Almost 15 years ago, the world experienced an influenza pandemic, caused by the influenza A (H1N1) virus. The scientific community, which carries out continuous genomic surveillance of the virus, warns that a new global epidemic is not a question of “if”, but “when”.
Avian flu, a disease that primarily affects birds, is caused by an influenza virus in the Orthomyxoviridae family. According to its subtype, it can be classified as having a high or low capacity to cause disease – a concept technically known as pathogenicity. Thus, the virus can show different symptoms in infected birds.
According to the World Health Organization (WHO), Low Pathogenic Avian Influenza Virus (LPAIV) can cause mild illness, often unnoticed or without symptoms. The Highly Pathogenic Avian Influenza Virus (HPAIV) caused by subtypes (H5 and H7) of type A, causes severe disease in birds and can spread rapidly, resulting in high mortality rates in different avian species.
The most common way for the virus to enter a territory is through migratory wild birds. Most influenza viruses circulating in birds are not capable of infecting humans. However, some strains with this ability pose a threat to public health.
The main risk factor is direct or indirect exposure to infected animals or contaminated environments and surfaces. Plucking, handling infected poultry carcasses and preparing poultry for consumption, especially in domestic environments, can also be factors related to transmission.
When avian flu is transmitted to humans, symptoms can range from a mild infection with fever and cough to severe pneumonia associated with difficulty breathing and risk of death, depending on factors related to the virus and the host. Rarely, gastrointestinal or neurological symptoms have been reported, according to the WHO.
What explains the increase in outbreaks of H5N1
Between 2003 and 2023, 874 cases and 458 deaths from H5N1 influenza were recorded in 23 countries, according to the World Health Organization (WHO). In addition, three human infections with influenza A virus (H5 – unspecified), 84 cases with the H5N6 strain and seven cases of infection with the H5N8 virus have been reported to WHO.
The avian influenza strain was first detected in the Americas in birds in December 2014. Earlier in the year, the Pan American Health Organization (PAHO) issued an alert in response to the increasing detection of avian influenza outbreaks in birds in ten countries in the Americas region.
PAHO emphasized the importance of infection control in birds as the main measure to reduce the risk to humans and recommended that countries strengthen surveillance of seasonal and zoonotic influenza in animal and human populations.
At the end of March, Chile registered the first human case of infection with the influenza A (H5N1) virus. The case, a 53-year-old patient, was the first human infection with the virus in the country and the third reported in the Americas region to date. The virus has not been detected in humans in Brazil.
The president of the Brazilian Society of Virology (SBV) and professor at the University of São Paulo (USP), Helena Lage Ferreira, explains that the increased circulation of the virus is associated with microscopic structures of the virus.
During infection, the immune system is affected by two proteins present on the surface of the Influenza A virus, called hemagglutinin and neuraminidase. These proteins, essential for influenza’s ability to infect, make up the initials H and N that establish the name of each genetic variety of the virus.
There are at least 18 subtypes of hemagglutinins and 11 subtypes of neuraminidases described. Virus A (H5N1), for example, contains hemagglutinin subtype 5 and neuraminidase subtype 1.
“The highly pathogenic H5N1 virus emerged in Asia in 1996 and has evolved over the years. In 2021, the H5 hemagglutinin reassorted with a new N1 from wild birds and a new virus emerged. And quickly this new virus became prevalent in Asia, Africa, Europe and the Middle East by the end of the year 2021. The virus was introduced in late 2021 by wild birds in Canada and the United States. During 2022, it spread across North America and, in October 2022, the virus was found in South America as well”, explains Helena.
strain characteristics
Like other avian influenza viruses, H5N1 has wild waterfowl as natural reservoirs. Against this background, he is able to multiply well in other birds. The infection has been associated with a high mortality rate among birds, especially among farm animals, causing great damage to livestock.
“Several reports of high wild bird mortalities are being observed around the world. However, some species do not show clinical signs and are able to disseminate, or excrete, high viral loads in the environment. The H5N1 virus has already been found in more than 160 different species of wild birds”, details Helena.
“We can say that the virus is already considered endemic among wild aquatic birds and they are the main disseminators of the virus between countries, as they move during their migration during the year in search of food and for reproduction”, he adds.
Influenza viruses are able to infect mammals, including people, sporadically. As the H5N1 virus is being detected on all continents except Antarctica, exposure events of wild mammals (marine and terrestrial) to the virus are more common. This way the virus has a better chance of adapting to mammals.
“A fact that caused concern in the scientific community was the identification of the virus in commercial views in Spain in October 2022. Some protocols for the identification of mortality were established because of SARS-CoV-2 and quickly identified the virus, which was capable of transmitting between mammals and had mutations in its genome. The virus was eliminated and no one became infected. However, the transmission of the virus in mammals has not yet been demonstrated. This is the only case so far”, says Helena.

Possibility of a new pandemic
Predicting when a new flu pandemic will occur is still a challenge. Although the virus circulates widely around the world, with seasonal epidemics, especially in winter, a pandemic phenomenon has distinct characteristics.
Influenza pandemics happen when a new viral strain arises from rearrangements in the virus genome. Despite the high surveillance capacity, anticipating an event like this is still not possible.
“The possibility of these viruses gaining greater adaptability and being able to be transmitted efficiently between humans exists. But so far, since the beginning of monitoring in 2003, it has been observed that this capacity has not yet been reached for the H5N1 subtype. We have to monitor the genetic diversity of these viruses and this ability very closely,” says Paola Resende, a scientist at the Oswaldo Cruz Institute (IOC/Fiocruz).
Researchers estimate that the H5N1 influenza can cause a new flu pandemic, if there are rearrangements in the genome, which can happen with increased transmission of the virus, for example.
“The virus still needs to develop some mechanisms to acquire the ability to be transmitted from person to person. As it is a virus that is transmitted through the respiratory route, such as SARS-CoV-2, once adapted for transmission between people, it can be spread around the world quickly”, says Helena.
“With regard to cases in people, we can divide the virus into two waves: 2003 to 2021 and 2022 to 2023 with the emergence of the new virus. In this current wave of H5N1 outbreaks, from January 2022 to March 29, 2023, 11 cases were registered, distributed in seven countries. Of the 11 cases, six people, including three children and three adults, developed the severe form of the disease, and two of them died, according to the WHO”, adds the researcher.
The emergence of infectious diseases in the last 25 years and the recent outbreaks of diseases originating in animals draw attention to the movement of microorganisms between different species. Of the 1,415 known human pathogens, 61% are of animal origin, according to PAHO.
It is estimated that the increase in outbreaks of emerging and re-emerging livestock diseases worldwide since the mid-1990s has cost the world US$80 billion.
An important factor in the emergence of new zoonoses is closer contact with wildlife, both of humans and their domesticated animals, mainly caused by increased invasion of wildlife habitats. Other general factors include environmental changes, globalization of food production and trade, microbiological adaptation, and human behavioral factors.

Virologist Flávio Fonseca assesses that the world is experiencing conditions conducive to the emergence of new pandemics, as in 2009 and 2020.
“This is because global borders are much reduced due to the movement of people, the speed with which people move around the globe, taking pathogens from one place to another very quickly, a global trade. Globalization in general favors the very rapid exchange of pathogens that arise in a given geographic location and these pathogens are quickly transmitted even before people show signs of illness, in a period called incubation, they travel without apparent signs of illness and they arrive contaminated in another place”, he details.
The specialist states that globalization, with faster travel and trade and movement of people and products between countries, allows a rapid spread of infectious diseases from their initial focus. However, it is difficult to estimate the burden of zoonoses on human health, mainly because endemic infections are underreported worldwide.
The public health risk of the influenza virus is periodically assessed by the WHO. Currently, the likelihood of sustained human-to-human transmission of these viruses remains low. According to the WHO, human infections with viruses of animal origin are expected at the human-animal interface wherever these viruses circulate in animals.
“Although small clusters of A(H5) virus infections have been reported, including those involving healthcare workers, current epidemiological and virological evidence suggests that influenza A(H5) viruses have not acquired the capacity for sustained human-to-human transmission, therefore, the probability is low,” says the recent WHO document.
Remember the 2009 pandemic
On June 11, 2009, the World Health Organization (WHO) declared an influenza pandemic situation due to the large-scale impact caused by a strain of the A (H1N1) virus.
The episode, which was known as “swine flu” at the time, caused the death of 151,000 to 575,000 people worldwide, according to a study published by researchers from the Centers for Disease Control and Prevention (CDC), the United States, in the scientific journal Lancet Infectious Diseases, in 2012.
Since 2009, the WHO, together with the countries that make up the Global Influenza Surveillance and Response System, has undertaken a series of measures aimed at improving strategies for a new pandemic event.
“There is a movement at a global level in terms of organizing working groups, holding scientific meetings and advising countries. The Influenza virus is contemplated in several international treaties, due to the harmful potential of a next pandemic, both in relation to health, as well as the economic and social impacts”, says Marilda Siqueira, researcher at the Oswaldo Cruz Institute (IOC/Fiocruz).
Source: CNN Brasil

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