The zoonotic influenza virus passes from animals to humans. Treatment of zoonotic influenza includes antiviral drugs, like oseltamivir or zanamivir. Read more at Meri Sehat.

Zoonotic Influenza Viruses

Overview

At the end of the 19th century, German physician Dr Rudolph Virchow came up with the term &ldquo;zoonosis&rdquo; for diseases that can be transferred from animals to humans<a href="#accordion">[1]</a>. The word has a Greek origin &ndash; &lsquo;zoon&rsquo; for animals and &lsquo;nosos&rsquo; for disease. Since then, researchers have discovered hundreds of diseases that can be transmitted between the two species. Among them is zoonotic influenza, a disease caused by animal influenza viruses that easily infect humans<a href="#accordion">[2]</a>.

In 1958, researchers discovered the first evidence of an animal influenza virus causing infection in humans. Since then, 16 different zoonotic influenza A virus subtype groups have caused human infections across the world<a href="#accordion">[3]</a>. The frequency of infections with influenza A subtypes, such as H5N1 and H7N9, has significantly increased over the years<a href="#accordion">[3]</a>. Unlike human seasonal influenza viruses, zoonotic flu viruses typically do not transmit between humans. 
&nbsp;

Zoonotic influenza viruses circulate in pigs, birds, dogs, and even horses. Humans contract the virus through direct or indirect contact with infected animals. Although the infection can manifest as diseases of varying severity, the virus does not easily transmit between humans. However, if the virus mutates and develops the ability to transmit from person to person, it can lead to deadly pandemics<a href="#accordion">[4]</a>.

For example, the 2009 swine flu pandemic resulted from a triple reassortment of swine, bird, and human flu viruses. According to the US Centers for Disease Control and Prevention (CDC), approximately 151,700-575,400 people died from the viral infection during the first year of its circulation<a href="#accordion">[5]</a>. Moreover, the 1918 Spanish influenza pandemic was caused by an H1N1 virus of avian origin<a href="#accordion">[7]</a>. An estimated one-third of the world&rsquo;s population was infected with the virus and at least 50 million people died due to infection<a href="#accordion">[7]</a>. 
&nbsp;

Researchers blame the recurrent outbreaks of zoonotic influenza viruses on increasing urbanization, travel, unhygienic living conditions, overcrowding, and domestication of pets<a href="#accordion">[1]</a>. 
&nbsp;

There are various types of zoonotic influenza viruses. These include:

<ul>
	<li>Avian Influenza Virus: The word &lsquo;avian&rsquo; denotes the virus exists in birds naturally. H5N1 and H7N9 are the most common avian influenza viruses to infect humans. The virus is transmitted via direct contact with the saliva, feces, and mucous secretions of the infected birds. Any contact with surfaces or water that&rsquo;s been contaminated with bird droppings is also a mode of transmission. Other avian influenza variants that have caused human infections in the past include H9N2, H5N6, H10N7, H6N1, H7N2, and H7N4<a href="#accordion">[7]</a>. 
	&nbsp;</li>
	<li><a href="https://merisehat.pk/disease/swine-flu">Swine Influenza Virus</a>: Common swine influenza variants include H1N1, H1N2, and H3N2. Although these viruses cause infections in pigs, they also transmit to humans in rare events. Moreover, pigs are susceptible to both human and avian influenza viruses. Hence, they often act as a &lsquo;mixing vessel&rsquo;, to reassort genes and produce a novel virus that can transmit to humans.&nbsp; 
	&nbsp;</li>
</ul>

The CDC divides flu viruses of public health concern into<a href="#accordion">[5]</a>:

<ul>
	<li>Novel Zoonotic Influenza Viruses: These non-human viruses previously caused infections in humans. For example, avian influenza viruses H5N1 and H7N9.</li>
	<li>Zoonotic Origin Viruses: These viruses have not caused human infections in the past. However, they have the potential to cause infections and, therefore, they remain a public health concern. 
	&nbsp;</li>
</ul>

&nbsp;
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Seasonal influenza viruses circulate in humans and involve influenza types A and B. They cause annual respiratory illnesses in humans ranging from mild to severe. 
&nbsp;

Comparatively, zoonotic influenza viruses are influenza virus type A that cross from animals to humans. Moreover, they rarely cause human-to-human transmission. They are also called non-seasonal influenza, as the infection can occur at any time of the year when people are exposed to the zoonotic flu strains. 
&nbsp;

Signs and Symptoms

The signs and symptoms of zoonotic influenza are similar to those of the typical flu. These include:

<ul>
	<li>Fever</li>
	<li>Chills and sweating</li>
	<li>Dry cough</li>
	<li>Sore throat</li>
	<li>Malaise</li>
	<li>Myalgia</li>
	<li>Runny nose</li>
	<li>Headache</li>
	<li>Fatigue</li>
	<li><a href="https://merisehat.pk/disease/allergic-conjunctivitis">Conjunctivitis</a></li>
	<li><a href="https://merisehat.pk/disease/diarrhea">Diarrhea</a> 
	&nbsp;</li>
</ul>

Causes

Influenza viruses belong to the Orthomyxoviridae family. There are 3 major types (A, B, and C); a 4th type (D) has also been discovered recently<a href="#accordion">[3]</a>. Humans, birds, pigs, horses, cats, and dogs can all host the influenza type A virus. Humans are also the natural host for influenza type B. Influenza C, however, infects only humans and pigs, whereas influenza D is only found in cattle and is not known to cause infections in humans. 
&nbsp;

The influenza virus has 7 genera, but only influenza A is currently zoonotic. Avian subtypes H5, H7, and H9, and swine variants of subtypes H1 and H3 are very important<a href="#accordion">[7]</a>. Direct contact with infected animals or contaminated surfaces and environments can transmit these viruses to humans. Therefore, poultry farm workers and those who work in pig farms specially are commonly affected. 
&nbsp;

Several factors contribute to these viruses&#39; ability to transmit to humans and cause pandemics. According to research, the influenza A virus possesses a segmented RNA genome that allows the reassortment of genes and the creation of a novel virus i.e. a potential to cause a pandemic<a href="#accordion">[3]</a>. Mutations also play a key role in causing the emergence of novel zoonotic flu strains. Moreover, both pigs and birds can serve as mixing vessels for both zoonotic and human viruses. Thus, the constantly evolving influenza viruses pose a real challenge to researchers. 
&nbsp;

There are currently no screening tests for zoonotic influenza viruses. However, genomic surveillance in poultry and pig farms helps researchers to timely identify novel viral strains and reduce the risk of a pandemic. Moreover, surveillance in human populations who are in direct contact with these viral hosts (e.g., poultry or pig farm workers) can also contribute to reducing the risk. 
&nbsp;

Diagnosis

Doctors typically rely on the patient&rsquo;s history to diagnose the disease. However, it is difficult to separate seasonal influenza from zoonotic based on just clinical features. Therefore, doctors may also take occupation exposure or visits to bird markets into consideration when diagnosing zoonotic influenza.

Laboratory investigations used to diagnose zoonotic influenza include:

<ul>
	<li>Reverse transcription polymerase chain reaction (RT-PCR)</li>
	<li>Viral cultures of nasopharyngeal or throat samples 
	&nbsp;</li>
</ul>

Treatment

While there is no specific treatment for zoonotic influenza, various antiviral medications can help treat the infection. 
&nbsp;

<h5>Antiviral Medications</h5>

<ul>
	<li>Adamantanes And Neuraminidase inhibitors are the two classes of drugs approved for influenza infections. These are usually prescribed to individuals at high risk of complications. However, a combination therapy of adamantanes and NAIs are not currently recommended for humans.</li>
	<li>Amantadine And Rimantadine are the two adamantane derivatives currently available against the influenza virus.</li>
	<li>Neuraminidase inhibitors include zanamivir, oseltamivir and peramivir. The World Health Organization (WHO) recommends oseltamivir as first-line therapy for H5N1 infections<a href="#accordion">[4]</a>. 
	&nbsp;</li>
</ul>

In severe cases of avian influenza infections, complications include<a href="#accordion">[4]</a>:

<ul>
	<li>Cardiac dysfunction</li>
	<li>Renal dysfunction</li>
	<li>Pulmonary hemorrhage</li>
	<li>Pneumothorax</li>
	<li>Acute respiratory distress syndrome</li>
	<li>Septic shock</li>
	<li>Multiorgan failure 
	&nbsp;</li>
</ul>

H5N1 and H7N9 avian influenza viruses are commonly associated with more complications than other avian flu strains.

Swine influenza viruses typically cause complications in those of extreme age or with chronic medical illness. Complications, in that case, include severe respiratory failure and multiorgan failure. 
&nbsp;

The following factors increase an individual&rsquo;s risk of contracting zoonotic influenza viruses:

<ul>
	<li>Working with poultry or swine</li>
	<li>Not washing hands after contact with animals</li>
	<li>Visiting live bird markets</li>
	<li>Being in contact with infected dead or alive poultry 
	&nbsp;</li>
</ul>

Preventing the spread of zoonotic influenza viruses involves decreasing the spread within the animal population first. Unfortunately, researchers are yet to develop a universally effective swine or avian influenza vaccine. Currently, the most effective prevention strategy is to avoid exposure.

Preventive measures can be divided into: 
&nbsp;

<ol>
	<li>
	<h5>Non-Pharmaceutical Strategies</h5>
	</li>
</ol>

<ul>
	<li>Avoid contact with infected animals or those suspected of being sick</li>
	<li>Wash hands thoroughly after coming in contact with animals</li>
	<li>Avoid eating raw, uncooked meat</li>
	<li>Separate pig farms from poultry or duck farms to prevent reassortment of influenza viruses</li>
	<li>Discourage live bird marketing</li>
	<li>Implement good hygiene practices at farms</li>
	<li>Wear effective personal protective equipment when among poultry and pigs 
	&nbsp;</li>
</ul>

<ol start="2">
	<li>
	<h5>Pharmaceutical Strategies</h5>
	</li>
</ol>

<ul>
	<li>Regular vaccinations for poultry against avian influenza</li>
	<li>Human novel influenza vaccines also help prevent infection among the human population 
	&nbsp;</li>
</ul>

As per the latest data by the European Centre for Disease Prevention and Control (ECDC), the 2021-2022 highly pathogenic avian influenza epidemic season was the largest observed in Europe so far<a href="#accordion">[8]</a>. The report showed more than 2,000 outbreaks in poultry, 3,573 wild bird infections, and the culling of 48 million birds due to the outbreak. Although no human infections were recorded during the recent outbreaks in the region, ECDC states that those working in the animal sector have the highest risk of exposure. Therefore, they advise occupational safety and health measures, such as proper ventilation, avoidance of aerosol or dust inhalation, and asking workers to separate work and personal clothing items. 
&nbsp;

Key Points

<ul>
	<li>Zoonotic influenza is a notification priority disease in Pakistan, and all confirmed or suspected cases must be relayed to concerned authorities immediately.</li>
	<li>Zoonotic influenza viruses transfer from animals to humans. However, unlike human seasonal influenza viruses, zoonotic flu viruses do not typically transmit between humans.</li>
	<li>The influenza virus has 7 genera, but only influenza A is currently zoonotic. Avian subtypes H5, H7, and H9, and swine variants of subtypes H1 and H3 are of most importance.</li>
	<li>According to research, the influenza A virus possesses a segmented RNA genome that allows the reassortment of genes and the creation of a novel virus i.e. a potential to cause a pandemic.</li>
	<li>The signs and symptoms of zoonotic influenza are similar to the typical flu. These include fever, cough, headache, malaise, myalgia, conjunctivitis, and diarrhea.</li>
	<li>The 2 classes of drugs approved for influenza infections are adamantanes and neuraminidase inhibitors. They are usually prescribed to individuals at high risk of complications.</li>
	<li>Preventing the spread of zoonotic influenza viruses involves decreasing the spread within the animal population first. 
	&nbsp;</li>
</ul>

[1] Chomel BB. Zoonoses. Encyclopedia of Microbiology. 2009;820-829. doi:10.1016/B978-012373944-5.00213-3

[2] Zoonotic Influenza. World Health Organization.

[3] Widdowson MA, Bresee JS, Jernigan DB. The Global Threat of Animal Influenza Viruses of Zoonotic Concern: Then and Now. J Infect Dis. 2017;216(suppl_4):S493-S498. doi:10.1093/infdis/jix331

[4] Mehta K, Goneau LW, Wong J, L'Huillier AG, Gubbay JB. Zoonotic Influenza and Human Health-Part 2: Clinical Features, Diagnosis, Treatment, and Prevention Strategies. Curr Infect Dis Rep. 2018;20(10):38. Published 2018 Aug 1. doi:10.1007/s11908-018-0643-8