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Spotted Fever Rickettsioses in Sweden: Aspects of Epidemiology, Clinical Manifestations and Co-infections
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine. (Kenneth Nilsson)
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The spotted fever group rickettsiae are emerging diseases. They cause damage in their hosts by invading the endothelium in small to medium-sized blood vessels, which results in vasculitis that can cause clinical manifestations from most organs.

The present thesis describes the prevalence of Rickettsia helvetica in ticks, the incidence of rickettsial infection based on seroreactivity and seroconversion in humans and their symptoms, from different parts of Sweden and the Åland Islands in Finland. This was accomplished through serological analysis of both retrospective and prospective serum samples from confirmed and suspected tick-bitten individuals compared to individuals with no knowledge of tick exposure (blood donors). We found a comparable seroprevalence to Rickettsia spp. in different geographical areas where ticks are present; it was also comparable to the seroprevalence of Borrelia spp. Seroprevalence was also more common, as suspected, in the tick-exposed group compared to blood donors. In comparison with co-infections with other tick-borne infections (Anaplasma spp. and Borrelia spp.), we could conclude that co-infections do exist and that, based on clinical findings, it is difficult to distinguish which microorganism causes certain clinical manifestations. For reliable conclusions regarding the causative microorganism, the diagnosis should basically rely on diagnostic tests. In comparison with Borrelia spp., seroconversion to Rickettisa spp. was more common in the areas we investigated, indicating that rickettsiosis is a common tick-borne infection in Sweden and most likely underdiagnosed.

When investigating patients with meningitis, we found R. felis in cerebrospinal fluid from two patients with subacute meningitis. This was the first report in which R. felis was found and diagnosed in patients in Sweden. The patients recovered without sequelae and without causal treatment. To provide guidelines on when to treat Rickettisa spp. infections, more investigations are needed.

The present thesis shows that Rickettsia spp. are common in ticks and do infect humans. Rickettsial infection should be considered in both non-specific or specific symptoms after a tick bite. It was also shown in the thesis that flea-borne rickettsiosis (R. felis) occurs in Sweden and may cause invasive infections

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. , 64 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1253
Keyword [en]
Rickettsia helvetica, Rickettsia felis, co-infection, erythema migrans, meningitis, serology, PCR, western blot
National Category
Infectious Medicine
Research subject
Infectious Diseases
Identifiers
URN: urn:nbn:se:uu:diva-302137ISBN: 978-91-554-9677-7 (print)OAI: oai:DiVA.org:uu-302137DiVA: diva2:956560
Public defence
2016-10-26, Mikrobiologens hörsal, Dag Hammarskjöldsväg 17, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2016-10-03 Created: 2016-08-30 Last updated: 2016-10-11
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
Identifiers
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. Seroreactivity for spotted fever rickettsiae and co-infections with other tick-borne agents among habitants in central and southern Sweden
Open this publication in new window or tab >>Seroreactivity for spotted fever rickettsiae and co-infections with other tick-borne agents among habitants in central and southern Sweden
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2013 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 32, no 3, 317-323 p.Article in journal (Refereed) Published
Abstract [en]

Patients seeking medical care with erythema migrans or flu-like symptoms after suspected or observed tick bite in the southeast of Sweden and previously investigated for Borrelia spp. and/or Anaplasma sp. were retrospectively examined for serological evidence of rickettsial infection (Study 1). Twenty of 206 patients had IgG and/or IgM antibodies to Rickettsia spp. equal to or higher than the cut-off titre of 1:64. Seven of these 20 patients showed seroconversion indicative of recent or current infection and 13 patients had titres compatible with past infection, of which five patients were judged as probable infection. Of 19 patients with medical records, 11 were positive for Borrelia spp. as well, and for Anaplasma sp., one was judged as positive. Five of the 19 patients had antibodies against all three pathogens. Erythema migrans or rash was observed at all combinations of seroreactivity, with symptoms including fever, muscle pain, headache and respiratory problems. The results were compared by screening an additional 159 patients (Study 2) primarily sampled for the analysis of Borrelia spp. or Mycoplasma pneumoniae. Sixteen of these patients were seroreactive for Rickettsia spp., of which five were judged as recent or current infection. Symptoms of arthritis, fever, cough and rash were predominant. In 80 blood donors without clinical symptoms, approximately 1 % were seroreactive for Rickettsia spp., interpreted as past infection. The study shows that both single and co-infections do occur, which illustrate the complexity in the clinical picture and a need for further studies to fully understand how these patients should best be treated.

National Category
Infectious Medicine Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-183804 (URN)10.1007/s10096-012-1742-3 (DOI)000314774000003 ()22961007 (PubMedID)
Note

De två första författarna delar förstaförfattarskapet

Available from: 2012-11-01 Created: 2012-11-01 Last updated: 2017-12-07
3. Prevalence of Rickettsia spp. in Ticks and Serological and Clinical Outcomes in Tick-Bitten Individuals in Sweden and on the Åland Islands
Open this publication in new window or tab >>Prevalence of Rickettsia spp. in Ticks and Serological and Clinical Outcomes in Tick-Bitten Individuals in Sweden and on the Åland Islands
Show others...
2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11, e0166653Article in journal (Refereed) Published
Abstract [en]

Tick-transmitted diseases are an emerging health problem, and the hard tick Ixodes ricinus is the main vector for Borrelia spp., tick-borne encephalitis virus and most of the spotted fever Rickettsiae in Europe. The aim of the present study was to examine the incidence of rickettsial infection in the southernmost and south central parts of Sweden and the Aland Islands in Finland the risk of infection in humans and its correlation with a bite of a Rickettsia-infected tick, the self-reported symptoms of rickettsial disease, and the prevalence of co-infection between Rickettsia spp. and Borrelia spp. Persons with a recent tick bite were enrolled through public media and asked to answer a questionnaire, provide a blood sample and bring detached ticks at enlistment and at follow-up three months later. Blood samples were previously analysed for Borrelia spp. antibodies and, for this report, analysed for antibodies to Rickettsia spp. by immunofluorescence and in 16 cases also using Western Blot. Ninety-six (44.0%) of the 218 participants were seropositive for IgG antibodies to Rickettsia spp. Forty (18.3%) of the seropositive participants had increased titres at the follow-up, indicating recent/current infection, while four (1.8%) had titres indicating probable recent/current infection (>= 1: 256). Of 472 ticks, 39 (8.3%) were Rickettsia sp. positive. Five (31.3%) of 16 participants bitten by a Rickettsia-infected tick seroconverted. Experience of the selfreported symptoms nausea (p = 0.006) and radiating pain (p = 0.041) was more common among those with recent, current or probable infection compared to those who did not seroconvert. Participants who showed seroreactivity or seroconversion to Rickettsia spp. had more symptoms than those who were seronegative. Seven (3.2%) participants showed seroconversion to Borrelia spp., and three (1.4%) of these showed seroconversion to both Rickettsia spp. and Borrelia spp., in accordance with previous studies in Sweden. Symptoms of rickettsial disease were in most of the cases vague and general that were difficult to differentiate from other tick-borne diseases.

National Category
Infectious Medicine
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:uu:diva-298936 (URN)10.1371/journal.pone.0166653 (DOI)000387794600098 ()
Available from: 2016-07-12 Created: 2016-07-12 Last updated: 2017-11-28Bibliographically approved
4. Rickettsia felis infection in Sweden: report of two cases with subacute meningitis and review of the literature
Open this publication in new window or tab >>Rickettsia felis infection in Sweden: report of two cases with subacute meningitis and review of the literature
2010 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 42, no 11-12, 906-909 p.Article, review/survey (Refereed) Published
Abstract [en]

Two patients with headache and pleocytosis were diagnosed with Rickettsia felis infection using a polymerase chain reaction of cerebrospinal fluid and serological testing. Sequencing of the amplified products showed that they were 99-100% homologous to R. felis. These cases add to our knowledge of the clinical manifestations, as well as the geographical distribution, of this spotted fever agent.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:uu:diva-133705 (URN)10.3109/00365548.2010.508466 (DOI)000284168300019 ()20735330 (PubMedID)
Available from: 2010-11-16 Created: 2010-11-15 Last updated: 2016-09-30Bibliographically approved

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