Unmasking Bartonella henselae infection in the shadows of long COVID thanks to clinical metagenomics.

The diagnosis of long COVID often relies on symptoms post-COVID-19, occasionally lacking biological evidence. This case study illustrates how investigating long COVID uncovered an underlying bartonellosis through clinical metagenomics. Following mild COVID-19, a 26-year-old woman experienced persistent symptoms during 5 months, including axillary adenopathy. Pathological examination, 16 S rRNA PCR, and clinical metagenomic analysis were done on an adenopathy biopsy. The latter revealed Bartonella henselae DNA and RNA. Treatment with clarithromycin improved symptoms. This case underscores the relevance of clinical metagenomics in diagnosing hidden infections. Post-COVID symptoms warrant thorough investigation, and bartonellosis should be considered in polyadenopathy cases, regardless of a recent history of cat or flea exposures.

Epidemiology and treatment of invasive Bartonella spp. infections in the United States.

OBJECTIVES: Bartonella spp., renowned for cat-scratch disease, has limited reports of dissemination. Tissue and blood cultures have limitations in detecting this fastidious pathogen. Molecular testing (polymerase chain reaction, PCR) and cell-free DNA have provided an avenue for diagnoses. This retrospective observational multicenter study describes the incidence of disseminated Bartonella spp. and treatment-related outcomes. METHODS: Inclusion criteria were diagnosis of bartonellosis via diagnosis code, serology testing of blood, polymerase chain reaction (PCR) of blood, 16/18S tests of blood or tissue, cultures of blood or tissue, or cell-free DNA of blood or tissue from January 1, 2014, through September 1, 2021. Exclusions were patients who did not receive treatment, insufficient data on treatment course, absence of dissemination, or retinitis as dissemination. RESULTS: Patients were primarily male (n = 25, 61.0%), white (n = 28, 68.3%), with mean age of 50 years (SD 14.4), and mean Charlson comorbidity index of 3.5 (SD 2.1). Diagnosis was primarily by serology (n = 34, 82.9%), with Bartonella henselae (n = 40, 97.6%) as the causative pathogen. Treatment was principally doxycycline with rifampin (n = 17, 41.5%). Treatment failure occurred in 16 (39.0%) patients, due to escalation of therapy during treatment (n = 5, 31.3%) or discontinuation of therapy due to an adverse event or tolerability (n = 5, 31.3%). CONCLUSIONS: In conclusion, this is the largest United States-based cohort of disseminated Bartonella spp. infections to date with a reported 39% treatment failure. This adds to literature supporting obtaining multiple diagnostic tests when Bartonella is suspected and describes treatment options.

Post-COVID reactivation of latent Bartonella henselae infection: a case report and literature review.

Cat scratch disease (CSD) is caused by Bartonella henselae (B. henselae) and presents as lymphadenopathy following close contact with cats. However, in context of the global COVID-19 pandemic, clinical manifestations of CSD may vary, posing new challenges for healthcare professionals. Here we describe a case of a 54-year-old male with painful left upper arm mass, which gradually resolved until he was infected with COVID-19. The mass then rapidly progressed before admission. Meanwhile, pulmonary symptoms including pleural effusion emerged simultaneously. The cause was undetermined with routine blood culture and pathological test until the next generation sequencing (NGS) confirmed the presence of B. henselae. We believe this case is the first to report localized aggravation of CSD after COVID-19 infection and hopefully, offers treatment experience for clinicians worldwide.

A Case of Parinaud Oculoglandular Syndrome in Which Bartonella DNA Was Detected in the Cornea and Conjunctiva by Polymerase Chain Reaction.

Background and Objectives: Parinaud oculoglandular syndrome (POS) is unilateral granulomatous follicular conjunctivitis with ipsilateral afferent lymphadenopathy, primarily caused by cat-scratch disease, tularemia, and sporotrichosis. We report a case of POS in which Bartonella DNA was detected using polymerase chain reaction (PCR) in corneal and conjunctival specimens. Methods: A 29-year-old man, who started keeping a stray cat two months prior, became aware of right preauricular lymphadenopathy and right ocular conjunctival hyperemia one month prior. Subsequently, he developed a fever of approximately 37.9 °C, with a purulent ocular discharge appearing 1 week before being referred to our department for a detailed ophthalmological examination. The patient's right eye showed hyperemia and edema in the bulbar conjunctiva, along with palpebral conjunctival hyperemia, follicles, and white ulcers. Two weeks later, his serum IgM titer for Bartonella henselae was 1:20, and Bartonella DNA was detected by PCR in the corneal and conjunctival specimens. Based on these findings, the patient was diagnosed with POS caused by cat-scratch disease (CSD). Oral doxycycline, rifampicin, topical gatifloxacin, betamethasone phosphate, and erythromycin eye ointments were prescribed. Results: After 2 weeks of oral treatment and 2 months of eye drop treatment, the deterioration of the cornea and conjunctiva improved when the patient recovered good visual acuity. Conclusions: PCR assays of corneal and conjunctival specimens are useful for the diagnosis of CSD presenting with POS. These results suggested that Bartonella may be directly involved in the ocular surface pathogenesis of POS.

Atypical Haemorrhagic Presentation of Neuro-Retinitis and Serous Retinal Detachment Secondary to Cat-Scratch Disease.

Cat-scratch disease (CSD) is a self-limited disease caused by Bartonella henselae, a fastidious gram-negative intracellular bacillus bacterium. Neuroretinitis, a form of optic neuropathy characterised clinically by optic disc swelling and a macular star, is an uncommon manifestation of CSD occurring in approximately 1-2% of cases. We report a case of a 14-year-old female who presented to the emergency department with a chief complaint of acute painless vision loss described as a large black spot in the centre of her right eye vision 2 weeks after being scratched by cats. Fundus examination revealed Frisen grade 5 disc oedema with an atypically diffuse disc and peripapillary haemorrhages with associated subretinal fluid and a macular star in the right eye. Optical coherence tomography (OCT) of the macula and retinal nerve fibre layer showed subretinal fluid involving the fovea, a serous retinal detachment of the nasal macula, and significant optic disc oedema in the right eye. The patient was admitted and treated with doxycycline, rifampin, and prednisone taper. After completing the treatment course, the patient's vision improved, fundus examination showed significantly improved disc oedema and haemorrhages, and OCT demonstrated resolution of the subretinal fluid in the right eye.

Bartonella spp. Infections Identified by Molecular Methods, United States.

Molecular methods can enable rapid identification of Bartonella spp. infections, which are difficult to diagnose by using culture or serology. We analyzed clinical test results of PCR that targeted bacterial 16S rRNA hypervariable V1-V2 regions only or in parallel with PCR of Bartonella-specific ribC gene. We identified 430 clinical specimens infected with Bartonella spp. from 420 patients in the United States. Median patient age was 37 (range 1-79) years; 62% were male. We identified B. henselae in 77%, B. quintana in 13%, B. clarridgeiae in 1%, B. vinsonii in 1%, and B. washoensis in 1% of specimens. B. quintana was detected in 83% of cardiac specimens; B. henselae was detected in 34% of lymph node specimens. We detected novel or uncommon Bartonella spp. in 9 patients. Molecular diagnostic testing can identify Bartonella spp. infections, including uncommon and undescribed species, and might be particularly useful for patients who have culture-negative endocarditis or lymphadenitis.

Autoimmune Thyroiditis Induced by Bartonella henselae (Cat-Scratch Disease) Might Be Reversible.

INTRODUCTION: Bartonella henselae infection leads to development of cat-scratch disease (CSD) but may also trigger of autoimmune thyroiditis (AIT). CASE PRESENTATION: We describe a 4-year-old boy with a severe fever of unknown etiology, disseminated neck lymphadenopathy, and a headache. Treatment with antibiotics was employed, but finally a left tonsillectomy, selective left lymphadenectomy, and immunophenotyping were performed to exclude lymphoma. Histologic examination excluded lymphoma but revealed CSD. IgG against B. henselae and Bartonella quintana was positive. A goiter was also found and positive anti-thyroid antibodies confirmed AIT. Two months later, the thyroid was not palpable, normal on ultrasound, and both anti-thyroid antibodies were negative. The full reversibility was documented, and 6-year follow-up showed that the patient remains disease free. CONCLUSION: This is the first report that AIT triggered by B. henselae/B. qunitana might be reversible if the pathogenetic factor is eliminated at an early stage of disease.

Cat-scratch disease manifesting as uveitis and binocular fundus nodular lesions: a case report.

BACKGROUND: Cat-scratch disease typically presents with various ocular manifestations such as uveitis, vitritis, retinitis, retinochoroiditis, and optic neuritis. However, fundus nodular lesions was rarely reported. In our study, we reported a case of Cat-Scratch disease with binocular fundus nodular lesions. CASE PRESENTATION: An 11-year old male presented with uveitis in the right eye and bilateral fundus nodular lesions after indirect contact with unvaccinated cats. Comprehensive ancillary examinations including wide-angle fundus photography, ultrasonography, fluorescein fundus angiography, optical coherence tomography, and orbital magnetic resonance imaging were performed to elucidate the multidimensional features of the binocular lesions. Metagenomics next-generation sequencing was utilized to confirm the diagnosis of Cat-scratch disease. The patient's condition showed improvement after a 6-month combination treatment regimen involving systemic administration of doxycycline hyclate and methylprednisolone tablets, as well as local application of mydriatic and corticosteroid eye drops. CONCLUSIONS: We firstly reported a case of Cat-scratch disease presenting simultaneously with uveitis and fundus nodular lesions caused by Bartonella henselae infection in a child. Timely diagnosis and treatment with antibiotics and corticosteroids showed promising outcomes for the prognosis of these ocular disorders.

Exploring the seasonal and regional features of cat-scratch disease on the basis of anti-Bartonella henselae IgM/IgG positive rates in Japan.

OBJECTIVES: This study aimed to explore the seasonal and regional features of cat-scratch disease (CSD) based on 15-years of test results for anti-Bartonella henselae IgG and IgM by immunofluorescence assay (IFA) performed as a laboratory specialized in diagnostic testing of CSD in Japan. A literature search was performed to put our findings in perspective. METHODS: A total of 956 sera from patients suspected of CSD were submitted to our laboratory from nationwide. Seasonal changes in the monthly positive rates of IgG/IgM antibodies and regional distribution of the test specimens were analyzed. RESULTS: The monthly positive rates of anti-B. henselae IFA of IgG and IgM were both significantly high between September and January and low between March and July. The seasonal pattern observed in this study was similar to the ones reported from US and France, which were analyzed from a clinical database (monthly incidence of CSD diagnosis) or from monthly positive rates of either B. henselae PCR or anti-B. henselae IFA. However, fluctuations in the IFA monthly positive rates in this study were more pronounced than other reports. Regarding regionality, the test specimens submitted to us for IFA were prominently more from southwestern areas than from northern/middle-northern areas of Japan. The distribution coincided well with the regional distribution of CSD case reports and with a known regional prevalence of Bartonella-species bacteremia among pet cats in Japan. CONCLUSION: These epidemiological features in Japan are of relevance in the clinical diagnoses of CSD.

Clinical utility of whole body diffusion-weighted imaging in an immunocompetent adult with atypical cat scratch disease.

BACKGROUND: Cat scratch disease (CSD) is an infectious disease caused by Bartonella henselae. CSD follows a typical course, characterized by regional lymphadenopathy. In atypical CSD, the lesions spread to systemic organs and can cause fever of unknown origin (FUO). A previous study showed the usefulness of whole-body magnetic resonance imaging (WB-MRI) with diffusion-weighted imaging (DWI) for limited areas in the diagnosis of FUO, but there are no studies on the clinical utility of whole-body DWI (WB-DWI). We herein report the case of an immunocompetent young man in whom contrast-enhanced CT-unidentifiable multiple liver abscess and osteomyelitis were successfully detected by WB-DWI. Follow-up with a liver biopsy helped confirm an atypical CSD diagnosis. CASE PRESENTATION: A 23-year-old previously healthy man was admitted for a 19-day history of high fever despite 3-day treatment by azithromycin. His physical examination was unremarkable and contrast-enhanced CT showed only a low attenuated area in the right lobe of the liver, indicating a cyst. WB-DWI revealed multiple nodular lesions of hypo-diffusion in the liver, spine, and pelvic region. The biopsy specimens of the liver abscess showed no evidence of tuberculosis/malignancy and the polymerase chain reaction (PCR) test of liver abscess aspirate showed positive findings for Bartonellahenselae, confirming the diagnosis of CSD. He completed minocycline monotherapy for a total of 60 days without any deterioration. CONCLUSIONS: WB-DWI can be useful for the diagnosis of atypical CSD with hepatic and bone involvement, which can cause FUO in young immunocompetent adults.

Bartonella endocarditis and diffuse crescentic proliferative glomerulonephritis with a full-house pattern of immune complex deposition.

BACKGROUND: Bartonella endocarditis is often a diagnostic challenge due to its variable clinical manifestations, especially when it is first presented with involvement of organs other than skin and lymph nodes, such as the kidney. CASE PRESENTATION: This was a 13-year-old girl presenting with fever, chest and abdominal pain, acute kidney injury, nephrotic-range proteinuria and low complement levels. Her kidney biopsy showed diffuse crescentic proliferative glomerulonephritis with a full-house pattern of immune complex deposition shown by immunofluorescence, which was initially considered consistent with systemic lupus erythematous-associated glomerulonephritis (lupus nephritis). After extensive workup, Bartonella endocarditis was diagnosed. Antibiotic treatment and valvular replacement surgery were undertaken with subsequent return of kidney function to normal range. CONCLUSION: This case demonstrates the importance of considering the full clinical picture when interpreting clinical, laboratory and biopsy findings, because the treatment strategy for infective endocarditis versus lupus nephritis is drastically different.

Epidemiological of cat scratch disease among inpatients in the Spanish health system (1997-2015).

Cat scratch disease, whose causative agent is Bartonella henselae, is an anthropozoonosis with a worldwide distribution that causes significant public health problems. Although it is an endemic disease in Spain, the available data are very limited. The aim of our study was to describe cat scratch disease inpatients in the National Health System (NHS) of Spain. This was a retrospective descriptive study using the minimum basic data set (CMBD in Spanish) in patients admitted to hospitals of the NHS between 1997 and 2015 with a diagnosis of cat scratch disease (ICD-9: 078.3). We found 781 hospitalized patients diagnosed with cat scratch disease. The mean age (± SD) was 30.7 ± 25.3 years old. The male/female ratio was 1.1:1. The incidence rate over the study period was 0.93 (95% CI, 0.86-0.99) cases per million person-years. The incidence rate in men was 0.98 cases per million person-years and that in women was 0.88 cases per million person-years. The cases were more frequent from September to January. A total of 652 (83.5%) cases were urgent hospital admissions. The average hospital stay was 8.4 ± 8.9 days. The overall lethality rate of the cohort was 1.3%. We have demonstrated that CSD causes a substantial burden of disease in Spain, affecting both adult and pediatric patients with a stable incidence rate. Our data suggest that CSD is benign and self-limited, with low mortality, and its incidence is possibly underestimated. Finally, there is a need for a common national strategy for data collection, monitoring, and reporting, which would facilitate a more accurate picture and the design of more strategic control measures. Hospital discharge records (HDRs) could be a good database for the epidemiological analysis of the hospital management of CSD.

Bartonella infections diagnosed in the French reference center, 2014-2019, and focus on infections in the immunocompromised.

We studied retrospectively 651 PCR-confirmed Bartonella infections diagnosed at the French reference center for bartonellosis from 2014 to 2019. The most common form was cat-scratch disease (89%) followed by endocarditis (9%). Disseminated forms (2%) mainly presented as bacillary angiomatosis or peliosis hepatis in solid organ transplant recipients.

Cerebral epidural empyema due to Bartonella henselae: a case report.

BACKGROUND: Cat scratch disease frequently involves a benign, self-limited disease. Neurological forms associated with Bartonella henselae are uncommon, consisting mostly in neuroretinitis, encephalitis and meningitis. Cerebral epidural empyema has never described. CASE PRESENTATION: An adult patient was hospitalized for isolated headaches. Magnetic Resonance Imaging (MRI) identified typical features of cerebral epidural empyema. The diagnosis of B. henselae was performed incidentally by 16S rDNA gene sequencing on the abscess fluid, and confirmed by specific qPCR. We report here the first case, to our knowledge, of cerebral epidural empyema associated with B. henselae. Further follow-up visits allowed identifying frequent cat scratches on the scalp as the presumptive source of infection. CONCLUSIONS: This case report alerts about such atypical clinical presentation, which requires an extensive clinical investigation. It also emphasizes on the usefulness of additional molecular diagnosis techniques in such CNS infection cases.

Bartonella henselae IgM seropositivity in both adult and pediatric patients with diverse clinical conditions in Turkey.

Bartonella henselae is the causative agent of cat scratch disease (CSD). In this study, we aimed to investigate the clinical data of patients with suspicion of CSD and delineate current epidemiological features.A total of 785 patients with suspected CSD were included in the study. B. henselae IgM antibody was determined by indirect fluorescent antibody (IFA) test using a commercial kit (Euroimmun, Germany). Sex, age, clinical pre-diagnosis and animal contact information of the patients were obtained from hospital electronic database records.Seventy-eight (9.9%) of 785 samples were seropositive. Out of 78 patients, 46 with animal contact data were further analyzed. Of these patients, 56% were male, and 41% were under 18 years of age. Seropositivity was more commonly observed in fall and winter. The most common finding was lymphadenitis (63%). Thirty-five patients (76%) had a previous history of animal contact (cat/dog). Of the 46 seropositive patients, 78.3, 15.2, 4.4, and 2.1% had titers of 1:80, 1:160, 1:320, and 1:640, respectively.Our study confirms that CSD is not rare in Turkey. Thus, it should always be considered in the differential diagnosis of patients presenting with lymphadenopathy in all age groups, particularly children. Questioning of cat exposure should never be neglected, especially in areas with intense population of stray cats, such as Istanbul.

Posterior Segment Manifestations of Cat-scratch Disease: A Mini-review of the Clinical and Multi-modal Imaging Features.

Bartonella henselae, an intracellular gram-negative bacillus, is usually transmitted from infected cats to humans by direct or indirect contact. The bacterium mainly infects erythrocytes and endothelial cells thereby leading to so called cat-scratch disease (CSD) and may present with various localised and/or systemic manifestations. The eye is the most commonly affected organ in disseminated CSD and ocular bartonellosis has been reported in 5-10% of CSD patients. The most well-known clinical feature of ocular bartonellosis is neuroretinitis but various sight-threatening posterior segment lesions involving the optic nerve, retinal vasculature, retinal and choroidal tissues may occur during the disease course. This mini-review aims to overview both the clinical and multi-modal imaging characteristics of posterior ocular segment manifestations of CSD.

Cat Scratch Disease Presenting as Fever of Unknown Origin Is a Unique Clinical Syndrome.

BACKGROUND: Fever of unknown origin (FUO) is a rare manifestation of cat scratch disease (CSD). Data regarding CSD-associated FUO (CSD-FUO), particularly in adults, are limited. We aimed to study disease manifestations and long-term clinical outcome. METHODS: A national CSD surveillance study has been conducted in Israel since 1991. Data are obtained using questionnaires, review of medical records, and telephone interviews. FUO was defined as fever of ≥14 days without an identifiable cause. CSD-FUO patients were identified in the 2004-2017 CSD national registry. Follow-up included outpatient clinic visits and telephone/e-mail surveys. RESULTS: The study included 66 CSD-FUO patients. Median age was 35.5 years (range, 3-88). Median fever duration was 4 weeks (range, 2-9). Relapsing fever pattern was reported in 52% of patients, weight loss in 57%, and night sweats in 48%. Involvement of ≥1 organs occurred in 59% of patients; hepatosplenic space-occupying lesions (35%), abdominal/mediastinal lymphadenopathy (20%), ocular disease (18%), and multifocal osteomyelitis (6%) were the most common. Malignancy, particularly lymphoma, was the initial radiological interpretation in 21% of patients; 32% underwent invasive diagnostic procedures. Of the 59 patients available for follow-up (median duration, 31 weeks; range, 4-445), 95% had complete recovery; 3 patients remained with ocular sequelae. CONCLUSION: This is the first attempt to characterize CSD-FUO as a unique syndrome that may be severe and debilitating and often mimics malignancy. Relapsing fever is a common clinical phenotype. Multiorgan involvement is common. Recovery was complete in all patients except in those with ocular disease.

Atypical Manifestations of Cat-Scratch Disease, United States, 2005-2014.

Atypical manifestations that can be severe and difficult to diagnosis develop in 5%-20% of patients with cat-scratch disease. To clarify the epidemiology of atypical cat-scratch disease in the United States, we analyzed data from the 2005-2014 MarketScan national health insurance claims databases by using the International Classification of Diseases, 9th Revision, Clinical Modification, codes for cat-scratch disease and selected atypical manifestations: retinitis/neuroretinitis, conjunctivitis, neuritis, encephalitis, hepatosplenic disease, osteomyelitis, erythema nodosum, and endocarditis. Atypical cat-scratch disease accounted for 1.5% of all cases, resulting in an average annual incidence of 0.7 cases/100,000 population. Atypical cat-scratch disease was associated with increased risk for hospitalization (risk ratios 8.77, 95% CI 6.56-11.72) and occurred most often in female patients 10-14 years of age. Ocular (48.7%), hepatosplenic (24.6%), and neurologic (13.8%) manifestations were most common among patients. A more comprehensive understanding of atypical cat-scratch disease can improve patient diagnosis and potentially elucidate pathophysiology of the disease.

Hemophagocytic lymphohistiocytosis is associated with Bartonella henselae infection in a patient with multiple susceptibility genes.

BACKGROUND: Adult-onset hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition, which is often triggered by certain types of infection, cancer and numerous autoimmune diseases; however, of the numerous infectious triggers associated with HLH, the consequences of Bartonella henselae infection have been rarely reported. CASE PRESENTATION: A 48-year-old female presented with a 20-day history of intermittent fever accompanied by systemic rash, fatigue, anorexia and weight loss later she developed shock and unconsciousness. Blood tests showed a reduction of leukocyte, anemia and thrombocytopenia, and pathological results of a bone marrow biopsy confirmed hemophagocytic activity. Metagenomic next-generation sequencing (mNGS) analysis of the lymph node detected the presence of B. henselae. Whole exome sequencing revealed two gene variants, STXBP2 and IRF5, in this adult patient with secondary HLH. Then, she received minocycline and rifampin combination anti-infective therapy. Intravenous immunoglobulin for 5 days followed by a high dose of methylprednisolone were also administered. The patient was successfully discharged from the intensive care unit and remained in good condition after 2 months of follow-up. CONCLUSIONS: mNGS served crucial roles in obtaining an etiological diagnosis, which suggested that screening for B. henselae should be considered in patients with HLH, especially those with a cat at home. In addition, the genetic defects were discovered to not only be present in primary HLH, but also in secondary HLH, even in the elderly.

Bartonella henselae encephalopathy in a paediatric patient: A case report and treatment review.

WHAT IS KNOWN AND OBJECTIVES: Bartonella henselae is the etiologic agent of "cat scratch disease (CSD)". We describe a case of atypical CSD in a paediatric patient and include a review of the antibiotic treatment for this disease. CASE DESCRIPTION: A 2-year-old child, with convulsive status and loss of consciousness, was admitted to hospital. Several antiepileptics and antibiotics were prescribed due to suspected central nervous system infection. When serology revealed Bartonella henselae antibodies, targeted antibiotic therapy was initiated and symptoms improved. However, seizures reappeared days after finishing the treatment so antiepileptics and antibiotics were reintroduced. WHAT IS NEW AND CONCLUSION: A wide variety of antibiotic regimens have been used for the treatment of atypical CSD in paediatric patients. This report includes the case of a paediatric patient diagnosed with atypical CSD who presented neurological manifestations, and for which a regimen consisting of azithromycin and rifampin was employed to achieve recovery.