The Evolving Biomedical Importance of Bartonella Species Infections

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 86873

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Professor of Internal Medicine, Vector Borne Disease Diagnostics, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA
Interests: animal and human bartonellosis; infectious diseases; immunology; nephrology; vector-transmitted; intracellular pathogens; neuropsychiatric illness and rheumatological presentations
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Dear Colleagues,

The genus Bartonella is comprised of fastidious Gram-negative, slow growing, and facultative intracellular bacteria belonging to the Alpha-2 subgroup of the class Proteobacteria, and the order Rhizobiales. These microorganisms are most often transmitted to humans through animal bites or scratches (cats, dogs, and other animals), by scratch inoculation of infected flea or body louse feces into the skin, and potentially, by bites of other vectors including ants, biting flies, keds, mites, spiders, and ticks. Prior to the HIV epidemic in the early 1990s, Bartonella species were not known to have infected animals or humans in North America or throughout much of the world. Currently, at least 40 Bartonella species or subspecies have been characterize, of which 17 Bartonella species have been implicated in association with zoonotic infections in humans. These bacteria have become globally important, but medically underappreciated emerging pathogens impacting animal and human health. The increasing number of animal reservoir hosts known to be infected with various Bartonella species, in conjunction with the increasing number of competent or suspected arthropod vectors makes this genus of substantial biomedical importance to microbiologists, diagnosticians, physicians, vector biologists, and veterinarians. The spectrum of longstanding, complex cardiovascular, dermatologic, neurological, and rheumatologic disease manifestations make this genus substantially important to patients.

Prof. Dr. Edward B. Breitschwerdt
Guest Editor

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Keywords

  • epidemiology
  • microbiology
  • medicine
  • vector biology
  • animal and human bartonellosis
  • health

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Published Papers (18 papers)

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Research

14 pages, 319 KiB  
Article
Bartonella Endocarditis in Spain: Case Reports of 21 Cases
by Lara García-Álvarez, Concepción García-García, Patricia Muñoz, María del Carmen Fariñas-Álvarez, Manuel Gutiérrez Cuadra, Nuria Fernández-Hidalgo, Elisa García-Vázquez, Encarnación Moral-Escudero, María del Mar Alonso-Socas, Dácil García-Rosado, Carmen Hidalgo-Tenorio, Fernando Domínguez, Josune Goikoetxea-Agirre, Juan Carlos Gainzarain, María Ángeles Rodríguez-Esteban, Xerach Bosch-Guerra, José A. Oteo and On behalf of Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España (GAMES)
Pathogens 2022, 11(5), 561; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11050561 - 10 May 2022
Cited by 11 | Viewed by 3236
Abstract
Blood culture negative endocarditis (BCNE) is frequent in infective endocarditis (IE). One of the causes of BCNE is fastidious microorganisms, such as Bartonella spp. The aim of this study was to describe the epidemiologic, clinical characteristics, management and outcomes of patients with Bartonella [...] Read more.
Blood culture negative endocarditis (BCNE) is frequent in infective endocarditis (IE). One of the causes of BCNE is fastidious microorganisms, such as Bartonella spp. The aim of this study was to describe the epidemiologic, clinical characteristics, management and outcomes of patients with Bartonella IE from the “Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España (GAMES)”cohort. Here we presented 21 cases of Bartonella IE. This represents 0.3% of a total of 5590 cases and 2% of the BCNE from the GAMES cohort. 62% were due to Bartonella henselae and 38% to Bartonella quintana. Cardiac failure was the main presenting form (61.5% in B. hensalae, 87.5% in B. quintana IE) and the aortic valve was affected in 85% of the cases (76% in B. henselae, 100% in B. quintana IE). Typical signs such as fever were recorded in less than 40% of patients. Echocardiography showed vegetations in 92% and 100% of the patients with B. henselae and B. quintana, respectively. Culture was positive only in one patient and the remaining were diagnosed by serology and PCR. PCR was the most useful tool allowing for diagnosis in 16 patients (100% of the studied valves). Serology, at titers recommended by guidelines, only coincided with PCR in 52.4%. Antimicrobial therapy, in different combinations, was used in all cases. Surgery was performed in 76% of the patients. No in-hospital mortality was observed. One-year mortality was 9.4%. This article remarks the importance for investigating the presence of Bartonella infection as causative agent in all BCNE since the diagnosis needs specific microbiological tools and patients could benefit of a specific treatment. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
23 pages, 4141 KiB  
Article
Bartonella henselae Recombinant Pap31 for the Diagnosis of Canine and Human Bartonelloses
by Pradeep Neupane, Ricardo G. Maggi, Manoj Basnet, Erin Lashnits, Gerard P. Andrews and Edward B. Breitschwerdt
Pathogens 2022, 11(2), 182; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11020182 - 28 Jan 2022
Cited by 1 | Viewed by 2674
Abstract
Bartonella spp. comprise a genus of Gram-negative alphaproteobacteria that are slow growing, fastidious, and facultative intracellular pathogens with zoonotic potential. Immunofluorescent antibody assays (IFAs), Western blot (WB), and enzyme-linked immunosorbent assays (ELISAs), the frequently used modalities for the serological diagnosis of canine and [...] Read more.
Bartonella spp. comprise a genus of Gram-negative alphaproteobacteria that are slow growing, fastidious, and facultative intracellular pathogens with zoonotic potential. Immunofluorescent antibody assays (IFAs), Western blot (WB), and enzyme-linked immunosorbent assays (ELISAs), the frequently used modalities for the serological diagnosis of canine and human Bartonelloses, generate numerous false negative results. Therefore, the development of a reliable serodiagnostic assay for Bartonelloses is of clinical and epidemiological importance. Pap31, a heme binding surface protein of B. henselae, is associated with bacterial adhesion and related to bacterial colonization. To our knowledge, B. henselae Pap31 and its fragments (N-terminal (NTD), middle (MD), and C-terminal (CTD) domains) have not been investigated for the serodiagnosis of canine and human Bartonelloses. In this study, we evaluate the diagnostic utility of B. henselae recombinant whole Pap31 (rPap31) and Pap31 fragments by ELISA using sera from 70 dogs (36 Bartonella spp. IFA-positive (naturally infected), and 34 Bartonella spp. IFA- and PCR-negative (control dogs)) and 36 humans (18 Bartonella spp. IFA-positive (naturally infected) and 18 controls)). In the dogs, the area under the curve (AUC) score of recombinant whole Pap31 was 0.714 with a sensitivity of 42% and specificity of 94% at an OD cutoff value of 0.8955. Among the evaluated recombinant Pap31 proteins for the diagnosis of canine Bartonelloses, rPap31-NTD yielded the highest AUC score of 0.792 (95% CI 0.688–0.895) with a sensitivity of 44% and specificity of 100% at a cutoff value of 1.198. In concordance with this finding, rPap31-NTD also had the highest AUC score of 0.747 (95% CI 0.581–0.913) among the Pap31 recombinant proteins for the diagnosis of human Bartonelloses, with 39% sensitivity and 94% specificity at a cutoff value of 1.366. Recombinant whole Pap31 (rPap31) resulted in 72% sensitivity and 61% specificity at a cutoff value of 0.215 for human Bartonelloses. Due to either low sensitivity or questionable specificity, our findings indicate that recombinant Pap31 and the selected fragments may not be appropriate diagnostic targets in detecting anti-Bartonella antibodies in Bartonella-infected dogs and humans. The findings from this study can be used to further assess the antigenicity and immunogenicity of B. henselae Pap31 as a diagnostic target. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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9 pages, 620 KiB  
Article
Misleading Positive Serology for Cat Scratch Disease following Administration of Intravenous Immunoglobulin
by Michal Yakubovsky, Yoav Golan, Alex Guri, Itzhak Levy, Daniel Glikman, Moshe Ephros and Michael Giladi
Pathogens 2022, 11(2), 177; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11020177 - 27 Jan 2022
Cited by 1 | Viewed by 2629
Abstract
Cat scratch disease (CSD), caused by Bartonella henselae, usually presents as regional lymphadenopathy/lymphadenitis, known as typical CSD or as atypical CSD, which includes, among others, neurological manifestations. Serology for anti-B. henselae IgG antibodies is the most commonly used diagnostic tests for [...] Read more.
Cat scratch disease (CSD), caused by Bartonella henselae, usually presents as regional lymphadenopathy/lymphadenitis, known as typical CSD or as atypical CSD, which includes, among others, neurological manifestations. Serology for anti-B. henselae IgG antibodies is the most commonly used diagnostic tests for CSD. Intravenous immunoglobulin (IVIG) is given for an increasing number of medical conditions and may cause interference with serological testing. We report six patients with neurological manifestations and two patients with Kawasaki disease mimicking typical CSD, mistakenly diagnosed as CSD due to false-positive serology following IVIG therapy. Bartonella IgG serology was positive one to six days after IVIG administration and reverted to negative in seven of eight patients or significantly decreased (1 patient) ≤30 days later. In patients with CSD, IgG titers remained essentially unchanged 15–78 days after the positive serum sample. An additional eight patients treated with IVIG for various conditions were evaluated prospectively. All were seronegative one day pre-IVIG infusion, five patients demonstrated an increase in the IgG titers one to three days after IVIG administration, one interpreted as positive and four as intermediate, whereas three patients remained seronegative, suggesting that false seropositivity after IVIG therapy may not occur in all patients. Treatment with IVIG can result in false-positive serology for B. henselae. Increased awareness to the misleading impact of IVIG is warranted to avoid misinterpretation. Repeat testing can distinguish between true and false serology. Preserving serum samples prior to IVIG administration is suggested. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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21 pages, 5285 KiB  
Article
Development of a Multiplex Droplet Digital PCR Assay for the Detection of Babesia, Bartonella, and Borrelia Species
by Ricardo Maggi, Edward B. Breitschwerdt, Barbara Qurollo and Jennifer C. Miller
Pathogens 2021, 10(11), 1462; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10111462 - 11 Nov 2021
Cited by 9 | Viewed by 5430
Abstract
We describe the development, optimization, and validation of a multiplex droplet digital PCR (ddPCR) assay for the simultaneous detection of Babesia, Bartonella, and Borrelia spp. DNA from several sample matrices, including clinical blood samples from animals and humans, vectors, in-vitro infected [...] Read more.
We describe the development, optimization, and validation of a multiplex droplet digital PCR (ddPCR) assay for the simultaneous detection of Babesia, Bartonella, and Borrelia spp. DNA from several sample matrices, including clinical blood samples from animals and humans, vectors, in-vitro infected human and animal cell lines, and tissues obtained from animal models (infected with Bartonella and/or B. burgdorferi). The multiplex ddPCR assay was able to detect 31 Bartonella, 13 Borrelia, and 24 Babesia species, including Theileria equi, T. cervi, and Cytauxzoon felis. No amplification of Treponema or Leptospira spp. was observed. Sensitivity of 0.2–5 genome equivalent DNA copies per microliter was achieved for different members of the Bartonella and Borrelia genus, depending on the species or matrix type (water or spiked blood DNA) tested. The ddPCR assay facilitated the simultaneous detection of co-infections with two and three vector-borne pathogens comprising four different genera (Babesia, Bartonella, Borrelia, and Theileria) from clinical and other sample sources. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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9 pages, 6286 KiB  
Article
Biomolecular Investigation of Bartonella spp. in Wild Rodents of Two Swiss Regions
by Sara Divari, Marta Danelli, Paola Pregel, Giovanni Ghielmetti, Nicole Borel and Enrico Bollo
Pathogens 2021, 10(10), 1331; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10101331 - 15 Oct 2021
Cited by 4 | Viewed by 1732
Abstract
Rodents represent a natural reservoir of several Bartonella species, including zoonotic ones. In this study, small wild rodents, collected from two sites in rural areas of Switzerland, were screened for Bartonella spp. using molecular detection methods. In brief, 346 rodents were trapped in [...] Read more.
Rodents represent a natural reservoir of several Bartonella species, including zoonotic ones. In this study, small wild rodents, collected from two sites in rural areas of Switzerland, were screened for Bartonella spp. using molecular detection methods. In brief, 346 rodents were trapped in two rural sites in the Gantrisch Nature Park of Switzerland (Plasselb, canton of Fribourg, and Riggisberg, canton of Bern). Pools of DNA originating from three animals were tested through a qPCR screening and an end-point PCR, amplifying the 16S-23S rRNA gene intergenic transcribed spacer region and citrate synthase (gltA) loci, respectively. Subsequently, DNA was extracted from spleen samples belonging to single animals of gltA positive pools, and gltA and RNA polymerase subunit beta (rpoB) were detected by end-point PCR. Based on PCR results and sequencing, the prevalence of infection with Bartonella spp. in captured rodents, was 21.10% (73/346): 31.78% in Apodemus sp. (41/129), 10.47% in Arvicola scherman (9/86), 17.05% in Myodes glareolus (22/129), and 50% in Microtus agrestis (1/2). A significant association was observed between Bartonella spp. infection and rodent species (p < 0.01) and between trapping regions and positivity to Bartonella spp. infection (p < 0.001). Similarly, prevalence of Bartonella DNA was higher (p < 0.001) in rodents trapped in woodland areas (66/257, 25.68%) compared to those captured in open fields (9/89, 10.11%). Sequencing and phylogenetic analysis demonstrated that the extracted Bartonella DNA belonged mainly to B. taylorii and also to Candidatus “Bartonella rudakovii”, B. grahamii, B. doshiae, and B. birtlesii. In conclusion, the present study could rise public health issues regarding Bartonella infection in rodents in Switzerland. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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9 pages, 268 KiB  
Article
Seroprevalence of Bartonella henselae and Bartonella quintana Infection and Impact of Related Risk Factors in People from Eastern Slovakia
by Katarína Petríková, Monika Halánová, Ingrid Babinská, Mariia Logoida, Karin Kaliariková, Peter Jarčuška, Sylvia Dražilová, Vladimíra Sobolová and Martin Janičko
Pathogens 2021, 10(10), 1261; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10101261 - 29 Sep 2021
Cited by 3 | Viewed by 1717
Abstract
The genus Bartonella is a rapidly expanding group of ubiquitous bacteria that occur mainly in different animal species, but some can also be transmitted to humans. Three species, B. henselae, B. bacilliformis, and B. quintana, are responsible for the majority [...] Read more.
The genus Bartonella is a rapidly expanding group of ubiquitous bacteria that occur mainly in different animal species, but some can also be transmitted to humans. Three species, B. henselae, B. bacilliformis, and B. quintana, are responsible for the majority of human cases. The severity of the clinical symptoms often depends on the immune status of the patient, but others factors such as the species of the pathogen, virulence factors, and bacterial load also can play an important role. As the information on the occurrence of bartonellosis in the human population in Slovakia is absent, the aim of our pilot study was to determine the seroprevalence against B. henselae and B. quintana in the population of people living in Eastern Slovakia, and to identify the impact of related risk factors. Of 536 people included in the study, 126 (23.5%) showed positivity for anti-B. henselae antibodies and 133 (24.8%) against B. quintana. A statistically higher prevalence was confirmed only in the case of B. quintana in women regardless of the risk group. In analyzing the risk factors, we found significant differences between B. henselae seropositive and seronegative groups only in uric acid levels and serum creatinine, both, however, clinically irrelevant. Significant, but clinically irrelevant differences were observed also in alanine aminotransferase (ALT) levels and creatinine in people seropositive to B. quintana. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
17 pages, 2131 KiB  
Article
Prevalence of Vector-Borne Pathogens in Reproductive and Non-Reproductive Tissue Samples from Free-Roaming Domestic Cats in the South Atlantic USA
by Charlotte Manvell, Kelli Ferris, Ricardo Maggi, Edward B. Breitschwerdt and Erin Lashnits
Pathogens 2021, 10(9), 1221; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10091221 - 21 Sep 2021
Cited by 8 | Viewed by 2434
Abstract
Reservoir to multiple species of zoonotic pathogens, free-roaming cats (FRCs) interact with domestic and wild animals, vectors, and humans. To assess the potential for feline vector-borne pathogens to be vertically transmitted, this study surveyed ear tip and reproductive tissues of FRCs from two [...] Read more.
Reservoir to multiple species of zoonotic pathogens, free-roaming cats (FRCs) interact with domestic and wild animals, vectors, and humans. To assess the potential for feline vector-borne pathogens to be vertically transmitted, this study surveyed ear tip and reproductive tissues of FRCs from two locations in the South Atlantic United States for Anaplasma, Bartonella, Ehrlichia, hemotropic Mycoplasma, and Rickettsia species. We collected ovary (n = 72), uterus (n = 54), testicle (n = 74), and ear tip (n = 73) tissue from 73 cats, and fetal (n = 20) and placental (n = 19) tissue from 11 queens. Pathogen DNA was amplified utilizing qPCR, confirmed by sequencing. Cats were more frequently Bartonella henselae positive on reproductive tissues (19%, 14/73) than ear tip (5%, 4/73; p = 0.02). B. henselae was amplified from fetus (20%, 4/20) and placenta samples (11%, 2/19). Bartonella spp. infection was more common in cats from North Carolina (76%, 26/34) than Virginia (13%, 5/39; p < 0.0001). Fourteen percent (10/73) of both ear tip and reproductive tissues were positive for hemotropic Mycoplasma spp. Anaplasma, Ehrlichia, and Rickettsia spp. DNA was not amplified from any cat/tissue. These findings suggest that B. henselae preferentially infected cats’ reproductive tissue and reinforces the importance of investigating the potential for B. henselae vertical transmission or induction of reproductive failure. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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10 pages, 1070 KiB  
Article
Bartonella Infections in Cats and Cat Fleas in Lithuania
by Miglė Razgūnaitė, Indrė Lipatova, Algimantas Paulauskas, Birutė Karvelienė, Vita Riškevičienė and Jana Radzijevskaja
Pathogens 2021, 10(9), 1209; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10091209 - 17 Sep 2021
Cited by 8 | Viewed by 2451
Abstract
Bartonella are vector-borne parasitic bacteria that cause zoonotic infections in humans. One of the most common infections is cat-scratch disease caused by Bartonella henselae and Bartonella clarridgeiae. Cats are the major reservoir for these two species of bacteria, while cat fleas are [...] Read more.
Bartonella are vector-borne parasitic bacteria that cause zoonotic infections in humans. One of the most common infections is cat-scratch disease caused by Bartonella henselae and Bartonella clarridgeiae. Cats are the major reservoir for these two species of bacteria, while cat fleas are vectors for the transmission of infection agents among cats. The aim of the present study was to investigate the presence of Bartonella infections in stray and pet cats and in cat fleas in Lithuania. Blood samples were taken from 163 cats presented in pet clinics and animal shelters. A total of 102 fleas representing two species, Ctenocephalides felis and Ctenocephalides canis, were collected from 12 owned cats that live both outdoors and indoors. Bartonella DNA in samples was detected using a nested PCR targeting the 16S–23S rRNA intergenic spacer (ITS) region. Bartonella DNA was detected in 4.9% (8/163) of the cats and 29.4% (30/102) of the fleas. Sequence analysis of the ITS region showed that the cats and fleas were infected with B. henselae, B. clarridgeiae and Bartonella sp., closely related to B. schoenbuchensis. This study is the first report on the prevalence and molecular characterization of Bartonella spp. in cats and cat fleas in Lithuania. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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13 pages, 2463 KiB  
Article
Immunogenic Peptides from Pap31 and SCS-α of Bartonella bacilliformis: One Step Closer to a Rapid Diagnostic Tool for Carrion’s Disease
by Cláudia Gomes, Maria J. Pons, Juana del Valle-Mendoza, Mayumi Matsuoka and Joaquim Ruiz
Pathogens 2021, 10(8), 917; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10080917 - 21 Jul 2021
Cited by 3 | Viewed by 2126
Abstract
Bartonella bacilliformis is the causal agent of Carrion’s disease, an overlooked illness endemic in the Andean Mountains with Peru being the most affected country. The diagnostic of this illness is a challenge due to the limited resources and the common symptomatology with other [...] Read more.
Bartonella bacilliformis is the causal agent of Carrion’s disease, an overlooked illness endemic in the Andean Mountains with Peru being the most affected country. The diagnostic of this illness is a challenge due to the limited resources and the common symptomatology with other infectious diseases. The goal of this study was to identify immunogenic peptides from Pap31 and succinyl-CoA synthetase α (SCS-α) of B. bacilliformis that might be suitable for developing a serologic tool. The immunodominant character of Pap31 and SCS-α was determined by Western blotting and in-silico analysis. Subsequently, 35 peptides were selected for epitope mapping and their immunoreactivity was tested by enzyme-linked immunosorbent assay (ELISA). A total of 30 sera were tested including pre-exposed people with high IgM levels for Pap31/SCS-α (23 sera), patients (2 sera) as well as 5 sera with no reactivity to Pap31/SCS-α. The results indicate that Pap31-8 (187QAIGSAILKGTKDTGT202) and SCS-α-12 (59IFASVAEGKEKTGANA74) are the most immunogenic peptides, with Pap31-8 showing potential to discriminate between B. bacilliformis and the remaining Bartonella spp., and SCS-α-12 differentiating Bartonella spp. from other microorganisms. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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10 pages, 1265 KiB  
Article
Molecular Characterization of Fluoroquinolone-Resistant Bartonella bacilliformis
by Giovanna Mendoza-Mujica, Diana Flores-León and Joaquim Ruiz
Pathogens 2021, 10(7), 876; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10070876 - 10 Jul 2021
Cited by 2 | Viewed by 2212
Abstract
The presence of amino acid changes in GyrA, GyrB, ParC, ParE, and in a proposed chromosomal chloramphenicol acetyl transferase (CAT), as well as mutations at 23S rRNA, were established by PCR and sequencing in 38 B. bacilliformis clinical isolates from four different [...] Read more.
The presence of amino acid changes in GyrA, GyrB, ParC, ParE, and in a proposed chromosomal chloramphenicol acetyl transferase (CAT), as well as mutations at 23S rRNA, were established by PCR and sequencing in 38 B. bacilliformis clinical isolates from four different areas in Peru. Eighteen out of 24 (75%) isolates showing ciprofloxacin resistance for both disk-diffusion and e-test presented amino acid substitutions in GyrA (G89C, six isolates, A91V, 1 isolate) GyrB (S474F, 10 isolates) or both (GyrA D95N and GyrB S474F, one isolate). Two out of 14 susceptible isolates presented amino acid substitutions at GyrB (S474F) or a double substitution GyrA D95N and GyrB S474F. Of note, ciprofloxacin-resistant isolates were recovered in the four areas studied. No amino acid change was observed at ParC or ParE. Only one isolate showed chloramphenicol resistance, but no alteration was present in either 23S rRNA or CAT. B. bacilliformis resistant to quinolones are extended throughout Peru, with amino acid substitutions at GyrA or GyrB as the main, albeit not exclusive, cause. B. bacilliformis seems to have an apparent facility to develop mutations on GyrB outside the classical positions 91, 95 of GyrA and 85, 88 of ParC. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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18 pages, 496 KiB  
Article
Comparison of Serological and Molecular Assays for Bartonella Species in Dogs with Hemangiosarcoma
by Erin Lashnits, Pradeep Neupane, Julie M. Bradley, Toni Richardson, Ricardo G. Maggi and Edward B. Breitschwerdt
Pathogens 2021, 10(7), 794; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10070794 - 23 Jun 2021
Cited by 9 | Viewed by 4072
Abstract
Currently, a gold standard diagnostic test for Bartonella infection in dogs is lacking. This represents a critical limitation for the development and evaluation of new diagnostic tests, as well as for the diagnosis of, and research on, bartonellosis in dogs. This retrospective observational [...] Read more.
Currently, a gold standard diagnostic test for Bartonella infection in dogs is lacking. This represents a critical limitation for the development and evaluation of new diagnostic tests, as well as for the diagnosis of, and research on, bartonellosis in dogs. This retrospective observational study aims to compare the results of commonly performed and newly-reported Bartonella spp. diagnostic tests in banked clinical specimens from 90 dogs with hemangiosarcoma (HSA) using composite reference standard (CRS) and random effects latent class analysis (RE-LCA) techniques. Samples from each dog were tested using six serological or molecular diagnostic assays, including indirect fluorescent antibody (IFA) and Western blot (WB) for the detection of antibodies in serum, and qPCR and droplet digital PCR (ddPCR) in blood and fresh frozen tissue biopsy samples (mainly splenic HSA tumors and histopathologically normal spleen or skin/adipose tissue). Bartonella infection prevalence was estimated to be 78% based on the CRS (parallel testing with all six assays), and 64% based on the RE-LCA model. The assay with the highest diagnostic accuracy was qPCR performed on fresh frozen tissue biopsy samples (sensitivity: 94% by RE-LCA and 80% by CRS; specificity: 100%). When comparing newly-reported to traditional Bartonella diagnostic assays, ddPCR was more sensitive for the detection of Bartonella DNA than qPCR when testing blood samples (36% vs. 0%, p < 0.0001). Dogs that were positive on serological assays alone with negative molecular assays were highly unlikely (<3%) to be classified as infected by the RE-LCA model. These data indicate that Bartonella spp. DNA can be PCR amplified from fresh frozen tissues from a majority of dogs with HSA using both qPCR and ddPCR, supporting the use of these methods for future controlled studies comparing the prevalence of Bartonella spp. DNA in the tissue of dogs with HSA to that of unaffected controls. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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14 pages, 2708 KiB  
Article
Antibiotic Susceptibility of Bartonella Grown in Different Culture Conditions
by Shiva Kumar Goud Gadila and Monica E. Embers
Pathogens 2021, 10(6), 718; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10060718 - 08 Jun 2021
Cited by 4 | Viewed by 9068
Abstract
Bartonellosis is caused by a Gram-negative intracellular bacterium with a zoonotic transmission. The disease, caused by any of several genospecies of Bartonella can range from a benign, self-limited condition to a highly morbid and life-threatening illness. The current standard of care antibiotics are [...] Read more.
Bartonellosis is caused by a Gram-negative intracellular bacterium with a zoonotic transmission. The disease, caused by any of several genospecies of Bartonella can range from a benign, self-limited condition to a highly morbid and life-threatening illness. The current standard of care antibiotics are generally effective in acute infection; these include azithromycin or erythromycin, doxycycline, gentamicin, rifampin, and ciprofloxacin. However, treatment of chronic infection remains problematic. We tested six different antibiotics for their ability to stop the growth of Bartonella sp. in the standard insect media and in an enrichment media. All antibiotics (ceftriaxone, doxycycline, gentamycin, azithromycin, ampicillin, and azlocillin) had minimum inhibitory concentrations (MICs) below 0.5 µg/mL in the BAPGM enrichment media but were ineffective at inhibiting growth when the standard insect media was used. Azlocillin was the most potent, with a MIC of 0.01 µg/mL. When Bartonella was tested under intracellular growth conditions, none of the antibiotics were efficacious singly. However, growth inhibition was observed when azlocillin and azithromycin were combined. These studies illustrate the impact of growth medium and intracellular environment on antibiotic susceptibility testing and indicate that azlocillin combined with azithromycin may be an effective drug combination for the treatment of Bartonellosis. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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10 pages, 3047 KiB  
Article
Molecular Detection of Bartonella quintana among Long-Tailed Macaques (Macaca fascicularis) in Thailand
by Wanat Sricharern, Supakarn Kaewchot, Phirabhat Saengsawang, Sarawan Kaewmongkol and Tawin Inpankaew
Pathogens 2021, 10(5), 629; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10050629 - 19 May 2021
Viewed by 2121
Abstract
Bartonella quintana is a zoonotic pathogen with a worldwide distribution. Humans and non-human primates are considered to be natural reservoir hosts for B. quintana. However, information on the molecular epidemiology of this organism is very limited in regard to long-tailed macaques (Macaca [...] Read more.
Bartonella quintana is a zoonotic pathogen with a worldwide distribution. Humans and non-human primates are considered to be natural reservoir hosts for B. quintana. However, information on the molecular epidemiology of this organism is very limited in regard to long-tailed macaques (Macaca fascicularis) in Thailand. Therefore, this study aimed to investigate the occurrence and genetic diversity of Bartonella spp. among long-tailed macaques in Thailand. In total, 856 blood samples were collected from long-tailed macaques in Thailand. All specimens were screened for Bartonella spp. using a polymerase chain reaction (PCR) assay targeting the 16S rRNA, gltA and ftsZ genes. All positive samples were further analyzed based on nucleotide sequencing, phylogenetic analysis and multiple sequence alignment analysis. Only one macaque showed a positive result in the PCR assays based on the 16S rRNA, gltA and ftsZ genes. Nucleotide sequencing and phylogenetic analysis revealed that the obtained sequences were closely related to B. quintana previously detected in non-human primates. Single-nucleotide polymorphisms (SNPs) were detected in the gltA and ftsZ gene sequences. This study revealed that long-tailed macaques in Thailand carried B. quintana. Despite the low infection rate detected, long-tailed macaques may be a reservoir of B. quintana. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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16 pages, 3343 KiB  
Article
Molecular Detection of Bartonella spp. and Hematological Evaluation in Domestic Cats and Dogs from Bangkok, Thailand
by Phirabhat Saengsawang, Gunn Kaewmongkol and Tawin Inpankaew
Pathogens 2021, 10(5), 503; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10050503 - 22 Apr 2021
Cited by 15 | Viewed by 2964
Abstract
(1) Background: Bartonella spp. are Gram-negative, facultative, intracellular bacteria transmitted by hematophagous insects. Several species cause zoonotic diseases such as cat-scratch disease. Bartonella henselae and Bartonella clarridgeiae are the main species found in Thailand, however, there have been few studies on Bartonella spp. [...] Read more.
(1) Background: Bartonella spp. are Gram-negative, facultative, intracellular bacteria transmitted by hematophagous insects. Several species cause zoonotic diseases such as cat-scratch disease. Bartonella henselae and Bartonella clarridgeiae are the main species found in Thailand, however, there have been few studies on Bartonella spp. In addition, the hematological evaluation of Bartonella-infected animals is limited in Thailand. The aims of this study were prevalence investigation and hematological evaluation of Bartonella-infected dogs and cats residing in Bangkok, Thailand. (2) Methods: In total, 295 dogs and 513 cats were molecularly evaluated to detect Bartonella spp. using PCR with primers targeting the partial gltA, rpoB, ftsZ, ribC, and groEL genes. In total, 651 domestic animals were evaluated for hematological parameters compared between Bartonella-positive and Bartonella-negative animals. (3) Results: Overall, the prevalence of Bartonella spp. was 1.61% which was found only in free-ranging cats (2.83%). Bartonella henselae and B. clarridgeiae were confirmed from a concatenated phylogenetic tree of partial gltA and ribC genes, with 100% bootstrapping replication. For other housekeeping gene sequences, mixed infection was expected from the amplicons of rpoB, ftsZ, and groEL. Importantly, the mean corpuscular volume (MCV) was significantly increased in Bartonella-positive cats. (4) Conclusions: We suggest that B. henselae and B. clarridgeiae are important species and are still circulating in domestic animals, especially cats. The evaluation of blood parameters, especially a raised MCV, should be of concern in Bartonella infection in asymptomatic cats. Additionally, the knowledge of how to prevent Bartonella-related diseases should be promoted with people in at-risk situations. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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12 pages, 1171 KiB  
Article
Exposure of Domestic Cats to Three Zoonotic Bartonella Species in the United States
by Lynn M. Osikowicz, Kalanthe Horiuchi, Irina Goodrich, Edward B. Breitschwerdt, Bruno Chomel, Brad J. Biggerstaff and Michael Kosoy
Pathogens 2021, 10(3), 354; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10030354 - 17 Mar 2021
Cited by 6 | Viewed by 1913
Abstract
Cat-associated Bartonella species, which include B. henselae, B. koehlerae, and B. clarridgeiae, can cause mild to severe illness in humans. In the present study, we evaluated 1362 serum samples obtained from domestic cats across the U.S. for seroreactivity against three species [...] Read more.
Cat-associated Bartonella species, which include B. henselae, B. koehlerae, and B. clarridgeiae, can cause mild to severe illness in humans. In the present study, we evaluated 1362 serum samples obtained from domestic cats across the U.S. for seroreactivity against three species and two strain types of Bartonella associated with cats (B. henselae type 1, B. henselae type 2, B. koehlerae, and B. clarridgeiae) using an indirect immunofluorescent assay (IFA). Overall, the seroprevalence at the cutoff titer level of ≥1:64 was 23.1%. Seroreactivity was 11.1% and 3.7% at the titer level cutoff of ≥1:128 and at the cutoff of ≥1:256, respectively. The highest observation of seroreactivity occurred in the East South-Central, South Atlantic, West North-Central, and West South-Central regions. The lowest seroreactivity was detected in the East North-Central, Middle Atlantic, Mountain, New England, and Pacific regions. We observed reactivity against all four Bartonella spp. antigens in samples from eight out of the nine U.S. geographic regions. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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11 pages, 5571 KiB  
Article
Bartonella henselae Antibodies in Serum and Oral Fluid Specimens from Cats
by Alejandra Álvarez-Fernández, Marta Baxarias, David Prandi, Edward B. Breitschwerdt and Laia Solano-Gallego
Pathogens 2021, 10(3), 329; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10030329 - 11 Mar 2021
Cited by 7 | Viewed by 2688
Abstract
Cats are the primary reservoir host for Bartonella henselae(B. henselae), an etiological agent of human bartonellosis, including cat scratch disease. Although Bartonella DNA has been amplified from salivary swabs from cats, dogs and humans, we are not aware of studies investigating [...] Read more.
Cats are the primary reservoir host for Bartonella henselae(B. henselae), an etiological agent of human bartonellosis, including cat scratch disease. Although Bartonella DNA has been amplified from salivary swabs from cats, dogs and humans, we are not aware of studies investigating Bartonella antibodies in oral fluid (OF). Using inhouse and commercial immunofluorescence antibody assays (IFA), the objective of this study was to detect and compare antibodies against B. henselae in paired OF and serum specimens from cats. Specimens were collected from shelter and client-owned cats. For serum specimens, B. henselae seroreactivity was 78% for both the inhouse and commercial IFA assays and 56.8% for OF specimens. Comparing serum and OF specimens, there was moderate Kappa agreement (Cohen’s k = 0.434) for detection of B. henselae antibodies. Oral fluid antibodies were more likely measurable in cats with high B. henselae serum antibody titers when compared with low antibody titers. In conclusion, B. henselae OF IFA antibody measurements were less sensitive compared to serum IFA measurements of ≥1:64. Oral fluid antibodies were detected more often in cats with high B. henselae serum antibody titers. Therefore, OF antibodies, detectable by IFA, is of limited utility for epidemiological or diagnostic testing in cats. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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15 pages, 2214 KiB  
Article
Bartonella henselae Detected in Malignant Melanoma, a Preliminary Study
by Marna E. Ericson, Edward B. Breitschwerdt, Paul Reicherter, Cole Maxwell, Ricardo G. Maggi, Richard G. Melvin, Azar H. Maluki, Julie M. Bradley, Jennifer C. Miller, Glenn E. Simmons, Jr., Jamie Dencklau, Keaton Joppru, Jack Peterson, Will Bae, Janet Scanlon and Lynne T. Bemis
Pathogens 2021, 10(3), 326; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10030326 - 10 Mar 2021
Cited by 9 | Viewed by 5259
Abstract
Bartonella bacilliformis (B. bacilliformis), Bartonella henselae (B. henselae), and Bartonella quintana (B. quintana) are bacteria known to cause verruga peruana or bacillary angiomatosis, vascular endothelial growth factor (VEGF)-dependent cutaneous lesions in humans. Given the bacteria’s association with the dermal niche and [...] Read more.
Bartonella bacilliformis (B. bacilliformis), Bartonella henselae (B. henselae), and Bartonella quintana (B. quintana) are bacteria known to cause verruga peruana or bacillary angiomatosis, vascular endothelial growth factor (VEGF)-dependent cutaneous lesions in humans. Given the bacteria’s association with the dermal niche and clinical suspicion of occult infection by a dermatologist, we determined if patients with melanoma had evidence of Bartonella spp. infection. Within a one-month period, eight patients previously diagnosed with melanoma volunteered to be tested for evidence of Bartonella spp. exposure/infection. Subsequently, confocal immunohistochemistry and PCR for Bartonella spp. were used to study melanoma tissues from two patients. Blood from seven of the eight patients was either seroreactive, PCR positive, or positive by both modalities for Bartonella spp. exposure. Subsequently, Bartonella organisms that co-localized with VEGFC immunoreactivity were visualized using multi-immunostaining confocal microscopy of thick skin sections from two patients. Using a co-culture model, B. henselae was observed to enter melanoma cell cytoplasm and resulted in increased vascular endothelial growth factor C (VEGFC) and interleukin 8 (IL-8) production. Findings from this small number of patients support the need for future investigations to determine the extent to which Bartonella spp. are a component of the melanoma pathobiome. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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19 pages, 4291 KiB  
Article
Bartonella Associated Cutaneous Lesions (BACL) in People with Neuropsychiatric Symptoms
by Edward B. Breitschwerdt, Julie M. Bradley, Ricardo G. Maggi, Erin Lashnits and Paul Reicherter
Pathogens 2020, 9(12), 1023; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9121023 - 04 Dec 2020
Cited by 22 | Viewed by 28922
Abstract
Bartonella species are globally important emerging pathogens that were not known to infect animals or humans in North America prior to the human immunodeficiency virus (HIV) epidemic. Ongoing improvements in diagnostic testing modalities have allowed for the discovery of Bartonella species (spp.) DNA [...] Read more.
Bartonella species are globally important emerging pathogens that were not known to infect animals or humans in North America prior to the human immunodeficiency virus (HIV) epidemic. Ongoing improvements in diagnostic testing modalities have allowed for the discovery of Bartonella species (spp.) DNA in blood; cerebrospinal fluid; and the skin of patients with cutaneous lesions, fatigue, myalgia, and neurological symptoms. We describe Bartonella spp. test results for participants reporting neuropsychiatric symptoms, the majority of whom reported the concurrent development of cutaneous lesions. Study participants completed a medical history, a risk factor questionnaire, and provided cutaneous lesion photographs. Bartonella spp. serology and Bartonella alpha proteobacteria enrichment blood culture/PCR were assessed. Within a 14-month period, 33 participants enrolled; 29/33 had serological and/or PCR evidence supporting Bartonella spp. infection, of whom 24 reported concurrent cutaneous lesions since neuropsychiatric symptom onset. We conclude that cutaneous lesions were common among people reporting neuropsychiatric symptoms and Bartonella spp. infection or exposure. Additional studies, using sensitive microbiological and imaging techniques, are needed to determine if, or to what extent, Bartonella spp. might contribute to cutaneous lesions and neuropsychiatric symptoms in patients. Full article
(This article belongs to the Special Issue The Evolving Biomedical Importance of Bartonella Species Infections)
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