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Serological Parameters of Bartonella spp. Infection: Focus on Prevalences in Various Subgroups of the Swedish Population
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Bartonella spp. are emerging bacterial pathogens which continue to achieve an ever-increasing level of clinical importance and awareness.  As Bartonella infections are common zoonoses in the U.S., the existence of Bartonella infection in Sweden, which had not been documented prior to the onset of our investigations, was of considerable interest.

Initially, serological parameters of Bartonella infection were evaluated using a series of immunoblot analyses in an effort to elucidate the human humoral immunity induced by this pathogen.  An immunodominant epitope of B. henselae was identified, designated Bh83, which was hypothesized to be a conserved antigen during Bartonella infection. Further, an in-depth characterization of the immunoglobulin (Ig) isotype and IgG subclass response revealed a primary role of IgA and IgG1 in the immune induction during Bartonella infection.

As the presence and degree of exposure to Bartonella spp. in Sweden was previously unknown, several studies were initiated to evaluate the level of seroreactivity to Bartonella spp. antigen in various subgroups of the Swedish human and animal population using indirect fluorescent-antibody assay (IFA).  A preliminary study of a select group of patients and blood donors represented the first documentation of Bartonella exposure in Sweden, as well as identified the first two cases of B. quintana-like infections in Sweden.  To assess the endemic level of antibodies to Bartonella spp. in Sweden, a large sampling of blood donor sera collected nationwide were subsequently analyzed for reactivity to six Bartonella strains.  The largest seroprevalence was to B. elizabethae, with relatively low baseline levels of reactivity to the other Bartonella antigens tested.  Correlated risk factors for infection included working outdoors and contact with cats, among others.  Further studies of sera obtained from elite orienteers and intravenous drug users in Sweden revealed a high level of exposure to Bartonella spp. in such cohorts, predominantly to B. elizabethae antigen.  Consistent with the aforementioned findings of elevated titers to B. elizabethae in humans, a high seroprevalence was found in cats, a known reservoir for Bartonella spp., as well.

With relatively little known of the pathogenicity and epidemiology of Bartonella infection, these studies provide insight into various aspects of the distribution, risk factors for infection, specific humoral immune response to infection, and the prevalence of Bartonella spp. in human and cat populations in Sweden and serve as a framework for future studies.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2012. , 81 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 730
Keyword [en]
Bartonella, Sweden, serological studies
National Category
Other Medical Sciences not elsewhere specified
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-162504ISBN: 978-91-554-8238-1 (print)OAI: oai:DiVA.org:uu-162504DiVA: diva2:461167
Public defence
2012-01-21, Uppsala, Sweden, 09:00 (English)
Opponent
Supervisors
Available from: 2012-01-10 Created: 2011-11-30 Last updated: 2012-01-16Bibliographically approved
List of papers
1. Evaluation of human seroreactivity to Bartonella species in Sweden
Open this publication in new window or tab >>Evaluation of human seroreactivity to Bartonella species in Sweden
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1999 (English)In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 37, no 5, 1381-1384 p.Article in journal (Refereed) Published
Abstract [en]

Among the species that compose the expanding genus Bartonella, thus far only B. henselae and B. quintana have reportedly been isolated from humans in Europe. To evaluate the prevalence of Bartonella infection in Sweden,we conducted a retrospective serological examination of 126 human serum samples. These samples were analyzed for antibodies to B. henselae, B. quintana, and B. elizabethae, Serum samples from 100 blood donors, who spanned the ages of 20 to 60 and had no apparent clinical signs of illness, were also studied as a control group. An immunoglobulin G indirect fluorescence antibody assay revealed 4 and 8.3% Bartonella positivity rates for the blood donor and patient group, respectively, when a cutoff titer of greater than or equal to 64 was chosen. Among the blood donors, four were seropositive to B, elizabethae; one of these also had concordant positive titer to B. henselae, In the patient group, 14 serum samples were positive against Bartonella spp, These serum specimens represented nine patients. In three of these seropositive patients, paired serum samples displayed a fourfold increase in antibody titer to at least one of the three antigens, These three patients are discussed. In this report we also present a case study of a 60-year-old Swedish male with fatal myocarditis, Postmortem serological analysis revealed a high titer against B. elizabethae, PCR and nucleotide sequencing of the myocardial tissue from this patient, and of Liver tissue from one of the other three patients, showed sequences similar to B. quintana, The age, geographical origin, animal contacts, and serological response pattern to the different Bartonella antigens differed among the four patients. This study substantiates the presence of Bartonella spp, in Sweden, documents the seroreactivity to three Bartonella antigens in Swedish patients, and reports the first two cases of B. quintana-like infections in Sweden.

National Category
Other Medical Sciences not elsewhere specified
Identifiers
urn:nbn:se:uu:diva-54537 (URN)000079792400029 ()
Available from: 2013-04-24 Created: 2008-10-17 Last updated: 2017-12-04Bibliographically approved
2. Serological and epidemiological analysis of the prevalence of Bartonellaspp. antibodies in Swedish elite orienteers 1992-93.
Open this publication in new window or tab >>Serological and epidemiological analysis of the prevalence of Bartonellaspp. antibodies in Swedish elite orienteers 1992-93.
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2001 (English)In: Scand J Infect Dis, Vol. 33, 423- p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-62885 (URN)
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2012-01-16
3. Prevalence of antibodies to Bartonella henselae, B. elizabethae and B.quintana in Swedish domestic cats
Open this publication in new window or tab >>Prevalence of antibodies to Bartonella henselae, B. elizabethae and B.quintana in Swedish domestic cats
2002 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 34, no 3, 192-196 p.Article in journal (Refereed) Published
Abstract [en]

Sera from 292 cats were analyzed by means of indirect immunofluorescence for antibodies to Bartonella henselae, B. quintana and B. eliazabethae. The sera were sent to the Swedish National Institute of Veterinary Medicine for health monitoring and were tested retrospectively for antibodies to Bartonella. The most prevalent antibodies (25%) reacted with the B. elizabethae antigen. Cats with such antibodies were older than those without antibodies. The prevalence of antibodies to B. elizabethae was higher in the south of Sweden than in the north, with the highest prevalence (46%) being found in cats living in the Stockholm region. There was no difference in sex distribution. A low prevalence (1%,) of antibodies to B. henselae was found and no sera reacted with B. quintana. The high prevalence of antibodies to B. elizabethae is consistent with previous findings in Swedish patients. The small number of cats with B. henselae antibodies observed in this study could be due to the cold climate and the low occurrence of cat fleas in Sweden.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-64412 (URN)10.1080/00365540110080188 (DOI)
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2017-11-30Bibliographically approved
4. A study on forensic samples of Bartonella spp. antibodies in Swedish intravenous heroin addicts
Open this publication in new window or tab >>A study on forensic samples of Bartonella spp. antibodies in Swedish intravenous heroin addicts
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2003 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, APMIS, ISSN 0903-4641, Vol. 111, no 4, 507-513 p.Article in journal (Refereed) Published
Abstract [en]

Infection with Bartonella, an emerging bacterial pathogen which often affects immunodeficient patients, has been reported in Sweden over the past few years, with a high seroprevalence of B. elizabethae. A high prevalence of antibodies against B. elizabethae has also been found in urban intravenous drug users in the USA. Using immunofluorescence, we retrospectively examined serum samples taken at autopsy from 59 Swedish intravenous drug addicts from the Stockholm area for evidence of antibodies against 6 pathogenic strains of Bartonella. The 59 addicts died following heroin injection during the years 1987–1992 and include 24 individuals (41%) who were additionally HIV-positive. An overall seropositivity rate for Bartonella spp. of 39% (23/59) was found with the following antigenic reactivities: B. elizabethae, 39% (23/59); B. grahamii, 3% (2/59); B. henselae (Houston-1), 14% (8/59); and B. quintana, 3% (2/59). There were no positive reactions for B. henselae (Marseille) or B. vinsonii subsp. vinsonii. The Bartonella-seropositive cases included 11/23 (48%) individuals who were HIV-positive. Subacute to chronic myocarditis was seen in 2/11 microscopically investigated Bartonella-seropositive cases that were HIV-negative and in 1/14 seronegative cases. No cases of endocarditis or other common manifestations of Bartonella infection were found. An overall Bartonella seropositivity of 21% (9/44) was observed in control forensic autopsy samples.

Keyword
Adult, Antibodies; Bacterial/*blood, Bartonella/*immunology, Bartonella Infections/blood/immunology/*microbiology, Female, Fluorescent Antibody Technique; Indirect, Heroin, Humans, Male, Middle Aged, Myocarditis/epidemiology/microbiology, Research Support; Non-U.S. Gov't, Retrospective Studies, Seroepidemiologic Studies, Substance Abuse; Intravenous/blood/etiology/immunology/*microbiology, Sweden/epidemiology
National Category
Other Medical Sciences not elsewhere specified
Identifiers
urn:nbn:se:uu:diva-74385 (URN)10.1034/j.1600-0463.2003.1110409.x (DOI)12780526 (PubMedID)
Available from: 2008-04-20 Created: 2008-04-20 Last updated: 2017-12-14Bibliographically approved
5. Bartonella spp. seroprevalence in healthy Swedish blood donors
Open this publication in new window or tab >>Bartonella spp. seroprevalence in healthy Swedish blood donors
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2005 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 37, no 10, 723-730 p.Article in journal (Refereed) Published
Abstract [en]

Serum samples were collected from healthy blood donors in 5 regions in Sweden in 1999, i.e. from the local Blood Centres (collecting facilities) in Boden, Jönköping, Lund, Skövde, and Uppsala. In total, 498 serum samples (63% males, 37% females) were received and tested by immunofluorescence assay for antibodies against B. elizabethae, B. grahamii, B. henselae (Houston-1), B. henselae (Marseille), B. quintana, and B. vinsonii subsp. vinsonii. An overall Bartonella spp. seroprevalence of 16.1% was found, with a predominance of immunoreactivity to B. elizabethae, at 14.1%; B. grahamii, 2.6%; B. henselae (Houston-1), 1.2%; B. henselae (Marseille), 1.8%; B. quintana, 0.2%; and B. vinsonii subsp. vinsonii, 0.0%. Univariate and multivariate analyses of epidemiological and demographical information revealed an increased rate of B. elizabethae seropositivity in blood donors working outdoors, being out in the wild a minimum of once a week, hunting moose, having cat contact, and travelling to Eastern Europe. Living in the southern region of Sweden (Lund area) was associated with decreased seropositivity to B. elizabethae.

Keyword
Animals, Antibodies; Bacterial/*blood, Bartonella/classification/*immunology, Bartonella Infections/*epidemiology/immunology, Bartonella henselae/immunology, Blood Donors, Cats, Cattle, Cricetinae, Dogs, Female, Humans, Male, Research Support; Non-U.S. Gov't, Risk Factors, Seroepidemiologic Studies, Sweden/epidemiology
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-75484 (URN)10.1080/00365540510012152 (DOI)16191889 (PubMedID)
Available from: 2008-04-20 Created: 2008-04-20 Last updated: 2017-12-14Bibliographically approved

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