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INFEKTTAG 2013 _ TRENDS
Outdoor Infektionen _ Carol Strahm
infekttag_2013
OUTDOOR
INFEKTIONEN ...
... Trends ... zu den von Zecken
übertragenen Krankheiten in der
Schweiz
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1. LYME
BORRELIOSE
Alte und neue Trends
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LYME BORRELIOSE
๏ häufigste zeckenübertragene Krankheit in der Schweiz
๏ 6000-12000 Fälle pro Jahr
๏ unbehandelt: chronischer Infekt mit verschiedenen
typischen Stadien
๏ Stadium I früh lokalisiert (ECM)
๏ Stadium II früh disseminiert (Bannwarth, Lymphozytom, Carditis)
๏ Stadium III spät/ chronisch (Arthritis, ACA, Neuroborreliose)
๏ Erreger: Borrelia burgdorferi sensu lato
Altpeter et al., Swiss Med Wkly. 2013;143:0.
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ASE STUDY
St. I St. II
Tick bite
Erythematous rash
Stadium III
Right-elbow pain
Right-shoulder pain
Patient had not
taken amoxicillin
Symptoms improved
Left-ankle pain
and swelling
Mild headache
Stiff neck
Left-knee pain
and swelling
Swelling recurred
Swelling worsened for 9 days
Pain in right knee
Left-knee swelling
No sign
of arthritis
1 year
Homeopathic remedies
No antibiotics
Homeopathic remedies
No antibiotics
Rash improved
Homeopath
Lyme arthritis diagnosed
Patient declined
recommendation of
doxycycline
Acupuncturist
First presentation
Lyme arthritis confirmed
Amoxicillin prescribed
for 30 days
Acupuncture
Left-knee swelling
improved
Rheumatologist
Acupuncture
Left-knee swelling
persisted
Homeopath prescribed
doxycycline for 14 days
Discontinued after no
improvement
Headache and weakness
confine patient to bed
Second presentation
Doxycycline
administered
for 30 days
Swelling improved
Figure 1 | Timeline of the case illustrating the natural history of Lyme disease. Visits to the homeopath, acupuncturist and
rheumatologist are color-coded and displayed below the timeline.
KLINIK DER UNBEHANDELTEN LYME
BORRELIOSE (USA)
therapy. She confined herself to bed for 24 days because
of the knee pain, weakness and a headache. One month
later, she had some decrease in the left-knee swelling and
resolution of the headache and weakness.
Following her self-confinement, the patient returned
to the rheumatologist (Figure 1; second presentation).
He reviewed the testing done 1 month previously by the
acupuncturist, including the repeat Lyme-disease testing,
Schoen, Nat Rev Rheumatol. 2011 Mar;7(3):179–84.
for which she was positive (ELISA >5.00; Western Blot,
negative for IgM, positive for IgG), and the erythrocyte
disease has expanded and Lyme disease is now the most
common vector-borne disease in both North America
and Europe.5
Lyme disease has characteristic, well-recognized clinical features and is generally classified into early and late
stages;6 early disease can be localized or disseminated
(Figure 2b). Lyme disease typically begins with erythema
migrans (EM) or other early-stage disease manifestations.7 Such early disease can be localized to the skin
or can involve hematogenous dissemination to other
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BORRELIEN: AKTUELLE
TRENDS (OST)SCHWEIZ
Sentinella Daten 2008-2012
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303
REGION 5 (AR,
AI, GL, SG, SH,
TG, ZH, FL)
Inzidenz CH 131/100000
156
Altpeter et al., Swiss Med Wkly. 2013;143:0.
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JAHRESTRENDS 2010-12
www.bag.admin.ch
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SENTINELLA-RESULTATE
๏ 90% Erythema chronicum migrans (ECM)
๏ ∼10% spätere Stadien - Stadium II/III
๏ 4-5%: Acrodermatitis chronica atrophicans (ACA), Lyme
Arthritis, benignes Lymphozytom
๏ frühe und chronische Neuroborreliosen, Karditis: sehr selten
Altpeter et al., Swiss Med Wkly. 2013;143:0.
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FRAGE
Welches ist die optimale Behandlung eines
Erythema chronicum migrans?
1. Clamoxyl 3x1000mg für 14 Tage
2. Doxycyclin 2x100mg für 21 Tage
3. Doxycyclin 2x100mg für 14 Tage
4. Doxycyclin 2x100mg für 10 Tage
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igrans
.5)
.5)
3)
After
Enrollment, to 15-Day and 10-Day Regimens of Doxycycline
Daša Treatment
Stupica,1 Lara Lusa,2 Eva Ružić-Sabljić,3 Tjaša Cerar,3 and Franc Strle1
1
= 108)
–62)
Treatment of Erythema Migrans With
Doxycycline
for 10 ofDays
Versus
15 Days
Table 2. Achievement
Complete
Response,
by Time
Department of Infectious Diseases, University Medical Center Ljubljana, 2Institute for Biostatistics and Medical Informatics, Ljubljana, and 3Institute
of Microbiology and Immunology, Faculty of Medicine Ljubljana, Slovenia
a
Background. The efficacy of 10-day doxycycline treatment in patients with erythemaDifference
migrans has been
assessed in the United States but not in Europe. Experts disagree on the significance of post–Lyme borreliosis
b sympTime
15-Day
Group
10-Day
Group
(95%
CI
)
toms.
Methods. In a noninferiority trial, the efficacies of 10 days and 15 days of oral doxycycline therapy were
14 day
71/117 (60.7)
60/108 (55.6)
5.1 (16.8)
evaluated in adult European patients with erythema migrans. The prevalence of nonspecific symptoms was compared2between
patients with erythema migrans
and(86.7)
81 control subjects
without
a history of Lyme
borreliosis. The
months
98/113
88/104
(84.6)
2.1 (10.9)
efficacy of treatment, determined on the basis of clinical observations and microbiologic tests, was assessed at 14
95/101
(94.1)
(84.4)
9.7at(17.9)
days 6
andmonths
at 2, 6, and 12 months. Nonspecific
symptoms
in patients 81/96
and controls
were compared
6 months after
enrollment.
12 months
85/91 (93.4)
79/86 (91.9)
1.6 (9.1)
Results. A total of 117 patients (52%) were treated with doxycycline for 15 days, and 108 (48%) received
doxycycline
for 10 days. Twelve months
after enrollment,
91 patients (93.4%)
15-day group
Last evaluable
107/117
(91.5)85 of 101/108
(93.5)in the −2.1
(4.6)and 79 of
86 (91.9%) in the 10-day group had complete response (difference, 1.6 percentage points; upper limit of the 95%
visit
confidence interval, 9.1 percentage points). At 6 months, the frequency of nonspecific symptoms in the patients
was similar to that among controls.
Data are The
No.10-day
of patients
completewasresponse/no.
receiving
treatment
Conclusions.
regimen ofwith
oral doxycycline
not inferior to the
15-day regimen
among adult
(%),patients
unlesswith
otherwise
indicated.
European
solitary erythema
migrans. Six months after treatment, the frequency of nonspecific symptoms among erythema migrans patients was similar to that among control subjects.
Abbreviation: CI, confidence interval.
Clinical Trials Registration. NCT00910715.
a
Percentage-point difference in the proportion of patients in each group with
complete response.
Stupica et al., CID 2012 May 21
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FRAGE
Kann man eine Neuroborreliose in der Praxis
diagnostizieren und behandeln?
1. Ja, ich habe schon mehrere diagnostiziert und erfolgreich
ambulant therapiert
2. Therapieren ja, diagnostizieren mach ich nicht selber
3. nein, ich weise Verdachtspatienten immer ins Spital ein
4. weiss nicht
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Table 2 Suggested case definitions for Lyme neuroborreliosis (LNB)
Definite neuroborreliosisa
All three criteria fulfilled
1
2
3
Possible neuroborreliosisb
Two criteria fulfilled
Neurological symptoms suggestive
of LNB without other obvious
reasons
Cerebrospinal fluid pleocytosis
Intrathecal Bb antibody production
a
These criteria apply to all subclasses of LNB except for late LNB with
polyneuropathy where the following should be fulfilled for definite
Diagnose:
es braucht
einechronica
LP
diagnosis: (I)
peripheral neuropathy
(II) immmer
acrodermatitis
inkl
Liquor/antibodies
Serum Antikörper
für
atrophicans (III)
Bb-specific
in serum.
b
If criteria III is lacking; after
a duration of 6 weeks, there have to be
Reiber-Quotient!
found Bb-specific IgG antibodies in the serum.
concentr
that ora
efficacy a
A recent
showed
14 days)
axone (2
Duration
residual
led to s
eventual
no class
In most
ged from
long as 2
response
Mygland et al., Eur. J. Neurol. 2010 Jan;17(1):8–16, e1–4.
Journal compil
Possible diseases
Coexisting
Symptom
Tick
bite duration >6 months
Ljøstad et al., Lancet Neurol. 2008 Aug 1;7(8):690–5.
Mean duration
of symptoms (weeks)
Erythema
migrans
Mean
count
(n)
MeanCSF
agecell
(years)
Neuroborreliosis
diagnosis
17 (41%)
(31%)
14 (29%)
22
Oral
doxycycline Intravenous
6 (56%)
(11%)
4 (54%)
(8%)
30
26
(n=54)
ceftriaxone
10
(19)
85 (10%)
(13)
17 (31%)
2x100mg (n=48)
1x2g
194
178
(187)
54 (237)
(13)
52 (13)
Sex
(female)
Mean
CSF
Defi
nite protein (g/L)
Coexisting
Mean
clinicaldiseases
score
Possible
26
(48%)
(0·7)
371·2
(69%)
22
(41%)
8·2
(4·1)
17
(31%)
17
(35%)
(0·8)
341·3
(71%)
14
(29%)
8·9
(4·1)
14
(29%)
Tick bite
Mean
subjective
score
Symptom
duration
>6 months
Erythema
migrans
Main
objective
fiofndings
Mean
duration
symptoms (weeks)
30
(56%)
4·3
(2·3)
6
(11%)
17 (19)
(31%)
10
2645·1
(54%)
(2·3)
(8%)
58 (10%)
(13)
18 (237)
(33%)
194
371·2
(69%)
12
(22%)
(0·7)
17
(31%)
2 (4%)
8·2
(4·1)
12 (187)
(25%)
178
3491·3
(71%)
(19%)
(0·8)
148·9
3 (29%)
(6%)
(4·1)
6 (24%)
(11%)
13
4·3
(2·3)
10
(19)
2 (4%)
45·1
(8%)
18
(38%)
(2·3)
80 (13)
(0%)
194
(237)
(2%)
181 (33%)
(0·7)
01·2
(0%)
12
(22%)
178
0 (187)
(0%)
12
(25%)
1·3
(0·8)
(2%)
91 (19%)
42 (4%)
(7%)
4
(8%)
0 (0%)
Neuroborreliosis
diagnosis
Bannwarth’s
syndrome*
Mean
CSF cell count
(n)
DefiCSF
nite
Facial
palsy
Mean
protein (g/L)
Possible
Other
cranial
neuropathies
Mean
clinical
score
Symptom
duration
>6 months
Radiculopathy
Mean
subjective
score
Mean
durationfiof
symptoms (weeks)
Ataxia
Main
objective
ndings
Mean
CSF cell count
(n)
Myelopathy
Bannwarth’s
syndrome*
Mean
CSF
protein
(g/L)
Cognitive
deficiency
Facial
palsy
Mean
Arm clinical
paresis
Other
cranialscore
neuropathies
Mean
score
ACA subjective
and paraesthesias
Radiculopathy
Main
findings
Onlyobjective
subjective
complaints
Ataxia
8·2
(4·1)
(2%)
21 (4%)
(2·3)
1 (24%)
(2%)
134·3
8·9
(4·1)
(2%)
31 (6%)
5·1
(2·3)
0 (38%)
(0%)
18
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Possible diseases
Coexisting
Symptom
Tick
bite duration >6 months
Ljøstad et al., Lancet Neurol. 2008 Aug 1;7(8):690–5.
Mean duration
of symptoms (weeks)
Erythema
migrans
Mean
count
(n)
MeanCSF
agecell
(years)
Neuroborreliosis
diagnosis
17 (41%)
(31%)
14 (29%)
22
Oral
doxycycline Intravenous
6 (56%)
(11%)
4 (54%)
(8%)
30
26
(n=54)
ceftriaxone
10
(19)
85 (10%)
(13)
17 (31%)
2x100mg (n=48)
1x2g
194
178
(187)
54 (237)
(13)
52 (13)
Sex
(female)
Mean
CSF
Defi
nite protein (g/L)
Coexisting
Mean
clinicaldiseases
score
Possible
26
(48%)
(0·7)
371·2
(69%)
22
(41%)
8·2
(4·1)
17
(31%)
17
(35%)
(0·8)
341·3
(71%)
14
(29%)
8·9
(4·1)
14
(29%)
Tick bite
Mean
subjective
score
Symptom
duration
>6 months
Erythema
migrans
Main
objective
fiofndings
Mean
duration
symptoms (weeks)
30
(56%)
4·3
(2·3)
6
(11%)
17 (19)
(31%)
10
2645·1
(54%)
(2·3)
(8%)
58 (10%)
(13)
Neuroborreliosis
diagnosis
Bannwarth’s
syndrome*
18
(33%)
12 (187)
(25%)
Mean
CSF cell count
194
(237)
178
Outcome
(LP,(n)klinischer Score,
Follow-up
4 Monate):
DefiCSF
nite
371·2
(69%)
3491·3
(71%)
Facial
palsy
12
(22%)
(19%)
Mean
protein
(0·7)
(0·8)
kein(g/L)
signifikanter Unterschied!
Possible
17
(31%)
148·9
Other
cranial
neuropathies
2 (4%)
3 (29%)
(6%)
Mean
clinical
score
8·2
(4·1)
(4·1)
Symptom
duration
>6 months
Radiculopathy
Mean
subjective
score
Mean
durationfiof
symptoms (weeks)
Ataxia
Main
objective
ndings
Mean
CSF cell count
(n)
Myelopathy
Bannwarth’s
syndrome*
Mean
CSF
protein
(g/L)
Cognitive
deficiency
Facial
palsy
Mean
Arm clinical
paresis
Other
cranialscore
neuropathies
Mean
score
ACA subjective
and paraesthesias
Radiculopathy
Main
findings
Onlyobjective
subjective
complaints
Ataxia
6 (24%)
(11%)
13
4·3
(2·3)
10
(19)
2 (4%)
45·1
(8%)
18
(38%)
(2·3)
80 (13)
(0%)
194
(237)
(2%)
181 (33%)
(0·7)
01·2
(0%)
12
(22%)
178
0 (187)
(0%)
12
(25%)
1·3
(0·8)
(2%)
91 (19%)
42 (4%)
(7%)
4
(8%)
0 (0%)
8·2
(4·1)
(2%)
21 (4%)
(2·3)
1 (24%)
(2%)
134·3
8·9
(4·1)
(2%)
31 (6%)
5·1
(2·3)
0 (38%)
(0%)
18
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EFNS GUIDELINES
(EUROPEAN FEDERATION OF
NEUROLOGICAL SOCIETIES)
Frühe Neuroborreliose (< 6 Monate)
๏ PNS (Bannwarth)/ Meningitis:
๏ Penicillin IV, Ceftriaxon 2g IV, Doxycyclin 2x100mg für 14 Tage,
๏ ZNS (Myelitis, cerebrale Vaskulitis, Enzephalitis)
๏ Ceftriaxon 2g IV tgl für 14 Tage
Späte Neuroborreliose (> 6 Monate)
๏ 3 Wochen therapie (Ceftriaxon), Ausnahme ACA und PN
Mygland et al., Eur. J. Neurol. 2010 Jan;17(1):8–16, e1–4.
infekttag_2013
EFNS GUIDELINES
(EUROPEAN FEDERATION OF
NEUROLOGICAL SOCIETIES)
Frühe Neuroborreliose (< 6 Monate)
๏ PNS (Bannwarth)/ Meningitis:
๏ Penicillin IV, Ceftriaxon 2g IV, Doxycyclin 2x100mg für 14 Tage,
๏ ZNS (Myelitis, cerebrale Vaskulitis, Enzephalitis)
๏ Ceftriaxon 2g IV tgl für 14 Tage
Späte Neuroborreliose (> 6 Monate)
๏ 3 Wochen therapie (Ceftriaxon), Ausnahme ACA und PN
Mygland et al., Eur. J. Neurol. 2010 Jan;17(1):8–16, e1–4.
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SEROLOGIE
alte Trends
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FRAGE
Wie hoch ist die Seroprävelnz der Borreliose bei
der gesunden Bevölkerung?
1. ca 2%
2. ca 5%
3. ca 10%
4. >10%
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SEROPRÄVALENZ SCHWEIZ (%)
40
30
20
35
26
10
10
WALDARBEITER
OL LÄUFER
0
BLUTSPENDER
Altpeter et al., Swiss Med Wkly. 2013;143:0. // Nadal et al., Eur J Clin Microbiol Infect Dis. 1989 Nov;8(11):992–5. // Altpeter et al. SMW. 1992 Jan
8;122(1-2):22–6. // Fahrer et al., JID 1991 Feb;163(2):305–10.
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SEROLOGIE IN RISIKOGRUPPEN
OL LÄUFER (950)
BLUTSPENDER >1000 MÜM (51)
4%
negativ
74%
positiv
26%
Baseline (248 positive
Serologien)
Anamnese positiv (1.9-3.1%)
•18 hatten eine sichere LB
•11 hatten eine mögliche
Fahrer et al., JID 1991 Feb;163(2):305–10.
96%
FREIWILLIGE STADT BERN (50)
6%
94%
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SEROLOGIE IN RISIKOGRUPPEN
OL LÄUFER (950)
BLUTSPENDER >1000 MÜM (51)
4%
negativ
74%
positiv
26%
Baseline (248 positive
Serologien)
Anamnese positiv (1.9-3.1%)
•18 hatten eine sichere LB
•11 hatten eine mögliche
Fahrer et al., JID 1991 Feb;163(2):305–10.
96%
FREIWILLIGE STADT BERN (50)
6%
94%
Halbjahresfollow-up:
•Serokonversion: 8% (45/558)
•nur eine symptomatische LB
•klinische LB Inzidenz 0.8% (6/755)
With early Lyme disease
(n p 40)
Test, antibody, result
During
active infection
At follow-up
With Lyme arthritis
(n p 39)
During
active infection
infekttag_2013
At follow-up
ELISA
IgM
Table 1. Positive and indeterminate antibody responses to Borrelia burgdorferi, as
Positive by ELISA, Western20blot,
(50)or both, in patients
0
0
determined
who had4 (10)
early Lyme disease
or
Lyme
arthritis.
Indeterminate
17 (43)
9 (23)
22 (56)
13 (33)
IgG
Positive
Indeterminate
Western blot
IgM
Test, antibody, result
IgG
ELISA
ELISA and Western blot
IgM
IgM
Positive
IgG
Indeterminate
IgM or IgG
IgG
Positive
No. (%) of patients
17 (43)
11 (28)
39 (100)
28 (72)
With
early Lyme disease
11 (28)
12 (30)
0With Lyme arthritis
10 (26)
(n p 40)
(n p 39)
During
35 (88)
active infection
20 (50)
7 (18)
At follow-up
10 (25)
During
21 (54)
active infection
39 (100)
33 (83)
20 (50)
19 (48)
17 (43)
35 (88)
4 (10)
0
10 (25)
9 (23)
14 (35)
15 (38)
4 (10)
39 (100)
22 (56)
39 (100)
0
24 (62)
13 (33)
26 (67)
17 (43)
11 (28)
39 (100)
28 (72)
Indeterminate
(28) not
uring active infection,
including several 11
bands
WesternIn
blot
e diagnostic criteria.
the follow-up evaluation, the
f IgM and IgG IgM
bands had decreased, but35at(88)
least 2
Kalish et al., CID. 2001 Sep 15;33(6):780–5.
(50)
IgM bands wereIgG
still apparent. Altogether, 20
14 patients
ELISA and Western blot
12
(30)
long-term
9 (23)
At follow-up
24 (62)
6 (15)
0
10 (26) IgG antibody re
follow-up
had a positive
patients in this group (5%) had a positive IgM resp
7 (18) active 21
(54)
9 (23)
During
infection,
both of
these patients had
10
24 (62) proteins. In th
IgG(25)
responses 39
to (100)
multiple spirochetal
infekttag_2013
SCHLUSSFOLGERUNG
๏ hohe Seroprävalenz in der Schweiz (4-30% je nach Risiko
und Alter)
๏ positive Serologie ohne Klinik nicht verwertbar
๏ viele asymptomatische Infektionen
๏ Serologie unspezifisch (Screening-Test)
immer
Bestätigung mittels Western-Blot
๏ Stadium I: Serologie oft negativ
๏ Serologie kann nicht als Verlauf verwertet werden
infekttag_2013
TELEFONKONSIL
Ein Landwirt hatte bereits vor 3 Jahren ein
erfolgreich behandeltes Erythema migrans (EM)
und kommt nun mit einem erneutem EM an
anderer Stelle.
1. Rezidiv?
2. Reinfektion?
3. Immunität?
infekttag_2013
IMMUNITÄT DER BORRELIOSE
๏ früher: keine antibiotische Therapie, schubweiser Verlauf
mit teilweise wiederholten EM war häufig
๏ heute: Erreger bekannt, EM wird meist behandelt
๏ Immunität:
๏ frühe Lymeborreliose (Stadium I/II): ungenügende Immunität
๏ keine Serokonversion nach EM-Therapie: keine Immunität
๏ späte Borreliose: protektive Immunität ((Sub)Speziesspezifisch)
Huegli et al., Ticks Tick Borne Dis. 2011 Sep;2(3):129–36. // Steere. N Engl J Med. 2012 Nov 15;367(20):1950–1. // Nadelman et al., CID. 2007
Oct 15;45(8):1032–8.
infekttag_2013
new england
journal of medicine
The
established in 1812
november 15, 2012
vol. 367
no. 20
Differentiation of Reinfection from Relapse
in Recurrent Lyme Disease
Robert B. Nadelman, M.D., Klára Hanincová, Ph.D., Priyanka Mukherjee, B.S., Dionysios Liveris, Ph.D.,
John Nowakowski, M.D., Donna McKenna, A.N.P., Dustin Brisson, Ph.D., Denise Cooper, B.S., Susan Bittker, M.S.,
Gul Madison, M.D., Diane Holmgren, R.N., Ira Schwartz, Ph.D., and Gary P. Wormser, M.D.
A bs t r ac t
Background
Erythema migrans is the most common manifestation of Lyme disease. Recurrences
are not uncommon, and although they are usually attributed to reinfection rather
than relapse of the original infection, this remains somewhat controversial. We
used molecular typing of Borrelia burgdorferi isolates obtained from patients with
culture-confirmed episodes of erythema migrans to distinguish between relapse
and reinfection.
Nadelman et al., NEJM. 2012 Nov 15;367(20):1883–90.
Methods
We determined the genotype of the gene encoding outer-surface protein C (ospC) of
From the Division of Infectious Diseases,
Department of Medicine (R.B.N., J.N.,
D.M., D.C., S.B., G.M., D.H., G.P.W.), and
the Department of Microbiology and Immunology (K.H., P.M., D.L., I.S.), New
York Medical College, Valhalla; and the
Department of Biology, University of
Pennsylvania, Philadelphia (D.B.). Address reprint requests to Dr. Nadelman
at the Division of Infectious Diseases,
New York Medical College, Munger Pavilion, Rm. 245, Valhalla, NY 10595, or at
infekttag_2013
new england
journal of medicine
The
established in 1812
november 15, 2012
vol. 367
no. 20
Differentiation of Reinfection from Relapse
in Recurrent Lyme Disease
Robert B. Nadelman, M.D., Klára Hanincová, Ph.D., Priyanka Mukherjee, B.S., Dionysios Liveris, Ph.D.,
John Nowakowski, M.D., Donna McKenna, A.N.P., Dustin Brisson, Ph.D., Denise Cooper, B.S., Susan Bittker, M.S.,
๏ Gul Madison, M.D., Diane Holmgren, R.N., Ira Schwartz, Ph.D., and Gary P. Wormser, M.D.
in keinem von 22 konsekutiven Episoden (17 Patienten)
bs t r ac t kulturell derselbe
von Erythema migransAwurde
Background Borrelien-Stamm nachgewiesen
Erythema migrans is the most common manifestation of Lyme disease. Recurrences
are not uncommon, and although they are usually attributed to reinfection rather
๏
than relapse of the original infection, this remains somewhat controversial. We
used molecular typing of Borrelia burgdorferi isolates obtained from patients with
culture-confirmed episodes of erythema migrans to distinguish between relapse
and reinfection.
es handelte sich um Reinfektionen
Nadelman et al., NEJM. 2012 Nov 15;367(20):1883–90.
Methods
We determined the genotype of the gene encoding outer-surface protein C (ospC) of
From the Division of Infectious Diseases,
Department of Medicine (R.B.N., J.N.,
D.M., D.C., S.B., G.M., D.H., G.P.W.), and
the Department of Microbiology and Immunology (K.H., P.M., D.L., I.S.), New
York Medical College, Valhalla; and the
Department of Biology, University of
Pennsylvania, Philadelphia (D.B.). Address reprint requests to Dr. Nadelman
at the Division of Infectious Diseases,
New York Medical College, Munger Pavilion, Rm. 245, Valhalla, NY 10595, or at
infekttag_2013
RISIKO EINES ZECKENSTICHS...
Huegli et al., Ticks Tick Borne Dis. 2011 Sep;2(3):129–36.
infekttag_2013
RISIKO EINES ZECKENSTICHS...
EM NACH ZECKENSTICH (14/259)
EM
5.2%
kein Sy
94.8%
Huegli et al., Ticks Tick Borne Dis. 2011 Sep;2(3):129–36.
infekttag_2013
RISIKO EINES ZECKENSTICHS...
EM NACH ZECKENSTICH (14/259)
ASYMPTOMATISCHE SEROKONVERSION (9/255)
EM
5.2%
kein Sy
94.8%
Huegli et al., Ticks Tick Borne Dis. 2011 Sep;2(3):129–36.
Serokonversion
3.5%
keine Konversion
96.5%
infekttag_2013
RISIKO EINES ZECKENSTICHS...
EM NACH ZECKENSTICH (14/259)
ASYMPTOMATISCHE SEROKONVERSION (9/255)
BORRELIENINFIZIERTE ZECKEN
EM
5.2%
Serokonversion
3.5%
33%
67%
kein Sy
94.8%
keine Konversion
96.5%
B. burg. ss
1
B. garinii
2
B. valasiana
3
B.afzelii
25
Huegli et al., Ticks Tick Borne Dis. 2011 Sep;2(3):129–36.
infekttag_2013
,CHRONIC LYME DISEASE‘
The
n e w e ng l a n d j o u r na l
of
m e dic i n e
Category 1
Category 2
Category 3
Category 4
Symptoms of unknown
cause, with no evidence
of Borrelia burgdorferi
infection
A well-defined illness
unrelated to B. burgdorferi
infection
Symptoms of unknown
cause, with antibodies
against B. burgdorferi but
no history of objective
clinical findings that are
consistent with Lyme disease
Post–Lyme disease
syndrome
Figure 1. The Four Predominant Categories of Disease Associated with Chronic Lyme Disease.
Only patients with category 4 disease have post–Lyme disease symptoms.
1st
RETAKE
ICM
REG F
CASE
AUTHOR: Agger (Wormser)
2nd
3rd
FIGURE: 1 of 1
Revised
Line Antibiotic
4-C
additional antibiotic treatmentEMail
for patients
who
therapy
SIZE can cause considerable harm
ARTIST: ts
H/T
33p9 for chronic Lyme disease or
Enon
have long-standing subjective symptoms
after ap- H/T
to
patients
treated
Combo
2 Life-threatening
propriate initial treatment for an episode of
Lyme
post–Lyme
disease
symptoms.
AUTHOR, PLEASE NOTE:
33 reset.
Figure has been redrawn anaphylaxis
and type has been
and biliary complications requiring
disease.32-34
Please check carefully.
One of these trials enrolled 78 patients who cholecystectomy35 have occurred after ceftriaxone
were seropositive for antibodies
B. burgdor- administration.
Candidemia from infection of an
35715
JOB: against
ISSUE: 10-04-07
feri at trial entry; a second trial enrolled 51 patients intravenous catheter has resulted in death.36 In an
who were seronegative.32 All patients had anteced- unpublished study in which 37 patients underwent
et al., NEJM. 2007 Oct 4;357(14):1422–30. // Stupica et al., CID 2012 May 21
entFeder
objective
signs of Lyme disease, most often randomization to receive 10 weeks of treatment
infekttag_2013
,CHRONIC LYME DISEASE‘
The
n e w e ng l a n d j o u r na l
of
m e dic i n e
Category 1
Category 2
Category 3
Category 4
Symptoms of unknown
cause, with no evidence
of Borrelia burgdorferi
infection
A well-defined illness
unrelated to B. burgdorferi
infection
Symptoms of unknown
cause, with antibodies
against B. burgdorferi but
no history of objective
clinical findings that are
consistent with Lyme disease
Post–Lyme disease
syndrome
Figure 1. The Four Predominant Categories of Disease Associated with Chronic Lyme Disease.
Only patients with category 4 disease have post–Lyme disease symptoms.
1st
RETAKE
ICM
REG F
AUTHOR: Agger (Wormser)
2nd
3rd
FIGURE: 1 of 1
CASE
Studien
Kategorie
4:
additional antibiotic treatmentEMail
for patients who
Revised
Line Antibiotic
4-C
therapy
SIZE can cause considerable harm
ARTIST: ts
H/T
33p9 for chronic Lyme disease or
Enon
have long-standing subjective symptoms
after ap- H/T
to
patients
treated
Combo
2 Life-threatening
propriate initial treatment for an episode of
Lyme
post–Lyme
disease
symptoms.
AUTHOR, PLEASE NOTE:
33 reset.
Figure has been redrawn anaphylaxis
and type has been
and biliary complications requiring
disease.32-34
Please check carefully.
35
๏ Drei randomisierte Studien: keine Benefit von zusätzlicher
Antibiotikatherapie
One of these trials enrolled 78 patients who cholecystectomy have occurred after ceftriaxone
๏ prospektive
Kontrollgruppe
CID-Studie
von10-04-07
Stupica: nach
Mt of an
were seropositive
for antibodies
B. burgdoradministration.
Candidemia
from6infection
35715
JOB: against
ISSUE:
feri at trial entry;
trial enrolled
51 patients intravenous catheter has resulted in death.36 In an
keina second
signifikanter
Unterschied)
who were seronegative.32 All patients had anteced- unpublished study in which 37 patients underwent
et al., NEJM. 2007 Oct 4;357(14):1422–30. // Stupica et al., CID 2012 May 21
entFeder
objective
signs of Lyme disease, most often randomization to receive 10 weeks of treatment
infekttag_2013
Table 4. Demographic Characteristics and Frequency and Severity of 14 Nonspecific Symptoms in Patients in the 15-Day and
10-Day Treatment Groups and in Controls at 6 Months After
Enrollment
Characteristic
15 Days
(n = 101)
10 Days
(n = 96)
Controls
(n = 81)
Pa
Age
Male sex
52 (39–60) 56 (44.8–62) 51 (34–63) .19
46 (45.5)
39 (40.6)
38 (46.9)
.66
Comorbidities
40 (39.6)
45 (49.5)
36 (44.4)
.58
Nonspecific symptoms at 6 months
Any
72 (71.3)
79 (82.3)
60 (74.1)
.18
57 (56.4)
55 (57.3)
44 (54.3)
.92
Malaise
Arthralgias
40 (39.6)
42 (41.6)
40 (41.7)
47 (49.0)
37 (45.7)
34 (42.0)
.71
.52
Headache
44 (43.6)
44 (45.8)
33 (40.7)
.79
Myalgias
Paresthesias
36 (35.6)
37 (36.6)
39 (40.6)
39 (40.6)
30 (37.0)
25 (30.9)
.76
.40
Dizziness
30 (29.7)
33 (34.4)
13 (16.1)
.02
Nausea
Insomnia
21 (20.8)
36 (35.6)
19 (19.8)
42 (43.8)
16 (19.8)
29 (35.8)
.98
.42
Sleepiness
42 (41.6)
44 (45.8)
38 (46.9)
.74
Forgetfulness
Concentration
difficulties
38 (37.6)
36 (35.6)
43 (44.8)
42 (43.8)
28 (34.6)
29 (35.8)
.35
.42
Irritability
Pain in spine
37 (36.6)
57 (56.4)
44 (45.8)
53 (55.2)
42 (51.9)
45 (55.6)
.11
.98
No. of symptoms
5 (0–9)
6 (1–10.3)
6 (0–9)
.51
11 (4–30.8)
10 (0–30)
.61
Symptom severity score 10 (0–25)
Data are median (interquartile range), or number (%) of patients.
a
Determined by the χ2 test (for categorical variables) or by the Kruskal-Wallis
test (for numerical variables).
Scandinavia [30]. The present study in European patients with
erythema migrans shows that treatment with doxycycline 100
mg twice daily for 10 days is not less effective than the 15-day
Regardless
Stupica et treatment.
al., CID 2012
May of
21treatment assignment, the outcome
was excellent. We found no evidence of objective manifestations of the disease during the 12-month follow-up period.
MIGRANS
Downloaded from http://cid.oxfordjournals.org/ at Universitaet Zuerich on July 10, 2
Fatigue
SYMPTOME 6 MT
NACH THERAPIE
DES ERYTHEMA
[32], but according to some reports it is not related to duration
of therapy [33].
The multivariable logistic regression model for repeated
measurements indicated that reaching a complete response increased with time from enrollment and that it was higher for
males and patients without NOIS at baseline, whereas age,
positive results of skin culture, and duration of treatment were
not significantly associated with complete response (Table 3).
We do not have a reliable explanation for the higher rate of
complete response in males. Other findings, which are in
accordance with previous results, suggest that subjective longterm sequelae of Lyme borreliosis correlate with greater severity of illness (ie, presence of NOIS) at presentation but not
with the duration of the initial antibiotic treatment (when the
choice of antibiotic and duration of treatment accord with
recommendations) [34]. Our previous study [35] found that
patients with positive results of skin cultures had a lower
probability of reaching complete response than patients who
had negative results of culture (OR, 0.39 [95% CI, .17–.88];
P = .02), whereas in the present study this association was not
statistically significant, although the direction of association,
albeit weak, was preserved (Table 3).
The proportions of patients with complete response were
similar in the 2 treatment groups. With the exception of the
14-day time point, when 26.2% of patients had still visible erythema migrans, at all later time points no objective manifestations were found, and those with incomplete response had
relatively benign subjective symptoms without functional compromise. The upper limits of the 1-sided 95% CIs for differences in complete response rates between the 2 treatment
groups at 14 days, 2 months, 6 months, 12 months, and the
last available visit were 16.8, 10.9, 17.9, 9.1, and 4.6 percentage
points, respectively. These results indicate that 15 days of treatment could have been associated with only a small improvement in outcome, at most, 4.6–17.9 percentage points
(Table 2). Such small potential differences in efficacy are consistent with results of other antibiotic trials involving patients
„Patients were asked to refer their
spouse, another family member, or
a friend whose age was +/−5 years
of the patient’s age and who had
no history of Lyme borreliosis to
serve as a control“
infekttag_2013
2. FRÜHSOMMER-MENINGOENZEPHALITIS (FSME)
neue Trends?
infekttag_2013
FRÜHSOMMER-MENINGO-ENZEPHALITIS
๏ zweithäufigste zeckenübertagene Erkrankung in der
Schweiz
๏ ca 100-250 Fälle jedes Jahr
๏ Erreger: Flavivirus
๏ Symptome: asymptomatisch - grippale Symptome -
Meningitis/ Enzephalitis - Tod
Altpeter et al., Swiss Med Wkly. 2013;143:0.
infekttag_2013
2.9
FSME - INZIDENZ IN DER OSTSCHWEIZ
Altpeter et al., Swiss Med Wkly. 2013;143:0.
infekttag_2013
2006
2008 2009 2010 2011 2012
122
115
98
172
2.9
3.0
2.0
3.6
82
TRENDS- INZIDENZ FSME
(Graphik aus Bull BAG 2008; Nr. 7: 124-127)
Altpeter et al., Swiss Med Wkly. 2013;143:0. // www.bag.admin.ch
infekttag_2013
NEUSTE TRENDS FMSE (2008-11)
๏ 79% der Patienten waren hospitalisiert
๏ 1% Mortalität
๏ 50-60% zweigipfliger Verlauf mit initial Grippe-Symptomen
๏ 19% Meningitis - 59% Meningoenzephalitis - 9% keine
Neurologie
๏ Verdachtsdiagnose meist klinisch - 20% Zeckenstich
๏ Diagnose: meist Serologie - 3% Liquor
Altpeter et al., Swiss Med Wkly. 2013;143:0.
Bundesamt für Gesundheit BAG
Bundesamt für Gesundheit BAG i n f e k t t a g _ 2 0 1 3
Direktionsbereich Öffentliche Gesundheit
Direktionsbereich Öffentliche Gesundheit
Zeckenenzephalitis
(FSME) - Schweiz
Zeckenenzephalitis
(FSME) - Schweiz
Bekannte
Endemiegebiete (Naturherde)
Bekannte Endemiegebiete
(Naturherde)
2006
2010
2011
Wil/Jonschwil/Zuzwil/
Niederhelfenschwil,
Mörschwil, St. Magrethen/
Balgach, Jona/Wagen,
BAG: Stand Mai 2010
Mels/Sargans/Vilters
Ganzer nördlicher
Kantonsteil (unteres
Toggenburg bis unteres
Rheintal), Jona/Wagen,
Mels/Sargans/Vilters
FSME-Regionen (Die Liste ist nicht vollständig! Die aufgeführten Orte umschreiben nur grob die auf der Karte
dargestellten Endemiegebiete. Neue Regionen sind unterstrichen.):
SG - FSME VERBREITUNG
Baselland:
BAG: Stand Dezember 2011
Rheinfelden/Möhlin/Wallbach, Oberfrick/Bezirk Laufenburg, Koblenz/Döttingen/Zurzach,
Birr/Brugg/Würenlingen, Baden/Wettingen, Rothrist/Zofingen/Brittnau, Gontenschwil/Schöftland/Muhen/Gränichen
FSME-Regionen (Die Liste ist nicht vollständig! Die aufgeführten Orte umschreiben nur grob die au
dargestellten Endemiegebiete. Neue Regionen sind unterstrichen.):
Liesberg
Bern:
Gampelen/Erlach,
Grosses
Moos, Lyss/Jens/Port, Moutier,
Vallon de Saint-Imier,
Mühle- Koblenz/Döttingen/Zurza
Aargau:
Rheinfelden/Möhlin/Wallbach,
Oberfrick/Bezirk
Laufenburg,
Aargau:
infekttag_2013
MASSNAHMEN: PRÄVENTION...
Zeckenenzephalitis
Impfung gegen Zeckenenzephalitis (FSME):
empfohlen für Risikogruppen.
๏ „Alle erwachsenen Personen sowie Kinder im
Allgemeinen ab 6 Jahren, welche in Endemiegebieten
wohnen oder sich dort zeitweise aufhalten, sollten sich
gegen FSME impfen lassen.“
๏ Impfschutz nach 3 Dosen: 96-99%
๏ Geschlossene Kleidung, geschlossene Schuhe und
Repellentien reduzieren das Risiko
www.bag.admin.ch
infekttag_2013
NEUE KRANKHEIT
NEOEHRLICHIOSE
ein neuer Trend?
Blick am Abend 31.10.12
infekttag_2013
TREND... NEOEHRLICHIOSE
๏ 1999 Ehrlichia-like “Schotti variant”: Nachweis in Zecken
in den Niederlanden, 2004 „Candidatus Neoehrlichia
mikurensis“
๏ 2009/ 2010 6 Infektionen bei Menschen in Europa
๏ 2012 6.4% der Zecken infiziert (Westschweiz), 3.5-8%
(ZH)
๏ 2012 2 Infektionen in Zürich und Nachweis in Zecken in
der Umgebung
Maurer et al., JCM. 2012 Oct 31. // Fehr et al. 2010. Emerg. Infect. Dis. 16:1127–1129. // Lommano et al., Appl Environ Microbiol. 2012 Jul;78(13):4606–
12.
infekttag_2013
NEOEHRLICHIOSE: ZH FÄLLE
๏ Fall 1: 68-jähriger Mann, CLL, kommt mit FUO, Risiko:
regelmässige Spaziergänge im Wald mit dem Hund
๏ Fall 2: 58-jähriger Mann, Lymphom, R-CHOP, kommt
mit FUO, Risiko: regelmässige Spaziergämge im Wald
๏ Diagnose: PCR im Blut und Knochenmark
๏ Verlauf: rasche Entfieberung unter Doxycyclin
Maurer et al., JCM. 2012 Oct 31.
infekttag_2013
4. NEUER TREND: TULARÄMIE
zum Schluss...
infekttag_2013
WAS IST TULARÄMIE
๏ Infektion mit Francisella tularensis (Reservoir unbekannt)
๏ Übertragung: Direkter Kontakt mit infizierten Tieren
(Hasenpest), Zecken, Aerosole
๏ Inkubationszeit 3-5 Tage (range 1-14d)
๏ Initialsymptome: Fieber, Schüttelfrost, Kopfschmerzen, Myalgien,
im Verlauf Adynamie, Malaise
๏ Lymphknotenschwellung +++
๏ Eintrittsstelle (Eschar!) wird oft übersehen oder ist schon
abgeheilt (glanduläre Formen)
eight
whole
cisella
s, and
s, but
cisella
ed by
ed by
stems
rgdorsensidition,
pies of
Brugg (710)
596
Kloten/Bülach (3717) 3201
Neuenburg (89)
80
Thun/Spiez (1099)
1009
Ticino (456)
450
Total
5336
60
320
3
10
3
396
54
196
6
80
3
339
infekttag_2013
ÜBERRASCHUNG IM JAHRE 2000!
Table 2 Total rates of tick infections
Pathogen
Francisella tularensis
Ehrlichia phagocytophila a
Borrelia burgdorferi sensu lato
TBEV
Prevalence
Percent
Positive pools/
total pools
0.12
1.18
26.54
0.32
7/607
68/607
563/590
19/607
The
was as a
TaqMan PCR specific for members of theEhrlichia phagocytoadult
phila genogroup
seven TBEV, tick-borne encephalitis virus
qManWicki et al., Eur J Clin Microbiol Infect Dis. 2000 Jun 1;19(6):427–32
-eight
infekttag_2013
TULARÄMIE IN DER SCHWEIZ: 2004-2012
number of patients
40
30
20
10
0
04 005 006 007 008 009 010 011 012 013
0
2
2
2
2
2
2
2
2
2
2
year
©Urs Karrer, Kantonsspital Winterthur
infekttag_2013
FÄLLE 2004 BIS 2012
©Urs Karrer, Kantonsspital Winterthur
infekttag_2013
total (n=98)
2012 (n=37)
55 %
61 %
ulzeroglandulär
32
33
glandulär
19
25
okuloglandulär
3
3
oropharyngeal
1
0
32 %
38 %
typhoidal
4
5
pneumonisch
25
30
abdominal
3
3
keine Information
12
3
Lokal
Systemisch
©Urs Karrer, Kantonsspital Winterthur
infekttag_2013
total (n=98)
2012 (n=37)
55 %
61 %
ulzeroglandulär
32
33
glandulär
19
25
okuloglandulär
3
3
oropharyngeal
1
0
32 %
38 %
typhoidal
4
5
pneumonisch
25
30
abdominal
3
3
keine Information
12
3
Lokal
Systemisch
©Urs Karrer, Kantonsspital Winterthur
infekttag_2013
!
Text
Text
Text
Text
Text
Text
©Peter Graber, Kantonsspital Liestal
infekttag_2013
Tag 0
Tag 4-7
Tag 13
Ein Jogger wurde bei
einer MäusebussardAttcke am Kopf verletzt
Plötzlich Fieber,
Schüttelfrost,
Kopfschmerzen und
zervikale
Lymphknotenschwellung,
keine Besserung auf
Augmentin und NSAR
Hospitalisation, Therapie
mit Augmentin IV und
Tobramycin mit rascher
Besserung, Diagnose:
ulzeroglanduläre
Tularämie mittels FNP
und Kultur
©Urs Karrer, Kantonsspital Winterthur
infekttag_2013
IST AUCH IN ST. GALLEN
ANGEKOMMEN...
infekttag_2013
Eintritt
Verlauf
Blutkultur
Trockener Husten,
ausgeprägte Müdigkeit
und Schwäche mit
Synkope
Keine Besserung unter
Therapie mit Augmentin
und Klacid
Wachstum von Francisella
tularensis susp holarctica.
Diagnose: Pulmonale
Tularämie
Risikofaktor: Rasenmähen!
Feldman et al., NEJM. 2001 Nov 29;345(22):1601–6. // Poster SGINF 2012
infekttag_2013
TULARÄMIE: 2 FORMEN
Typ A Infektion (USA):
๏ Fulminant, geht bis septischer Schock
๏ Früher Mortalität 5-10%, seit AB 1-2%
๏ Pulmonale Form: 30-60%, nun 3-13%
Typ B Infektion (Europa):
๏ „Type B tularaemia is virtually nonlethal in humans, even when
appropriate treatment is not inserted“
Tärnvik and Berglund. Eur Respir J. 2003
infekttag_2013
DIAGNOSTIK
๏ Kultur (bei Verdacht: nur in Speziallaboratorien
durchführen (Bio Safty))!
๏ PCR aus Ulcusmaterial der Eintrittspforte oder aus
Biopsiematerial des Lymphknotens
๏ Serologie (Ende 2. Krankheitswoche positiv)
Tärnvik and Berglund. Eur Respir J. 2003
infekttag_2013
THERAPIE
๏ Streptomycin 97% Heilung, kein Relaps
๏ Ds. 10mg /kg i.m. alle 12 h für 10 Tage
๏ Gentamicin 86% Heilung, 6% Relaps
๏ Ds. 3-5 mg/kg in drei Dosen / d i.m. oder iv.
๏ Tetrazyklin / Doxycyclin 88% Heilung, 12% Relaps
๏ Ds. Vibramycin 2 x 100 mg /d für 14 Tage
Tärnvik and Berglund. Eur Respir J. 2003
infekttag_2013
- OUTDOOR AKTIVITÄT
- LOKALE LYMPHADENOPATHIE
- SYSTEMISCHE ENTZÜNDUNG
- KEIN ANSPRECHEN AUF BETALAKTAME
AN TULARÄMIE DENKEN!!
Fazit
infekttag_2013
FRAGEN UND DISKUSSION