No 1-2 - 2017

Infectious diseases in 2016

Zika virus epidemic

Very few people would have thought that the next major infection threat against the public health would be a known but often overlooked virus that is primarily transferred by mosquitoes, but also sexually. Infection of pregnant women may lead to very serious neurological malformations in the foetus. On this backdrop, the WHO declared the Zika virus a public health emergency of international concern.

Besides, the infection only rarely causes serious disease, apart from the fact that Guillain-Barré syndrome (GBS) was described as a complication to Zika virus infection. Nevertheless, GBS is also seen as a complication to other infections. The latest situation report from the WHO reports Zika virus infection in 75 countries or territories, 29 of which have reported an association with microcephaly, other late neurological sequelae or congenital infection (congenital Zika syndrome). A total of 20 countries have reported an increase in the occurrence of GBS.

The Zika virus epidemic demonstrates that infections remain unpredictable and the epidemic underlines that it is important to have in place a set of centralised infection preparedness measures. The epidemic has given rise to a considerably heightened activity level related to diagnostics, risk assessment and counselling alike, EPI-NEWS 14/16, 21/16 and 41/16.

On 18 November 2016, the WHO declared that the Zika virus has ceased to constitute a public health emergency of international concern. Thus, Zika virus is on its way to becoming one of the viruses that we will need to live with in the future. Zika virus will expectedly become endemic in areas harbouring the mosquitoes that can transmit the infection and where there is a reservoir that may pass on the infection.

Compared with the pre-2015 situation and based on the geographical spreading observed in 2016, the infection is expected to become more widespread in the future. Therefore, an assessment of the risk for pregnant women will form part of future travel advice. Even though many scientific questions remain unanswered, it is important to underline that the risk of congenital malformations is documented from countries with endemic spreading (South and Central America, primarily), but not from areas where Zika virus infection has been endemic for decades. This may be because infection in the latter areas will most frequently occur before child-bearing capacity is achieved, or because the infectious pressure is generally reduced when shifting from the epidemic to the endemic level. It is therefore likely that the risk assessment will be lowered as Zika virus becomes endemic and starts forming part of the “normal” infection scenario.

Coverage for the HPV vaccination programme plummets

The HPV vaccine is safe and effective, and only few years after its introduction several Danish and international studies documented that the vaccine protects effectively against precursors to cervical cancer and genital warts. Despite these positive experiences, concern has been raised concerning the vaccine's safety, a concern harboured, in particular, by many Danes.

The coverage of the HPV vaccine among girls born in 1998-2000 was 92%. It has dropped to 46 % for girls born in 2003; and presently only 23 % of girls born in 2004, i.e. girls who turned 12 years old in 2016, have been vaccinated.

This constitutes a major drawback for cancer prevention. The SSI has conducted research (links:http://www.bmj.com/content/347/bmj.f5906.long; http://jamanetwork.com/journals/jama/fullarticle/1886177; http://jamanetwork.com/journals/jama/fullarticle/2088853), documenting that the vaccine is not associated with any serious side effects.

A study performed in 2016 demonstrated that among cases in which either a physician or the citizen herself had reported side effects, there was an over-representation of medically unexplained symptoms already before the initial HPV vaccination. This speaks against the girls’ symptoms being caused by the vaccine in general, but does, of course, not exclude that some girls may, in fact, have experienced side effects.

Research and the generally more nuanced debate in the press have triggered renewed hope that the vaccination coverage will once again start to increase, but we still have a long way to go before trust has been restored. In this context it is important to listen to the concerned families and to enter into a dialogue about the benefits and risks of the HPV vaccine. This will be an important task in 2017.

2016 also recorded preliminary success after the first year with statutory registration of vaccinations in the Danish Vaccination Register, EPI-NEWS 45/16. This means that in future we will be able to conduct better studies of the safety and effect of vaccines. These data have, among others, been employed to determine the effectiveness of the influenza vaccines among elderly people and they are used in the important studies on HPV vaccine safety.

In collaboration with the Danish Health Authority and the Danish Medicines Authority, the SSI prepared the first annual reports about the childhood vaccination programme in 2014 and 2015 . We expect to publish the next report covering 2016 in connection with the European Immunization Week in week 17 2017.

Antimicrobial drug resistance

For the past 20 years, Danish monitoring of antimicrobial drug consumption and development of resistance in animals, humans and foods has provided the scientific basis for measures aiming to fight antimicrobial resistance. DTU Food, DTU Vet and Statens Serum Institut are the main partners behind the DANMAP monitoring programme. The programme was the first of its kind worldwide and is frequently presented abroad as an example to follow.

Large-scale European collaboration has yielded the first ever detailed overview of the prevalence of carbapenemase-producing enterobacteria, CPE, in Europe. The increase in CPE is one of several concerning trends in the occurrence of resistant bacteria.

Multiresistance in the gram-negative rods is particularly worrying as these bacteria frequently cause infection, which - in the case of carbapenemase-resistant bacteria, is very difficult to treat with common antibiotics.

Another great challenge is the vancomycin-resistant enterococci that have increased considerably in numbers and which have, among others, caused outbreaks at hospitals in the Capital Region of Denmark. MRSA continues to follow an increasing trend in the community. This includes cases directly associated with travel activity as well as community-acquired cases. The number of new cases of livestock MRSA has not increased since it peaked in 2014. It is encouraging that MRSA infections acquired at hospitals remain rare, and thereby the Danish Health Authority’s MRSA action plan meets its main purpose, EPI-NEWS 23/16.

Increased use of sequencing methods for characterisation of micro-organisms

The field of microbiology currently evolves in exciting ways - many older phenotypic methods and not quite as old molecular biology methods are being replaced by or supplemented by sequencing of the entire genetic material in micro-organisms (whole-genome sequencing or simply WGS). WGS has proven its strength in the form of both complete and detailed characterisation of micro-organisms, which enhances our understanding of the evolution, virulence and pathogenesis, detection of resistance properties and as a tool for establishing routes of infection and transmission in outbreak investigations.

In future diagnostics, the next step will expectedly be microbiome tests focusing not only on the individual micro-organism, but on populations of micro-organisms. These findings have already proven to have a surprising influence on the development of very different diseases, both infectious diseases and also non-communicable diseases , e.g., obesity and neurological conditions, and the new microbiome tests will increasingly find their way into standard clinical diagnostics.

Where this trend will eventually take us, we do not know. But already now we can see that, compared with yesterday’s technology, it is cost-effective in relation to some bacteria to use WGS and it also allows us to gain more knowledge. Nevertheless, the efforts required to quality ensure these methods and to store and analyse the considerable amounts of data involved and, not least, to interpret and disseminate the information should not be underestimated. These tasks require considerable and often cross-disciplinary efforts.

Monitoring of the food-borne bacterium Listeria monocytogenes is one of the first areas within which the SSI initiated WGS typing. Thanks to this initiative, we now understand the sources of infection better and part of the knowledge gained has already been put into action by the Danish Veterinary and Food Administration thereby increasing the safety of the food we - and particularly elderly and sick people - eat.

The food-borne outbreaks and field epidemiology at Statens Serum Institut

One of the important activities that Statens Serum Institut takes part in is the investigation of food-borne outbreaks. These investigations require microbiological and epidemiological knowledge and experience. Statens Serum Institut has a high level of outbreak investigation preparedness, and we continuously handle a range of outbreak cases and typically perform around 20 major investigations every year.

Among the outbreaks that received much media attention in 2016 were 23 linked norovirus outbreaks that occurred in a single week in April affecting a minimum of 412 people. The outbreaks were handled in the context of an inter-institutional collaboration with the Danish Veterinary and Food Administration and DTU Food; a collaboration that has been in place for many years and is unique for Denmark. The source was green lettuce from France, and in the investigation of this outbreak the full range of investigational tools was applied; among others, sub-typing of virus allowed us to link patients from different parts of the outbreak and to identify the salad as the source, EPI-NEWS 20/16.

Enhancement of digital surveillance

The modernisation of the national surveillance systems continued in 2016, among others through the initiation of the eRES project, which aims to develop a tool for timely surveillance of antimicrobial drug resistance that may strengthen the regions’ treatment and infection control efforts and ensure that reports like DANMAP may be published without delay.

More and more infections are being monitored via the microbiology database, the MiBa, including neuroborreliosis, chlamydia, gonorrhoea and several airway infections. The MiBa is an indispensable tool for the regions and is an example that data from surveillance and diagnosis may inform the meeting with the patient and contribute to ensuring safe treatment courses, among others for patients who carry resistant bacteria.

The HAIBA database for monitoring of hospital infections was enriched with information about post-operative infections following hip replacement surgery, EPI-NEWS 20/16 and 47/16. The algorithm for admissions which was developed for the HAIBA is also being used for monitoring of, e.g., influenza, where information about admissions, including intensive care, is used to assess the seriousness of influenza. In future, this method may be used more broadly for monitoring of the seriousness of other pathogens, e.g. mycoplasma, pneumococci, whooping cough bacteria and resistant bacteria.

Whooping cough and mycoplasma epidemics and an increase in gonorrhoea and syphilis

2016 was a remarkable year with endemic occurrence of whooping cough, and we need to go back as far as 2002 to find a similar epidemic, EPI-NEWS 46/16. In 2013, a booster vaccination was introduced that protects against whooping cough (5-year booster). It seems that the honeymoon period following the introduction of the whooping cough component to the 5-year vaccination has now ended, even though it deserves mention that the focus on whooping cough among adults is now stronger, and better diagnostic methods have also been developed.

For the second autumn season running, the Danish population was burdened by Mycoplasma pneumoniae infections,EPI-NEWS 41/16; and towards year’s end we recorded signs of increases in the RSV occurrence and an early influenza season, INFLUENZA-NYT 51/16 (in Danish language).

But the airway infections are not the only group of infections to draw attention. Sexually transmitted diseases like gonorrhoea, EPI-NEWS 38/16, and syphilis, EPI-NEWS 36/16, are increasing sharply; and enhanced efforts are required to reduce these conditions which, unfortunately, are spreading beyond the traditional risk groups.

With this summary of important events from 2016, I take the opportunity to extend my wishes for a happy New Year to all readers of EPI-NEWS.
(K. Mølbak, Division of Infection Preparedness)

Measles case in North Zealand

Statens Serum Institut has detected a measles case in a 10-year-old child residing in North Zealand.

The child returned from a vacation journey to Thailand on 29 December 2016 and had measles detected on 4 January 2017. The child’s vaccination status remains uncertain. The Danish Patient Safety Authority, Supervision and Guidance East, was informed immediately and has initiated preventive measures among persons who may have become exposed to infection.

The National Danish Reference Laboratory for Measles at Statens Serum Institut has studied the detected measles virus further and has established that it belongs to genogroup D8 and that it is identical to the measles virus detected in another traveller who returned from Thailand in August 2016. The measles type in question has been in circulation in Asia for a considerable period of time.

All non-immune travellers to areas with a measles risk are recommended measles vaccination prior to their departure (in the form of MMR vaccine).

Physicians, particularly in the Capital Region of Denmark, are encouraged to be extra attentive to the diagnosis in the coming weeks. It is important that any person who is suspected of having measles avoids being in waiting rooms with other patients as measles is extremely infectious.

2016 saw only three detected cases of measles all of which had become infected abroad in Pakistan (1) and Thailand (2), respectively.

Sampling

On suspicion of measles, the following samples should be taken:

1. A blood sample for IgM/IgG antibody determination. IgM antibodies may be confirmed by rash.
2. Pharyngeal swab and urine for virus detection (PCR). The greatest possibility for detecting measles virus is in the early phases of the disease course, but the virus is frequently detectable for several weeks after the acute disease occurs. A negative finding does not exclude measles.

We request that all measles-positive samples be sent to the National WHO Reference Laboratory for Morbilli and Rubella, Section for Virology Surveillance and Research, Statens Serum Institut for characterisation which is free of charge.

For further details, please see the SSI's measles theme page.

Vaccination and prophylaxis following exposure

The primary form of prevention is MMR vaccination. MMR vaccination is normally offered to all children at 15 months and 4 years of age.

As post-exposure prophylaxis (PEP), MMR vaccination may be given to non-immune contacts within 3 days and normal human immunoglobulin within 6 days after certain exposure to infection. Certain exposure is defined as contact with a laboratory-confirmed or epidemiologically linked MMR case. Delimitation of the contacts needing PEP is done by the on-duty physician at the Danish Patient Safety Authority, Division for Supervision and Guidance (formerly the Medical Officers of Health). Expenses are covered by the regional authorities.

For more details on post exposure prophylaxis, please see here.

(L.K. Knudsen, P.H. Andersen, Infectious Disease Epidemiology and Prevention, T.V. Sydenham, Virus and Special Microbiological Diagnostics, L.D. Rasmussen, T.K. Fischer, Virology Surveillance and Research, G. Ertner, the Danish Patient Safety Authority, Supervision and Guidance East)

Link to previous issues of EPI-NEWS

11 January 2017