No 1/2 - 2024

Infectious diseases 2023

Even though COVID-19 demanded less public attention in 2023 than previously, the SSI followed developments related to SARS-CoV-2 virus closely as is the case for the remaining airway infections. Additionally, 2023 marked the intensified return of several infectious diseases in the wake of the pandemic.

Amended executive order on notification of infectious diseases and electronic notification of MRSA cases

On 1 November 2023, the amended Executive Order on Notification of Infectious Diseases (Exec. Ord. no. 2023 of 27/10/2023) of the Danish Health Authority became effective, EPI-NEWS no. 44b/2023. Among others, the notification ensures that laboratory data may play a more important role in disease monitoring. In addition to laboratory data notified by the departments of clinical microbiology (DCM) to the Danish Microbiology Database (MiBa), other laboratory data of relevance to infections are reported by clinical biochemistry departments and clinical immunology departments to the laboratory data bank (LABA). Currently, test results from LABA concerning hepatitis B, C, HIV and syphilis form part of the monitoring efforts. This means that Denmark is now in the process of establishing a more comprehensive, updated and therefore hopefully more effective monitoring of infectious diseases.

2023 also marked the introduction of electronic notification of MRSA cases. EPI-NEWS no. 34b/2023. Notification of MRSA is different from the other notifiable diseases as detection of a new type of MRSA in any patient triggers an alert to the ordering physician in the form of an auto-generated e-mail from the SSI saying that the case must be notified. In future, the same system may be used for other notifiable diseases.

Sexually transmittable infections on the rise

The number of gonorrhea cases has followed an increasing trend for a number of years, but the increase recorded from 2021 to 2022 was exceptionally steep (46%) reaching 5,204 cases. The corresponding figure for 2023 is expected to remain at this high level, EPI-NEWS no. 50/2023. The occurrence of gonorrhoea remains high among men who have sex with men (MSM), but is now also rising among young heterosexual people. It is important to remember using a condom and to get tested if you are at risk of having become infected. This helps break infection chains.

Chlamydia cases also increased by 14% from 2021 to a total of 41,634 cases in 2022, EPI-NEWS 38/2023. A total of 86% of all chlamydia cases are seen in 15-29-year-olds - most frequently in women. However, the number of persons tested in this age group is considerably lower among men than among women. The preventive measures therefore need to be strengthened through information about safe sexual behaviour, increased sampling activity and, once chlamydia has been detected, partner tracing.

The number of notified syphilis cases has been fluctuating somewhat these past years. In 2022, a total of 676 cases were notified, EPI-NEWS no. 51a/2023. Even though MSM remains the group that accounts by far for the greatest number of syphilis cases, a slight increase is observed among heterosexually infected persons. This trend is cause for concern as it may indicate that syphilis is gaining a foothold in the general population. The increase observed among heterosexuals should be considered an important topic for doctors who need to consider syphilis as a possible differential diagnosis, also among heterosexuals. We may possibly also expect an increase among pregnant women as a direct consequence of the increase recorded among heterosexual people. In various countries, including the US, a considerable increase is seen in the number of congenital syphilis cases. Since 1 January 2010, the general screening of pregnant women in Denmark has included syphilis, EPI-NEWS no. 27-33/2010.

Integrated monitoring of COVID-19 and other airway infections

As COVID-19 is starting to behave more like the other seasonal viral airway infections, the SSI has launched a new platform that presents all figures and data from the national monitoring of COVID-19, influenza and RS virus in addition to data from the current (2023) Mycoplasma pneumoniae (MP) and whooping cough epidemics. This weekly assessment provides an overview of current infections, admission trends and virus types and variants in circulation.

The SSI monitors a range of airway infections all year round, and intensifies and expands this monitoring in the autumn and winter months when the infections tend to increase.
The monitoring of airway diseases is based on a host of monitoring systems, including reporting from citizens, enquiries to general practice and emergency physicians, laboratory tests and hospitalisations. These elements form part of the constant monitoring provided by the SSI to follow current infection trends and keep track of how transmission evolves in Denmark.

Project “Measuring Virus in Denmark” was initiated when the COVID-19 monitoring was down-scaled and the publicly available test centres closed in late March 2023. The project is based on voluntary self swabs performed in the participants’ homes in case of disease with symptoms of airway infections. Approx. 50,000 persons can participate from selected workplaces, and more than 200,000 randomly selected citizens and their households have also been invited to participate. The test results contribute to the integrated monitoring and are also presented separately on the platform.

This project - in line with Danish waste water monitoring - is an example of a novel monitoring tool developed in connection with the COVID-19 pandemic. Both of these tools may be developed to monitor additional pathogens, thereby contributing to the monitoring of existing disease and, potentially, any future disease epidemics. The system based on self-testing, and symptom reporting using an app is a scalable testing tool that may be used in connection with larger outbreaks or future threats.

Whooping cough and Mycoplasma pneumoniae epidemics and an early start of the RS virus and influenza virus seasons

In early July, the SSI informed of an increase in the occurrence of whooping cough, EPI-NEWS no. 27/2023. The increase continued throughout the summer, and the number of whooping cough cases in August reached a total of 439. This was about four times higher than the level normally seen between epidemics; and as the increase was observed in nearly all Danish areas, the SSI assessed that an epidemic was in progress, EPI-NEWS no. 36/2023. Subsequently, the detected number of cases increased even more, exceeding 1,660 cases in November, and the occurrence peaked in week 48 when a total of 479 cases were recorded. From then, a decline has been observed in the number of detected cases, but the number of tested samples has also been declining during the holiday season, and it is yet too early to call off the epidemic. Previously, the Danish Health Authority had recommended to the Danish Ministry of the Interior that a permanent free vaccination offer be introduced for pregnant women in order to protect neonates. Based on the increase, the offer, which had previously been time limited, was reintroduced as per 1 August 2023, EPI-NEWS 28-31/2023. In the period from August to November 2023, this vaccination programme has recorded an uptake of approx. 66%.

In the course of autumn, the occurrence of Mycoplasma pneumoniae also increased to an epidemic level after having remained at a low level for the previous 3½ years. The condition typically affects population groups that have not yet acquired immunity. Therefore, the condition is also typically seen among school children aged 6-12 years. (The occurrence of MP infections is also currently increasing in various other countries within and beyond Europe, including China).

For the third year running, Denmark is experiencing an early RS virus season. The RS virus season started as early as October; and by the end of December, the number of detected cases per week exceeded that of the 2022/23 season. The 2023/24 influenza season has also started early, and influenza A is almost the only type in circulation.

Analyses of the effect of variant-updated COVID-19 vaccines and seriousness of sub-variants, including BA.2.86

2023 has witnessed continuous community transmission of SARS-CoV-2 of varying intensity, driven by new variants and waning immunity, and following an increasing trend throughout the autumn and winter period.

Denmark has good public registries, including the Danish Vaccination Register, which is updated daily at very limited lag. Therefore, we can explore the level of protection provided by our vaccines shortly after vaccines have started being administered.

As from 1 October 2023, all Danes aged 65 years or more and persons belonging to select risk groups have been offered COVID-19 booster vaccination. This year, these vaccination efforts are based on updated vaccines targeting the so-called XBB.1.5 variant. This is the SARS-CoV-2 Omicron sub-variant that has dominated in the past year or so in Denmark and in many other countries globally. SSI studies of the vaccine protection that include follow-up through November show that people who have received booster vaccination have an approx. 75% lower risk of hospitalisation due to COVID-19 than people who have not been vaccinated.

In the course of autumn 2023, the share of SARS-CoV-2 infections with the sub-variant BA.2.86 increased, and in November the emergence of the new JN.1 sub-type meant that BA.2.86 became dominant. Based on the latest analyses, we see no signs that these infections are more serious than the previous ones measured by hospitalisations or need for intensive unit care. The vaccine-induced protection against infection and hospitalisation due to the BA.2.86 and JN.1 subtype remain in place, but at a lower level than for other variants.

High occurrence of group A streptococcal infections in 2022-2023

From late 2022 through the summer of 2023, a high level of group A streptococcal (GAS) infections was recorded in Denmark. EPI-NEWS no. 3 and 4/7, 2023, and the same situation was observed in various other countries. The number of infections peaked in January 2023 with at least a three-fold increase in the incidence of both GAS and invasive GAS compared to the peak observed in 2018/19 before the corona lock-down.

The reasons explaining the increase in invasive GAS include the appearance of a new variant, M1DK, and - as is the case for the current mycoplasma pneumonia and whooping cough epidemics - reduced immunity in the population following the corona lock-down.

Increase in the number of identified Cryptosporidium infections acquired in Denmark

2022 recorded nearly 800 episodes, which is more than ever before and a marked increase from the numbers recorded in previous years, EPI-NEWS no. 26b/2023. The number of episodes is expected to reach the same level in 2023. The increase may be explained by the fact that the DCMs in Slagelse, Odense, Herlev and now also Aalborg have introduced a new diagnostic PCR panel for intestinal pathogens, which is approved under the EU regulation on in vitro diagnostic equipment, that also includes cryptosporidia. This means that the majority of stool samples processed at these DCMs are now tested for the same panel of intestinal pathogenic parasites, bacteria and viruses without any need for a specific order from the treating doctor.

Cryptosporidia were previously considered a rare cause of gastrointestinal infection acquired in Denmark, but they now seem to be relatively commonly occurring. Cryptosporidia are a diverse population of parasites for which the infection sources and routes of infection are currently poorly understood. Therefore, in February 2024, the SSI launches a three-year project in collaboration with the regional DCMs to explore to which extent population health status in Denmark is affected by cryptosporidia, and how Danes become infected. In Denmark, cryptosporidia findings in humans are now notifiable to the SSI. This provision came into effect with the recently revised executive order on notification of notifiable diseases (see above), EPI-NEWS no. 44b/2023.

Increase in findings of other gastrointestinal infections

The introduction of PCR diagnostics in stool samples and now also syndrome testing at the DCMs have generally given rise to changes in our understanding of the diagnostics of gastrointestinal conditions. Cryptosporidia is not the only area affected. In recent years, we have observed a considerable increase in the number of positive cases of shiga toxin-producing E. coli (STEC). This, however, has not been accompanied by any substantial increase in the number of serious STEC cases, including HUS-associated cases. Notification of STEC changed with the introduction of the amended executive order on notification of infectious diseases in the autumn of 2023, EPI-NEWS no. 44b/2023. Thus, only HUS-associated STEC cases and clinical HUS cases require notification in writing to the SSI and the STPS, whereas all STEC cases (including non-HUS-associated STEC) are subject to laboratory notification. Another gastrointestinal infection to follow a gradually increasing trend in recent years is campylobacter. An analysis of the gradual shift to PCR diagnostics in Danish DCMs made it possible to adjust for the effect of this shift. It is assessed that PCR diagnostics is more sensitive and that this is reflected in an approx. 40% increase in the number of recorded disease cases, which means that 17-25% more cases would have been detected in the 2018-21 period if all DCMs had used PCR rather than culture at the time.

Foodborne disease outbreaks in 2023

The SSI is an important part of the national collaboration to explore foodborne outbreaks, among others with the Danish Veterinary and Food Administration and DTU Food. The SSI has in place an outbreak investigation preparedness service within which microscopical and epidemiological expertise is used in conjunction when foodborne disease outbreaks are explored to identify sources of infection and prevent any more people from being affected. Various outbreaks are investigated continuously. Typically, around 20 larger investigations are completed annually.

Among the outbreaks that received most attention in 2023 were a Salmonella Enteritidis outbreak, comprising 22 registered disease cases in the period from May through August 2023. The outbreak was linked to a larger European outbreak, and the investigation revealed that imported chicken kebab meat from Poland was the source of infection.

Another serious outbreak was recorded in August 2023 when six persons were found to form part of an outbreak with a specific type of STEC bacterium. One of the patients developed acute kidney failure - also coined haemolytic uraemic syndrome (HUS). The outbreak investigation indicated that the disease outbreak was caused by hanger steak.

Increase in the number of detected TBE cases

TBE (tick-borne encephalitis, Central European encephalitis) is the serious manifestation of a virus disease transmitted to humans by ticks. Only about one in every twelve persons who become infected with TBE virus end up developing TBE. The number of detected TBE cases who were presumably infected in Denmark has followed an increasing trend since 2018, including people infected in possible new risk areas. In 2023, a total of 12 cases were diagnosed; five on Bornholm and seven on Zealand, primarily in North Zealand. This is an increase from the seven and five cases recorded in 2021 and 2022, respectively. In 2023, the SSI prepared a TBE risk assessment.

Overall, the individual level risk of TBE infection in Denmark is considered to be very limited and, in line herewith, the risk of developing the disease (encephalitis) is also considered very low also for the next five years, even though an increase is expected in the number of patients with TBE along with a wider geographic extension. Currently, only Bornholm and the municipalities comprising the North Zealand risk area have a disease incidence >1/100,000/year. The SSI concludes that TBE vaccination is effective and safe and may be considered for persons who use paths in risk areas and regularly pick up ticks or who spend time in woods and shrubbery beyond the paths during the transmission season from May through October. Because of the limited number of cases, the SSI assesses that to prevent a single TBE case, vaccination will be needed of 50,000 persons who engage in risk behaviour within known risk areas, defined as an area with a minimum of two TBE cases within the past three-year period.

High level of threat for infection with avian influenza from wild birds to poultry

In December 2023, the Danish Veterinary and Food Administration increased to high the threat level for infection with avian influenza from wild birds to poultry. This occurred after Statens Serum Institut had detected high-pathogenic avian influenza in samples from a Zealand producer of duck meat. This outbreak occurred in the wake of three outbreaks with highly pathogenic avian influenza (HPAI) H5N1 in Denmark in the course of November.

Since late 2020, Europe has been affected by outbreaks with H5 HPAI in wild birds, poultry and other birds held in captivity which exceed previously recorded extent in terms of the number of wild birds that have the HPAI virus detected, the number of outbreaks in poultry flocks, geographical spread and the number of affected bird species. Furthermore, H5 HPAI virus was detected in various mammals in several countries.

Generally, influenza viruses that circulate in animal populations may sporadically be transmitted to humans and cause mild to serious disease. New human cases caused by zoonotic influenza viruses, i.e. influenza viruses that are transmitted from animals to humans, should be monitored, tested in order to type and whole-genome sequence virus and reported internationally to the WHO. This is a good example that a One Health approach is needed to counter infectious threats. Denmark is well-positioned to adopt such an approach as we have in place a joint human and veterinary preparedness programme allowing us to reap the benefits of synergies relating to laboratory facilities and knowledge about the prevalence and spreading of infectious diseases.

Commentary

The COVID-19 epidemic and associated restrictions have also affected infection patterns. COVID-19 has contributed a considerable disease burden measured as hospitalisations in addition to the other well-known airway infections. The avian influenza outbreak with spreading to mammals and possibly infection of humans underlines the importance of One Health collaboration. The development in TBE depends on a host of factors, but may be the result of climate changes. We need to be aware that climate change may lead to changes in infection patterns in Denmark, including an increase of the risk of water- and vector-borne transmission.

With this outline of 2023, we wish all EPI-NEWS readers a happy New year!

(P. Valentiner-Branth, Department of Infectious Disease Epidemiology and Prevention)
10 January 2024