MEDICINE

Original Article

Monkeypox in Germany
Initial Clinical Observations

Christian Hoffmann, Heiko Jessen, [...*], Christoph Boesecke

*Affiliations of the
other authors are
listed at the end of Summary
the article.
Background: Many cases of monkeypox have been reported across Europe from early May 2022 onward. Initial publications
Infectious Disease
Medical Center Ham-
suggest that nearly all of the affected persons to date have been men who have sex with men (MSM).
burg: Prof. Dr. med.
Christian Hoffmann, Methods: To characterize the German cases, an anonymous questionnaire was sent via the mailing lists of the German AIDS
University Hospital Society (Deutsche AIDS-Gesellschaft, DAIG) and the German Association of Outpatient Physicians for Infectious Diseases and
Schleswig-Holstein, HIV Medicine (Deutsche Arbeitsgemeinschaft ambulant tätiger Ärztinnen und Ärzte für Infektionskrankheiten und HIV-Medizin
Campus Kiel: Prof. e.V., DAGNAE).
Dr. med. Christian
Hoffmann
Results: 301 PCR-verified cases had been registered as of 23 June 2022. All of the affected persons were MSM, including 141
Practice of Jessen² + (46.7%) with HIV infection and 135 (44.7%) with pre-exposure prophylaxis (PrEP). The great majority of skin lesions were in the
Colleagues, Dr.
Heiko Jessen and Dr. anal and genital areas. The most common general symptoms were fever, headache, limb pain, and, often, painfully swollen
Arne Jessen, Berlin: lymph nodes. Most infections to date have taken a relatively mild course: 5.0% of the patients were hospitalized, and none died.
Dr. med. Heiko
Jessen A high frequency of sexually transmitted infections (STI) was noted: only 41.0% of the patients had not been given a diagnosis
of an STI in the six months before their monkeypox infection.
Department of Medi-
cine I, Bonn Univer-
sity Hospital: PD Dr. Conclusion: Monkeypox seems to be establishing itself as a new type of STI among MSM. In view of the rising case numbers,
med. Christoph Boe- there is a need for a rapid information and vaccination campaign in the population at risk. Heightened alertness among phy-
secke sicians is needed as well.

Cite this as:

Hoffmann C, Jessen H, Teichmann J, Wyen C, Noe S, Kreckel P, Köppe S, Krauss AS, Schuler C, Bickel M; Lenz J,
Scholten S, Klausen G, Lindhof HH, Jensen B, Glaunsinger T, Pauli R, Härter G, Radke B, Unger S, Marquardt S, Masuhr A,
Esser S, Flettner TO, Schäfer G, Schneider J, Spinner CD, Boesecke C: Monkeypox in Germany—initial clinical observations.
Dtsch Arztebl Int 2022; 119: 551–7. DOI: 10.3238/arztebl.m2022.0287

M
onkeypox virus (MPXV) belongs to the genus individuals. Smear and droplet infections are pos-
orthopoxvirus. The natural hosts of the monkey- sible. The reasons for the current increase in case
pox virus are rodents; monkeys and humans are numbers are still unclear, and there are still unan-
considered false hosts. The first case of monkeypox in swered questions about the transmission. Initial
humans was observed in 1970 in a nine-year-old boy in genome sequence data suggest a close relationship
the Democratic Republic of Congo (1). Since then, mon- with the MPXV variant circulating in West Africa
keypox has mostly been identified in people from Central (6–8). This one possibly causes milder disease and
and West African countries. In recent years, sporadic out- may have lower mortality rates than the variant first
breaks outside Africa was limited to a few cases, for described in Central Africa (9, 10). However, in a
example in the United Kingdom and Israel (2). This cohort from Nigeria, from where relevant case
changed in 2022. Unusually high numbers of cases are numbers with the West African variant have been con-
now being reported from all over Europe. Initial publi- tinually reported since 2017, case-mortality was 6%,
cations suggest that, to date, almost exclusively men who and among the deaths were predominantly male and
have sex with men (MSM) are affected (3). In Germany, female patients with AIDS (11). Little is known so far
the first case from Munich was published on May 20 (4). about other risk factors for severe diseases courses;
By June 17, the Robert Koch Institute (RKI) was aware of probably children and pregnant women in particular
338 confirmed cases; a week later, this number had have an increased risk (12).
doubled to 676 (5). In view of the unexpected dynamics of the out-
Transmission of MPXV takes place from person to break, the aim of the present article was to report on
person through close physical contact with possibly the affected patient population and clinical presenta-
not only symptomatic but also infected asymptomatic tion.

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MEDICINE

FIGURE 1

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PCR diagnosis Symptom onset Cases not documented by all centers

Trend in case numbers per day

The exact date of symptom onset was not documented in all patients.

Methods scriptive analyses. All patients gave their written in-

Registered centers were contacted via the distribution formed consent for the clinical Figures. In cases of
lists of the German AIDS Society (DAIG) and the the same age, nationality and city of entry, a check
German Association of Outpatient Physicians for In- was made for double entries. The study was submitted
fectious Diseases and HIV Medicine (DAGNAE) and to the Ethics Committee of the Technical University
invited to participate. The centers were encouraged to of Munich for review prior to starting, in accordance
retrospectively document from May 19 to June 23, with Section 67 (6) of the German Medicines Act
2022, if possible, all cases from 2022 confirmed by (AMG), and approval was granted (file number
polymerase chain reaction (PCR) from various swab 2022–338-S-NP).
samples. The anonymized, one-page questionnaire
comprised questions on demographics (age, sex, eth- Results
nicity) and comorbidities, including possible HIV As of June 23, 2022, a total of 301 PCR-confirmed
infection (stating current CD4 cell counts and HIV cases had been reported and recorded from 32 centers
RNA copies/mL). Any previous viral hepatitis (hepa- (after excluding five double-reported cases). By far the
titis B and hepatitis C) was asked, as were sexually most cases were reported from Berlin with 161
transmitted infections (STIs) in the previous six (53.3%), followed by Hamburg with 43 (14.2%) and
months. The date of diagnosis of monkeypox virus in- Cologne with 29 (9.6%). Others came from Frankfurt
fection, probable country of infection, symptom (17), Munich (13), Düsseldorf (12), Ulm (5), Bonn (5),
onset, site and number of lesions were ascertained, as Stuttgart (4), Freiburg (4), Essen (3), Aachen (2), and
were the results of any throat swabs, previous small- Braunschweig, Magdeburg and Waake/Göttingen with
pox vaccinations, and severity of monkeypox disease, one case each.
including the number of lesions (categorized), as well Figure 1 shows the number of cases confirmed by
as possible general symptoms such as fever, head- PCR per day. With a total of 227 (75.4%), the vast
ache/aching limbs, night sweats, and lymph node majority of patients had probably acquired the MPXV
swellings. Any specific treatments and any hospitaliz- infection by autochthonous transmission in Germany.
ations with their main reason were also asked. Viro- A total of 25 patients (8.3%) had acquired the infec-
logical PCR diagnostics were performed on a decen- tion in Spain, the majority in Gran Canaria. Many of
tralized basis in the partner laboratories of participat- these cases were primarily seen early in the outbreak;
ing centers and/or in the Consultant Laboratory for for example, among those cases diagnosed by May
Poxviruses at the Robert Koch Institute. Statistical 30, more than one-third (11/31) cited Spain as the
methods in the present article are limited to purely de- source of infection.

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Affected groups, prevalent co-infections TABLE 1

The affected individuals were exclusively MSM,
including 141 (46.7%) living with HIV, of whom the Demographic characteristics and presenting co-infections*
vast majority had normal immune status and adequate Case history details Values
viral suppression on antiretroviral therapy (ART).
Age in years, median (range) 39 (20–64)
Median CD4 cell counts were 691/μL (range 275–1603
cells/μL). Seven patients in total were viremic at their Male sex, % (n) 100 % (301/301)
last test, with their HIV RNA above 50 copies/mL, Ethnicity Caucasian, % (n) 85.9 % (231/269)
including only three with HIV RNA above 200 copies/ Nationality German, % (n) 72.5 % (166/229)
mL. In the case with the highest viral load, the HIV
Previous smallpox vaccination documented, % (n) 12.5 % (28/224)
infection was diagnosed at the time of the presenting
MPXV infection. The second largest affected group, HIV infection
with 135 (44.7%) cases, were MSM without HIV infec- documented HIV infection, % (n) 46.8 % (141/301)
tion who were receiving pre-exposure prophylaxis CD4 cells ≥500/μL, % (n) 80.3 % (102/127)
(PrEP). The remaining 25 cases (8.3%) were MSM
with no HIV infection and no PrEP. No heterosexual CD4 cells 350–499/μL, % (n) 16.5 % (21/127)
men, and no women or children were affected in our CD4 cells <350/μL, % (n) 3.1 % (4/127)
cohort. Characteristics and co-infections are listed in HIV RNA <50 copies/mL, % (n) 94.6 % (123/130)
Table 1.
HIV RNA ≥50–200 copies/mL, % (n) 3.1 % (4/130)
The median age of the patients was 39 years. Only
a total of 26 (8.6%) patients were either under 25 (n = HIV RNA ≥200 copies/mL, % (n) 2.3 % (3/130)
6) or over 55 years of age (n = 20). Only three patients Hepatitis B infection
were over the age of 60. Altogether, 12.5% were anti-HBc negative, % (n) 88.3 % (234/265)
documented as having been vaccinated against small-
anti-HBc positive, HBsAG negative, % (n) 10.9 % (29/265)
pox at least once. The majority of patients were of
German nationality and Caucasian ethnicity. Relevant HBsAG positive, % (n) 0.8 % (2/265)
non-infectious and somatic comorbidities were pres- Hepatitis C infection
ent in very few patients (n = 11), namely psoriatic anti-HCV negative, % (n) 85.7 % (87/273)
arthritis in three cases, and diabetes mellitus, bron-
anti-HCV positive, HCV-PCR negative, % (n) 11.0 % (30/273)
chial asthma, arterial hypertension in two cases each.
The proportion of patients who had suffered another anti-HCV positive, HCV-PCR positive, % (n) 0.4 % (1/273)
STI within the previous six months was quite con-
* Note: Entries vary because not all information was available from all patients.
siderable (Figure 2). More than half were diagnosed
within the previous four weeks before MPXV infec-
tion or at the same time and most commonly with
gonorrhea. Only 41.0% were not diagnosed with an
STI within six months prior to MPXV infection. ings, extensive involvement of the entire skin, bleed-
ing, or due to refractory pain that could not be
Clinical presentation controlled on an outpatient basis, especially in cases
Because a large proportion of infections were only of anal involvement. The average length of hospital
diagnosed in the last few days of the study, the observa- stay was four days (range 3–6 days); however, seven
tion period was very short, with a median of three days of the 15 patients were still in hospital at the end of
(range 0–35 days). Only 130 patients had a follow-up the observation period. At least one hospitalized
of at least five days. The median time between symp- patient received antiviral therapy with tecovirimat
tom onset and MPXV diagnosis was four days (range (off-label).
0–21 days). It is therefore to be expected that in subse- Disease manifestations are listed in Table 2. Three
quent days some of the cases will present themselves in cases remained without lesions and were diagnosed
an even more severe condition than before. Nevertheless, during STI screening. By far the majority of the mon-
the disease characteristics will be briefly outlined below. keypox lesions manifested anally or genitally. In only
Most of the diseases so far appear to have been 36 (12.0%) cases was there neither genital nor anal
relatively mild. No deaths were reported. A total of 18 involvement. Other sites such as trunk or extremities
patients were admitted to hospital as inpatients, of were also affected in just under one half of cases.
whom at least three were clearly not due to the sever- Only 16 patients (5%) had disease without any geni-
ity of the clinical picture or (imminent) complications tal, anal, or oral manifestations. Only few patients had
but for quarantine reasons or for diagnostic purposes. extensive findings with 50 or more lesions. These
A total of 15 hospitalizations (5.0% of all patients, rates changed insignificantly when the analysis was
8.4% in patients with an observation period of at least restricted to cases with at least 5 or 10 days of illness
five days) occurred because of the severity of the (data not presented). The most common general
clinical picture or due to complications. These were symptoms were fever, headache, and aching limbs,
predominantly massive lymph node and genital swell- and often painful swelling of the lymph nodes.

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FIGURE 2 loads above 200 copies/mL. In one case, HIV infec-

tion was diagnosed as a result of the MPXV infection,
100 % suggesting that diagnostic testing for HIV is likely to
90 % be worthwhile in HIV-negative persons with MPXV
80 %
infection, as with other STIs.
70 %
The high number of other STIs diagnosed either in
81.2 72.8 62.8 91.5 41.09 parallel or shortly before was particularly noteworthy.
60 %
Almost two-thirds had been diagnosed, or documented,
50 %
with at least one STI within the last six months, and al-
40 %
32.1 most one-third within the last month or even at the
30 %
9.4 19.3 same time. Since there was no systematic screening for
20 %
5.6 3.3 STI, it is quite possible that the documented cases are
10 %
13.2 17.7 17.8 5.1 26.9 an underestimate of the actual rates. This high coinci-
0% dence highlights the fact that in the current situation,
Syphilis Chlamydia Gonorrhea Mycoplasma Any other
when an STI is diagnosed, MPXV infection should
definitely be considered as well (and vice versa).
subacute acute not documented
No deaths were reported, and the clinical course was
predominantly mild to moderate. It should be noted,
Percentage of documented sexually transmitted infections (STIs) in the past 6 months (acute
however, that the observation period was very short
= diagnosed within the past four weeks or concurrent with MPXV infection, subacute = diag-
nosed in the past six months but not acute). and it is possible that the observed hospitalization rate
may still increase somewhat, as may the number of ob-
served lesions. However, the data did not change dra-
matically when analysis was limited to the (still quite
Discussion small) number of patients with longer observation peri-
In the present retrospective study, a total of 301 cases of ods. On the other hand, it is also possible that patients
PCR-confirmed MPXV infection from 32 participating with few symptoms may have escaped diagnosis and
centers were analyzed by June 23, corresponding to were therefore not enrolled in the study.
approximately 45% of the cases reported in 2022 to the It should be noted that the patients were predomi-
RKI by that time. Several entries occurred just at the nantly young and otherwise generally healthy.
beginning of the outbreak from Gran Canaria, possibly Whether the currently circulating West African vari-
on the occasion of the Maspalomas Gay Pride 2022, ant is associated with low severity, as suggested by
which had been taking place until May 15, 2022. Mean- studies using the monkey model (9), remains to be
while, entries from other countries tend to be sporadic. seen. So far, little is known about risk factors associ-
By far the most cases were reported from major ated with severe disease, but children and pregnant
cities, with 233 cases (77%) from Berlin, Hamburg women in particular may be at increased risk of
and Cologne alone. The observed cases were found severe disease (12). So far, these populations have not
exclusively among MSM, more than 90% of whom been identified in the present cohort. Also, among the
either had HIV infection or were taking HIV PrEP. In HIV-infected patients included in this cohort, there
over 90% of cases, the age range was between 25 and have been only very few individuals with severe
55 years. It should be noted as a limitation that, to a immunodeficiency or viremia. Risk factors were not
considerable extent, the involved centers treat MSM identified in the present study because of the small
with and without HIV infection and thus a bias is number of cases with severe courses of the disease.
quite possible. It cannot therefore be ruled out that In the present cohort, a total of 12.5% had evidence
individuals outside the aforementioned affected group of smallpox vaccination. The date of smallpox vacci-
have already been infected and that they have either nation was probably at least 40 years ago; mandatory
not yet been diagnosed or are being treated in centers vaccination in West Germany ended in 1976, and in
that did not participate in this survey. A bias is there- East Germany in 1982. Laboratory studies and clini-
fore likely. However, it is also evident that awareness cal observations suggest that previously administered
campaigns on risks and modes of transmission focus smallpox vaccines provide some, but by no means
on major German cities and may initially remain complete, protection against monkeypox (14–19).
target-group specific, such as via messages in dating The present analysis also shows that smallpox vacci-
apps, but without stigmatizing these people. The Joint nation does not give complete protection, although a
United Nations Programme on HIV/AIDS (UNAIDS) certain degree of protection against severe infections
has already stated that the fact that so far mainly cannot be excluded. The high proportion of young,
MSM have been affected could create homophobic unvaccinated patients was notable. Although this
and racist stereotypes and reinforce stigmatization could also be due to absence of protective immunity
(13). from not having been vaccinated against smallpox,
The majority of patients with HIV had a good behavioral factors are equally possible.
immune status and were on viral suppression with For now, a prompt awareness and vaccination cam-
antiretroviral therapy. Only three patients had viral paign targeted at at-risk populations is called for; the

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240,000 vaccine doses (two doses per person) so far TABLE 2

ordered by the German government may not be
enough. The expected availability of the smallpox Disease manifestations*
vaccine IMVANEX (modified form of the vaccinia Case history details Values
virus Ankara, live) from Bavarian Nordic has not
Site
been studied in severely immunocompromised
patients (20) and is not currently licensed for mon- Genital, % (n) 49.0 % (146/298)
keypox vaccination in the European Union (although of which exclusively genital, % (n) 45.2 % (66/146)
it is in the United States and Canada). Therefore, even Anal, % (n) 50.8 % (152/299)
in healthy individuals, available data are relatively
of which exclusively anal, % (n) 35.5 % (54/152)
limited, and the number of exposed individuals is still
low. Response rates and seroconversion rates appear Oral, perioral, head, % (n) 24.4 % (72/296)
to be worse in people with HIV (21). Experiments of which exclusively oral/head, % (n) 33.3 % (24/72)
using the monkey model would also suggest this (22). Extremities and/or trunk, % (n) 41.7 % (122/292)
Therefore, a study to accompany the upcoming vacci-
nation campaign would be desirable, which would of which exclusively, % (n) 13.1 % (16/122)
also investigate seroconversion rates and evaluate Number of lesions
possible breakthrough infections. none (only positive swabs), % (n) 1.1 % (3/279)
Apart from vaccination, a comprehensive aware-
1–3, % (n) 44.1 % (123/279)
ness campaign is also needed, focused on the
involved groups, as open as possible, close to the 4–10, % (n) 33.3 % (93/279)
community, digital and on-site, low-threshold and 11–50, % (n) 18.3 % (51/279)
non-judgmental. Physicians specializing in HIV and >50, % (n) 3.2 % (9/279)
those who prescribe HIV PrEP are now called upon to
General symptoms
do likewise. In particular, situations should be
addressed where PrEP appears to be necessary and Fever, % (n) 61.3 % (168/274)
useful. Places where transmission is common (such as Headache and aching limbs, % (n) 46.7 % (126/270)
sex clubs and sex parties with large numbers of par- Night sweats, % (n) 19.9 % (53/266)
ticipants) should be avoided until the ongoing
Lymph node swelling, % (n) 44.1 % (116/263)
outbreak is under control.
According to RKI estimates, the risk for the gen- * in each case, only cases with available information listed
eral population in Germany is “currently low” (as of
June 17, 2022). However, current outbreak kinetics
suggest that monkeypox will establish itself as a new
Infectious Disease Medical Center Hamburg: Dr. med. Guido Schäfer
STI, and spread into populations outside MSM seems
at least possible. It is likely that many patients will Practice of Jessen² + Colleagues Heiko Jessen and Arne Jessen, Berlin:
present outside of HIV-focused practices, especially Jörn Teichmann
urology, proctology, or even dermatology practices. Practice at Ebertplatz, Cologne: PD Dr. med. Christoph Wyen
Small lesions in sexually active MSM, especially
genitoanal lesions, should also be examined for Department for Internal Medicine I, University Hospital Cologne:
PD Dr. med. Christoph Wyen
MPXV. In larger centers, infection is often already a
visual spot diagnosis, but swabs are needed for confir- Medical Care Center Munich at Goetheplatz, Munich: PD Dr. med. Sebas-
tian Noe
mation and should also be tested for other STIs. A
quick diagnosis is essential in order to prevent further Group Practice for Internal Medicine m-50.de, Berlin: Peter Kreckel, Sieg-
infections – including infection of medical staff. In fried Köppe
view of the considerable number of cases, it seems Doctors’ Forum for Infectious Diseases, Seestrasse, Berlin: Dr. med. Anja-
sensible to offer the medical staff of, among others, Sophie Krauss
HIV-focused practices not only postexposure vacci- Turmstrasse Practice, Berlin: Dr. med. Christoph Schuler, Johannes Lenz
nations, as recommended by the Standing Committee
on Vaccination, but also indication-based vacci- Infectious Diseases Center, Frankfurt: PD Dr. med. Markus Bickel
nations. Individual cases of nosocomial transmission Dr. Scholten & Schneeweiss Partnership, Cologne: Dr. med. Stefan
have been reported (23–25). The present study and Scholten
especially the Figures should help to avoid this.
Subspecialized Practice for Infectious Disease at the Oranienburg Gate,
Berlin: Dr. med. Gerd Klausen
*Additional authors
Jörn Teichmann, Christoph Wyen, Sebastian Noe, Peter Kreckel, Department of Dermatology, University Hospital Düsseldorf: Dr. med.
Siegfried Köppe, Anja-Sophie Krauss, Christoph Schuler, Harm-Henning Lindhof
Markus Bickel, Johannes Lenz, Stefan Scholten, Gerd Klausen,
Harm-Henning Lindhof, Björn Jensen, Tobias Glaunsinger, Ramona Pauli, Department for Gastroenterology, Hepatology and Infectious Diseases,
Georg Härter, Billy Radke, Stefan Unger, Simone Marquardt, University Hospital Düsseldorf: Dr. med. Björn Jensen
Anja Masuhr, Stefan Esser, Tim Oliver Flettner, Guido Schäfer,
Jochen Schneider, Christoph D. Spinner Prenzlauer Berg Practice, Berlin: Dr. med. Tobias Glaunsinger

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orthopoxviruses: recommendations of the Advisory Committee on Im-
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sungen, BioNtech, Gilead Sciences, Janssen-Cilag, Eli Lilly, Formycon, Rep 2022, 71: 734–42.
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556 Deutsches Ärzteblatt International | Dtsch Arztebl Int 2022; 119: 551–7
 MEDICINE

Cite this as:

Hoffmann C, Jessen H, Teichmann J, Wyen C, Noe S, Kreckel P,
Köppe S, Krauss AS, Schuler C, Bickel M, Lenz J, Scholten S,
Klausen G, Lindhof HH, Jensen B, Glaunsinger T, Pauli R, Härter G, Radke B,
Unger S, Marquardt S, Masuhr A, Esser S, Flettner TO, Schäfer G,
Schneider J, Spinner CD, Boesecke C:
Monkeypox in Germany—initial clinical observations.
Dtsch Arztebl Int 2022; 119: 551–7. DOI: 10.3238/arztebl.m2022.0287

CLINICAL SNAPSHOT
Bloodstream Infection by Neisseria meningitidis
A 33-year-old, previously healthy female patient presented with a 3-week history of skin rash and fever (up
to 40 ° C) as well as arthritic symptoms in the left upper ankle. On physical examination, monomorphic,
bright red subcutaneous nodules measuring up to approximately 1 × 1 cm without ulceration were striking;
these were disseminated over the entire integument, in particular the extremities, excluding the head and
mucous membranes (Figure). Laboratory results revealed leukocytosis (14/nL) and elevated creatinine le-
vels (88 mg/L, normal value <5 mg/L). Four serial blood cultures detected the growth of Neisseria mening-
itidis serogroup C. We initiated antibiotic treatment with high-dose penicillin G. The further diagnostic work-
up to identify an immune defect yielded no abnormalities. Antibiotic treatment achieved a complete resol-
ution. Blood cultures represent a central diagnostic tool in disorders involving fever of unknown origin; bac-
teremia due to Neisseria meningitidis, a rare differential diagnosis, should be taken into consideration in
the case of cyclic fever with maculopapular rash.
Dr. med. Jonas Jaromier Staudacher, Berlin Institute of Health at Charité – Universitätsmedizin Berlin Charité;
Universitätsmedizin Berlin, Campus Benjamin Franklin, [email protected]
Dr. Marcel Wittenberg, Prof. Dr. Dr. Thomas Schneider, Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin
Conflict of interest statement: The authors state that no conflict of interest exists.
Translated from the original German by Christine Rye.
Cite this as: Wittenberg M, Schneider T, Staudacher JJ: Bloodstream infection by Neisseria meningitidis.
Dtsch Arztebl Int 2022; 119: 557. DOI: 10.3238/arztebl.m2022.0156

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