No 38/39 - 2021

Influenza vaccination and surveillance of influenza in the 2021/2022 season

Statens Serum Institut monitors the occurrence of influenza in Denmark all year round. But during the annual influenza season, defined as the period from week 40 in the autumn to week 20 in the spring, this monitoring is extended by various WHO-recommended epidemiologic and laboratory-based systems, which are described below. The monitoring numbers are updated regularly at the SSI website and described in the newsletter INFLUENZA-NEWS along with the monitoring of a wide range of other respiratory viral infections.

As in previous seasons, the 2021/2022-season brings an offer of free vaccination to special groups at risk of running a serious influenza course and having complications to influenza. These groups include elderly people aged 65 years or more and people who have turned 65 years old before 15 January 2022. However, the vaccination offer is extended until the end of February 2022 for pregnant women in their 2nd or 3rd trimester and for immunosuppressed persons and their household contacts.

Employees in the health and care sectors will again be offered free vaccination, as was the case for the first time in 2020/2021.

Furthermore, as a new initiative in 2021/2022, an offer is introduced of free influenza vaccination for all children aged 2 through 6 years of age. Children who have initiated vaccination before 15 January 2022, but who lack their second vaccination or who have turned seven years old after having received their first vaccination may conclude their vaccination course before 1 March 2022. Vaccination will primarily protect the children in the age group and their families against becoming infected, but will also contribute to slowing down influenza infection in the population in general and thereby serve to avoid disease in vulnerable groups.

Influenza vaccination not only reduces the risk of infection with influenza; it also reduces the risk of developing serious disease, of admission to hospital and of death due to influenza if you fall ill even though you have received vaccination. As last year, influenza vaccination is extra important this year because influenza carries an increased risk for many of the same people who also risk a serious disease course if they become infected with COVID-19. If these people are affected by both diseases concurrently, their disease course may be further aggravated.

In the past ten years, the mean vaccination coverage in Denmark among people aged 65 years or more has only reached approx 50%, but in 2020/2021 a record-high 75% coverage was achieved thanks to a higher than normal number of purchased vaccines and a massive information campaign, including personal e-boks letters to all citizens who have an increased risk because they are 65 years old or more. Thus, for the first time ever, Denmark has met the WHO’s recommendation that at least 75% of the population aged 65 years or more is vaccinated against influenza ahead of the new season, EPI-NEWS 22/21. The objective for 2021/2022 is to achieve an even higher vaccination coverage among the risk groups. Therefore, even more vaccines were bought this year in addition to which comes the introduction of the paediatric vaccination offer.

As last year, the SSI in collaboration with the Danish Health Authority will send a reminder this week to all citizens aged 65 years or more to inform them of free influenza vaccination. Persons who have not received the 23-valent pneumococcal vaccine within the past six years will also be reminded of this vaccine. Furthermore, in week 39, a reminder letter will be sent out to parents to children.

The free influenza vaccination offer starts on 1 October 2021.

The executive order on free influenza vaccination for specific population groups, 2021/2022 (Executive Order no. 1841), published on 22 September 2021.

The offer of free influenza vaccination for children aged 2-6 years is comprised by the executive order on free vaccination against certain diseases, etc. (Executive Order no. 1862), amended 26 September 2021.

Influenza vaccines of the 2021/2022 season

I Denmark, inactivated vaccines are typically used for influenza vaccination. These are the most frequently used influenza vaccines worldwide. The vaccines contain components of the vaccine strains recommended by the WHO. Inactivated influenza vaccines contain the surface proteins from influenza virus that were cultured in chicken eggs and then inactivated. These surface proteins activate the immune system, triggering the creation of antibodies.

In the 2021/2022 influenza season, for the first time ever, a live attenuated influenza vaccine will also be available. This vaccine is used in children aged 2-6 years and is administered as a nasal spray. The dose is delivered as a spray into each nostril.

The WHO recommends that the influenza vaccines used in 2021/2022 have the following antigen contents:

• A/Victoria/2570/2019 (H1N1)pdm09-like virus
• A/Cambodia/e0826360/2020 (H3N2)-like virus
• B/Washington/02/2019-like virus (the Victoria line)
• B/Phuket/3073/2013-like virus (the Yamagata line).

This year, three inactivated influenza vaccines are used in Denmark; all three are 4-valent and their composition is in line with WHO’s recommendations. Two of the vaccines are the same 4-valent standard dose vaccines, InfluvacTetra^® and VaxigripTetra^®. The third 4-valent influenza vaccine, Fluzone^®, is a high-dose vaccine.

The live attenuated influenza vaccine for children is the 4-valent vaccine Fluenz Tetra^®, which contains the same recommended types of type A and B influenza A virus.

The high-dose influenza vaccine has a higher antigen content than the standard influenza vaccines (60 μg in the high-dose influenza vaccine and 15 μg in the standard influenza vaccines). The high-dose vaccine yields a higher level of protective antibodies in elderly persons, who generally have a weaker immune system than younger persons and who therefore have a poorer response to the standard vaccine (i.e. achieve a lower antibody level, and in whom the antibody level drops more rapidly). The high-dose influenza vaccine is approved for use in persons aged 65 years or more. In the 2021-2022 season, the vaccine will be offered in Denmark to persons aged 82 years or more, to persons who turn 82 years old before 15 January 2022 and to persons aged 65 years of age, who live in a nursing home, a private or public assisted living facility, or similar.

The high-dose vaccine may also be used in persons who do not tolerate the other available vaccines, provided they have turned 65 years old.

None of the 4-valent vaccines contain thiomersal or adjuvant. InfluvacTetra^® and VaxigripTetra^® may contain trace amounts of egg/chicken protein, formaldehyde, neomycin or gentamicin. The 4-valent high-dose vaccine may contain trace amounts of egg/chicken protein and formaldehyde, but does not contain neomycin or gentamicin. Therefore, the limited number of persons ≥ 65 years of age who are allergic to gentamicin or neomycin may be offered the Fluzone^® vaccine instead. Unfortunately, this year it has not been possible to secure supply of the inactivated cell-based vaccine that was available for persons with egg allergy in the previous season.

For additional information about influenza vaccines, contraindications, doses, etc., please see the Vaccine Encyclopaedia (Vaccineleksikon).

The influenza vaccines may be given in conjunction with the pneumococcal vaccine offered free of charge for all persons aged 65 years or more and to some other high-risk groups. Also, no minimum interval needs to be observed between administration of an influenza vaccine and a COVID-19 vaccine.

The 4-valent standard dose vaccines (InfluvacTetra^® and VaxigripTetra^®) and the 4-valent high-dose vaccine (Fluzone^®) will be available for delivery in week 39/40, whereas the live attenuated influenza vaccine for children (Fluenz Tetra^®)) will be available for delivery as from week 40.

Who is comprised by the free influenza vaccination offer?

The offer of free influenza vaccination is available from 1 October to 15 January for special person groups residing in Denmark or who are entitled to vaccination services without residing in Denmark.

For pregnant women in their 2nd or 3rd trimester and for immunosuppressed persons and their household contacts, the period is extended until the end of February.

In pursuance of Executive Order on free influenza vaccination to specific population groups 2021/2022 (Executive Order no. 1841), the following persons are entitled to free influenza vaccination:

• Persons who are 65 years old on 15 January 2022
• Early retirement pensioners
• Chronically ill persons who suffer from the following conditions, upon medical assessment:
  o Chronic pulmonary conditions
  o Cardiovascular diseases (barring high blood pressure)
  o Diabetes 1 or 2
  o Congenital or acquired immunodeficiency
  o Patients whose respiration is affected due to muscular weakness
  o Chronic liver or kidney failure
  o Persons with other chronic diseases which, according to the physician’s assessment, pose a serious health risk in conjunction with influenza.
• Persons with other serious diseases that, according to the doctor’s assessment, pose a serious health risk in conjunction with influenza
• Severely obese people (recommended BMI > 35), upon medical assessment.
• Children as from six months of age and adults with other serious diseases that, according to the doctor’s assessment, pose a serious health risk in conjunction with influenza
• Persons in the same household as children at an increased risk of running a serious influenza course, cf. Section 1 No. 5.
• Persons with other serious diseases that, according to the doctor’s assessment, pose a serious health risk in conjunction with influenza.
• All pregnant women in their 2nd or 3rd trimester
• Household contacts to patients with congenital or acquired immune deficiency may, upon medical assessment, be offered vaccination. Household contacts are members of the household and persons with close contact comparable to that of household members.
• Staff in the healthcare and nursing sectors tasked with nursing, care and treatment of citizens who are at special risk of running a serious influenza course, including:
  o Doctors
  o Nurses
  o Chemists
  o Chiropractors
  o Dentists
  o Relaxation therapists
  o Surgical appliance makers (orthoists)
  o Bioanalysts
  o Ergotherapists
  o Physiotherapists
  o Midwives
  o Clinical dietitians
  o Optometrists
  o Radiographers
  o Audiology assistants
  o Pharmaconomists
  o Chiropodists
  o Neurophysiology assistants
  o Dental assistants
  o Dental hygienists
  o Dental technicians
  o Employment counsellors
  o Carers
  o Nursing-home assistants
  o Social and healthcare assistants
  o Social and healthcare aids
  o Psychologists
  o Medical secretaries
  o Health service secretaries
  o Orderlies
  o Paramedics
  o Ambulance therapists
  o Ambulance drivers
• Vaccination is also offered to students, pupils or unskilled workers, etc. who provide services similar to the professions listed above and who provide care, nursing and treatment for citizens who are at an increased risk of running a serious influenza disease course.

Children and influenza vaccination

As described above, the Danish Health Authority has recommended and the Danish Minister of Health has decided that children aged 2 through 6 years are offered free influenza vaccination in the 2021/2022 season. Children more often become infected with influenza and are more infectious than adults. Therefore, vaccinating the 2-6-year-olds will hopefully limit disease and worry in the families while avoiding absence and isolation of children and other family members. Due to the special situation with the COVID-19 epidemic, the aim is to prevent influenza disease to the extent possible. Therefore, children are offered influenza vaccination. This will contribute to preventing that influenza virus spreads in the population. Thereby, vulnerable groups are protected and the healthcare system avoids overloading. Currently, the offer of vaccination of children is available only in the 2021/2022 season.

An agreement was entered into by the General Practitioner’s Association (DMA) and Danish Regions ensuring that children are offered influenza vaccination in general practice as part of the prophylaxis agreement.

Children will be offered influenza vaccine in the form of a nasal spray by which half a dose is sprayed into each nostril. The vaccine used (Fluenz Tetra^®) is a live attenuated vaccine. If the child has not previously received influenza vaccination, he or she is vaccinated twice at a minimum four-week interval. If the child has initiated influenza vaccination before turning seven years old, but will turn seven years old before the second dose is given, the second dose may be given free of charge until 15 January 2022. The most common side effects are reduced appetite, nasal congestion and malaise. Furthermore, muscle soreness, headache and fever may occur.

The Fluenz Tetra^® vaccine is specially developed and approved for use in children. For a number of years, the vaccine has been used in children in England and Finland, among others.

Even so, it is important to be aware that a limited number of children should not be vaccinated with the live attenuated vaccine and should therefore be offered another influenza vaccine. These include immunocompromised children, in particular, but also children who are household contacts to severely immunocompromised persons (e.g., people who have received a bone marrow transplant and persons receiving high-dose chemo therapy, who require isolation). The Danish Paediatric Society has published the following contraindications to vaccination with Fluenz Tetra^®.

• Age below two years or above 18 years.
• Previous anaphylaxis to influenza vaccine or a vaccine component, including gentamicin.
• Systemic allergic reaction to egg that requires admission to hospital.
• Immunodeficiency caused by conditions like acute or chronic leukaemia, lymphoma, symptomatic HIV infection and asplenia.
• Primary immunodeficiency
• Acquired immunodeficiency due to high-dose immunosupressive therapy.
• Severe or uncontrolled asthma, including asthma requiring admission to hospital in the past three months.
• Asthmatic bronchitis within the past 72 hours.
• Salicylate treatment (due to the connection between Reyes’ syndrome and salicylates and wildtype influenza infection). Salicylates may not be used in children and young people in the four weeks following the vaccination.
• Children with non-operated craniofacial malformations or with cochlear implant (due to lacking data).

Fluenz Tetra^® may be given to persons with asymptomatic HIV infection, to persons receiving topical/inhaled corticosteroids or low-dose systemic corticosteroids and to persons who are receiving replacement therapy with corticosteroid as, e.g., in case of adrenal insufficiency.

For further information about influenza vaccination of children, risk children and contraindications for Fluenz Tetra^®, please see the summary of product characteristics and the influenza guidance section at the website of the Danish Paediatric Society, see link above.

Children who have previously had anaphylaxis to eggs have not experienced systemic allergic reactions following vaccination with Fluenz Tetra^®. Based on a cautionary principle and until further notice, we recommend that these children are referred to a hospital for Fluenz Tetra^® vaccination.

If the child has contraindications to a live attenuated vaccine or falls beyond the age indication of Fluenz Tetra^® under the vaccination programme, one of the two inactivated vaccines may be used. Both InfluvacTetra^® and VaxigripTetra^® are authorised for use in children as from six months of age.

Children aged from 6 months through 8 years who have not previously been vaccinated against influenza and who will be vaccinated with one of the inactivated influenza vaccines should receive two vaccinations at a minimum four-week interval. The same dose is used children and adults.

It may be relevant to vaccinate household contacts and other persons who come into close contact with children belonging to the risk groups, including children below 6 months of age who cannot be vaccinated.

Pregnancy and breast-feeding

Pregnant women are at a higher risk of suffering serious complications from influenza infection than non-pregnant women, and this is particularly evident for influenza A (H1N1) pdm09, which has been in circulation since 2009. The Danish Health Authority therefore recommends influenza vaccination of all pregnant women in their 2nd or 3rd trimester. Pregnant women in their 1st trimester should also be offered vaccination if they belong to a risk group. Many years of experience with vaccination of pregnant women globally have show that influenza vaccination during pregnancy is safe for the mother and her child. Influenza vaccination of pregnant women also protects the child in the first months of life as antibodies are transferred from mother to child. The influenza vaccine may also be given during the breastfeeding period.

About the effect of the vaccine

The influenza vaccines provide protection against the specific influenza strains in the vaccine after 2-3 weeks. Immunity typically remains for 6-12 months, but as early as six months after vaccination, the antibody level has fallen to 50% of the peak antibody level. Furthermore, it is important to know that the influenza vaccines do not provide 100% protection against influenza. The degree of protection depends on how well the virus antigens in the vaccine match the viruses in circulation and on the strength of the immune defence of the person vaccinated.

Studies have shown that if they become infected with influenza despite having been vaccinated, persons who have been vaccinated frequently have milder disease and are not admitted to hospital as often at people who have not been vaccinated. Elderly people respond less strongly to the vaccine; i.e. their antibodies are at a lower level, and the antibody level decreases more rapidly in elderly people than in young people. The amount of antibodies increases with time, and therefore you are not sufficiently protected the subsequent year. Therefore, we recommend that risk group persons are vaccinated every year.

Furthermore, influenza virus shifts genetically. Therefore, the protection you achieve against one influenza virus following vaccination will not necessarily cover the changed virus. Consequently, every year a new vaccine is manufactured that contains components from the virus strains that are expected to be circulating. Every year, the WHO recommends which viruses should be included in the upcoming season’s vaccines. The assessment of the content of influenza vaccines for the Northern hemisphere is also influenced by knowledge about the viruses that have shortly before dominated in the Southern hemisphere.

Adverse reactions and contraindications

Fever, malaise, rigours and tiredness are common vaccination reactions. They typically recede after 1-2 days. The inactivated influenza vaccines cannot cause influenza disease, but the side effects of the vaccine are often misinterpreted by citizens as influenza disease.

Allergy to formaldehyde will most frequently manifest itself as contact dermatitis in which case patch tests may be positive. However, this does not constitute a contraindication. To avoid such reaction, the vaccine may be administered as a deep intramuscular injection.

Neuraminidase inhibitors can be used for treatment and in some cases also for prevention following specific exposure in persons who cannot be vaccinated due to contraindications.

For specific information about contraindications to influenza vaccination of children, please see above.

Registration of vaccinations

All influenza vaccinations shall be registered in the Danish Vaccination Register (DVR) in accordance with Executive Order on Access to and Registration, etc. of Medicinal Product and Vaccination Information. If the vaccination information is not automatically reported to the DVR via integration with the electronic patient record used, vaccinations can be registered at www.fmk-online.dk.

The service codes used to settle the influenza vaccines are available at the DMA’s website.

Influenza surveillance

As usual, the SSI’s influenza surveillance scheme will run as from week 40. Data from the influenza surveillance will be updated on the SSI website continuously, and news will be published when the influenza situation changes.

The influenza monitoring scheme is, among others, based on the number of positive laboratory samples, the number of enquiries made by citizens to on-call doctors and to a group of GPs (sentinel doctors) about influenza-like disease (ILD). Furthermore, the number of patients admitted to hospital with influenza is monitored, including patients admitted to intensive care units with serious influenza disease and the number of influenza-related deaths.

In the upcoming influenza season, influenza monitoring will once again be challenged by COVID-19, partly due to overlapping symptoms between influenza and COVID-19, partly because of changed patient appointment patterns with treating physicians and changed sampling routines for COVID-19, influenza and other airway conditions. This year, the SSI has established an extended sentinel surveillance system covering influenza, COVID-19 and other airway infections in which the SSI hopes that many physicians will participate. Physicians who would like to participate are encouraged to contact the Department of Infectious Disease Epidemiology and Prevention.

(L.S. Vestergaard, L.K. Knudsen, Sidsel B. Asmussen, Department of Infectious Disease Epidemiology and Prevention)

Information campaign targeting groups who are recommended influenza vaccination

In connection with the offer of free influenza vaccination for special risk groups, the Danish Health Authority initiates a campaign to inform the target groups of the offer and the backdrop of the vaccination recommendation. This year, the main message of the campaign is “Influenza vaccination - a healthy decision”.

The campaign will run on a variety of platforms, e.g. digital TV, outdoor posters, social media, home page banners and adds in papers and periodicals. This campaign track targets parents to children aged 2-6 years of age in particular.

You can read more about the vaccination offer and the campaign at the website of the Danish Health Authority, where you may also download various information materials for the different target groups, e.g. folders, posters and info screen video clips. These materials target different groups of citizens.

When vaccines are sent to GPs, a poster and some copies of the folder targeting adults will be included. Similarly, a poster and folders targeting parents to children aged 2-6 years will be included with the paediatric vaccines when provided. Additional materials are available for download at sst.dk/influenza. This year, it is not possible to order additional printed material.

The maternity wards will also receive printed materials targeting pregnant women. Additionally, relevant patient associations will receive digital material packages as will Danish municipalities and any trade unions that have health and nursing staff among their members.

(A. Rygaard, Communication, Danish Health Authority)

Finally it’s here: notification of infectious diseases goes electronic

On 1 October 2021, the first step will be taken in the transition to electronic notification of notifiable diseases. As from the beginning of October, practising medical specialists, including GPs, will have access to the new electronic form “Infectious diseases” in the Danish Health Data Authority’s electronic notification system (SEI2).

The form “Infectious diseases” is a one-stop notification site for all of the notifiable diseases previously notified on Form 1515, on the syphilis and gonorrhoea forms at www.ssi.dk and on HIV form 4001-9 (the pink form). The form was prepared as a collaborative effort between the Department of Infectious Disease Epidemiology and Prevention at Statens Serum Institut and the Danish Health Data Authority.

We are currently also working to replace the MRSA paper form 5001 with an electronic form, but cannot yet say when the form will be available.

The future use of SEI2 for notification of infectious diseases ends the use of paper-based notifications with carbon copies and forms that need to be scanned or sent to various organisations. The Danish Patient Safety Authority and the Department of Infectious Disease Epidemiology and Prevention, SSI, will be able to collect the information notified from SEI2. Physicians’ notification work becomes easier as the electronic form is adapted to the disease in question, ensuring that the person filling in the form can focus on providing information that is relevant to the disease being notified.

Furthermore, the notifying doctor may find help to complete the form by using the instructive drop down menus of the form. We expect that the transition to electronic notification will increase data quality, thereby strengthening the monitoring of infectious diseases in Denmark.

The transition to electronic notification benefits greatly from the fact that most doctors already use the web-based SEI2 and know the system as, e.g., death certificates are also notified using this system. This means that the transition to electronic notification does not make it necessary to purchase and/or install any new systems or software and also there is no need for user training. It is still possible for doctors to delegate the notification of notifiable diseases to an assistant. Assistants may either be authorised or non-authorised healthcare workers.

Initially, only practicing medical specialists, including GPs, will have access to using the electronic form as from 1 October 2021. This is because the SDS are in charge of giving privately practicing doctors access to the form. The SDS will ensure access to the “Infectious diseases” form for all privately practicing doctors who already have access to filling in death certificates in the SEI2. Hospital doctors will be given access via the local administrators in the five Danish regions. We intend to also make the “Infectious diseases” form automatically available to all hospital doctors who currently have access to filling in death certificates. Week 38, the regions approved the transition to electronic notification and the work to establish groups and give access to the form can therefore proceed now. Each region will let its employees know when the form becomes operational in the region.

Doctors or assistants who do not get access to the “Infectious diseases” form but who want access may create a user in SEI2 and request rights to use the “Infectious diseases” form.

During a transitional period until 1 July 2022, notification may be made using either electronic notification or the methods used to date.

As is the case with any new facility, some adaptation of the “Infectious diseases” form will likely be necessary. We very much intend to ensure that notification becomes as easy and intuitive as at all possible, and we are highly interested in receiving user feedback. That will allow us to adapt any inexpediencies related to the form. Feedback may be sent to sisv@ssi.dk.

Read more

For more information, please see the Danish Data Health Authority’s user guide “Login and introduction to SEI2” (in Danish language).

Find information about how to notify an infectious disease electronically in the guide “How to notify infectious diseases” (in Danish language). The guide also includes a list of all notifiable diseases and a list of the information needed to notify each of these diseases.

Need help?

Questions about the system and how to use it may be sent to SEIsystemet@sundhedsdata.dk, or directed directly to Helle Rejnhold Sørensen (3268 5210) or Sandra Sarosi Thomasen (3268 9173).
Questions relating to the completion of the form and its use for notification may be submitted to sygdomsanmeldelse@ssi.dk, or directed directly to Sidsel Skou Voss (3268 8577) or Anne Kathrine Colstrup Hvass (3268 8453)

(S.S. Voss, A.K.C. Hvass, S. Cowan, Department of Infectious Disease Epidemiology and Prevention)

29 September 2021