Bartonella quintana Endocarditis: A Systematic Review of Individual Cases.

BACKGROUND: Bartonella quintana is a louse-borne bacterium that remains a neglected cause of endocarditis in low-resource settings. Our understanding of risk factors, clinical manifestations, and treatment of B. quintana endocarditis are biased by older studies from high-income countries. METHODS: We searched Pubmed Central, Medline, Scopus, Embase, EBSCO (CABI) Global Health, Web of Science and international trial registers for articles published before March 2023 with terms related to Bartonella quintana endocarditis. We included articles containing case-level information on B. quintana endocarditis and extracted data related to patient demographics, clinical features, diagnostic testing, treatment, and outcome. RESULTS: A total of 975 records were identified, of which 569 duplicates were removed prior to screening. In total, 84 articles were eligible for inclusion, describing a total of 167 cases. Infections were acquired in 40 different countries; 62 cases (37.1%) were acquired in low- and middle-income countries (LMICs). Disproportionately more female and pediatric patients were from LMICs. More patients presented with heart failure (n = 70/167 [41.9%]) than fever (n = 65/167 [38.9%]). Mean time from symptom onset to presentation was 5.1 months. Also, 25.7% of cases (n = 43/167) were associated with embolization, most commonly to the spleen and brain; 65.5% of antimicrobial regimens included doxycycline. The vast majority of cases underwent valve replacement surgery (n = 154/167, [98.0%]). Overall case fatality rate was 9.6% (n = 16/167). CONCLUSIONS: B. quintana endocarditis has a global distribution, and long delays between symptom onset and presentation frequently occur. Improved clinician education and diagnostic capacity are needed to screen at-risk populations and identify infection before endocarditis develops.

Bartonella henselae- and quintana-associated uveitis: a case series and approach of a potentially severe disease with a broad spectrum of ocular manifestations.

PURPOSE: To evaluate the clinical manifestations of intraocular inflammation associated with Bartonella infection and describe the assessment and management of patients with cat-scratch disease (CSD). METHODS: This is a retrospective review of the clinical records of patients diagnosed with Bartonella henselae and Bartonella quintana intraocular inflammation from 2011 to 2018 in the Department of Ocular Inflammations and Infections of the University Eye Clinic of Ioannina (Greece). An analysis of the current literature concerning Bartonella-related intraocular infections was also carried out. RESULTS: This is a retrospective study of 13 patients (7 males and 6 females) with a mean age of 39.2 years that were diagnosed with unilateral intraocular inflammation, except one case with bilateral affection, attributed to Bartonella (either henselae or quintana). Twelve (12) patients (92.3%) had a positive history of traumatic cat contact. The main ocular clinical findings with regard to the type of uveitis included neuroretinitis in 5 eyes (38.5%), vasculitis in 3 eyes (23.1%), iridocyclitis in 2 eyes (15.4%), intermediate uveitis in 2 eyes (15.4%), posterior uveitis in 1 eye (7.7%), panuveitis in 2 eyes (15.4%), retinochoroiditis in 2 eyes (15.4%), vitritis in 1 eye (7.7%), peripheral choroidal granuloma in 1 eye (7.7%). Immunoglobulin (Ig) G was positive in all cases. All patients were treated with antibiotics (mainly rifampicin, doxycycline and azithromycin). The visual acuity was noted to be improved in all patients after treatment, but some of them experienced disturbing complications. CONCLUSION: CSD may manifest with various ocular pathological findings. Taking into consideration the increasing frequency of infections by B. henselae and B. quintana, clinicians should always incorporate CSD in the differential diagnosis of such presentations of uveitis. Educating vulnerable groups (children, immunosuppressed, etc.) and also general population, the appropriate preventing measures can contribute in limiting the risk of infection.

Quintessential Culture-Negative Endocarditis.

Bartonella spp are important causes of culture-negative endocarditis, generally causing a subacute insidious form of endocarditis, often leading to a delay in diagnosis. Most patients have fever and often present with signs and symptoms of heart failure. The diagnosis is frequently established only on meticulous examination of the resected heart valve with the polymerase chain reaction technique. We present a case of B quintana mitral and aortic valve endocarditis with associated severe valvular insufficiency and decompensated heart failure precipitated by Streptococcus pneumoniae bacteremia, necessitating urgent surgical valve replacement. Pathologic examination of the valve complemented by serologic and molecular testing established the surprising diagnosis of B quintana endocarditis.

Bartonella quintana Aortitis in a Man with AIDS, Diagnosed by Needle Biopsy and 16S rRNA Gene Amplification.

A man with newly diagnosed AIDS presented with months of back pain and fever. Computed tomography (CT) results demonstrated aortitis with periaortic tissue thickening. DNA amplification of biopsy tissue revealed Bartonella quintana, and Bartonella serologies were subsequently noted to be positive. The patient improved with prolonged doxycycline and rifabutin treatment. This case illustrates how molecular techniques are increasingly important in diagnosing Bartonella infections.

Duplex PCR assay simultaneously detecting and differentiating Bartonella quintana, B. henselae, and Coxiella burnetii in surgical heart valve specimens.

A duplex PCR (dPCR) assay was developed to simultaneously detect and differentiate Bartonella quintana, Bartonella henselae, and Coxiella burnetii from surgical heart valve tissue specimens with an analytic sensitivity of 10 copies/reaction. Among 17 specimens collected from patients with a clinical diagnosis of culture-negative endocarditis, 2, 4, and 2 were positive for B. quintana, B. henselae, and C. burnetii, respectively, by the dPCR assay, which matched the results obtained by universal bacterial 16S rRNA gene amplification and sequencing.

Isolation and characterization of Bartonella quintana from the parotid gland of an immunocompetent man.

We describe a case of the isolation of Bartonella quintana from the parotid gland of an apparently healthy man. Pathological examination showed intraparotid granulomatous abscessual lymphadenitis. Diagnosis was made on the basis of high titers of immunoglobulin G (IgG) and IgM antibodies and of culture isolation of a causative agent from parotid aspirate.

[Bartonella infection in hematological practice].

AIM: To characterize the clinical and histological features of Bartonella infection in patients asking for hematological advice and to assess the significance of serological and molecular methods for the diagnosis of this infection. MATERIALS AND METHODS: The case histories of 747 patients asking for advice at the Hematology Research Cancer, Russian Academy of Medical Sciences, for lymphadenopaphy were retrospectively studied. The study included 10 patients in whom Bartonella infection could be suspected. For verification of the diagnosis, the authors conducted a serological study of the patients' sera and a molecular study of archival paraffined lymph node biopsy specimens. RESULTS: The study showed it possible to make a retrospective diagnosis of cat-scratch disease (CSD) by polymerase chain reaction (PCR) used in the study of archival lymph node biopsy specimens and stained preparations. CONCLUSION: CSD should be suspected when a patient has sustained lymphadenopathy and a respective epidemiological history (feline contact). Bartonella infection should be diagnosed on the basis of a dynamic serological study and, if possible, PCR of cells from biopsy specimens of lymph nodes or the lesion developed at the site of Bartonella penetration into the human body (primary affect).

Presumed oculoglandular syndrome from Bartonella quintana.

BACKGROUND: To describe a case of clinically diagnosed oculoglandular syndrome in a 17-year-old patient that was presumed to be due to Bartonella quintana, as suggested by a positive serologic titer. METHODS: The patient presented to the Massachusetts Eye and Ear Infirmary emergency room with signs and symptoms suggestive of oculoglandular syndrome. He had a follicular conjunctivitis with a conjunctival granuloma of the right eye and an ipsilateral large, tender submandibular lymph node. He had recently acquired a kitten and a clinical diagnosis of cat-scratch disease was made. A laboratory workup was initiated to determine the cause of this clinical presentation and empirical treatment with antibiotics was started. RESULTS: All laboratory results were negative or normal except for the IgM titer to Bartonella quintana, which was elevated. The patient responded well to treatment and his symptoms resolved within a few weeks. DISCUSSION: Bartonella quintana infection, a pathogen prevalent in HIV-infected, homeless, or alcoholic patients, is a possible etiologic agent of cat-scratch disease and the associated condition of oculoglandular syndrome.

[Lice and lice-borne diseases in humans]. / Les poux et les maladies transmises á l'homme.

Among the three lice which parasite the human being, the human body louse, Pediculus humanus humanus, is a vector of infectious diseases. It lives and multiplies in clothes and human infestation is associated with cold weather and a lack of hygiene. Three pathogenic bacteria are transmitted by the body louse: 1) Rickettsia prowazekii, the agent of epidemic typhus of which the most recent outbreak (and the largest since World War II) was observed during the civil war in Burundi; 2) Borrelia recurrentis, the agent of relapsing fever, historically responsible of massive outbreaks in Eurasia and Africa, which prevails currently in Ethiopia and neighboring countries; 3) Bartonella quintana, the agent of trench fever, bacillary angiomatosis, chronic bacteremia, endocarditis, and lymphadenopathy. Body louse infestation, associated with a decline in social and hygienic conditions provoked by civil unrest and economic instability, is reemergent worldwide. Recently, a forth human pathogen, Acinetobacter baumannii, has been associated to the body louse.

Pericardial effusion in a homeless man due to Bartonella quintana.

Bartonella quintana may cause trench fever, endocarditis, bacillary angiomatosis, and chronic bacteremia, and a reemergence among homeless populations in cities has been noted. Pericarditis from Rickettsia conorii and Coxiella burnetii infection has been described, but there have been no reports of pericarditis due to Bartonella spp. We report a case of pericardial effusion due to Bartonella quintana in a homeless man, diagnosed on the basis of PCR detection of Bartonella quintana in a pericardial biopsy sample and a fourfold rise in antibody titers. The patient recovered within 2 weeks with antibiotics active against bartonellae.

What do we (not) know about the human bartonelloses?

The human bartonelloses are a group of diseases with a rapidly increasing clinical spectrum. Well known manifestations such as Carrion's disease, trench fever, cat-scratch disease, and bacillary angiomatosis are examples of Bartonella sp. infection. Along with these diseases, recurrent bacteremia, endocarditis, septicemia, erythema nodosum, erythema multiforme, trombocytopenic purpura and other syndromes have been reported having been caused by bacteria of this genus. The infectious process and the pathogenesis of these microorganisms are poorly understood. The bartonelloses may have a benign and self-limited evolution in a host, or a potentially fatal one. These bacteria can provoke a granulomatous or an angioproliferative histopathologic response. As these diseases are not yet well defined, we have reviewed the four main human bartonelloses and have examined unclear points about these emergent diseases.

[Bartonellosis]. / Bartonellosi.

In the last years the number of Bartonella species significantly raised, often with an epidemiological profile of emergent disease. B. bacilliformis is the etiological agent of Carrion's disease. B. clarridgeiae has been associated, together with B. henselae, to Cat-Scratch Disease (CSD), whereas B. elizabethae to endocarditis and B. grahamii to neuroretinitis. B. henselae has been associated to CSD and, in patients with immunodeficiency, together with B. quintana, to bacillary angiomatosis, to peliosis and to endocarditis. B. quintana is the etiological agent of "trench fever", in its "classical" and "urban" form. B. vinsonii subsp. arupensis and subsp. berkhoffii have been associated to bacteremia and endocarditis. The diagnosis foresees pathological examination of the lesions, germ isolation and use of specific serological test and of polymerase chain reaction. Prognosis is, generally, favourable. Therapy foresees the use of numerous antibacterial agents, like: penicillins, cephalosporins, aminoglycosides, tetracyclines, macrolides, quinolones, trimethoprim-sulfomethoxazole and rifampicin.

What do we (not) know about the human bartonelloses?

The human bartonelloses are a group of diseases with a rapidly increasing clinical spectrum. Well known manifestations such as Carrion's disease, trench fever, cat-scratch disease, and bacillary angiomatosis are examples of Bartonella spp. infection. Along with these diseases, recurrent bacteremia, endocarditis, septicemia, erythema nodosum, erythema multiforme, trombocytopenic purpura and other syndromes have been reported having been caused by bacteria of this genus. The infectious process and the pathogenesis of these microorganisms are poorly understood. The bartonelloses may have a benign and self-limited evolution in a host, or a potentially fatal one. These bacteria can provoke a granulomatous or an angioproliferative histopathologic response. As these diseases are not yet well defined, we have reviewed the four main human bartonelloses and have examined unclear points about these emergent diseases

[Bartonella infection]. / Infectia cu Bartonella.

Bartonella species have been recently recognized as an important human pathogen associated with a wide spectrum of diseases. Four members of the genus are known to cause human infection: Bartonella baciliformis, B. henselae, B. quintana and B. elizabethae. B. baciliformis, the first identified Bartonella species, is the agent of two disease entities, Oroya fever and verruga peruana., B. henselae and B. quintana are two species involved in producing bacteremic syndromes (relapsing fever, trench fever, endocarditis), chronic lymphadenopathy in immunocompetent patients (cat-scrath disease) and chronic vascular lesions in immunocompromised hosts (bacillary angiomatosis and bacillary peliosis hepatis-recognized as new opportunistic infections in HIV-infected patients).

Bartonella quintana and urban trench fever.

Contemporary Bartonella quintana infections have emerged in diverse regions of the world, predominantly involving socially disadvantaged persons. Available data suggest that the human body louse Pediculus humanus is the vector for transmission of B. quintana. Descriptions of the clinical manifestations associated with contemporary B. quintana infections have varied considerably and include asymptomatic infection, a relapsing febrile illness, headache, leg pain, "culture-negative" endocarditis, and, in human immunodeficiency virus-infected persons, bacillary angiomatosis. Laboratory diagnosis is most convincing when B. quintana is isolated in blood culture, but growth often takes 20-40 days; problems exist with both sensitivity and specificity of serological assays. On the basis of available information, use of doxycycline, erythromycin, or azithromycin to treat B. quintana infections is recommended. Treatment of uncomplicated B. quintana bacteremia for 4-6 weeks and treatment of B. quintana endocarditis (in a person who does not undergo valve surgery) for 4-6 months are recommended, with the addition of a bactericidal agent (such as a third-generation cephalosporin or an aminoglycoside) during the initial 2-3 weeks of therapy for endocarditis.

The body louse as a vector of reemerging human diseases.

The body louse, Pediculus humanus humanus, is a strict human parasite, living and multiplying in clothing. Louse infestation is associated with cold weather and a lack of hygiene. Three pathogenic bacteria are transmitted by the body louse. Borrelia recurrentis is a spirochete, the agent of relapsing fever, recently cultured on axenic medium. Historically, massive outbreaks have occurred in Eurasia and Africa, but currently the disease is found only in Ethiopia and neighboring countries. Bartonella quintana is now recognized as an agent of bacillary angiomatosis bacteremia, trench fever, endocarditis, and chronic lymphadenopathy among the homeless. Rickettsia prowazekii is the agent of epidemic typhus. The most recent outbreak (and the largest since World War II) was observed in Burundi. A small outbreak was also reported in Russia in 1997. Louse infestation appears to become more prevalent worldwide, associated with a decline in social and hygienic conditions provoked by civil unrest and economic instability.

Culture of Bartonella quintana and Bartonella henselae from human samples: a 5-year experience (1993 to 1998).

Bartonella quintana and Bartonella henselae are fastidious gram-negative bacteria responsible for bacillary angiomatosis, trench fever, cat scratch disease, and endocarditis. During a 5-year period, we received 2,043 samples for culture of Bartonella sp. We found Bartonella sp. to be the etiologic agent in 38 cases of endocarditis, 78 cases of cat scratch disease, 16 cases of bacteremia in homeless people, and 7 cases of bacillary angiomatosis. We correlated the results of positive cultures with the clinical form of the disease, type of sample, culture procedure, PCR-based genomic detection, and antibody determination. Seventy-two isolates of B. quintana and nine isolates of B. henselae from 43 patients were obtained. Sixty-three of the B. quintana isolates and two of the B. henselae isolates, obtained from patients with no prior antibiotic therapy, were stably subcultured. The sensitivity of culture was low when compared with that of PCR-based detection methods in valves of patients with endocarditis (44 and 81%, respectively), skin biopsy samples of patients with bacillary angiomatosis (43 and 100%, respectively), and lymph nodes of cat scratch disease (13 and 30%, respectively). Serological diagnosis was also more sensitive in cases of endocarditis (97%) and cat scratch disease (90%). Among endocarditis patients, the sensitivity of the shell vial culture assay was 28% when inoculated with blood samples and 44% when inoculated with valvular biopsy samples, and the sensitivity of both was significantly higher than that of culture on agar (5% for blood [P = 0.045] and 4% for valve biopsy samples [P < 0.0005]). The most efficient culture procedure was the subculture of blood culture broth into shell vials (sensitivity, 71%). For patients with endocarditis, previous antibiotic therapy significantly affected results of blood culture; no patient who had been administered antibiotics yielded a positive blood culture, whereas 80% of patients with no previous antibiotic therapy yielded positive blood cultures (P = 0.0006). Previous antibiotic therapy did not, however, prevent isolation of Bartonella sp. from cardiac valves but did prevent the establishment of strains, as none of the 15 isolates from treated patients could be successfully subcultured. For the diagnosis of B. quintana bacteremia in homeless people, the efficiency of systematic subculture of blood culture broth onto agar was higher than that of direct blood plating (respective sensitivities, 98 and 10% [P < 10(-7)]). Nevertheless, both procedures are complementary, since when used together their sensitivity reached 100%. All homeless people with positive blood cultures had negative serology. The isolation rate of B. henselae from PCR-positive lymph nodes, in patients with cat scratch disease, was significantly lower than that from valves of endocarditis patients and skin biopsy samples from bacillary angiomatosis patients (13 and 33%, respectively [P = 0.084]). In cases of bacillary angiomatosis for which an agent was identified to species level, the isolation rate of B. henselae was lower than the isolation rate of B. quintana (28 and 64%, respectively [P = 0.003]). If culture is to be considered an efficient tool for the diagnosis of several Bartonella-related diseases, methodologies need to be improved, notably for the recovery of B. henselae from lymph nodes of patients with cat scratch disease.

Serological cross-reactions between Bartonella quintana, Bartonella henselae, and Coxiella burnetii.

The clinical manifestations of Q fever and bartonelloses can be confused, especially in cases of infectious endocarditis. Differential diagnosis of the diseases is important because the treatments required for Q fever and bartonelloses are different. Laboratory confirmation of a suspected case of either Q fever or bartonelloses is most commonly made by antibody estimation with an indirect immunofluorescence assay. With an indirect immunofluorescence assay, 258 serum samples from patients with Q fever were tested against Bartonella henselae and Bartonella quintana antigens, and 77 serum samples from patients with infection by Bartonella sp. were tested against Coxiella burnetii antigen. Cross-reactivity was observed: more than 50% of the chronic Q fever patients tested had antibodies which reacted against B. henselae antigen to a significant level. This cross-reaction was confirmed by a cross-adsorption study and protein immunoblotting. However, because the levels of specific antibody titers in cases of Bartonella endocarditis are typically extremely high, low-level cross-reaction between C. burnetii antibodies and B. henselae antigen in cases of Q fever endocarditis should not lead to misdiagnosis, provided serology testing for both agents is performed.