No 5 - 2024

Measles case presumably infected in Denmark

The Department of Clinical Microbiology (DCM) at Amager and Hvidovre Hospital and Statens Serum Institut (SSI) have detected a measles case in an adult person residing in Region Zealand who also stayed in the Capital Region of Denmark in the infectious period.

The patient had IgM antibodies to measles virus detected at the DCM in a sample taken in a dermatology department on 26 January 2024.The diagnosis was confirmed at the SSI by positive PCR diagnostics in samples from two localisations obtained on 26 and 29 January 2024.

The patient has no current travel activity outside of Denmark, but did, in early January, come into occupational contact with persons from areas with known measles virus circulation. The SSI will attempt to genotype the virus to establish the likely source of infection.

The Danish Patient Safety Authority, Supervision and Guidance East, has been informed and has initiated infection tracing measures in relation to the contacts of the infected person, privately as well as any healthcare contacts who may have been exposed to infection before the diagnosis was made.

Physicians, particularly on Zealand, are encouraged to be extra attentive to the diagnosis in weeks to come. 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.

The detected case underlines that measles remains in circulation in many places globally and that infection may be introduced by tourists or others visiting Denmark who do not necessarily feel ill when entering the country. Additionally, all non-immune travellers from Denmark to areas with a measles risk should receive measles vaccination prior to their departure (in the form of MMR vaccine).

Sampling

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

1. Pharyngeal swab and urine for detection of measles virus (morbili virus) RNA by 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.
2. A blood sample for measles virus IgM/IgG antibody determination. IgM antibodies may be confirmed by rash.
   We recommend that all measles virus-positive samples be sent to the National WHO Reference Laboratory for Morbilli and Rubella, Laboratory for Virus Surveillance and Research, SSI, for characterisation, which is free of charge.

On suspicion of measles disease, it is important that the diagnostics and work-up are performed as rapidly as possible with a view to continued isolation of the patient and also tracking and, if relevant, treatment of any non-immune persons who may have become exposed to infection. Serological detection is insufficient for measles diagnostics, and virus detection by PCR is necessary.

Virus detection by PCR analysis is the quickest and safest method for laboratory diagnostics of measles. The analysis may be performed at the SSI, among others.

The National WHO Reference Laboratory for Measles and Rubella at the SSI handles the characterisation (sequencing and typing) of all measles virus-RNA-positive samples in Denmark. As characterisation of the measles virus is important in relation to infection tracing, all suspected and confirmed measles virus-positive samples should be forwarded hereto as quickly as is practically possible. We recommend contact by phone to the virologist in charge at the SSI (in the daytime pho.: 40336379, after 15.30 to the virologist on call pho.: 41317404) to inform the laboratory that samples are underway and thereby avoid any unnecessary delay of the diagnosis.

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

Vaccination and prophylaxis following exposure

The primary form of prevention is MMR vaccination. In Denmark, MMR vaccination is offered to all children at 15 months and four years of age as part of the Danish childhood vaccination programme. Following certain exposure to infection, i.e. contact to a laboratory-confirmed or epidemiologically linked case, MMR vaccination may be given within three days of exposure to infection and normally human immunoglobulin within six days as post-exposure prophylaxis (PEP) to non-immune contacts. Delimitation of the contacts who need PEP is done by the on-duty physician at the Danish Patient Safety Authority, Division for Supervision and Guidance of the area in question. Subsequently, expenses are reimbursed by the regional authorities.

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

Notification

As from 1 November 2023, measles is notifiable by phone to the local supervision and guidance unit in case of enhanced suspicion or confirmed measles disease, EPI-NEWS no. 44b/2023. Additionally, confirmed measles cases are notifiable in writing to the Danish Patient Safety Authority, Division for Supervision and Guidance East/West as well as to the SSI. Notification is made via the electronic notification system (SEI2). See link for further information and guidance.

(M. G. Ahlström, K.T. Franck, Virus Monitoring & Research, National Reference Laboratory for Measles and Rubella, S. Bjerrum, Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), L.K. Knudsen, P.H. Andersen, Department of Infectious Disease Epidemiology and Prevention, G. Jehu, Danish Patient Safety Authority, Supervision and Guidance East)

Mycoplasma genitalium in Denmark, 2022

Mycoplasma genitalium (MG) is a sexually transmitted infection (STI) in both men and women that can cause urethritis, cervicitis and pelvic inflammatory disease. Symptoms, including discharge and discomfort, are indistinguishable from chlamydia and a significant portion of cases are asymptomatic. Following chlamydia, MG is the most common STI. Infection is detected exclusively through molecular methods (nucleic acid amplification tests, NAT). Below is the incidence of MG in Denmark in 2022. For a more detailed description and a 20-year report, refer to Mycoplasma genitalium – Incidence and Antibiotic Resistance, 2003 to 2022.

Treatment and Resistance

Primary treatment for MG is azithromycin given as 500 mg on day 1, followed by 250 mg daily from days 2 to 5. However, an increasing proportion of infections are caused by macrolide-resistant strains. Upon detecting MG, testing for macrolide resistance is performed and treatment should await the results of this examination. If resistance is confirmed, moxifloxacin 400 mg daily for 7 days is the standard treatment. In cases of suspected MG pelvic inflammatory disease, moxifloxacin 400 mg daily for 14 days is initiated without waiting for resistance determination. Moxifloxacin treatment can, in rare cases, lead to serious and irreversible side effects. Given that >60% of all MG infections are now caused by macrolide-resistant strains, it is crucial that MG testing is only conducted in symptomatic patients. There is no indication for screening, as the frequency of severe sequelae after MG infection is unknown and the risk of serious side effects from treatment is deemed to exceed the risk of sequelae in asymptomatic individuals.

Treatment failure after moxifloxacin is increasing, especially in Asia and Australia. Quinolone resistance-associated mutations (QRAM) can be detected by sequencing, a test currently only performed at Statens Serum Institut (SSI). QRAM testing should only be done after treatment failure, as some patients with QRAM may actually respond to moxifloxacin and treatment failure often results from re-infection or lack of compliance. Patients with QRAM cannot be treated with drugs registered in Denmark and must be referred to clinics for sexually transmitted diseases that have special dispensation for pristinamycin or other third-line treatments.

Data for this report include all examinations submitted for primary diagnosis of MG to Statens Serum Institut from the Danish healthcare system in 2022. Samples submitted solely for macrolide or quinolone resistance determination from a Clinical Microbiological Department are not included in the report.

In 2022, there were 437 episodes of MG out of 4,681 examinations (9.3%), distributed among 209 out of 1,517 men (positivity rate 13.8%) and 228 out of 3,164 women (positivity rate 7.2%). A case is defined when there are over 42 days between two positive test results. Since 2003, there has been an increase in the positivity rate of MG from 4.1% to 13.5% in 2021 but decreasing to 9.3% in 2022.

Most cases are from the age group 20-24 for both genders, with generally more women examined than men in all age groups under 50. Both men and women have the highest proportion of positives in the 20-24 age group, with an overall positivity rate of 17.3% for men and 10.6% for women in the selected years from 2003 to 2022 (2003, 2007, 2011, 2015, 2019, 2020, 2021, 2022).

In 2022, an increase in the number of submissions was observed from the Region of Zealand and the Region of Southern Denmark. SSI examined 1,772 patients from the Region of Zealand and 1,539 patients from the Region of Southern Denmark compared to 898 and 940, respectively, in 2021. There is no immediate explanation for the increase in the number of submissions, but the rise is most pronounced for women examined by gynecologists and an explanation could be that women are being examined before the insertion of an intrauterine device. This is not part of international recommendations, as there is no evidence of risk, but it is considered relevant since there is an increased risk of post-abortion pelvic inflammatory disease after surgical abortion. Cervical barrier rupture is therefore considered a risk in younger women, where the infection is most common. The Capital Region and the Central Jutland Region have implemented local testing for MG and are therefore not included in this report, but among the remaining regions, the highest positivity percentage in recent years was observed in the Northern Jutland Region.

In 2022, a macrolide resistance rate of 71.3% was observed based on 311 of 436 examinations. The resistance rate was 72.7% for women and 69.9% for men with no significant difference, which is unusual in international contexts, where macrolide resistance is higher in men, especially men who have sex with men. The high macrolide resistance is assumed to be caused by the use of azithromycin 1 g for the treatment of uncomplicated chlamydia infection, leading to the selection of macrolide resistance in 12% of MG-positive cases for each treatment episode. Therefore, the recommendation for the treatment of uncomplicated chlamydia in Denmark was changed in 2018 to doxycycline, which is also more effective in treating rectal chlamydia, which is common in women.

Unfortunately, as indicated in the 2022 annual report, only about half of chlamydia treatments have switched to doxycycline.

Random testing for quinolone resistance-associated mutations (QRAM) was performed on 108 MG-positive patients in 2022 and QRAM was detected in four (3.7%) of these, including resistance to both macrolide and quinolone in two (1.9%) patients. The incidence of resistance to moxifloxacin is thus still limited in Denmark, but with over half of diagnosed cases already having macrolide resistance, a large number of patients will be treated with moxifloxacin and treatment failure will therefore occur.

Monitoring of MG infections is a new area and hopefully the recent update to the regulation on the notification of infectious diseases will allow for increased detail using data from across Denmark.

(S. Tulsiani Drud, T. Roland Pedersen, A. Skafte-Holm, J. Skov Jensen, Section for Reproductive Microbiology, Bacteria, Parasites, and Fungi)