No 49 - 2015

New HPV vaccine as from 1 February 2016

In pursuance of the statutory standard vaccine tender, a new HPV vaccine, Cervarix®, shall be used in the childhood vaccination programme as from 1 February 2016. The vaccine tender is used for publicly funded vaccines not produced by Statens Serum Institut. The criteria applied in the assessment of any tenders received for the HPV vaccine are available here (in Danish language).

The Cervarix® vaccine protects against the two highly pathogenic HPV types (16 and 18) that cause 70% of all cases of cervical cancer.

Protection against cervical cancer and the adverse event profile of Cervarix® are comparable with those of the previously used vaccine, Gardasil®. In contrast to Gardasil®, the new Cervarix® vaccine does not provide protection against condyloma. Cervarix® is approved for use as from 9 years of age. The Danish Health Authority recommends that the vaccine is given in the childhood vaccination programme at 12 years of age.

All girls who receive HPV vaccination under the childhood vaccination programme as from 1 February 2016 shall therefore initiate vaccination with Cervarix®. For all girls who are under 15 years at their first vaccination, the vaccination schedule consists of 2 doses given at a minimum interval of 5 months. For girls who are 15-17 years of age and who have not previously received HPV vaccination, the vaccination schedule consists of 3 doses given on days 0, 30 and 180. The previously used settlement codes will continue to apply.

No data on combined vaccination with various HPV vaccines are available, and girls/women who have already received a minimum of 1 dose of Gardasil® shall conclude the schedule using this vaccine.

More detailed information will be provided in a future issue of EPI-NEWS.
(P.H. Andersen, Department of Infectious Disease Epidemiology)

Mycoplasma pneumoniae epidemic

In the course of the past 3 weeks (Weeks 46, 47 and 48), each week has brought the detection of approx. 250 new cases of Mycoplasma pneumoniae by PCR in Denmark. With a positive rate among the tested persons exceeding 10% in all 5 Danish regions (the mean share exceeds 13%), this is now considered a national epidemic. Nevertheless, the epidemic seems to be less extensive than the 2011-2012 outbreak, and we now seem to have passed the peak of the epidemic. Even so, many new cases should be expected in the next 4-8 weeks.

The majority of cases are still seen in children aged 7-12 years of age, but a relatively large number of cases is also observed in smaller children, particularly in those aged 4-6 years of age. For more information about Mycoplasma pneumoniae, including diagnostics, please see EPI-NEWS 45/15 and The SSI's disease encyclopaedia (in Danish language) at ssi.dk.
(S. Uldum, Microbiology and Infection Control)

Zika virus in several countries in South, Central and North America and in Cape Verde

The WHO has informed of a Zika virus outbreak in Brazil, which started in South America in 2014 after an outbreak of the same virus in French Polynesia in 2013-14. The outbreak is now linked to an observed increase in the number of malformations in foetuses/neonates in the two countries.

Historical and current epidemiology

Zika virus belongs to the flavivirus family and is transmitted to humans via mosquito bites. Zika virus has been known since 1947; and since then, the virus has caused sporadic infections in Africa and Asia. Zika virus belongs to the group of emerging viruses that may potentially spread to new areas where the Aedes mosquito is found. In 2007, the virus was detected outside of Africa and Asia for the first time ever - on the island of Yap in the Western Pacific. The virus spread to other islands, and in 2013-14 it caused an epidemic in French Polynesia. By early 2014, the virus had been detected in the Easter Island (Chile) from where it spread to the South American mainland, where Brazil reported the first confirmed cases in May 2015 . Subsequently, Zika virus has spread to the majority of Brazil and now also to a range of other countries.

As per 2 December 2015, a considerable number of Zika virus infections have been reported from Brazil (18 states) and Columbia and also a number of cases from Cape Verde. From the American continent, reports have also been received about a limited number of cases in Surinam, Paraguay and Venezuela and in the North and Central American states of Mexico, Guatemala and El Salvador. 2015 also saw cases on the islands of Fiji, Vanuatu, Samoa, New Caledonia, the Solomon Islands and Indonesia.

Zika virus is transmitted through mosquitoes (primarily Aedes aegypti, but also A. hensilii and A. albopictus) and generally causes a mild infection that frequently runs a completely symptom-free course. It is estimated that only 1 in every 4 infectees carries symptoms. The incubation period is 3-12 days.

Symptoms

Zika virus is similar to other pathogenic vector-borne flaviviruses such as dengue, West Nile and Japanese encephalitis virus, but only runs a relatively mild course in humans. Symptoms may include a slight fever (normally below 38.5 degrees Celsius), transient arthralgia and possibly swelling of minor joints in the hands and feet, a rash that spreads from the face to the rest of the body, red eyes or eye inflammation without pus and more unspecific symptoms like myalgia, fatigue and headache. The illness is brief, from 2 to 7 days.

Previously, during the epidemic, cases of muscle paralysis (Guillan-Barré syndrome) have been associated with the infection, but any causal link has yet to be determined.

In 2015, the Brazilian authorities have observed a considerable increase in neonates with microcephaly (head circumference < 5% percentile), primarily in the Eastern states and co-occurring with the spreading of Zika virus in the country . A possible connection between Zika virus infection in pregnant women and abortion/birth of children with microcephaly has also been observed in French Polynesia, where a Zika epidemic was observed in the period from September 2013 to March 2014. Likewise, in French Polynesia in 2014 and 2015, an increase was subsequently observed in the number of abortions/children born with microcephaly and other anatomical development defects of the brain/central nervous system by mothers who were in their first or second trimesters during the epidemic (12 cases compared with normally 0-2 annual cases).

Furthermore, five cases of lacking swallowing function in neonates born in the same period has been observed. All four tested mothers had antibodies to the flavivirus family of which Zika virus is a member. Normally, this condition is rarely seen in French Polynesia.

The association is temporal; a certain causal association has yet to be demonstrated. In two cases, Zika virus has been detected in the amniotic fluid in pregnant women who had relevant symptoms. Both foetuses presented with signs of microcephaly in utero. This shows that the virus is capable of crossing the placental barrier, which is a precondition to causing infection in the foetus.

Diagnostics

Physicians should consider Zika virus infection as a differential diagnosis in patients presenting with fever following stays in the affected areas, particularly in South America and French Polynesia. The diagnosis is made at Statens Serum Institut during acute illness and through specific PCR "Zika virus RNA" (R2027, Diagnostisk Håndbog) in EDTA blood. This detection of virus may be supplemented by serological tests for Zika virus IgG and IgM antibodies (R2017) in case of acute or recently surpassed infection. Antibody cross-reaction to other flaviviruses such as dengue may occur, but the titre increase is specific to Zika virus.

Commentary

Zika virus may potentially spread to new areas where the Aedes mosquito is found. Cases imported to Europe from Asia and French Polynesia have been reported, but at present transmission of Zika virus has yet to be observed in Europe. The current major outbreak in South America may be followed by more travel-associated cases. The risk that the infection may spread in Europe is real as the vector Aedes albopictus is present in several European countries, particularly around the Mediterranean. Nevertheless, the risk is currently assessed as being very low by the European Centre for Disease Prevention and Control because of the climatic conditions with low European winter temperatures.

Until further notice, travellers to the affected areas, and pregnant women in particular, should protect themselves against mosquito bites from sunrise to sunset. The Aedes is a day-biting mosquito, which is particularly active around sunrise and sunset, but which bites throughout the day. For pregnant women, the best protection is to wear long-sleeved and full-legged clothes and to limit the use of mosquito spray to the exposed skin areas. If possible, the clothes should be impregnated with a repellent or an insecticide.

Physicians should consider Zika virus infection as a differential diagnosis for dengue and chikungunya fever, among others, in patients who have recently travelled to any of the risk areas.
(P.H. Andersen, Department of Infectious Disease Epidemiology, A. Fomsgaard, Virus Research and Development Laboratory (VRDL), Department of Microbiological Diagnostics and Virology)

Link to previous issues of EPI-NEWS

2 December 2015