#28: Rapid, Non-invasive Detection of Invasive Bartonella Infections in Pediatric Patients Using the Karius Test, A Next-Generation Sequencing Test for Microbial Cell-free DNA in Plasma

2021 ◽  
Vol 10 (Supplement_2) ◽  
pp. S11-S11
Author(s):  
Nicholas Degner ◽  
Matt Smollin ◽  
Ozlem Equils ◽  
Aparna Arun ◽  
Christiaan DeVries ◽  
...  
Keyword(s):  
Prosthetic Valve ◽  
Fever Of Unknown Origin ◽  
Bartonella Henselae ◽  
Prosthetic Valve Endocarditis ◽  
Unknown Origin ◽  
Cat Scratch Disease ◽  
Bartonella Quintana ◽  
Non Invasive ◽  
Free Dna ◽  
Generation Sequencing

Abstract Background Bartonella henselae and Bartonella quintana are the etiologic agents of cat scratch disease (CSD) and “trench fever”, respectively. Both are important causes of culture-negative endocarditis and fever of unknown origin (FUO). The diagnosis of Bartonella infections is limited by (1) the nonspecific, protean manifestations of the disease and its broad differential diagnosis; (2) the fastidious nature of Bartonella spp., leading to rare detections with traditional culture based methods; (3) the insensitivity and poor specificity of Bartonella serologies. Rapid, non-invasive diagnosis of Bartonella through next-generation sequencing (NGS) of plasma microbial cell-free DNA (mcfDNA) offers a means to overcome these limitations. Here we describe the diagnosis of 23 Bartonella infections in children from August 2017 – December 2020 using plasma mcfDNA NGS. Methods The Karius Test (KT), developed and validated in Karius’ CLIA certified/CAP accredited lab, detects mcfDNA in plasma. After mcfDNA is extracted and NGS performed, human reads are removed, and remaining sequences are aligned to a curated database of > 1400 organisms. McfDNA from organisms present above a statistical threshold are reported and quantified in molecules/μL (MPM). Clinical information was included from data submitted with the requisition or obtained at the time of reporting from clinical consultations with the provider. Results KT detected Bartonella henselae mcfDNA in 22 cases and Bartonella quintana in 1. Detections included 10 cases of endocarditis (7 prosthetic valve), 12 cases of CSD/FUO, and a single case of osteomyelitis. Glomerulonephritis was reported in 5 the cases of endocarditis. Six cases had splenic involvement; three had hepatic involvement. History of cat exposure was elicited in 8 cases. The mean MPMs was highest for prosthetic valve endocarditis (mean 47,272 +/- 67,526) followed by native valve endocarditis (3,881 +/- 2,458), FUO/CSD (1,922 +/- 3,416), and osteomyelitis (119 +/- 0) (p<0.05). Three subjects had serial mcfDNA monitoring. Predictable declines in Bartonella mcfDNA were observed in response to therapy in all three patients. The duration of positive Bartonella mcfDNA signal ranged from 22–42 days (30.7, +/- 10.3). Conclusion Open-ended, plasma-based NGS for mcfDNA provides a rapid, non-invasive method to diagnose diverse clinical manifestations of invasive pediatric Bartonella infection against a competing broad differential diagnosis. The quantification of mcfDNA may further help in differentiating the various clinical syndromes caused by Bartonella. Finally, serial monitoring to trend MPMs may serve as an indicator of burden of infection, provide a means to monitor treatment efficacy and ultimately help define the length of therapy for optimal outcomes. All detections are Bartonella henselae except for one case of *Bartonella quintana (prosthetic valve endocarditis). MPM=molecules/μL; GN=glomerulonephritis, LN=lymph node involvement, FUO=fever of unknown origin, CSD=cat scratch disease

scholarly journals A case of Bartonellosis presenting as a puzzling multisystem disorder complicated by nosocomial COVID-19 infection

2021 ◽  
Vol 14 (8) ◽  
pp. e244002
Author(s):  
Huw Garland ◽  
Sarah Stoll ◽  
Shalinee Patel ◽  
Rahul Mogal
Keyword(s):  
Fever Of Unknown Origin ◽  
Bartonella Henselae ◽  
Unknown Origin ◽  
Cat Scratch Disease ◽  
Invasive Ventilation ◽  
Multisystem Disorder ◽  
Unique Case ◽  
Non Invasive ◽  
Non Invasive Ventilation ◽  
History Of

The most commonly considered infection with a Bartonella species is cat-scratch disease caused by Bartonella henselae. Here, we discuss a unique case of a 60-year-old man who presented with Bartonella infection complicated by nosocomial COVID-19. He was admitted with a history of chest pain, persistent fever, rash and influenza-like symptoms. Positive Bartonella serology confirmed diagnosis and the patient developed complications of pericardial effusion in addition to COVID-19 infection, requiring non-invasive ventilation and admission to the intensive care unit. We discuss his symptoms, investigations, treatment and outcomes, while also highlighting the challenges of assessing patients presenting with fever of unknown origin during the COVID-19 pandemic.

scholarly journals Abscess-forming lymphadenopathy and osteomyelitis in children with Bartonella henselae infection

2008 ◽  
Vol 57 (4) ◽  
pp. 519-524 ◽  
Author(s):  
Regina Ridder-Schröter ◽  
Aleander Marx ◽  
Meinrad Beer ◽  
Dennis Tappe ◽  
Hans-Wolfgang Kreth ◽  
...  
Keyword(s):  
Lymph Node ◽  
Fever Of Unknown Origin ◽  
Bartonella Henselae ◽  
Systemic Infection ◽  
Unknown Origin ◽  
Lymph Node Biopsy ◽  
Cat Scratch Disease ◽  
Node Biopsy ◽  
Systemic Complication ◽  
Draining Lymph Nodes

Bartonella henselae is the agent of cat-scratch disease (CSD), a chronic lymphadenopathy among children and adolescents. A systemic infection is very rare and most of these cases are found in patients with immunodeficiency. Here, cases involving four children of 6–12 years of age are reported. Three of the children had an abscess-forming lymphadenopathy and surrounding myositis in the clavicular region of the upper arm. The diagnosis was made serologically and, in one case, using eubacterial universal PCR. One child was treated with erythromycin for 10 days, the second received cefotaxime and flucloxacillin for 14 days and the third child was not treated with antibiotics. The fourth child had a different course: a significantly elevated signal intensity affecting the complete humerus was found in magnetic resonance imaging, consistent with osteomyelitis. A lymph node abscess was also found in the axilla. Diagnosis was established by indirect fluorescence assay and lymph node biopsy. Antibiotic therapy using clarithromycin, clindamycin and rifampicin was gradually successful. Immunodeficiency was excluded. All described lesions healed without residues. In immunocompetent patients, infection affects skin and draining lymph nodes; however, prolonged fever of unknown origin as in the fourth patient indicated a systemic complication of CSD.

scholarly journals SystemicBartonella henselaeInfection in Immunocompetent Adult Presenting as Fever of Unknown Origin

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Thierry Zenone
Keyword(s):  
Clinical Picture ◽  
Fever Of Unknown Origin ◽  
Bartonella Henselae ◽  
Unknown Origin ◽  
Diagnosis And Treatment ◽  
Cat Scratch Disease ◽  
Immunocompetent Adult ◽  
Clinical Presentations ◽  
Splenic Involvement ◽  
Immunocompetent Adults

Systemic clinical presentations of infection caused byBartonella henselaeare rare in immunocompetent adults. We report four cases with hepatic and/or splenic involvement, presenting as fever of unknown origin. We discuss diagnosis and treatment of this infection.Bartonella henselaeserology allows an easy diagnosis of hepatosplenic involvement in cat scratch disease, a clinical picture that appears to be underrecognized.

scholarly journals 670. Rapid, Non-invasive Detection of Invasive Mycoplasma hominis Infection using the Karius Test, A Next-Generation Sequencing Test for Microbial Cell-free DNA in Plasma

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S390-S390
Author(s):  
Priya Edward ◽  
William V La Via ◽  
Mehreen Arshad ◽  
Kiran Gajurel
Keyword(s):  
Next Generation Sequencing ◽  
Case Series ◽  
Mycoplasma Hominis ◽  
Microbial Cell ◽  
Next Generation ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Hominis Infection ◽  
Generation Sequencing

Abstract Background Mycoplasma hominis is typically associated with genital infections in women and is a rare cause of musculoskeletal infections often in immunocompromised hosts. Diagnosis of invasive Mycoplasma hominis infections are difficult due to challenges in culturing these organisms. Molecular diagnostics require an index of suspicion which may not be present at the time of tissue sampling. Accurate, rapid diagnosis of Mycoplasma hominis infections are important for antibiotic management. Methods Two cases of invasive Mycoplasma hominis infections are presented in which the Karius test (KT) was used to make the diagnosis. The KT is a CLIA certified/CAP-accredited next-generation sequencing (NGS) plasma test that detects microbial cell-free DNA (mcfDNA). After mcfDNA is extracted and NGS performed, human reads are removed and remaining sequences are aligned to a curated database of > 1400 organisms. Organisms present above a statistical threshold are reported. Case review was performed for clinical correlation. Results A young woman with lupus nephritis status post renal transplant developed persistent fever with progressive multifocal culture-negative osteoarticular infection despite empiric ceftriaxone. An adolescent female presented with an ascending pelvic infection progressing to purulent polymicrobial peritonitis (see table) requiring surgical debridement and cefipime, metronidazole and micafungin therapy; her course was complicated by progressive peritonitis/abscesses. Karius testing detected high-levels of Mycoplasma hominis mcfDNA in both cases – at 3251 molecules/microliter (MPM) in the first case and 3914 MPM in the second case. The normal range of Mycoplasma hominis mcfDNA in a cohort of 684 normal adults is 0 MPM. The patients rapidly improved with atypical coverage with doxycycline and levofloxaxin. Clinical findings in 2 patients with M. hominis infection detected by the Karius Test Conclusion Open-ended, plasma-based NGS for mcfDNA provides a rapid, non-invasive method to diagnose invasive Mycoplasma hominis infection. This case series highlights the potential to diagnose infections caused by fastidious pathogens to better inform antimicrobial therapy and achieve favorable outcomes. Disclosures William V. La Via, MD, Karius (Employee)

Cat-Scratch Disease Presenting as Fever of Unknown Origin

Consultant ◽  
2021 ◽  
Author(s):  
Sajiv Alias ◽  
◽  
Nathan F. Bradford ◽  
Zachary J. Grey ◽  
◽  
...  
Keyword(s):  
Fever Of Unknown Origin ◽  
Unknown Origin ◽  
Cat Scratch Disease

scholarly journals Cat Scratch Disease: The Story Continues

1997 ◽  
Vol 8 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Mary Anne Opavsky
Keyword(s):  
Clinical Characteristics ◽  
Bartonella Henselae ◽  
Data Extraction ◽  
Significant Risk ◽  
Unknown Origin ◽  
Etiological Agent ◽  
Cat Scratch Disease ◽  
Serological Tests ◽  
Medline Search ◽  
Atypical Presentations

OBJECTIVE: To present a perspective on the current state of knowledge of cat scratch disease (CSD), including the evidence forBartonella henselaeas the etiological agent, epidemiological and clinical characteristics of the disease, available diagnostic tests and current therapeutic options.DATA SOURCES: MEDLINE search of the literature published from 1966 to 1995 using ‘cat scratch disease’, ‘Bartonella henselae’, ‘Rochalimaea henselae’ as key words and bibliographies of selected papers.DATA EXTRACTION: Selected studies reporting data on etiology, epidemiology, clinical characteristics, diagnosis and therapy of CSD were evaluated.DATA SYNTHESIS AND CONCLUSIONS: Evidence accumulated to date supportsB henselaeas the etiological agent of CSD. The most significant risk factors for CSD are being licked on the face, scratched or bitten by a kitten and owning a kitten with fleas. Available serological tests can confirm classic CSD and identifyB henselaeas the cause of more atypical presentations, such as fever of unknown origin, granulomatous hepatitis, encephalitis and osteomyelitis. Symptomatic management is appropriate for isolated lymphadenopathy caused by CSD in healthy individuals; however, antibiotic therapy may be indicated for patients with more severe manifestations of the disease and immunocompromised hosts. Further study of CSD, in particular the epidemiology and therapy, is warranted. A better understanding of the pathogenesis ofB henselaeinfection will have important implications in both immunocompetent and immunocompromised individuals.

scholarly journals COMP-20. THE NON-INVASIVE DETECTION OF GLIOBLASTOMA-DERIVED CELL-FREE DNA IN PLASMA USING NEXT-GENERATION SEQUENCING AND AN UNTARGETED VARIANT SEARCH

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi67-vi68
Author(s):  
Hunter Underhill ◽  
Sabine Hellwig ◽  
David Nix ◽  
Preetida Bhetariya ◽  
Carrie Fuertes ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Next Generation ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Generation Sequencing

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

2019 ◽  
Vol 71 (11) ◽  
pp. 2818-2824 ◽  
Author(s):  
Michal Landes ◽  
Yasmin Maor ◽  
Diego Mercer ◽  
Zohar Habot-Wilner ◽  
Efraim Bilavsky ◽  
...  
Keyword(s):  
Fever Of Unknown Origin ◽  
Unknown Origin ◽  
Complete Recovery ◽  
National Registry ◽  
Clinical Syndrome ◽  
Ocular Disease ◽  
Mediastinal Lymphadenopathy ◽  
Cat Scratch Disease ◽  
Relapsing Fever

Abstract 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.

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