Bartonella species as a cause of culture-negative endocarditis in South Africa.

Previous reports have highlighted the high prevalence of blood culture negative endocarditis (BCNE) in South Africa. The Tygerberg Endocarditis Cohort (TEC) study is an ongoing prospective cohort study of patients with confirmed or suspected IE presenting to Tygerberg Academic Hospital, Cape Town, South Africa. Current analysis includes patients that presented between November 2019 and August 2020. Forty four (44) patients have been included in this ongoing study. Fourteen of the 44 patients (31.8%) had BCNE. Further analysis of the patients with BCNE identified Bartonella species as the most common causative organism (n=6; 43%). Other causes included Mycoplasma species (n=2). No cause could be identified in 4 of the 44 patients (9%). Bartonella quintana was identified with PCR of valvular tissue as the causative organism in 4 of the 5 patients that underwent urgent surgery. The patients with Bartonella IE (n=6) had an average age of 39 years with equal gender distribution. The common clinical features were clubbing (n=5; 83%), anemia (n=4; 66.6%), haematuria (n=3; 50%), acute on chronic severe regurgitant lesion (n=3; 50%) and acute severe regurgitant lesion (n=2; 33.3%).The aortic valve was involved in 5 of 6 patients. During a mean follow-up period of 251 days after diagnosis, no major adverse events occurred. Bartonella-associated IE is an important cause of BCNE in the Western Cape of South Africa. Imaging findings (in patients with BCNE) of significant valvular destruction with large vegetations on the aortic valve not affected by congenital or rheumatic valve disease should raise the suspicion of Bartonella-associated IE.

Genetic diversity of human head lice and molecular detection of associated bacterial pathogens in Democratic Republic of Congo.

BACKGROUND: Head louse, Pediculus humanus capitis, is an obligatory blood-sucking ectoparasite, distributed worldwide. Phylogenetically, it occurs in five divergent mitochondrial clades (A-E); each exhibiting a particular geographical distribution. Recent studies suggest that, as in the case of body louse, head louse could be a disease vector. We aimed to study the genetic diversity of head lice collected in the Democratic Republic of the Congo (DR Congo) and to screen for louse-borne pathogens in these lice. METHODS: A total of 181 head lice were collected from 27 individuals at the Monkole Hospital Center located in Kinshasa. All head lice were genotyped and screened for the presence of louse-borne bacteria using molecular methods. We searched for Bartonella quintana, Borrelia recurrentis, Rickettsia prowazekii, Anaplasma spp., Yersinia pestis, Coxiella burnetii and Acinetobacter spp. RESULTS: Among these head lice, 67.4% (122/181) belonged to clade A and 24.3% (44/181) belonged to clade D. Additionally, for the first time in this area, we found clade E in 8.3% (15/181) of tested lice, from two infested individuals. Dual infestation with clades A and D was observed for 44.4% individuals. Thirty-three of the 181 head lice were infected only by different bacterial species of the genus Acinetobacter. Overall, 16 out of 27 individuals were infested (59.3%). Six Acinetobacter species were detected including Acinetobacter baumannii (8.3%), Acinetobacter johnsonii (1.7%), Acinetobacter soli (1.7%), Acinetobacter pittii (1.7%), Acinetobacter guillouiae (1.1%), as well as a new potential species named "Candidatus Acinetobacter pediculi". CONCLUSIONS: To our knowledge, this study reports for the first time, the presence of clade E head lice in DR Congo. This study is also the first to report the presence of Acinetobacter species DNAs in human head lice in DR Congo.

Bartonella quintana, past, present, and future of the scourge of World War I.

During World War I, a mysterious new disease affected soldiers on both sides of battle field. The first reports described a relapsing fever of unknown origin with body lice being suggested as the vector. The outbreak affected >1 000 000 people, mostly soldiers fighting in front-line trenches. Shortly afterward, the illness was known as Trench fever, of which the causal infectious agent is currently classified as Bartonella quintana.

Detection of Bartonella spp. in fleas by MALDI-TOF MS.

BACKGROUND: Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) has recently emerged in the field of entomology as a promising method for the identification of arthropods and the detection of associated pathogens. METHODOLOGY/PRINCIPAL FINDINGS: An experimental model of Ctenocephalides felis (cat fleas) infected with Bartonella quintana and Bartonella henselae was developed to evaluate the efficacy of MALDI-TOF MS in distinguishing infected from uninfected fleas, and its ability to distinguish fleas infected with Bartonella quintana from fleas infected with Bartonella henselae. For B. quintana, two groups of fleas received three successive blood meals, infected or not. A total of 140 fleas (100 exposed fleas and 40 control fleas) were engorged on human blood, infected or uninfected with B. quintana. Regarding the second pathogen, two groups of fleas (200 exposed fleas and 40 control fleas) were fed in the same manner with human blood, infected or not with Bartonella henselae. Fleas were dissected longitudinally; one-half was used for assessment of B. quintana and B. henselae infectious status by real-time PCR, and the second half was subjected to MALDI-TOF MS analysis. Comparison of MS spectra from infected fleas and uninfected fleas revealed distinct MS profiles. Blind queries against our MALDI-TOF MS arthropod database, upgraded with reference spectra from B. quintana and B. henselae infected fleas but also non-infected fleas, provided the correct classification for 100% of the different categories of specimens tested on the first model of flea infection with Bartonella quintana. As for Bartonella henselae, 81% of exposed qPCR-positive fleas, 96% of exposed qPCR-negative fleas and 100% of control fleas were correctly identified on the second model of flea infection. MALDI-TOF MS successfully differentiated Bartonella spp.-infected and uninfected fleas and was also able to correctly differentiate fleas infected with Bartonella quintana and fleas infected with Bartonella henselae. MALDI-TOF MS correctly identified flea species as well as their infectious status, consistent with the results of real-time PCR. CONCLUSIONS/SIGNIFICANCE: MALDI-TOF is a promising tool for identification of the infection status of fleas infected with Bartonella spp., which allows new possibilities for fast and accurate diagnosis in medical entomology and vector surveillance.

Rapid, Sensitive Detection of Bartonella quintana by Loop-Mediated Isothermal Amplification of the groEL Gene.

Trench fever, caused by Bartonella quintana, is recognized as a re-emerging and neglected disease. Rapid and sensitive detection approaches are urgently required to monitor and help control B. quintana infections. Here, loop-mediated isothermal amplification (LAMP), which amplifies target DNA at a fixed temperature with high sensitivity, specificity and rapidity, was employed to detect B. quintana. Thirty-six strains, including 10 B. quintana, 13 other Bartonella spp., and 13 other common pathogens, were applied to verify and evaluate the LAMP assay. The specificity of the LAMP assay was 100%, and the limit of detection was 125 fg/reaction. The LAMP assay was compared with qPCR in the examination of 100 rhesus and 20 rhesus-feeder blood samples; the diagnostic accuracy was found to be 100% when LAMP was compared to qPCR, but the LAMP assay was significantly more sensitive (p < 0.05). Thus, LAMP methodology is a useful for diagnosis of trench fever in humans and primates, especially in low-resource settings, because of its rapid, sensitive detection that does not require sophisticated equipment.

A Mixed Outbreak of Epidemic Typhus Fever and Trench Fever in a Youth Rehabilitation Center: Risk Factors for Illness from a Case-Control Study, Rwanda, 2012.

In August 2012, laboratory tests confirmed a mixed outbreak of epidemic typhus fever and trench fever in a male youth rehabilitation center in western Rwanda. Seventy-six suspected cases and 118 controls were enrolled into an unmatched case-control study to identify risk factors for symptomatic illness during the outbreak. A suspected case was fever or history of fever, from April 2012, in a resident of the rehabilitation center. In total, 199 suspected cases from a population of 1,910 male youth (attack rate = 10.4%) with seven deaths (case fatality rate = 3.5%) were reported. After multivariate analysis, history of seeing lice in clothing (adjusted odds ratio [aOR] = 2.6, 95% confidence interval [CI] = 1.1-5.8), delayed (≥ 2 days) washing of clothing (aOR = 4.0, 95% CI = 1.6-9.6), and delayed (≥ 1 month) washing of beddings (aOR = 4.6, 95% CI = 2.0-11) were associated with illness, whereas having stayed in the rehabilitation camp for ≥ 6 months was protective (aOR = 0.20, 95% CI = 0.10-0.40). Stronger surveillance and improvements in hygiene could prevent future outbreaks.

Japanese Macaques (Macaca fuscata) as Natural Reservoir of Bartonella quintana.

Bartonella quintana bacteremia was detected in 6 (13.3%) of 45 wild-caught Japanese macaques (Macaca fuscata). Multilocus sequence typing of the isolates revealed that Japanese macaques were infected with a new and specific B. quintana sequence type. Free-ranging Japanese macaques thus represent another natural reservoir of B. quintana.

Bartonella quintana deploys host and vector temperature-specific transcriptomes.

The bacterial pathogen Bartonella quintana is passed between humans by body lice. B. quintana has adapted to both the human host and body louse vector niches, producing persistent infection with high titer bacterial loads in both the host (up to 10(5) colony-forming units [CFU]/ml) and vector (more than 10(8) CFU/ml). Using a novel custom microarray platform, we analyzed bacterial transcription at temperatures corresponding to the host (37°C) and vector (28°C), to probe for temperature-specific and growth phase-specific transcriptomes. We observed that transcription of 7% (93 genes) of the B. quintana genome is modified in response to change in growth phase, and that 5% (68 genes) of the genome is temperature-responsive. Among these transcriptional changes in response to temperature shift and growth phase was the induction of known B. quintana virulence genes and several previously unannotated genes. Hemin binding proteins, secretion systems, response regulators, and genes for invasion and cell attachment were prominent among the differentially-regulated B. quintana genes. This study represents the first analysis of global transcriptional responses by B. quintana. In addition, the in vivo experiments provide novel insight into the B. quintana transcriptional program within the body louse environment. These data and approaches will facilitate study of the adaptation mechanisms employed by Bartonella during the transition between human host and arthropod vector.

Human louse-transmitted infectious diseases.

Several of the infectious diseases associated with human lice are life-threatening, including epidemic typhus, relapsing fever, and trench fever, which are caused by Rickettsia prowazekii, Borrelia recurrentis, and Bartonella quintana, respectively. Although these diseases have been known for several centuries, they remain a major public health concern in populations living in poor-hygiene conditions because of war, social disruption, severe poverty, or gaps in public health management. Poor-hygiene conditions favour a higher prevalence of body lice, which are the main vectors for these diseases. Trench fever has been reported in both developing and developed countries in populations living in poor conditions, such as homeless individuals. In contrast, outbreaks of epidemic typhus and epidemic relapsing fever have occurred in jails and refugee camps in developing countries. However, reports of a significantly high seroprevalence for epidemic typhus and epidemic relapsing fever in the homeless populations of developed countries suggest that these populations remain at high risk for outbreaks of these diseases. Additionally, experimental laboratory studies have demonstrated that the body louse can transmit other emerging or re-emerging pathogens, such as Acinetobacter baumannii and Yersinia pestis. Therefore, a strict survey of louse-borne diseases and the implementation of efficient delousing strategies in these populations should be public health priorities.

Fatal bacillary angiomatosis mimicking an infiltrative vascular tumour in the immune restoration phase of an HIV-infected patient.

Bacillary angiomatosis mainly affects the HIV-infected population. Information is limited on the evolution of bacillary angiomatosis during immune restoration following initiation of HAART. We report an unusual case of fatal Bartonella quintana bacillary angiomatosis occurring in an HIV-infected man during the immune restoration phase.

Persistence of Bartonella spp. stealth pathogens: from subclinical infections to vasoproliferative tumor formation.

Bartonella spp. are facultative intracellular bacteria that typically cause a long-lasting intraerythrocytic bacteremia in their mammalian reservoir hosts, thereby favoring transmission by blood-sucking arthropods. In most cases, natural reservoir host infections are subclinical and the relapsing intraerythrocytic bacteremia may last weeks, months, or even years. In this review, we will follow the infection cycle of Bartonella spp. in a reservoir host, which typically starts with an intradermal inoculation of bacteria that are superficially scratched into the skin from arthropod feces and terminates with the pathogen exit by the blood-sucking arthropod. The current knowledge of bacterial countermeasures against mammalian immune response will be presented for each critical step of the pathogenesis. The prevailing models of the still-enigmatic primary niche and the anatomical location where bacteria reside, persist, and are periodically seeded into the bloodstream to cause the typical relapsing Bartonella spp. bacteremia will also be critically discussed. The review will end up with a discussion of the ability of Bartonella spp., namely Bartonella henselae, Bartonella quintana, and Bartonella bacilliformis, to induce tumor-like vascular deformations in humans having compromised immune response such as in patients with AIDS.

Trimeric autotransporter adhesin-dependent adherence of Bartonella henselae, Bartonella quintana, and Yersinia enterocolitica to matrix components and endothelial cells under static and dynamic flow conditions.

Trimeric autotransporter adhesins (TAAs) are important virulence factors of Gram-negative bacteria responsible for adherence to extracellular matrix (ECM) and host cells. Here, we analyzed three different TAAs (Bartonella adhesin A [BadA] of Bartonella henselae, variably expressed outer membrane proteins [Vomps] of Bartonella quintana, and Yersinia adhesin A [YadA] of Yersinia enterocolitica) for mediating bacterial adherence to ECM and endothelial cells. Using static (cell culture vials) and dynamic (capillary flow chambers) experimental settings, adherence of wild-type bacteria and of the respective TAA-negative strains was analyzed. Under static conditions, ECM adherence of B. henselae, B. quintana, and Y. enterocolitica was strongly dependent on the expression of their particular TAAs. YadA of Y. enterocolitica did not mediate bacterial binding to plasma or cellular fibronectin under either static or dynamic conditions. TAA-dependent host cell adherence appeared more significant under dynamic conditions although the total number of bound bacteria was diminished compared to the number under static conditions. Dynamic models expand the methodology to perform bacterial adherence experiments under more realistic, bloodstream-like conditions and allow dissection of the biological role of TAAs in ECM and host cell adherence under static and dynamic conditions.

A SacB mutagenesis strategy reveals that the Bartonella quintana variably expressed outer membrane proteins are required for bloodstream infection of the host.

Bartonella bacteria adhere to erythrocytes and persistently infect the mammalian bloodstream. We previously identified four highly conserved Bartonella quintana adhesin genes that undergo phase variation during prolonged bloodstream infection. The variably expressed outer membrane proteins (Vomp) encoded by these genes are members of the trimeric autotransporter adhesin family. Each B. quintana Vomp appears to contribute a different adhesion phenotype, likely mediated by the major variable region at the adhesive tip of each Vomp. Although studies document that the Vomp adhesins confer virulence phenotypes in vitro, little is known about in vivo virulence strategies of Bartonella. We sought to determine whether the B. quintana Vomp adhesins are necessary for infection in vivo by using a vomp null mutant. It first was necessary to develop a system to generate in-frame deletions of defined genes by allelic exchange in a wild-type Bartonella background, which had not been achieved previously. We utilized sacB negative selection to generate a targeted, in-frame, markerless deletion of the entire vomp locus in B. quintana. We also recently developed the first animal model for B. quintana infection, and using this model, we demonstrate here that the deletion of the entire vomp locus, but not the deletion of two vomp genes, results in a null mutant strain that is incapable of establishing bloodstream infection in vivo. The Vomp adhesins therefore represent critical virulence factors in vivo, warranting further study. Finally, our allelic exchange strategy provides an important advance in the genetic manipulation of all Bartonella species and, combined with the animal model that recapitulates human disease, will facilitate pathogenesis studies of B. quintana.

Bartonella quintana variably expressed outer membrane proteins mediate vascular endothelial growth factor secretion but not host cell adherence.

Bartonella quintana causes trench fever, endocarditis, and the vasculoproliferative disorders bacillary angiomatosis and peliosis hepatis in humans. Little is known about the interaction of this pathogen with host cells. We attempted to elucidate the interaction of B. quintana with human macrophages (THP-1) and epithelial cells (HeLa 229). Remarkably, only B. quintana strain JK-31 induced secretion of vascular endothelial growth factor (VEGF) from THP-1 and HeLa 229 cells upon infection similar to the secretion induced by B. henselae Marseille, whereas other strains (B. quintana 2-D70, B. quintana Toulouse, and B. quintana Munich) did not induce such secretion. Immunofluorescence testing and electron microscopy revealed that the B. quintana strains unable to induce VEGF secretion did not express the variable outer membrane proteins (Vomps) on their surfaces. Surprisingly, the increase in VEGF secretion mediated by B. quintana JK-31 was not paralleled by elevated host cell adherence rates compared with the rates for Vomp-negative B. quintana strains. Our results suggest that the Vomps play a leading role in the angiogenic reprogramming of host cells by B. quintana but not in the adherence to host cells.

Localized bacillary angiomatosis in the oral cavity: observations about a neoplasm with atypical behavior. Description of a case and review of the literature.

Bacillary angiomatosis is a rather frequent infectious pathology appearing mainly in the skin but can also affect the liver, spleen, heart, bones, lungs, muscles, central nervous system and other organs. The localization of the lesion in the oral cavity is rather rare, as it is evident in the literature. Bacillary angiomatosis can be clinically similar to the Kaposi's sarcoma and histologically confused with angiosarcoma, epitheloid hemangioma and pyogenic granuloma. A case of bacillary angiomatosis of the oral cavity in an immuno-competent patient is described. The high tendency to relapse, the capability in migration and to involve several localizations at the same time have induced the authors to deepen the research to exclude the possibility that it could be a Kaposi's sarcoma or a pyogenic granuloma and to get to an accurate diagnosis in order to resolve the disease.

Bartonella quintana associated neuroretinitis.

We report an observational case of Bartonella quintana-associated neuroretinitis. The patient had a positive IgM IFA titer for Bartonella quintana early in the disease. After treatment, the neuroretinitis and IgM resolved. Given the patient's history, symptoms, response to treatment, and IgM course, we believe his neuroretinitis was secondary to Bartonella quintana.

Antiangiogenic effect of erythromycin: an in vitro model of Bartonella quintana infection.

BACKGROUND: Bartonella quintana, the etiological agent of bacillary angiomatosis (BA), causes endothelial cell proliferation. Erythromycin has dramatic effects on BA, and the effects are largely unexplained by the compound's bacteriostatic properties. Our aim here was to evaluate the possibility that erythromycin alters angiogenesis. METHODS: The effect of erythromycin on B. quintana-induced endothelial cell proliferation was studied using a wild-type strain and an erythromycin-resistant B. quintana mutant. The latter was generated by serial subcultures on blood agar plates. RESULTS: We show that erythromycin significantly inhibits the proliferation of dermal microvascular endothelial cells induced either by wild-type B. quintana or by our erythromycin-resistant mutant. Doxycycline and gentamycin failed to exert such an effect. Finally, we found that the resistant strain harbored a 27-bp insertion in the highly conserved region of the gene encoding the ribosomal protein L4; this insertion may explain the existence of the resistance to erythromycin. CONCLUSION: The data presented here indicate that erythromycin profoundly down-modulates endothelial cell proliferation irrespective of its bacteriostatic effects and suggest that this may be a key component of the efficacy of the compound in the treatment of patients with BA.

[Detection of the Bartonella DNA by the method of nested PCR in patients after tick bites in Novosibirsk region].

Arthropod-borne bacterial pathogen Bartonella DNA was detected in human blood cells after tick bites in summer 2003 and 2004 in Novosibirsk region by nested PCR with primers specific to groEL gene of HSP60 protein. Comparative assay of 190 p.b. of long PCR fragment revealed that the nucleotide sequences might belong to Bartonella henselae and Bartonella quintana.

Enfermedades producidas por Bartonella spp / Diseases produced by Bartonella

Las bacterias del género Bartonella son responsables de un amplio grupo de enfermedades infecciosas emergentes y reemergentes. Las manifestaciones clínicas varían en dependencia de la especie de Bartonella y de la situación inmunológica del paciente. En las infecciones por Bartonella spp. no existe un tratamiento universalizado, por lo que debe adaptarse a la situación clínica de cada paciente. Al ser responsables de cuadros clínicos potencialmente graves (endocarditis, bacteriemias prolongadas, angiomatosis bacilar, enfermedad de Carrión, etc.), la sospecha clínica, la rapidez con que se realice el diagnóstico y el inicio precoz del tratamiento puede conducir a una evolución favorable (AU)

The genus Bartonella is cause of a broad number of emerging and re-emerging infectious diseases. Clinical manifestations depend on the implicated Bartonella sp. and the immunity of the host. Because there is not a universal therapy for this infection, treatment should be chosen individually. Bartonella sp. is responsible of potentially serious clinical pictures (endocarditis, chronic bacteremia, bacillary angiomatosis, Carrion's disease, etc.), so clinical suspicion, a quickly diagnosis and an early treatment provide a better resolution (AU)

Bartonella quintana-induced apoptosis inhibition of human endothelial cells is associated with p38 and SAPK/JNK modulation and with stimulation of mitosis.

Previous studies demonstrated that live Bartonella quintana often induces angioproliferative lesions in humans. It modulates endothelial cell apoptotic and inflammatory patterns, thus inducing a very early overexpression of caspase 8 and Apaf-1 and increasing mRNA production of TNF-alpha, interleukin-8, and E-selectin. However, starting at 10 hours postinfection, the bacteria provoke antiapoptotic effects that induce an increase of bcl-2 gene transcription. To gain further insight into the cellular mechanisms that regulate apoptosis, survival and proliferation, we studied the modulation of mitogen-activated protein kinase (MAPK) and the activation state of cdc2 kinase, which regulates progression into mitosis. Confocal microscopy findings indicated a maximum rate of Bartonella entry into host cells between postinfection hours 6 and 10. Live bacteria caused substantially higher apoptosis of human umbilical vein endothelial cells-cryopreserved (HUVEC-C) than heat- and trypsin-inactivated microorganisms. During the first 6 hours postinfection, B. quintana triggered a peak of apoptosis, induced activation of p38 MAPK and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), with bacterial clusters appearing at the cellular surface of the HUVEC-C. However, at 8 to 24 hours postinfection, B. quintana was internalized and inhibited proapoptotic signals such as p38 MAPK and SAPK/JNK while inducing antiapoptotic signals. Indeed, expression of the bcl-2 gene and the increase of the bcl-2 kinase active form was concomitant to activation of mitosis, as shown by cdc2 protein activation. These data thus suggest that mechanisms that induce mitotic activity and inhibit apoptotic signals may contribute to the ability of B. quintana to cause vascular proliferation.