No 42/43 - 2019

Temporary free whooping cough vaccination for pregnant women

Due to the current whooping cough epidemic, the Danish Minister of Health has decided to introduce a temporary free vaccination offer of vaccination against whooping cough for pregnant women in their 3rd trimester. The vaccination offer comes into force on 1 November 2019 and concludes on 31 January 2020 at which time the epidemic will expectedly have ended.

Many children below six months of age require admission to hospital if they are affected by whooping cough. Fortunately, serious complications are rare and fatalities even rarer. The objective of whooping cough vaccination during pregnancy is to protect neonates in their first months of life until the child can be vaccinated, thereby preventing hospitalisation of the child.

The Danish Health Authority recommends that vaccination of pregnant women be given at the third routine pregnancy examination performed by the woman’s GP at 32 full weeks of gestation. Pregnant women in their 3rd trimester who attended the examination before the offer comes into force on 1 November 2019 may be offered vaccination at another visit, and need to schedule such a visit with their GP themselves.

The Danish Health Authority does not recommend vaccination of pregnant women less than one week before the expected labour date, e.g. because of the upcoming labour date, planned initiation of labour, etc. This is so because there is no documentation that the vaccine is effective if given less than a week before the expected birth date.

Furthermore, the Danish Health Authority recommends that pregnant women with multiple pregnancy and other childbearing women at risk of giving birth prematurely discuss vaccination with their GP or the midwife at their department of obstetrics where they are being monitored. In this group, vaccination may also be offered in the 2nd trimester, provided medical assessment warrants that birth is not expected within one week, though not earlier than at 16 full weeks of gestation. The offer of vaccination to pregnant women in this group may be given as part of in-hospital treatment. 

Vaccination against whooping cough is used routinely in many countries, including, e.g., the US, Great Britain, Australia and Austria. In the countries where pregnant women have been vaccinated, follow-up studies have shown no increased risk for the pregnant woman or her foetus. The effect of protection against whooping cough in the initial months after birth has been established to fall in the 40-90% range.

For more information, please see the Danish Ministry of Health’s Executive Order no. 1043 of 11/10/2019 and the Danish Health Authority’s Guideline no. 9899 of 16/10/2019 on free vaccination against certain infectious conditions, etc.

The vaccine

For vaccination under the temporary vaccination scheme, the diTekiBooster (diTeki = diphtheria, tetanus and pertussis) from AJ Vaccines A/S is to be used. This vaccine is approved for adults. No vaccine studies have been performed in pregnant women, but knowledge about use of the vaccine among pregnant women is being collected continuously by the manufacturer. Based on a substantial data material, no increased risk has been documented for whooping cough vaccination of pregnant women with respect to pregnancy, labour, complications in neonates or breast-feeding. It is the opinion of the Danish Health Authority that the advantages associated with vaccination of pregnant women during the current epidemic outweigh the potential drawbacks.

The vaccine is delivered in Swedish packaging and dispensed with the authorisation of the Danish Medicines Agency.

The vaccine also protects against diphtheria and tetanus, and it is assessed that it may be used even in cases of recent booster vaccination against these two conditions. Even so, a minimum of four weeks should pass from the latest diTe booster vaccination due to the risk of a strong local reaction at the injection site. If a diTe booster vaccination or a diTe-containing vaccine has been given within the preceding 12 months, the risk remains of a local reaction at the injection site.

diTekiBooster is given intramuscularly in the deltoid muscle and may be given concurrently with an influenza vaccine, but on opposite sides.

Contraindications

The vaccine may not be given to persons with known hypersensitivity to its active ingredients, one or more of the excipients or formaldehyde, which may be present in the vaccine in trace amounts. 

Furthermore, the vaccine may not be given to persons who have experienced encephalopathy of unknown aetiology occurring within seven days after a previous vaccination with a pertussis-containing vaccine.

Furthermore, persons who suffer from progressive neurological conditions may not be vaccinated.

Finally, immunisation should be delayed during the course of acute febrile illness.

Side effects and enhanced monitoring

The most commonly occurring side effects are transient itching, reddening, swelling and soreness at the injection site along with fever. These reactions usually present within 48 hours after vaccination. For further information about reported side effects, please see the approved summary of product characteristics.

The Danish Medicines Agency has introduced enhanced monitoring of the vaccine’s use in pregnant women. This means that doctors and midwifes have a duty to report all presumed side effects of the vaccine in pregnant women as well as in their children. All presumed side effects include known side effects.

If the side effects are serious, they must be reported to the Danish Medicines Agency no later than 15 days after the symptoms presented.

It is important to remember that reporting is to be made based exclusively on the basis of a presumption of a connection between the symptoms and the vaccine. Presumed side effects may be reported electronically at meldenbivirkning.dk.

How to order

The diTekiBooster may be ordered using Form 6; and for use in the temporary vaccination scheme, it is available in 1- and 10-piece packings:

The 1-piece packs have issue number 101469.
The 10-piece packs have issue number 101468.

To ensure an adequate supply and avoid wasting vaccines, healthcare workers are recommended ordering only the number of vaccines currently needed. It will be possible to order the vaccine throughout the entire period.

Settlement and notification

The Danish General Practitioners’ Organisation (PLO) and the Regional Board for Wages and Tariffs (RLTN) have made an addition to the Prophylaxis agreement on whooping cough for pregnant women. Therefore, a new service is introduced: Service 8803: whooping cough vaccination for pregnant women

When pregnant women are vaccinated at their 3rd medical examination (at approx 32-33 weeks of gestation), service 8130 is used: 3rd medical examination + service 8803: vaccination against whooping cough. 

When pregnant women are vaccinated independently of the 3rd medical examination or visit (0101), service 8803 is used: whooping cough vaccination + service 8901: additional vaccination fee.

Monitoring of the coverage of the temporary vaccination programme is based on the statutory notification of vaccinations to the Danish Vaccination Register (DVR) through www.fmk-online.dk or via integration of the DVR into the electronic health record system used.

Vaccination beyond the temporary vaccination programme

If a pregnant woman wants vaccination late in her pregnancy before 1 November or if a pregnant woman is not covered by the executive order, the vaccine may be ordered for her. However, the patient will defray any costs associated with the vaccine herself and the vaccines are available only in packs containing 5 vaccines (in Danish packaging):
5-vaccine packs have issue number 98952. 

If the doctor does not want to acquire 5 doses, the pregnant woman may be referred to a vaccination clinic that stocks the vaccine.

(P. H. Andersen, L.K. Knudsen, Department of Infectious Epidemiology and Prevention, B. Neale, Provisions, B. Søborg, M.G. Aabye, Danish Health Authority, K.M. Harboe, Danish Medicines Agency)

Influenza vaccination 2019/2020

The influenza season runs from Week 40 in the autumn until Week 20 in the spring. SSI is monitoring the occurrence of influenza in the population throughout the season, among others based on the number of positive laboratory samples, the number of patients presenting to on-call doctors with influenza-like illness, and the number of patients admitted to hospital with influenza, including patients being admitted to intensive care units with serious influenza illness. Furthermore, the number of influenza-related deaths is monitored.

As in previous influenza seasons, free influenza vaccination is offered during the 2019/2020 season to special groups at risk of developing serious and complicated influenza illness. The risk groups include for example people aged 65 years and above, pregnant women and chronically ill people (please see further in the section below). Vaccination not only reduces the risk of infection with influenza; it also reduces the risk of developing serious conditions, risk of admission to hospital and risk of death if you do get infected with influenza, even though you received the vaccination.

During the 2018/2019 influenza season, the average vaccination coverage among elderly people aged ≥65 years in Denmark was 52%, which is slightly higher than in the preceding years, but nevertheless far below the 75% vaccination coverage recommended by the WHO.

The free influenza vaccination offer starts on 1 November

As previously described in EPI-NEWS 26/19, the free influenza vaccination offered to special risk groups is available from 1 November 2019 until 15 January 2020. However, for pregnant women in their 2nd or 3rd trimester and for immunosuppressed persons and their household contacts, the vaccination offer is extended until the end of February 2020.

In previous seasons, the vaccination offer started on 1 October. The change in date is due to the fact that, in 2019, it has been difficult for the manufacturers to provide the vaccines by 1 October.

Furthermore, medical considerations favour a later initiation of the influenza vaccination as the effect of the influenza vaccines declines over time, while the occurrence of influenza in Denmark typically occurs late in the period, mostly in the January-March period.

Influenza vaccines in the 2019/2020 season

In the 2019/2020-season, 4-valent inactivated influenza vaccines are used, which will protect against two types of influenza A virus and two types of influenza B virus. In previous seasons, 3-valent vaccines were used that protected against two types of influenza A virus and one type of influenza B virus. Even so, in the 2018/2019-season, approx. 1/7 of the vaccines given were 4-valent. Generally, the 4-valent vaccine will yield a higher level of protection, even though this will eventually depend on the type of influenza virus in circulation during the season.

This year, influenza vaccines have been purchased from two manufacturers, InfluvacTetra and VaxigripTetra, respectively. The composition of the vaccines is based on WHO's recommendations, containing surface proteins from the four seasonal influenza viruses that have been in circulation globally. None of the vaccines contain thiomersal or adjuvant, but may contain trace amounts of egg/chicken protein, formaldehyde, neomycine and gentamicine.

The composition of the 4-valent vaccines is as follows:

• A/Brisbane/02/2018 (H1N1)pdm09-like virus (NEW VIRUS)
• A/Kansas/14/2017 (H3N2)-like virus (NEW VIRUS)
• B/Colorado/06/2017-like virus (Victoria line)
• B/Phuket/3073/2013-like virus (the Yamagata line).

The InfluvacTetra vaccine may be used for vaccination of children as from three years of age, whereas the VaxigripTetra is approved for use in children as from six months of age.

It is also possible to order a 4-valent inactivated cell-based influenza vaccine for persons who have egg allergy, named FlucelvaxTetra. This vaccine contains components from influenza virus that has been cultured in cell cultures rather than in egg, as is the case for the other influenza vaccines. Therefore, the vaccine is egg-free and may be used in persons who have egg allergy. The vaccine may be given to adults and children (from 9 years of age). The vaccine is ordered via the SSI Order Office (Ordremodtagelsen).

Who is covered by the free influenza vaccination offer

In accordance with Executive Order of 25 September 2019 on free influenza vaccination to select population groups, the following persons residing in Denmark are entitled to free influenza vaccination:

1. Persons who are 65 years old on 15 January 2020 (born before 15 January 1955).
2. Early retirement pensioners.
3. Chronically ill persons, as from 6 months of age, who suffer from the following conditions, upon medical assessment:
   - Persons with chronic pulmonary conditions
   - Persons with cardiovascular diseases (barring high blood pressure with no concurrent conditions)
   - Persons with diabetes
   - Persons with congenital or acquired immunodeficiency
   - Persons whose respiration is affected due to muscular weakness
   - Persons with chronic liver or kidney failure
   - Persons with other chronic conditions, for whom their condition may cause influenza to constitute a serious health risk for them, as assessed by a doctor
4. Severely obese people (recommended BMI > 40), upon medical assessment
5. Persons with other serious diseases that, according to the doctor’s assessment, pose a serious health risk in conjunction with influenza
6. Pregnant women in their 2nd or 3rd trimester
7. Household contacts to severely immunosuppressed patients (congenital or acquired immune deficiency) upon medical assessment.

Children

Children aged from 6 months through 8 years who have not previously been vaccinated against influenza should receive two vaccinations at a minimum interval of 4 weeks. The same dose is used in children as in adults.

It may be relevant to vaccinate household contacts and other persons who have had 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 increased risk of suffering serious complications from influenza infection compared with 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 are also offered vaccination if they belong to a risk group.

Several years of experience in vaccination of pregnant women globally show that influenza vaccination during pregnancy is safe for the child and is not associated with an increased risk of adverse reactions for the pregnant woman. Influenza vaccination of pregnant women also protects the child during the first months of life, as antibodies are transferred from mother to child. The influenza vaccine can also be given while breast feeding. During the 2018/2019 season, almost 17,000 pregnant women agreed to get the free vaccination offer, see Influenza Season – Report on disease occurrence 2018/19. The influenza vaccine may be given concurrently with the vaccine against whooping cough, but should be injected in the opposite shoulder.

Level of protection

Protective immunity against influenza acquired through vaccination based on the inactivated influenza virus is generally effective from 2-3 weeks after vaccination. The protective effect usually lasts for 6-12 months. The degree of protection depends mainly on the level of agreement between the type of virus in circulation in the population and the types of virus included in the vaccine. Among younger, healthy individuals, vaccination overall prevents about 60% of influenza cases. Among the elderly, the protection against influenza conferred by the vaccine is somewhat lower, but even so, influenza vaccination is the best option available to protect against serious complications, hospital admission and influenza-related death.

Adverse reactions and contraindications

Fever, body malaise, rigors and tiredness are common vaccination reactions, but typically resolve after 1-2 days. The inactivated influenza vaccines do not cause influenza illness.

Individuals who have hypersensitivity to chicken egg/chicken protein may be vaccinated using the new vaccine produced in cell culture (see above). Allergy to formaldehyde most commonly manifest itself as contact dermatitis, in which case patch tests may be positive. However, this does not constitute a contraindication to being vaccinated. To reduce the risk of such reactions, the vaccine may be administered intramuscularly.

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.

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.

Influenza surveillance

Statens Serum Institut's influenza surveillance has been in place since Week 40. Data from the influenza surveillance will be updated on the SSI website weekly, and news will be published continuously as the influenza situation evolves over the season..

Information campaign from the Danish Health Authority

This year, the Danish Health Authority once again runs the campaign “Time for vaccination against influenza”. The campaign informs risk groups about influenza vaccination. Doctors and healthcare workers can find information about the campaign and about this year’s vaccine at www.influenzakampagne.dk. Here you may also download various patient information and electronic campaign materials, etc. Furthermore, printed posters and business cards will be sent out to GPs, pharmacies, municipalities and leading midwives. Via this website, it is possible to order a selection of posters and visiting cards, as needed. The campaign also has a Facebook page targeting citizens: “Tid til vaccination mod influenza” (Danish for Time for vaccination against influenza), which includes an advertisement campaign that will run in the media while the offer of free influenza vaccination is effective.

(L.S. Vestergaard, L.H. Knudsen, T.G. Krause, Department of Infectious Disease Epidemiology and Prevention, B. Søborg, Unit for Evidence, Education and Emergency Services, Danish Health Authority)

This week, the first group of parents will receive reminders about upcoming childhood vaccinations

This week, the first reminders about upcoming childhood vaccination under the new 2019 reminder scheme will be sent to parents. This is so because the first children covered by the scheme will turn 3 months, 4 years and 12 years old, respectively, within two weeks.

The following children are covered by the scheme:

• Children born after 1 August 2019.

• Children who turn 4 years old as from 1 November 2019.

• Children who turn 12 years old as from 1 November 2019.

For these children, the Danish Vaccination Register (DVR) will be included in the childhood vaccination programme relevant for their age. The reminders are sent to both parents’ e-Boks two weeks before the planned time of vaccination and also one month after, if no registration has been made of the child’s vaccination. Parents residing in Denmark who have opted out of e-Boks will receiveprinted letters. The objective of the scheme is to ensure that even more children are vaccinated timely.

Additional information about the 2019 reminder scheme is available at the SSI website.

(T.G. Krause and L. Krause Knudsen, Infection Epidemiology and Prevention)