No 1/2 - 2020

Infectious diseases 2019

Disease outbreaks

The year started with a measles outbreak related to travellers from the French ski sports area of Val Thorens. In recent years, Europe has been affected by large measles outbreaks and nearly half of the cases occur in persons who are 20 years of age or more. 2019 saw a total of 15 measles cases in Denmark, among whom six had become infected abroad. Even so, Denmark is expected to maintain its measles elimination status, EPI-NEWS 37/17. MMR vaccination that protects against measles, mumps and rubella is important for non-immunised children and adults and should also be considered as a travel vaccine.

2019 witnessed several food-borne disease outbreaks. In spring, a large Yersinia enterocolitica outbreak was observed which affected Denmark and Sweden concurrently. The outbreak was eventually traced back to fresh imported spinach. Use of whole-genome sequencing on samples from both patients and foods means that food-borne disease outbreaks due to, e.g., yersinia and salmonella can be detected and solved more rapidly, and therefore they can also be prevented earlier. Additionally, whole-genome sequencing may contribute to establishing that patients form part of a single outbreak developing over a prolonged period of time. In 2019, six listeria cases occurring in the course of a 4-year period were shown to form part of a single outbreak  associated with a local greengrocer whose production was temporarily discontinued.

As part of a one-year project counting the participation of the Department of Clinical Microbiology in Aalborg, the Danish Veterinary & Food Authority and Statens Serum Institut (SSI), campylobacter bacteria were sequenced regularly in 2019, which is not normally the case. This meant, among others, that a massive and prolonged outbreak with Campylobacter jejuni  was detected. The outbreak comprised more than 10% of the sequenced patient isolates, which could be linked to chicken meat from a single chicken abattoir. Normally, approx. 4,500 cases of campylobacter are diagnosed annually, but in 2019 more than 5,300 cases were recorded. It has now become clear that outbreaks account for some of the many campylobacter cases, and the project underlines the potential of using new microbiological methods.

Towards the end of the summer, two deaths occurred within a short period of time due to haemolytic uraemic syndrome (HUS), a rare complication to infection with Shiga-toxin-producing E. coli (STEC). Whole-genome sequencing of the isolates revealed that the cases were sporadic and did not form part of an outbreak, i.e., did not share the same source of infection. An increase has been observed in the number of STEC cases detected in recent years. Part of the explanation may be the introduction of more sensitive diagnostic methods and that the clinical criteria for STEC testing changed at several departments of microbiology in the 2014-2018 period. Because of the potentially very serious complications of the HUS-associated types, it is important that patients experiencing bloody diarrhoea have samples taken for STEC testing.

In 2019, the SSI in collaboration with the University of Copenhagen (UC) identified a new risk area for tick-borne encephalitis (TBE) around Tisvilde Hegn, where four patients presumably became infected in the course of the summer. Subsequently, the SSI confirmed and sequenced TBE in ticks collected by the UC in the vicinity of a popular nature playground in the area. As climate changes proceed, we should expect that new TBE risk areas, co-called microfoci, may occur across Denmark, and doctors therefore need to be attentive to TBE as a differential diagnosis in all patients with symptoms of encephalitis, regardless of their travel history, to ensure that the patients’ symptoms are explained, and that new Danish risk areas are identified as early as possible.

In 2019, the SSI detected two hospital-associated cases of infection with a rare bacterium coined Mycobacterium chimaera, EPI-NEWS 40/19. T he patients had very probably become infected via specialised equipment used to regulate the temperature during open heart surgery (a so-called heater-cooler unit). The two Danish cases form part of a global outbreak counting more than 200 cases associated with heater-cooler units. Nationally as well as internationally, various preventive measures have been introduced for using the equipment to prevent further transmission from the equipment to humans. In Denmark, active tracing of possible patients has been performed in the cardiac centres of the Danish regions and through registers, but, to date, no further cases have been identified. These efforts were made in collaboration counting the Danish Patient Safety Authority, the Danish Medicines Agency, the Danish Health Authority, the SSI and the affected regions.

Infection with Mycobacterium chimaera may present after years of delay and with unspecific symptoms. Therefore, additional late cases cannot be fully ruled out. The bacterium grows slowly, is difficult to detect and requires special diagnostics at the SSI. For more information about the Mycobacterium chimaera outbreak, please see here.

The autumn was marked by a prolonged whooping cough epidemic that was announced in September, EPI-NEWS 38/19. 2019 saw the detection of more than 3,000 whooping cough cases, the highest number of laboratory-confirmed cases in recent history. To protect infants as well as possible, the Danish Health Authority introduced a temporary whooping cough vaccination programme for pregnant women as per 1 November, and preliminary reports indicate that the programme has gained a very high coverage, EPI-NEWS 51/19.

Internationally, the ongoing Ebola outbreak  in the Democratic Republic of the Congo has attracted considerable attention. The outbreak started in the summer of 2018 and has yet to be contained despite ring vaccination with a new active vaccine and massive efforts made by the WHO, the UN and a wide range of aid organisations. Nearly 3,400 cases have been recorded, and the epidemic has caused 2,200 fatalities. The most recent cases have been observed in the North Kivu area. In the course of the outbreak, more than 240,000 contacts have been recorded, and 259,000 persons, including health workers, have been vaccinated. Due to the instable political context, the aid work is marred by considerable logistic challenges, including challenges related to ensuring the safety of aid workers. Furthermore, the main problem is spreading of Ebola virus at hospitals because basic infectious hygiene principles are not observed. This is worrying in an international preparedness perspective, as spreading of infections via hospitals has also been a hallmark of SARS, MERS-CoV and Lassa fever outbreaks. Additionally, observing infectious hygiene guidelines in healthcare - including in low and middle-income countries - is essential to limit the spreading of antibiotics-resistant bacteria and fungi.

The vaccine area

In addition to the temporary whooping cough vaccination programme for pregnant women, HPV vaccination was introduced for boys who turn 12 years old as from 1 July 2019. The coverage among girls has followed an increasing trend in recent years, and as per 8 December 2019, 77% of all girls who have turned or would turn 13 years old in 2019 (born in 2006) had received the first HPV vaccination. In addition to protecting boys against HPV-associated cancer types and condyloma, vaccination of boys will also contribute to the overall population herd immunity.

Unfortunately, HPV vaccines are in short supply globally, meaning that the manufacturer cannot provide vaccines not forming part of the programme, EPI-NEWS 45/19. Possibly, pharmacies may obtain vaccines through parallel imports. Recent years have seen several examples of global vaccine shortage. This is due to difficulties regulating supply and demand, that vaccine production is in the hands of fewer/larger manufacturers, and probably also increasing quality assurance requirements on the entire production chain, leading to an increased risk of production errors and delays.

The SSI is obliged to ensure the supply of vaccines for vaccination programmes only; however, in a wider perspective, we will see more vaccine shortage situations in the future.

In the autumn of 2019, the SSI and the Danish Health Data Authority implemented a new vaccination reminder scheme under which parents receive reminders both before and after childhood vaccination, both in their e-Boks and by NemSMS, if they have signed up for this service, EPI-NEWS 42-43/19. For the scheme to work optimally, general practice needs to register vaccinations from the list of recommended vaccination courses in the Danish Vaccination Register, which has caused some initial problems, EPI-NEWS 50/19. Hopefully, in the long term, the scheme will allow more children to receive the recommended vaccinations timely.

Antimicrobial resistance

Antimicrobial resistance (AMR) is one of the primary threats against public health. According to this year’s DANMAP report, the total consumption of antimicrobials for animals as well as humans remains low in Denmark compared with the EU and the rest of the world, EPI-NEWS 46/19. Since 2012, primary healthcare has observed a sustained decrease in the number of dispensed prescriptions. Since 2017, when the National Action Plan on Human Antibiotics was published, consumption in primary healthcare has decreased further. In contrast, the total consumption of antibiotics in hospitals continues to rise. Here, the main focus has been on the share used of critically important antibiotics (cephalosporins, fluoroquinolones and carbapenems) of the total consumption. This share followed a declining trend in 2011-2017, but despite enhanced measures, no further decrease has been achieved since then.

Furthermore, a worrying development has been detected in the occurrence of some AMR types. 2018 recorded a total of 788 patients with a minimum of one admission with blood poisoning due to Enterococcus fæcium. Among these, 97 patients (12% ) had the vancomycin-resistant type of Enterococcus fæcium (VRE). This constitutes a substantial increase compared with 2017, when the share was 7%; and, for comparison, the share recorded in 2008 was 0.5%. In 2018, a total of 156 cases were recorded of carbapenemase-producing intestinal bacteria (CPE) in 141 patients. In 2017, a total of 104 cases of CPE were recorded in 96 patients, which constitutes an almost 50% increase in a single year. For comparison, only 31 CPE samples were recorded in 2008-2013. Part of the increase may be owed to increased recording of CPE cases, as CPE became notifiable in September 2018, but this cannot explain the entire increase observed.

Both VRE and CPE infections can be very difficult to treat, as very few antibiotics remain effective for treatment of these infections. Additionally, spreading often occurs with these micro-organisms within and between hospitals. The SSI, in collaboration with the regions, is developing an outbreak database, which will cover CPE in the pilot phase. In the longer term, the database may ensure a better overview and therefore also enhanced handling of hospital outbreaks across regions.

Recent years have also seen resistance in fungi that may cause infections in humans, among others due to the use of agricultural fungicides. In 2018, it was decided to introduce national monitoring of the Aspergillus fumigatus fungus following signs of rising resistance to azole-containing agents used in the treatment of fungal infections. Azoles are the best and most widely used agents in the treatment of these infections. Aspergillus fumigatus may, among others, cause infections in leukaemia patients and among patients with chronic pulmonary conditions, including cystic fibrosis, advanced COLD or previous tuberculosis. Monitoring of the results from the first nine months (October 2018-June 2019) showed that 6% of the approximately 500 patients with Aspergillus infection had become infected with azole-resistant Aspergillus fumigatus fungi, and that 69% of these strains had acquired resistance due to use of azoles in the environment. Environment-resistant Aspergillus fumigatus fungi were found in samples from all five Danish regions.

One Health

The AMR issue along with several of the outbreaks recorded in Denmark this year, e.g., with TBE and other zoonoses, underline the importance of adopting a One Health approach to prevention of infections, i.e., a view encompassing animal, human and environmental health. As from 1 January 2020, the UC and the SSI have fully implemented their takeover of veterinary preparedness activities, thereby further enhancing the basis for a One Health approach to infections in Denmark. In 2020, Denmark holds the chairmanship of the Nordic One-Health collaboration on AMR.

In 2018, the Danish government announced that Denmark will be participating in collaborative efforts with the World Bank to establish an ”International Centre for Antimicrobial Resistance Solutions” (ICARS). ICARS will work cross-sectorially and globally to develop and implement research-based solutions in the prevention of AMR in low-income and middle-income countries. The reason why the World Bank contacted Denmark was that Denmark is an early adopter of a One Health approach to the AMR problem. In 2019, an ICARS secretariat was established on the premises of the SSI.

The secretariat works to consolidate the organisation and commit international stakeholders as part of this visionary and ambitious initiative.
With this summary of 2019, we would like to wish all readers of EPI-NEWS a happy New Year!

(T.G. Krause, Department of Infectious Disease Epidemiology and Prevention)