No 1/2- 2023

Disease outbreaks

Monitoring of COVID-19, subvariants and vaccine effect

2022 started with steeply increasing transmission of the Omicron variant. Luckily, Denmark had prepared well for this situation as test data, whole-genome sequencing and mathematical modelling already in the first half of December 2021 had shown how the Omicron variant would spread. Therefore, it was possible to advance the already initiated roll-out of the third vaccination shot to most of the population.

Vaccine effectiveness (VE) proved to be considerably higher against infection with the Omicron variant after the third shot than after the second shot. Even though the third shot increased protection against the Omicron variant, the protection achieved against infection with the Omicron variant was lower than against previous variants (Alpha and Delta). However, VE remained high against hospitalisation after being infected with the Omicron variant.

In the course of 2022, various Omicron subvariants have been dominant in Denmark. Initially, BA.1 and BA.2 dominated, but by early summer, BA.5 had become the dominant variant. As the variant that drives the epidemic shifts regularly, constant monitoring is essential. Monitoring allows us to discover new variants, determine how serious they are and explore to which degree vaccination and previous infection protect against infection and serious disease.

During the vaccination campaign implemented in the autumn using variant-updated vaccines, more than 75% of +50-year-olds accepted the offer to receive a booster shot. Overall, persons who have received a booster this autumn have a 73% lower risk of being hospitalised due to COVID-19 than those who received their third vaccination shot more than 140 days ago.
Several of the subvariants that are currently on the rise have mutations that allow them to spread more readily than previous variants. They are more capable of infecting people who have previously become infected or who have been vaccinated. This applies, e.g., to the BA.5 subvariant BQ.1.1, which accounted for 49% of the sequenced samples in Week 51. Luckily, there are no signs that BQ.1.1 leads to more serious disease than the other BA.5 subvariants.

Possible derived effects on other infections before and after Corona restrictions

As from March 2020, the Danish society saw restrictions and lock-downs of varying magnitudes. Apart from exerting an effect on transmission of the COVID-19 infection, the measures seem to have affected other airway infections as well as a considerable decline in other airway infections including whooping cough, invasive meningococcal disease and pneumococcal disease, and to some degree also for foodborne diseases was observed. In line herewith, fewer antibiotics were prescribed for treatment of bacterial airway infections, and the level of antimicrobial resistance decreased for some of the monitored types of bacteria, including MRSA. These conclusions were drawn in the DANMAP 2021 report, which describes the consumption of antibiotics and resistance against antimicrobials in humans, animals and foods in Denmark, EPI-NEWS no. 45-46a/2022.

As from 1 February 2022, COVID-19 was no longer categorised as a critical threat in Denmark, and the remaining restrictions were lifted. Few weeks later, an influenza epidemic started, which peaked in Week 12, recording the highest number of detected cases observed in the past five seasons. This should be interpreted keeping in mind that the testing activity was unusually high, but the increase in case numbers was clear compared with the 2020/2021 season, when influenza was largely absent.

Other outbreaks

Mpox

Monkeypox (now coined mpox) is found endemically in Central and West Africa. Previously, transmission mainly occurred from animals to humans. On 23 May 2022, the first human case of mpox was detected in Denmark, and on 23 July, the WHO declared mpox a public emergency of international concern. Statens Serum Institut rapidly developed a PCR analysis capable of detecting suspected cases, and this diagnostic modality was made available to the Danish regions. Mpox primarily affects men who have sex with men (MSM) and who have various sex partners.

The SSI, the Danish Health Authority and the Danish Patient Safety Authority (DPSA) in collaboration with clinicians ensured that guidelines were prepared on handling, notification and monitoring. The DPSA traced contacts, informed close contacts to infected persons and facilitated post-exposure prophylaxis at the various infectious disease departments. In collaboration with interest organisations such as AIDS-Fondet, HIV Denmark and LGBT+ Denmark, among others, information was disseminated on prevention of mpox among MSM. As from 11 August 2022, in addition to vaccination of close contacts, vaccination was also offered to the groups considered to carry the greatest risk of becoming infected with mpox: MSM who receive pre-exposure HIV prophylaxis or who meet the criteria to receive such treatment.

So far, 192 mpox cases have been confirmed in Denmark, and 82,522 cases have been confirmed globally. Since October, only a limited number of sporadic cases have been observed in Denmark.

A total of 3,875 persons have initiated vaccination and 3,174 have concluded their vaccination course. We expect that mpox will continue to spread globally between people who have many sexual partners, but it also seems clear that transmission of mpox can be contained in countries where mpox vaccination is offered to high-risk groups.

Hepatitis of unknown cause among children

In early April 2022, Great Britain reported an increase compared with expectations in hepatitis (inflammation of the liver) of unknown cause among children. A report published by the WHO on 12 July 2022 showed that the outbreak in Great Britain comprised a total of 272 cases. Approx. 1,010 cases had been recorded in 35 countries, 46 of the affected patients needed a liver transplant and 22 deaths were recorded. Most of the cases, 484, were recorded in Europe.

In Denmark, 2022 has brought a total of eight cases of hepatitis of unknown cause in children aged less than 16 years of age. Three of the affected children developed hepatic failure. None of the eight Danish cases received a liver transplant.

Hepatitis of unknown cause in children is not an unknown phenomenon. Normally, Denmark records approx. two annual cases of hepatitis of unknown cause in which children develop hepatic failure. It has been hypothesised that the cause of the outbreak in Great Britain may be concurrent infection with commonly occurring virus, which was transmitted to the children outside of the normal season due to COVID-19 restrictions.

The situation is currently being monitored closely, nationally as well as internationally. In Denmark, extended monitoring has been introduced, including a duty to notify hepatitis of unknown cause by phone to the DPSA and close collaboration between Danish paediatricians and paediatric departments, the DHA, DPSA and the SSI.

The outbreaks of mpox and hepatitis of unknown cause stress the importance of having in place preparedness measures that facilitate the rapid establishment of monitoring of new infections or “syndromes” not covered by current monitoring schemes.

Listeria outbreak from cold cuts and salmonella in chocolate

2022 turned out to be a “listeria year” as an increase was recorded from 43-61 cases of invasive listeriosis in the past five years to more than 80 cases in 2022. Furthermore, spring brought two food-borne outbreaks with Listeria monocytogenes. The source of infection for one of the listeria outbreaks was identified as rolled seasoned meat produced at a Danish plant in Germany. The product was withdrawn from the market. In autumn, the second listeria outbreak was resolved, and a large number of Danish produced fish paddies were withdrawn from the market. A large international outbreak with monophasic Salmonella Typhimurium occurred in the first half of 2022. The source of infection was chocolate from a Belgian production plant.

The outbreak triggered a major EU withdrawal shortly before Easter - also comprising Denmark. Denmark recorded a total of four persons forming part of this outbreak. Extended use of new molecular biology methods such as whole-genome sequencing for the identification of identical pathogens in humans and foods, linked with classic epidemiological studies, has strengthened the monitoring and resolution of food-borne outbreaks nationally and internationally. It is important to collect samples for analysis from persons suspected of food-borne diseases even though there may be no indication for treatment of the individual patient. Collecting samples may help resolve and curb outbreaks.

RS virus

RS virus, also known as respiratory syncytial virus, leads to airway conditions. Anyone may be affected by RS virus, but infants in particular, and elderly or immune-compromised people carry a risk of running a serious disease course. Even so, RS virus among children is only rarely fatal in Denmark.

As in 2021, EPI-NEWS 35/2021 and 37/2021, 2022 recorded an increase in the number of RS virus cases outside of the normal season. The increase in the number of confirmed cases was first recorded in Week 31, and the epidemic then gained a stronger footing in Week 34. The condition seems to have initially spread among children after which it passed to elderly people. Overall, the epidemic peaked in Week 45, recording more cases and also more hospitalisations than we used to see before the COVID-19 epidemic.

Internationally, efforts are underway to develop RS virus vaccines. Several vaccine candidates are currently being tested in clinical trials, and some of these vaccines are expected to be approved shortly.

The atypical pattern seen in the past two RSV seasons should be interpreted in light of the COVID-19 restrictions imposed in the preceding years, which have also suppressed infection with RSV.

Polio

Since 1988, the WHO has as one of its objectives to eradicate polio. Since then, the global case number has declined by more than 99%, and two of three wild polio types have been eradicated. The final wildtype polio virus, type 1, remains in circulation in limited areas of a short list of countries, primarily in Afghanistan and Pakistan. But polio may also spread via special types of polio virus, originating from the live-attenuated polio vaccine, which is given orally (“polio sugar”). In this vaccine type, virus may mutate (in areas with low vaccination coverage) and regain its ability to cause polio disease including, among others, paralysis. In recent years, this ability has challenged the eradication of polio, and since 2014 the WHO has classified the polio situation as a public health emergency of international concern. In 2022, a case of polio disease was detected in New York which had been caused by a circulating virulent polio vaccine type 2 virus. The case occurred in an unvaccinated person who had not recently travelled to other countries. The same type of polio virus was detected in waste water in New York and London, and in a limited number of cases in Northern Ireland and Canada.

Waste water monitoring has thus been identified as a useful tool for detection of possible transmission of polio virus - A tool which may be used to underpin preventive measures such as vaccination roll-out in areas there the polio vaccination coverage is low.

Ebola

Internationally, the ongoing Ebola outbreak in Uganda has attracted considerable attention. The outbreak originated from the Mubende District in the South-western part of Uganda. Various deaths were observed in people who were not tested for ebola but were presumably the first cases of the epidemic. Subsequently, the outbreak spread to the capital of Kampala, which gave rise to a second wave of infections. Since Week 46, only sporadic cases have been detected, and the outbreak is now considered to be under control thanks to classic infection-preventive methods such as testing, isolation, contact tracing, vaccination and attention to infectious hygiene, particularly at hospitals and during burial services. As per 3 January 2023, a total of 132 confirmed cases had been recorded, including 55 deaths.

Tuberculosis

During the COVID-19 epidemic, Denmark has recorded a historically low number of tuberculosis cases. However, it was observed that the samples from those diagnosed were more often microcopy positive, which is a sign of more advanced disease, EPI-NEWS 44/22. In practice, this means more complications for the individual patient and more transmission in the community. Therefore, it remains uncertain if the decline in the number of tuberculosis cases in Denmark will continue in years to come. Furthermore, 2022 registered a record-high number of multiple-resistant tuberculosis cases. Normally, approx. 2-3 multiple-resistant cases are seen annually, but in 2022 Statens Serum Institut recorded 11 cases, ten of which were from international areas with a high occurrence of multiple resistance. The areas concerned include Eastern Europe, South-east Asia and the Southern Africa.

One of the 11 cases is a Danish-born person with relation to a previously described outbreak of multiple resistance among Danish-born persons.

Avian influenza

Since late 2020, Europe has been affected by outbreaks with H5 high-pathogenic avian influenza (HPAI) in wild birds, poultry and other birds held in captivity. The outbreaks exceed any previously recorded HPAI outbreaks in terms of the number 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.

Among the HPAI viruses that are currently in circulation in birds in Europe, isolated cases in humans have been reported from Russia, the UK, the US and Spain. The persons affected presented with no or very mild symptoms and tested positive owing to screening of persons who had come into close contact with infected burds/poultry flocks. None of these cases occurred in Denmark.

In 2022, the SSI detected a case of influenza in a citizen, which probably originated from pigs (ref). Generally, influenza viruses that circulate in animal populations may sporadically be transmitted to humans and cause mild to serious disease. Zoonotic influenza viruses, i.e. influenza viruses that are transmitted from animals to humans, therefore cause concern for the health of humans. This is a good example underscoring 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.

Pneumococcal vaccination for elderly people and risk groups

On 22 April 2020, a vaccination programme comprising a 23-valent pneumococcal vaccine came into force to limit the pressure on healthcare services as much as possible during the COVID-19 pandemic. The programme started as an offer targeting the more vulnerable patients and was then extended to include persons who have turned 65 years old and other persons at an increased risk of serious pneumococcal disease. The programme will be discontinued as per 15 January 2023, EPI-NEWS 51/2022. The programme has enjoyed a high vaccination coverage, >75% among persons aged 65 years or more. A report from September 2021, comprising more than 948,000 participants, revealed that among persons ≥65 years of age, vaccinated persons are protected against 42% of invasive pneumococcal disease cases regardless of the type of pneumococcal bacterium, and that the protection increased to 58% when exploring the effect for the 23 types of bacterium targeted by the vaccine.

Digitalisation of the notification system

In 2022, a new notification system for infectious diseases was implemented in the form of the Electronic Notification System (SEI2) of the Danish Health Data Authority. Electronic notification of MRSA and of data from the screening of pregnant women is planned for 2023. In 2022, the development of automatised disease monitoring via use of laboratory data was also given priority. This is a broad collaborative project that will be several years in the making. These efforts will render more robust the digital monitoring of known as well as new infectious threats in relation to infections that are not exclusively detected based on data from microbiological laboratories, e.g. hepatitis.

With this outline of 2022, we wish all EPI-NEWS readers a happy New year.

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