Vortrag C. Strahm, 8.8.12

Transcription

LEPTOSPIROSE
Carol Strahm
Infektiologie
8.8.2012
Leptospira interrogans
Historisches
„Herbstfieber“ bei Reisernte im alten China und Japan
1886 A.Weil: Erstbeschreibung der Erkrankung
(1907 Stimson: Spirochaeta interrogans in Nieren eines
Mannes der an einem ,Gelbfieber‘ verstarb)
1915/16 Mehrere Teams (2 dt. und 1 jp.) beschreiben
gleichzeitig Krankheitsbild mit Erreger
1917 Zoonose/ Berufskrankheit: Ratte
wurde als Quelle entdeckt
Levett, Clin Microbiol Rev, 2001 vol. 14 (2) pp. 296-326
Verbreitung/ Inzidenz
Weltweite Zoonose; endemisch in (Sub)tropen
350000 - 500000 Fälle / Jahr
Inzidenz (schwerere Verläufe, leichte unbekannt)
0.1 – 1 /100,000 pro Jahr in gemässigten Zonen (CH:
0.05)
10 – 100 /100,000 pro Jahr in (Sub)tropen
>100 pro 100,000 während outbreaks
keine genaue Zahlen (oligosymptomatisch, kein effektives
Bharti, Lancet Infect Dis 2003; 3: 757–71
Überwachungssystem)
Hartskeerl, CMI 2011; 17(4):494–501
Leptospirose-Erkrankungen in der Schweiz, Meldungen der Laboratorien und Ärzte 1988–1999. OFSP
Epidemiologie/ Pathophysiologie
meist verbreitete Zoonose weltweit
Quelle: meist asymptomatische Träger bei Nagern (Mäuse,
Ratten, Fledermäuse, Mungos, Beutelratten, Eichhörnchen)
Auch Nutztiere/ Haustiere: Rinder, Schafe, Ziegen,
Schweine, Hunde
Leptospiren können lebenslang im proximalen Tubulus von
infizierten Tieren persistieren und werden mit dem Urin
ausgeschieden
Ansteckung über Urin, kontaminiertes Wasser und Böden
Adler, Vet Microbiol, 2010 vol. 140 (3-4) pp. 287-96
mic Development by
Leptospirosis
he world.
th water, food or
r diseases.
ng renal
ase.
atterns
Investing in reliable global huma
Epidemiologie
burden estimates
To coordinate and direct global res
leptospirosis the World Health O
Leptospirosis Burden Epidemio
maintenance host
a group of leading experts with a br
ing with multiple international acto
accidental host
The LERG is assigned with the foll
years:
 reviewing and appraising epid
commissioned reviews and stu
 developing epidemiological to
 estimating and expressing dis
measures of population healt
WHO
life years (DALY))
 identifying technical gaps for re
Leptospiren-DNA (PCR) in Nieren von
Mäusen (CH) in einer Schweizer Innenstadt
Arvicola terrestris (Wühlmaus)
Leptospira PCR+ 13.3%
(8/60)
Apodemus sylvaticus (Waldmaus)
(7/60)
Clethrionomys glareolus (Rötelmaus)
(5/50)
Crocidura spp, Sorex spp (Spitzmäuse)
(4/20)
Adler H et al. Epidemiol Infect 2002;128:107-109
Epidemiologie
Gemässigte Zonen / Industrialisierte Welt
Berufskrankheit
Kanalarbeiter, Bauern, Fischer, Metzger, Tierärzte, Militär, Mineure...
Protektive Massnahmen hat zu einer Verminderung der Inzidenz geführt
Homeless schlechte Hygiene
,Outdooraktivitäten‘ mit Wasserkontakt
Entwicklungsländer / (Sub)tropen
Beruflich (zB Reisfelder)
Tägliches Leben vor allem während der Regenzeit, Slums
Überschwemmungen / Outbreaks
Adler, Vet Microbiol, 2010 vol. 140 (3-4) pp. 287-96
1. Berufskrankheit
obiology (2004), 53, 1259–1262
Percutaneous exposure resulting in laboratoryacquired leptospirosis – a case report M A J O R A R T I C L E
rt
004
DOI 10.1099/jmm.0.45735-0
A. P. Sugunan, K. Natarajaseenivasan, P. Vijayachari and S. C. Sehgal
WHO Collaborative Centre for Diagnosis, Research, Reference and Training in Leptospirosis,
Regional Medical Research Centre, Indian Council of Medical Research, Post Bag No. 13,
Port Blair 744 101, Andaman & Nicobar Islands, India
Resurgence of Field Fever in a Temperate Country:
An Epidemic of Leptospirosis among Seasonal
Strawberry Harvesters in Germany in 2007
A screw-capped glass tube containing a Leptospira culture accidentally broke and the laboratory
1,5
2
1
6
worker
who
wasvan
handling
the tube
sustained
a cut on
his hand.
TheSarbu,
wound
was flooded with the
Sarika
Desai,
Ulrich
Treeck,4 Michael
Lierz,
Werner Espelage,
Lavinia
Zota,6 Anca
7
8
3
3
Michal
Czerwinski,
Malgorzata
Maria347
Avdicová,
Jochen to
Reetz,
Enno Luge,
Beatrizrecovered
Guerra,3
culture.
The3 culture
wasSadkowska-Todys,
that 1of strain 7MG
belonging
serovar
Australis
from a
Zoonoses and Public Health
Karsten Nöckler, and Andreas Jansen
patient, and it had undergone 52 passages in Ellinghausen McCullough Johnson Harris medium.
Robert Koch Institute, Department for Infectious Disease Epidemiology, Free University, Veterinary Faculty, and Federal Institute for Risk
O
R I G Ilaboratory
N A LBerlin,
A R T Iand
C L Eworker
Assessment,
State Institute
of Health and Labor
of North Rhine-Westphalia,
Germany;
European and
Programme
for
The
developed
a headache
21 daysMünster,
after the
accident
became
febrile the next
Intervention Epidemiology Training, European Centre for Disease Prevention and Control, Stockholm, Sweden; National Centre for Prevention and
Leptospirosis
in a SmallforAnimal
Veterinarian:
Reminder
to and Regional Institute
day.ofHe
was hospitalized
5 days
andInstitute
was oftreated
initially
and
later with
Control
Communicable
Diseases, Bucharest,
Romania;
National
Public Health,
Warsaw,with
Poland;doxycycline
of Public
Follow
Infection Control Procedures
Health,
BanskáStandardized
Bystrica, Slovakia
ciprofloxacin.
A blood sample collected on the second day of illness, after starting doxycycline
R. Baer , W. Turnberg , D. Yu and R. Wohrle
therapy,
yielded
leptospires
andisthe
isolate,
HZ
651,ofwas
identified
as outbreaks
serovar Australis.
Background.
Although
leptospirosis
aof Health,
reemerging
zoonosis
global
importance,
related to ag-Monoclonal
Communicable
Disease Epidemiology,
Washington
State Department
Shoreline, WA,
USA
Baer, Zoonoses Public Health. 2010 1;57(4):281–4
Thurston
County
Public
Health
and
Social
Services
Department,
Olympia,
WA,
USA
ricultural
exposures
areand
primarily
situatedamplified
in tropicalpolymorphic
countries. In July
2007,fingerprinting
a suspected leptospirosis
antibody
patterns
randomly
DNA
patternsoutbreak
of the isolate and Desai, CID 2009 15;48(6):691–7
Zoonotic and Vector-borne
Disease Program,
Washington State Department
of Health, Olympia, WA, USA
was recognized among strawberry harvesters from Eastern Europe who were working in Germany. An investigation
Sugunan, J Med Microbiol. 2004 1;53:1259–62
strain
MGto347
were
thusand
indicating
that for
HZinfection.
651 and MG 347 were clonal.
was
initiated
identify
the identical,
outbreak source
the risk factors
Impacts
1
2
4
3
5
6
7
1
1
2
8
3
1
2
3
Methods.
We conducted a retrospective cohort study with use of a questionnaire administered to harvesters
A small animal veterinarian developed leptospirosis after exposure to pet
by health
rat urine.authorities in Romania, Slovakia, and Poland. Collected serum samples were tested by microscopic
• Leptospirosis test
is an occupational
risk for both largeM
andenzyme-linked
small animal
agglutination
and immunoglobulin
immunosorbent assay. A case patient was defined as a
•
veterinarians.
Brockmann et al. BMC Infectious Diseases 2010, 10:91
http://www.biomedcentral.com/1471-2334/10/91
2. ,Outdooarktivitäten‘
RESEARCH ARTICLE
Open Acce
Outbreak of leptospirosis among triathlon
participants in Germany, 2006
Stefan Brockmann1, Isolde Piechotowski1, Oswinde Bock-Hensley2, Christian Winter1,3, Rainer Oehme1,
Stefan Zimmermann4, Katrin Hartelt1, Enno Luge5, Karsten Nöckler5, Thomas Schneider6, Klaus Stark7,
Leitthema
Andreas
Jansen7*
J. P. Sperhake · F. Schulz
Institut
für Rechtsmedizin, Universitätsklinikum, Hamburg-Eppendorf
Abstract
Background: In August 2006, a case of leptospirosis occurred in an athlete after a triathlon held around
Heidelberg and in the Neckar river. In order to study a possible outbreak and to determine risk factors for infecti
an epidemiological investigation was performed.
Tod eines Wassersportlers
durch Leptospirose
Methods: Participants of the triathlon were contacted by e-mail and were asked to fill out a standardized
questionnaire. In addition, they were asked to supply a serum sample for laboratory diagnosis of leptospirosis. A
Rechtsmedizin
2006 16:156–160
confirmed case patient was defined as a clinical case (i.e. fever and at least Sperhake,
one additional
symptom
suggestive
Brockmann BMC Infect Dis. 2010 1;10:91
leptospirosis) with at least two of the following tests positive: ELISA IgM, latex agglutination testing, or microscop
agglutination testing. Rainfall and temperature records were obtained.
Nochmals Olympische Spiele...
Oktober 2010 The Telegraph
Forbes QJM 2012 Jul 27
3. Environmental drivers of leptospirosis
Although leptospirosis is common and widespread,
there remain significant gaps in our understanding of its
transmission dynamics and of the trigger factors for disease outbreaks. However, epidemiological studies have
identified various environmental risk factors for infection or outbreaks that differ between ecological settings.
A number of these factors are likely to be influenced by
climate change and urbanisation and will be discussed
below.
environmental forces, including sociodemographic factors, climate and
land use.
3.1. Rainfall and flooding
Heavy rainfall and flooding increase the risk of leptospirosis by bringing bacteria and their animal hosts into
closer contact with humans. Numerous outbreaks of leptospirosis have been reported following extreme weather
events around the world, in geographically diverse areas
including India,10,11 Laos,12 Indonesia,13 Italy,14 Brazil,15
3. Endemiegebiete
Table 1
Examples of leptospirosis outbreaks associated with heavy rainfall and flooding
Country/region
Year
Flooding event
Mumbai, India10
2005
Kerala, India11
Orissa, India22
2002
1999
Laos12
Indonesia13
Italy14
Guyana16
Nicaragua17
2006
2002
2002
2008
1995
Puerto Rico18
1996
New Caledonia20
2008
944 mm of rain in 24 h resulted in an eight-fold rise in the number of cases compared with the
previous 4 years
Peaks in leptospirosis incidence seen
7–10
days
after peaks
of heavy rainfall
Rodents
and
Leptospirosis
in Hyper-Endemic
Areas
19.2% of study subjects in flooded villages after a cyclone were found to have serological evidence of
symptomatic leptospiral infection
Flooding in home property associated with seropositivity for leptospirosis (odds ratio 2.12)
Outbreak followed massive flooding in Jakarta in January 2002
Devastating flooding in suburban area resulted in 6.8% seroconversion rate for leptospirosis
Epidemic followed severe flooding, with 30% of Guyana’s inhabitants displaced from their homes
Epidemic of leptospirosis followed severe rainfall and flooding in 2005. Over 5000 mm of rain
compared with annual average of 1300 mm
Leptospirosis
Leptospirosis diagnosed in 6% of non-dengue febrile illnesses pre-hurricane versus 24% of non-dengue
febrile illnesses post-hurricane
High rainfall and flooding associated with La Niña in early 2008. Epidemic of leptospirosis in 135
people. Incidence of 500/100 000 population in Bourail region
Review
Perez PLoS Negl Trop Dis. 2011;5(10):e1361
Lau, Trans R Soc Trop Med Hyg. 2010;104(10):631–8
Figure 1. Hot spots of leptospirosis and identification of the study site and meteorological data collection point. (Map produced using
PopGis, as described in the Methods section and demographic data from the Institut de la Statistique et des Études Économiques, http://www.isee.
nc/.).
Leptospirosis and Weil’s disease in the UK
Klinik
prominent features at outset are, headache, fever
and myalgia.38–41
A study of leptospirosis in eight developing countries commonly visited by British tourists, found
result in cardiovascular collapse and pulmonary
haemorrhagic pneumonitis where the mortality rate
can reach 50%.3,44,45
In the UK, the mortality for Weil’s disease was in
9
Downloaded from http://qjmed.oxfordjournals.org/ at Universitaet Z
Forbes QJM 2012 Jul 27
Figure 6. Clinical features of leptospirosis and Weil’s disease. The number of cases in the UK with asymptomatic infection is
unknown, as is the number who suffer only brief, uncomplicated febrile illness. Other symptoms are shown in order of
incidence (not to scale) depicting the small proportion of infections that result in severe (Weil’s) disease and death in the UK.
(1) Mild disease ‘Phase 1’: this may be self-limiting or may progress to severe disease after a period of resolution of symptoms
and (2) severe disease ‘Phase 2’.
353 patients. Persons without formal employment (e.g., unemployed, retired, student, homemaker) accounted for 102
(31%) of 328 cases. Farmers or ranchers (including sugarcane
workers) accounted for 92 cases (28%). Blue-collar workers
(e.g., construction workers, day laborers, carpenters) accounted
for 51 cases (16%). Twelve cases (4%) were in active-duty military personnel.
Information allowing for an exposure “classification” was
possible for 335 (95%) of 353 cases. Occupationally related
exposures were reported for 137 (41%) of 335 cases (e.g., farming, ranching, aquaculture, abattoir, veterinarian); 143 (43%)
of 335 cases were exposed through recreational activities, including freshwater swimming, hiking, camping, and hunting.
Among confirmed cases, 81 (23%) of 353 were diagnosed
by culture isolates from the following clinical specimens: blood
samples, for 66 cases; urine samples, for 6 cases; CSF specimens,
for 2 cases; blood and urine samples, for 1 case; blood and
CSF samples, for 1 case; and an unspecified source, for 5 cases.
The 81 culture-confirmed cases included 48 with diagnostic
MAT results and 33 diagnosed using culture alone. The diagnoses were made using serologic testing without culture confirmation for 270 cases, and 2 cases demonstrated antibodies
to Leptospira species in postmortem tissue specimens by means
of a direct fluorescent antibody test.
Among confirmed cases, the most frequently reported symptoms were fever, myalgia, and headache. Pertinent laboratory
results included evidence of renal abnormalities, hepatic abnormalities, or both in 49%–73% of patients (table 1). Moresevere
disease
manifestations
associated
Katz,
Clin Infect
Dis, 2001 vol. 33were
(11) pp.
1834-41 with infection by
the Icterohemorrhagiae serogroup (table 2). Among 353 confirmed cases during this 25-year interval, 5 patients died (case-
Klinik
Hawaii 1974-1998, 350 Fälle
90% selbstlimitierende milde
febrile Krankheit!
Table 1. Clinical findings for 353 confirmed cases of leptospirosis, Hawaii, 1974–1998.
No. of
patients
with data
available
No. (%)
of patients
affected
Fever
346
343 (99)
Myalgia
333
304 (91)
Headache
329
292 (89)
Chills
321
280 (87)
Anorexia
303
248 (82)
Nausea
306
235 (77)
Vomiting
300
220 (73)
Arthralgia
285
168 (59)
Diarrhea
290
154 (53)
Abdominal pain
283
144 (51)
Backache
275
139 (51)
Jaundice
286
111 (39)
Conjunctival suffusion
265
74 (28)
Nuchal rigidity
268
73 (27)
Oliguria or anuria
270
71 (26)
Hepatomegaly
234
38 (16)
Pneumonia
175
29 (17)
Rash
253
21 (8)
Splenomegaly
218
9 (4)
Elevated blood urea nitrogen (120 mg/dL)
241
118 (49)
Elevated creatinine (11.5 mg/dL)
142
77 (54)
Hematuria
239
171 (72)
Proteinuria
229
124 (54)
Sign, symptom, and result (definition)
Selected sign or symptom
Laboratory results
Renal
CSF samples, for 1 case; and an unspecified source, for 5 cases.
The 81 culture-confirmed cases included 48 with diagnostic
MAT results and 33 diagnosed using culture alone. The diagnoses were made using serologic testing without culture confirmation for 270 cases, and 2 cases demonstrated antibodies
to Leptospira species in postmortem tissue specimens by means
of a direct fluorescent antibody test.
Among confirmed cases, the most frequently reported symptoms were fever, myalgia, and headache. Pertinent laboratory
results included evidence of renal abnormalities, hepatic abnormalities, or both in 49%–73% of patients (table 1). Moresevere disease manifestations were associated with infection by
the Icterohemorrhagiae serogroup (table 2). Among 353 confirmed cases during this 25-year interval, 5 patients died (casefatality rate, 1.4%). Increasing age was associated with an increase in leptospirosis related mortality (x2 for linear trend, 5.5;
P p .02).
Initial clinical impressions were recorded for 312 (88%) of
353 patients. The most common initial diagnoses were leptospirosis (193 cases [62%]), influenza (20 cases [6%]), viral
syndrome (19 cases [6%]), hepatitis (19 cases [6%]), fever of
unknown etiology (12 cases [4%]), gastroenteritis (10 cases
[3%]), and meningitis (9 cases [3%]).
An incubation period was estimated for 150 patients for
whom exposure and onset dates were recorded. The incubation
period ranged in duration from 1 to 21 days (median, 8 days).
Information on the duration of illness was obtained from 245
patients and ranged from 2 to 84 days (median, 14 days). A
total of 239 (68%) of 349 patients were hospitalized.
Information regarding antibiotic therapy was obtained from
Clin Infect
Dis, 2001
33 (11) pp.
1834-41
327 Katz,
of 353
patients.
Twovol.
hundred
ninety-four
(90%) of the
327 patients received antibiotics. Untreated patients had a minimum 7-day duration of illness, whereas ∼25% of those treated
Labor
- sehr hohes Bilirubin bei nur
leicht erhöhter ALAT, erhöhtes
Kreatinin (DD virale Hepatitis)
- Thrombopenie
- Hypokaliämie
Backache
275
139 (51)
Jaundice
286
111 (39)
Conjunctival suffusion
265
74 (28)
Nuchal rigidity
268
73 (27)
Oliguria or anuria
270
71 (26)
Hepatomegaly
234
38 (16)
Pneumonia
175
29 (17)
Rash
253
21 (8)
Splenomegaly
218
9 (4)
Elevated blood urea nitrogen (120 mg/dL)
241
118 (49)
Elevated creatinine (11.5 mg/dL)
142
77 (54)
Hematuria
239
171 (72)
Proteinuria
229
124 (54)
Elevated alanine aminotransferase level
(serum glutamic-pyruvic transaminase;
140 U/L)
172
126 (73)
Elevated total bilirubin level (11.0 mg/dL)
178
128 (70)
Elevated WBC count (110,000 cells/mm3)
238
92 (39)
Decreased WBC count (!4300 cells/mm3)
230
17 (7)
Thrombocytopenia (!140,000 cells/mm3)
239
139 (58)
Decreased hematocrit (!34%)
236
76 (32)
Laboratory results
Renal
Hepatic
Hematologic
with antibiotics recovered within 7 days. However, the observed
difference in illness duration for people treated with or without
antibiotics was not statistically significant (Wilcoxon-MannWhitney test, P p .4).
For 210 (71%) of 294 patients who received antibiotics, we
had information on date of symptom onset and date of initiation of antibiotic therapy. Of 210 patients who received antibiotics, 205 (98%) had initiated therapy within 9 days of onset
Klinik
Aseptische
Meningitis
Uveitis
105
Ikterische
Leptospirose
5-10%
Temperature (° F)
104
103
102
101
100
99
98
97
0
10
20
30
Day of illness
40
M. Weil
Akutes
Nierenversagen
16-40%
Hämorrhagien
Myocarditis
10%?
Pulmonale
Hämorrhagie
fast immer, oft
subklinisch
50
specially
an body
cratches
mbranes
irosis is
reational
ies such
ded rice
ies with
of cases
so been
that the
/100,000
00 cases/
[14, 15].
osure to
pulation
n in the
predomiferences
y do not
me popce, men
nfection
problem
nvolving
Biphasischer Verlauf
Lung (2011) 189:1–9
Table 1 Clinical features of leptospirosis
Unspecific febrile Anicteric. Headache, chills, abdominal pain, and
disease
conjunctival suffusion. Myalgias are
remarkable.
Normal CSF. May be self-limited or progress to
the forms described below. Easily confounded
with dengue fever, yellow fever, malaria, and
other acute febrile diseases.
Meningitis
1
‘‘leptospiremic’’ phase
lasts 4–9 days
May follow the anterior form or appear
unaccompanied. CSF pleocytosis. Benign, selflimited,
and ‘‘aseptic’’ meningitis usually mistaken as
viral.
Weil syndrome
Deep jaundice despite mild hepatic involvement.
Severe renal dysfunction and usually
minor hemorrhagic manifestations. Dialysis is
the standard supportive therapy.
High mortality rate ([10%).
Severe pulmonary Hemorrhagic pneumonitis. May occur in the
form
absence of jaundice or as an element of Weil
syndrome.
Adult respiratory distress syndrome and sudden
massive pulmonary hemorrhages result in high
mortality
([50%) even when optimal treatment is
provided. Must be distinguished from atypical
pneumonias
and hantavirus pulmonary syndrome.
2
‘‘immune’’ phase
3
CSF cerebral spinal fluid
high ([10% and [50%, respectively), even when optimal
treatment is provided [10].
4 Ausheilung
Marchiori, Lung. 2011Feb.;189(1):1–9.
Mortalität und Spätfolgen
Leichte Formen haben eine gute Prognose
Mortalität in hospitalisierten Fällen: 4-52%
M. Weil (Trias: Ikterus, ANV, Blutungen) >10%
SPHS (severe pulmonary hemorrhagic syndrome) >50%
Spätfolgen (10-Jahresdaten aus aus Holland)
27% hatten Langzeitbeschwerden (Müdigkeit, Myalgien,
Arthralgien, Kopfschmerzen, Tinnitus, ...)
11% schwere Beschwerden (>1 Jahr, Arztbesuche)
1.3% konnten nicht mehr arbeiten
Hartskeerl, CMI 2011; 17(4):494–501
Diagnose
Serologie
ELISA (Se >90% / Sp 88-95%), MAT (Goldstandard) (90% / >90%)
MAT microscopic agglutination test
Kultur (5-50% / 100%)
schwierig, Spezialkulturmedien erforderlich, 6-8 Wochen
(optimal bis 4 Monate) Bebrütung nötig
PCR (100% / 93%)
Hartskeerl, CMI 2011; 17(4):494–501
Prävention / Therapie
Berufskleidung: Handschuhe, Brillen und gutes Schuhwerk
Tiere: Impfung für Vieh, Hunde und Schweine
Mensch: Impfung nur in China, Kuba, Frankreich und Russland
Therapie: Penicillin, Doxycyclin
5-7 Tage, cave Jarisch-Herxheimer-Reaktion
Hartskeerl, CMI 2011; 17(4):494–501
Antibiotics for leptospirosis (Review)
Brett-Major
DM, Coldren
R
random-effects OR is 1.16 (95% CI 0.23 to 5.95). The heterogeneity among these four trials for the mortality
outcome
was moderate
(I
2 = 50%). Only one trial (253 patients) reported days of hospitalisation. It compared parenteral penicillin to placebo without significant
effect of therapy (8.9 versus 8.8 days; mean difference (MD) 0.10 days, 95% CI -0.83 to 1.03). The difference in days of clinical
illness was reported in two of these trials (71 patients). While parenteral penicillin therapy conferred 4.7 to 5.6 days of clinical illness in
contrast to 7.7 to 11.6 days in the placebo arm, the size of the estimate of effect increased but statistical significance was lost under the
random-effect model (fixed-effect: MD -2.13 days, 95% CI -2.46 to -1.80; random-effects: MD -4.04, 95% CI -8.66 to 0.58). I2 for
this outcome was high (81%). When duration of fever alone was assessed between antibiotics and placebo in a single trial (79 patients),
no significant difference existed (6.9 versus 6.6 days; MD 0.30, 95% CI -1.26 to 1.86). Two trials with 332 patients in relatively
severe and possibly late leptospirosis, resulted in trends towards increased dialysis when penicillin was used rather than placebo, but
the estimate of effect was small and did not reach statistical significance (42/163 (25.8%) versus 31/169 (18.4%); OR 1.54, 95% CI
0.91 to 2.60). When one antibiotic was assessed against another antibiotic, there were no statistically significant results. For mortality
in particular, these comparisons included cephalosporin versus penicillin (2 trials, 6/176 (3.4%) versus 9/175 (5.2%); fixed-effect: OR
0.65, 95% CI 0.23 to 1.87, I2 = 16%), doxycycline versus penicillin (1 trial, 2/81 (2.5%) versus 4/89 (4.5); OR 0.54, 95% CI 0.10
to 3.02), cephalosporin versus doxycycline (1 trial, 1/88 (1.1%) versus 2/81 (2.5%); OR 0.45, 95% CI 0.04 to 5.10). There were no
adverse events of therapy which reached statistical significance.
Antibiotische Therapie
Cochrane 2012
Authors’ conclusions
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2012, Issue 2
http://www.thecochranelibrary.com
Insufficient evidence is available to advocate for or against the use of antibiotics in the therapy for leptospirosis. Among survivors who
were hospitalised for leptospirosis, use of antibiotics for leptospirosis may have decreased the duration of clinical illness by two to four
days, though this result was not statistically significant. When electing to treat with an antibiotic, selection of penicillin, doxycycline, or
cephalosporin does not seem to impact mortality nor duration of fever. The benefit of antibiotic therapy in the treatment of leptospirosis
remains unclear, particularly for severe disease. Further clinical research is needed to include broader panels of therapy tested against
placebo.
Antibiotics for leptospirosis (Review)
Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
PLAIN LANGUAGE SUMMARY
Antibiotics for the treatment of leptospirosis
Leptospirosis is a common disease both in the developed and developing world. It is caused by a bacteria spread by the urine of animals.
Zukunft der Leptospiren...
globale Erwärmung
vermehrt Regen / Überschwemmungen
Migration / Krisengebiete
Wachstum der Weltbevölkerung und zunehmende
Urbanisierung / Slums
tropische Länder als beliebte Reisedestinationen
Hochrisikoaktivitäten: Rafting, Höhlenbesuche,
Urwaldbesuche
Hartskeerl, CMI 2011; 17(4):494–501
reported to the NRC between July 1999 and February 2000, of
whom 22 were excluded from further analysis because they
were either not hospitalized (14 patients), had died (5), resided
outside of France (2), or could not be traced (1). Of the remaining 102 case patients, correctly matched control subjects
were recruited for 90 (88%). Of the 189 control subjects who
were recruited, 20 were excluded because of incorrect matching
of age (11 control subjects), history of hospitalization (5), or
having been hospitalized 11 month before or after the case
patient (4). The matched case-control analysis was performed
tospirosis by univariable analysis were included in the multivariable conditional logistic regression analysis (table 1). Only
4 such variables were independently associated with a case of
leptospirosis (table 1): skin lesions (aOR, 7.01; 95% CI, 2.70–
17.56), canoeing (aOR, 15.53; 95% CI, 1.64–147.00), contact
with wild rodents (aOR, 4.75; 95% CI, 1.39–16.21), and a home
in the countryside (aOR, 2.87; 95% CI, 1.09–7.57). No interaction between having a skin lesion and either canoeing or
contact with wild rodents was reported. The etiologic fraction
in the population demonstrated that nearly two-thirds (65.5%)
Zurück zum Patient
Table 1. Univariable analysis and conditional logistic regression of risk factors associated with leptospirosis in France, 1999–2000.
Multivariate analysis
Univariate analysis
Risk factor
Skin lesions
High-risk occupation
Professional risks
Location of residence
Countryside
Near a canal
Near a river
Leisure activity
Camping
Walking in the countryside
Paddling
Swimming
Fishing
Canoeing
Travel outside France
Animal contact
Rodents
Any
At home
At work
Farm animals
NOTE.
No. of
samples
Mantel-Haenszel OR
(95% CI)
220
257
257
257
259
259
P
Adjusted OR (95% CI)
P
7.7 (3.8–22.6)
3.1 (1.4–7.7)
3.0 (1.5–14.7)
!.001
7.0 (2.7–17.6)
…
…
!.001
4.8 (2.4–8.8)
1.8 (1.0–3.1)
3.0 (1.6–5.6)
!.001
.002
!.001
…
.031
!.001
2.9 (1.1–7.6)
…
…
.033
…
…
259
259
259
259
259
259
259
5.3
2.3
3.1
2.8
5.1
21.5
3.0
(1.2–29.8)
(1.2–4.5)
(1.6–7.9)
(1.0–7.8)
(2.4–12.6)
(3.1–907.5)
(1.0–10.0)
.010
.004
!.001
.021
!.001
!.001
.026
…
…
…
…
…
15.5 (1.6–147.0)
…
…
…
…
…
…
.017
…
259
249
239
259
3.0
3.1
3.5
2.4
(1.6–7.6)
(1.7–6.0)
(1.3–11.4)
(1.1–5.7)
!.001
4.8 (1.4–16.2)
…
…
…
.013
…
…
…
!.001
!.001
.011
There were 201 records included in the multiple logistic regression analysis.
752 • CID 2004:39 (1 September) • BRIEF REPORT
Case control study
aus Frankreich
90 Cases und 169
Kontrollgruppe
Nardone, CID, 2004 vol. 39 (5) pp. 751-3
Zurück zum Patient
Univariate analysis
Risk factor
Skin lesions
Professional risks
Countryside
Near a canal
Near a river
Leisure activity
Camping
Paddling
Swimming
Fishing
Canoeing
Animal contact
Rodents
Any
At home
At work
Farm animals
NOTE.
No. of
samples
Mantel-Haenszel OR
(95% CI)
220
257
257
257
259
259
P
P
7.7 (3.8–22.6)
3.1 (1.4–7.7)
3.0 (1.5–14.7)
!.001
7.0 (2.7–17.6)
…
…
!.001
4.8 (2.4–8.8)
1.8 (1.0–3.1)
3.0 (1.6–5.6)
!.001
.002
!.001
…
.031
!.001
2.9 (1.1–7.6)
…
…
.033
…
…
259
259
259
259
259
259
259
5.3
2.3
3.1
2.8
5.1
21.5
3.0
(1.2–29.8)
(1.2–4.5)
(1.6–7.9)
(1.0–7.8)
(2.4–12.6)
(3.1–907.5)
(1.0–10.0)
.010
.004
!.001
.021
!.001
!.001
.026
…
…
…
…
…
15.5 (1.6–147.0)
…
…
…
…
…
…
.017
…
259
249
239
259
3.0
3.1
3.5
2.4
(1.6–7.6)
(1.7–6.0)
(1.3–11.4)
(1.1–5.7)
!.001
4.8 (1.4–16.2)
…
…
…
.013
…
…
…
!.001
!.001
.011
Case control study
aus Frankreich
90 Cases und 169
Kontrollgruppe
Zurück zum Patient
Univariate analysis
Risk factor
Skin lesions
Professional risks
Countryside
Near a canal
Near a river
Leisure activity
Camping
Paddling
Swimming
Fishing
Canoeing
Animal contact
Rodents
Any
At home
At work
Farm animals
NOTE.
No. of
samples
Mantel-Haenszel OR
(95% CI)
220
257
257
257
259
259
P
P
7.7 (3.8–22.6)
3.1 (1.4–7.7)
3.0 (1.5–14.7)
!.001
7.0 (2.7–17.6)
…
…
!.001
4.8 (2.4–8.8)
1.8 (1.0–3.1)
3.0 (1.6–5.6)
!.001
.002
!.001
…
.031
!.001
2.9 (1.1–7.6)
…
…
.033
…
…
259
259
259
259
259
259
259
5.3
2.3
3.1
2.8
5.1
21.5
3.0
(1.2–29.8)
(1.2–4.5)
(1.6–7.9)
(1.0–7.8)
(2.4–12.6)
(3.1–907.5)
(1.0–10.0)
.010
.004
!.001
.021
!.001
!.001
.026
…
…
…
…
…
15.5 (1.6–147.0)
…
…
…
…
…
…
.017
…
259
249
239
259
3.0
3.1
3.5
2.4
(1.6–7.6)
(1.7–6.0)
(1.3–11.4)
(1.1–5.7)
!.001
4.8 (1.4–16.2)
…
…
…
.013
…
…
…
!.001
!.001
.011
Case control study
aus Frankreich
90 Cases und 169
Kontrollgruppe
Zurück zum Patient
Univariate analysis
Risk factor
Skin lesions
Professional risks
Countryside
Near a canal
Near a river
Leisure activity
Camping
Paddling
Swimming
Fishing
Canoeing
Animal contact
Rodents
Any
At home
At work
Farm animals
NOTE.
No. of
samples
Mantel-Haenszel OR
(95% CI)
220
257
257
257
259
259
P
P
7.7 (3.8–22.6)
3.1 (1.4–7.7)
3.0 (1.5–14.7)
!.001
7.0 (2.7–17.6)
…
…
!.001
4.8 (2.4–8.8)
1.8 (1.0–3.1)
3.0 (1.6–5.6)
!.001
.002
!.001
…
.031
!.001
2.9 (1.1–7.6)
…
…
.033
…
…
259
259
259
259
259
259
259
5.3
2.3
3.1
2.8
5.1
21.5
3.0
(1.2–29.8)
(1.2–4.5)
(1.6–7.9)
(1.0–7.8)
(2.4–12.6)
(3.1–907.5)
(1.0–10.0)
.010
.004
!.001
.021
!.001
!.001
.026
…
…
…
…
…
15.5 (1.6–147.0)
…
…
…
…
…
…
.017
…
259
249
239
259
3.0
3.1
3.5
2.4
(1.6–7.6)
(1.7–6.0)
(1.3–11.4)
(1.1–5.7)
!.001
4.8 (1.4–16.2)
…
…
…
.013
…
…
…
!.001
!.001
.011
Case control study
aus Frankreich
90 Cases und 169
Kontrollgruppe
Weltweite Zoonose, vor allem (Sub)tropen
,neglected tropical diseases‘
In der Schweiz Rarität
keine typische DD bei Hepatitis u/o ANV
nur bei entsprechenden Risikoexpositionen (Beruf,
Tierkontakte, Wassersport, Reiserückkehrer) suchen
Schwierige Diagnose; meist harmlos, potentiell tödlich
LEPTOSPIROSE
Take Home Messages

Vortrag C. Strahm, 8.8.12

Transcription

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