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VILKA MIKROORGANISMER EXPONERAS VI FÖR VID FÄSTINGBETT-RISKER?
Pia Forsberg
Professor emerita Infektionsmedicin
Department of Clinical and Experimental Medicine
Linköping University
TICK-BORNE MICROBES
Bacteria
Borrelia spp.
Anaplasma phagocytophilum
Rickettsia spp.
Candidatus Neoehrlichia mikurensis
Bartonella spp.
Francisella tularensis
Parasites and viruses
Babesia spp.
Toxoplasma gondii
TBE virus
Nairovirus
Few studies have investigated
the incidence of infection
by tick-borne microbes
after a tick bite
E.G.
BORRELIA BURGDORFERI SENSU LATO
No investigations of Borrelia in ticks that have bitten humans have been performed in Sweden
E.G. BORRELIA BURGDORFERI SENSU LATO
but worldwide: 20 % on the Dutch island of Ameland (Jacobs et al., 2008)
10 % in the western part of Switzerland (Nahimana et al., 2004)
1% in Texas, United States (Williamson et al., 2010)
BUT
Serological and clinical data were not notified
No attempts to quantify Borrelia cells were made
Duration of feeding was empirically estimated by direct observation of the ticks
THE
TBD STING
STUDY
AIMS
How large is the RISK to become infected/develop disease after a
tick bite?
How many of the ticks that have bitten humans contain
tick-borne microbes - which?
AIMS
What tick-borne microbes are present in ticks from Nordic countries?
Geographical differences?
Species/subtypes of microbes?
Do the risk of developing disease correlate with the ticks:
Quantity of microbes?
Species/subtype of microbes?
Feeding time duration?
TBD STING STUDY
2007 - 2015
10 000 fästingar DNA
3 mån studieperiod
5500 bitna individers blod x 2
5500 enkäter x 2
18år, mest kvinnor, 60-65 år
> 60 vårdcentraler Norge
Sverige
Åland, Finland
Questionnaires
Tick
Blood sample
Hmm...
Intressant
Real-time PCR
Tick-borne microbes?
Serology
Immune response?
Antibody production?
STUDY DESIGN
Health status?
Clinical diagnosis?
• 3 months follow-up
• Collection of
additional ticks
• Health records
ANNONSEN + MASSMEDIAL KOMMUNIKATION
Questionnaires
Tick
Blood sample
Hmm...
Intressant
Real-time PCR
Tick-borne microbes?
Serology
Immune response?
Antibody production?
STUDY DESIGN
Health status?
Clinical diagnosis?
• 3 months follow-up
• Collection of
additional ticks
• Health records
Blood sample
0mo. + 3mos.
Health status?
Clinical outcome?
2 ELISA tests
(anti-flagellum
& anti-C6)
New production of
antibodies?
Borrelia-caused infection? Line immunoblot
(8 antigens, 4 species)
Questionnaires
0mo. + 3mos.
+ medical records
ANALYSING THE TICK-BITTEN INDIVIDUALS - SEROLOGY AND CLINICAL OUTCOME
Jeremy Gray, Gerold Stanek, Michael Kundi, Elena Kocianova
International Journal of Medical Microbiology 295 (2005) 567-572
DinoLite USB-microscope
> 24h
< 24h
Photo & measure
Scutal index, SI = A/B
Coxal index, CI = A/c
Analysing the ticks
TICKS IN SWEDEN
11 species– Ixodes ricinus > 95%
Ticks are active down to 4°C
Life stages: egg, larva, nymph and adult
Food for parasitoid wasps, beetles, birds, ants and spiders
Lack eyes but have a good ”sense of smell”
RESULTS BORRELIA SPP.
WHAT DID THE TICKS CONTAIN?
26% of the 2154 ticks were Borrelia positive
50%
20%
6%
4%
2% 1%
0.5%
0.5% 16%
Detected Borrelia species, n=556
B. afzelii
B. garinii
B. valaisiana
B. burgdorferi
B. miyamotoi
B. spielmanii
B. lusitaniae
mixed species
untypeable
* p < 0.05
** p < 0.01
*** p < 0.001
BORRELIA SPECIES AND CELL QUANTITY
BORRELIA
26% (n=428/1546) were bitten by Borrelia-positive ticks
BORRELIA
In total:
2.1% (n=32) of all 1546 participants
developed LB.
2.5% (n=39) of all participants developed
asymptomatic infection (seroconversion)
BORRELIA INFECTION
22
428 bitten by Borrelia-positive
ticks
32 (7.5%)
Borrelia-infected individuals
16
LB cases
16 seroconversions (no LB cases)
396
uninfected individuals
1118 bitten by Borrelia-negative
ticks
39 (3.5%)
Borrelia-infected individuals
16
LB cases
23 seroconversions (no LB cases)
1079
uninfected individuals
CLINICAL MANIFESTATIONS
32 participants received a LB diagnosis during the 3 months study period
27 (84%) EM
2 (6%) NB
2 (6%) non-specific LB
1 (3%) Borrelia lymphocytoma
23
SELF-REPORTED NON-SPECIFIC SYMPTOMS
23% (349/1546) of all participants reported non-specific symptoms possibly associated with LB
Of which 20.3% (n=71) visited health care
24
Symptoms:
Fatigue
Myalgia/
Arthralgia
Headache
Neck pain
Numbness
Radiating
pain
Vertigo
Cognitive
difficulties
Nausea
Loss of
appetite
Fever
Loss of
weight
CONCLUSION BORRELIA
Every fourth tick Borrelia infected
7 Borrelia species detected
2.1% was diagnosed with LB 84% EM
68.8 % of all seroconversions did not experience non-specific symptoms or developed LB
Wilhelmsson P et al Parasites & Vectors, 2013 Wilhelmsson P et al PLoS One, 2013
Wilhelmsson P et al Ticks Tick Borne Dis. 2016
RESULTS TBE-VIRUS
5 / 2167 ticks positive for TBE-
V
Åland Kalmar Åland Saringe
Month of tick-bite
August August September June July
Life stage Nymph Nymph Nymph Nymph Nymph
Feeding time (h) < 12 24-36 < 12 12-24 >60
Virus copies in tick
< 400 ~ 4200 < 400 ~ 1800 ~ 7 700 000
Location of tick Leg Waist Back thigh Leg Behind ear
Visited health care
No Yes (Borrelia) No No Yes
Symptoms No Yes (Borrelia) No No Yes
TBE vaccinated Yes Yes Yes No Vacc, after
Co-infection Borrelia No Anaplasma No Borrelia
Location: Åland
Results: TBE-V qPCR
Conclusion TBE-V
• Over all very low risk of TBE-V
• 5 / 2167 (0,23 %) ticks that had bitten persons were positive for TBE-V. One developed symptoms (not serious)
• To few for conclusions on feeding-time and virus copy number or the riskassesment
Lindblom P et al Ticks and Tick Borne Diseases, 2014
RESULTS ANAPLASMA PHAGOCYTOPHILUM
ANAPLASMA
1291 ticks were analysed
40 of 1291 (3.1%) were positive for A. phagocytophilum
0.8% of all ticks were co-infected with Borrelia and Anaplasma
24% of the Anaplasma positive ticks were co-infected with Borrelia
No symptoms
Henningsson AJ et al Ticks Tick Borne Dis. 2015
RESULTS RICKETTSIA SPP.
RICKETTSIA
473 ticks were analysed
23 of 473 (4.9%) were positive for Rickettsia helvetica
Kalmar (n=1/82)
Östergötland (4/98)
Jönköping (7/97)
Lidköping (11/98)
All samples from Åland were negative (98)!!!!!!
Vague symptoms, nausea, radiating pain more common in seroconverted persons.
Lindblom A et al European Journal of Clinical Microbiology and Infectious Diseases, 2013
Lindblom A et al PLoS One. 2016
RESULTS NEOEHRLICHIA
3248 tick-bitten individuals
103 to primary health care center (during study period 3 m)
2/103 pos PCR in blood (1,9%)
EM
Co-infection Borrelia (1) serology
Co-infection Anaplasma (1) serology
Grankvist A et al Emerg Infect Dis. 2015
RESULTS BABESIA 65/2098 ticks pos Babesia (3,1%) from 1769 bitten persons
B microti 50,8%
B venatorum 41,5%
B divergens 7,7%
46% of the 65 Babesia pos ticks were Co-infected with Borrelia
Number of Babesia / tick = <10 - 1miljon
Feeding time <24h - >72h
65 BITTEN PERSONS BY BABESIA POS TICK
PCR in blood neg
Serology:
no seroconversion during 3 months
6% had Babesia ab:s in the 1:st blood sample!!
10 persons had vague ospecific symptoms
To be submitted M
Lövmar et al
ON GOING INVESTIGATION
Francisella tularensis
Bartonella spp.
Toxoplasma gondii
TICK-BORNE MICROBES
Bacteria
Borrelia spp.
Anaplasma phagocytophilum
Rickettsia spp.
Candidatus Neoehrlichia mikurensis
Bartonella spp.
Francisella tularensis
Parasites and viruses
Babesia spp.
Toxoplasma gondii
TBE virus
Nairovirus
CO-INFECTIONS
TBD STING STUDY
Infectious Medicine, LiU
Pia Forsberg
Johanna Sjöwall
Liselott Lindvall
Lisa Gunnarsson
Clinical Immunology, LiU
Christina Ekerfelt
Linda Fryland
Mari-Anne Åkeson
Karin Söderman
Medical Microbiology, LiU
Per-Eric Lindgren
Peter Wilhelmsson
Pontus Lindblom
Others
Sven Bergström
Anna Jonsson Henningsson
Barbro Hedin Skogman
Johan Berglund
Katharina Ornstein
Ivar Tjernberg
Dag Nyman (Åland)
Marika Nordberg (Åland)
Peter Nolskog
Mats Haglund
Clas Ahlm
Knut Eirik Eliassen (Norway)
Harald Reiso (Norway)
Matilda Lövmar
and other collaborating partners
FINANCIAL SUPPORT
The Swedish Research Council
Linköping University
County Council of Östergötland
The Medical Research Council of Southeast Sweden
Wilhelm and Else Stockmann Foundation
Foundation for Åland Medical Research
of the Åland Culture Foundation
EU Interreg IV A, ScandTick
www.liu.se
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