Written by Dr Tom Barrett, Senior Medical Officer, National Immunisation Office
Influenza is a very common acute viral respiratory illness which affects all age groups. The virus is seen all year round but peaks every winter. The degree of influenza infection is unpredictable, however, each year in Ireland influenza is responsible for between 200 and 500 deaths and as many as 1,000 during a particularly severe season (2008/2009).
As we head into autumn the 2022/2023 influenza season presents a significant challenge to the delivery of healthcare services both in primary care and in hospitals, especially as there may also be a resurgence of cases of COVID-19.
During the 2020-2021 flu season, the first flu season of the pandemic, influenza cases were not reported in Ireland because the public health measures recommended to prevent COVID-19 infection were very successful in preventing influenza virus transmission. In the 2021-2022 flu season, though influenza cases numbers increased, they remained far below pre-pandemic levels because of ongoing COVID-19 preventative measures. However, throughout the 2022/2023 influenza season there is likely to be a limited recent community natural immunity to influenza, especially for children born since 2020.
In this year’s southern hemisphere flu season, Australia reported influenza–like-illness notifications that peaked at the beginning of the influenza season and the weekly number of notifications has exceeded the 5 year average. During this influenza season in Australia, the groups with the highest rates of disease are among children aged 5-9 years, followed by children aged under 5 years, and adolescents.
Influenza in children
Children are among the most susceptible to influenza infection. It is estimated that 20-30% of children develop influenza during each influenza season compared to 5 to 10% of adults. Children, because they have limited pre-existing immunity, are primary vectors of influenza transmission in the community and shed the virus at higher viral titres. Children transmit the influenza virus for a longer period than adults; they can transmit the influenza virus for 10 or more days, compared to 6 days in adults, therefore increasing spread of the disease and contributing significantly to influenza outbreaks.
Influenza vaccination of young children can not only protect against severe illness in children but may also assist in reducing influenza transmission to other vulnerable populations, such as those aged 65 years or older who due to immunosenescence develop less immunity after vaccination.
Approximately 10% of children under 15 attend their GP with influenza in an average influenza season. Influenza is an important cause of pneumonia, bronchitis, otitis media, croup and bronchiolitis in children. Incidence rates are highest in the younger age groups leading to high rates of excess GP and outpatient visits, hospital admissions and medicines prescriptions, increasing pressure on the healthcare system.
In Ireland during the 2018/2019 influenza season, 1245 children were hospitalised with influenza. Children aged less than 5 years had the second highest hospitalisation rates for influenza after those aged 65 years and older.
Between the 2009/2010 and 2018/2019 influenza seasons:
4750 children aged 0-14 years have required hospitalisation as a result of influenza.
Influenza vaccination for children in Ireland
For the 2022/2023 influenza season the Department of Health, will continue to provide funding to the HSE to offer Quadrivalent Live Attenuated Influenza (LAIV) vaccine free to all children aged 2 to 17 years inclusive. This vaccine was introduced during the 2020/2021 influenza season, however uptake of the LAIV vaccine remains very low. For 2021/2022 Flu season vaccine uptake in children aged 2 to 17 was 16.6%. Therefore it is important to encourage up take of the LAIV vaccine.
The aim of the childhood influenza programme is to reduce:
• morbidity and mortality from influenza in children
• transmission of influenza to the elderly and persons in risk groups
• the number of hospital admissions
• transmission to health care workers in families with children
• absenteeism of children from school and their parents from work
Influenza vaccination for children in other countries
Nine European countries, US, Canada and Australia recommend influenza vaccine for children. The UK offer LAIV to children. Finland, US and Canada offer LAIV or QIV to children.
In the US, LAIV has been recommended since 2004. LAIV has been authorised for use in Canada since 2011.
In 2013, the UK introduced trivalent LAIV for 2 and 3 year olds with pilot programmes for primary school children. Quadrivalent LAIV was introduced during the 2014/2015 influenza season. The programme has extended year on year to include all children from 2 up to 11 years.
In Finland, annual inactivated influenza vaccine was recommended for children aged 6–35 months in 2007. LAIV was introduced in 2015 to enhance vaccine uptake. Since then, all 2 and 3 year old children have been eligible for vaccination with either LAIV or inactivated influenza vaccine. The programme is now extended to include all children to 6 years of age.
Live Attenuated Influenza vaccine (LAIV) for 2022/2023 influenza season
Quadrivalent Live Attenuated Influenza vaccine (LAIV) Fluenz Tetra is manufactured by Astra Zeneca. It is administered intra-nasally.
The vaccine contains the following four vaccine virus strains as recommended by the World Health Organization (WHO):
Egg-based influenza vaccines
• an A/Victoria/2570/2019 (H1N1) pdm09-like virus;
• an A/Darwin/9/2021 (H3N2)-like virus;
• a B/Austria/1359417/2021 (B/ Victoria lineage)-like virus; and
• a B/Phuket/3073/2013 (B/ Yamagata lineage)-like virus.
LAIV may contain residues of egg proteins (ovalbumin), with a maximum amount of less than 0.024 micrograms and gentamicin. LAIV does not contain any adjuvants, or preservatives.
Since LAIV contains live attenuated viruses, it mimics natural infection with wild-type viruses, with the development of both mucosal and systemic immunity. Local mucosal antibodies protect the upper respiratory tract and may be more important for protection than serum antibodies, inducing more durable immune memory and so providing better longterm protection to children than inactivated influenza vaccines such as QIV.
In some studies, LAIV has been shown to be more effective in children compared with inactivated influenza vaccines. In addition, LAIV may offer some protection against strains not contained in the vaccine, as well as virus strains that have undergone antigenic drift.
A recent meta-analysis of LAIV suggested an efficacy against confirmed disease of 83% (95% confidence interval 69-91%).
The UK pilot primary school programme introducing LAIV was evaluated in 2014/2015 and showed:
• 94% reduction in primary school age children GP influenza-like consultations
• 74% reduction primary school age Emergency Department attendances with respiratory complaints
• 93% reduction in primary school age confirmed influenza hospitalisations
• 59% reduction in adults GP influenza-like illness consultations.
LAIV dose and administration
Each LAIV vaccine comes as a prefilled nasal applicator and each applicator contains 0.2ml nasal suspension. The vaccine is administered by the nasal route. One dose of LAIV is 0.2ml administered in divided doses into each nostril i.e. 0.1ml in each nostril.
If the child’s nose drips after vaccination, the vaccine dose does not need to be repeated. The vaccine is immediately absorbed after administration. For the same reason, the vaccine does not need to be repeated if the child sneezes or blows their nose after vaccination.
LAIV can be given together with or at any time before or after the administration of any other live attenuated (e.g. MMR) or inactivated vaccines including COVID-19 vaccines.
In Ireland the National Immunisation Advisory Committee (NIAC) has recommended healthy children require one dose of LAIV. However children in a medically at risk group aged 2 to 8 years inclusive are recommended 2 doses of LAIV if they have never had any influenza vaccine before. (Table 1). The two doses should given 4 weeks apart.
The following are NOT contraindications
• Asymptomatic HIV infection
• Children receiving
◦ topical or inhaled corticosteroids
◦ low dose systemic corticosteroids
◦ replacement therapy corticosteroids (e.g. adrenal insufficiency).
Contraindications to LAIV:
• Anaphylaxis following a previous dose of influenza vaccine or any of its constituents 1 (other than ovalbumin – see Precautions)
• Acute exacerbation of symptoms increased wheezing and/or additional bronchodilator treatment in the last 72 hours
• Seek specialist advice if on regular oral steroids or previous ICU admission
• Significant immunosuppression due to disease or treatment
• Children who live with severely immunosuppressed persons (i.e. post haematopoietic stem cell transplant)
• Concomitant use of aspirin/ salicylates
• Influenza antiviral medication within the previous 48 hours
• Those with severe neutropoenia (absolute neutrophil count <0.5 × 109/L) to avoid an acute vaccine related febrile episode
• Those on combination checkpoint inhibitors (e.g. ipilumumab plus nivolumab) because of a potential association with immune related adverse reactions.
Defer until recovered from an acute severe febrile illness.
As LAIV has an ovalbumin content <0.1 micrograms per dose, it can be given to children with confirmed egg anaphylaxis or egg allergy in a primary care setting except children who have required ICU admission to hospital for a previous severe anaphylaxis to egg who should be given LAIV in hospital.
Aspirin/salicylates should not be be used for 4 weeks after vaccination unless medically indicated, as Reye’s syndrome has been reported following the use of salicylates during wild-type influenza infection.
Avoid influenza antiviral medication for 2 weeks post vaccination.
Children aged 2 to 17 years for whom LAIV is contraindicated should be offered QIV vaccine (provided there are no contraindications to QIV).
LAIV side effects
Very common or common (More than 1 in 10 to 1 in 100): Nasal congestion/rhinorrhoea, decreased appetite, malaise, fever, headache, and myalgia. In post marketing surveillance, overall rates of fever were similar to the rates following other childhood vaccines and were generally mild and of short duration.
Very rare (less than 1 in 10,000): Immediate allergic reactions.
Very rare cases of Guillain-Barré syndrome (GBS) have been observed in the post-marketing setting following influenza vaccination. The risk of GBS following influenza infection is significantly greater than that following influenza vaccination.
Can LAIV vaccine cause virus shedding?
The attenuated vaccine viruses in LAIV are cold adapted. They can replicate at the lower temperatures found in the nose but cannot replicate efficiently at body temperature elsewhere in the body.
Vaccinated children can shed the attenuated virus for a few days after vaccination but the virus that is shed cannot cause infection. Peak incidence of shedding occurred 2-3 days post-vaccination in Fluenz clinical studies. Therefore the weakened viruses do not cause flu infection in others, or in the person vaccinated.
Increasing uptake of influenza vaccine
Influenza remains a major public health issue and never more than after more than two years of the COVID-19 pandemic. Influenza vaccination is the best intervention available to prevent
influenza. Extending the influenza vaccination programme to all children aged 2-17 years aims to protect children and reduce transmission to others, thereby reducing the burden on our health services at this crucial time.
Research, both in Ireland and elsewhere, has consistently shown that doctors and other healthcare professionals are the most trusted sources of information on vaccination. A recommendation by a trusted healthcare professional for their patients who are at an increased risk of influenza-related complications to attend their GP or pharmacist for vaccination has been shown to increase vaccine uptake.
Medical conditions that are associated with an increased risk of influenza-related complications:
• Those with chronic illness, e.g. chronic heart disease (including acute coronary syndrome), chronic liver disease, chronic neurological disease (where the neurological condition compromises clearance of respiratory secretions), chronic renal failure, chronic respiratory disease (including chronic obstructive pulmonary disease, cystic fibrosis, moderate or severe asthma, and bronchopulmonary dysplasia), diabetes mellitus, or haemoglobinopathies
• Those with immunosuppression due to disease or treatment, including asplenia or hyposplenism, and all cancer patients
• Those with any condition that can compromise respiratory function (e.g. spinal cord injury, seizure disorder, or other neuromuscular disorder,) especially those attending special schools/ day centres
• Children and adults with Down syndrome
• Children with moderate to severe neurodevelopmental disorders such as cerebral palsy and intellectual disability
• Children on long-term aspirin therapy (because of the risk of Reye syndrome)
• Those with morbid obesity (Body mass index >40)
• Residents of nursing homes, old people’s homes, and other long stay facilities where rapid spread is likely to follow introduction of infection
COVID-19 vaccinations: National Immunisation Advisory Committee (NIAC) new COVID-19 vaccines recommendations (July 2022)
NIAC strongly recommends those who to date are unvaccinated or are incompletely vaccinated should complete a primary COVID-19 vaccination course and booster vaccination to protect themselves against COVID-19 infection.
Using currently available mRNA COVID-19 vaccines, NIAC advise the following groups are recommended COVID-19 booster vaccination 4 months after their last COVID-19 vaccination (a 3 months interval may be used in exceptional circumstances):
1. A third mRNA COVID-19 booster vaccine is recommended for
• those aged 65 years and older (5 th COVID-19 vaccine)
• those aged 12–64 years with immunocompromise associated with a sub optimal response to vaccines at the time of their primary or booster vaccination (6 th COVID-19 vaccine).
When practicable, these booster doses of COVID-19 vaccine and influenza vaccine can be given at one visit.
2. A second mRNA COVID-19 booster vaccine is now recommended for
• those aged 50-64 years (4th COVID-19 vaccine).
• those aged 12–49 years who have underlying medical conditions associated with a higher risk of severe COVID-19 e.g. DM (4th COVID-19 vaccine)
• those aged 12–49 years who have underlying medical conditions who are residents of long term care facilities (4th COVID-19 vaccine).
3. A second mRNA COVID-19 booster vaccine is recommended for
• healthcare workers, and when practicable, should be given at the same time as seasonal influenza vaccine (4 th COVID-19 vaccine).
4. To enhance maternal protection and provide optimal benefit to the infant, an additional mRNA COVID-19 booster vaccine is recommended in pregnancy at 16 weeks gestation or later for those who have not received a booster vaccine in the current pregnancy (4 th COVID-19 vaccine). This timing is to enhance protection to the mother and the infant.
New recommendations for children aged 5 to 11 years with immunocompromise
5. A first mRNA COVID-19 booster vaccine is now recommended for those aged 5–11 years with immunocompromise associated with a sub optimal response to vaccines at the time of their primary or additional vaccination (3 rd COVID-19 vaccine).
https://www.hse.ie/eng/health/ immunisation/hcpinfo/guidelines/ covid19.pdf mRNA booster vaccines should be given as follows:
• aged 30 years and older: Comirnaty ® (0.3ml/30 mcg) or Spikevax ® (0.25ml/50 mcg)
• aged 12-29 years: Comirnaty ® (0.3ml/30 mcg)
• aged 5-11 years: Comirnaty ® (0.2ml/10mcg)
Nuvaxovid ® Novavax vaccine is recommended if there is a contraindication to an mRNA vaccine. Jcovden ® Jansen vaccine is recommended only if there is a contraindication to both Novavax and the mRNA vaccines.
Implementation of these new NIAC COVID-19 vaccine recommendations has now commenced.
References available from National Immunisation Office
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