The dynamics between limited-term and lifelong coinfecting bacterial parasites in wild rodent hosts.

Interactions between coinfecting parasites may take various forms, either direct or indirect, facilitative or competitive, and may be mediated by either bottom-up or top-down mechanisms. Although each form of interaction leads to different evolutionary and ecological outcomes, it is challenging to tease them apart throughout the infection period. To establish the first step towards a mechanistic understanding of the interactions between coinfecting limited-term bacterial parasites and lifelong bacterial parasites, we studied the coinfection of Bartonella sp. (limited-term) and Mycoplasma sp. (lifelong), which commonly co-occur in wild rodents. We infected Bartonella- and Mycoplasma-free rodents with each species, and simultaneously with both, and quantified the infection dynamics and host responses. Bartonella benefited from the interaction; its infection load decreased more slowly in coinfected rodents than in rodents infected with Bartonella alone. There were no indications for bottom-up effects, but coinfected rodents experienced various changes, depending on the infection stage, in their body mass, stress levels and activity pattern, which may further affect bacterial replication and transmission. Interestingly, the infection dynamics and changes in the average coinfected rodent traits were more similar to the chronic effects of Mycoplasma infection, whereas coinfection uniquely impaired the host's physiological and behavioral stability. These results suggest that parasites with distinct life history strategies may interact, and their interaction may be asymmetric, non-additive, multifaceted and dynamic through time. Because multiple, sometimes contrasting, forms of interactions are simultaneously at play and their relative importance alternates throughout the course of infection, the overall outcome may change under different ecological conditions.

Necrotizing interstitial pneumonia and suppurative myocarditis associated with Bartonella henselae infection in three Florida pumas.

Three Florida pumas ( Puma concolor coryi) that had spent time in captivity prior to being released in the wild were found exhibiting respiratory signs and reluctance to move. All 3 pumas died shortly after immobilization, despite supportive veterinary care. Significant autopsy findings included necrotizing interstitial pneumonia, with pulmonary edema and hyaline membranes, and suppurative myocarditis. Organisms morphologically consistent with Bartonella henselae were identified in intravascular histiocytes in the lung of one of the pumas on histopathology and confirmed via transmission electron microscopy. B. henselae was detected in fresh lung tissue and confirmed by PCR and sequence analysis (16S-23S spacer region, pap31, and rpoB genes) from one of the affected pumas. In all affected pumas, B. henselae was detected by PCR in formalin-fixed, paraffin-embedded lung tissue, and positively staining organisms were identified in sections of lung by immunohistochemistry for B. henselae. In situ hybridization detected B. henselae DNA in lung tissue from 2 of 3 affected pumas. Our case series suggests that B. henselae can be associated with a fatal disease syndrome in Florida pumas. The cause of susceptibility to fatal disease associated with B. henselae infection in these pumas remains unknown.

Rheumatological presentation of Bartonella koehlerae and Bartonella henselae bacteremias: A case report.

INTRODUCTION: Systemic Bartonella spp. infections are being increasingly reported in association with complex medical presentations. Individuals with frequent arthropod exposures or animal contact appear to be at risk for acquiring long standing infections with Bartonella spp. CASE REPORT: This case report describes infections with Bartonella koehlerae and Bartonella henselae in a female veterinarian whose symptoms were predominantly rheumatologic in nature. Infection was confirmed by serology, polymerase chain reaction (PCR), enrichment blood culture, and DNA sequencing of amplified B koehlerae and B henselae DNA. Long-term medical management with antibiotics was required to achieve elimination of these infections and was accompanied by resolution of the patient's symptoms. Interestingly, the patient experienced substantial improvement in the acquired joint hypermobility mimicking Ehlers-Danlos Syndrome (EDS) type III. CONCLUSION: To facilitate early and directed medical interventions, systemic bartonellosis should potentially be considered as a differential diagnosis in patients with incalcitrant rheumatological symptoms and frequent arthropod exposures or extensive animal contact.

Co-infection with Bartonella bacilliformis and Mycobacterium spp. in a coastal region of Peru.

OBJECTIVE: This study investigated an outbreak of Bartonellosis in a coastal region in Peru. RESULTS: A total of 70 (n = 70) samples with clinical criteria for the acute phase of Bartonellosis and a positive peripheral blood smear were included. 22.85% (n = 16) cases of the samples were positive for Bartonella bacilliformis by PCR and automatic sequencing. Of those positive samples, 62.5% (n = 10) cases were positive only for B. bacilliformis and 37.5% (n = 6) cases were positive to both Mycobacterium spp. and B. bacilliformis. The symptom frequencies were similar in patients diagnosed with Carrion's disease and those co-infected with Mycobacterium spp. The most common symptoms were headaches, followed by malaise and arthralgia.

Hallucinations, sensory neuropathy, and peripheral visual deficits in a young woman infected with Bartonella koehlerae.

A young woman experiencing depression, anxiety, mood swings, severe headaches, muscle spasms, interphalangeal joint stiffness, decreased peripheral vision, diminished tactile sensation, and hallucinations was persistently Bartonella koehlerae seroreactive and bacteremic. Following antibiotic treatment, B. koehlerae antibodies and DNA were not detected and all symptoms resolved.

Expressive aphasia as a presentation of encephalitis with Bartonella henselae infection in an immunocompetent adult.

OBJECTIVE: To show the first clinically reported case of Cat Scratch Disease (CSD) presenting as a focal neurologic deficit in an immunocompetent adult. PATIENT: 59-year-old male with a history of a previous stroke. RESULTS: Examination showed an expressive aphasia, word substitution errors, and impaired repetition. A head CT and MRI showed no acute changes. The EEG findings were non-focal and did not show any epileptiform activity. The patient had a history of contact with stray kittens and previous axillary lymphadenopathy. Bartonella henselae serology titers were IgG positive 1:1024 (< 64) and IgM positive 1:20 (< 16). After antibiotic administration, the patient's symptoms and aphasia resolved. CONCLUSIONS: Focal presentations concerning for stroke or partial seizure activity may have underlying infectious etiology. We recommend consideration of CSD in the differential diagnosis of any adult with a history of lymphadenopathy, fever, and recent contact with a cat who presents with neurologic complications.

An immunocompromised murine model of chronic Bartonella infection.

Bartonella are ubiquitous gram-negative pathogens that cause chronic blood stream infections in mammals. Two species most often responsible for human infection, B. henselae and B. quintana, cause prolonged febrile illness in immunocompetent hosts, known as cat scratch disease and trench fever, respectively. Fascinatingly, in immunocompromised hosts, these organisms also induce new blood vessel formation leading to the formation of angioproliferative tumors, a disease process named bacillary angiomatosis. In addition, they cause an endothelial-lined cystic disease in the liver known as bacillary peliosis. Unfortunately, there are as yet no completely satisfying small animal models for exploring these unique human pathologies, as neither species appears able to sustain infection in small animal models. Therefore, we investigated the potential use of other Bartonella species for their ability to recapitulate human pathologies in an immunodeficient murine host. Here, we demonstrate the ability of Bartonella taylorii to cause chronic infection in SCID/BEIGE mice. In this model, Bartonella grows in extracellular aggregates, embedded within collagen matrix, similar to previous observations in cat scratch disease, bacillary peliosis, and bacillary angiomatosis. Interestingly, despite overwhelming infection later in disease, evidence for significant intracellular replication in endothelial or other cell types was not evident. We believe that this new model will provide an important new tool for investigation of Bartonella-host interaction.

The pathophysiology of the acute phase of human bartonellosis resembles AIDS.

Human bartonellosis is a South American anthroponosis caused by Bartonella bacilliformis. The disease has an acute phase characterized by invasion of red blood cells by parasites, and consequent severe anemia; and a chronic phase presenting with benign vascular tumors. During the acute phase, affected individuals are prone to developing opportunistic infections with a variety of organisms similar to the ones seen in AIDS. After antibiotic treatment is instituted, a subgroup of patients may develop atypical symptoms which potentially represent clinical manifestations of the restoration of macrophage function. We speculate that the pathophysiology of the acute phase of human bartonellosis resembles AIDS, with a period of immunosuppression following the infection and later, clinical manifestations of immune reconstitution subsequent to treatment.

Insights in Bartonella host specificity.

The genus Bartonella comprises a unique group of emerging gram-negative, intracellular bacteria that can cause a long-lasting intraerythrocytic bacteremia in their reservoir hosts. In recent years, the widespread occurrence and diversity of these bacteria has been increasingly recognized. This has resulted in a dramatic expansion of the genus Bartonella to 24 currently described species or subspecies, among which at least half have been associated with human disease. Bartonella infections have been observed in virtually all species examined, extending from humans to carnivores, ungulates, rodents, lagomorphs, insectivores, and bats. Adaptation by Bartonellae to such a diverse range of mammals has resulted in host specificity, and all validated Bartonella species described to date are capable of parasitizing only a limited number of animal species. In this review, the possible mechanisms explaining the specificity of each Bartonella species for its reservoir host are discussed.

Bartonella henselae: subversion of vascular endothelial cell functions by translocated bacterial effector proteins.

Bartonella henselae (Bh) is a worldwide distributed zoonotic pathogen. Depending on the immune status of the infected individual this bacterium can cause a wide spectrum of clinical manifestations, ranging from cat scratch disease (CSD) to bacillary angiomatosis (BA) and bacillary peliosis (BP). BA and BP are characterized by tumor-like lesions at the skin or in the inner organs, respectively. These structures display pathological sprouting of capillaries with enlarged and hyperproliferated vascular endothelial cells (ECs) that are frequently found in close association with bacteria. Here we review the cellular changes observed upon Bh infection of ECs in vitro and outline the role of the VirB type IV secretion system (T4SS) and its translocated effector proteins in the modulation of EC signalling cascades. The current model how this virulence system could contribute to the vasoproliferative activity of Bh is described.

Isolation and characterization of Bartonella bacilliformis from an expatriate Ecuadorian.

Carrion's disease is typically biphasic with acute febrile illness characterized by bacteremia and severe hemolytic anemia (Oroya fever), followed by benign, chronic cutaneous lesions (verruga peruana). The causative agent, Bartonella bacilliformis, is endemic in specific regions of Peru and Ecuador. We describe atypical infection in an expatriate patient who presented with acute splenomegaly and anemia 3 years after visiting Ecuador. Initial serology and PCR of the patient's blood and serum were negative for Bartonella henselae, Bartonella quintana, and B. bacilliformis. Histology of splenic biopsy was suggestive of bacillary angiomatosis, but immunohistochemistry ruled out B. henselae and B. quintana. Bacilli (isolate EC-01) were subsequently cultured from the patient's blood and analyzed using multilocus sequence typing, protein gel electrophoresis with Western blotting, and an immunofluorescence assay (IFA) against a panel of sera from patients with Oroya fever in Peru. The EC-01 nucleotide sequences (gltA and internal transcribed spacer) and protein band banding pattern were most similar to a subset of B. bacilliformis isolates from the region of Caraz, Ancash, in Peru, where B. bacilliformis is endemic. By IFA, the patient's serum reacted strongly to two out of the three Peruvian B. bacilliformis isolates tested, and EC-01 antigen reacted with 13/20 Oroya fever sera. Bacilliary angiomatosis-like lesions were also detected in the spleen of the patient, who was inapparently infected with B. bacilliformis and who presumably acquired infection in a region of Ecuador where B. bacilliformis was not thought to be endemic. This study suggests that the range of B. bacilliformis may be expanding from areas of endemicity in Ecuador and that infection may present as atypical clinical disease.

The expanded spectrum of bartonellosis in children.

Bartonella spp cause various clinical syndromes immunocompetent and immunocompromised hosts. Domestic cats are the natural reservoir, and vectors of B henselae. B henselae infection usually occurs early in childhood, is generally asymptomatic, and in most cases revolves spontaneously. It may, however, produce a wide spectrum of clinical symptoms, the most frequent feature being cat-scratch disease. Disseminated atypical B. henselae infection may follow cat-scratch disease alter a symptom-free period or may present de novo mimicking a wide range of clinical disorders. A careful clinical history researching an intimate contact with a kitten associated with a specific serology and an abdominal ultrasound for typical hepatosplenic involvement may follow a rapid and accurate diagnosis.

Bartonellae as elegant hemotropic parasites.

Bartonella species are hemotropic bacterial parasites of a wide range of mammals that occasionally cause disease in humans. The low prevalence of clinical manifestations compared to the high prevalence of infection underlines the elegance of these parasites that carefully exploit their hosts in a manner that optimizes their transmission. Recent research efforts have begun to determine the strategies involved in this exploitation, and significant progress has been made in unraveling an unusually complex natural cycle. Studies aimed at determining bacterial attributes involved in parasitism characterized several "virulence" factors and explored their modes of action. These efforts have provided an intriguing foundation on which future efforts aimed at comprehending these sophisticated parasites can be soundly based.

[Bartonella and bartonellosis--emerging and re-emerging infections. Taxonomy, bacteriology, pathogenesis and genetics]. / Bartonelly i bartonellezy--novye i vozvrashchaiushchiesia. Taksonomiia, bakteriologiia, patogenez i genetika.

The review updates knowledge on the taxonomy, bacteriology and genetics of Bartonella as well as pathogenesis of bartonellosis. The role of Bartonella in human pathology, formerly considered to be rather modest, causes now growing anxiety. In this connection Bartonella are now believed to be the causative agents of so-called emerging and re-emerging diseases, i.e. diseases, formerly unknown to man, and diseases, believed to be eradicated and playing at present no important role in human pathology. These microorganisms are a bright example of successes of molecular biology in the detection of microorganisms, as well as in their phylogenetics and systematics.

Prevalence of Bartonella infection among human immunodeficiency virus-infected patients with fever.

Bartonella infection can be difficult to diagnose, especially when it manifests as bacteremia, which is usually accompanied by nonspecific symptoms, such as fever. Therefore, we hypothesized that Bartonella infection represents an underrecognized cause of febrile illness. To determine the prevalence of Bartonella infection among patients presenting with fever, we evaluated 382 patients in San Francisco. Overall, 68 patients (18%) had evidence of Bartonella infection detected by culture, indirect fluorescent antibody testing, or polymerase chain reaction (PCR). Twelve patients (3%) had either Bartonella henselae or Bartonella quintana isolated from specimens of blood, tissue, or both or had DNA detected in tissue; all 12 had concomitant human immunodeficiency virus (HIV) infection. Bartonella antibodies were detected in 17% of febrile patients, including 75% of culture-positive or PCR-positive patients. In a nested, matched case-control study aimed at identifying clinical features of febrile illness associated with Bartonella infection, only bacillary angiomatosis and elevated alkaline phosphatase levels were associated with Bartonella infection (P< or =.03 for both). The prevalence of Bartonella infection among patients with late-stage HIV infection and unexplained fever is much greater than has previously been documented.

Clinical impact of persistent Bartonella bacteremia in humans and animals.

Bartonella spp. are emerging vector-borne pathogens that cause persistent, often asymptomatic bacteremia in their natural hosts. As our knowledge progresses, it appears that chronic infection may actually predispose the host to mild, insidious nonspecific manifestations or induce, in selected instances, severe diseases. Persistent asymptomatic bacteremia is most common in animals that serve as the main reservoir for the specific Bartonella. In humans, these organisms are B. bacilliformis and B. quintana. Other Bartonella species, for which humans are not the natural reservoir, tend to cause persistent bacteremia only in immunodeficient individuals. In some of these individuals, endothelial cell proliferation may create lesions such as bacillary angiomatosis or bacillary peliosis. In cats, bacteremia of variable level and continuity may last for years. Some strains of B. henselae may induce clinical manifestations, including fever, mild neurological signs, reproductive disorders, whereas others do not induce clinically obvious disease. Reproductive disorders have also been reported in mice experimentally infected with B. birtlesii. Finally, canids constitute the most interesting naturally occurring animal model for the human disease. Like immunocompetent people, healthy dogs only occasionally demonstrate long-term bacteremia when infected with Bartonella spp. However, some dogs develop severe clinical manifestations, such as endocarditis, and the pathologic spectrum associated with Bartonella spp. infection in domestic dogs is rapidly expanding and resembles the infrequently reported clinical entities observed in humans. In coyotes, persistent bacteremia is more common than in domestic dogs. It will be of interest to determine if coyotes develop clinical or pathological indications of infection.