Influenza News
An Encyclopedia of Forever Changing Viruses
Culex Modestus Orthomyxo-like Virus
These mosquitoes thrive during the summer. The larvae of the modest mosquito live in fresh to brackish water in irrigation canals, marshes and rice fields. Adult females are quite bloodthirsty and feed on the blood of vertebrates, especially birds, horses and humans. The males feed on nectar.
This annoying habit of aggressively feeding on both birds and humans causes problems, because this behaviour gives it a considerable potential for the transmission of zoonotic infections from birds to humans.
Scientific research has now shown that the modest mosquito is a carrier of an influenza-like virus especially adapted to this mosquito. This virus has been provisionally designated culex modestus orthomyxo-like virus[2].
The Orthomyxoviruses are a group of viruses that also include the influenza viruses. The discovery of a related virus suggests a potential novel pathway whereby Influenza viruses can again find new possibilities to mutate.
[1] Soto, Delang: Culex modestus: the overlooked mosquito vector in Parasites and Vectors - 2023
[2] Konstantinidis et al: Defining virus-carrier networks that shape the composition of the mosquito core virome of a local ecosystem in Virus Evolution - 2022. See here.
Chicharrita del Maiz Orthomyxo-like Virus
But scientists suspected that the maize leafhopper could harbour even more virusses. They comprehensively characterized the RNA virome of the maize leafhopper, revealing novel and diverse RNA viruses. They characterized six new viral members belonging to distinct families, but the scientists also discovered a previously unknown orthomyxo-like virus (Orthomyxoviridae)[2].
This highly divergent orthomyxo-like virus showed a relationship with other known insect associated orthomyxo-like viruses[3]. The researchers provisionally named that virus the Chicharrita del maiz orthomixo-like virus (ChMOMLV).
This new member of the ever-extending family of Orthomyxovirusses reveals a potential new vector for Influenza-like diseases in humans.
[1] Martins de Oliveira, Frizzas: Eight Decades of Dalbulus maidis (DeLong & Wolcott) (Hemiptera, Cicadellidae) in Brazil: What We Know and What We Need to Know in Neotropical Entomology - 2022
[2] Debat et al: Insights into the RNA Virome of the Corn Leafhopper Dalbulus maidis, a Major Emergent Threat of Maize in Latin America in Virusses – 2024. See here.
[3] Käfer et al: Re-assessing the diversity of negative strand RNA viruses in insects in PLoS Pathogens - 2019
Influenza A(H5N1) in Ferrets
Since 2020, there has been unprecedented global spread of highly pathogenic avian influenza A(H5N1) in wild bird populations with spillover into a variety of mammalian species and sporadically humans.
In March 2024, Influenza A(H5N1) virus was first detected in dairy cattle in the USA, with subsequent detection in numerous states, leading to date to over a dozen confirmed human cases.
In a study, scientists employed the ferret model, a species that permits concurrent investigation of viral pathogenicity and transmissibility in the evaluation of A/Texas/37/2024 (TX/37) A(H5N1) virus isolated from a dairy farmworker in Texas[1].
The results show that the virus has a 'remarkable ability' for robust systemic infection in ferrets, leading to high levels of virus shedding and spread to naïve contacts. Ferrets inoculated with TX/37 rapidly exhibited a severe and fatal infection. The virus efficiently transmitted in a direct contact setting and was capable of indirect transmission via fomites.
Airborne transmission was corroborated by the detection of infectious virus shed into the air by infected animals, albeit at lower levels compared to the highly transmissible human seasonal and swine-origin H1 subtype strains. Our results show that despite maintaining an avian-like receptor binding specificity, A/Texas/37/24 displays heightened virulence, transmissibility, and airborne shedding relative to other clade 2.3.4.4b virus isolated prior to the 2024 cattle outbreaks, underscoring the need for continued public health vigilance.
Ferrets represent an invaluable model for the study of influenza virus pathogenicity and transmissibility in humans[2].
In conclusion: Influenza (H5N1), isolated from a farmworker, was tested in ferrets. All animals died as a result of an infection 2 to 3 days post-inoculation. High virus titers were detected in systemic tissues from all ferrets, including the brain. Airborne transmission was also detected.
In another study it was found that A/Texas/37/2024 transmits by respiratory droplets in mammals without prior adaptation[3].
This doesn't bode at all well for the future.
[1] Joanna Pulit-Penaloza et al: Transmission of a human isolate of clade 2.3.4.4b A(H5N1) virus in ferrets in Nature - 2024
[2] Thakur et al: Ferrets as a Mammalian Model to Study Influenza Virus-Bacteria Interactions in Journal of Infectious Diseases - 2024
[3] Gu et al: A human isolate of bovine H5N1 is transmissible and lethal in animal models in Nature - 2024.
Influenza A(H5N1) in Cattle and Goats
Now, in March 2024, both cattle and goats are reported to be infected across multiple states of the United States. Potentially worse, there are some signs that cow-to-cow transmission may already have occurred.
Influenza A(H5N1) is highly virulent and was first detected in dairy cows in Texas and Kansas at the end of March 2024. Since then the virus has spread to additional herds. As of early April 2024, cases have been reported among dairy herds in Texas (7), Kansas (2), Michigan (1), New Mexico (1), and Ohio (1).
Cattle impacted by Influenza A(H5N1) exhibit flu-like symptoms, including fever and thick and discolored milk accompanied by a sharp reduction in milk production. Economic impacts to facilities are ongoing as herds that are greatly impacted may lose up to 40% of their milk production for 7 to 10 days until symptoms subside.
Cattle is a known mixing vessel for Influenza. The virus will have mutated to better infect these cows and goats. Which means that Influenza A(H5N1) is one step closer to become virulent enough to infect humans on the large scale.
On April 1, 2024 news appeared that the first human case of Influenza A(H5N1) infection was found in Texas. Also, the next day, a cat was found positive for Influenza A(H5N1).
Sequences from the dairy cows matched with those from wild bird samples collected from Texas about the same time. However, the goat samples from Minnesota are most similar to a pheasant sequence from Colorado.
Worldwide, Influenza A(H5N1) virus infections have been reported in more than 890 people with an approximately 50% case fatality rate since 1997. Mild upper respiratory tract symptoms, lower respiratory tract disease, severe pneumonia with respiratory failure, encephalitis, and multi-organ failure have been reported.
Luckily, a vaccine is already in development[1].
[Update 01 November 2024]
Since April 2024, 41 human cases of avian influenza A(H5) virus infection have been reported in the United States; 21 in total since 2022. 19 of these cases were associated with exposure to H5N1 bird flu-infected poultry and 21 were associated with exposure to sick or infected dairy cows. See here.
[1] Beukenhorst et al: A pan-influenza monoclonal antibody neutralizes H5 strains and prophylactically protects through intranasal administration in Science Reports - 2024
Composition of Influenza Virus vaccine for the 2024-2025 northern hemisphere
The periodic replacement of viruses contained in influenza vaccines is necessary in order for the vaccines to be effective due to the constant evolving nature of influenza viruses, including those circulating and infecting humans.
Twice annually, WHO organizes consultations to analyse influenza virus surveillance data generated by the WHO Global Influenza Surveillance and Response System (GISRS), and issues recommendations on the composition of the influenza vaccines for the following influenza season.
Recommendations
The WHO recommends that trivalent vaccines for use in the 2024-2025 northern hemisphere influenza season contain the following:
Egg-based vaccines - an A/Victoria/4897/2022 (H1N1)pdm09-like virus;
- an A/Thailand/8/2022 (H3N2)-like virus; and
- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus.
Cell culture- or recombinant-based vaccines
- an A/Wisconsin/67/2022 (H1N1)pdm09-like virus;
- an A/Massachusetts/18/2022 (H3N2)-like virus; and
- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus.
For quadrivalent egg- or cell culture-based or recombinant vaccines for use in the 2024-2025 northern hemisphere influenza season: While the B/Yamagata lineage vaccine component should be excluded as it is no longer warranted, where quadrivalent vaccines are still in use, the B/Yamagata lineage component remains unchanged: Egg-, cell- or recombinant-based Vaccines:
- a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.
Source.
Influenza A(H1N2) Virus in Humans
Sporadic human infections with swine Influenza A viruses have been reported since the late 1950s, usually after direct or indirect exposure to pigs or contaminated environments. Since 2018, sporadic influenza A(H1N2)v cases among humans have been detected in other countries in Europe (Austria, Denmark, France and the Netherlands), the Americas (Brazil, Canada and the United States of America), Asia (China) and in Australia. Infections in humans have primarily been acquired through direct contact with infected animals or contaminated environments. Risk factors include proximity to infected pigs or visiting locations where pigs are exhibited. However, in some cases, no known exposure to swine was reported.
On 25 November 2023, the United Kingdom notified the WHO of a human case of Influenza A(H1N2)v virus infection. The case reported onset of mild symptoms on 5 November 2023. The male patient visited his general practitioner on 9 November 2023. During this visit, a respiratory sample was collected and further analyzed as part of the national routine Influenza surveillance programme. On 23 November 2023 the sample was tested positive for Influenza A(H1N2)v virus. On 25 November, a follow-up RT-PCR test was performed and tested negative for influenza. The patient now fully recovered. Thus far we've seen no indication of additional cases, although contract tracing is apparently still ongoing.
Further analysis indicated that this Influenza A(H1N2)v virus belongs to the swine influenza virus genetic clade 1B.1.1. Similar A(H1N2) viruses from this genetic clade have been previously detected in pigs in the United Kingdom. However, this is the first time a virus from this swine genetic clade has been detected in a human in the United Kingdom.
It is still a mystery how the patient got infected - it has since been confirmed that the patient does not work with pigs or keep any as pets.
White Lung Syndrome in China
Major pediatric hospitals are recording 7,000 admissions per day in some areas of Beijing, reports suggest.
The largest hospital in Tianjin — a province on the coast near Beijing — has allegedly been receiving more than 13,000 sick children through its doors daily. There have also been reports of spikes in child illnesses in the province of Liaoning and in Shanghai — the country's biggest city.
Patients being admitted to hospitals are reportedly suffering from high fever and lung inflammation, but without a cough or pulmonary nodules — lumps on the lungs that are usually the result of a past infection. China also shared data that showed the country had been recording an increased number of children sick with mycoplasma pneumoniae — bacteria that causes mild infections of the respiratory system — since May.
Chinese officials say that no novel virus has been detected and that the cases are instead being caused by a resurgence of other known illnesses. Pediatric cases of Respiratory Synctial Virus (RS Virus), adenovirus, influenza and COVID-19 have also been surging since the fall, according to the data seen by the WHO.
The world was first alerted to the outbreak of 'mystery pneumonia' in China by a report published on ProMED in November 2023 — the same system that alerted the world to the emergence of Covid in Wuhan.
Repeated lockdowns and other measures — which were harshest in China — suppressed the spread of these diseases and weakened immunity against them, setting the stage for a rebound once restrictions were lifted. Experts have also suggested that the fact mostly children are being sickened in this outbreak suggests the diseases causing it are ones adults have already been infected by and have immunity against.
The US faced a similar wave of illnesses during the winter of 202-2023 in its own 'exit wave' from the pandemic with many pediatric units overflowing.
Genetically engineered chickens (partially) resist influenza
The researchers focused on a gene that is key to enabling avian influenza viruses to grow in chicken but not, typically, human cells. The gene codes for a protein, ANP32A, that normally plays a role in transcribing DNA into messenger RNA. The chicken ANP32A has 33 more amino acids than the human version, and an avian influenza enzyme called polymerase can co-opt it to make new virions.
The researchers also found chickens have a second gene for the same protein, ANP32B, that lacks this vulnerability. The virus can’t exploit its protein because it differs in two amino acids from ANP32A. So for the new work, they used CRISPR to introduce those mutations into the ANP32A gene in chicken primordial germ cells—the precursors of eggs and sperm—paving the way to breed chicks with the desired mutations. The altered birds appeared healthy.
To see whether they could resist infection, the researchers put an avian influenza virus into the nostrils of 20 2-week-old chicks, only half of which had the modified gene. All the wild-type birds became infected, but only one of the 10 genetically edited ones. That infected bird did not transmit to other birds with the resistance gene, further work showed. However, when the researchers inoculated them with 1000-fold higher doses of the virus, all became infected.
An analysis of the viruses that grew in the 'modified' birds revealed something more disturbing: mutations in their polymerase genes. The mutations allowed the enzyme to still get some help from the edited ANP32A protein and also from ANP32B and a third member of the same family, ANP32E, which like ANP32B typically plays no role in influenza replication.
Scientist now are worried that there is a 'high probability' that, if mutant viruses arise because of gene edits in chickens, they will be better adapted to mammals as well.
[1] Idoko-Akoh et al: Creating resistance to avian influenza infection through genome editing of the ANP32 gene family in Nature Communications - 2023. See here.
Influenza A Virus in Cats
Some cats developed severe symptoms including difficulty in breathing, bloody diarrhoea, and neurological signs, with rapid deterioration and death in some cases. In total, 20 cats had neurological signs, 19 had respiratory signs, and 17 had both neurological and respiratory signs.
Sporadic infection of cats with Influenza A(H5N1) Virus has previously been reported, but this is the first report of a high numbers of infected cats over a wide geographical area within a country.
As of 12 July, no human contacts of cats that tested positive with Influenza A(H5N1) Virus have reported symptoms, and the surveillance period for all contacts is now complete.
The risk of human infections following exposure to infected cats at the national level is (still) assessed as low for the general population, and (still) low to moderate for cat owners and those occupationally exposed to H5N1-infected cats (such as veterinarians) without the use of appropriate personal protective equipment.
This specific Influenza A(H5N1) Virus has been circulating in wild birds and which caused outbreaks in poultry recently in Poland.
[1] WHO: Influenza A(H5N1) in cats – Poland - July 16, 2023. See here.
Influenza A Virus in Bats [3]
[Image credit: BatWorld - Egyptian Fruit Bat] |
Here and here, I had already reported about strange Influenza viruses, A(H17N10) and A(H18N11), in South-American bats, the little yellow-shouldered bat (Sturnira lilium) in Guatemala and the flat-faced fruit-eating bat (Artibeus jamaicensis) in Peru, respectively. With a sense of relief, the researchers were unable to propagate this virus in cell cultures, suggesting it was a long way from being able to pose a threat to humans.
In 2015 serological evidence was published of Influenza A Viruses in Frugivorous Bats from Africa - which suggested prior H9 influenza infection in bats tested in Ghana - raising new questions about the range of flu viruses carried by bats[1]. The researchers were a bit worried about this and concluded 'As H9Nx is associated with human infections, the implications of the findings from a public health context remain to be investigated'.
In 2018 nature surprised us again when a study was published that described the isolation and characterization of a genetically distinct Influenza A H9-like virus from Egyptian fruit bats (Rousettus aegyptiacu), captured in an abandoned mudbrick house in a village in the Nile Delta region in March 2017. The virus already had the ability to replicate in the lungs of experimentally infected mice[2].
Then, in 2023, preliminary news arrived that bat Influenza A (H9N2) Virus identified in Egypt exhibited high replication and transmission potential in ferrets, efficient infection of human lung explant cultures, and marked escape from the antiviral activity of MxA (Myxovirus Resistance Protein A, a marker). Together with low antigenic similarity to N2 of seasonal human strains, bat Influenza A (H9N2) Virus meets key criteria for pre-pandemic Influenza A viruses[3].
[1] Freidl et al: Serological Evidence of Influenza A Viruses in Frugivorous Bats from Africa in PloS One – 2015. See here.
[2] Kandeil et al: Isolation and Characterization of a Distinct Influenza A Virus from Egyptian Bats in Journal of Virology – 2019. See here.
[3] Halwe et al: The bat-borne influenza A virus H9N2 exhibits a set of unexpected pre-pandemic features in Brief Communications – 2023. See here.
Influenza C Virus mutates
Less well known are Influenza C viruses and Influenza D viruses appear to have limited abilities to infect humans. That situation might end quite soon, because the Influenza C Virus is mutating.
Influenza C Virus was first isolated in 1947 in the US from a human patient having mild respiratory symptoms. The virus has a worldwide distribution and and the initial exposure or infection occurs during childhood. The majority of humans thus develop antibodies against Influenza C Virus early in life. Humans are the main reservoir of Influenza C Virus, but occasionally the virus may also infect dogs and pigs.
During the COVID-19 pandemic, the influenza epidemic increased in China and caused the influenza outbreak in 2021–2022. On 14 June, 2022, there was an abnormal increase in influenza-like illness in a kindergarten in Guangzhou, involving 68 children aged from 3 to 4. Results showed that one tested positive for the influenza C virus[1].
The case infected with Influenza C Virus was a four-year-old girl, who had symptoms, including runny nose, stuffy nose, slight cough, pharyngeal congestion, breathing sound aggravated, and conjunctival congestion, no vomiting and diarrhoea. She got fever for six days intermittently, with the highest temperature of 38.7°C on June 14, 2022.
The HE genes of Influenza C Virus fall into six genetic lineages that correspond to antigenic clusters. The the newly detected virus, named C/Guangzhou/05166/2022, was triple reassortant, with the gene of HE belonged to KA176-like lineage, the genes of PB2, PB1, M, and NS belonged to PB11581-like lineage, the genes of P3 and NP belonged to MS80-like lineage.
Phylogenetic analysis demonstrated that the genotype of C/Guangzhou/05166/2022 was different from the prevalent strains isolated from Hong Kong (2015–2020) and Japan Philippines (2009–2013), though the HE gene belongs to the same evolutionary branch of KA176 as the Hong Kong epidemic strain. This similar genotype strain could be traced back to the C/Miyagi/9/96 and C/Saitama/3/2000 of Japanese epidemic strains from 1996 to 2000, which revealed that the diversity of Influenza C Virus genes pool in Asia provided conditions that various gene segments could be mixed and reassorted.
The problem that an Influenza C infection has the same symptoms as a mild and asymptomatic COVID-19 infection, so it is difficult to distinguish clinically. So, Influenza C Virus can happily mutate further and become more dangerous.
[1] Lu et al: Emerging triple-reassortant influenza C virus with household-associated infection during an influenza A(H3N2) outbreak, China, 2022 in Emerging Infections - 2022. See here.
Composition of Influenza Virus vaccine for the 2023-2024 northern hemisphere
The periodic replacement of viruses contained in influenza vaccines is necessary in order for the vaccines to be effective due to the constant evolving nature of influenza viruses, including those circulating and infecting humans.
Twice annually, WHO organizes consultations to analyse influenza virus surveillance data generated by the WHO Global Influenza Surveillance and Response System (GISRS), and issues recommendations on the composition of the influenza vaccines for the following influenza season.
Recommendations
The WHO recommends that quadrivalent vaccines for use in the 2023-2024 influenza season in the northern hemisphere contain the following:
Egg-based vaccines
- an A/Victoria/4897/2022 (H1N1)pdm09-like virus;
- an A/Darwin/9/2021 (H3N2)-like virus;
- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus.
Cell culture- or recombinant-based vaccines
- an A/Wisconsin/67/2022 (H1N1)pdm09-like virus;
- an A/Darwin/6/2021 (H3N2)-like virus;
- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus.
For quadrivalent egg- or cell culture-based or recombinant vaccines for use in the 2023-2024 northern hemisphere influenza season, the WHO recommends inclusion of the following as the B/Yamagata lineage component:
- a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.
Source.
Composition of Influenza Virus vaccine for the 2023 southern hemisphere
The periodic replacement of viruses contained in influenza vaccines is necessary in order for the vaccines to be effective due to the constant evolving nature of influenza viruses, including those circulating and infecting humans.
Twice annually, WHO organizes consultations to analyse influenza virus surveillance data generated by the WHO Global Influenza Surveillance and Response System (GISRS), and issues recommendations on the composition of the influenza vaccines for the following influenza season.
Recommendations
The WHO recommends that quadrivalent vaccines for use in the 2023 influenza season in the southern hemisphere contain the following:
Egg-based vaccines
- an A/Sydney/5/2021 (H1N1)pdm09-like virus;
- an A/Darwin/9/2021 (H3N2)-like virus;
- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus; and
- a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.
Cell culture- or recombinant-based vaccines
- an A/Sydney/5/2021 (H1N1)pdm09-like virus;
- an A/Darwin/6/2021 (H3N2)-like virus;
- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus; and
- a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.
The WHO recommends that trivalent vaccines for use in the 2022-2023 influenza season in the northern hemisphere contain the following:
Egg-based vaccines
- an A/Sydney/5/2021 (H1N1)pdm09-like virus;
- an A/Darwin/9/2021 (H3N2)-like virus; and
- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus.
Cell culture- or recombinant-based vaccines
- an A/Sydney/5/2021 (H1N1)pdm09-like virus;
- an A/Darwin/9/2021 (H3N2)-like virus; and
- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus.
Source.
Influenza A(H5N1) Virus in Foxes
To determine whether these red foxes were susceptible to infection with Influenza A(H5N1) Virus, researchers infected three foxes intratracheally. They excreted virus pharyngeally for 3 to 7 days and had severe pneumonia, myocarditis, and encephalitis.
To see whether foxes can become infected by the presumed natural route, they fed infected bird carcasses to three other red foxes. These foxes excreted virus pharyngeally for 3 to 5 days, but only mild or no pneumonia developed.
This study demonstrated that if red foxes fed on bird carcasses, infected with Influenza A(H5N1) Virus, they can excrete virus while remaining free of severe disease, thereby potentially playing a role in virus dispersal.
Well, that was in 2008 and in a laboratory. What about infections in nature?
During the 2020-2022 epizootic of Influenza A(H5N1) Virus several infections of mammalian species were reported in Europe. In the Netherlands, Influenza A(H5N1) Virus infections were detected in three wild red foxes that were submitted with neurological symptoms between December 2021 and February 2022[2].
Analysis demonstrated the virus was mainly present in the brain, with limited or no detection in the respiratory tract and other organs. Further analysis showed the three fox viruses were not closely related. In addition, limited virus shedding was detected suggesting the virus was not transmitted between the foxes.
Genetic analysis demonstrated the presence of mammalian adaptation E627K in the polymerase basic two (PB2) protein of the two fox viruses. In both foxes the avian (PB2-627E) and the mammalian (PB2-627K) variant were present as a mixture in the virus population, which suggests the mutation emerged in these specific animals.
[Actress Kate Beckinsale with a wild fox: Not a good idea] |
Experiments showed mutation PB2-627K increases replication of the virus in mammalian cell lines compared to a chicken cell line, and at the lower temperatures of the mammalian upper respiratory tract. This study showed the Influenza A(H5N1) Virus is capable of adaptation to mammals, however more adaptive mutations are required to allow efficient transmission between mammals.
[1] Reperant et al: Highly Pathogenic Avian Influenza Virus (H5N1) Infection in Red Foxes Fed Infected Bird Carcasses in Emerging Infectious Diseases – 2008. See here.
[2] Bordes et al: Highly pathogenic avian influenza H5N1 virus infections in wild red foxes (Vulpes vulpes) show neurotropism and adaptive virus mutations in BioRxiv – 2022. See here.
Composition of Influenza Virus vaccine for the 2022-2023 northern hemisphere
The periodic replacement of viruses contained in influenza vaccines is necessary in order for the vaccines to be effective due to the constant evolving nature of influenza viruses, including those circulating and infecting humans.
Twice annually, WHO organizes consultations to analyse influenza virus surveillance data generated by the WHO Global Influenza Surveillance and Response System (GISRS), and issues recommendations on the composition of the influenza vaccines for the following influenza season.
Recommendations
The WHO recommends that quadrivalent vaccines for use in the 2022-2023 influenza season in the northern hemisphere contain the following:
Egg-based vaccines
- an A/Victoria/2570/2019 (H1N1)pdm09-like virus;
- an A/Darwin/9/2021 (H3N2)-like virus;
- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus;
- a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.
Cell culture- or recombinant-based vaccines
- an A/Wisconsin/588/2019 (H1N1)pdm09-like virus;
- an A/Darwin/6/2021 (H3N2)-like virus;
- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus;
- a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.
The WHO recommends that trivalent vaccines for use in the 2022-2023 influenza season in the northern hemisphere contain the following:
Egg-based vaccines
- an A/Victoria/2570/2019 (H1N1)pdm09-like virus;
- an A/Darwin/9/2021 (H3N2)-like virus;
- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus.
Cell culture- or recombinant-based vaccines
- an A/Wisconsin/588/2019 (H1N1)pdm09-like virus;
- an A/Darwin/6/2021 (H3N2)-like virus;
- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus
Influenza A(H3N8) Virus in Humans
An example is Influenza A(H3N8) Virus that is known to infect wild birds, although it has also been detected in live poultry markets in Asia. Occasionally, Influenza A(H3N8) viruses have been associated with disease in dogs, horses, pigs, donkeys, and most recently seals.
But on 25 April 2022, the Chinese health authorities reported an influenza A(H3N8) infection in a 4-year-old boy from Henan Province. He developed fever on 5 April 2022, cough and shortness of breath in the following days and was admitted to the hospital in critical condition on 10 April 2022 with severe pneumonia.
No human infection with influenza A(H3N8) Virus had been recorded before this case. Genetic analysis of the virus confirmed it is of avian origin. As said above, avian Influenza A(H3N8) viruses are commonly found - but not associated with disease - in wild birds and live poultry markets in Asia.
However, the genetic composition of A(H3N8) viruses detected in animals to date is different from that detected in the patient.
While further human infections with Influenza A(H3N8) viruses cannot be excluded, the Chinese authorities claim that the risk is low. The likelihood of sustained human-to-human transmission is also regarded as low.
That the Chinese authorities downplay the severity of this novel variant is nothing new. I think that a novel variant of Influenza A(H3N8) Virus that is able to infect humans should be regarded with some anxiety.
At the moment, we know know next to nothing about its ability to spread and to infect people. But we do know that a little boy was admitted to hospital with severe pneumonia.
Influenza D Virus (Worryingly) Mutates Further
Cattle were found to serve as its primary reservoir. Although there is an increasing number of strains, their origin remain unclear.
Phylogenetic analyses, published in 2021, suggest that there existed three major Influenza D Virus lineages designated as D/Yama2016, D/OK and D/660 as well as some intermediate lineages. Influenza D viruses show strong association with geographical location indicating a high level of local transmission, which suggests that this new family of viruses tend to establish a local lineage of in situ evolution[1].
However, the research mentioned above failed to include another Influenza D Virus lineage that was isolated from cattle in Japan with respiratory disease[2]. It was designated D/Yama2019.
Thus, then there were four distinct Influenza D Virus lineages.
But it didn't take long before another novel Influenza D Virus group was identified with broad antigenicity in American bovine herds, which is genetically different from previously known lineages of Influenza D Virus. Since these herds were grazing in the US state of California, this newly discovered lineage was given the designation D/CA2019[3].
Now there are five.
Are humans still safe, you might ask. The answer is that people are 'relatively safe' for now. Individuals working with cattle can become infected with Influenza D Virus, though they show (or have shown) no symptoms of disease.
Until Influenza D Virus mutates again. And again.
My advice: don't hug or kiss your cows anymore.
[1] He et al: Emergence and adaptive evolution of influenza D virus in Microbial Pathogenesis – 2021
[2] Murakami et al: Influenza D Virus of New Phylogenetic Lineage, Japan in Emerging Infectious Diseases – 2020. See here
[3] Huang et al: Emergence of new phylogenetic lineage of Influenza D virus with broad antigenicity in California, United States in Emerging Microbes and Infections – 2021. See here.
Influenza Vaccination and Dementia
On average, the veterans were 75.5 years of age. Of them 3.8% were female and 96.2% were male. The results were that veterans who had their regular influenza vaccination were significantly less likely to develop dementia compared to veterans without vaccination.
However, veterans with less than six yearly vaccination vs. none at all had similar risks for dementia. But veterans who had six or more Influenza vaccinations vs. none at all had a significant lower risk for dementia.
Thus, getting vaccinated against Influenza is associated with lower risk for dementia but only if you have received the vaccine for at least six years. This is consistent with the hypotheses that vaccinations may reduce risk of dementia by training the immune system and not by preventing specific infectious disease.
If vaccines are identified as causative factors in reducing incident dementia, the researcher think, they offer an inexpensive, low-risk intervention with effects greater than any existing preventive measure.
Which means that scientists have found another reason to get yourself vaccinated against Influenza (and by extension against Covid-19).
[1] Wiemken et al: Dementia risk following influenza vaccination in a large veteran cohort in Vaccine – 2021
Is Influenza B/Yamagata extinct?
Influenza B doesn’t have subtypes, but its viruses divide into two 'lineages', B/Victoria and B/Yamagata. Usually, only one of the Influenza B viruses was included in the yearly Influenza vaccines. Which might or might not work against the prevailing virus.
But the measures we have taken to manage the corona pandemic may have solved this problem. Measures like mask wearing, school closures, and travel restrictions were driving influenza transmission rates to historically low levels around the world. It appears that Influenza B/Yamagata might even have gone extinct.
It hasn't been spotted in over a year. In fact, March 2020 was the last time viral sequences from Influenza B/Yamagata were uploaded into the international databases used to monitor flu virus evolution.
It would be time to celebrate if only we knew that humans were the only host of Influenza B. Sadly, that is not the case. While some medical textbooks still maintain that the Influenza B Virus is only infecting humans, current research has indicated that this view is redundant. It is now known to infect seals and horses.
e So, it may hide in other animals, waiting to infect us again and in the mean time, it may mutate.
Influenza A(H10N3) virus in Humans
On April 28, 2021 a male patient from the city of Zhenjiang located in northeastern China was hospitalised with fever and other influenza-like symptoms. A few days later, the patient was in a stable condition and could be discharged form hospital. All close contacts were under medical observation.
The Chinese Center for Disease Control and Prevention conducted a whole genome sequence determination of the patient specimens. The result was positive for the Influenza A(H10N3) virus.
Scientists think that – at the moment – Influenza A(H10N3) has a low pathogenicity, which means it causes relatively less severe disease in poultry and is unlikely to cause a large-scale outbreak. They hope. No other cases of human infection with Influenza A(H10N3) have ever been reported globally.
Only around 160 isolates of the virus were reported in the 40 years to 2018, mostly in wild birds or waterfowl in Asia and some limited parts of North America, and none had been detected in chickens so far.
Analysing the genetic data of the virus will be necessary to determine whether it resembles older viruses or if it is a novel mix of different viruses.
[1] Wisedchanwet et al: Influenza A virus surveillance in live-bird markets: first report of influenza A virus subtype H4N6, H4N9, and H10N3 in Thailand in Avian Diseases – 2011
[2] Zhang et al: Characterization of the Pathogenesis of H10N3, H10N7, and H10N8 Subtype Avian Influenza Viruses Circulating in Ducks in Science Reports – 2017
Influenza A(H5N8) Virus in Humans
The virus was found in seven employees at a poultry farm in southern Russia, where outbreaks of Influenza A(H5N8) had previously been reported in the bird population. Anna Popova, the head of Russia’s consumer health watchdog, described the human cases as "mild".
“The virus can be transmitted from birds to humans, it has overcome the interspecies barrier,” Popova said. “This variant of the influenza virus is not transmitted from person to person. Only time will tell how quickly future mutations will allow it to overcome this barrier.”
Popova said the discovery will help researchers to prepare for the possibility of human-to-human transmission of the Influenza A(H5N8) virus. Information about the cases has been submitted to the World Health Organization (WHO).
Human cases of H5 viruses are rare but are sometimes found in people who are exposed to sick or dead birds.
239 human cases of H5N1 bird flu have been reported in China and Southeast Asia since 2003, killing 134 people, according to the WHO. Two people in China were also infected with H5N6 bird flu in January 2021, resulting in the death of a three-year-old girl.
Viral Interference: Influenza and Corona
Scientists assume that most cases of viral interference are mediated by interferon, a signaling protein, that is produced and released by cells in response to several viruses. Such an interferon release will cause nearby cells the heighten their anti-viral defenses.
In theory, if you have had an infection with an Influenza virus, you might be (partially) protected from an infection of a totally different virus, such as a coronavirus. And, because a vaccine is containing a part of a virus, being vaccinated may have the same results.
At this moment the world is suffering from disease and death of a novel coronavirus, Covid-19 and its many mutations. Would a previous infection with an Influenza virus or vaccination to counter such an infection have any impact on an infection with this new coronavirus?
But how do you prove that viral interference actually works?
In the United States about 50 percent of children receive a vaccination against Influenza viruses. Researchers investigated the effect of influenza vaccines on the disease course of coronavirus in the pediatric population and the possibility of viral interference[1].
They looked at medical records of 905 children who tested positive for Covid-19 when they were admitted to Arkansas Children's Hospital System between February 1 and August 30, 2020. As could be expected, roughly half had been given the seasonal Influenza vaccine. The data showed children that had received their Influenza vaccine were 29 per cent less likely to develop symptoms of Covid-19 following infection with the coronavirus.
Those who were vaccinated for influenza were also found to a have 32 percent reduced risk of developing respiratory symptoms and a 33 percent drop in the chance of developing severe disease, the scientists found.
While the study only looked at children, the scientists expect that the same results may be observed in the adult population.
[1] Patwardhan, Ohler: The Flu Vaccination May Have a Protective Effect on the Course of COVID-19 in the Pediatric Population: When Does Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Meet Influenza? In Cureus – 2021. See here.
Influenza A(H1N2)v Virus in Humans
The case was a 4 year-old female who lives on a farm which also functions as a swine slaughter in Irati municipality, Paraná state. On 16 November 2020, the patient had an illness onset with a fever, cough, coryza, headache and dyspnea, and was provided ambulatory care on the same day at Darcy Vargas Hospital. She was treated with medication for fever and headache and has since recovered. No symptomatic contacts were found among the case’s family.
On 18 and 19 November, respiratory samples were collected for testing. The Parana State Laboratory detected an unsubtypeable influenza A virus and the samples were sent to the the National Influenza Centre (NIC) in Rio de Janeiro for complete viral genome sequencing, where influenza A(H1N2)v virus was confirmed on 14 December 2020.
This case is actually the third human infection of influenza A(H1N2)v virus reported in Brazil. The first case was detected in 2015[1] and the second, 22-year-old female, in April 2020. These two confirmed cases lived in rural areas with pig farming and one case worked in a pig slaughterhouse.
The A(H1N2)v virus is genetically different from other variant viruses previously detected in humans in Brazil in 2015 and in April 2020, based on preliminary genetic analysis. The preliminary analysis shows that all genes are most similar to those from currently circulating influenza A(H1N1)pdm09 viruses, except for neuraminidase which is most similar to those from influenza A(H3N2) viruses.
This novel virus is the result of a reassortment of three different Influenza viruses: H1N2 (hemagglutinin), H3N2 (neuraminidase), and H1N1 (remaining genes). At the moment the Influenza A(H1N2)v virus appears not to be very contagious and does not result in serious illness. But all that can change rapidly.
[1] Resende et al: Whole-Genome Characterization of a Novel Human Influenza A(H1N2) Virus Variant, Brazil in Emerging Infectious Diseases - 2017. See here.
Composition of Influenza Virus vaccines in the 2021 southern hemisphere
The periodic replacement of viruses contained in influenza vaccines is necessary in order for the vaccines to be effective due to the constant evolving nature of influenza viruses, including those circulating and infecting humans.
Twice annually, WHO organizes consultations to analyse influenza virus surveillance data generated by the WHO Global Influenza Surveillance and Response System (GISRS), and issues recommendations on the composition of the influenza vaccines for the following influenza season.
Recommendations
It is recommended that quadrivalent vaccines for use in the 2021 southern hemisphere influenza season contain the following:
- an A/Victoria/2570/2019 (H1N1)pdm09-like virus;
- an A/Hong Kong/2671/2019 (H3N2)-like virus;
- a B/Washington/02/2019 (B/Victoria lineage)-like virus;
- a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.
Cell- or recombinant-based Vaccines:
- an A/Wisconsin/588/2019 (H1N1)pdm09-like virus;
- an A/Hong Kong/45/2019 (H3N2)-like virus;
- a B/Washington/02/2019 (B/Victoria lineage)-like virus;
- a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.
It is recommended that trivalent influenza vaccines for use in the 2021 southern hemisphere influenza season contain the following:
Egg-based Vaccines:
- an A/Victoria/2570/2019 (H1N1)pdm09-like virus;
- an A/Hong Kong/2671/2019 (H3N2)-like virus;
a B/Washington/02/2019 (B/Victoria lineage)-like virus.
Cell- or recombinant-based Vaccines:
- an A/Wisconsin/588/2019 (H1N1)pdm09-like virus;
- an A/Hong Kong/45/2019 (H3N2)-like virus;
- a B/Washington/02/2019 (B/Victoria lineage)-like virus.
Influenza H3N2v Virus on Hawaï
The patient is a child younger than 18 years of age, was not hospitalized, and has recovered from its illness. While no exposure to swine has been reported to date, an investigation is ongoing into the source of the patient’s infection.
According to officials, this is the first influenza A(H3N2)v virus infection detected in the United States since 2018.
The CDC describes variant influenza viruses as follows:
When an influenza virus that normally circulates in swine (but not people) is detected in a person, it is called a “variant influenza virus.” For example, if a swine origin influenza A H3N2 virus is detected in a person, that virus will be called an “H3N2 variant” virus or “H3N2v” virus.
Most commonly, human infections with variant viruses have occurred in people exposed to infected pigs (e.g. children near pigs at a fair or workers in the swine industry). In addition, there have been documented cases of multiple persons becoming sick after exposure to one or more sick pigs. Also some cases of limited person-to-person spread of variant viruses have occurred.
Influenza A(H1N2)v case reported in Brazil
According to a World Health Organization (WHO) report, a human infection with Influenza A(H1N2) variant virus or A(H1N2)v has been reported in an individual in Brazil.
The patient is a 22-year-old female, with no comorbidities, worked in a swine slaughterhouse in Ibiporã Municipality, Paraná State, and developed an influenza-like illness on 12 April 2020.
The patient initially sought medical care on 14 April and a respiratory specimen was obtained on 16 April as part of routine surveillance activities. The patient was treated with oseltamivir, was not hospitalized and has recovered.
On 26 June 2020, local authorities started a retrospective and prospective investigation in the slaughterhouse in Ibiporã Municipality and other municipalities where the slaughterhouse workers live. According to the preliminary epidemiological investigation, a second individual who also worked at the slaughterhouse developed respiratory symptoms during the same timeframe as the confirmed case, but no sample was collected from this person. No other suspected cases amongst contacts of the confirmed case have been identified.
To date, 26 cases of influenza A(H1N2)v have been reported to WHO since 2005, including two from Brazil. Most of the cases have presented with mild illness and there has been no evidence of person-to-person transmission.
Trump: Can Influenza Vaccine work against Corona?
Leonard Schleifer, CEO of the biotechnology company Regeneron, said that while millions of people were vaccinated for the Influenza, no one had yet gotten a vaccine to prevent SARS-2, caused by COVID-19.
"But the same vaccine could not work?" Trump said. "You take a solid flu vaccine — you don't think that would have an impact, or much of an impact, on corona?"
"No," Schleifer replied truthfully.
However, the president appeared to not understand basic information about how a vaccine works, is tested or produced and had to be repeatedly corrected by public health officials. While influenza and COVID-19 are both respiratory illnesses that involve similar symptoms, the two viruses belong to a different genus and have major structural differences.
It takes 18 to 24 months to develop and test an effective vaccine, and that is already an accelerated timetable. Cost estimates have ranged from $200 million to $1.5 billion. And while researchers may be able to develop a vaccine for this particular coronavirus strain, it might not be until after this outbreak has ended.
Only days later, during a visit to the CDC, Trump bragged about him having a 'natural ability to understand science'. As Joseph de Maistre (1753-1821) so eloquently observed 'every nation gets the government it deserves'.
For an insight into Trump's muddled mindset, read Miranda Carter's essay 'What Happens When a Bad-Tempered, Distractible Doofus* Runs an Empire?' here.
FDA approves Influenza A(H5N1) vaccine
AUDENZ is designed to be rapidly deployed to help protect the U.S. population and can be stockpiled for first responders in the event of pandemic.
An influenza A (H5N1) pandemic would be a global epidemic caused by the emergence of a new influenza virus to which there is little or no pre-existing immunity in the human population. Pandemics are impossible to predict and can cause catastrophic morbidity and mortality globally. The World Health Organization (WHO) Global Influenza Strategy for 2019-2030 states that a severe pandemic can result in widespread social and economic effects, including a loss of national economic productivity and severe economic burdens on affected citizens and communities.
Like the spread of the novel Corona virus, pandemic influenza viruses can also be deadly and spread rapidly, making production of safe, effective vaccines essential in saving lives.
Rondônia Virus
[Antricola tick] |
They identified a large number of novel viral sequences from various families, among them a novel Orthomyxovirus that had a 45% sequence identity to known thogotoviruses, such as Bourbon Virus, Oz Virus and Dhori Virus.
So, again we have a new Influenza-like virus that has the built-in potential to jump from bats, ticks or mosquitoes to humans. It is just a matter of time before we fall victim to one of these previously unknown virusses, just like the novel Coronavirus that is now ravaging China.
[1] Mandl: Going to Bat(s) for Studies of Disease Tolerance in Frontiers of Immunology 2018
[2] Blomström et al: Novel Viruses Found in Antricola Ticks Collected in Bat Caves in the Western Amazonia of Brazil in Viruses - 2019. See here.
Pilchard Orthomyxovirus
However, this was simply an accidental finding by diagnostic tests as these pilchard weren't dying from Pilchard Orthomyxovirus. This virus probably has been in pilchards for a very long time.
Pilchard Orthomyxovirus has been detected in pilchards and Atlantic salmon in Australia in 1998 and then went off the radar. It was rediscovered in 2006 in Tasmanian waters in Atlantic salmon on the Tamar River. The first outbreak of Pilchard Orthomyxovirus in Atlantic salmon occured in 2012 in the south east of Tasmania.
As pilchards are small enough to swim through the nets on salmon farms, and salmon are susceptible to the virus, it can be passed from pilchards to salmon, salmon to salmon, and potentially salmon to pilchards.
Pilchard Orthomyxovirus is distantly related to the Infectious Salmon Anaemia Virus, which causes disease in Atlantic salmon on both sides of the Atlantic Ocean. However, as a result of the observed differences, Pilchard Orthomyxovirus is the first virus to be characterised from a new genus within the Orthomyxoviridae[2].
As is the case with Pilchard Orthomyxovirus, Infectious Salmon Anaemia virus causes disease in Atlantic salmon, but does not cause disease in herring, brown trout, or other fish species.
[1] Pilchard Orthomyxovirus (POMV) fact sheet. See here.
[2] Mohr et al: Pilchard Orthomyxovirus (POMV). I. Characterisation of an Emerging Virus Isolated From Pilchards Sardinops Sagax and Atlantic Salmon Salmo Salar in Diseases of Aquatic Origin - 2020
Influenza and Low Humidity
While experts know that cold temperatures and low humidity promote transmission of the Influenza Virus, less is understood about the effect of decreased humidity on the immune system’s defenses against an Influenza infection.
The research team explored the question using mice genetically modified to resist viral infection as humans do. The mice were all housed in chambers at the same temperature, but with either low or normal humidity. They were then exposed to an Influenza A Virus.
The researchers found that low humidity hindered the immune response of the animals in three ways[1]. It prevented cilia, which are hair-like structures in airways cells, from removing viral particles and mucus. It also reduced the ability of airway cells to repair damage caused by the virus in the lungs. The third mechanism involved interferons, or signaling proteins released by virus-infected cells to alert neighboring cells to the viral threat. In the low-humidity environment, this innate immune defense system failed.
The study offers insight into why Influenza is more prevalent when the air is dry. "It’s well known that where humidity drops, a spike in flu incidence and mortality occurs. If our findings in mice hold up in humans, our study provides a possible mechanism underlying this seasonal nature of flu disease," said lead scientist Iwasaki.
While the researchers emphasized that humidity is not the only factor in Influenza outbreaks, it is an important one that should be considered during the winter season. Increasing water vapor in the air with humidifiers at home, school, work, and even hospital environments is a potential strategy to reduce Influenza symptoms and speed recovery, they said.
[1] Kudo et al: Low ambient humidity impairs barrier function and innate resistance against influenza infection in PNAS – 2019. See here.
Why Influenza Vaccines do not work as well in the elderly
Scientists compared how B-cells and antibodies from younger adults (ages 22 to 64) and elderly adults (ages 71 to 89) responded to vaccines for recent Influenza strains. The B-cells of younger people were good at recognizing mutations of the virus and producing protective antibodies. But the older people’s B-cells were less adept at fighting the rapidly changing influenza virus. Their B-cells were more stagnant and the antibodies they produced were less diverse and less potent than the younger people’s.
"[Their B-cells] are 'stuck in the past'. The influenza viruses mutate and evolve with time, but with age, our B-cells can no longer keep up," said author Patrick Wilson, researcher at the University of Chicago.
Our immune systems learn from exposure, and B-cells play a major role in the immunity process. With the help of other cells in the immune system, B-cells churn out antibodies when we get sick or receive an immunization. Antibodies are Y-shaped proteins that bind to harmful invaders and mark them for destruction. Once the infection is cleared, a type of record-keeping B-cell, known as memory B-cells, remain in the bloodstream and stand ready to produce antibodies if the threat is encountered again.
As we age, something hampers our immune system’s ability to produce ever-stronger antibodies in response to infections. As a result, older people are relying on mostly memory B-cells to make antibodies from long-past immune responses that are ill-equipped to squash rapidly evolving pathogens like theInfluenzavirus.
While new Influenza strains were problematic for the elderly participant’s B-cells, they were very proficient at combatting mutations of the virus that circulated during their childhoods. Young people’s B-cells, however, struggled when faced with older strains of Influenza.
The strength of our immune response diminishes over time once we reach a certain age. The researchers observed that participants between 50 and 70-years-old had intermediate declines in their influenza-fighting power, with steeper drops typical after age 70.
That’s why vaccines are so necessary for the elderly. But because the ever-changing Influenza virus is capable of outsmarting young and old immune systems alike, even a well-matched vaccine may only reduce the chances of illness by 40 to 60 percent in the general population. Effective rates are typically less for the elderly, but Wilson stressed that "not as effective" does not mean "not at all effective". With vaccination, the duration and severity of illness will be reduced, which is extremely important for older people as the severity of infection is already much worse.
[1] Henry et al: Influenza Virus Vaccination Elicits Poorly Adapted B Cell Responses in Elderly Individuals in Cell Host & Microbe – 2019. See here.