No 39 - 2017

Novel HPV vaccine in the childhood vaccination programme

As part of the Danish childhood vaccination programme, 12-year-old girls will now be offered an HPV vaccine that covers more types of HPV. Statens Serum Institut has recently concluded a tender for a new vaccine, and the winner is a so-called 9-valent type that protects against 90% of the HPV types that cause cervical cancer. The vaccine will be marketed as Gardasil^®9.

The expected programme initiation date is 1 November 2017. In general, it is not recommended to postpone HPV vaccination until November, but to have the vaccination when turning 12 years old.

Since no studies have been conducted to explore the safety, antibody level or vaccine efficacy of a combination of the three HPV vaccines, we recommend concluding the vaccination schedule with the vaccine that was used when you initiated vaccination.

This means that young women who started with Cervarix^® should complete the entire vaccination series with Cervarix^®.

The four-valent Gardasil vaccine, which previously formed part of the childhood vaccination programme, is no longer available with all doctors. If any young women have initiated the vaccination series with this vaccine and have not yet completed their vaccination series, Gardasil^®9 may replace one or more lacking doses in the series. The doses are then given at the intervals recommended for Gardasil^®9.

Detailed guidelines on how to conclude vaccination will be published as the date for the start of the Gardasil^®9 programme approaches.
Gardasil^®9 is delivered as 10x1 doses and may be ordered using item number 99204 as from Week 40 using Form 6 or at ordre@ssi.dk.

The vaccines will be delivered in the course of weeks 42/43 for initiation of vaccination by 1 November. A maximum of two packages may be ordered per provider number in the first order.

More detailed information will be provided in a future issue of EPI-NEWS.

(P. Valentiner-Branth, Department of Infectious Disease Epidemiology and Prevention)

Outbreak of Chikungunya virus infection in the Lazio region of Italy

The Italian health authorities have reported an outbreak of Chikungunya virus infection in the Lazio region, specifically in the area around the coastal town of Anzio, and in the Rome area. Furthermore, two cases were detected in Latina, which is located approx. 30 km east of Anzio. Neither of the cases has visited either Rome or Anzio.

Until 20 September 2017, a total of 111 confirmed cases were reported from the Lazio region. Additionally, 68 probable and 95 suspected cases were observed. This constitutes a sharp increase compared with 14 September, when a total of 15 confirmed cases had been reported. Among the 111 confirmed cases, 71 reside in or have visited the town of Anzio. Furthermore, the local health authorities in the regions of Emilia Romagna and Marche have both reported one confirmed case who had visited Anzio.

A total of 38 confirmed cases reside in Rome.

The local health authorities of the Lazio region have initiated control measures to limit transmission, partly by anti-mosquito spraying, by precautions to avoid blood-borne transmission and by dissemination of information to the local population of the area.

Chikungunya virus infection is caused by an enveloped mosquito-transmitted RNA virus that belongs to the alphaviridae family. After a 2-4-day incubation period, a high fever presents rapidly with shivers, myalgia and severe symmetrical arthralgia in several joints simultaneously, and frequently the affected joints have previously caused pain. Unspecific, concurrent symptoms may occur, including fatigue, nausea, vomiting and redness of the eyes. The disease lasts 7-10 days, but the arthralgia may persist for more than 9 months, particularly in people with the HLA-B27 tissue type. Young children, elderly people above 65 years of age and pregnant women are particularly exposed to serious Chikungunya virus infection with haemorrhagic fever and meningitis, in some cases with convulsions.

Differential diagnostic considerations should include other mosquito-transmitted viruses like dengue fever, West Nile fever, Usutu virus or Zika virus, if the traveller has stayed in an area where these viruses also occur. Double infections with these viruses can also occur. The infection is transmitted by the mosquito Aedes albopictus (the tiger mosquito), which is common in the Mediterranean area, but which has been observed as far north as in Holland in the summer period.

Diagnostically Chikungunya virus may be detected using real time PCR (Chikungunya virus (RNA) R. No. 2011, SSI), in EDTA blood or plasma as early as possible in the acute febrile phase. Subsequently, Chikungunya virus can be detected using specific positive IgM and IgG antibodies (Chikungunya IgG/IgM, R. No. 2021, SSI). As Chikungunya virus is an alphavirus rather than a flavivirus like the remaining relevant mosquito-transmitted viruses, there are no issues relating to risk of a serological cross-reaction.

Outbreak of Chikungunya virus infection in the Var region of France

Statens Serum Institut (SSI) has previously informed of two cases of Chikungunya virus infection in the town of Cannet-des-Maures in the Var region in the South of France near the Mediterranean Sea in August 2017. Subsequently, another four confirmed and two possible cases have been detected in the same area.

On 21 September 2017, the French health authorities informed of another two confirmed cases in a village located approx. 10 km from Cannes-des-Maures. An epidemiological link has been established between the two clusters, and genotyping with comparison of the detected genotypes will serve to substantiate a connection between the clusters.

The local authorities have implemented vector control, door-to-door visits to identify any further suspected cases and dissemination of information to the local population in the area.

Commentary

This is the second time that Italy sees a Chikungunya outbreak. The first time was in 2007 in the Emilia-Romagna region in northeastern Italy, where approx. 330 confirmed or suspected cases were recorded. This outbreak was the first known outbreak of Chikungunya virus infection in Europe. Subsequently, minor outbreaks have been recorded in the South of France in 2010 and 2014, and now once more in 2017 following the detection of the two small clusters in the department of Var.

The SSI has tested several samples from Danish travellers for Chikungunya virus, but to date no infections have been detected. It remains unclear to which degree climate conditions, particularly climatic fluctuations with hot summers in Southern Europe and varying occurrence of mosquitoes, contribute to these repeated outbreaks. Travellers to the currently affected areas are advised to use protective gear against mosquitoes in the form of mosquito repellent and, in come cases, long sleeves and long pants.

(P.H. Andersen, Department of Infectious Epidemiology and Prevention, A. Fomsgaard, Department of Virology and Microbiological Special Diagnostics)

Sporadic cases of malaria in Southern Europe

In the course of the summer of 2017, several Southern European countries have reported sporadic cases of locally acquired malaria, presumably introduced into the local areas by travellers.

Greece

As per 17 August 2017, Greece had reported five locally acquired cases of vivax malaria, four in the Ditiki Ellada region and one in the Stella Ellada region.

Additionally, a locally acquired case of falciparum malaria was reported in the Ipeiros region. The person in question had not travelled in malaria areas, but had been admitted to hospital at the same time as a patient who was being treated for falciparum malaria. The mode of infection was assessed to be either via local mosquitoes or possibly acquired in hospital in connection with a non-sterile invasive procedure. However, no specific shortcomings have been observed in hospital hygiene.

Italy

In Italy, a four-year-old girl died due to locally acquired falciparum malaria. The girl was admitted on 13 August 2017 to the Trento hospital in the Veneto region where she was diagnosed with diabetes. On 2 September 2017, the girl was re-admitted and diagnosed with falciparum malaria. She died on 4 September 2017. The girl had not visited any known malaria areas ever.

Epidemiological investigation showed that two children with imported falciparum malaria were admitted to the same department as the girl during her stay in the Trento hospital. The investigation, however, could not identify any breaches to the medical procedures that might have caused the infection.

An entomological survey in the Trento area and in Bibione north of Venice, where the girl had spent her holidays, failed to confirm the presence of Anopheles mosquitoes there. At a very low occurrence of malaria mosquitoes it may, nevertheless, be difficult to detect these.

The molecular genotyping of the Plasmodium falciparum parasite detected in the girl and the two other children admitted to the hospital has not yet been concluded.

France

On 7 September 2017, the French health authorities reported two locally acquired malaria cases in the Allier department of the Auvergne-Rhône-Alpes region in central France. Both participated at a wedding party from 11 to 16 August 2017 in Moulins in the Allier department. Both presented with symptoms on 26 August, and were diagnosed with falciparum malaria on 30 August and 1 September 2017, respectively.

Investigation has revealed that none of the wedding guests had recently travelled to a malaria area or had symptoms of malaria.

Nevertheless, an imported case of falciparum malaria was detected in a person from Burkina Faso who had stayed in Moulins and in the surrounding area for several days in the two weeks leading up to the wedding. Entomological investigation failed to detect the presence of the Anopheles mosquitoes that can transmit malaria.

Molecular genotyping of the detected Plasmodium falciparum parasites will be performed to assess if there is any connection between the imported and the two locally acquired cases.

Cyprus

On 8 September 2017, the English health authorities reported three imported cases of vivax malaria in travellers from Esentepe in the northern (Turkish) part of Cyprus.

Two 12-year-old siblings and a third person had all stayed in the northern part of Cyprus for 2-3 weeks in August 2017. All three developed symptoms on 29 August 2017, and infection with vivax malaria was confirmed in England after they returned home. No information is available about ethnicity or previous journeys to malaria-endemic areas, and the remaining conditions relating to the mode of infection also remain unknown, but the presence of malaria mosquitoes and the climatic conditions in Cyprus facilitate local transmission.

Commentary

According to the European Surveillance System for infectious diseases (TESSy), the EU area witnessed 12 cases of locally acquired malaria in 2016: Eight cases in Greece, two in France, one in Spain and one in Lithuania. All cases were classified as sporadic cases of malaria introduced by people who had previously stayed in malaria areas, or, in some cases, so-called airport-acquired malaria, where malaria infected Anopheles mosquitoes are introduced into a limited area surrounding an airport following the arrival of an airplane from a malaria-endemic area. No persisting circulation of malaria was reported in the EU/EEA area in 2016, and the risk of malaria spreading in the EU in connection with the current cases is assessed to be very low.

For travellers to areas with reports of locally introduced malaria, the risk of transmission is also very low. However, as other mosquito-transmitted conditions have also been detected in Southern Europe (Chikungunya and West Nile fever), the general recommendation is that travellers to Southern Europe should protect themselves against mosquito bites.

Locally acquired cases of malaria have been recorded since 2009 in Greece, with the highest number being recorded in 2011, EPI-NEWS 48/11. Since 2012, limited local malaria transmission has been seen. The infection has been introduced by arriving travellers, and the outbreaks have been localised to various locations in Greece, why the country's (and the World Health Organization's Europe Region’s) status as a malaria-free zone has not been threatened.

Hospital-acquired transmission of falciparum malaria has previously been described in the EU, but it is very rare and does not constitute a significant public health problem. Hospital-acquired transmission was most frequently described in connection with blood transfusion, and re-use and incorrect handling of syringes and intravenous catheters, but is rare in countries with advanced healthcare systems.

Healthcare workers should, nevertheless, always be attentive to the risk of hospital-acquired infection, and they should ensure that all relevant procedures are observed when a malaria patient is admitted to ensure that blood-borne transmission is avoided.

There is no knowledge of any occurrence of hospital-acquired malaria infection in Denmark, and the presence of Anopheles mosquitoes is very limited. Therefore, malaria transmission is not seen in Denmark.

(A.H. Christiansen, L.S. Vestergaard, P.H. Andersen, Department of Infectious Disease Epidemiology and Prevention)

Link to previous issues of EPI-NEWS

27 September 2017