Avian and Other Zoonotic Influenza: Risk factors, Clinical features, Treatment and Other Key Facts

There are 3 types of influenza viruses: types A, B, and C. Influenza A viruses infect humans and many different animals. Influenza B viruses only circulate among humans and cause seasonal epidemics. Influenza C viruses can infect both humans and pigs but infections are generally mild and are rarely reported.

Influenza type A viruses are classified into subtypes according to the combinations of different virus surface proteins haemagglutinin (H) and neuraminidase (N). There are 18 different haemagglutinin subtypes and 11 different neuraminidase subtypes. Depending on the origin host, influenza A viruses can be classified as avian influenza, swine influenza, or other types of animal influenza viruses. Examples include avian influenza "bird flu" virus subtypes A(H5N1) and A(H9N2) or swine influenza "swine flu" virus subtypes A(H1N1) and A(H3N2). All of these animal influenza type A viruses are distinct from human influenza viruses and do not easily transmit between humans.

Aquatic birds are the primary natural reservoir for most subtypes of influenza A viruses. Most cause asymptomatic or mild infection in birds, where the range of symptoms depends on the virus properties. Viruses that cause severe disease in birds and result in high death rates are called highly pathogenic avian influenza (HPAI). Viruses that cause outbreaks in poultry but are not generally associated with severe disease are called low pathogenic avian influenza (LPAI).

Human infections with avian and zoonotic influenza viruses

Human infections with avian and zoonotic influenza viruses have been reported. Human infections are primarily acquired through direct contact with infected animals or contaminated environments, but do not result in efficient transmission of these viruses between people.

In 1997, human infections with the HPAI A(H5N1) virus were reported during an outbreak in poultry in Hong Kong SAR, China. Since 2003, this avian virus has spread from Asia to Europe and Africa, and has become entrenched in poultry populations in some countries. Outbreaks have resulted in millions of poultry infections, several hundred human cases, and many human deaths. The outbreaks in poultry have seriously impacted livelihoods, the economy and international trade in affected countries. Other avian influenza A(H5) subtype viruses have also resulted in both outbreaks in poultry and human infections.

In 2013, human infections with the LPAI A(H7N9) virus were reported in China. Since then, the virus has spread in the poultry population across the country and resulted in several hundred human cases and many human deaths.

Other avian influenza viruses have resulted in sporadic human infections including the A(H7N7) and A(H9N2) viruses. Some countries have also reported sporadic human infections with swine influenza viruses, particularly the A(H1) and A(H3) subtypes.

Clinical features of avian and other zoonotic influenza infections in humans

Avian and other zoonotic influenza infections in humans may cause disease ranging from mild conjunctivitis to severe pneumonia and even death. Disease features such as the incubation period, severity of symptoms and clinical outcome depends on the subtype causing infection.

For avian influenza A(H5N1) virus infections in humans, current data indicate an incubation period averaging 2 to 5 days and ranging up to 17 days. For human infections with the A(H7N9) virus, incubation period ranges from 1 to 10 days, with an average of 5 days. For both viruses, the average incubation period is longer than that for seasonal influenza (2 days). For human infections with swine influenza viruses, an incubation period of 2–7 days has been reported.

In many patients infected by A(H5) or A(H7N9) avian influenza viruses, the disease has an aggressive clinical course. Common initial symptoms are high fever (greater than or equal to 38°C) and cough. Signs and symptoms of lower respiratory tract involvement including dyspnoea or difficulty breathing have been reported. Upper respiratory tract symptoms such as sore throat or coryza are less common. Other symptoms such as diarrhoea, vomiting, abdominal pain, bleeding from the nose or gums, and chest pain have also been reported in the clinical course of some patients. Complications of infection include hypoxemia, multiple organ dysfunction, and secondary bacterial and fungal infections. The case fatality rate for A(H5) and A(H7N9) subtype virus infections among humans is much higher than that of seasonal influenza infections.

For human infections with avian influenza A(H7N7) and A(H9N2) viruses, disease is typically mild or subclinical. Only one fatal A(H7N7) human infection has been reported in the Netherlands. For human infections with swine influenza viruses, most cases have been mild with a few cases hospitalized and very few reports of deaths resulting from infection.

Antiviral treatment

Evidence suggests that some antiviral drugs, notably oseltamivir, can reduce the duration of viral replication and improve prospects of survival.

In suspected cases, oseltamivir should be prescribed as soon as possible (ideally, within 48 hours following symptom onset) to maximize its therapeutic benefits. However, given the significant mortality currently associated with A(H5) and A(H7N9) subtype infections and evidence of prolonged viral replication in these diseases, administration of the drug should also be considered in patients presenting later in the course of illness. The use of corticosteroids is not recommended. In cases of severe infection with the A(H5) or A(H7N9) virus, clinicians may need to consider increasing the recommended daily dose or the duration of treatment.

In severely ill A(H5) or A(H7N9) patients or in patients with severe gastrointestinal symptoms, drug absorption may be impaired. This possibility should be considered when managing these patients. Most recent A(H5) and A(H7N9) viruses have been resistant to adamantine antiviral drugs, which are therefore not recommended for use.

Risk factors for infection

For avian influenza viruses, the primary risk factor for human infection appears to be direct or indirect exposure to infected live or dead poultry or contaminated environments, such as live bird markets. Slaughtering, defeathering, handling carcasses of infected poultry, and preparing poultry for consumption, especially in household settings, are also likely to be risk factors.

There is no evidence to suggest that the A(H5), A(H7N9) or other avian influenza viruses can be transmitted to humans through properly prepared poultry or eggs. A few influenza A(H5N1) human cases have been linked to consumption of dishes made with raw, contaminated poultry blood. Controlling the circulation of avian influenza viruses in poultry is essential to reducing the risk of human infection. Given the persistence of the A(H5) and A(H7N9) viruses in some poultry populations, control will require long-term commitments from countries and strong coordination between animal and public health authorities.

For swine influenza viruses, close proximity to infected pigs or visiting locations where pigs are exhibited has been reported for most human cases, but some limited human-to-human transmission has occurred.

Pandemic potential

Influenza pandemics (outbreaks that affect a large proportion of the world due to a novel virus) are unpredictable but recurring events that can have health, economic and social consequences worldwide. An influenza pandemic occurs when key factors converge: an avian or zoonotic influenza virus emerges with the ability to cause sustained human-to-human transmission, and the human population has little to no immunity against the virus. With the growth of global trade and travel, a localized epidemic can transform into a pandemic rapidly, with little time to prepare a public health response.

Ongoing circulation of some avian influenza subtypes in poultry, such as A(H5) or A(H7N9) viruses, are of public health concern as these viruses commonly cause severe disease in humans and the viruses have the potential to mutate to become more transmissible between humans. To date, although human-to-human transmission of these viruses is thought to have occurred in some rare instances when there had been very close and prolonged contact between a very sick patient and caregivers such as family members, there has been no sustained human-to-human transmission. If these viruses adapt or acquire certain genes from human viruses, they could trigger a pandemic.

Whether currently-circulating avian and other zoonotic influenza viruses will result in a future pandemic is unknown. However, the diversity of avian and other zoonotic influenza viruses that have caused human infections necessitates ongoing surveillance in both animal and human populations, detailed investigation of every human infection and risk-based pandemic planning.

Key facts

Humans can be infected with avian and other zoonotic influenza viruses, such as avian influenza virus subtypes A(H5N1), A(H7N9), and A(H9N2) and swine influenza virus subtypes A(H1N1) and (H3N2).

Human infections are primarily acquired through direct contact with infected animals or contaminated environments, but do not result in efficient transmission of these viruses between people. There is no evidence that the avian or zoonotic influenza viruses can infect humans through properly cooked food.

Avian and other zoonotic influenza infections in humans may cause disease ranging from mild conjunctivitis to severe pneumonia and even death.

The majority of human cases of A(H5N1) and A(H7N9) infection have been associated with direct or indirect contact with infected live or dead poultry. Controlling the disease in the animal source is critical to decrease risk to humans.

Influenza viruses, with the vast silent reservoir in aquatic birds, are impossible to eradicate. Zoonotic influenza infection in humans can continue to occur. To minimize public health risk, quality surveillance in both animal and human populations, thorough investigation of every human infection and risk-based pandemic planning are essential.

WHO response

WHO, in its capacity for providing leadership on global health matters, is monitoring avian and other zoonotic influenza viruses closely through its Global Influenza Surveillance and Response System (GISRS). Specifically, WHO, the World Organisation for Animal Health (OIE), and the Food and Agriculture Organization (FAO) collaborate to track and assess the risk from avian and other zoonotic influenza viruses of public health concern.

Based on risk assessment findings, WHO develops and adjusts appropriate interventions in collaboration with its partners, including animal health agencies and national veterinary authorities responsible for the control and prevention of animal diseases, including influenza.

Updated findings of risk assessment and recommendations on interventions are communicated timely with Member States to enhance preparedness and response.

Reference(s)
1). World Health Organization: Avian and other zoonotic influenza - WHO Fact Sheets. Accessed 04.12.17. Available here: http://who.int/mediacentre/factsheets/avian_influenza/en/
2). Centers for Disease Control: Information on Avian Influenza. Accessed 04.12.17. Available here: https://www.cdc.gov/flu/avianflu/index.htm
3). Control of Communicable Diseases Manual 20th Edition. American Public Health Association (2015). APHA Press, Washington DC. ISBN: 978-0-87553-018-5
4). Epidemiology of Human Infections with Avian Influenza A(H7N9) Virus in China. Li, Q et al (2014). New England Journal of Medicine, 370:520-532.
5). Emergence of the Virulence-Associated PB2 E627K Substitution in a Fatal Human Case of Highly Pathogenic Avian Influenza Virus A(H7N7) Infection as Determined by Illumina Ultra-Deep Sequencing. Jonges, M et al (2014). Journal of Virology. Feb; 88(3): 1694–1702.