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Studies of Spotted Fever Rickettsia - Distribution, Detection, Diagnosis and Clinical Context: With a Focus on Vectors and Patients in Sweden
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Klinisk mikrobiologi och infecktionssjukdomar)
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The spotted fever rickettsia, Rickettsia helvetica, is an endemic tick-borne bacteria in Sweden. It causes infections in humans, manifested as aneruptive fever, headache, arthralgia and myalgia, and sometimes an inoculation eschar or a rash. There have also been two known cases of human infections with R. felis in Sweden.

The present thesis starts by investigating dispersal of ticks and Rickettsia spp. by migrating birds flying from Africa to Europe. Almost 15,000 birds were searched and 734 ticks collected, mainly of the species Hyalomma marginatum complex. Almost half (48%) of the ticks were infected with Rickettsia spp., 96% of which was R. aeschlimannii, the remaining R. africae and undefined species.

The next study focused on questing ticks over a large area in Sweden and determining the prevalence of Rickettsia spp., Anaplasma spp. and Coxiella burnetii. Rickettsia spp. was found in 9.5-9.6% of the ticks and A. phagocytophilum in 0.7%; no C. burnetii was found.

The last three papers in the thesis focused on the clinical presentation of rickettsiosis, the symptoms associated with the infection in general and particularly in patients with neurological complications. A tick-exposed population in Sweden was investigated to gain a better understanding of symptoms due to rickettsioses, also in relation to co-infections with other tick-borne bacteria. Based on symptoms, it was not possible to distinguish what pathogen caused the infections. Most patients had erythema migrans, some had serological reactions to Rickettsia spp., Borrelia spp. or co-infections by Rickettsia spp., Borrelia spp. and/or Anaplasma spp. In the fourth and fifth papers, we found associations between antibodies against Rickettsia spp. and sudden deafness (in 10-24% of patients) and facial nerve paralysis (in 8.3-25% of patients). In three patients R. felis was detected in the cerebrospinal fluids.   

Briefly, the thesis helps to clarify our knowledge about tick dispersal, shows a narrower prevalence estimate of Rickettsia spp. in Swedish ticks, and illuminates symptoms of rickettsioses and co-infections with other tick-borne infections. It also shows that presence of erythema migrans may be explained by more than Lyme disease and indicates a possible association between rickettsiosis and sudden deafness and facial nerve paralysis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. , 77 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1195
Keyword [en]
tick-borne infections, co-infections, ticks, Ixodes ricinus, zoonosis, Rickettsia helvetica, migrating birds, Bell’s pares, erythema migrans, Rickettsia aeschlimannii, sudden deafness, facial nerve paralysis, Hyalomma marginatum, Rickettsia africae, western blot, PCR, serology
National Category
Clinical Medicine Basic Medicine
Research subject
Clinical Bacteriology
Identifiers
URN: urn:nbn:se:uu:diva-280667ISBN: 978-91-554-9512-1 (print)OAI: oai:DiVA.org:uu-280667DiVA: diva2:911975
Public defence
2016-05-04, Hörsalen, Klinisk Mikrobiologi, Akademiska sjukhuset, Ing D1, Dag Hammarskjöldsväg 17, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2016-04-11 Created: 2016-03-14 Last updated: 2016-04-12
List of papers
1. Spotted fever Rickettsia species in Hyalomma and Ixodes ticks infesting migratory birds in the European Mediterranean area
Open this publication in new window or tab >>Spotted fever Rickettsia species in Hyalomma and Ixodes ticks infesting migratory birds in the European Mediterranean area
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2014 (English)In: Parasites & Vectors, ISSN 1756-3305, E-ISSN 1756-3305, Vol. 7, 318Article in journal (Refereed) Published
Abstract [en]

Background: A few billion birds migrate annually between their breeding grounds in Europe and their wintering grounds in Africa. Many bird species are tick-infested, and as a result of their innate migratory behavior, they contribute significantly to the geographic distribution of pathogens, including spotted fever rickettsiae. The aim of the present study was to characterize, in samples from two consecutive years, the potential role of migrant birds captured in Europe as disseminators of Rickettsia-infected ticks. Methods: Ticks were collected from a total of 14,789 birds during their seasonal migration northwards in spring 2009 and 2010 at bird observatories on two Mediterranean islands: Capri and Antikythira. All ticks were subjected to RNA extraction followed by cDNA synthesis and individually assayed with a real-time PCR targeting the citrate synthase (gltA) gene. For species identification of Rickettsia, multiple genes were sequenced. Results: Three hundred and ninety-eight (2.7%) of all captured birds were tick-infested; some birds carried more than one tick. A total number of 734 ticks were analysed of which 353 +/- 1 (48%) were Rickettsia-positive; 96% were infected with Rickettsia aeschlimannii and 4% with Rickettsia africae or unidentified Rickettsia species. The predominant tick taxon, Hyalomma marginatum sensu lato constituted 90% (n = 658) of the ticks collected. The remaining ticks were Ixodes frontalis, Amblyomma sp., Haemaphysalis sp., Rhipicephalus sp. and unidentified ixodids. Most ticks were nymphs (66%) followed by larvae (27%) and adult female ticks (0.5%). The majority (65%) of ticks was engorged and nearly all ticks contained visible blood. Conclusions: Migratory birds appear to have a great impact on the dissemination of Rickettsia-infected ticks, some of which may originate from distant locations. The potential ecological, medical and veterinary implications of such Rickettsia infections need further examination.

Keyword
Migratory birds, Spotted fever Rickettsia, Rickettsia aeschlimannii, Rickettsia africae, Transmission, Tick, Hyalomma marginatum, Hyalomma rufipes, Ixodes frontalis
National Category
Infectious Medicine Biological Sciences
Identifiers
urn:nbn:se:uu:diva-231125 (URN)10.1186/1756-3305-7-318 (DOI)000339579100001 ()25011617 (PubMedID)
Available from: 2014-09-04 Created: 2014-09-04 Last updated: 2017-12-05Bibliographically approved
2. Prevalence of Rickettsia spp., Anaplasma phagocytophilum and Coxiella burnetii in adult Ixodes ricinus ticks from 29 study areas in central and southern Sweden
Open this publication in new window or tab >>Prevalence of Rickettsia spp., Anaplasma phagocytophilum and Coxiella burnetii in adult Ixodes ricinus ticks from 29 study areas in central and southern Sweden
2012 (English)In: Ticks and Tick-borne Diseases, ISSN 1877-959X, E-ISSN 1877-9603, Vol. 3, no 2, 100-106 p.Article in journal (Refereed) Published
Abstract [en]

A total of 887 adult Ixodes ricinus ticks (469 females and 418 males) from 29 different localities in Sweden were screened for Rickettsia, Anaplasma, and Coxiella DNA using PCR and then subjected to gene sequencing. Rickettsial DNA was detected in 9.5–9.6% of the ticks. Most of the positive ticks were infected with Rickettsia helvetica. One tick harbored another spotted fever rickettsia, closely related to or identical with R. sibirica not previously found in I. ricinus nor in Sweden. Six of the ticks (0.7%) were infected with an Anaplasma sp., presumably A. phagocytophilum. Coxiella burnetii DNA was not detected in any of the ticks. The detection of R. helvetica and A. phagocytophilum in several of the localities sampled suggests that these potentially human-pathogenic agents are common in Sweden.

Keyword
Ixodes ricinus, Rickettsia, Anaplasma, Coxiella, PCR
National Category
Microbiology in the medical area
Research subject
Microbiology
Identifiers
urn:nbn:se:uu:diva-168814 (URN)10.1016/j.ttbdis.2011.11.003 (DOI)000304570200006 ()
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2012-02-15 Created: 2012-02-15 Last updated: 2017-12-07Bibliographically approved
3. 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
4. Bell’s palsy and sudden deafness associated with Rickettsia spp . infection in Sweden: A retrospective and prospective serological survey including PCR findings
Open this publication in new window or tab >>Bell’s palsy and sudden deafness associated with Rickettsia spp . infection in Sweden: A retrospective and prospective serological survey including PCR findings
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2014 (English)In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 21, no 2, 206-214 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE:

Sixty patients with facial palsy and 67 with sudden deafness were retrospectively or prospectively examined for serological evidence of rickettsial infection; in six cases where cerebrospinal fluid was available, patients were also examined for presence of rickettsial DNA.

METHODS:

Rickettsial antibodies were detected in single or paired serum samples using immunofluorescence with Rickettsia helvetica as the antigen and in four cases also using western blot. Using PCR and subsequent direct cycle sequencing, the nucleotide sequences of the amplicons (17 kDa protein gene) in cerebrospinal fluid were analysed.

RESULTS:

Five out of 60 (8.3%) patients with facial palsy and eight of 67 (11.9%) with hearing loss showed confirmative serological evidence of infection with Rickettsia spp. An additional three and four patients in the facial palsy and hearing loss groups, respectively, showed evidence of having a recent or current infection or serological findings suggestive of infection. In four cases, the specificity of the reaction was confirmed by western blot. An additional 70 patients were seroreactive with IgG or IgM antibodies higher than or equal to the cut-off of 1:64, whereas 37 patients were seronegative. Only two of 127 patients had detectable antibodies to Borrelia spp. In three of six patients, rickettsial DNA was detected in the cerebrospinal fluid, where the obtained sequences (17 kDa) shared 100% similarity with the corresponding gene sequence of Rickettsia felis.

CONCLUSIONS:

These results highlight the importance of considering Rickettsia spp. as a cause of neuritis, and perhaps as a primary cause of neuritis unrelated to neuroborreliosis.

Keyword
PCR, Bell's palsy, deafness, neuritis, serology, spotted fever rickettsia
National Category
Infectious Medicine
Research subject
Infectious Diseases; Microbiology; Oto-Rhino-Laryngology
Identifiers
urn:nbn:se:uu:diva-205365 (URN)10.1111/ene.12218 (DOI)000329547200008 ()23790098 (PubMedID)
Available from: 2013-08-16 Created: 2013-08-16 Last updated: 2017-12-06
5. Immunofluorescence and Western Blots analysis of antibodies against Rickettsia spp. and Borrelia spp. in serum from patients with peripheral facial nerve palsy. A retrospective serological survey
Open this publication in new window or tab >>Immunofluorescence and Western Blots analysis of antibodies against Rickettsia spp. and Borrelia spp. in serum from patients with peripheral facial nerve palsy. A retrospective serological survey
(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Research subject
Clinical Bacteriology
Identifiers
urn:nbn:se:uu:diva-280022 (URN)
Available from: 2016-03-10 Created: 2016-03-07 Last updated: 2016-04-12

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