No 4 - 2016

Settlement codes for HPV vaccination as from 1 February 2016
New temporary BCG vaccine from Japan
Major Danish case-control study on risk factors for infection with campylobacter
Two Danish case-control studies on risk factors for infection with livestock MRSA
Danish case-control study among HPV vaccinated women on determinants for notification with a presumed serious adverse effect

Settlement codes for HPV vaccination as from 1 February 2016

As previously described, from 1 February 2016 a new HPV vaccine, Cervarix®, shall be used in girls who initiate HPV vaccination, EPI-NEWS 2/16.

The following codes shall be used for registration and settlement with the National Danish Health Insurance (Sygesikringen).
1. HPV vaccination with Cervarix® = 8334 (normally given when the girl is 12 years old).

2. HPV vaccination with Cervarix® = 8335 (a minimum of 5 months after the first vaccination in a two-dose schedule).

3. HPV vaccination with Cervarix® = 8336 (see EPI-NEWS 2/16 for indication for giving a third vaccination. A minimum of 5 months after the second vaccination).

Girls who have initiated vaccination with Gardasil® shall complete vaccination with this HPV vaccine, and the settlement codes used until now still apply.
(P.H. Andersen, Department of Infectious Disease Epidemiology)

New temporary BCG vaccine from Japan

Due to production issues and rehabilitation of the BCG production line at Statens Serum Institut (SSI), the SSI’s BCG vaccine against tuberculosis has been on back order for a substantial period of time, and the current outlook is that the SSI will remain unable to provide the vaccine at least until end of 2016.

Furthermore, there is a general lack of BCG vaccine on the world market, including in countries which have included the vaccine into their childhood vaccination programme. Nevertheless, we have procured a consignment of BCG vaccine from a Japanese manufacturer (Japan BCG Laboratory), which the SSI expects to be able to provide as from the beginning of February. This BCG vaccine is currently also being used in Sweden. Whereas the SSI’s BCG vaccine is provided as vials with 10 doses (20 infant doses) of lyophilised vaccine, the Japanese product comes in packages of 10 ampoules each counting 10 doses of lyophilised vaccine, i.e. 100 doses (200 infant doses).

It is not possible to repack the vaccine into more limited volumes, which causes logistic challenges in ensuring prioritised supply to the clinics/hospitals that have the greatest need for the vaccine, in order to minimise vaccine waste.

Therefore, and because the product is not registered in Denmark, it will be possible to order BCG vaccine only by calling the SSI Order Office (Ordremodtagelsen).

Furthermore, we urge general practitioners who find that there is indication for vaccination of a patient to consider referring the patient to a larger unit, e.g. a vaccination clinic or hospital department that administers more vaccinations and therefore may use more doses per package within the limited shelf-life period after opening and reconstituting the vaccine.

About the vaccine

The BGC vaccine from Japan BCG Laboratory is a lyophilised vaccine which contains 0.5 mg live attenuated BCG per ampoule. The powder is reconstituted in the supplied solvent (2 mg sodium glutamate/ml/ampoule) before injection. Only the supplied solvent may be used.

After reconstitution and gentle shaking, a homogeneous suspension is achieved with a concentration of 0.5 mg/ml. One ml reconstituted vaccine is sufficient for a maximum of ten 0.1 ml doses (> 1 year) or a maximum of twenty 0.05 ml infant doses (< 1 year).

Both before and after reconstitution, the vaccine should be protected against direct sunlight and stored between +2 and +8 degrees Celcius; and after reconstitution, the vaccine shall be used within a 6-hour period.

The recommended vaccination site is laterally in the mid-section of one upper arm. The skin should not be wiped with alcohol before vaccination. The vaccination is given intradermally. The vaccine may be given concurrently with other live and non-live vaccines.

If it is not given with another live vaccine, the minimum interval between the two vaccines is 4 weeks. Due to the risk of local lymphadenitis, vaccinations in the arm where the BCG vaccination was given should be avoided for a minimum period of 3 months.

It is normal to see a local reaction following the vaccination in the form of a small, sore and red swelling which gradually transforms into a vesicle and then an ulcer in the course of 2-4 weeks. The ulcer normally dries out after 2-5 months and nearly always leaves the vaccinee with a superficial 2-10 mm scar. Excessively deep injection is associated with a risk of local reactions in the form of abscesses and lymphadenitis.

The vaccine is contraindicated in case of cellular immune insufficiency and in HIV positives.

The vaccines item number is 97778.

For further information, please see the included package leaflet and the summary of product characteristics.

Indications for BCG vaccination

The primary indication for BCG vaccination is pronged (a minimum of 3-6 months) stay in countries with a high prevalence of tuberculosis combined with close contact to the local population. Vaccination will be indicated mainly in children and teenagers in whom the protection against the most serious types of TB (TB meningitis and miliary TB) is most well-documented. Vaccination may also be indicated in health workers who will be stationed abroad to perform local work and who will come into contact with tuberculosis patients. Booster vaccination is not recommended.

In Denmark, there is normally only indication for vaccination of children who are born into or live in families or communities where tuberculosis is known to occur. Apart from neonates, these children should be tested for latent infection (Mantoux or IGRA test) before any vaccination. Vaccination of these children will typically be handled at paediatric departments or pulmonary medicine departments in connection with contact tracing of infectees.

If a general practitioner finds that there is indication for BCG vaccination of a child, the child should be referred to a paediatric department for assessment and, if relevant, vaccination, due to the current lack of BCG vaccine.
(P.H. Andersen, Department of Infectious Disease Epidemiology, G. L. Germod, Planning Division)

Major Danish case-control study on risk factors for infection with campylobacter

Campylobacter is the leading cause of bacterial gastroenteritis in Denmark and in the entire Western World. In Denmark, nearly 4,000 annual cases are reported, primarily in children and young persons below 30 years of age. Despite the large number of infectees, a number of basic conditions regarding the routes of infection remain poorly understood.

As per 1 January 2016, Statens Serum Institut and the Danish Veterinary and Food Administration have initiated two major, related studies to elucidate risk factors for Campylobacter infection through patient interviews and typing of isolates from confirmed cases.

A case-control study will be done for which approx. 1,000 patients and 5,000 healthy Danes aged 1-30 years will be invited. The controls are drawn randomly from the CPR register, and the patients will be identified via the notification system for gastrointestinal bacteria.

All participants will receive a letter containing a link to a questionnaire, which is to be filled in on-line if the person agrees to participate in the study. Furthermore, a microbiological study will be initiated of a minimum of 1,200 isolates from persons infected in Denmark (including those who are also participating in the questionnaire study) based on whole genome sequencing. Typing of these isolates will be compared with isolates from food, household animals and from the environment. These isolates will be collected and sequenced by the Danish Veterinary and Food Administration.

The case-control study focuses on the identification of risk factors for infection, including specifically Danish citizens’ contact with sources of infection in nature and in the environment which in relation to foods now presumably play a far more important role than previously assumed. Sequencing of Campylobacter isolates will also determine if specific behaviours are associated with an increased risk of infection with some types of Campylobacter.

We expect that the results of the study will contribute to an enhanced understanding and handling of transmission, outbreak detection and disease prevention.
(K.G. Kuhn, Department of Infectious Disease Epidemiology)

Two Danish case-control studies on risk factors for infection with livestock MRSA

Since livestock MRSA (MRSA 398) was first detected in animals and humans in 2005, the number of infected persons has increased substantially. The majority are symptom-free carriers. Contact to pigs is a clear risk factor for infection, but an increasing number of infectees have been identified who have not come into contact with pigs.

In 2016, Statens Serum Institut will initiate two case-control studies on livestock MRSA. One of the studies is to expose possible routes of infection for persons who are infected with MRSA 398 and who have no known contact with pigs. The other study shall determine to which degree MRSA 398 infection will cause disease.

The studies are based on interviews in which a number of MRSA 398 infected persons, persons infected with other MRSA types and randomly drawn controls who have no known MRSA infection will be contacted by SSI telephone interviewers. The study on routes of infection includes 200 MRSA 398-infected persons with no known contact to pigs, 400 infected persons with other MRSA types and 200 CPR controls. The study on disease burden includes 200 MRSA 398-infected persons with known contact to pigs as cases, and the controls are the 600 MRSA-infected persons who participate in the study on routes of infection. MRSA-infected persons are interviewed several times (6 and 12 months), whereas CPR controls are only interviewed once. The studies will run for the next two years.
(A. Koch, Department of Infectious Disease Epidemiology)

Danish case-control study among HPV vaccinated women on determinants for notification with a presumed serious adverse effect

HPV vaccination has formed part of the childhood vaccination programme as an offer given to young women since 1 January 2009. The offer has covered girls born in 1996 or later. Catch-up programmes have been in place to ensure that all women from the birth cohorts 1985-1995 have also been offered HPV vaccination, and more than half a million women have been vaccinated in Denmark.

Already now, a decrease in the occurrence of cell lesions and genital warts has been observed among the vaccinees. Unfortunately, recent years have seen the notification of more than 650 presumed serious adverse effects following HPV vaccination. It has been suggested that very active young female athletes are affected by serious adverse effects.

More knowledge is needed, and Statens Serum Institut is therefore initiating a case-control questionnaire study to improve our understanding of any differences between the group of women who have reported serious adverse effects from the HPV vaccine and the group consisting of women who have also been vaccinated, but who have not reported any adverse effects.

The study starts in February 2016, and we will write to 250 women who have reported presumed serious adverse effects and to 1,000 women who have not reported adverse effects following HPV vaccination. Women can participate in the study by answering the printed questionnaire, by answering an electronic questionnaire or by participating in a telephone interview. Among others, the questionnaire contains questions on physical activity, health, alcohol and smoking habits, work and education and dietary and sleeping habits.
(S.U. Jacobsen, P. Valentiner-Branth, K. Mølbak, Department of Infectious Disease Epidemiology)

Link to previous issues of EPI-NEWS

27 January 2016