11. Influenza

Influenza A and B viruses undergo frequent small changes (mutations) in their segmented RNA genome over time. The mutations can occur in the coding regions responsible for H and N surface antigens. This ‘antigenic drift’ leads to the emergence of new antigenic variants or virus strains.

These new strains are described by the geographic site of isolation, laboratory number and year of isolation; for example, A/Hong Kong/4801/2014 (H3N2). Because of this ongoing antigenic drift, WHO reviews seasonal influenza virus vaccine formulations bi-annually.

New influenza A virus subtypes emerge periodically that have caused pandemics in humans. The new virus subtype has novel H and N surface antigens result from the mixing of genomic segments of two or more influenza A viruses. This is known as ‘antigenic shift’. Other possible mechanisms for the emergence of new influenza viruses are through the adaptation of avian influenza viruses to infect humans and the re-assortment of the genomic segments of multiple viruses (ie, human, avian and pig influenza viruses).

Influenza is an important cause of disease worldwide. Annual epidemics are estimated to result in about 3 to 5 million cases of severe illness, and about 290,000 to 650,000 respiratory deaths globally.[17, 18] For example, it was estimated globally that 11.5 percent of lower respiratory tract infections (LRTI), 5.6 percent of LRTI deaths and 9.5 million LRTI hospitalisations were attributable to influenza in 2017.[19]

In temperate climates, seasonal epidemics occur mainly during winter, while in tropical regions, influenza occurs throughout the year causing outbreaks more irregularly.[17]

From time to time, pandemics occur when a new virus arises and spreads globally (see section 11.3.3). The last influenza pandemic was caused by the A(H1N1)pdm09 virus. More than 214 countries and overseas territories reported laboratory-confirmed influenza, including over 18,449 deaths.[20] Many more deaths were found to associated with the pandemic due to respiratory and cardiovascular complications.[21]

New Zealand experiences the typical temperate climate epidemiology of influenza, with the peak incidence occurring during the winter months, however, influenza activity occurs throughout the year.

The impact of influenza in New Zealand is substantial in terms of general practice consultations, hospitalisations and deaths. The highest burden of disease is in the very young, the elderly, pregnant women, those with co-morbid conditions, people from low-income groups, and Pacific and Māori ethnic groups.

Influenza surveillance

The New Zealand influenza surveillance system compiles information from a variety of sources, including:

• national sentinel general practice-based influenza-like illness surveillance (part of the WHO’s Global Influenza Programme)
• year-round laboratory-based surveillance by the regional virus diagnostic laboratories
• hospital-based severe acute respiratory infection surveillance in Auckland and Counties Manukau districts
• data from Healthline, HealthStat, publicly funded hospital discharges, and the AIR.

Influenza prevalence and circulating strains are monitored through general practice surveillance for influenza-like illness (ILI); hospitalisations are monitored for severe acute respiratory infection (SARI) admissions; and severity is determined by the proportion of hospitalisations requiring intensive care unit (ICU) admission.[22]

For example, during the 2019 season the levels of influenza-like illness and the overall impact were low and generally just above seasonal baseline.[23] However, SARI hospitalisation rates increased earlier than in previous years and, during the winter, a higher than usual proportion of viral respiratory illnesses were due to influenza. A(H3N2) and B/Victoria strains were co-circulating. Seriousness was similar to other A(H3N2) predominant years. Influenza A viruses were detected most frequently in hospitalised patients whereas influenza B was detected more in the community. In contrast, in 2018 the predominant strain was A(H1N1)pdm09 strain which is associated with high severity in those aged younger than 65 years.[24] Over one-half of those admitted to ICUs with influenza-associated SARI in 2018 did not report any pre-existing medical risk factors, consistent with being younger.[24]

In 2020 and 2021, due to COVID-19 pandemic restrictions, transmission of influenza in the community was interrupted: no cases with ILI symptoms and 0.6 percent of hospitalised SARI cases had detectable influenza virus in 2020 and no community influenza cases were detected during 2021.[25, 26] In 2022, there was very high incidence of influenza-associated acute respiratory infections in the community and a high influenza-associated hospitalisation burden, but the seriousness was low (as measured by the ratio of SARI-ICU to SARI case admissions).(SHIVERS data). A spike in influenza was seen earlier than usual, coming in mid-June, with a very high rate of influenza-positive SARI hospitalisation activity (7.89 per 100,000 population).[27]

For detailed information, including influenza surveillance and influenza reports, see the ESR website.

Influenza immunisation uptake

Around 1.3 million doses of influenza vaccine were distributed to 25 November 2022.[25] This equated to around one third of the whole population (approximately 251 doses per 1,000 population).[25] According to Ministry of Health data, based on reporting from funding claims, publicly funded influenza vaccine uptake for individuals aged 65 years and older was around 71.2 percent in 2022; this is likely to be an underestimate of the coverage.

The natural ecology of influenza type A viruses is among wild aquatic avian species, and from time to time, these viruses spill over into other species, including humans. These avian influenza virus infections are usually severe and associated with a high mortality; however, they are rarely transmitted from human to human. In the past, avian viruses have become transmissible either through adaptation or the acquisition of swine or human genomic material, and when natural immunity has been lacking in the population, have resulted in a pandemic with global spread. There have been four influenza pandemics recorded since 1918.

Pandemics have the potential to result in large numbers of severe infections, but the degree of severity is hard to predict and will depend upon many factors, including whether there is any previous community immunity. The most severe recorded influenza pandemic was the ‘Spanish flu’ A(H1N1) pandemic of 1918–1920, which caused an estimated 20–50 million deaths worldwide. The most recent pandemic was the 2009 A(H1N1)pdm09 strain. It was estimated that 18 percent (800,000) of the New Zealand population were infected with the virus during the first wave, including one in every three children.[28] Risk factors for severe outcomes included obesity, pregnancy,[29] diabetes mellitus and Pacific or Māori ethnicity.[28] This strain is now established as a circulating seasonal influenza strain.

Globally, in the first 16 months of the 2009 H1N1 influenza pandemic, 18,500 deaths were attributed to laboratory-confirmed influenza. When investigated further, it was estimated that over 201,000 respiratory deaths and an additional 83,300 cardiovascular deaths were associated with the pandemic – producing a rate 15 times higher than the laboratory-confirmed deaths. Of these deaths, 80 percent were younger than 65 years of age.[21]

Monitoring, surveillance and response for new pandemic strains are in place. See section 11.8.3.

Funded vaccines

International data

The efficacy (prevention of illness among vaccinated individuals in controlled trials) and effectiveness (prevention of illness in vaccinated populations) of influenza vaccine depends on several factors. The age and immune competence of the vaccine recipient are important factors, as well as the match between the virus strains in the vaccine and those in circulation each year. Mismatches can evolve during a season or due to mutations occurring during vaccine manufacture (egg adaptation).[45] Previous vaccination history has been suggested to reduce the vaccine effectiveness in some cases; possibly more so when the previous vaccination was mismatched with the circulating strains at the time.[47] More recently, prior-season vaccination history has not been associated with reduced vaccine effectiveness in children or adults, and findings support annual revaccination.[45, 48, 49, 50, 51] With increasing complexity, this continues to be researched.

Prior to 2020, two influenza B strains have frequently co-circulated, and due to the challenges involved in predicting which B strains will circulate in the upcoming season, mismatches between the B strain selected for TIVs and the circulating B strains have occurred in up to one-half of influenza seasons. The capacity of QIVs (containing two B influenza strains) to provide broader immune responses against B strains and cross-protection during B-mismatched seasons was expected to prevent more influenza cases, hospitalisations and deaths than TIVs.[1] The composition of future vaccines will consider the status of influenza B virology.

Data for vaccine efficacy and effectiveness of TIVs is summarised in Table 11.1.

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017 (2nd edition).

Store in the dark at +2°C to +8°C. Do not freeze.

The funded quadrivalent influenza vaccine should be administered by intramuscular, or subcutaneous injection, if indicated (see section 2.2.3). The contents of the syringe must be shaken thoroughly before use.

Individuals aged 6 months and older 

Individuals aged 6 months and older receive a single 0.5 mL intramuscular dose of a QIV vaccine.

Children aged under 9 years who have not previously received influenza vaccine require two doses of vaccine four weeks apart to produce a satisfactory immune response. 

The influenza vaccine is strongly recommended, and funded, for people who will be pregnant while the vaccine is available. Pregnant women can receive influenza vaccination at any stage of pregnancy to protect themselves, their fetus and their newborn for each season they are pregnant. When pregnancy spans two influenza seasons, two vaccinations (one from each season) are recommended to protect against all the predicted strains.

Influenza vaccine is safe to administer during any stage of pregnancy or while lactating. There is no evidence that influenza vaccine prepared from inactivated split virus or subunits causes damage to the fetus or neonate[109] and there is some evidence it may be protective against stillbirth.[12]

Pregnant women are at greater risk from complications associated with influenza illness.[8, 11] When pregnancy is superimposed on high-risk conditions such as asthma or diabetes, influenza-related morbidity is three to four times greater than in non‑pregnant women with similar high-risk conditions.

Globally, about one-quarter of influenza-associated hospital admissions and over one-third of in-hospital deaths are in infants under 6 months.[110] Because there is no registered or effective vaccine for children aged under 6 months, vaccination during pregnancy is highly recommended to improve maternal-fetal passive antibody transfer.[11] Influenza vaccination of pregnant women has been shown to significantly decrease influenza in their newborn babies.[41, 55, 74, 76] Breastfeeding is also recommended, to deliver passive immunity to the infant.[41] (See also section 4.1.2.)

Influenza vaccine is recommended and funded for children aged 6 months and over with certain chronic illnesses (see Table ‎11.2) and for children aged under 4 years a history of significant respiratory disease (including a history of measles). Children with the following conditions should be prioritised to receive influenza vaccine due to their increased risk, including:

• all asthmatics on regular preventive therapy
• other children with chronic respiratory disorders (eg, cystic fibrosis, non-cystic fibrosis bronchiectasis and chronic lung disease of infancy).

Special considerations apply to children, as follows (see also section 4.3):

• Immunisation is occasionally associated with fever between 6 and 24 hours after administration. In children aged 6–24 months with significant chronic medical conditions fever may cause an exacerbation of the underlying condition.
• Children receiving cancer chemotherapy may have a weaker response to influenza vaccine. Vaccination is recommended three to four weeks after the preceding dose of chemotherapy, when the neutrophil and lymphocyte counts are each ≥1.0 × 109/L. Children who are no longer receiving chemotherapy can be expected to show seroconversion to vaccine three months after the cessation of chemotherapy.

Adults aged 65 years and older

In adults aged 65 years and older, influenza vaccine has been shown to be effective against non-fatal and fatal influenza complications, influenza-like illness and laboratory-confirmed influenza (see Table 11.1). Influenza vaccination protects against loss of independence due to increasing levels of frailty associated with hospitalisation.[9, 90, 111]

Adults with underlying medical conditions

Influenza has been associated with increased morbidity and mortality in adults with underlying medical conditions (see Table 11.2). Risk increases with multiple conditions. These also include those with serious mental health conditions and accessing mental health or addiction services. (See also Pregnancy and breastfeeding). 

Generally, influenza vaccination is recommended annually for all individuals aged from 6 months. It is particularly important for the groups listed in Table 11.2.

There are certain conditions that individually do not render a person eligible for funded influenza vaccine, but when combined, significantly increase the risk of influenza complications (this is described as ‘risk stacking’). Such risks are further increased by smoking, alcohol dependency and obesity.

To optimise the protection of high-risk infants and toddlers, including those aged under 6 months, all household members and close contacts are recommended to receive influenza vaccine (not funded between ages 13–64 years, unless eligibility criteria are met). Influenza vaccine is recommended and funded to be received at any stage of pregnancy, for those aged 65 years or over and for children aged 6 months to 12 years. 

Adults of Māori or Pacific ethnicity aged 55 years and over

Māori and Pacific people are at greater risk of developing underlying health conditions, such as cardiovascular disease and chronic respiratory disease, at a younger age than other ethnicities,[112] which increases the risk of influenza severity and complications. Factors contributing to this risk an increased risk of respiratory virus transmission can included overcrowding due to lack of appropriate multigenerational housing and close-knit communities.  

Healthy individuals of any age from 6 months and older

Healthy individuals are encouraged to have an influenza vaccine, annually, especially if they are in close contact with individuals at high risk of complications. Employers are encouraged to provide influenza vaccine to avoid illness in their employees, especially those engaged in health care and other essential community services (see Table 4.9). Immunising healthy individuals has been shown to be cost-effective.

To optimise the protection of high-risk infants and toddlers, including those aged under 6 months (see Table 11.2), all household members and close contacts are recommended to receive influenza vaccine (not funded for those aged under 65 years, unless eligibility criteria are met). Influenza vaccine is recommended and funded to be received at any stage of pregnancy, for those aged 65 years or over.

Health care workers

Health New Zealand | Te Whatu Ora strongly recommends, and expects, that all health care workers will receive annual influenza vaccination for their own protection and the protection of those in their care.

Travellers

Influenza vaccine is recommended for people travelling outside New Zealand, especially those who are in the at-risk groups who have not received vaccine during the previous autumn, depending on the season and their destination. In tropical countries, influenza activity can occur throughout the year but is more likely during the winter (wet) and summer seasons, while in the northern hemisphere activity is commonest between the months of December and March. Outbreaks of influenza among organised tourist groups (eg, on cruise ships) can occur throughout the year.

Influenza vaccine should not be administered to people with a history of an anaphylactic reaction to a prior dose of influenza vaccine or to a vaccine component. Egg allergy, including anaphylaxis, is not a contraindication or precaution: see section 11.6.3.

History of Guillain–Barré syndrome

Influenza vaccination has been suggested to increase the risk of GBS. However, no association was found between administering 16 million doses of influenza vaccine and GBS in adults aged from 65 years in the US.[113] Any potential risk increase would be less than one additional case per million doses administered.[4, 42, 114] The risk of developing GBS is increased following influenza infection, and the magnitude of the risk is several times greater than that possibly occurring following influenza vaccination.[4, 114, 115]

New Zealand hospitalisations for GBS showed no increase during the 1990s despite the marked increase in vaccine use during this period but apparent year-to-year variation was observed. In particular, the doubling of vaccine use (with the introduction of funded vaccine) in 1997 was not associated with any increase in GBS hospitalisations. No excess risk for GBS following influenza vaccine in children has been documented. No association between influenza vaccines and any other neurological disease has been substantiated.

The risks and benefits of withholding vaccination should be considered on an individual basis, based on the potential morbidity and mortality associated with influenza for that individual, including the potential risk of recurrent GBS following influenza infection.

Co-administration with PCV13

Individuals (or their parents/guardians) who receive both influenza vaccine and 13‑valent pneumococcal conjugate vaccine (PCV13) should be advised of the increased risk of fever following concomitant administration of these vaccines.[106, 107, 116] Separation of the vaccines by two days can be offered, but is not essential (see also section 16.6.2).

Influenza vaccine can be safely administered to people with a history of egg allergy, including anaphylaxis, at general practices, pharmacies or at the workplace.[117]

Reported cases of anaphylaxis after influenza vaccination in egg-allergic individuals all occurred over 30 years ago, at a time when vaccine egg (ovalbumin) content was much higher than it is now. Recent studies have shown that influenza vaccines containing less than 1 µg of ovalbumin do not trigger anaphylaxis in sensitive individuals.[117]

Studies in New Zealand and overseas have found that provider attitudes and provider recommendations are key to improving influenza vaccine uptake. Organised registers for recall and opportunistic immunisation are also likely to be important factors in achieving high uptake.

Every effort should be made during April to immunise all people at risk, particularly those aged 65 years and older, those aged under 65 years (including children) who have certain medical conditions, pregnant women and health care workers, and those of Māori or Pacific ethnicity aged 55 to 64 years. During an influenza outbreak, recommend influenza vaccination to anyone at risk who was not immunised during the current season or to those who have not received an influenza vaccination for more than six months. Availability of an appropriate vaccine is the most pertinent of these factors.

Vaccination of all healthy adults and children from age 6 months is encouraged but not funded. Adult vaccination, especially for those in close contact with high-risk groups, may be funded by employers.

Influenza antiviral drugs can be used to treat or to prevent influenza and can be adjuncts to influenza vaccination. Early use of antivirals, especially within the first 48 hours of illness, can reduce the duration of symptoms and the risk of complications from influenza. They are likely to be most effective against severe influenza and for those with high-risk comorbidities.

It has been shown that when patients with influenza-like illness were treated in primary care with oseltamivir, recovery time was shortened compared with usual care. In older patients and those with comorbidities, in particular, even with longer previous symptom duration (48–72 hours), recovery was likely to be 2–3 days sooner following antiviral treatment than it would have been with than standard care alone.[128] Meta‑analyses of the effectiveness of oseltamivir in treating uncomplicated influenza show shortened duration of symptoms for healthy adults and adolescents of around one day,[129] a 63 percent (95% CI: 19–83) decrease in risk of hospitalisation for any cause and a 44 percent (95% CI: 25–58) decrease in risk of antibiotic prescription use.[130]

For use with severe influenza, observational studies show early treatment can lead to a decreased risk of death.[131, 132] Early treatment upon hospital admission was significantly associated with reduced length of stay (by 19 percent), regardless of time since symptoms onset, compared with later or no treatment initiation. Greater reductions in length of stay were seen for pregnant women and obese patients (by 39 percent and 27 percent, respectively).[133]

Antivirals should be particularly considered for unimmunised or recently immunised contacts who are at high risk of severe disease. When used to limit the size of an institutional outbreak, antiviral drugs are usually given for a period of two weeks after immunisation or until one week after the end of the outbreak. Institutional outbreaks should be notified to the local medical officer of health.[134]

At the time of a pandemic, recommended public health advice, priority groups and the timing of vaccination may be quite different from those during inter-pandemic periods. The New Zealand Influenza Pandemic Plan: A framework for action describes the key phases of a pandemic and the actions and responsibilities within each phase.[135]

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