Systematic Review & Meta-Analysis: First-Trimester Influenza Infection Increases the Odds of Non-Chromosomal Birth Defects

 

Photo Credit – CDC

#17,155

We've long known that influenza and pregnancy are a bad combination - one that can endanger both the mother and unborn child’s life – and that women are more susceptible to influenza while (and just after) they are pregnant (see Study: Outcomes Of Infants Born To Women With Influenza A(H1N1)pdm09).

It is for this reason that the CDC encourages all pregnant women to get the flu shot (see Pregnant Women & Influenza (Flu)), but uptake is far from optimal. 

 

Some of this reluctance is due to the persistent anti-vaccine rhetoric on the internet and in the media - including unfounded claims that the 2009 H1N1 vaccine was responsible for `thousands’ of miscarriages. 

The science, however, overwhelmingly supports the safety of flu shots for pregnant women (see here, here, and here).

At the same time we've seen numerous studies suggesting that the offspring whose mothers were infected - with influenza, or other viral illnesses - during their pregnancy may be at higher risk of a wide spectrum of psychological, developmental, or physical problems later in life. 

A few examples include:

Pregnancy, Influenza & Elevated Psychosis Risks In Adult Offspring

JAMA Psych: Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero

Pregnancy, Influenza & Elevated Psychosis Risks In Adult Offspring

JAMA Psych: Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero

Molecular Psy.: Increased Autism Risk Linked To Prenatal Fever

With influenza currently raging across the nation (see CDC FluView Week 47: Most of The Nation at High or Very High Levels Of ILI), we've a timely Systematic Review and Meta-Analysis published last week in the Journal Viruses on the increased risk of congenital abnormalities (CAs) in the offspring of women who were infected with influenza during their first trimester.

I've only posted the Abstract, and some excerpts from the discussion, so you'll want to follow the link to read it in its entirety.  I'll have a postscript when you return.

First-Trimester Influenza Infection Increases the Odds of Non-Chromosomal Birth Defects: A Systematic Review and Meta-Analysis

Ákos Mátrai 1,2,3,Brigitta Teutsch 2,4,Alex Váradi 4, Péter Hegyi 2,4,5, Boglárka Pethő 1,2, Akari Fujisawa 2,6, Szilárd Váncsa 2,4,5, Balázs Lintner 1,2, Zsolt Melczer 1,2 andNándor Ács 1,2,*

Viruses 2022, 14(12), 2708; https://doi.org/10.3390/v14122708  

ABSTRACT

Viral infections during pregnancy raise several clinical challenges, including birth defects in the offspring. Thus, this systematic review and meta-analysis aims to prove and highlight the risk of birth defects after first-trimester maternal influenza infection. Our systematic search was performed on 21 November 2022. Studies that reported maternal influenza infection in the first trimester and non-chromosomal congenital abnormalities were considered eligible.

 

We used odds ratios (OR) with 95% confidence intervals (CIs) to measure the effect size. Pooled ORs were calculated with a random effects model. Heterogeneity was measured with I² and Cochran’s Q tests.

 

We found that first-trimester maternal influenza was associated with increased odds of developing any type of birth defects (OR: 1.5, CI: 1.30–1.70). Moreover, newborns were more than twice as likely to be diagnosed with neural tube defects (OR: 2.48, CI: 1.95–3.14) or cleft lip and palate (OR: 2.48, CI: 1.87–3.28). We also found increased odds of developing congenital heart defects (OR: 1.63, CI: 1.27–2.09).

 

In conclusion, influenza increases the odds of non-chromosomal birth defects in the first trimester. The aim of the present study was to estimate the risk of CAs in the offspring of mothers affected by first-trimester influenza infection.

          (SNIP) 

4. Discussion

The importance of viral infections will increase as we face growing risks of pandemics, which may affect the pregnant mother and the fetus [42]. Viral infections during pregnancy raise several clinical challenges, including adverse pregnancy outcomes and birth defects in the offspring [3]. During embryogenesis, the development of different organs and organ systems occurs one after the other and parallel to others. Almost every organ system develops in the first 12 weeks of pregnancy, so any effect on the embryo during this period may significantly influence the development of birth defects.

 

This systematic review and meta-analysis evaluated the effects of influenza infection in the first trimester of pregnancy on the development of non-chromosomal birth defects.

          (SNIP)

5. Conclusions

In conclusion, our systematic review found that influenza in the first trimester is associated with non-chromosomal birth defects, primarily congenital heart defects, neural tube defects and oral clefts. Therefore, influenza prevention by vaccination before or during pregnancy is highly recommended. Moreover, if influenza has already manifested itself, proper antipyretic treatment should be started.

          (Continue . . . )

Although this review and meta-analysis was restricted to women who had lab-confirmed influenza during their first trimester, we've seen other studies - involving influenza and other viral infections (including COVID) - which have produced similar findings. 

While the exact mechanism behind these birth defects hasn't been identified, prolonged maternal fever has often been cited as a likely factor (see Molecular Psy.: Increased Autism Risk Linked To Prenatal Fever). 

 The authors cite the importance of limiting fever in today's report, writing:

Further studies have shown that if fever during an influenza infection was relieved effectively with antipyretic drugs, malformations are less likely to develop [30]. Several studies have also shown that taking folic acid and maternal vitamins during the first trimester of pregnancy can reduce the odds of developing birth defects [30,56].

 The authors further state:

Translating scientific results into everyday practice has crucial importance [56]; therefore, we should make efforts to prevent influenza during pregnancy and highlight the importance of vaccination against flu and antipyretic therapy.

Whether it is influenza, COVID, or any other viral illness, the benefits of avoiding infection - particularly during a woman's first trimester - are becoming increasingly obvious.

USDA/APHIS Snapshot: HPAI H5N1 In The United States (Update)

#17,154

Since our last USDA update on Nov 9th, commercial poultry losses from our current HPAI H5N1 epizootic - which arrived in the United States in January of this year - officially exceeded the record losses from the 2015 H5Nx epizootic. 

Other important metrics - including the number of states reporting poultry outbreaks (46 vs 15), the number of wild birds dying (minimal in 2015), and the number of mammalian infections reported - were all eclipsed months ago. 

The impacts on the poultry industry, the economy, and the consumer's pocketbook have all been substantial, with record prices for eggs - and occasional shortages - reporting in many parts of the country. 

While the number of wild birds lost to HPAI will never be fully known, already the USDA/APHIS has confirmed more than 4,238 outbreaks across 47 states; an increase of more than 25% over last month's reported total (n=3,375)

Aside from its enhanced carriage by migratory birds, and an extended avian-host range, we've also seen evidence of the continual evolution - and increased virulence - of the H5 virus as it reassorts its way across the nation (see Preprint: Rapid Evolution of A(H5N1) Influenza Viruses After Intercontinental Spread to North America).

Starting last month, the USDA added a dashboard tracking mammalian infections with HPAI H5, which initially included 78 known spillover events in the United States. 

While it requires a certain amount of luck to detect these types of infections - meaning many go undetected - that number has grown by 20% in their latest update to 98.

2022 Detections of Highly Pathogenic Avian Influenza in Mammals

This increased susceptibility of mammalian hosts of HPAI H5N1 is an obvious concern - particularly given the reports of severe illness and neurological manifestations - but so far all 4 known human infections  (1 in the US, 1 in the UK, and 2 in Spain) have been mild or asymptomatic.

For now the health threat to the general public from these viruses is considered very low, and it is mainly of concern to those who work closely with poultry.

While the future course and impact of HPAI H5 is unpredictable, for now this virus is on the ascendant around the globe, infecting and killing millions of birds (wild and domesticated), and trying its hand at infecting mammals.

Given the rapid rise in outbreaks during the month of November - and the unprecedented spikes in outbreaks in the UK and Europe - there could be a long and difficult avian flu season ahead. 

Taiwan CDC Reports 2nd Case of Swine-Origin H1N2v Infection

 

#17,153

In June of 2021 Taiwan reported their first swine variant (H1N2v) infection (see Taiwan CDC Reports Human Infection With Swine Variant H1N2v Virus) in a 5-year-old girl. That report indicated that that 3 of the patient's contacts had `flu-like' symptoms, but they were unable to identify H1N2v in any of them.

As we've discussed often, swine variant infections in humans - while believed to be rare - undoubtedly happen more frequently than we know. Testing for, and subtyping of, influenza viruses is only rarely done - particularly in those with mild disease.

Today Taiwan's CDC has announced a 2nd case, this time in a 7-year-old girl with mild influenza who lived in the central region. As with the previous case, among her 6 closest contacts, 2 had reported flu-like symptoms, but H1N2v was not detected in any of them.

Note: We don't know the exact timing of the testing of these contacts, which might have adversely affected the ability to detect a specific subtype. Their CDC states, however, `There is no evidence of human-to-human transmission'. 

Analysis of the virus indicated it was similar - but not identical - to previously sequenced swine-origin H1N2v viruses.  The (translated) report from Taiwan's CDC follows, after which I'll return with a bit more. 

The second case of H1N2v influenza virus isolated from a respiratory disease patient in China has been recovered. The CDC urges the public to manage their personal health

Release date: 2022-12-05

The Centers for Disease Control and Prevention stated today (5) that it received a report from the hospital in October 2022 that a type A influenza virus that could not be subtyped was isolated from the respiratory specimen of a 7-year-old girl with mild influenza who lived in central China , which was further tested and sequenced by the department as H1N2v influenza virus.

After investigation, there were 6 close contacts of the case, 2 of whom had flu-like symptoms, and no H1N2v influenza virus infection was found after inspection. After inviting the agricultural administration unit and relevant medical experts to hold a meeting to discuss, based on the above-mentioned existing epidemiological investigation results, the case was judged. It should be a sporadic case, which is similar to past international cases. There is no evidence of human-to-human transmission. The health and agricultural authorities will continue to strengthen the monitoring of humans, animals and the environment.

The Centers for Disease Control and Prevention pointed out that this case is the second case of H1N2v influenza virus in my country. The case has no recent travel history abroad, and his family is engaged in poultry farming. On September 24 this year, he developed symptoms such as fever, muscle aches, loss of appetite, cough and runny nose. , On September 26, he went to the doctor due to a high fever. The rapid COVID-19 test was negative and the rapid influenza test was positive for type A. After the doctor's evaluation, he did not need to be hospitalized. He returned home after prescribing influenza antiviral drugs and has recovered.

The CDC further pointed out that the H1N2v influenza virus was isolated from the girl's respiratory specimen on October 18, and tests for common viruses in respiratory infections such as adenovirus, respiratory fusion virus, enterovirus, and rhinovirus were all negative. . In addition, the agricultural administration unit also collected specimens from pigs in the pig farm run by the case family, and the results showed that no H1N2 influenza virus was detected. In response to the second confirmed case in my country, the CDC will simultaneously notify the World Health Organization through the IHR contact window.

According to the CDC, the first case of H1N2v type A influenza in my country was detected in April last year (2021). It was a 5-year-old girl who lived in the central region. The source of feed and pigs, the slaughterhouse where the livestock is raised, the route of the transport vehicle, and the gene of the virus are all different, and the two cases are determined to be unrelated.

H1N2v is a low-pathogenic influenza virus that exists in pigs, and there are occasional cases of human infection reported, and most of them are mild. Since 2011, there have been at least 45 confirmed cases of H1N2v influenza in the world, with 41 cases in the Americas. Most of the cases have a history of contact with pigs or exposure to contaminated environments. There is no case of infection through eating meat. The gene sequence of the virus isolated from the patient this time is similar to the H1N2 virus strain isolated from pigs in the past, but not the same. It is sensitive to the current public-funded influenza antiviral drugs.

The CDC reminds that to prevent the new type A influenza, the public should abide by the "5 Dos and 6 Don'ts" principle. and contact history, those who have long-term contact with poultry and livestock should be vaccinated against influenza, have a balanced diet and exercise properly; "6 don'ts": do not eat raw poultry eggs or products, do not smuggle or buy meat from unknown sources, do not touch or feed Livestock, do not release or discard livestock at will, do not mix livestock with other livestock, and do not go to places with poor air circulation or crowded places. For relevant information, please visit the global information website of the CDC (https://www.cdc.gov.tw/), or call the free epidemic prevention hotline 1922 (or 0800-001922).

Prior to 2017, the H1N2v strain of swine flu was only rarely reported, with H3N2v far outpacing it.  Since 2017, H1N2v has become far more common, with numerous cases reported in the United States, along with scattered cases reported from Canada, Brazil, and France. 

The CDC's IRAT (Influenza Risk Assessment Tool) lists 3 North American swine viruses as having at least some pandemic potential (2 added in 2019). 

H1N2 variant [A/California/62/2018]  Jul   2019   5.8  5.7 Moderate

H3N2 variant [A/Ohio/13/2017]          Jul   2019   6.6  5.8 Moderate

H3N2 variant [A/Indiana/08/2011]      Dec 2012   6.0  4.5 Moderate 

While in 2021 the CDC ranked a Chinese Swine-variant EA H1N1 `G4' as having the highest pandemic potential of any flu virus on their list (see EID Journal: Zoonotic Threat of G4 Genotype Eurasian Avian-Like Swine Influenza A(H1N1) Viruses, China, 2020).

So far, the good news is that currently circulating swine variant viruses haven't become biologically `fit' enough spark a pandemic. In order to be successful, they need to be able to replicate and transmit on par with already circulating human flu viruses. 

The bad news is there are an unknown number swine-variants spreading - and reassorting - among hundreds of millions of pigs around the world, and most of that goes on out of our sight.   

And as with the last swine-flu pandemic (2009), the first sign that a swine-variant virus has made the leap to a pandemic may not come until days or even weeks after it has begun its world tour.

Upcoming COCA Call (Dec 8th): Multisystem Inflammatory Syndrome in Children (MIS-C) - Epidemiology, Case Definition, and Prevention

#17,152

While children and adolescents generally experience less severe disease with COVID than adults, they are not exempt from being infected, and a substantial number can experience serious, even life-threatening, illness and/or sequelae.

Often these severe impacts occur after the acute phase of their infection, sometimes masking their  cause.

Last month, in Neurology: Incidence of Epilepsy and Seizures Over the First 6 Months After a COVID-19 Diagnosis: A Retrospective Cohort Study, we looked study showing an increased risk in seizures and epilepsy following COVID infection. 

This increased risk was most pronounced in patients under the age of 16 and among those who were not hospitalized for their illnesses, showing that even mild illness can cause serious, and sometimes lasting, sequelae.

Four months ago we looked at an MMWR report on Post-COVID conditions in children and adolescents, and found that the risks of experiencing several rare conditions rose sharply following COVID infection. While the absolute risk of these complications remains low, the relative risk in some cases more than doubles.

But perhaps the most serious post-COVID sequelae for adolescents and children is Multisystem inflammatory syndrome (MIS). The CDC describes the syndrome.

What is MIS?

Multisystem inflammatory syndrome (MIS) can affect children (MIS-C) and adults (MIS-A). MIS is a rare but serious condition associated with COVID-19 in which different body parts become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs.

This syndrome was first identified in the spring of 2020, and prompted a CDC HAN (see CDC HAN: Multisystem Inflammatory Syndrome In Children (MIS-C)), and a COCA call (see Multisystem Inflammatory Syndrome in Children (MIS-C)) in May of that year.

We've revisited the topic a number of times since then, including:

COCA Call Tomorrow (Feb 10th) :Multisystem Inflammatory Syndrome in Children (MIS-C)

CHOP Research: COVID-linked MIS-C Associated with Myocardial Injury

J. Peds: Pediatric SARS-CoV-2: Clinical Presentation, Infectivity, and Immune Responses

As of the end of November 2022, more than 9,000 children and adolescents in the United States have been diagnosed with MIS-C, and 74 deaths have been reported.  Like with pediatric influenza deaths, this is likely an undercount. 

On Thursday (Dec 8th) the CDC will hold a one-hour COCA Call for clinicians on MIS-C, and review a recently revised CSTE 2023 MIS-C case definition. These presentations are often technical, and are of greatest interest to clinicians and healthcare providers, but also may be of interest to the general public.

As always, If you are unable to attend the live presentation, these (and past) webinars are archived and available for later viewing at this LINK.

Details on this week's presentation follows:

Updates on Multisystem Inflammatory Syndrome in Children (MIS-C): Epidemiology, Case Definition, and Prevention

Overview

The Council of State and Territorial Epidemiologists (CSTE) and the Centers for Disease Control and Prevention (CDC) have developed a new multisystem inflammatory syndrome in Children (MIS-C) surveillance case definition to help reduce misclassification and complexity. This CDC/CSTE MIS-C surveillance case definition is based on an extensive review of data from 2020–2022. MIS-C is a rare, but severe condition that may occur 2-6 weeks after acute SARS-CoV-2 infection. CDC has been actively involved in MIS-C surveillance, public health investigations, and development of resources to support the public health and healthcare community. The updated CSTE/CDC MIS-C case definition will become effective on January 1, 2023.

During this COCA Call, presenters will review MIS-C epidemiologic and clinical trends, provide a rationale and description of changes in criteria for the new CSTE/CDC MIS-C surveillance case definition compared with the 2020 CDC MIS-C case definition, and discuss information relating to MIS-C and COVID-19 vaccination.

Presenters

Angela Campbell, MD, MPH, FAAP, FPIDS, FIDSA
Medical Officer
Severe Respiratory Illness and Multisystem Inflammatory Syndrome (SIM) Team Lead
Epidemiology Branch
Coronavirus and Other Respiratory Viruses Division (proposed)
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention

Michael Melgar, MD
Medical Officer
Severe Respiratory Illness and Multisystem Inflammatory Syndrome (SIM) Team
Epidemiology Branch
Coronavirus and Other Respiratory Viruses Division (proposed)
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention

Anna Yousaf, MD
Medical Officer
Severe Respiratory Illness and Multisystem Inflammatory Syndrome (SIM) Team
Epidemiology Branch
Coronavirus and Other Respiratory Viruses Division (proposed)
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention

Call Materials

None at this time.

Call Details

When:
Thursday, December 8, 2022,
2:00 PM – 3:00 PM ET

Webinar Link:
https://www.zoomgov.com/j/1610894085

Webinar ID: 161 089 4085

Passcode: 510428

Telephone:
US: +1 669 254 5252 or +1 646 828 7666 or +1 669 216 1590 or +1 551 285 1373

One-tap mobile:
US: +16692545252,,1610894085#,,,,*510428# or +16468287666,,1610894085#,,,,*510428#

International numbers

PAHO Epidemiological Update: Outbreaks of Avian Influenza and Public Health Implications - 3 Dec 2022

#17,151

While cold comfort for a pandemic-weary population about to enter their 4th year living under COVID-19, public health agencies around the globe are quietly preparing for a potential new threat to global health; the spread of avian H5Nx influenza in humans. 

Although only a handful of extremely mild human infections have been reported with this current strain (clade 2.3.4.4b) of H5N1, other - closely related clades - have infected hundreds of people over the past 20 years, often with fatal results. 

Over that time we've seen clusters of cases, and mini-epidemics, in a number of countries (Vietnam, China, Indonesia, Cambodia, Egypt, etc.). But after months - or sometimes years - the virus has lost its punch, likely mutating slightly into a less `humanized' strain. 

But mutations are random, and there is no reason to suspect that another reassortment, or the right combination of amino acid changes due to antigenic drift - or both - couldn't turn our current H5N1 virus into something more formidable. 

Two weeks ago, in Preprint: Rapid Evolution of A(H5N1) Influenza Viruses After Intercontinental Spread to North America, we looked at the mammalian adaptations occurring in avian H5N1 as it spread across the US and Canada, producing serious - often fatal -  infections in mink, bears, foxes, seals, and other small terrestrial mammals.

As H5N1 moves into South America (see map below), it will have even more opportunities to mutate, adapt, and evolve. While it doesn't guarantee the virus will continue to evolve toward becoming a bigger threat, it is a possibility that public health agencies can't afford to ignore. 

Over the past few months we've seen a ramping up of preparations by governments around the globe for such an eventuality, including:

UK APHA: Technical risk assessment for avian influenza (human health): influenza A H5N1 2.3.4.4b

PAHO: Epidemiological Alert - Outbreaks of Avian Influenza and Public Health Implications in the Region of the Americas

ECDC Guidance For Testing & Identification Of Zoonotic Influenza Infections In Humans In The EU/EAA

CDC On Preventive Measures to Protect Against Bird Flu Viruses

 

WHO DON & Risk Assessment: Two Human Infections With H5N1 In Spain

HPAI H5 isn't the only other pandemic threat out there (think: MERS-CoV, Swine EA H1N1 `G4', new COVID variants, among others), but it is making enough noise around the world to have raised concerns. 

Yesterday PAHO (Pan-American Health Organization) updated their earlier (Nov 19th) Epidemiological Alert on H5N1, warning:

Given the increase in outbreaks of highly pathogenic avian influenza in poultry farms, backyards, and wild birds in countries of the Region of the Americas and other Regions, the Pan American Health Organization/World Health Organization (PAHO/WHO) recommends that the Member States strengthen coordination between sectors involved in alerting and responding to zoonotic events and implement the necessary measures to contain emerging pathogens that may put public health at risk. PAHO/WHO recommends monitoring the occurrence of influenza-like illness (ILI) or severe acute respiratory infection (SARI) in people exposed to birds (domestic, wild, or in captivity) infected with influenza viruses

The updated 11-page PDF provides summaries of H5N1 activity in the United States, Canada, Colombia, Ecuador, Mexico, Peru, and Venezuela, and then provides recommendations for health authorities in member states. 

Epidemiological Update

Outbreaks of avian influenza and public health implications in the Region of the Americas

3 December 2022

(Excerpt)

Recommendations for health authorities in Member States 

Both HPAI and LPAI viruses can be rapidly spread among poultry through direct contact with infected waterfowl or other poultry, or through direct contact with fomites or surfaces, or water contaminated with the viruses. Infection of poultry with HPAI viruses can cause severe disease with high mortality. LPAI viruses are more associated with subclinical infection. The terms HPAI and LPAI apply only to the symptoms in birds (chickens in particular), and both types of viruses have the potential to cause infections in humans.

While the potential exists for these viruses to cause human infections, infections with avian influenza viruses are generally rare and when they have occurred, these viruses have not spread easily from person-to-person. To date, no person-to-person human transmission caused by avian influenza A(H5N8), A(H5N2), or A(H5N1) viruses has been reported either in the Americas or globally.

Intersectoral coordination

Control of the disease in animals is the first measure to reduce the risk to humans. For this reason, it is important that prevention and control actions, both in the animal and human health sectors, are carried out in a coordinated and concerted manner. Agile information exchange mechanisms will have to be established and/or strengthened to facilitate coordinated decision - making.

Implementation of a comprehensive surveillance program, including wild birds and both backyard and commercial poultry, is essential. Targeted risk-based surveillance strategies should be combined with a strengthening of general surveillance. In this regard, sensor awareness tasks are key, particularly in the backyard, to encourage the detection and notification of suspicious events. These programs also provide information that enables spread modeling and more accurate risk analysis.

Full recommendations for strengthening intersectoral work on surveillance, early detection, and investigation of influenza events at the human-animal interface are available at: https://bit.ly/3glEUNN

Surveillance in humans

People at risk of contracting infections are those directly or indirectly exposed to infected birds, for example, poultry keepers who maintain close and regular contact with infected birds or during slaughter or cleaning and disinfection of affected farms. For this reason, the use of adequate personal protective equipment and other protection measures is recommended to avoid zoonotic transmission in these operators.

In order to identify early transmission events at the human-animal interface, surveillance of exposed persons is recommended. In this sense, it is recommended to monitor the appearance of influenza-like illness (ILI) or severe acute respiratory infection (SARI) in people exposed to birds (domestic, wild, or in captivity) infected with influenza viruses during zoonotic events.

 

Given the detection of an infection in humans, early notification is essential for an investigation and implementation of adequate measures that include the early isolation and treatment of the case, the active search for other cases associated with the outbreak, as well as the identification of close contacts for management and follow-up (11).

Health personnel in areas where transmission of avian influenza (HPAI or LPAI) in birds is taking place should be alerted about the possibility of infection in people exposed to these viruses.

PAHO/WHO reiterates to Member States the need to maintain influenza virus surveillance and to immediately ship human influenza samples to the US CDC WHO Collaborating Center. 

         (Continue . . . )

This update goes on to provide detailed information on how to report cases, and technical guidance for laboratory testing of samples.  The entire document is worth reading, although some sections will be of greatest interest to public health officials. 

There is still some debate over whether H5 viruses can spark a human epidemic (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), but by the time we have a definitive answer to that, we could be hip-deep in cases.

But even if it requires an H1, H2, or H3 virus to really take off in humans, a co-infection between human seasonal (H1N1 or H3N2) and an avian or swine flu virus could produce an enhanced seasonal virus.  

Reassortment isn't just for the birds. 

Influenza A's superpower is its ability to simultaneously infect an animal (avian, swine, human, canine, etc.) host with two or more subtypes, and by swapping genetic material, create a new hybrid virus (reassortant). 

In 1968, when the world was dominated by the H2N2 flu virus - an avian-origin H3 emerged (H3N2) in Hong Kong - and sparked a pandemic that quickly supplanted H2N2 and killed more than 1 million people.  

That virus was a reassortment consisting of 2 genes from a low path avian influenza H3 virus, and 6 genes from H2N2.  And while it was not initially as deadly as the 1957 or 1918 pandemics -  it is still with us 54 years later - and has caused millions of additional deaths over the past half century. 

Which is why - as tired as we are of dealing with COVID - we can't afford to sit back and ignore the rise of H5N1 (or any other novel flu virus).

Given how often it has happened before, we can be pretty sure it will happen again.  We just don't know where, when, or how bad it will be. 

Venezuela Detects HPAI H5 In Wild Birds - Declares Health Alert

 

#17,150

Five weeks ago HPAI H5N1 was reported for the first time in a South American country when two outbreaks were reported by Colombia very close to their border with Panama (see WOAH: Colombia Reports Two Outbreaks of HPAI H5N1).

A couple of weeks later Peru announced the detection of HPAI in pelicans (see Peru: SENASA Reports HPAI H5 In Pelicans) on "Los cangrejos" beach in Paita. 

Since then, roughly 14,000 birds have been reported to have died in numerous locations across Peru, and both Peru and neighboring Ecuador have reported outbreaks in poultry (see Peru & Ecuador Declare Animal Health Emergencies Over HPAI H5).

Yesterday Venezuela became the 4th South American country to confirm the arrival of HPAI H5 - again in seabirds - and has declared a 90-day health alert.  This press release from the Venezuelan Ministry of Popular Power for Science and Technology

H5N1 avian influenza virus detected in wild birds in Anzoátegui state
December 2, 2022 by Karina Depablos

Mincyt Press.- This Friday, December 2, the Bolivarian Government of Venezuela reported on the detection of the highly pathogenic H5N1 avian influenza virus in wild birds (pelicans), located in the north-coastal region of Anzoátegui state.

For this reason, the Ministry of Popular Power for Productive Agriculture and Land, through the National Institute of Comprehensive Agricultural Health (INSAI), with the support of the Ministry of Popular Power for Science and Technology, launched immediate preventive measures and decreed health alert in the states of Anzoátegui, La Guaira, Nueva Esparta, Sucre and Miranda for 90 days.

Likewise, quarantine was decreed in these four entities of the country , with the possibility of incorporating other states in accordance with the results and progress of epidemiological investigations of avian influenza, as it is also known.

In this sense, the mobilization of live birds and fertile eggs from the municipalities of Fernando de Peñalver, San Juan de Capistrano, Manuel Ezequiel Bruzual and others determined by the National Institute of Integral Agricultural Health (INSAI) in accordance with risk analysis is prohibited. epidemiological that are carried out. Also, they will intensify epidemiological surveillance in backyard and commercial birds, and will proceed to the sanitary culling of positive birds, contacts, with an epidemiological link or that generate a high health risk for viral transmission.

The Venezuelan Government urges the general population to immediately inform the Insai and other competent State entities about any indication or suspicion of the presence of signs of disease or mortality in birds of any species, due to unusual causes.

To comply with all these preventive measures, the national government will intensify the work of the human health and animal health teams, jointly and articulated. The Venezuelan population will be informed about the evolution of this situation.

It is worth noting that the Venezuelan Institute for Scientific Research (IVIC), an entity attached to the Ministry for Science and Technology, will deploy its staff to carry out genomic surveillance of the H5N1 avian influenza virus.

To read the health alert resolution, enter here: Resolution

Given the extent, and overlapping, of the north-south migratory flyways (see map below), it is likely that the HPAI H5 will will rapidly infiltrate across the width and length of the South American continent. 

 Although they have yet to report any outbreaks, yesterday - in anticipation of the virus's arrival - Bolivia's SENASAG issued a 90 day health alert 

(Translation)

AVIAN INFLUENZA

In view of the health emergency in neighboring countries due to avian influenza, SENASAG recommends:

1. Not introducing birds from another country without the Official Zoosanitary Certificate of Origin is a crime.
2. Do not introduce birds from countries affected by Avian Influenza.
3. For the entry of wild or domestic birds into Bolivia, the current sanitary standards and procedures established by SENASAG must be complied with.

Aside from the obvious threat to poultry and wild birds, HPAI H5 evolve easily and often (see Preprint: Rapid Evolution of A(H5N1) Influenza Viruses After Intercontinental Spread to North America), meaning new, and potentially more dangerous, variants may emerge as the virus spreads. 

Despite 4 known (mild) human infections, the health threat to the general public from these HPAI H5 viruses remains very low, and it is mainly of concern to those who work closely with poultry.

That assessment is subject to change, however.  Which is why the CDC has issued guidance for the public On Preventive Measures to Protect Against Bird Flu Viruses.