Influenza and emerging respiratory infections

Introduction

Influenza is caused by an RNA virus of the family Orthomyxoviridae. It is a highly contagious common respiratory infection with an attack rate that varies between 5% and 10% of adults and 20% and 30% of children and a mortality that varies between 1.4 and 16.7 deaths per 100,000. Every year, seasonal epidemics of influenza result in 3 to 5 million cases of severe illness and 290,000 to 650,000 deaths worldwide. Mortality from seasonal influenza is highest among the elderly, infants and the immunocompromised, but considerable morbidity and productivity loss also occur in terms of worker and school absenteeism. General practice clinics, emergency departments and hospitals can be overwhelmed during peak seasonal influenza periods. Influenza pandemics occur as a result of a mutation that produces a novel virus. Pandemics have the potential to cause widespread disruption of the health sector and economy.

Microbiological classification

The influenza viruses are classified into three types (A, B, C) based on their core proteins. Influenza A and B cause seasonal winter epidemics in Australia; influenza C causes rare cases of respiratory illness in humans and is not thought to cause epidemics. Influenza A is more virulent than the other two types and causes the most severe disease. Type A viruses are further divided into subtypes or strains based on two surface proteins―haemagglutinin (H) and neuraminidase (N). There are 18 different haemagglutinin subtypes and 11 different neuraminidase subtypes. Haemagglutinin binds to the cell surface receptors and mediates viral attachment and entry into the host cell. The specificity of this binding partly explains the species barrier between animal and human influenza viruses. Neuraminidase is essential for the release of virus from infected cells, which, in turn, facilitates the spread of virus. Both haemagglutinin and neuraminidase are targets for antiviral drugs. Influenza B viruses are not divided into subtypes but can be divided into lineages and strains. Currently circulating influenza B viruses belong to either the B/Yamagata or the B/Victoria lineage.

Influenza viruses are named according to an international convention that recognizes the antigenic type, the host origin, the geographical origin, the strain number and the year of isolation. If the virus is type A, it is further classified by its H and N antigens (e.g. H1N1, H5N1).

Epidemiology

Antigenic drift results from a minor change in the antigenicity of the haemagglutinin or neuraminidase (H or N). It is caused by a point mutation that enables the virus to evade immune recognition and is responsible for most seasonal influenza epidemics.

Antigenic shift is a major change in the antigenicity of H and/or N proteins. It is caused by genetic reassortment between different subtypes of influenza A during coinfection of a single host. Reassortment between animal and human influenza strains can also occur, producing entirely new antigens that are unrecognizable to the human immune system. This, along with efficient human transmissibility and high virulence, may produce a lethal pandemic. The most significant pandemic recorded was the 1918 Spanish flu (H1N1), which led to an estimated 30 to 50 million deaths worldwide; but there have been subsequent pandemics with lower numbers of fatalities, including the 1957 Asian flu (H2N2), the 1968 Hong Kong flu (H3N2) and the 2009 swine flu (H1N1).

Avian and other zoonotic influenzas

The specificity of haemagglutinin binding limits the transmissibility of zoonotic influenza viruses such as the avian influenza subtypes (H5N1, H7N9) and the swine flu subtypes (H1N1, H3N2). Transmission to humans requires close direct or indirect contact with infected live or dead animals. This type of contact is common in wet markets and in slaughtering or the preparation of food. Person-to-person transmission requires close personal contact, as when individuals are being nursed or when procedures are performed that aerosolizes infectious secretions. There is no evidence that zoonotic influenza can infect humans through properly cooked food.

In 1997, human infections with H5N1 were reported during a poultry outbreak in Hong Kong. Since 2003, this virus has spread from Asia to Europe and Africa, becoming endemic in many poultry populations. In 2013, human infections with H7N9 were reported in China, with subsequent cases detected in other parts of Asia. Both viruses possess novel antigens that ensure widespread human susceptibility; however, neither is capable of ready human-to-human transmission. These two viruses, like many, are capable of acquiring pandemic potential, but they are differentiated from many of the others because of the high human mortality they have caused and their persistence and international spread in poultry stock.

Incubation period and infectivity

The incubation period is typically 2 days (range 1–4 days). Transmission occurs primarily by droplet spread via sneezing and coughing, but it may also occur by direct or indirect contact with surfaces (particularly as touched by the hands). Health care workers are at great risk of acquiring influenza infection, with a subsequent risk of nosocomial spread, particularly to vulnerable individuals.

An infected person can be infectious from the day before until 5 to 7 days after symptoms develop. Children and the immunosuppressed may remain infectious for up to 3 weeks. The amount of virus shed is proportional to the severity of the illness and the degree of temperature elevation. Immunity from previous vaccination or from infection by antigenically similar influenza strains may be partially protective.

Survival of the virus is enhanced under conditions of low humidity and in the cold, hence human influenza epidemics in temperate climates typically occur during the winter months. The virus survives for 24 to 48 hours on hard, non-porous surfaces, 8 to 12 hours on cloth/paper/tissue and up to 5 minutes on hands. Disinfectants and detergents easily inactivate influenza viruses.

Clinical features

Uncomplicated influenza is characterized by the abrupt onset of fever, rigors, myalgia, headache and malaise, followed by the occurrence of respiratory symptoms such as sore throat and a non-productive cough. Rhinitis may occur but it is not common or pronounced. Gastrointestinal symptoms are more commonly seen in children and include nausea, vomiting and diarrhoea as well as otitis media.

Examination findings are non-specific, with fever (37.8°C–40.0°C), tachycardia and non-exudative hyperaemic pharyngitis.

Influenza causes disease in all age groups. The severity of illness ranges from asymptomatic infection to severe disease, including respiratory failure and death. Patients with partial immunity may have milder manifestations. Symptoms typically resolve within 5 to 7 days, although cough and malaise may persist for at least 2 weeks. Complications, hospitalization and death occur predominantly in high-risk groups. This group includes the following:

• The elderly (above 65 years of age)

• Children below 5 years of age (especially below 2 years)

• Pregnant women (especially during the third trimester) and women within 2 weeks of delivery

• Those with chronic medical conditions (chronic cardiac, pulmonary, renal, metabolic neurodevelopmental, liver or hematologic diseases)

• Individuals with immunosuppressive conditions (such as Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS), those receiving chemotherapy or steroids, and those with malignancy)

• Indigenous persons

• Individuals with morbid obesity (body mass index (BMI) >40)

• Residents of nursing homes or long-term-care facilities