The Australian Immunisation Handbook 10th Edition
This chapter was amended on July 2016.
- 4.7.1 - Virology
- 4.7.2 - Clinical features
- 4.7.3 - Epidemiology
- 4.7.4 - Vaccines
- 4.7.5 - Transport, storage and handling
- 4.7.6 - Dosage and administration
- 4.7.7 - Recommendations
- 4.7.8 - Pregnancy and breastfeeding
- 4.7.9 - Contraindications
- 4.7.10 - Precautions
- 4.7.11 - Adverse events
- 4.7.12 - Public health management of influenza
- 4.7.13 - Variations from product information
The influenza viruses are single-stranded RNA orthomyxoviruses. They are classified antigenically as types A, B or C, but generally only influenza A and B cause severe disease in humans.1 Influenza viruses possess two surface glycoprotein antigens: the haemagglutinin (H), which is involved in cell attachment during infection, and the neuraminidase (N), which facilitates the release of newly synthesised virus from the cell. Influenza A viruses can be classified into subtypes based on differences in these surface antigens, whereas influenza B cannot. Antibody against the surface antigens, particularly the haemagglutinin, reduces infection or severe illness due to influenza.
Both influenza A and influenza B viruses undergo frequent changes in their surface antigens, involving stepwise mutations of genes coding for H and N glycoproteins. This results in cumulative changes in influenza antigens, or ‘antigenic drift’, which is responsible for the annual outbreaks and epidemics of influenza and is the reason that the composition of influenza vaccines requires annual review. ‘Antigenic shift’, defined as a dramatic change in influenza A H (and other) antigen, occurs occasionally and unpredictably and can cause pandemic influenza.1 Pandemic subtypes arise following antigenic shift, which is due to direct adaptation to humans of an avian or animal virus, or to this adaptation occurring by genetic reassortment (mixing) with a human virus.
Influenza is transmitted from person to person by virus-containing respiratory aerosols produced during coughing or sneezing, or by direct contact with respiratory secretions.1,2 Influenza virus infection causes a wide spectrum of disease, from no or minimal symptoms, to respiratory illness with systemic features, to multisystem complications and death from primary viral or secondary bacterial pneumonia. Severe disease from seasonal influenza is more likely with advanced age; infancy; lack of previous exposure to antigenically related influenza virus; greater virulence of the viral strain; chronic conditions, such as heart or lung disease, renal failure, diabetes and chronic neurological conditions; immunocompromise; obesity (class III); pregnancy; and smoking. In pandemics, severe disease may also occur in otherwise healthy young adults. Annual attack rates in the general community are typically 5 to 10%, but may be up to 20% in some years. In households and ‘closed’ populations, attack rates may be 2 to 3 times higher.3,4 However, as asymptomatic or mild influenza illness is common and symptoms are non-specific, a large proportion of influenza infections are not detected.
In adults, the onset of illness due to influenza is often abrupt, usually after an incubation period of 1 to 3 days, and includes systemic features such as malaise, feverishness, chills, headache, anorexia and myalgia. These may be accompanied by a cough, nasal discharge and sneezing. Fever is a prominent sign of infection and peaks at the height of the systemic illness. Symptoms are similar for influenza A and B viruses. However, infections due to influenza A (H3N2) strains are more likely to lead to severe morbidity and increased mortality than influenza B or seasonal influenza A (H1N1) strains.1,2
The clinical features of influenza in infants and children are similar to those in adults. However, temperatures may be higher in children (and may result in febrile convulsions in this susceptible age group), and otitis media and gastrointestinal manifestations are more prominent.5 Infection in young infants may be associated with more non-specific symptoms.5,6
Complications of influenza include: acute bronchitis, croup, acute otitis media, pneumonia (both primary viral and secondary bacterial pneumonia), cardiovascular complications including myocarditis and pericarditis, post-infectious encephalitis, Reye syndrome, and various haematological abnormalities. Primary viral pneumonia occurs rarely, but secondary bacterial pneumonia is a frequent complication in persons whose medical condition makes them vulnerable to the disease. Such persons are at high risk in epidemics and may die of pneumonia or cardiac decompensation.
In most years, minor or major epidemics of type A or type B influenza occur, usually during the winter months in temperate regions. On average, 85 deaths and approximately 4000 hospitalisations are recorded as being directly attributed to influenza annually in Australia, although this has long been recognised as a substantial under-estimate of the impact of influenza.7 Among Australians aged over 50 years alone, it is estimated that there are over 3000 deaths and more than 13 500 hospitalisations due to influenza per year.8 Influenza activity varies from year to year and is dependent on the circulating virus and the susceptibility of the population.8,9 Changes in influenza detection methods, such as an increase in the routine use of highly sensitive polymerase chain reaction (PCR)-based laboratory testing in recent years, has impacted influenza detection and notification patterns. 10
In Australia, like other developed countries, the highest rates of influenza notifications and hospitalisations are seen in the elderly and in children <5 years of age (Figure 4.7.1).9,11,12 The disease burden from influenza is greater in Aboriginal and Torres Strait Islander people than in non-Indigenous Australians, across all age groups.13 During annual epidemics of influenza, a greater rise in morbidity and mortality is seen among people with chronic diseases compared with otherwise healthy individuals.14-16
Figure 4.7.1: Average annual influenza notification and hospitalisation rates for 2010 to 2013,* Australia, by age group
* Notifications where the month of diagnosis was between January 2010 and December 2013; hospitalisations (ICD-coded; principal diagnosis) where the month of admission was between January 2010 and December 2013.
Three influenza pandemics were recognised in the 20th century, in 1918 (H1N1), 1957 (H2N2) and 1968 (H3N2). Each of these pandemic strains replaced the previously circulating influenza A subtype and went on to circulate as seasonal influenza. In 1977, the A (H1N1) re-emerged in the human population and, since then, A (H1N1) and A (H3N2) have co-circulated with influenza B. More recently, various avian influenza A virus subtypes, particularly H5N1 and H9N2, have caused human infections, but sustained human-to-human transmission has not been reported.17,18
In 2009, the World Health Organization (WHO) declared a pandemic of a novel subtype A (H1N1) influenza virus, A(H1N1)pdm09, which originated in swine. The pandemic started in Mexico and the United States before spreading globally.19 There were 44 403 confirmed A(H1N1)pdm09 cases and 213 deaths in Australia between May 2009 and November 2010.20 The predominant clinical presentation was mild to moderate illness; however, risk factors for severe disease included obesity, pregnancy, diabetes mellitus and, in Australia, being of Aboriginal or Torres Strait Islander descent (refer to 3.1 Vaccination for Aboriginal and Torres Strait Islander people). Young healthy adults and pregnant women were over-represented among severe A(H1N1)pdm09 cases compared with previous seasonal outbreaks. The A(H1N1)pdm09 virus rapidly established itself and has become the dominant influenza strain in most parts of the world.2 This strain has been included in all seasonal influenza vaccine formulations used in the southern hemisphere since 2010.
Since the early 2000s, two influenza B lineages, B/Victoria and B/Yamagata, have been co-circulating in Australia in varying proportions; in some years one B lineage predominates over the other while in other years both B lineages co-circulate in similar proportions.21 Quadrivalent influenza vaccines are now registered in Australia (refer to 4.7.4 Vaccines), providing the potential for greater coverage against circulating influenza B viruses.
The administration of influenza vaccine to persons at risk of complications of infection is the single most important measure in preventing or attenuating influenza infection and preventing mortality. After vaccination, most adults develop antibody levels that are likely to protect them against the strains of virus represented in the vaccine. In addition, there is likely to be protection against many related influenza variants.
Always check annual seasonal influenza vaccine availability statements on www.immunise.health.gov.au. Vaccines and age eligibility change from year to year.
Vaccines for intramuscular administration* listed by age group
(refer to Table 4.7.1 for dosage information for different age groups)
Children aged ≥6 months to <3 years
- FluQuadri Junior – Sanofi-Aventis Australia Pty Ltd (quadrivalent inactivated influenza virus). Each 0.25 mL pre-filled syringe contains 7.5 µg haemagglutinin of each of the four recommended influenza virus strains; ≤50 µg formaldehyde; ≤125 µg octoxinol 9; ≤0.5 µg ovalbumin.
- Influvac Junior – Abbott Australasia Pty Ltd (trivalent inactivated influenza virus). Each 0.25 mL pre-filled syringe contains 7.5 µg haemagglutinin of each of the three recommended influenza virus strains. May contain traces of formaldehyde, CTAB, polysorbate 80, gentamicin and egg protein.
- Vaxigrip Junior – Sanofi-Aventis Australia Pty Ltd (trivalent inactivated influenza virus). Each 0.25 mL pre-filled syringe contains 7.5 µg haemagglutinin of each of the three recommended influenza virus strains; ≤0.025 µg ovalbumin; ≤15 µg formaldehyde; ≤100 µg octoxinol 9; <10 pg neomycin.
Children aged ≥6 months† and adults
- Agrippal – Novartis Vaccines and Diagnostics Pty Ltd (trivalent inactivated influenza virus). Each 0.5 mL pre-filled syringe contains 15 µg haemagglutinin of each of the three recommended influenza virus strains. May contain traces of kanamycin, neomycin, formaldehyde, barium sulphate, cetrimonium bromide (CTAB), polysorbate 80 and egg protein.
- Fluarix – GlaxoSmithKline Australia Pty Ltd (trivalent inactivated influenza virus). Each 0.5 mL pre-filled syringe contains 15 µg haemagglutinin of each of the three recommended influenza virus strains; ≤0.05 µg ovalbumin; ≤5 µg formaldehyde; polysorbate 80; octoxinol 10. May contain traces of gentamicin, hydrocortisone and sodium deoxycholate.
- Influvac – Abbott Australasia Pty Ltd (trivalent inactivated influenza virus). Each 0.5 mL pre-filled syringe contains 15 µg haemagglutinin of each of the three recommended influenza virus strains. May contain traces of formaldehyde, CTAB, polysorbate 80, gentamicin and egg protein.
- Vaxigrip – Sanofi -Aventis Australia Pty Ltd (trivalent inactivated influenza virus). Each 0.5 mL pre-filled syringe contains 15 µg haemagglutinin of each of the three recommended influenza virus strains; ≤0.05 µg ovalbumin; ≤30 µg formaldehyde; ≤200 µg octoxinol 9; <20 pg neomycin.
Children aged ≥ 3 years and adults
- Fluarix Tetra – GlaxoSmithKline Australia Pty Ltd (quadrivalent inactivated influenza virus). Each 0.5 mL pre-filled syringe contains 15 µg haemagglutinin of each of the four recommended influenza virus strains; ≤0.05 µg ovalbumin; ≤5 µg formaldehyde; polysorbate 80; octoxinol 10. May contain traces of gentamicin, hydrocortisone and sodium deoxycholate.
- FluQuadri – Sanofi-Aventis Australia Pty Ltd (quadrivalent inactivated influenza virus). Each 0.5 mL pre-filled syringe contains 15 µg haemagglutinin of each of the four recommended influenza virus strains; ≤100 µg formaldehyde; ≤250 µg octoxinol 9; ≤1 µg ovalbumin.
Children aged ≥9 years‡ and adults
- Fluvax – Seqirus (previously bioCSL)‡ (trivalent inactivated influenza virus). Each 0.5 mL pre-filled syringe contains 15 µg haemagglutinin of each of the three recommended influenza virus strains; ≤5 µg sodium taurodeoxycholate, ≤1 µg ovalbumin; ≤3 ng neomycin, ≤5 ng polymyxin B, ≤4 ng β-propiolactone.
Adults aged ≥65 years
- Fluad – Novartis Vaccines and Diagnostics Pty Ltd (trivalent inactivated influenza virus). Each 0.5 mL pre-filled syringe contains 15 µg haemagglutinin of each of the three recommended influenza virus strains, adjuvanted with MF59C.1 (which includes 9.75 mg squalene and 1.175 mg polysorbate 80). May contain traces of kanamycin, neomycin, formaldehyde, barium sulphate, CTAB and egg protein.
* The preferred route of administration for influenza vaccines is by IM injection; however, they may also be given by the SC route (refer to Table 2.2.1 Route of administration for vaccines used in Australia).
† Children aged 6 months to <3 years require a 0. 25 mL dose (refer to 4.7.6 Dosage and administration and Table 4.7.1 Recommended doses of influenza vaccine).
‡ Seqirus Fluvax (previously bioCSL) is registered by the Therapeutic Goods Administration (TGA) for administration in children ≥5 years of age; however, it is not recommended for use in children < 9 years of age (refer to 4.7.11 Adverse events and 4.7.13 Variations from product information below).
All the influenza vaccines currently available in Australia are either split virion or subunit vaccines prepared from purified inactivated influenza virus that has been cultivated in embryonated hens’ eggs. The influenza virus composition of vaccines for use in Australia is determined annually by the Australian Influenza Vaccine Committee following recommendations by the World Health Organization based on global influenza epidemiology.22
Since the late 1970s, influenza vaccines have contained three strains of influenza virus – two influenza A subtypes and one influenza B lineage (i.e. trivalent influenza vaccines or TIVs). Inactivated quadrivalent influenza vaccines (QIVs) containing four influenza virus strains (the same strains in TIV and an additional influenza B virus strain from the other B lineage) have been registered for use in Australia since 2014.
The efficacy and effectiveness of influenza vaccine depends primarily on the age and immunocompetence of the vaccine recipient and the degree of similarity between the virus strains in the vaccine and those circulating in the community.23-31 The majority of effectiveness studies have been done with TIV due to their widespread use. Although the burden of influenza in young children is large, historically there has been limited data on the efficacy and effectiveness of influenza vaccines in this age group. However, there is a growing body of evidence demonstrating that similar levels of protection are achieved in young children as in older children and adults.32-36 A recent systematic review estimated the overall efficacy of inactivated vaccines against laboratory-confirmed influenza in healthy adults <65 years of age to be 59%, although efficacy varied by influenza season.37 The efficacy of inactivated influenza vaccine against influenza-like illness in persons ≥65 years of age living in the community is estimated to be 43% when viral circulation is high, although there have been few randomised controlled trials of influenza vaccine in elderly people.38 In nursing home settings, influenza vaccination is approximately 45% effective against hospitalisations due to influenza and pneumonia and 60% effective against all-cause mortality in persons aged >65 years.38
QIV is expected to be at least as effective as TIV. This is based on clinical studies in children and adults which have shown QIV to be as immunogenic as TIV (an accepted surrogate for protection against influenza) for the three shared influenza virus strains.39-42 In these studies, QIV stimulated a similar level of antibodies against the additional B strain not in TIV as for the shared strains. Thus, QIV has the potential to protect against a greater proportion of circulating influenza strains in any season than TIV. The magnitude of this potential additional benefit from QIV over TIV cannot be predicted for any influenza season as it depends on a number of factors. In previous years, the proportion of all circulating influenza viruses attributable to the influenza B lineage that was not in the TIV (but would have been in a QIV) ranged from 0% (in 2000 and 2001) to 32% (in 2008).21 Other factors, such as antigenic mismatch between vaccine and circulating strains, cross-protection against non-vaccine B strains afforded by the strain in the TIV and an individual’s pre-existing immunity to the circulating strains of influenza, may all influence the potential additional benefit of QIV over TIV.
Currently available influenza vaccines confer protection for about a year. Low levels of protection may persist for a further year, if the prevalent strain remains the same or undergoes only minor antigenic drift.23,31 Continuing protection requires annual vaccination with vaccine containing the most recent strains.
Split virion and subunit vaccines are generally considered to be equivalent with respect to safety. One exception is Seqirus (previously bioCSL) Fluvax, which in 2010 resulted in higher rates of fevers and febrile convulsions in children aged <5 years, in comparison with other influenza vaccines (refer to 4.7.11 Adverse events below).43 Because influenza vaccine viruses are cultivated in embryonated hens’ eggs, these vaccines may contain traces of egg-derived proteins; however, the majority of influenza vaccines currently used in Australia contain less than 1 μg of ovalbumin per dose. (Refer to 4.7.10 Precautions below and also to ‘Vaccination of persons with a known egg allergy’ in 3.3.1 Vaccination of persons who have had an adverse event following immunisation.)
Live attenuated intranasal influenza vaccines are not currently registered in Australia.44 Influenza vaccines presented in a purpose-designed syringe for intradermal administration were registered for use in Australia in 2009 but are no longer available.
Transport according to National vaccine storage guidelines: Strive for 5.45 Store at +2°C to +8°C. Do not freeze. Protect from light.
At the end of each year, influenza vaccines should be appropriately discarded to avoid inadvertently using a product with incorrect formulation in the following year.
4.7.6 Dosage and administration
Vaccines registered by the TGA, and the ages for which they are indicated, can change from year to year. Always check annual seasonal influenza vaccine availability statements published by ATAGI on the Immunise Australia website, and consult individual product information.
Influenza vaccines available in Australia are presented in pre-filled syringes, of either 0.5 mL or 0.25 mL. The dose of vaccine to be administered varies by age, with children aged 6 months to <3 years requiring a 0.25 mL dose. Refer to Table 4.7.1 for the recommended doses of influenza vaccine for different age groups. Some 0.5 mL syringes have a graduated mark to indicate where the plunger can be depressed to provide a 0.25 mL dose, if indicated. If a child aged 6 months to <3 years inadvertently receives a 0.5 mL dose of influenza vaccine, no immediate action is necessary, and any additional dose(s) required that season or in future seasons should be given following standard recommendations (refer below). There is some evidence that a 0.5 mL dose of inactivated influenza vaccine is immunogenic and safe in children <3 years of age.40,46
Shake the pre-filled syringe vigorously before injection.
The preferred route of administration for influenza vaccines is by IM injection; however, they may also be given by the SC route (refer to Table 2.2.1 Route of administration for vaccines used in Australia).Table 4.7.1: Recommended doses of influenza vaccine
|Age||Dose||Number of doses required in the first year of influenza vaccination||Number of doses required if previously received 1 or more doses of influenza vaccine|
|6 months to <3 years*||
|≥3 years to <9 years*||
* Children aged 6 months to <9 years receiving influenza vaccine for the first time require 2 doses, at least 4 weeks apart, to maximise the immune response to the vaccine strains. For children who have previously received 1 or more doses of trivalent or quadrivalent influenza vaccine, only 1 dose of influenza vaccine is required in the current season and all seasons thereafter (irrespective of whether TIV or QIV is being used).47-48
† If a child aged 6 months to <3 years inadvertently receives a 0.5 mL dose of influenza vaccine, no immediate action is necessary, and any additional dose(s) required that season or in future seasons should be given following standard recommendations (refer to 4.7.6 Dosage and administration above).
‡ Two doses, at least 4 weeks apart, are recommended for persons with certain immunocompromising conditions (i.e. haematopoietic stem cell transplant or solid organ transplant) receiving influenza vaccine for the first time post transplant (irrespective of their age) (refer to 4.7.7 Recommendations below and 3.3 Groups with special vaccination requirements).
Vaccination is best undertaken in autumn, in anticipation of winter outbreaks of influenza. However, vaccination can be given as early as February if vaccine is available, particularly for the northern areas of Queensland and in the Northern Territory where the seasonality of influenza differs from the southern states. In autumn, the opportunities to provide influenza vaccination to persons at increased risk of influenza should not be missed during visits for routine medical care.
As full protection is usually achieved within 10 to 14 days and there is evidence of increased immunity within a few days, vaccination can still be offered to adults and children after influenza virus activity has been documented in the community.
Co-administration with other vaccines
All inactivated influenza vaccines can be administered concurrently with any other vaccine, including pneumococcal polysaccharide vaccine and all scheduled childhood vaccines. Parents/carers of infants or children who are recommended to receive both influenza vaccine and 13-valent pneumococcal conjugate vaccine (13vPCV) should be advised of a possible small increased risk of fever following concomitant administration of these vaccines (refer to 4.7.10 Precautions below and 4.13 Pneumococcal disease).
To date, there are no studies that assess the co-administration of QIVs with other vaccines. However, based on first principles and the similar manufacturing methods of QIVs and TIVs, it is expected that the safety and immunogenicity of QIV and TIV would be similar when administered at the same time as other vaccines.
Interchangeability of influenza vaccines
Where 2 doses of influenza vaccine are indicated in a single season (refer to Table 4.7.1 Recommended doses of influenza vaccine), different brands of TIV or QIV are considered interchangeable (providing they are age-appropriate). Where possible, both doses should be administered using vaccines containing the same number of influenza strains (i.e. both with TIV or both with QIV) to ensure adequate priming of all influenza strains in the vaccine.
For individuals who only need 1 dose annually and have already received a TIV in the current influenza season, a further dose of QIV in the same season is not recommended but is not contraindicated.
Influenza vaccination is strongly recommended and should be actively promoted for the groups discussed below.
In circumstances where more than one influenza vaccine formulation is appropriate, ATAGI recommends the use of QIV in preference to TIV, due to the additional influenza B strain that QIV contains (refer to 4.7.4 Vaccines above). However, TIV is expected to protect against the majority of circulating influenza viruses in most seasons and is therefore an acceptable alternative to QIV. It is important that influenza vaccination is not delayed if an age-appropriate TIV is available and there are barriers to accessing QIV.
All adults aged ≥65 years
Persons at increased risk of complications from influenza infection
Persons aged ≥6 months with conditions predisposing to severe influenza,7 such as:
- Pregnancy – Pregnant women (and women planning pregnancy) are recommended to be immunised against influenza because they are at increased risk of morbidity and mortality from influenza. Influenza vaccination of pregnant women also protects infants against influenza for the first 6 months after birth due to transplacental transfer of antibodies from the vaccinated woman to the fetus.51-53 Influenza vaccine can be given during any stage of pregnancy. The timing of vaccination depends on the time of the year relative to the influenza season, vaccine availability, stage of pregnancy and the anticipated duration of immunity. The risk to the mother of complications from influenza increases in the later stages of pregnancy.51, 54-62 Most evidence around infant protection is from studies of maternal influenza vaccination in the second or third trimester.51, 52, 54-62 Although protection following a dose of influenza vaccine is thought to persist in an individual for up to a year, there is some evidence that immunity may wane from as early as 4 months following immunisation.
- Cardiac disease, including cyanotic congenital heart disease, coronary artery disease and congestive heart failure – Influenza causes increased morbidity and mortality in children with congenital heart disease and adults with coronary artery disease and congestive heart failure.50,63-66
- Down syndrome – Persons with Down syndrome should receive annual seasonal influenza vaccine whether or not they have congenital heart disease. This is due to the presence of anatomical abnormalities, which put them at increased risk of upper respiratory tract infections, as well as a high prevalence of other medical conditions that put them at increased risk of severe influenza.65
- Obesity – Persons with a BMI ≥40 kg/m2 (classified as class III obesity) should receive annual seasonal influenza vaccine due to their increased risk of severe outcomes, particularly observed following infection with the A(H1N1)pdm09 influenza strain.67-70 This increased risk is independent of the presence of underlying comorbidities.71 There is also some evidence that persons who have a BMI between 30 and <40 (class II obesity) are at increased risk of severe influenza and may benefit from annual influenza vaccine.69,71,72 Studies assessing the association of obesity and severe outcomes following infection with the A(H1N1)pdm09 strain demonstrate the greatest risk is in those with the highest BMI.67,69,70,73
- Chronic respiratory conditions, including:
- Suppurative lung disease, bronchiectasis and cystic fibrosis50,64 – Patients with these diseases are at greatly increased risk from influenza, which may cause irreversible deterioration in lung function.74
- Chronic obstructive pulmonary disease (COPD) and chronic emphysema50,75,76 – Data from several studies provide evidence that influenza vaccination has a clinically important protective effect on influenza-related COPD exacerbations, and probably an effect on the total number of exacerbations in COPD patients.75,76
- Severe asthma – In patients with severe asthma, defined as requiring frequent hospital visits and the use of multiple medications, annual influenza vaccine is an important part of routine care.50,64 There are insufficient data from randomised controlled trials of influenza vaccine to define efficacy across the whole spectrum of asthma, but influenza can cause severe exacerbations of wheezing, and about 10% of episodes of virus-induced wheezing are attributable to influenza.
- Chronic neurological conditions (e.g. multiple sclerosis, spinal cord injuries, seizure disorders or other neuromuscular disorders) – These conditions can compromise respiratory function or the expulsion of respiratory secretions that can then increase the risk for aspiration.50,64 Influenza vaccination is particularly important for children ≥6 months of age with chronic neurological conditions as these children can experience severe, even fatal, influenza.
- Immunocompromising conditions – Persons who are immunocompromised, including those with HIV infection, malignancy or chronic steroid use, are at an increased risk from influenza (refer to 3.3.3 Vaccination of immunocompromised persons).50,64 They may also have a reduced immune response to the vaccine, although influenza vaccination affords some protection.77 Influenza vaccination is recommended annually in all immunocompromised patients aged ≥6 months.
Persons with certain immunocompromising conditions (i.e. haematopoietic stem cell transplant or solid organ transplant) receiving influenza vaccine for the first time post transplant are recommended to receive 2 vaccine doses at least 4 weeks apart (irrespective of age) and 1 dose annually thereafter (refer to 3.3.3 Vaccination of immunocompromised persons). Where it is known that a new influenza vaccine strain is circulating in the community to which cross-protective immunity in the population is low (such as in the setting of an influenza pandemic), it may be appropriate that immunocompromised persons receive 2 doses of inactivated influenza vaccine, a minimum of 4 weeks apart, to achieve an optimal immune response, irrespective of their previous influenza vaccination history. For example, in the 2009–2010 H1N1 global influenza pandemic it was shown that seroconversion to influenza vaccination in immunocompromised adolescents and adults was improved following receipt of 2 vaccine doses.78 Further information and annual influenza vaccine recommendations are available on the Immunise Australia website (www.immunise.health.gov.au).
While patients with advanced HIV disease and low CD4+ T-lymphocyte counts may not develop protective antibody titres, there is evidence that for those with minimal symptoms and high CD4+ T-lymphocyte counts, protective antibody titres are obtained after influenza vaccination. Influenza vaccine has been shown to reduce the incidence of influenza in HIV-infected patients, and, although viral load may increase transiently, there was no impact on CD4+ count.77 (Refer also to 3.3 Groups with special vaccination requirements, Table 3.3.4.)
- Chronic liver disease – Persons with histological evidence of fibrosis or cirrhosis and/or clinical evidence of chronic liver disease due to various causes, including alcoholism, are at increased risk of severe outcomes following influenza infection.15,69,79
- Other chronic illnesses requiring regular medical follow-up or hospitalisation in the preceding year, including:
- diabetes mellitus50,64,80
- chronic renal failure50,64
- chronic inherited metabolic diseases (which includes amino acid disorders, carbohydrate disorders, cholesterol biosynthesis disorders, fatty acid oxidation defects, lactic acidosis, mitochondrial disorders, organic acid disorders, urea cycle disorders, vitamin/cofactor disorders, porphyrias)50,64
- Long-term aspirin therapy in children (aged 6 months to 10 years) – Such children are at increased risk of Reye syndrome after influenza.81,82
- Preterm infants (<37 weeks gestation) with underlying conditions such as chronic lung disease, heart disease and neurological conditions – These infants have an increased risk of complications from influenza (refer to 3.3.2 Vaccination of women who are planning pregnancy, pregnant or breastfeeding, and preterm infants).
Aboriginal and Torres Strait Islander people
Annual influenza vaccination is recommended for all Aboriginal and Torres Strait Islander people. In particular, Aboriginal and Torres Strait Islander children aged 6 months to <5 years and adolescents and adults aged ≥15 years are at greater risk of influenza and its complications (refer to 4.7.2 Clinical features above) than their non-Indigenous counterparts.13 (Refer also to 3.1 Vaccination for Aboriginal and Torres Strait Islander people.) The risk of influenza complications is not as high in children aged 5–14 years.13 However, annual influenza vaccination of children in this age group can still offer individual protection against influenza as well as potential indirect protection to other members of their household (refer to ‘Persons who may transmit influenza to persons at increased risk of complications from influenza infection’below).
Children aged <5 years
Infants and children aged <5 years are at increased risk of hospitalisation and increased morbidity and mortality following influenza (refer to Figure 4.7.1).9 This includes young children without pre-existing medical conditions who are at increased risk of hospitalisation compared with older children and adults.14,83,84 Specific brands of influenza vaccine are registered by the TGA for use in children ≥6 months of age and these may change from year to year (refer to 4.7.6 Dosage and administration above).
Residents of residential aged care facilities and long-term residential facilities
Annual influenza vaccination is recommended for residents of these facilities, including inmates of correctional facilities, due to high rates of influenza transmission and complications during outbreaks in such facilities.23,76,85
The living conditions and prevalence of underlying medical conditions among homeless people will predispose them to complications and transmission of influenza.
Persons who may transmit influenza to persons at increased risk of complications from influenza infection
The following groups of people can potentially transmit influenza to persons at increased risk of complications from influenza infection; vaccination of these groups is therefore recommended to protect those at risk:
- all healthcare providers (particularly those of immunocompromised patients)
- staff (or volunteers) working in nursing homes
- staff (or volunteers) working in long-term care facilities
- household contacts (including children ≥6 months of age) of those in high-risk groups, including providers of home care to persons at risk of high influenza morbidity
- staff working in early childhood education and care
- staff (or volunteers) providing care to homeless people.
Persons involved in the commercial poultry or pork industry or in culling poultry or pigs during confirmed avian or swine influenza activity
Vaccination using the seasonal influenza vaccine composition current at the time is recommended for poultry or piggery workers and others in regular close contact with poultry or pigs during an avian or swine influenza outbreak.86 Although routine seasonal influenza vaccine does not protect against avian or swine influenza, there is a possibility that a person who is infected at the same time with animal and human strains of influenza virus could act as a vessel for reassortment of the two strains to form a virulent strain, with the potential for spread from human to human (i.e. initiate a pandemic as was the case with swine influenza in 2009).87 In addition, vaccination can also prevent the transmission of influenza from humans to animals.
Persons providing essential services
Vaccination of those who provide essential community services will minimise disruption of essential activities during influenza outbreaks. Influenza viral infections can place considerable pressure upon both public and private healthcare services (refer to 3.3 Groups with special vaccination requirements, Table 3.3.7 Recommended vaccinations for persons at increased risk of certain occupationally acquired vaccine-preventable diseases).
Workers in other industries
Due to the high attack rate of influenza in the general population, influenza vaccination in the workplace can result in benefits such as increased productivity and reduced absenteeism among workers.88 Employers should consider the benefits of offering influenza vaccine in their individual workplace.
Influenza vaccine is particularly relevant if influenza epidemics are occurring at the traveller’s destination(s). Travellers in large tourist groups, especially those including older people, those travelling on cruises, and/or those who are likely to be in confined circumstances for days to weeks, are at risk of influenza, either acquired before departure or from travel to areas of the world where influenza is currently circulating. Influenza vaccination is recommended if travelling during the influenza season, especially if it is known before travel that influenza is circulating in the destination region.89 (Refer also to 3.2 Vaccination for international travel.)
4.7.8 Pregnancy and breastfeeding
Refer to 3.3 Groups with special vaccination requirements, Table 3.3.1 Recommendations for vaccination in pregnancy for more information.
The only absolute contraindications to influenza vaccines are:
- anaphylaxis following a previous dose of any influenza vaccine
- anaphylaxis following any vaccine component.
Refer 4.7.10 Precautions below for persons with a known egg allergy.
Persons with known egg allergy94-98
Several recently published reviews, guidelines and reports have indicated that the risk of anaphylaxis associated with influenza vaccination of egg-allergic patients is very low.94-98 Persons with egg allergy, including anaphylaxis, can be safely vaccinated with influenza vaccines that have less than 1 μg of residual egg ovalbumin per dose.94,96 Due to changes in influenza vaccine manufacturing, the majority of influenza vaccines currently used contain less than 1 μg of ovalbumin per dose.94 Note the amount of residual egg ovalbumin may vary from year to year due to manufacturing processes, batches and country of origin.94,96,97 The product information (PI) of the vaccine to be given should be checked for the vaccine’s ovalbumin content prior to vaccine administration. Allergy testing with influenza vaccine prior to administration is not recommended as there is poor correlation between test results and vaccine tolerance.94,96-98
However, there is still a low risk of anaphylaxis, so it is essential that such patients are vaccinated in facilities with staff able to recognise and treat anaphylaxis. Additional information on influenza vaccination of individuals with an allergy to eggs, including risk, dosage and observation period, can be found in the Australasian Society of Clinical Immunology and Allergy (ASCIA) guidelines.96 (Refer also to ‘Vaccination of persons with a known egg allergy’ in 3.3.1 Vaccination of persons who have had an adverse event following immunisation.)
Persons with a history of Guillain-Barré syndrome
Persons with a history of Guillain-Barré syndrome (GBS) have an increased likelihood in general of developing GBS again, and the chance of them coincidentally developing the syndrome following influenza vaccination may be higher than in persons with no history of GBS.99 Diagnosis of GBS is complex and must be made by a physician. (Refer also to 4.7.11 Adverse events below.)
Children requiring both influenza and 13-valent pneumococcal conjugate vaccine
One study has demonstrated a slightly higher risk of fever and febrile convulsions in children aged 6 months to <5 years (especially those aged 12–24 months) with the concurrent administration of inactivated trivalent influenza vaccine and 13vPCV (compared with giving the vaccines separately).100 The risk was estimated to be about 18 excess cases per 100 000 doses in children aged 6–59 months, with a peak of 45 per 100 000 doses in those aged 16 months. Given that the reported increase in risk was relatively small, and a more recent study did not demonstrate the same association between febrile seizures and the concurrent administration of these two vaccines,101 administration of 13vPCV and inactivated trivalent influenza vaccine at the same visit is acceptable when both vaccines are indicated. (Refer also to 4.13 Pneumococcal disease .) However, immunisation service providers should advise parents of the possible risk and provide the option of administering these two vaccines on separate days (with an interval of not less than 3 days).
4.7.11 Adverse events
Fever, malaise and myalgia occur commonly, in 1 to 10% of persons who receive inactivated influenza vaccination.102-104 These adverse events may commence within a few hours of vaccination and may last for 1 to 2 days.102-104 In children <5 years of age, these side effects may be more pronounced. In 2010, an excess of fever and febrile convulsions following influenza vaccination was reported in children aged <5 years, particularly children aged <3 years. This was associated only with one manufacturer’s vaccine (Seqirus (previously bio CSL) Fluvax and Fluvax Junior); following vaccination with this vaccine, febrile convulsions occurred at a rate of 4.4 per 1000 doses in children <5 years of age.105 This vaccine is no longer registered for use in children aged <5 years and is not recommended for administration in children aged <9 years (refer to 4.7.4 Vaccines above).
Local adverse events (induration, swelling, redness and pain) occur in more than 10% of vaccine recipients, following IM influenza vaccine administration.103,104 Studies directly comparing trivalent and quadrivalent inactivated influenza vaccine formulations in children and adults have demonstrated a similar safety profile.39-42
Post-vaccination symptoms may mimic influenza infection, but all currently available influenza vaccines do not contain live virus and so do not cause influenza.
Immediate adverse events (such as hives, angioedema or anaphylaxis) are a rare consequence of influenza vaccination. They probably represent an allergic response to a residual component of the manufacturing process, most likely egg protein.94,96 Persons with a history of anaphylaxis after eating eggs or a history of a severe allergic reaction following occupational exposure to egg protein may receive influenza vaccination after medical consultation.94,96
A small increased risk of GBS was associated historically with one influenza vaccine in the United States in 1976, but, since then, close surveillance has shown that GBS has occurred at a very low rate of up to 1 in 1 million doses of influenza vaccine, if at all.106 Diagnosis of GBS is complex and must be made by a physician (refer to 'Uncommon/rare AEFI' in 2.3.2 Adverse events following immunisation).
Narcolepsy (sudden sleeping illness) has been described predominantly in the Scandinavian population, in association with adjuvanted pandemic influenza vaccines.107,108 These vaccines were not used and are not available in Australia.
Laboratory-confirmed cases of influenza are notifiable in all states and territories in Australia. Detailed information regarding the management of influenza cases and contacts can be found in the national guidelines for control of influenza109 (www.health.gov.au/cdnasongs).
Further instructions about the public health management of influenza can also be obtained from state/territory public health authorities (refer to Appendix 1 Contact details for Australian, state and territory government health authorities and communicable disease control).
4.7.13 Variations from product information
The product information for influenza vaccines lists allergy to eggs, chicken feathers and/or some food proteins as a contraindication. The ATAGI recommends instead that patients with egg allergies and other allergies can be vaccinated under strict medical supervision, in accordance with ASCIA guidelines.96
The product information for Seqirus (previously bioCSL) Fluvax states that this vaccine is registered for use in children ≥5 years of age. However, the ATAGI does not recommend the use of this vaccine in children aged <9 years.
- Wright PF, Neumann G, Kawaoka Y. Orthomyxoviruses. In: Knipe DM, Howley PM, Griffin DE, et al., eds. Fields virology. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins, 2007.
- Australian Government Department of Health and Ageing. Australian influenza surveillance report. No. 9, 2011. Reporting period: 9 July to 22 July 2011. Available at: (www.health.gov.au/internet/main/publishing.nsf/Content/cda-ozflu-no9-11.htm) (accessed July 011).
- Neuzil KM, Zhu Y, Griffin MR, et al. Burden of interpandemic influenza in children younger than 5 years: a 25-year prospective study. Journal of Infectious Diseases 2002;185:147-52.
- Hurwitz ES, Haber M, Chang A, et al. Effectiveness of influenza vaccination of day care children in reducing influenza-related morbidity among household contacts. JAMA 2000;284:1677-82.
- Lester-Smith D, Zurynski YA, Booy R, et al. The burden of childhood influenza in a tertiary paediatric setting. Communicable Diseases Intelligence 2009;33:209-15.
- Iskander M, Kesson A, Dwyer D, et al. The burden of influenza in children under 5 years admitted to The Children's Hospital at Westmead in the winter of 2006. Journal of Paediatrics and Child Health 2009;45:698-703.
- Newall AT, Scuffham PA. Influenza-related disease: the cost to the Australian healthcare system. Vaccine 2008;26:6818-23.
- Newall AT, Wood JG, MacIntyre CR. Influenza-related hospitalisation and death in Australians aged 50 years and older. Vaccine 2008;26:2135-41.
- Chiu C, Dey A, Wang H, et al. Vaccine preventable diseases in Australia, 2005 to 2007. Communicable Diseases Intelligence 2010;34 Suppl:ix-S167.
- Kaczmarek MC, Ware RS, Lambert SB. The contribution of PCR testing to influenza and pertussis notifications in Australia. Epidemiology and Infection 2016;144:306-14.
- Thompson WW, Shay DK, Weintraub E, et al. Influenza-associated hospitalizations in the United States. JAMA 2004;292:1333-40.
- Poehling KA, Edwards KM, Weinberg GA, et al. The underrecognized burden of influenza in young children. New England Journal of Medicine 2006;355:31-40.
- Naidu L, Chiu C, Habig A, et al. Vaccine preventable diseases and vaccination coverage in Aboriginal and Torres Strait Islander people, Australia 2006–2010. Communicable Diseases Intelligence 2013;37 Suppl:S1-95.
- Izurieta HS, Thompson WW, Kramarz P, et al. Influenza and the rates of hospitalization for respiratory disease among infants and young children. New England Journal of Medicine 2000;342:232-9.
- Mertz D, Kim TH, Johnstone J, et al. Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis. BMJ 2013;347:f5061.
- Nielsen J, Mazick A, Glismann S, Mřlbak K. Excess mortality related to seasonal influenza and extreme temperatures in Denmark, 1994–2010. BMC Infectious Diseases 2011;11:350.
- Webster RG, Peiris M, Chen H, Guan Y. H5N1 outbreaks and enzootic influenza. Emerging Infectious Diseases 2006;12:3-8.
- Peiris M, Yuen KY, Leung CW, et al. Human infection with influenza H9N2. The Lancet 1999;354:916-7.
- World Health Organization (WHO). Global Alert and Response (GAR). Pandemic (H1N1) 2009 – update 112. 2010. Available at: (www.who.int/csr/don/2010_08_06/en/index.html) (accessed June 2012).
- Australian Government Department of Health and Ageing. Australian influenza surveillance report. No. 44, 2010, reporting period: 30 October – 5 November 2010. Available at: (www.health.gov.au/internet/main/publishing.nsf/Content/cda-ozflu-no44-10.htm) (accessed July 2011).
- Barr IG, Jelley LL. The coming era of quadrivalent human influenza vaccines: who will benefit? Drugs 2012;72:2177-85.
- Therapeutic Goods Administration. Australian Influenza Vaccine Committee (AIVC). 2014. Available at: (www.tga.gov.au/committee/australian-influenza-vaccine-committee-aivc) (accessed Nov 2014).
- Dean AS, Moffatt CR, Rosewell A, et al. Incompletely matched influenza vaccine still provides protection in frail elderly. Vaccine 2010;28:864-7.
- Kelly H, Carville K, Grant K, et al. Estimation of influenza vaccine effectiveness from routine surveillance data. PLoS ONE 2009;4(3):e5079. doi:10.1371/journal.pone.0005079.
- Kelly H, Jacoby P, Dixon GA, et al. Vaccine effectiveness against laboratory-confirmed influenza in healthy young children: a case-control study. Pediatric Infectious Disease Journal 2011;30:107-11.
- Jefferson T, Rivetti A, Di Pietrantonj C, Demicheli V, Ferroni E. Vaccines for preventing influenza in healthy children. Cochrane Database of Systematic Reviews 2012;(8):CD004879. doi:10.1002/14651858.CD004879.pub4.
- Shuler CM, Iwamoto M, Bridges CB, et al. Vaccine effectiveness against medically attended, laboratory-confirmed influenza among children aged 6 to 59 months, 2003–2004. Pediatrics 2007;119:e587-95.
- Joshi AY, Iyer VN, St Sauver JL, Jacobson RM, Boyce TG. Effectiveness of inactivated influenza vaccine in children less than 5 years of age over multiple influenza seasons: a case-control study. Vaccine 2009;27:4457-61.
- Heinonen S, Silvennoinen H, Lehtinen P, et al. Effectiveness of inactivated influenza vaccine in children aged 9 months to 3 years: an observational cohort study. The Lancet Infectious Diseases 2011;11:23-9.
- Jick H, Hagberg KW. Effectiveness of influenza vaccination in the United Kingdom, 1996–2007. Pharmacotherapy 2010;30:1199-206.
- Monto AS, Ohmit SE, Petrie JG, et al. Comparative efficacy of inactivated and live attenuated influenza vaccines. New England Journal of Medicine 2009;361:1260-7.
- Blyth CC, Jacoby P, Effler PV, et al. Effectiveness of trivalent flu vaccine in healthy young children. Pediatrics 2014;133:e1218-25.
- Heikkinen T, Heinonen S. Effectiveness and safety of influenza vaccination in children: European perspective. Vaccine 2011;29:7529-34.
- Pebody R, Andrews N, McMenamin J, et al. Vaccine effectiveness of 2011/12 trivalent seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: evidence of waning intra-seasonal protection. Eurosurveillance 2013;18(5):pii=20389.
- Treanor JJ, Talbot HK, Ohmit SE, et al. Effectiveness of seasonal influenza vaccines in the United States during a season with circulation of all three vaccine strains. Clinical Infectious Diseases 2012;55:951-9.
- Fu C, He Q, Li Z, et al. Seasonal influenza vaccine effectiveness among children, 2010–2012. Influenza and Other Respiratory Viruses 2013;7:1168-74.
- Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. The Lancet Infectious Diseases 2012;12:36-44.
- Jefferson T, Di Pietrantonj C, Al-Ansary LA, et al. Vaccines for preventing influenza in the elderly. Cochrane Database of Systematic Reviews 2010;(2):CD004876. doi:10.1002/14651858.CD004876.pub3.
- Kieninger D, Sheldon E, Lin WY, et al. Immunogenicity, reactogenicity and safety of an inactivated quadrivalent influenza vaccine candidate versus inactivated trivalent influenza vaccine: a phase III, randomized trial in adults aged ≥18 years. BMC Infectious Diseases 2013;13:343.
- Domachowske JB, Pankow-Culot H, Bautista M, et al. A randomized trial of candidate inactivated quadrivalent influenza vaccine versus trivalent influenza vaccines in children aged 3–17 years. Journal of Infectious Diseases 2013;207:1878-87.
- Pépin S, Donazzolo Y, Jambrecina A, Salamand C, Saville M. Safety and immunogenicity of a quadrivalent inactivated influenza vaccine in adults. Vaccine 2013;31:5572-8.
- Greenberg DP, Robertson CA, Landolfi VA, et al. Safety and immunogenicity of an inactivated quadrivalent influenza vaccine in children 6 months through 8 years of age. Pediatric Infectious Disease Journal 2014;33:630-6.
- Blyth CC, Currie AJ, Wiertsema SP, et al. Trivalent influenza vaccine and febrile adverse events in Australia, 2010: clinical features and potential mechanisms. Vaccine 2011;29:5107-13.
- Jin H, Subbarao K. Live attenuated influenza vaccine. Current Topics in Microbiology and Immunology 2015;386:181-204.
- National vaccine storage guidelines: Strive for 5. 2nd ed. Canberra: Australian Government Department of Health and Ageing, 2013. Available at: (www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/IMM77-cnt) (accessed Jan 2016).
- Skowronski DM, Hottes TS, Chong M, et al. Randomized controlled trial of dose response to influenza vaccine in children aged 6 to 23 months. Pediatrics 2011;128:e276-89.
- Walter EB, Neuzil KM, Zhu Y, et al. Influenza vaccine immunogenicity in 6- to 23-month-old children: are identical antigens necessary for priming? Pediatrics 2006;118:e570-8.
- Englund JA, Walter EB, Gbadebo A, et al. Immunization with trivalent inactivated influenza vaccine in partially immunized toddlers. Pediatrics 2006;118:e579-e85.
- Centers for Disease Control and Prevention (CDC). Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2011. MMWR. Morbidity and Mortality Weekly Report 2011;60:1128-32.
- Nokleby H, Nicoll A. Risk groups and other target groups – preliminary ECDC guidance for developing influenza vaccination recommendations for the season 2010–11. Eurosurveillance 2010;15(12):pii=19525.
- Zaman K, Roy E, Arifeen SE, et al. Effectiveness of maternal influenza immunization in mothers and infants. New England Journal of Medicine 2008;359:1555-64.
- Benowitz I, Esposito DB, Gracey KD, Shapiro ED, Vázquez M. Influenza vaccine given to pregnant women reduces hospitalization due to influenza in their infants. Clinical Infectious Diseases 2010;51:1355-61.
- Poehling KA, Szilagyi PG, Staat MA, et al. Impact of maternal immunization on influenza hospitalizations in infants. American Journal of Obstetrics and Gynecology 2011;204(6 Suppl 1):S141-8.
- Irving WL, James DK, Stephenson T, et al. Influenza virus infection in the second and third trimesters of pregnancy: a clinical and seroepidemiological study. BJOG: An International Journal of Obstetrics and Gynaecology 2000;107:1282-9.
- Mak TK, Mangtani P, Leese J, Watson JM, Pfeifer D. Influenza vaccination in pregnancy: current evidence and selected national policies. The Lancet Infectious Diseases 2008;8:44-52.
- Black SB, Shinefield HR, France EK, et al. Effectiveness of influenza vaccine during pregnancy in preventing hospitalizations and outpatient visits for respiratory illness in pregnant women and their infants. American Journal of Perinatology 2004;21:333-9.
- American College of Obstetricians and Gynecologists, Committee on Obstetric Practice. ACOG Committee Opinion No. 468: Influenza vaccination during pregnancy. Obstetrics and Gynecology 2010;116:1006-7.
- MacDonald NE, Riley LE, Steinhoff MC. Influenza immunization in pregnancy. Obstetrics and Gynecology 2009;114:365-8.
- Eick AA, Uyeki TM, Klimov A, et al. Maternal influenza vaccination and effect on influenza virus infection in young infants. Archives of Pediatrics and Adolescent Medicine 2011;165:104-11.
- France EK, Smith-Ray R, McClure D, et al. Impact of maternal influenza vaccination during pregnancy on the incidence of acute respiratory illness visits among infants. Archives of Pediatrics and Adolescent Medicine 2006;160:1277-83.
- Tamma PD, Steinhoff MC, Omer SB. Influenza infection and vaccination in pregnant women. Expert Review of Respiratory Medicine 2010;4:321-8.
- Englund JA, Mbawuike IN, Hammill H, et al. Maternal immunization with influenza or tetanus toxoid vaccine for passive antibody protection in young infants. Journal of Infectious Diseases 1993;168:647-56.
- Siriwardena AN, Gwini SM, Coupland CA. Influenza vaccination, pneumococcal vaccination and risk of acute myocardial infarction: matched case-control study. CMAJ Canadian Medical Association Journal 2010;182:1617-23.
- Dao CN, Kamimoto L, Nowell M, et al. Adult hospitalizations for laboratory-positive influenza during the 2005–2006 through 2007–2008 seasons in the United States. Journal of Infectious Diseases 2010;202:881-8.
- Pérez-Padilla R, Fernández R, García-Sancho C, et al. Pandemic (H1N1) 2009 virus and Down syndrome patients. Emerging Infectious Diseases 2010;16:1312-4.
- Ciszewski A. Why young healthy adults should become a target group for the influenza vaccination: a cardiologist's point of view [letter]. Vaccine 2008;26:4411-2.
- Louie JK, Acosta M, Samuel MC, et al. A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clinical Infectious Diseases 2011;52:301-12.
- González-Candelas F, Astray J, Alonso J, et al. Sociodemographic factors and clinical conditions associated to hospitalization in influenza A (H1N1) 2009 virus infected patients in Spain, 2009–2010. PLoS ONE 2012;7(3):e33139. doi:10.1371/journal.pone.0033139.
- Van Kerkhove MD, Vandemaele KA, Shinde V, et al. Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis. PLoS Medicine 2011;8:e1001053. doi:10.1371/journal.pmed.
- Phung DT, Wang Z, Rutherford S, Huang C, Chu C. Body mass index and risk of pneumonia: a systematic review and meta-analysis. Obesity Reviews 2013;14:839-57.
- Morgan OW, Bramley A, Fowlkes A, et al. Morbid obesity as a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1) disease. PLoS ONE 2010;5(3):e9694. doi:10.1371/journal.pone.0009694.
- Kwong JC, Campitelli MA, Rosella LC. Obesity and respiratory hospitalizations during influenza seasons in Ontario, Canada: a cohort study. Clinical Infectious Diseases 2011;53:413-21.
- Kok J, Blyth CC, Foo H, et al. Viral pneumonitis is increased in obese patients during the first wave of pandemic A(H1N1) 2009 virus. PLoS ONE 2013;8(2):e55631. doi:10.1371/journal.pone.0055631.
- Dixon GA, Moore HC, Kelly H, et al. Lessons from the first year of the WAIVE study investigating the protective effect of influenza vaccine against laboratory-confirmed influenza in hospitalised children aged 6–59 months. Influenza and Other Respiratory Viruses 2010;4:231-4.
- Poole P, Chacko EE, Wood-Baker R, Cates CJ. Influenza vaccine for patients with chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2006;(1):CD002733. doi:10.1002/14651858.CD002733.pub2.
- Schembri S, Morant S, Winter JH, MacDonald TM. Influenza but not pneumococcal vaccination protects against all-cause mortality in patients with COPD. Thorax 2009;64:567-72.
- Fritz S, Mossdorf E, Durovic B, et al. Virosomal influenza-vaccine induced immunity in HIV-infected individuals with high versus low CD4+ T-cell counts: clues towards a rational vaccination strategy. AIDS 2010;24:2287-9.
- Haller W, Buttery J, Laurie K, et al. Immune response to pandemic H1N1 2009 influenza A vaccination in pediatric liver transplant recipients. Liver Transplantation 2011;17:914-20.
- Zhang PJ, Cao B, Li XL, et al. Risk factors for adult death due to 2009 pandemic influenza A (H1N1) virus infection: a 2151 severe and critical cases analysis. Chinese Medical Journal 2013;126:2222-8.
- Allard R, Leclerc P, Tremblay C, Tannenbaum TN. Diabetes and the severity of pandemic influenza A (H1N1) infection. Diabetes Care 2010;33:1491-3.
- Sullivan-Bolyai JZ, Corey L. Epidemiology of Reye syndrome. Epidemiologic Reviews 1981;3:1-26.
- Glasgow JF. Reye's syndrome: the case for a causal link with aspirin. Drug Safety 2006;29:1111-21.
- Coffin SE, Zaoutis TE, Rosenquist AB, et al. Incidence, complications, and risk factors for prolonged stay in children hospitalized with community-acquired influenza. Pediatrics 2007;119:740-8.
- Ampofo K, Gesteland PH, Bender J, et al. Epidemiology, complications, and cost of hospitalization in children with laboratory-confirmed influenza infection. Pediatrics 2006;118:2409-17.
- Savulescu C, Valenciano M, de Mateo S, Larrauri A, cycEVA Study Team. Estimating the influenza vaccine effectiveness in elderly on a yearly basis using the Spanish influenza surveillance network – pilot case-control studies using different control groups, 2008–2009 season, Spain. Vaccine 2010;28:2903-7.
- World Health Organization (WHO), Western Pacific Region. WHO interim recommendations for the protection of persons involved in the mass slaughter of animals potentially infected with highly pathogenic avian influenza viruses. 26 January 2004. Available at: (www.wpro.who.int/emerging_diseases/documents/WHO_interim_recommendation_26012004/en/index.html) (accessed July 2011).
- Ma W, Kahn RE, Richt JA. The pig as a mixing vessel for influenza viruses: human and veterinary implications. Journal of Molecular and Genetic Medicine 2009;3:158-66.
- Nichol KL, D'Heilly SJ, Greenberg ME, Ehlinger E. Burden of influenza-like illness and effectiveness of influenza vaccination among working adults aged 50–64 years. Clinical Infectious Diseases 2009;48:292-8.
- Marti F, Steffen R, Mutsch M. Influenza vaccine: a travelers' vaccine? Expert Review of Vaccines 2008;7:679-87.
- Moro PL, Broder K, Zheteyeva Y, et al. Adverse events in pregnant women following administration of trivalent inactivated influenza vaccine and live attenuated influenza vaccine in the Vaccine Adverse Event Reporting System, 1990–2009. American Journal of Obstetrics and Gynecology 2011;204:146.e1-7.
- Munoz FM, Greisinger AJ, Wehmanen OA, et al. Safety of influenza vaccination during pregnancy. American Journal of Obstetrics and Gynecology 2005;192:1098-106.
- Pool V, Iskander J. Safety of influenza vaccination during pregnancy (letter). American Journal of Obstetrics and Gynecology 2006;194:1200.
- Tamma PD, Ault KA, del Rio C, et al. Safety of influenza vaccination during pregnancy. American Journal of Obstetrics and Gynecology 2009;201:547-52.
- Greenhawt MJ, Li JT, Bernstein DI, et al. Administering influenza vaccine to egg allergic recipients: a focused practice parameter update. Annals of Allergy, Asthma and Immunology 2011;106:11-6.
- Mullins RJ, Gold MS. Influenza vaccination of the egg-allergic individual [letter]. Medical Journal of Australia 2011;195:52-3.
- Australasian Society of Clinical Immunology and Allergy (ASCIA). Guidelines for medical practitioners: Influenza vaccination of the egg-allergic individual. 2010. Available at: (www.allergy.org.au/health-professionals/papers/influenza-vaccination-of-the-egg-allergic-individual) (accessed July 2011).
- Erlewyn-Lajeunesse M, Brathwaite N, Lucas JS, Warner JO. Recommendations for the administration of influenza vaccine in children allergic to egg. BMJ 2009;339:912-5.
- Kelso JM. Administration of influenza vaccines to patients with egg allergy: update for the 2010–2011 season (letter). Journal of Allergy and Clinical Immunology 2010;126:1302-4.
- Burwen DR, Ball R, Bryan WW, et al. Evaluation of Guillain-Barré Syndrome among recipients of influenza vaccine in 2000 and 2001. American Journal of Preventive Medicine 2010;39:296-304.
- Tse A, Tseng HF, Greene SK, Vellozzi C, Lee GM. Signal identification and evaluation for risk of febrile seizures in children following trivalent inactivated influenza vaccine in the Vaccine Safety Datalink Project, 2010–2011. Vaccine 2012;30:2024-31.
- Kawai AT, Martin D, Kulldorff M, et al. Febrile seizures after 2010–2011 trivalent inactivated influenza vaccine. Pediatrics 2015;136:e848-55.
- Kelly H, Carcione D, Dowse G, Effler P. Quantifying benefits and risks of vaccinating Australian children aged six months to four years with trivalent inactivated seasonal influenza vaccine in 2010. Eurosurveillance 2010;15(37):pii=19661.
- Mahajan D, Roomiani I, Gold MS, et al. Annual report: surveillance of adverse events following immunisation in Australia, 2009. Communicable Diseases Intelligence 2010;34:259-76.
- Mahajan D, Menzies R, Cook J, Macartney K, McIntyre P. Supplementary report: surveillance of adverse events following immunisation among children aged less than 7 years in Australia, 1 January to 30 June 2010. Communicable Diseases Intelligence 2011;35:21-8.
- Armstrong PK, Dowse GK, Effler PV, et al. Epidemiological study of severe febrile reactions in young children in Western Australia caused by a 2010 trivalent inactivated influenza vaccine. BMJ Open 2011;1:e000016. doi:10.1136/bmjopen-2010-000016.
- Nelson KE. Invited commentary: influenza vaccine and Guillain-Barré syndrome – is there a risk? American Journal of Epidemiology 2012;175:1129-32.
- Nohynek H, Jokinen J, Partinen M, et al. AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland. PLoS ONE 2012;7(3):e33536. doi:10.1371/journal.pone.0033536.
- Dauvilliers Y, Montplaisir J, Cochen V, et al. Post-H1N1 narcolepsy-cataplexy [letter]. Sleep 2010;33:1428-30.
- Communicable Diseases Network Australia (CDNA). Influenza infection: CDNA national guidelines for public health units. 2011. Available at: (www.health.gov.au/cdnasongs) (accessed July 2012).