No 1/2 - 2014

Infectious diseases 2013

Major food-borne hepatitis A outbreak

In February 2013, Statens Serum Institut (SSI) started an investigation into a hepatitis A outbreak, EPI-NEWS 48/13. Based on the epidemiological studies, including a case-control study, it was concluded that the source of infection was frozen strawberries imported from North Africa. The outbreak not only affected Denmark, but also Sweden, Norway and Finland. In all, the outbreak comprised 114 cases of which 71 were Danish cases.

For several reasons, hepatitis A outbreaks are difficult to investigate, among others because the incubation period is long and variable, which makes it difficult to obtain valid information on relevant exposure. As Denmark has not yet implemented timely laboratory-based monitoring of hepatitis A, the investigation depended on statutory notifications from the treating physicians received on Form 1515. The outbreak underlines that it is essential that doctors submit samples from patients with relevant hepatitis A symptoms even if the patients have no travel history, and that the cases are reported timely.

Finally, it is technically difficult to confirm the presence of hepatitis A in foods. In the current outbreak, virus was not detected in the analysed batches of berries. The epidemiological studies, which were supported by virological typing of virus from patient specimens, were therefore particularly important in the investigation of the outbreak. Thus, typing initially helped confirm the suspicion of a shared source of infection and later proved useful in relating the Danish cases to the patients of other Nordic countries. Typing also allowed us to show that the hepatitis A types of the Nordic outbreak were different from the types of the hepatitis A outbreaks occurring concurrently in other countries.

Food-borne hepatitis A outbreaks caused by frozen berries have previously been seen, among others in North America. Furthermore, in 2013 frozen berries were established as the source of infection in concurrent hepatitis A outbreaks in the USA, Italy and Ireland. It should be noted that these findings occurred in the wake of the Danish and subsequent Nordic study. It should also be noted that in relation to the Italian outbreak, investigators were successful in detecting virus in frozen berries. The outbreaks now give rise to consideration at the EU level as to whether frozen berries may also be the source of infection in sporadic hepatitis A cases for which no other probable exposures exist.

MERS coronavirus

For the period after September 2012, the World Health Organisation (WHO) has reported a total of 177 laboratory-confirmed cases of Middle East Respiratory Syndrome (MERS) coronavirus infections of which 74 were fatal. The majority of these cases occurred in citizens from the Middle East (particularly Saudi Arabia, but also Qatar, The United Emirates and Jordan). Furthermore, a limited number of cases were observed in France, Germany, England, Italy and Tunisia.

The majority of the European cases were observed shortly after the affected persons had returned from the Arabian Peninsula, but person-to-person transmission has also been seen to a limited extent. In 2013, several Danish patients with a relevant travel history and symptoms of serious airway infection were tested for MERS coronavirus, but they all tested negative.

The background for establishing a preparedness measure to counter this new virus is that it was also a coronavirus that caused the SARS outbreak in 2003. SARS is a severe acute airway infection, and the SARS outbreak placed the healthcare systems of several countries under considerable pressure and indirectly had a substantial, negative socio-economic impact, particularly in Asia and Canada. On that basis, the international reaction on the identification of the new coronavirus was justified.

Luckily, the finding of a new coronavirus did not mark the beginning of a new SARS outbreak. SARS coronavirus is capable of producing serious disease in otherwise healthy persons, including among healthcare professionals, whereas serious illness caused by MERS coronavirus has primarily been observed in patients suffering from serious chronic conditions. It is thus a more opportunistic infection.

A number of issues concerning infection reservoir and route of infection have yet to be established; recent studies have indicated that one source of infection might be dromedaries. It is still relevant to be aware of this new virus as a differential diagnostic option in severe infections among patients who have stayed on the Arabian Peninsula or in any neighbouring countries, EPI-NEWS 21/13.

Polio in Syria

In 2013, a polio outbreak was observed in Syria, which led to concern that the disease may spread with the influx of refugees from Syria to other countries in the region or to Europe, including Denmark, EPI-NEWS 46/13. At present, Syria has seen 17 confirmed cases of polio from a total of three geographic areas, which indicates a substantial circulation of wild poliovirus in Syria. Poliovirus infection causes clinical symptoms in the form of paresis in approx. one of every 200 infected. It follows, therefore, that a large number of persons have become infected and have excreted virus to their stools, the large majority of whom have remained symptom-free.

Genetic testing of the virus has demonstrated considerable similarity with a virus detected in wastewater in Egypt in December of 2012, which, in turn, seems to have originated from Pakistan. Wild poliovirus very similar to the current virus has also been found in wastewater in Israel, on the West Bank and in the Gaza Strip since February 2013, EPI-NEWS 38/13. In these areas, the virus has also been found in the stools of several fully vaccinated and symptom-free persons, but no polio cases have been detected here at present.

As a consequence of the outbreak and to stop it from spreading, major vaccination campaigns are being implemented in Syria, Lebanon, Turkey, Jordan, Egypt, Iraq and in the Palestinian Territories. These mass vaccinations comprise about 22 million children and will continue into 2014 depending on how the outbreak develops. The campaigns, however, are challenged by the security situation in parts of the region.

Globally, polio is closer to being eradicated than ever before, EPI-NEWS 34/12. However, polio remains endemic to three areas across the world: Afghanistan, Nigeria and Pakistan. Before the conflict started, Syria had a well-functioning childhood vaccination programme, and the most recent case of polio was observed in 1999. The current outbreak underlines the importance of maintaining a high coverage in the Danish childhood vaccination programme to avoid the risk of re-introduction of this feared condition.

The Danish childhood vaccination programme

Denmark has had an effective polio vaccination programme in place for nearly 60 years, and the population immunity is generally considered as being good. It is, however, important that even more children are fully vaccinated to avoid polio and other diseases from spreading in Denmark in case the virus is introduced to the country.

The need for a high coverage in the childhood vaccination programme was stressed in 2013 by a measles outbreak in the Silkeborg area, EPI-NEWS 13-14/13, and by the continued circulation of mumps virus in Denmark, EPI-NEWS 46/13.

Towards the end of 2013, the Danish Minister of Health and Prevention issued a proposal that reminders be sent out with a view to improving the coverage of the childhood vaccination programme. If this proposal is being adopted, the measure along with healthcare professionals' and parents' use of the Danish Vaccination Register may be instrumental in improving the coverage of the childhood vaccination programme.

Strengthening of disease monitoring, vaccination monitoring and risk assessment

Vaccination is one of the most effective methods for prevention of serious infectious diseases. Vaccines, however, are medicinal products, and all such products may be associated with side effects. As vaccines are given to healthy persons, it is particularly important that the vaccination programme is designed to ensure a sensible balance between advantages and risks.

The positive effects on public health shall, of course, by far overshadow the side effects and any other negative effects that may be associated with vaccination. It is important that patients' and citizens' concerns are taken seriously, and any suspected side effects are therefore to be reported to the Danish Health and Medicines Authority. 2013 saw debate concerning the safety of HPV vaccination.

Parents and patients who experience health problems following a vaccination will, of course, often attribute these symptoms to the vaccine. However, co-occurrence alone does not necessarily indicate that there is a causal relation. In 2013 a study was published comprising nearly one million girls aged 10-17 years from Denmark and Sweden of whom nearly 300,000 had received close to 700,000 doses of HPV vaccination.

The study was unable to demonstrate any association between HPV vaccination and the development of a series of autoimmune, neurological and thromboembolic conditions. This thorough work reduced the concern about side effects caused by HPV vaccination.

The SSI summarised a number of considerations concerning cervical cancer in a special theme on its website, and this theme also refers to the studies demonstrating that we are already now starting to harvest the beneficial effects of HPV vaccination.

Danish health registers often make it possible to undertake such studies. Not only can the registers be used to analyse associations between vaccination and side effects, but also to determine the specific and non-specific effects of vaccination. In future, the strengthening of the Danish disease surveillance achieved through increased use of data from the MiBa, EPI-NEWS 45/13, and the Danish Vaccination Register, EPI-NYT 16/13, will allow us to perform new and timely studies and risk assessments.

In 2013, Denmark was one of the first countries to determine the effect of seasonal influenza vaccines on laboratory-confirmed influenza among patients above 65 years of age. We were able to demonstrate that in this population the vaccine had effect on influenza B, but no effect on influenza A of the H3N2 type. These findings, which could be explained by changes in the influenza A H3N2 virus (i.e. genetic drift), contributed to the adjustments made by the WHO to the composition of the vaccine for the 2013/14 season.

A coming "digital infection preparedness" in which data are widely collected from registers and captured from existing data sources will provide exceptional opportunities to assess the risk and effect of vaccinations and other interventions — and it will thereby contribute to make available timely evidence so that any necessary adjustments may be made to the programmes to ensure that they optimally underpin Danish public health.
(K. Mølbak Department of Infectious Disease Epidemiology)

HPV vaccination under the childhood vaccination programme and for women born in the 1993-1997 period

On 1 January 2014, the age limitation was changed on the existing offer of free HPV (human papilloma virus) vaccination under the Danish childhood vaccination programme. As previously, the HPV vaccination is offered to all girls when they turn 12 years old, but the offer has now been broadened so that the vaccination may be given until the young women turn 18 years old (as opposed to the previous 15-year age limitation).

Furthermore, a temporary free HPV vaccination offer has been passed covering women from the 1993-1997 birth cohorts. The offer is available until the end of 2015. The vaccine is identical to the vaccine given to 12-year-old girls under the Danish childhood vaccination programme and thus protects against cervical cancer as well as genital warts (condyloma), EPI-NEWS 35/08.

Young women who have had their sexual debut may also benefit from vaccination. Either because they have not yet been infected with HPV or because they have not been infected with all the HPV types covered by the vaccine.

It is believed that the vaccine protects against 70% of cervical cancer cases in women who are not infected at the time of HPV vaccination. Consequently, the vaccine does not protect against all cervical cancer cases, and it is therefore essential that young women continue their participation in the screening programme from they turn 23 years old even though they have been vaccinated.

The vaccination programme

The vaccinations may be given by any physician who in pursuance of the Danish Act on Authorisation of Health Staff and Health Professional Activity is entitled to act independently as a physician.

A vaccination series consists of three doses of Gardasil® 0.5 ml administered at day 0 and after 2 and 6 months. The minimum interval separating the 1st and the 2nd vaccination is one month, and the 2nd and 3rd vaccinations should be given at a minimum interval of three months.

If possible, all three vaccinations should be administered within one year, and if one vaccination is delayed, the next should be given as soon as possible. If you have previously initiated a vaccination programme but have not yet concluded vaccination, the remaining vaccines are administered - you never start over again.

For further information about the HPV vaccination, please refer to Theme on vaccination against cervical cancer (In Danish) and to the website of the Danish Health and Medicines Authority www.sst.dk.

Service codes

For girls and young women up to the age of 18 years, the previous service codes remain in place:

1. HPV vaccination = 8328
2. HPV vaccination = 8329
3. HPV vaccination = 8330

For the temporary offer for women from the 1993-1997 birth cohorts, please use the special service codes also used for women from the 1985-1992 birth cohorts who are no longer comprised by the free vaccination offer as per 1 January 2014:

1. HPV vaccination = 8334
2. HPV vaccination = 8335
3. HPV vaccination = 8336

It is essential that the correct service codes are used for all vaccinations. The codes form the basis for assessment of vaccination coverage and facilitate monitoring of the long-term effects of vaccination on the occurrence of HPV-related conditions.
(L.K. Knudsen, P.H. Andersen, P. Valentiner-Branth, Department of Infectious Disease Epidemiology)

Temporary vaccine change in the childhood vaccination programme

As previously announced, EPI-NEWS 50/13, a temporary change of several of the vaccines under the childhood vaccination programme will be introduced as from 15 January 2014. Children who initiate the childhood vaccination programme as from 15 January will be vaccinated with the hexavalent vaccine Infanrix hexa®, which protects against hepatitis B in addition to the diseases normally covered (diphtheria, tetanus, pertussis, polio and Haemophilus influenzae B infection). Furthermore, for a period of time, the normal five-year booster vaccine will be administered as two separate vaccines, IPV monovaccine and dTap booster, respectively.

On 10 January 2014, a special theme page will be published on the SSI's website. (In Danish) The theme page will provide all the necessary information, including the codes with which the temporary vaccines should be settled. We will also publish a "Questions & Answers" page addressing frequently experienced issues. The majority of this information will be repeated in next week's issue of EPI-NEWS, which will be published on 15 January 2015.

The SSI will send out an information package to everyone on 15 January 2014. The package includes: 

• A letter with general information on the temporary vaccine changes
• A flowchart explaining which vaccines are to be used
• Folders prepared by the Danish Health and Medicines Authority to be handed out to parents in connection with vaccination (in Danish and English). 
• Copy of EPI-NEWS 50/13

The physicians who have already ordered the temporary basic vaccine Infanrix hexa® will receive it in the course of Week 3. In some cases, physicians will not receive the vaccines until 1-2 days after the established cut-off date for children who are to initiate vaccination with Infanrix hexa®.

The temporary booster vaccines which are to be administered at 5 years of age, the IPV monovaccine and the dTap booster, will not be available until Week 4.
(P.H. Andersen, P. Valentiner-Branth, Department of Infectious Disease Epidemiology, N. Thulstrup, Sales and Business Development)

Link to previous issues of EPI-NEWS

8 January 2014