Monkeypox outbreak 2022 – an overview of all cases reported to the Cologne Health Department

DOI: https://doi.org/10.21203/rs.3.rs-2251751/v1

Abstract

Purpose:

The international monkeypox outbreak in May 2022 marks the occurrence of another previously atypical infectious disease in Europe. This study’s objective was to present a comprehensive overview based on data gathered by the Health Department of the city of Cologne.

Methods:

In this retrospective observational study, 368 individuals reported to the Cologne Health Department as PCR-positive for monkeypox were included. Data were collected in structured telephone interviews and digitally processed.

Results:

The first monkeypox case in Cologne was recorded on May 24, 2022. The local outbreak lasted approximately 4 months and reached its peak in July. The last reported case in Cologne occurred on September 17. Transmissions mostly occurred through sexual contacts (67.4 %) or other close physical contacts (4.6 %) between men, but also through fomites, in the context of events or occasionally in the work environment. In 21.5 % of cases, no route of infection could be determined. The mean incubation period was 8.2 days. Clinically, monkeypox infections usually presented with skin and/or mucosal lesions accompanied by general symptoms. In 74.8 % of cases, a prodromal stage was absent. Initially, the rash often had an unspecific appearance, but in the further clinical course, it usually passed through the typical stages. Most infections resolved spontaneously under home care. In 3.5 % of cases, however, inpatient hospitalisation was required.

Conclusions:

Most transmissions occurred through sexual contact. Although the majority of infections in Cologne affected the MSM community, there were also cases outside this context. The observed average incubation period was shorter than initially assumed. Mucosal involvement and associated symptoms occur in a relevant number of cases and can lead to more severe clinical courses. In the case of an unclear rash or symptoms suggesting mucosal involvement, monkeypox should be considered as a differential diagnosis.
The surveillance data collected in the health authorities provided important information for adapting the public health measures taken against the spread of monkeypox in the population.

Introduction

In the wake of globalisation and climate change, the international monkeypox outbreak in May 2022 marked the emergence of a previously atypical infectious disease in Europe. This largest international monkeypox outbreak to date within Europe, North America and Asia (1) was declared a public health emergency of international concern by the WHO in July 2022.  

Case-related data from a total of 25183 confirmed cases from 42 European countries were reported to the ECDC and the WHO Regional Office for Europe via TESSy (the European Surveillance System) by 26 October 2022. Most cases occurred in Spain (7317), France (4084), Germany (3662) and the United Kingdom (3652). So far, 4 monkeypox-associated deaths were recorded in Europe (2). 

Monkeypox (MPX) is a zoonotic viral disease caused by the monkeypox virus (MPXV) The MPXV was first identified in monkeys under laboratory conditions in Copenhagen in 1958 (3). Despite the name “monkeypox”, monkeys are dead-end hosts and wild rodents are the actual reservoir of the pathogen. In 1970, the virus was first detected in a human. Since then, monkeypox cases have been increasingly observed in Central and West Africa. There, transmission to humans occurred mainly through direct contact with infected animals or their meat. Human-to-human transmission has rarely been observed (4) (5). 

Outside of the African continent, there have only been isolated outbreaks, such as in the USA in 2003 with 71 independent cases following contact with infected prairie dogs (6) (7).  In other cases, infected individuals reported a travel history to Africa (8). While children had been predominantly affected in the 1970s, the average age of those infected rose to around 20 years by 2019 (9).

Historically, monkeypox infection in humans typically presented with a non-specific prodromal stage (fever, muscle pain, night sweats, lymphadenopathy, general feeling of illness) and with a rash. The efflorescences were described as simultaneously passing through the stages from spot to papule, blister and pustule until a scab forms (10).

An affected person is considered to be infectious from the onset of the first symptoms until all of the scabs fall off (11).

The control of epidemic and pandemic infectious diseases is one of the core tasks of the public health service. The prompt identification of both suspected and confirmed cases of infection and the education of those affected and their contacts about necessary hygiene measures are of crucial importance as well as the ordering of domestic isolation and quarantine to prevent further spread. In Germany, infections with monkeypox virus are notifiable (according to §6 and §7 Infektionsschutzgesetz, IfSG, “Infection Protection Act”).

Since the first occurrence of monkeypox in Cologne on May 24, 2022 until October 30, 2022, 368 PCR-confirmed cases were registered by the public health department and regularly contacted via telephone during the period of their officially mandated isolation of at least 21 days. Thus, the Cologne Health Department, as one of the largest in Germany, has a complete overview of the local outbreak. The aim of the present analysis was therefore to evaluate routes of transmission, incubation periods and courses of disease on the basis of these data, in order to review current knowledge and official recommendations for dealing with monkeypox infections.

Methods

Study design and population:

This study takes the form of a retrospective observational study. 393 persons were reported to the Cologne health department with PCR-confirmed MPX infection according to §7 IfSG between 24 May, 2022 and 30 October, 2022.

7 of these persons were excluded because we were unable to contact them throughout their period of isolation. 18 individuals did not spend their isolation in Cologne and were therefore not under supervision by the Health Department of the City of Cologne. Thus, our evaluation includes complete data sets of 368 persons. 

The information processing within the Cologne Health Department then took place via Surv-Net and internally via DiKoMa, a digital contact management software developed in Cologne in the context of the COVID-19 pandemic (12). In accordance with WHO recommendations, all individuals with a PCR-confirmed MPX infection were contacted regularly via telephone during their isolation period starting from the date the public health department was notified of the infection and lasting until all of the skin lesions were fully healed (more specifically, until the last scabs have fallen off) (13). In the initial telephone call, a detailed structured interview was conducted by trained personnel.

Sociodemographic data, infection routes and incubation periods:

Demographic data (age and sex), previous illnesses, social history including occupation, recent foreign travel and recreational activities, presumed source of infection, and contact persons were recorded during the initial structured telephone interview. The route of infection was assumed to be probable if an identifiable risk contact had taken place within 21 days prior to symptom onset, even if no reliable tracing to a PCR-confirmed MPX case was possible due to unknown identity. The incubation period was calculated on the basis of the symptom onset of infected individuals and the date of their probable or confirmed exposure.

Classification of symptoms:

The symptoms were systematically recorded in a digital symptom diary during the initial interview and in the subsequent telephone conversations over the entire period of isolation. Infected persons were specifically asked about skin and mucosal lesions, as well as general symptoms such as fever, night sweats, muscle/limb pain, lymph node swelling, and fatigue. Furthermore, we asked all infected persons about psychological stress.

In order to evaluate the localisation of the rash, the body was divided into five regions: head, upper extremity, lower extremity, trunk, anogenital region.

Data processing:

All personal data were compiled in a de-identified database and analysed descriptively by mean ± standard deviation (SD), 95 % confidence interval (CI) and frequency (%). We fitted a lognormal distribution to the observed incubation periods using maximum likelihood estimation. All data were compiled and processed using Microsoft Excel 2013. 

Results

Case numbers:

Figure 1 shows the development of MPX case numbers in the observation period. The first MPX cases reported to the Cologne public health department occurred in calendar week (CW) 21. From CW 25 onwards, there was a clear increase in the weekly incidence of MPX cases. This development reached its peak in CW 28 and 29 with 67 reported cases each. In the following weeks, the incidence dropped significantly. On September 17, the last MPX case to date was reported to the Cologne Health Department. From CW 38 onwards, no new cases were recorded in Cologne.

Age and gender:

One infected person was female, the remaining 367 indicated male gender. The age distribution was between 12 and 80 years with a mean age of 41.2 years (SD = 10.4). In Cologne, there was one reported case below the age of 18. 

Travel history:

57 infected individuals (15.5 %) had been outside of Germany within the last 21 days prior to the onset of their symptoms (potential incubation period according to RKI (14)) and suspected to have become infected during their travel abroad. We were able to observe that the first 5 index cases in Cologne, which occurred in calendar weeks 21 and 22, had all stayed in other European countries (Spain, France and Belgium) during the incubation period (see Figure 1). In the further course of the outbreak, the proportion of persons with a history of recent foreign travel decreased significantly. In calendar weeks 28 and 29, only 13.4 % of the infected stated that they had been abroad during the incubation period and that they presumably had become infected during that time. Since CW 34 the observed origins of infection lay exclusively in Germany. None of the infected persons throughout the whole observation period had entered Germany from African countries prior to infection. 

Pre-existing conditions:

A total of 143 persons (38.9 %) reported a known HIV infection. Some individuals reported other sexually transmitted diseases in their medical history; however, we did not systematically record these throughout. In a few cases each, the following pre-existing conditions were mentioned (listed in decreasing frequency): arterial hypertension, diabetes mellitus, coronary heart disease, thyroid diseases, bronchial asthma, chronic inflammatory bowel diseases, and rheumatic diseases. 16 persons (4.3 %) had contracted COVID-19 at the same time as the monkeypox infection.

Previous or recent vaccination history:

96 individuals (26.1 %) reported having received smallpox vaccination in the past with the vaccine based on vaccinia virus or modified vaccinia ankara virus (MVA) used in the Federal Republic of Germany until 1976 and in the GDR until 1982. 
33 persons (9.0 %) had already received a vaccination with the smallpox vaccine Imvanex at the time of diagnosis. This was offered as post-exposure prophylaxis for contact persons of exposure category 3 according to the criteria of the Robert Koch Institute (RKI; German federal government agency and research Institute, responsible for disease control and prevention) from June 20, 2022 onwards in accordance with the Standing Committee on Vaccination at the Robert Koch Institute (STIKO) recommendations, and as a pre-exposure vaccination for people at higher risk of infection in the further course of the outbreak. Out of these 33, 19 persons (5.2 %) received Imvanex as post-exposure vaccination and 14 persons (3.8 %) as pre-exposure prophylaxis. 6 individuals (1.6 %) received both childhood smallpox vaccination and current Imvanex vaccination. All persons vaccinated against smallpox showed symptomatic courses of Monkeypox. The remaining 66.3 % of the infected persons denied a previous smallpox vaccination or were unable to provide any reliable information on the matter.

Route of infection:

In the evaluation, a distinction is made between sexual contacts, both within and outside of one's own household, and other contacts. Household transmission without sexual contact was rare. 248 persons (67.4 %) stated that they had presumably become infected through sexual contacts; 247 of these were reported as sexual contacts between men. 17 persons (4.6 %) suspected infection via non-sexual physical contact. 3 persons (0.8 %) suspected that they had been infected through fomites. In one case, transmission occurred via shared use of an insect bite heat pen. 18 persons (4.9 %) suspected a route of infection in the context of an event (festival or club attendance) without sexual contact or other close physical contact. Furthermore, 3 persons (0.8 %) indicated work contact as a probable source of infection. 79 persons (21.5 %) did not provide any information about a possible source of infection (see Figure 3).

45 persons (12.2 %) suspected having been infected with monkeypox through contacts while attending the Christopher Street Day (CSD) in Cologne (July 01 - 03, 2022). A confirmed source of infection, i.e. contact with a person who had tested positive, could be stated by 73 infected persons (19.8 %).

Incubation period:

209 persons (56.8 %) were able to name the date of the exposure to the suspected or subsequently confirmed source of infection. For those cases, we were able to calculate the incubation period as difference between symptom onset and date of exposure. The results are presented in Figure 4. In the observed group, the onset of symptoms occurred between 1 and 31 days after exposure. The mean incubation period was 8.2 days (SD = 4.7). In 77.5 % of cases, the incubation period was 10 or fewer days. When looking at only the incubation periods of cases with a confirmed source of infection, values between 2 and 20 days could be observed. For those cases, the mean incubation period was 7.6 days (SD = 4.1). We fitted a lognormal distribution to the observed incubation periods, as it visually matched the empirical probability density function and has already been used for MPX incubation periods by Miura et al. (15). Using this distribution, we estimated the mean incubation period to be 8.3 days (95% CI = 6.6 – 10.4) with an estimated standard deviation of 5.2.

Clinical course:

Skin and/or mucosal lesions occurred in 361 cases (98.1 %) during the observation period. 3 persons (0.8 %), in whom the MPX virus was detected via oral or rectal swab, did not show any symptoms during the period of isolation. 110 infected persons (29.9 %) initially showed exclusively non-specific symptoms, such as fatigue, fever or lymphadenopathy in the sense of a prodromal stage. In these persons, it took an average of 3.2 days until the first appearance of skin changes (SD = 2.0). Accordingly, 258 persons (70.1 %) showed skin and/or mucosal lesions as the first symptom. We observed that the lesions usually passed through different stages and were described as non-specific insect bite-like and itchy at the beginning, and as painful pustules, vesicles or crusts in the further course of the disease. Figure 5 shows the different stages of a perioral skin lesion, from the first appearance until the crust falls off, which were photographically documented by an affected person. 

The average duration from onset until absence of symptoms was 15.7 days (SD = 5.2, 95 % CI = 15.2 – 16.2) (Figure 6). In 45 subjects (12.2 %), mandated isolation had to be extended beyond the required minimum of 21 days due to persistent skin lesions. The mean time between the first appearance of skin or mucosal lesions and the date the swab was taken was 5.4 days (SD = 3.8).

The occurrence of skin efflorescences was described in all body regions. They occurred either localized or disseminated. 249 persons (67.7 %) reported efflorescences in the anogenital region, making this the most frequent localisation in the observed group. 86 persons (23.4 %) reported skin lesions on at least 3 different body regions. We observed that the lesions generally appeared and healed asynchronously, especially between the individual localisations. The primary lesion was often located in the area of the presumed site of inoculation. 
 Mucosal lesions and/or characteristic symptoms (anorectal pain, haematochezia; alguria, haematuria; sore throat, difficulty swallowing) were described by 147 infected persons (39.9 %). In 98 persons (26.6 %), anorectal mucosal lesions were presumed due to the described symptoms. Oral mucosal lesions were present in 56 persons (15.2 %), 12 persons (3.3 %) reported signs of urethral mucosal involvement. 28 individuals (7.6 %) initially presented exclusively with symptoms caused by mucosal lesions.
340 persons (92.4 %) described general symptoms in addition to skin/mucosal lesions during the course of the disease. These are listed below in descending order of frequency: fatigue fever, night sweats, and muscle/limb pain (Figure 7). Swollen and/or painful lymph nodes were seen in 192 persons (52.2 %), most commonly in the inguinal and/or cervical region. It was observed that the general symptoms mostly manifested at the beginning of the infection, often either at the same time as or shortly after the first skin lesions. Similar to the study of Patel et al., 7 persons (1.9 %) in this observation group also reported an urticaria-like rash, which subsided after two to three days (16).

Many infected persons reported increased psychological stress at the beginning or in the further course of the isolation. 

In the observed group, hospitalisation was necessary for 13 persons (3.5 %). 2 individuals (0.5 %) received antiviral therapy with Tecovirimat. In no case was treatment in an intensive care unit required due to the monkeypox infection. There were no deaths associated with the MPX virus in Cologne during the observation period.

Discussion

The MPXV was introduced into the Cologne MSM (men who have sex with men) community by singular index persons who had for the most part become infected at pride festivals abroad (e.g. “Gay Pride Maspalomas”, Gran Canary May 2022). After a few weeks of latency, community transmissions and case numbers increased significantly until reaching their peak in CW 28 and 29 (July 11 - 24). Unspecific symptom manifestation and initial lack of awareness for a then new disease among those infected, the MSM community, as well as clinicians may have contributed to the spread of the disease. CSD in Cologne, the largest pride event in the city and one of the largest in Germany (July 01 - 03, 2022; CW 26), and parties in the context of this event presumably played a role in the high number of new reported cases in the following weeks. 12.2 % of all infected persons suspected an infection while attending the CSD events. After this peak, the incidence declined again until the last MPX case in Cologne to date was recorded on September 17. The decline and eventual disappearance of MPX cases in Cologne may be attributed to several factors. The swift public health response comprising mandated isolation of infected persons, extensive contact tracing, targeted information of the risk groups and access to vaccination may have played a role in the containment of the outbreak. But also, the increasing immunity in a limited risk group either via vaccination or infection over the course of the outbreak may have led to a decreasing (effective) reproduction number. 
Monkeypox case numbers throughout Germany and Europe showed a comparable development with the first cases being recorded in April/May, a peak in the summer months and declining case numbers since August (17).
The origin of the infection of the first reported cases in Cologne lay in other European countries, whereas in the further course of the outbreak, most of the observed cases contracted MPX in Germany, oftentimes even within Cologne. This change from importation to autochthonous transmission is consistent with the published study results from Berlin (16). In Great Britain, monkeypox cases are also currently found without an obvious epidemiological connection to endemic areas in Africa (18).

 Data from the Cologne Public Health Department confirmed European findings that monkeypox predominantly affects MSM, often with multiple changing sexual partners (18) (19) (20). The proportion of HIV-infected people among MPX cases was 38.9 %, significantly higher than in the general population and correlated with the frequently reported sexual risk behaviour in the observed patient population. Since the likelihood of a concomitant STD is a third to 50% in MPX patients (18) (19), patients presenting with MPX infection should be offered a screening for STDs including HIV.
 Infections also occurred among persons who had received a smallpox vaccination either in childhood or as a current pre- or post- exposure vaccination. They also showed the typical symptoms of an infection. The extent to which a previous vaccination leads to milder clinical courses or completely prevents an infection cannot be assessed on the basis of the available data. 
 Sexual contacts were the main route of infection in the observed group. The contacts occurred in private settings, as well as in sauna clubs, discotheques or in the context of pride events. Many of the sexual contacts were reported as anonymous. Therefore, although they frequently represented the probable route of transmission, it was often not possible to confirm the source of infection and to identify further contact persons.
Nevertheless, there were also cases of non-sexual transmission via close physical contact or contact with fomites; some of these occurred outside of the MSM community. In Cologne, not a single infection could be traced back to an exclusive close encounter without physical contact or shared objects. It must be taken into account that about a quarter of the persons could only provide insufficient or no information on the presumed route of infection. This can partially be attributed to the anonymity and the high number of risk contacts in some cases. Furthermore, privacy concerns, the intimate nature of the topic, and also fear of stigmatisation may have lead infected persons to withhold information from the interviewers. However, the route of infection may have been truly unknown to at least some persons. It remains unclear whether transmission via non-memorable contact situations or fomites/contaminated surfaces (e.g. in public bathrooms) played a role in these cases.  
 
The mean incubation period was only 8.2 days and was thus shorter than assumed at the beginning of the international outbreak (6) (21). In a study from Spain with 181 test persons, a similarly shorter incubation period was determined (22). When only cases with a confirmed source of infection were taken into account, outliers of less than 2 or more than 20 days of incubation period disappeared completely in the observed group, while the overall probability distribution remained roughly similar (both visually and concerning mean and standard deviation). These results should be taken into account in official recommendations for the management of close contact persons, as the duration of monitoring or quarantine should reflect the incubation period.

 Almost all infected persons developed typical symptoms at the beginning or in the later course of the disease. However, asymptomatic courses of the disease were also observed in isolated cases in which screening swabs were taken due to risk contacts. 
Although we explicitly asked for non-specific symptoms before the onset of the skin lesions in our telephone calls, only about 30 % of the infected persons reported symptoms in the sense of a prodromal stage. This is consistent with other current study results (23). Therefore, a prodromal stage seems to occur much less frequently than historically assumed or the initial symptoms are so unspecific that people do not relate them to the infection despite explicit questioning. 
Accordingly, skin or mucosal lesions were the initial symptomatology in 70 % of the cases, with a very small proportion of asymptomatic infections. In our group, general symptoms largely occurred at the same time or shortly after the initial expression of the skin lesions. Characteristic skin or mucosal lesions were often observed in several body regions during the course of the disease. The anogenital region was named as the primarily affected region. This is probably due to transmission during sexual contact, which is the main route of infection in the observed group (16) (24).
The mean total duration of symptoms (15.7 d) was 5 days shorter than the minimum required isolation time for infected persons according to the RKI recommendations (14). Because of the unspecific clinical appearance and possible lack of general symptoms, monkeypox was often initially misjudged by those affected, but sometimes also by medical practitioners. This is evidenced by the rather long mean time span between the onset of the rash/mucosal lesions and the date the swab was taken. Mucosal involvement and corresponding symptoms were much more frequent than initially assumed. According to our findings, these are often responsible for increased suffering and an aggravated course of the disease, including hospitalisation. In case of a suitable medical history and the presence of such symptoms, a monkeypox infection should therefore always be considered.
 Monkeypox infections may require inpatient treatment. The observed reasons for hospitalisation were a necessary escalation of pain therapy, bacterial superinfections and diagnostic clarification of haematochezia.

The long isolation period and the pronounced symptoms in sensitive body regions such as the genital area or face were accompanied by increased psychological stress for many of the infected. Often, repeated counselling by our staff or, in individual cases, care by the social psychiatric service were necessary. Many infected persons expressed concern about social stigmatisation, especially in connection with their sexual orientation. 
Both in clinical management and in the care provided by the public health service, an especially sensitive approach to the interaction with those infected is necessary (23). However, transparent communication of the issue is equally important in order to protect the risk groups (25). In our experience, close cooperation between clinics, laboratories, general practitioners, and local health departments is essential for adequate care. 
 The public health system consisting of local, regional and national health authorities plays a vital role in the management of a new or previously rare infectious disease such as monkeypox. In Cologne, we were able to draw on experiences gained during the COVID-19 pandemic as well as staff structures in the health department created in response to the pandemic. Thus, starting from the first MPX cases in Cologne and throughout the entire outbreak, a high standard of individual care could be ensured. At the same time, the surveillance data collected in the health authorities provided important information for adapting the public health measures taken against the spread of monkeypox in the population.

Strengths and limitations:

All monkeypox cases in the city area of Cologne were included, in contrast to studies that focus on a pre-selected group of patients. After Berlin, the city of Cologne recorded the second highest number of MPX cases in Germany (as of October 30, 2022). Thus, a relatively high number of infected persons could be included in this study, while at the same time maintaining a high standard of data collection through the extensive structured telephone interviews conducted by selected trained personnel. All information provided by the infected persons was checked for plausibility. Through the regular telephone calls throughout the weeks-long isolation period, a relationship of trust could be established with many of the infected. This potentially leads to more complete data and fewer infected persons withholding information from our staff.

 While the number of cases in relation to the catchment area of a single health authority is very large, it still represents only a fraction of the total number of cases in Germany and worldwide. 

 As the number of cases increased, we also gained new insights. Only in the course of time were we able to understand, for instance, the significance of mucosal lesions and the corresponding symptoms.

Almost all data are based on the statements of the infected persons in the telephone interviews. These statements are, by nature, subjective as well as dependent on compliance and memory, as in any medical history. Particularly with regard to personal and intimate questions, for example concerning the route of infection and contact persons, and even though the infected persons were asked repeatedly in case of missing information, the information provided remained incomplete in a relevant number of cases.

Conclusions

In the wake of globalisation and climate change, the international monkeypox outbreak in May 2022 marked the emergence of another previously atypical infectious disease in Europe. Public health services play a crucial role in containing such outbreaks by isolating affected individuals and promptly identifying contact persons, and also by gathering and analysing health surveillance data. 

Key findings of this observational study are listed below: 

  1. Most infections occurred via sexual contact, but transmission via other physical contact or fomites was also reported.
  2. Most infections were recorded in the MSM community, but persons outside the community were also affected in some cases.
  3. The average incubation period was shorter than initially assumed, with the onset of symptoms occurring in the first 10 days after exposure in the majority of cases. 
  4. A prodromal stage was observed in only about 29.9 % of cases.
  5. Mucosal involvement and associated symptoms occurred in a relevant number of cases and could lead to increased suffering and more severe clinical courses.    

As of October 2022, the local monkeypox outbreak in Cologne appears fully contained. The number of new cases has been similarly declining throughout Germany and Europe. Regardless, monkeypox infections can still cause considerable individual suffering. In the case of unclear skin lesions or symptoms suggesting mucosal involvement, especially combined with a suitable medical history, monkeypox should therefore be considered for differential diagnosis. And even with declining case numbers in many parts of the world, a future monkeypox outbreak is certainly conceivable. 

As evidenced by the monkeypox situation 2022 and also the Covid-19 pandemic, a reactive and well-organised public health system will be critical for managing future outbreaks of known or unknown infectious diseases.

Declarations

Statements and Declarations:

Competing Interests: The authors have no competing interests to declare that are relevant to the content of this article.

Due to the retrospective nature of the analyses and use of anonymized data listings, ethical committee approval and consent statements were not required.

Data Availability Statement: The data used and analysed in the current study are not publicly available because they involve sensitive patient information and indirect identifiers.

Acknowledgements:

We would like to thank all the staff of the index management and quarantine communication teams involved in the collection of the data, as well as the Department for STI of the Cologne Health Department; the Department of Infectious Diseases at Cologne University Hospital; and the infectious diseases specialist practices in Cologne for their excellent cooperation.

We would also like to thank Christine Joisten and Eric J. Bernhard for revising the manuscript.

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