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Epidemiological and Bacteriological Aspects of Spotted Fever Rickettsioses in Humans, Vectors and Mammals in Sweden
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Rickettsiae are obligate intracellular gram-negative bacteria transmitted by arthropod vectors. Rickettsiae sometimes cause disease in humans, typically with high fever, headache and occasionally an eschar.

In Sweden, Rickettsia helvetica, belonging to the spotted fever group, is the only tick-transmitted rickettsia found free in nature. The pathogenic roll of R. helvetica has not been fully investigated, but it has been implicated in aneruptive fever and cardiac disease.

This thesis describes parts of the transmission pathways of rickettsiae in Sweden. Rickettsia infection rates in ticks collected from birds were analysed, and the birds’ role as disseminators and reservoirs was studied. We found that more than one in ten ticks was infected with rickettsia bacteria, predominantly R. helvetica, and that migrating birds contribute not only to long-distance dispersion of bacteria, but also to an inflow of novel and potentially pathogenic rickettsia species, in this case R. monacensis and R. sp. strain Davousti-like species, into Sweden.

Further, wild and domestic animals were found to have seroreactivity against R. helvetica, which shows that they are exposed and susceptible to rickettsia. Their role as reservoirs has not been determined, yet they may indirectly be involved in transmission of rickettsia to humans by infected ticks feeding on them.

The seroreactivity in humans was also studied. Patients investigated for suspected Borrelioses and blood donors had detectable antibodies against Rickettsia spp., with the highest prevalence detected in the suspected Borreliosis group. This shows that humans in Sweden are exposed to and develop an immune response against rickettsia. The suspicion that R. helvetica may cause severe symptoms was verified by a patient with subacute meningitis where the bacterium was shown for the first time to cause an invasive infection with CNS involvement and where the bacterium was isolated from the patient’s cerebrospinal fluid.

Growth characteristics and morphology of R. helvetica were studied to better understand invasiveness and virulence. The findings indicate that the invasiveness is comparable with other rickettsia, though R. helvetica seems to have a stable but slightly slower growth. 

Rickettsia helvetica is endemic in Sweden and therefore needs to be considered when investigating disease after a tick bite.

Abstract [sv]

Rickettsia är en liten, strikt intracellulär, gramnegativ bakterie som sprids med vektorer som fästingar, löss och loppor. Bakterien kan orsaka Rickettsios hos människa, en sjukdom där de vanligaste symtomen är hög feber, huvudvärk, muskelvärk och i vissa fall ett bettmärke (eschar). I Sverige är Rickettsia helvetica, som tillhör spotted fever gruppen (SFG), den enda fästingöverförda rickettsia bakterien som hittats allmänt i naturen. Patogeniciteten för R. helvetica är ofullständigt utredd, men ”aneruptive fever” och hjärtmuskelinflammation har rapporterats.

Avhandlingen beskriver delar av smittkedjan för SFG rickettsia i Sverige. Bakteriernas förekomst i fästingar plockade från fåglar har studerats, likaså det ekologiska tryck som flyttfåglars bärarskap av infekterade fästingar bidrar med när de korsar olika världsdelar. Mer än var tionde fästing var infekterad med rickettsia bakterier, i huvudsak R. helvetica. Det visade sig att flyttfåglar bidrar inte bara till långväga spridning av bakterier utan även till införsel av nya potentiellt patogena rickettsiaarter, i detta fall identifierades R. monacensis och en R. sp strain Davousti liknande art.

Vidare analyserades seroreaktivitet mot Rickettsia helvetica hos både tamdjur och vilda djur, vilket visade på antikroppsutveckling, som uttryck för smittexposition, i mer än vart femte djur. Djurens roll som reservoar för bakterien är inte klarlagd, men oavsett är djuren indirekt involverade i spridningen av bakterien till människa via infekterade fästingar som suger blod.

Seroreaktivitet hos människa har också studerats. Patienter, provtagna på grund av misstanke om borreliainfektion, samt blodgivare hade detekterbara antikroppar mot Rickettsiae, med högst prevalens i gruppen med misstänkt borreliainfektion. Fynden visar att människor i Sverige är exponerade för och utvecklar en immunreaktion mot rickettsia. Att R. helvetica skulle kunna ge allvarlig sjukdom verifieras av ett patientfall med subakut meningit där bakterien för första gången visats ge invasiv infektion med påverkan på nervsystemet (CNS engagemang) och där bakterien isolerats från patientens ryggmärgsvätska. 

Morfologi och tillväxtegenskaper för R. helvetica undersöktes för att bättre förstå bakteriens invasivitet och virulens. Fynden indikerar att invasiviteten är jämförbar med andra rickettsiaarter men R. helvetica verkar ha en stabil men något långsammare tillväxt.

Rickettsia helvetica är endemisk i Sverige och måste tas i beaktande vid sjukdomsutredning efter ett fästingbett.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. , 52 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 888
Keyword [en]
Rickettsia helvetica, ticks, cultivation, serology, polymerase chain reaction (PCR), DNA sequencing, western blot, electron microscopy, meningitis, seroprevalence
National Category
Clinical Laboratory Medicine Microbiology Microbiology in the medical area
URN: urn:nbn:se:uu:diva-197277ISBN: 978-91-554-8639-6OAI: oai:DiVA.org:uu-197277DiVA: diva2:614279
Public defence
2013-05-22, Hörsalen, Klinisk Mikrobiologi, Akademiska Sjukhuset, Dag Hammarskjöldsväg 17, Ing D1, Uppsala, 13:00 (Swedish)
Available from: 2013-04-26 Created: 2013-03-21 Last updated: 2013-08-30Bibliographically approved
List of papers
1. Seroprevalence of Rickettsia spp. infection among tick-bitten patients and blood donors in Sweden
Open this publication in new window or tab >>Seroprevalence of Rickettsia spp. infection among tick-bitten patients and blood donors in Sweden
2008 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 40, no 1, 74-77 p.Article in journal (Refereed) Published
Abstract [en]

Serum samples from 236 Swedish patients with symptoms of infectious disease appearing after a tick bite were analysed for the presence of antibodies to Rickettsia helvetica, the only rickettsial species so far isolated from ticks in Sweden. Of these subjects, 137 had tested seropositive for Borrelia burgdorferi. For control purposes, sera from 161 healthy blood donors were examined. A total of 10/397 samples (2.6%) showed IgG-antibodies to R. helvetica at or above a titre of 1/80 as cut-off. 6/137 (4.4%) belonged to the Borrelia positive group, 3/99 (3.0%) to the tick-bitten but Borrelia negative group and 1/161 (0.6%) to the control group. The difference between the tick-exposed groups and the control group was significant in Pearson's 2-sided chi(2) test. In 1 serum sample the presence of antibodies to R. helvetica was further confirmed by Western immunoblot. The study shows that infection with Rickettsia spp. as well as coinfection with Lyme borreliosis needs to be considered in the diagnosis of tick-transmitted infections in Sweden. Owing to a known occurrence of immunological cross-reactivites, however, the results must be cautiously interpreted with regard to species of Rickettsia involved.

National Category
Medical and Health Sciences
urn:nbn:se:uu:diva-103987 (URN)10.1080/00365540701509907 (DOI)000252311200014 ()17852905 (PubMedID)
External cooperation:
Available from: 2009-05-26 Created: 2009-05-26 Last updated: 2016-09-02Bibliographically approved
2. Dissemination of Spotted Fever Rickettsia Agents in Europe by Migrating Birds
Open this publication in new window or tab >>Dissemination of Spotted Fever Rickettsia Agents in Europe by Migrating Birds
Show others...
2010 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 5, no 1, e8572- p.Article in journal (Refereed) Published
Abstract [en]

Migratory birds are known to play a role as long-distance vectors for many microorganisms. To investigate whether this is true of rickettsial agents as well, we characterized tick infestation and gathered ticks from 13,260 migratory passerine birds in Sweden. A total of 1127 Ixodes spp. ticks were removed from these birds and the extracted DNA from 957 of them was available for analyses. The DNA was assayed for detection of Rickettsia spp. using real-time PCR, followed by DNA sequencing for species identification. Rickettsia spp. organisms were detected in 108 (11.3%) of the ticks. Rickettsia helvetica, a spotted fever rickettsia associated with human infections, was predominant among the PCR-positive samples. In 9 (0.8%) of the ticks, the partial sequences of 17kDa and ompB genes showed the greatest similarity to Rickettsia monacensis, an etiologic agent of Mediterranean spotted fever-like illness, previously described in southern Europe as well as to the Rickettsia sp.IrITA3 strain. For 15 (1.4%) of the ticks, the 17kDa, ompB, gltA and ompA genes showed the greatest similarity to Rickettsia sp. strain Davousti, Rickettsia japonica and Rickettsia heilongjiangensis, all closely phylogenetically related, the former previously found in Amblyomma tholloni ticks in Africa and previously not detected in Ixodes spp. ticks. The infestation prevalence of ticks infected with rickettsial organisms was four times higher among ground foraging birds than among other bird species, but the two groups were equally competent in transmitting Rickettsia species. The birds did not seem to serve as reservoir hosts for Rickettsia spp., but in one case it seems likely that the bird was rickettsiemic and that the ticks had acquired the bacteria from the blood of the bird. In conclusion, migratory passerine birds host epidemiologically important vector ticks and Rickettsia species and contribute to the geographic distribution of spotted fever rickettsial agents and their diseases.

Ixodes, ticks, birds, infestation, rickettsia, spotted fever
National Category
Microbiology in the medical area
urn:nbn:se:uu:diva-113683 (URN)10.1371/journal.pone.0008572 (DOI)000273338500015 ()20052286 (PubMedID)
Available from: 2010-02-02 Created: 2010-02-02 Last updated: 2015-03-31Bibliographically approved
3. Rickettsia helvetica in patient with meningitis, Sweden, 2006
Open this publication in new window or tab >>Rickettsia helvetica in patient with meningitis, Sweden, 2006
2010 (English)In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 16, no 3, 490-492 p.Article in journal (Refereed) Published
Abstract [en]

Pathogenicity of Rickettsia helvetica is relatively unknown. We isolated a spotted fever group rickettsial organism from a patient with subacute meningitis. Nucleotide sequences of the 16S rRNA, ompB, and 17kDa genes identified the isolate as R. helvetica. This organism may be associated with serious infections such as central nervous system disorders.

National Category
Medical and Health Sciences
urn:nbn:se:uu:diva-125294 (URN)10.3201/eid1603.090184 (DOI)000275404700018 ()20202426 (PubMedID)
Available from: 2010-05-14 Created: 2010-05-14 Last updated: 2013-08-30Bibliographically approved
4. Life cycle, growth characteristics and host cell response of Rickettsia helvetica in a Vero cell line
Open this publication in new window or tab >>Life cycle, growth characteristics and host cell response of Rickettsia helvetica in a Vero cell line
2012 (English)In: Experimental & applied acarology, ISSN 0168-8162, E-ISSN 1572-9702, Vol. 56, no 2, 179-187 p.Article in journal (Refereed) Published
Abstract [en]

Rickettsia helvetica, a spotted fever rickettsia and emerging pathogen with Ixodes ricinus ticks as the main vector, is an agent of human disease and may cause febrile illness as well as meningitis. In three parallel series the isolated standard type of R. helvetica, obtained from a PCR-positive I. ricinus tick, was high-passaged and propagated in a Vero cell line. By using quantitative real-time PCR, the generation time from inoculation to stationary phase of growth was calculated to 20-22 h. In the static cultivation system the stationary phase was observed from the seventh day after inoculation, and there was no observed degradation of R. helvetica DNA during the 14 days studied. Microscopy showed that the organisms invaded the host cells rapidly and were primarily found free in the cytoplasm and only occasionally located in the nucleus. Four days after inoculation some of the host cells were broken and many indifferent stages of cytoplasmic organic decomposition were seen. However the R. helvetica organism did not show any morphologic alterations and the number of organisms was stable after the replication peak which may indicate that R. helvetica is adapted to growth in a Vero cell line and/or that the phase of degradation occurs later than the 14 days studied. The findings differ from what has been reported for other rickettsiae of the spotted fever group and may be of importance for invasiveness and virulence of R. helvetica.

rickettsia, qPCR, vero cells, life cycle, ultrastructure
National Category
Research subject
Infectious Diseases
urn:nbn:se:uu:diva-166778 (URN)10.1007/s10493-011-9508-7 (DOI)000299078900010 ()

Correction in: Experimental and Applied Acarology, Vol 56, Issue 2, pp 189-190

DOI: 10.1007/s10493-011-9509-6

Available from: 2012-01-13 Created: 2012-01-13 Last updated: 2013-08-30Bibliographically approved
5. Seroreactivity to Rickettsia spp. in Wild and Domestic Mammals in Sweden
Open this publication in new window or tab >>Seroreactivity to Rickettsia spp. in Wild and Domestic Mammals in Sweden
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Sera were collected from wild and domestic mammals in Sweden and tested using indirect immunofluorescence assay to detect antibodies against Rickettsia spp. Considering sera with a titre > 1:64 as positive, 23.1% (104/450) of the animals scored positive. The percentages of seropositivity were: 21.5% (23/107) in deer, 23.3% (21/90) in moose, 36.5% (23/61) in horses, 22.2% (20/90) in cats and 17.0% (17/100) in dogs. In deer, 85% (91/107) also tested positive for Anaplasma phagocytophilum with a titre cut-off of 1:80. The findings indicate that these animal species may act as reservoir hosts of Rickettsia spp. and that deer may act as hosts for both tested organisms.

Rickettsia, Anaplasma, Serology, Host, Moose, Deer
National Category
urn:nbn:se:uu:diva-197803 (URN)
Available from: 2013-04-04 Created: 2013-04-04 Last updated: 2013-08-30

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