Influenza D Virus (Worryingly) Mutates Further

Since the discovery of the novel Influenza D Virus in 2014, we've seen that this virus also has the capacity to mutate. See here.
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

Regular Influenza vaccinations might also protect against dementia. A retrospective study of 120,000 American veterans suggests that vaccination reduced the risk of developing dementia by 12 percent[1].
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 A virusses are divided into almost countless subtypes. These subtypes are named after the glycoproteins hemagglutinin (H) and the neuraminidase (N) that are found on the surface of the virus. At the moment there are at least 18 different subtypes of hemagglutinin and 9 different subtypes of neuraminidase. Almost all possible combinations have been found in birds, the remaining in bats.
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

Influenza A(H10N3) virus is not truly new and has been circulating in domestic ducks in Southeast-Asia for a while[1,2]. No news there, but the interest bit of new news was that this virus has jumped a species barrier and now has been shown to be able to infect humans too.
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

Seven people at a poultry farm in southern Russia have tested positive for Influenza A(H5N8), officials reported on February 20, 2021, making it the first time that the highly pathogenic virus has been found in humans. There is no evidence (yet) of human-to-human transmission.
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

Viral interference is the inhibition of one virus caused by a previous exposure to another virus or vaccine. The exact mechanism for viral interference remains unknown.
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

On 15 December 2020, the Brazil Ministry of Health reported the second confirmed human infection with influenza A(H1N2) variant virus, shortened to A(H1N2)v, in Brazil in 2020.
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.

It is recommended that quadrivalent 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;
- 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 Centers for Disease Control and Prevention (CDC) reports a human infection with an influenza A(H3N2)v Virus in Hawaii.
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

Over the past 14 years we've seen over 460 human infections with swine variant viruses in the United States, with the H3N2v strain the most common, followed by H1N2v, and H1N1v. Although these infections are still relatively uncommon, all known human influenza pandemics have come from H1, H2, or H3 viruses.

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?

During a meeting with pharmaceutical executives and members of his administration's coronavirus task force, President Donald Trump asked whether the Influenza vaccine would be useful in fighting COVID-19, the disease caused by the new coronavirus.
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

Seqirus, a global leader in influenza prevention and pandemic response, today announced that the U.S. Food and Drug Administration (FDA) has approved their AUDENZ™ (Influenza A (H5N1) Monovalent Vaccine, Adjuvanted) to help protect individuals six months of age and older against influenza A (H5N1). AUDENZ is the first-ever vaccine designed to protect against influenza A (H5N1) in the event of a pandemic.
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

Many virusses, known and unknown, are maintained and spread by anthropods, like mosquitoes and ticks. Many of these viruses are maintained in nature by a natural vertebrate reservoir, such as bats. Bats seem to be able to 'tolerate' potential zoonotic viruses in greater numbers and can therefore act as a reservoir for many potential emerging diseases[1].
[Antricola tick]
Scientists investigated the virome of adult Antricola ticks, collected in a swelteringly hot bat cave in the state of Rondônia in the western Brazilian Amazonia[2]. All species of Antricola ticks are known to infect cave-dwelling bats.

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

Pilchard Orthomyxovirus was first discovered in Australia in 1998 in pilchards (Sardinops sagax) in South Australia[1]. At that time, there were largescale deaths of pilchards caused by a herpes virus and, while testing, Pilchard Orthomyxovirus was also found to be present in these fish. Infected pilchards are usually just show subclinical symptoms, but signs of disease and mortalities in salmons have been recorded.
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

Researchers have pinpointed a key reason why people are more likely to get sick and even die from Influenza during winter months: 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

Why aging decreases our immune system’s abilities has long been a mystery. But a new study finds that our infection-battling B-cells become blunted with age, making us less equipped to fight off the Influenza in our advanced years[1]. And because most vaccines rely on a B-cell response to work, the findings may explain why the influenza vaccine is less effective in this population.
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.

Risk of Tilapia Lake Virus transmission via frozen tilapia fillets?

Recent outbreaks of a novel Tilapia Lake Virus have raised concerns regarding the international spread of Tilapia Lake Virus via frozen tilapia products. You see, in theory it is quite possible that a virus might survive in the deep frozen fish fillets and, if thawed, could infect you.
[Naive red hybrid tilapia]
Like me, some scientists were also growing a bit worried and investigated the potential risks of frozen tilapia fillet as a source of transmission[1]. The results were that genomic RNA of the Tilapia Lake Virus could be detected in tilapia fillet and the virus isolated from non-frozen and frozen fillets with clinical Tilapia Lake Virus infection stored up to 28 days caused a cytopathic effect formation in the susceptible cell line in vitro.

However, frozen fillets from clinical Tilapia Lake Virus infection stored for 90 and 120 days did not cause a cytopathic effect in the susceptible cell line. Similarly, a cytopathic effect was not observed in Tilapia Lake Virus isolated from subclinically Tilapia Lake Virus-infected fish fillets. In addition, in vivo bioassay revealed that despite the presence of Tilapia Lake Virus isolated from subclinically Tilapia Lake Virus-infected fillet stored at -20°C for 14 days, there was no evidence of Tilapia Lake Virus disease in naïve red hybrid tilapia (Oreochromis mosssambicusxniloticus) based on the absence of clinical signs and mortality and without the detection of Tilapia Lake Virus genomic RNA using reverse transcription-quantitative polymerase chain reaction assay.

Collectively, the scientists conclude, these findings suggested minimal risk of transmission of Tilapia Lake Virus via frozen tilapia fillets.

But is it? While the scientists wrote quite a lot about conditions that resulted in non-transmission, they glossed over the bit that proved that a transmission of Tilapia Lake Virus via frozen fish fillets was quite possible.

[1] Thammatorn et al: Minimal risk of tilapia lake virus transmission via frozen tilapia fillets in Journal of fish Diseases – 2019

Influenza Vaccine and Llamas

Llamas (and other camelids) may hold the key to a long-lasting Influenza vaccine. New research showed a protein produced by llamas fought off the virus in mice[1].
A scientific team injected the llamas with a vaccine that contained three different Influenza viruses. The scientists then collected broadly neutralizing single-domain antibody (sdAbs). They were then able to isolate two influenza A (SD36 and SD38) and two influenza B (SD83 and SD84) sdAbs and analyzed their in vitro neutralizing activity.

SD36 potently neutralized influenza A group 2 (H3, H4, H7, and H10) but not group 1 (H1, H2, and H5) viruses, whereas SD38 potently neutralized group 1 (H1, H2, and H5) and some group 2 (H3, H7, and H10) viruses, albeit with lower potency. SD84 and SD83 neutralized representative viruses from both influenza B lineages.

When this protein was given to mice they were more likely to survive influenza A and B than untreated rodents. The study also showed the protein protected rhesus macques monkeys for at least four months.

Prof Ian Wilson, one of the researchers, said: "It's very effective, there were 60 different viruses that were used in the challenge and only one wasn't neutralised and that's a virus that doesn't infect humans".

[1] Laursen et al: Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin in Science - 2018. See here.

Influenza and Obesity

A new study finds that growth rates in obesity and diabetes, along with populations which are increasingly resistant to antibiotics, could turn even a mild outbreak of Influenza into an explosive global pandemic[1].
One of the authors of the study, virologist Dr Kirsty Short, explained the link between obesity and spread of dangerous diseases: "There has been an incredible rate of increase of diabetes and obesity even in my lifetime. This has significant implications on infectious diseases and the spread of infectious disease."
Dr. Short continued, "But because chronic diseases have risen in frequency in such a short period of time, we’re only starting to appreciate all of the consequences."

"As our population is ageing and chronic diseases are becoming so prevalent, that could turn even a mild pandemic into a chronic one," Dr. Short concluded.

Though modern medicine and vaccines are better prepared to mitigate the impact of a major outbreak than in 1918, issues like obesity and diabetes more broadly present in society will likely provide a significant hindrance to prevention and treatment, scientists fear, as these conditions could alter the body's immune response, leading to greater rates of hospitalization and even death.

Disturbingly, scientists have predicted that if something on the scale of the 1918 Spanish flu were to occur today, it could result in a death toll as high as 147 million people worldwide, according to estimates.
Meanwhile, nearly all recent studies of American obesity suggest the trend of increasingly overweight Americans will only continue.

[1] Short et al: Back to the Future: Lessons Learned From the 1918 Influenza Pandemic in Frontiers of Cellular and Infection Microbiology - 2018

Influenza 2017-2018: 80,000 people in the US died from Influenza

Following a particularly severe 2017-2018 influenza season with a record-breaking estimated 900,000 hospitalizations and more than 80,000 deaths in the US, everyone is advised to follow the Centers for Disease Control and Prevention (CDC) recommendation that everyone age 6 months and older get vaccinated against Influenza each year.
These new estimates are record-breaking, and emphasize the seriousness and severity of Influenza and serve as a strong reminder of the importance of vaccination.

During the 2017-2018 season, 180 Influenza deaths in children were reported to CDC, exceeding the previously recorded high of 171 for regular (non-pandemic) Influenza season. This number is thought to be underestimated, as not all Influenza-related deaths are reported. During most Influenza seasons, about 80 percent of reported pediatric deaths occur in children who have not been fully vaccinated against Influenza.

Influenza vaccination has been shown to reduce the risk of flu illness, and a growing body of evidence supports the fact that vaccination also reduces the risk of serious Influenza outcomes that can result in hospitalization and even death.

CDC estimates that Influenza vaccines prevent tens of thousands of hospitalizations each year and a CDC study in 2017 was the first of its kind to show vaccination reduced the risk of Influenza-associated death by half (51 percent) among children with underlying high-risk medical conditions and by nearly two-thirds (65 percent) among healthy children[1].

Most recently, a study showed that Influenza vaccination lessened the risk of severe Influenza among adults, including reducing the risk of hospitalization and admission to the intensive care unit, and also lessened severity of illness[2]. These benefits are especially important for people at high risk of serious complications, like people 65 and older, children younger than 5 years, pregnant women and people with certain underlying long-term medical conditions, such as heart and lung disease or diabetes.

So, dear antivaxxers, even if you do not believe in the efficacy of vaccines yourself, please have your child vaccinated against Influenza. Do you really want to risk losing your child?

[1] Flannery et al: Influenza Vaccine Effectiveness Against Pediatric Deaths: 2010–2014 in Pediatrics - 2017
[2] Thompson et al: Influenza vaccine effectiveness in preventing influenza-associated intensive care admissions and attenuating severe disease among adults in New Zealand 2012–2015 in Vaccine - 2018

Oz Virus

Orthomyxoviruses harbour a family of viruses which also includes the feared Influenza viruses. And, yet again, scientists have found a novel virus that will expand that family.

The Oz virus was isolated from a hard tick, Amblyomma testudinarium, that was 'caught' in Ehime Prefecture in Japan[1].
No, this is not a virus that has been named after the wizard of Oz, but honours the Japanese city of Ōzu (大洲市 Ōzu-shi), located in the Ehime Prefecture where the tick was caught.

After testing the Oz Virus was found to be closely related to the Bourbon Virus, a virus pathogenic to humans, discovered recently in the United States. Oz virus caused high mortality in suckling mice after intracerebral inoculation.

The tick itself is endemic in large areas of Southeast Asia. Adults parasitize various larger mammals such as buffalo and cattle, but also are known to attack humans[2].

[1] Ejiri et al: Characterization of a novel thogotovirus isolated from Amblyomma testudinarium ticks in Ehime, Japan: A significant phylogenetic relationship to Bourbon virus in Virus Research – 2018
[2] Kim et al: A Case of Amblyomma testudinarium Tick Bite in a Korean Woman in Korean Journal of Parasitology - 2010

Influenza and Apergillosis

Aspergillus is a genus consisting of a few hundred different mold or fungi species found in various climates worldwide. Some species, such as Aspergillus fumigatus and Aspergillus flavus, can cause serious disease in humans.
[Aspergillus fumigatus]
Aspergillus fumigatus infections are primary pulmonary infections and can potentially become a rapidly necrotizing pneumonia with a potential to disseminate. Aspergillosis is the name given to a wide variety of diseases caused by infection by any species of Aspergillus.

It is estimated that most humans inhale thousands of Aspergillus spores daily, but they do not affect most people’s health due to effective immune responses.

Invasive pulmonary aspergillosis typically occurs in an immunocompromised host. For almost a century, influenza has been known to set up for bacterial superinfections, but recently patients with severe influenza were also reported to develop invasive pulmonary aspergillosis.

To investigate, researchers collected data of 432 patients admitted to the hospital with an Influenza A or B infection. Invasive pulmonary aspergillosis was diagnosed in 83 (19%) of these patients[1].

For patients with influenza who were immunocompromised, incidence of invasive pulmonary aspergillosis was as high as 32% (38 of 117 patients), whereas in the non-immunocompromised influenza case group, incidence was 14% (45 of 315 patients).

The 90-day mortality was 51% in patients in the influenza cohort with invasive pulmonary aspergillosis and 28% in the influenza cohort without invasive pulmonary aspergillosis.

The results show that Influenza is an independent risk factor for invasive pulmonary aspergillosis and is associated with high mortality. If there ever was a sound reason to get vaccinated, this is it.

[1] Schauwvlieghe et al: Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study in Lancet – 2018

Zambezi Tick Virus 1

Ticks are primary vectors for many well-known disease-causing agents that affect human and animal populations globally.

In the vally of the mighty Zambezi river in Mozambique, scientists recently collected 51 adult Rhipicephalus spp. ticks to investigate what viruses were present in those ticks[1].
The results were startling: the majority of viral sequences showed a closest sequence identity to the Orthomyxoviridae family, the ever increasing family that also includes all Influenza viruses.

Nearly complete sequences of five orthomyxoviral segments (HA, NP, PB1, PB2, and PA) were obtained and these showed an amino acid identity of 32–52% to known Quaranjaviruses. The sequences were most closely related to the Wellfleet Bay Virus, Tjuloc Virus, Quaranfil Virus, Johnstol Atoll Virus and still unclassified Quaranja viruses.

Although the virus was most closely related to the Wellfleet Bay Virus, with a similarity of just 50%, it was sufficiently different to warrant its own name: Zambezi tick virus 1

Little is known about most Quaranja viruses, but the viruses within this genus are globally distributed throughout the Middle East, Africa and Pacific regions, suggesting birds as their major hosts as these regions are major birds migration routes.

Another virus, another possibility to mutate. At this point in time it is not known if this novel virus can infect humans. But I won't hold my breath.

[1] Choletti et al: Viral metagenomics reveals the presence of highly divergent quaranjavirus in Rhipicephalus ticks from Mozambique in Infection Ecology & Epidemology – 2018

Influenza A viruses and Honeysuckle

Influenza A viruses have the annoying habit of frequently mutating and thus succesfully evading vaccination. These virusses are constantly changing via antigenic drift, antigenic shift or even reassortment. That's the reason why we need to vaccinate ourselves every year to be protected during the winter season.
Honeysuckle-based teas have long been utilized in Chinese culture to combat cold and Influenza-like symptoms. The plant (not the actress Honeysuckle Weeks) is known for its heady, intoxicating scent. Several reports have indicated that a decoction of honeysuckle (Lonicera japonica) can suppress the replication of Influenza A viruses in the human body. However, the active compound or compounds in this decoction and the mechanism by which they block viral replication have long remained unclear.

If we accept the idea that the honeysuckle has some antiviral properties, it must be possible to identify the exact compound.

Scientists have tried to do just that. They identified a plant microRNA called miR2911[1]. MicroRNAs are small molecules found in plants and animals that play an important role in influencing the pathways responsible for many diseases. These miRNAs resemble the small interfering RNAs (siRNAs) of the RNA interference (RNAi) pathway.

In clinical trials, this molecule was able to suppress Influenza A(H1N1) Virus, Influenza A(H7N9) and Influenza A(H5N1) Virus. This suggests that it has a broad-spectrum antiviral activity.

The scientists delivered boiled honeysuckle to the plasma and lung tissue of mice infected with an Influenza A(H1N1) virus. Results showed that miR2911 quickly bound itself to the messenger RNA - the molecule containing the genetic information - of the two genes responsible for viral replication. This binding mechanism blocked the replication process, and eventually the virus was destroyed. Other plants, such as chamomille, were found to also contain high levels of miR2911[2].
It was previously thought that boiling honeysuckle would destroy the beneficial molecules, but miR2911 proved resilient and to retain its properties even after boiling. This suggests that honeysuckle tea might be an effective way to prevent or  treat an Influenza infection.

[1] Zhen et al: Honeysuckle-encoded atypical microRNA2911 directly targets influenza A viruses in Cell Research - 2015. See here.
[2] Yang et al: Detection of an Abundant Plant-Based Small RNA in Healthy Consumers in PLoS One - 2015

Influenza D Virus Infection in Feral Swine Populations, United States

Influenza D Virus was first discovered in domesticated pigs in the US in 2011. Later evidence arose that cattle were the primary reservoir for influenza D Virus. But, as with all Influenza-like viruses, the Influenza D Virus was unpredictable.

At the moment Influenza D Virus has been identified in domestic cattle, swine, camelid, and small ruminant populations across North America, Europe, Asia, South America, and Africa.
[Feral swine: not cuddly at all]

A new study investigated the seroprevalence and transmissibility of Influenza D Virus in feral swine[1]. Swine were introduced into what is now the United States in the 15th century. Since that time, populations of free-ranging swine have spread to about 40 states. During 2012-2013, scientists evaluated feral swine populations in four US states.

Of 256 swine tested, 57 (19.1%) were seropositive for Influenza D Virus, indicating a previous infection. Previous studies have suggested that domestic swine are major sources of Influenza A Virus exposure for feral swine[2]. Among 96 archived influenza A virus-seropositive feral swine samples collected from 16 US states during 2010-2013, 41 (42.7%) were also Influenza D Virus seropositive.

While Influenza D Virus was shown not to cross-react with Influenza A Virus (yet), the our study showed that 42.3% of the IAV-seropositive feral swine also had exposure to IDV. The rate of seroprevalence of Influenza D Virus in Influenza A Virus-seropositive feral swine was more than twice that observed among Influenza A Virus-negative feral swine.

The question is, therefore, why are feral swine, that are infected with Influenza A Virus, more susceptible to an infection with Influenza D Virus. Or vice versa.

[1] Ferguson et al: Influenza D Virus Infection in Feral Swine Populations, United States in Emerging Infectious Diseases – 2018. See here.
[2] Martin et al: Feral Swine in the United States Have Been Exposed to both Avian and Swine Influenza A Viruses in Applied and Environmental Microbiology – 2017

Influenza A(H6N2) Virus in Indian Ducks

As always, nature will surprise us over and over again. As Michael Coston said here: Nature's laboratory is open 24/7 and it never stops tinkering with the evolutionary process.

Influenza A(H6Nx) is well established in terrestrial poultry, has jumped species barriers and caused human infection, thus indicating the pandemic potential of the virus. Indian scientists have discovered two different novel reassorted Influenza A(H6N2) viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively[1].
Hemagglutination (HA) inhibition assay revealed antigenic divergence between the two isolates. This result was corroborated by amino acid differences at 55 positions (15.98%) between their hemagglutinin (HA). The sequence analysis of the viruses indicated avian receptor specificity, avian origin and low pathogenicity to poultry.

However, the isolate from Kerala had a V27I mutation marker for amantadine resistance in M2. The isolate from Assam had an additional N-linked glycosylation on HA2 (position 557) compared to the Kerala isolate. Analysis of the HA gene revealed that both the viruses belonged to distinct lineages. Analysis of neuraminidase (NA) and internal gene segments revealed distinct gene constellation indicating that both the viruses are novel reassortants and are genetically distinct.

The results suggest independent introductions of the two different Influenza A(H6N2) viruses into India. Migratory wild birds using the Central Asian flyway might be the source of these Influenza A(H6N2) viruses in ducks in India.

[1] Kumar et al: Emergence of novel reassortant H6N2 avian influenza viruses in ducks in India in Infection, Genetics and Evolution - 2018

Composition of Influenza Virus vaccines in the 2018-2019 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.
There was considerable variation in the predominant virus type circulating in different regions during the period September 2017 to January 2018. Influenza B viruses predominated in many countries, while A(H3N2) viruses predominated in some and A(H1N1)pdm09 viruses circulated widely in Africa, Asia, parts of Europe and in the Middle East.

The vast majority of influenza A(H1N1)pdm09 viruses belonged to genetic subclade 6B.1 and were antigenically indistinguishable from the vaccine virus A/Michigan/45/2015.

Influenza A(H3N2) viruses were associated with outbreaks in several countries. The majority of recent viruses were antigenically related to cell culture-propagated A/Hong Kong/4801/2014-like and A/Singapore/INFMH-16-0019/2016-like viruses; they reacted poorly with ferret antisera raised to many egg-propagated clade 3C.2a viruses, but somewhat better to egg-propagated A/Singapore/INFMH-16-0019/2016-like viruses.

Influenza B viruses of the B/Yamagata/16/88 lineage predominated in most regions of the world. Recent B/Yamagata/16/88 lineage viruses were antigenically and genetically closely related to the vaccine virus B/Phuket/3073/2013. Influenza B viruses of the B/Victoria/2/87 lineage were detected in low numbers but a substantial and increasing proportion of these viruses, containing a two amino acid deletion in their HAs, were antigenically distinguishable from the vaccine virus B/Brisbane/60/2008 but closely related to B/Colorado/06/2017.

It is recommended that quadrivalent vaccines for use in the 2018-2019 northern hemisphere influenza season contain the following:

- an A/Michigan/45/2015 (H1N1)pdm09-like virus;
- an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus;
- a B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage);
- a B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage).

It is recommended that the influenza B virus component of trivalent vaccines for use in the 2018-2019 northern hemisphere influenza season be
- a B/Colorado/06/2017-like virus of the B/Victoria/2/87-lineage.

China reports first human case of influenza A(H7N4) Virus

The China's Centre for Health Protection (CHP) of the Department of Health (DH) has received notification from the National Health and Family Planning Commission (NHFPC) that a human case of avian influenza A (H7N4) was confirmed from February 10 to 14.

According to the NHFPC, this is the first case of human infection with avian influenza A (H7N4) in the world. The case involved a 68-year-old female patient living in Liyang in Changzhou of Jiangsu Province who developed symptoms on December 25, 2017. She was admitted to hospital for medical treatment on January 1 and was discharged on January 22. She had contact with live poultry before the onset of symptoms. All her close contacts did not have any symptoms during the medical surveillance period.

According to a report from the Chinese Center for Disease Control and Prevention, upon analysis, the genes of the virus were determined to be of avian origin. Although a subtype of Influenza A (H7N4) Virus sparked a minor outbreak in chickens in Australia in 1997[1], and this subtype has been reported elsewhere in the world (South Africa, Texas, etc.), this is likely a new reassortant virus.

Like I said before: nature is unpredictable.

[1] Selleck et al: An outbreak of highly pathogenic avian influenza in Australia in 1997 caused by an H7N4 virus in Avian Diseases - 2003

Nanoparticle vaccine for universal protection against influenza

Scientists revealed that vaccinating mice against influenza viruses using double-layered protein nanoparticles was successful[1]. Tests showed that the mice were fully protected against various types of influenza A viruses. Commenting on the research outcome, lead researcher Professor Bao-Zhong Wang said: “We’re trying to develop a new vaccine approach that eliminates the need for vaccination every year. We’re developing a universal influenza vaccine.”
The aim of the vaccine was to induce responses to the protein stalk part of the influenza surface glycoprotein, instead of the typical target of the head. Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains, formed from a process called glycosylation.

While the stalk domain offered protection, it is not, in itself stable. The researchers needed to devise a way to make it stable. This was performed by assembling a stalk domain into a protein nanoparticle as a vaccine. The nanoparticles were unique to the research since the particles were generated to contain only the protein that was capable of inducing immune responses.

To show the effectiveness of the nanoparticle vaccine, the science team immunized mice on two occasions via an intramuscular shot. The rodents were then exposed to several influenza viruses (H1N1, H3N2, H5N1 and H7N9). Study of the mice indicated that the immunization provided universal protection.

The next step on the path to a vaccine to be used on humans is for the researchers to test out the nanoparticle vaccine in ferrets. Ferrets are similar to humans in relation to the orchestration of their respiratory system.

[1] Deng et al: Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses in Nature Communications - 2018. See here.

Influenza A Virus in Shrimps

Wild aquatic birds are the natural reservoirs of Influenza A viruses. These birds can contaminate the natural water bodies inhabited by them. The question is if the Influenza A viruses, secreted by the birds, can persist in the waters around them.
Research has now concluded that these Influenza A viruses can persist in the contaminated water from days to years depending upon the environmental conditions. Various aquatic species other than ducks can promote the persistence and transmission of Influenza A viruses. However, studies on the role of aquatic fauna in persistence and transmission of these viruses are scarce.

So, the researchers designed an experiment to evaluate the survivability of Influenza A(H9N2) Virus in water with and without the bamboo shrimp (Atyopsis moluccensis) for a period of 12 days. The infectivity and amount of virus in water were calculated and were found to be significantly higher in water with the bamboo shrimp than in water without the bamboo shrimp[1].

The study also showed that bamboo shrimp can accumulate the virus mechanically which can infect chicken eggs up to 11 days. Whatever the means of accumulation, shrimps have now been proven to be a novel host for Influenza A viruses.

[1] Pathak et al: Survivability of low pathogenic (H9N2) avian influenza virus in water in the presence of Atyopsis moluccensis (Bamboo shrimp) in Zoonoses and Public Health - 2017

Influenza A(H3N2): the return of Adamantane

Around 1933, adamantane was discovered in petroleum. Because the content of it varies from between 0.0001% and 0.03%, it is far too low for commercial production. Which means it has to be synthesized in a laboratory.
All medical applications known so far involve not pure adamantane, but its derivatives. The first adamantane derivative used as a drug was amantadine in 1967. It was prescribed as an antiviral drug for the prevention and therapy of various strains of influenza A[1]. Other derevitives followed. Rimantadine was believed to inhibit influenza's viral replication, possibly by preventing the uncoating of the virus's protective shells, which are the envelope and capsid.

However, effectiveness of both amantadine and rimantadine was lost when Influenza A viruses acquired an amino acid substitution at one of five critical residues of the M2 protein[2]. It was thought these antiviral drugs would be consigned to history.

But, when doctors stopped prescribing these drugs, the pressure on the viruses diminished: they 'thought' that the previous mutation wasn't useful anymore and the mutation was lost in favour of other mutations that were more useful.
Even though the Influenza A(H3N2) virus has continued to undergo substantial antigenic and genetic evolution over the last decade, the M2 residue has remained almost completely fixed, suggesting that during that time it contributed to viral fitness. However, the recent detection of M2 S31 and D31 viruses in Australia suggests that the importance of the M2 N31 residue in viral fitness may no longer be as strong as it was[3].

It may be that the M2 S31 viruses detected in Australasia in 2017 could be the progenitors for a reversion back to more widely circulating adamantane-sensitive Influenza A(H3N2) viruses, some 12 years after the resistant strain emerged and then dominated globally. If this were the case, it would revive the option of using adamantanes to treat Influenza A(H3N2) virus infections and improve the opportunities for using these drugs in combination with other antivirals[4].

[1] Maugh: Panel urges wide use of antiviral drug in Science – 1979
[2] Hayden et al: Emergence and transmission of influenza A viruses resistant to amantadine and rimantadine in Current Topical Microbiology and Immunology - 1992
[3] Beigel et al: Oseltamivir, amantadine, and ribavirin combination antiviral therapy versus oseltamivir monotherapy for the treatment of influenza: a multicentre, double-blind, randomised phase 2 trial in Lancet – 2017
[4] Hurt et al: Detection of adamantane-sensitive influenza A(H3N2) viruses in Australia, 2017: a cause for hope? in EuroSurveillance - 2017

Tilapia Lake Virus spreading fast

Since 2009, tilapia aquaculture had been threatened by mysterious mass die-offs in farmed fish in Israel and Ecuador[1] and took some time to understand that a Orthomyxovirus was the root cause of the death of these fishes.
In 2016, the world was alerted to Tilapia Lake Virus, a novel Orthomyxovirus, the family of viruses that also includes all the Influenza viruses[2].

Israel and Ecuador are half a world apart and therefore the question was: how did it get from one country to another. The answer was simple, because it now clear that the Tilapia Lake Virus is killing fish on a worldwide scale. Reports have come from Egypt[3], Thailand[4] and Colombia[5].

At the moment, Tilapia Lake Virus has infected tilapia only, no other aquatic or terrestrial animals. The virus is mutating. I won't say more, but you understand my drift.

[1] Aygnor et al: Identification of a novel RNA virus lethal to tilapia in Journal of Clinical Biology - 2014
[2] Bacharach et al: Characterization of a Novel Orthomyxo-like Virus Causing Mass Die-Offs of Tilapia in mBio – 2016. See here.
[3] Nicholson et al: Detection of Tilapia Lake Virus in Egyptian fish farms experiencing high mortalities in 2015 in Journal of Fish Diseases – 2017
[4] Surachetpong et al: Outbreaks of Tilapia Lake Virus Infection, Thailand, 2015-2016 in Journal of Emerging Infectious diseases – 2017. See here.
[5] Kembou Tsofack et al: Detection of Tilapia Lake Virus in Clinical Samples by Culturing and Nested Reverse Transcription-PCR in Journal of Clinical Microbiology - 2017

Influenza pandemics during the Eighteenth Century

The medical profession of the eighteenth century was ill equipped to deal with influenza at any level. For most doctors, especially in the first six or seven decades of the century, influenza seemed to be spread or 'created' by atmospheric factors. Such theories could be complex. They usually invoked an unknown poison or spores carried in the air and/or specific winds, temperature changes, barometric pressures, or other meteorological factors to explain the appearance and spread of endemic diseases like influenza. To that extent, most eighteenth and early nineteenth-century articles on influenza are much more likely to contain elaborate meteorological tables than geographical reconstructions or statistics on morbidity or mortality.
Of course, we don't know the exact subtypes, but Influenza pandemics occurred at least three times in the eighteenth century: 1729-1730, 1732-1733, and 1781-1782. In addition there were two major epidemics that could possibly be considered pandemics, in 1761-1762 and 1788-1789. Of these, two warrant further discussion: the pandemic of 1729-1730 and the great pandemic of 1781-1782.

The 1729-1730 pandemic was the first recorded pandemic, most likely fostered by the age of discovery. Influenza apparently did not break out in North America until October 1732, when the disease was discovered widespread along the New England coast from Boston to southern Maine. Although the origins and termination of the 1729-1730 outbreak are unclear, it obviously was a pandemic, the first of a series that western European observers perceived as coming from Russia. An origin in Russia seems plausible, but there is no documentation of this. Initial reports were of substantial outbreaks in two widely separated Russian cities, Moscow and Astrakhan, on the Caspian Sea, in April, 1729. There were no further reports during the summer, but Influenza prevailed in Sweden in September and in Vienna in October. During November, Influenza was prevalent in Hungary and Poland, swept deep into Germany and appeared in London, Plymouth, York and Durham England, as well in Dublin, Ireland.

While quantitative evidence is lacking, the 1729-1730 pandemic caused sickness but relatively few deaths. Morbidity was extensive, but mortality was generally low, although the case-fatality rate was considered serious in northern Italy. Persons of all ages were stricken, but deaths were most numerous among the elderly and pregnant women.

The pandemic of 1781-1782 ranks with those of 1889-1890 and 1918-1919 as amongst the most widespread and dramatic outbreaks of disease in history. Unlike other pandemics of the eighteenth century, the pandemic of 1781-1782 had some interesting features that can be compared to the epidemics of the 20th century. A few general characteristics of this pandemic were noticed.
1. Eevidence of a spring wave in North Africa and North America in 1781
2. Diffusion of Influenza into the Eastern Hemisphere in 1781
3. Widespread outbreaks occurred within China and British-occupied India during the autumn of 1781
4. The pandemic started in China and spread westward in 1782.

It caused tens of millions of cases, spread as rapidly as existing transportation systems permitted, and not surprisingly, elicited volumes of medical writings.

The Return of Influenza A(H2N2) Virus

Influenza viruses follow a distinct pattern and timeline: H2, H3, H1, H2, H3, H1, H1.
Influenza A(H2N2) viruses caused two pandemics (1898 and 1957), about 69 years apart;
Influenza A(H3Nx) viruses caused two pandemics (1900 and 1957), about 68 years apart;
Influenza A(H1N1) viruses caused two pandemics (1918 and 1977), about 59 years apart;
Then apparently out of sync, the novel Influenza A(H1N1) Virus reemerged in 2009.

If nature can be trusted (which it certainly cannot), the next potential pandemic could be cause by the return of Influenza A(H2N2) Virus.

In 2011, after the first shock over the 2009 H1N1 pandemic had finally died down, some researchers suggested it might make sense to add an H2N2 component to the seasonal vaccine to head off the `next' pandemic[1]. As could be predicted, nobody really took care of this futuristic idea.

Research from 2013 studied 22 H2N2 avian viruses collected from domestic poultry and wild aquatic birds between 1961 and 2008. The researchers found evidence that descendants of the Influenza A(H2N2) virus, that killed millions worldwide in the 1950s, still pose a threat to human health, particularly to those under 50[2].

So, Influenza A(H2N2) Virus still roams free in the wild and it was no real surpise when Russian scientists isolated a variant of Influenza A(H2N2) Virus in a muskrat (Ondatra zibethicus): A/muskrat/Russia/63/2014 (H2N2)[3].
Results suggest that interspecies transmission of Influenza A viruses from wild water birds to semiaquatic mammals occurs, facilitating the spread and evolution of Influenza A viruses in wetland areas of Western Siberia. At the moment this mammalian Influenza A(H2N2) Virus presents no evidence of virulence for humans or poultry. Thus, it may be a muskrat-adapted virus or a transient virus in the nasal cavity of muskrats. The researchers think that muskrats could serve as a new reservoir of Influenza A viruses, posing a potential risk to other animals in the food chain, including humans.

[1] Nabel et al: Vaccinate for the next H2N2 pandemic now in Nature - 2011
[2] Jones et al: Risk assessment of H2N2 influenza viruses from the avian reservoir in Journal of Virology – 2014
[3] Gulyaeva et al: Genetic characterization of an H2N2 influenza virus isolated from a muskrat in Western Siberia in Journal of Veterinary Medical Science - 2017