that is causing deaths in the previously unidentified Panzi health zone. 

''After a rigorous investigation, the results from the INRB laboratory have just confirmed that it is influenza caused by the Influenza AH1N1 virus, {rhinovirus, SARS-CoV-2, edited, in the article the terms are unreadable}, associated with malaria on the ground of malnutrition. 

''An epidemic that I am now officially declaring. I would therefore like to reassure each and every one of you that all necessary measures are being taken to slow the spread of this virus," said Willy Bitwisila.  

Source: Radio Okapi, https://www.radiookapi.net/2024/12/26/actualite/sante/la-province-du-kwango-affectee-par-le-virus-influenza-dans-la-zone-de

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Avian #Influenza Virus #Infections in #Felines: A Systematic Review of Two Decades of Literature

Abstract

As an avian influenza virus (AIV) panzootic is underway, the threat of a human pandemic is emerging. Infections among mammalian species in frequent contact with humans should be closely monitored. One mammalian family, the Felidae, is of particular concern. Domestic cats are susceptible to AIV infection and provide a potential pathway for zoonotic spillover to humans. Here, we provide a systematic review of the scientific literature to describe the epidemiology and global distribution of AIV infections in felines reported from 2004 – 2024. We identified 607 AIV infections in felines, including 302 associated deaths, comprising 18 countries and 12 felid species. We observed a drastic flux in the number of AIV infections among domestic cats in 2023 and 2024, commensurate with the emergence of H5N1 clade 2.3.4.4b. We estimate that this phenomenon is underreported in the scientific literature and argue that increased surveillance among domestic cats is urgently needed.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2024.04.30.24306585v2

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