Mycoplasma pneumoniae re-emergence in 2023 causes disease in adults in Europe

Extract

Mycoplasma pneumoniae is a common cause of respiratory tract infections in children and young adults [1]. An estimate of 3–10% of the children infected with M. pneumoniae develop community-acquired pneumonia (CAP) [2] and in rarer cases, complications are seen [2, 3]. Pulmonary complications such as pleural effusion or bronchiolitis obliterans [3], but also extrapulmonary complications such as mucocutaneus disease, manifestations of the central nervous system and autoimmune haemolytic anaemia, amongst others, have been described [3–6].

Shareable abstract

Data indicate increased severity of M. pneumoniae infections in the latest outbreak, especially in adults, compared to pre-COVID-19. Insights from this rapid questionnaire can improve outbreak research, strengthen preparedness and enable faster responses. https://bit.ly/4kN0zu3

To the Editor:

Mycoplasma pneumoniae is a common cause of respiratory tract infections in children and young adults [1]. An estimate of 3–10% of the children infected with M. pneumoniae develop community-acquired pneumonia (CAP) [2] and in rarer cases, complications are seen [2, 3]. Pulmonary complications such as pleural effusion or bronchiolitis obliterans [3], but also extrapulmonary complications such as mucocutaneus disease, manifestations of the central nervous system and autoimmune haemolytic anaemia, amongst others, have been described [3–6]. Prior to the COVID-19 pandemic, M. pneumoniae typically caused cyclic outbreaks every 3–7 years, lasting approximately 12–15 months [7]. However, during the COVID-19 pandemic, like other pathogens [8], a sudden dip in M. pneumoniae circulation was observed [9]. Where other pathogens rose again after lifting the first restrictions, M. pneumoniae incidence stayed low until 2023 [9].

In summer 2023, re-emergence of M. pneumoniae in Europe and Asia started, with increased numbers of cases of childhood CAP [9, 10]. Interestingly, available hospital data showed an increase in M. pneumoniae detections in adults in hospitals in The Netherlands and France, with severe cases needing admission to the hospital and supportive care in the intensive care unit (ICU) [11–14]. So, unlike other M. pneumoniae outbreaks, adults also appeared to be at risk for a more severe course of disease. However, information is scarce and fragmented, and up to now, apart from the global surveillance by the ESGMAC MAPS study [15], real-time monitoring in primary and secondary care on a national level in Europe is lacking.

Our objective was to conduct an initial analysis of data, collected within the European Clinical Research Alliance on Infectious Diseases (Ecraid) consortium, across Europe to determine if there was an increase or distinct pattern of disease compared to other outbreaks.

Ecraid is a European Union-funded clinical research network for infectious diseases that serves as a platform for clinical research preparedness and response to (re-)emerging infectious diseases threats. At the heart of ECRAID-Base are five perpetual observational studies (POSs) [16], which aim to support efficient implementation of observational studies and randomised trials by harmonised data collection through application of standardised definitions across study sites. The POSs in Ecraid are multicentre studies designed to address key clinical research gaps, including variations in clinical practices, incidence of infectious disease syndromes and associated risk factors.

In December 2023, a questionnaire was developed to evaluate M. pneumoniae cases throughout the Ecraid clinical network, in a short period of time with the timelines as shown in figure 1a. The questionnaire was developed with input and guidance from experts in the field of M. pneumoniae. It included questions about the medical specialty of the reporting physician, the country of practice and the testing policies in place. Moreover, the questionnaire collected information on the estimated number of M. pneumoniae cases for both paediatric and adult populations, as well as the estimated number of ICU admissions due to M. pneumoniae, for the post-COVID-19 season in 2023–2024 and for previous seasons (in time period of 2018–2022). As not all countries experienced the post-COVID-19 M. pneumoniae season simultaneously, we did not define exact start and end dates for the season. Answers were reviewed and data cleaning independently performed by two researchers to ensure data quality. Partially completed questionnaires (<22%), duplicates and questionnaires lacking either country or specialty of reporting physician were excluded from analysis.

FIGURE 1.

Overview of study procedures and main results. a) Timelines of setup of the questionnaire and data collection. The questionnaire was send out on 14 January 2024 and closed for further responses on 7 February 2024. b) Number of hospitals responding to the questionnaire categorised by country. In some centres, we received multiple responses from different medical specialists. These responses are counted as a single centre and categorised as intensive care unit (ICU) if an ICU response was included. c) Number of patients admitted to the general ward and ICU categorised per country. d) Ratio of number of clinical cases per country in before the 2023–2024 season/in the 2023–2024 season on the general ward and ICU. The pink threshold represents a ratio of 1. Created with BioRender.com.

Data are presented as absolute numbers and percentages. For the clinical case and ICU admission data, the ratio of the number of patients in 2023–2024 to the number of patients of previous seasons was computed. Analyses were performed using R (version 4.4.0).

The questionnaire was sent to ∼150 sites from the POS VAP, POS cUTI, POS ARI ER, PNEUMO and REMAP-CAP studies (figure 1a). Some sites were participating in multiple studies. 85 individual Ecraid participants replied to the questionnaire, with completed data from 66 (69%), representing 59 hospitals or medical centres, hereafter referred to as centres. In four reporting centres, multiple specialists from the same site responded to the questionnaire. Of all responses, the majority were from intensive care specialists (30 out of 66, 45%), 20 (30%) out of 66 were infectious diseases specialists and seven (11%) out of 66 were from the pulmonology department. Responses were received from 15 different countries within Europe (figure 1b). Most responding centres were in the UK (n=11, 19%), the Netherlands (n=9, 15%) and Spain (n=9, 15%). The physicians reported working mainly in general adult care; only one reported being a paediatrician.

In previous seasons, 20 (34%) out of 59 reported routine testing for M. pneumoniae, while 28 (47%) out of 59 tested only in selected cases. During the 2023–2024 season, testing in selected cases has increased to 29 (49%) out of 59 and routine testing to 27 (46%) out of 59. In previous seasons, diagnosis was mainly through a combination of PCR and serology in 18 (31%) out 59, with serology alone in 14 (24%) out of 59 and PCR alone in 12 (20%) out of 59. In the 2023–2024 season, the combination remained the most common (23 out of 59, 39%), but the use of serology alone has decreased to nine (15%) out of 59, while PCR alone has increased to 18 (31%) out of 59.

For the number or reported patients admitted to the hospital and ICU, the data were pooled per country and a ratio over time (numbers in 2023–2024 season/previous seasons) was calculated to give a more balanced indication of numbers. The reported numbers of patients with M. pneumoniae infection admitted to the hospital have increased in the 2023–2024 season in Croatia, France, the UK and the Netherlands (figure 1c and d), with the highest reported numbers in France, the UK and the Netherlands. In Belgium, Greece, Portugal and Serbia, the numbers were almost the same. For the remaining countries, no increase was seen in Czech Republic, Italy, Romania and Slovenia (figure 1c). In Estonia, for both the 2023–2024 and previous seasons, the participating centre reported no patients. Patients admitted to the ICU increased by ratios >2 in France, the UK and the Netherlands. Serbia reported almost an equal number of clinical cases but reported a higher number of ICU admissions with a ratio >1 (figure 1c and d).

We report an estimation of the M. pneumoniae cases with admission to the hospital in multiple countries in Europe using the Ecraid network. Our results suggest an increase in hospitalised M. pneumoniae cases throughout some countries in Europe and indication of an increase in disease severity with the need for ICU care. This observation was mainly reported by clinicians in France, the UK and the Netherlands. Some countries reported low rates of clinical cases and ICU admissions, suggesting that the current increase in M. pneumoniae-related hospital admissions is due to more localised transmission and spread of M. pneumoniae rather than across Europe.

We report, in some countries, a significant increase in numbers of adults requiring hospitalisation or ICU admission. This is unexpected, as M. pneumoniae is primarily associated with mild and self-limiting infections in children and adolescents [1]. However, immunity to M. pneumoniae wanes during periods of non-exposure and during the presence of COVID-19 pandemic restrictions, a decrease in detection of M. pneumoniae-specific IgM and IgG antibodies from 2020 to 2023 was reported [9, 17]. This waning immunity might have contributed to higher numbers of more severely ill adults.

This short report gives a glimpse of the current situation in the M. pneumoniae outbreak in Europe in 2023–2024. The study was set up during a short period of time enabling us to act fast and collect data at the time of outbreak. This approach also has limitations. First, the kind of data generated with this kind of research might be subject to bias. We did not retrieve data generated from the electronic patient files but asked the physicians to estimate numbers; this might also lead to recall bias from the estimated numbers of the period before 2023. However, since the aim of this rapid questionnaire rollout was to quickly gather information on the resurgence and number of M. pneumoniae cases across Europe in the 2023–2024 season, these estimates were sufficient to detect early signals. In some countries, we had low response to the questionnaire, leading to uneven participation in the questionnaire. This might give an over or underestimation in numbers or effects. Second, apart from one paediatrician, all reporting specialists were practitioners in adult medical care, which may be explained by the setup of the Ecraid network. As M. pneumoniae predominantly affects paediatric patients, this study underestimates the disease burden during the 2023–2024 season in children. Third, we did not specify or define case or disease severity. ICU care is organised differently throughout in countries in Europe, sometimes even within countries, with different in indications for ICU admission. This makes it impossible to use this factor as indication of severity of disease or draw conclusions from these data regarding severity of disease. Finally, the COVID-19 pandemic changed the testing policies and/or habits in physicians, leading to higher numbers of M. pneumoniae.

Here, we present the results of a rapid response inquiry of the resurgence and number of M. pneumoniae cases across Europe in the 2023–2024 season. Our data suggest an increase in the severity of infections, particularly among adults, compared to what was observed in previous years (pre-COVID-19). The lessons learned from this rapid questionnaire rollout can facilitate the setup of research during outbreaks, potentially contributing to improved pandemic and outbreak preparedness, and enabling faster responses.