6 results on '"Slater, Damien"'
Search Results
2. Association between chlorine-treated drinking water, the gut microbiome, and enteric pathogen burden in young children in Haiti: An observational study
- Author
-
Chac, Denise, Slater, Damien M., Guillaume, Yodeline, Dunmire, Chelsea N., Ternier, Ralph, Vissières, Kenia, Juin, Stanley, Lucien, Mentor Ali Ber, Boncy, Jacques, Sanchez, Vanessa M., Dumayas, Mia G., Augustin, Gertrude Cene, Bhuiyan, Taufiqur R., Qadri, Firdausi, Chowdhury, Fahima, Khan, Ashraful I., Weil, Ana A., Ivers, Louise C., and Harris, Jason B.
- Published
- 2024
- Full Text
- View/download PDF
3. Effectiveness of the Euvichol® oral cholera vaccine at 2 years: A case-control and bias-indicator study in Haiti
- Author
-
Matias, Wilfredo R., Guillaume, Yodeline, Cene Augustin, Gertrude, Vissieres, Kenia, Ternier, Ralph, Slater, Damien M., Harris, Jason B., Franke, Molly F., and Ivers, Louise C.
- Published
- 2024
- Full Text
- View/download PDF
4. Clinical and Genomic Characterization of a Cohort of Patients With Klebsiella pneumoniae Bloodstream Infection.
- Author
-
Roach, David J, Sridhar, Sushmita, Oliver, Elizabeth, Rao, Sowmya R, Slater, Damien M, Hwang, Wontae, Vater, Kian Hutt, Dinesh, Anupama, Qadri, Firdausi, Chisti, Mohammod J, Pierce, Virginia M, Turbett, Sarah E, Bhattacharyya, Roby P, Worby, Colin J, Earl, Ashlee M, LaRocque, Regina C, and Harris, Jason B
- Subjects
BACTEREMIA ,KLEBSIELLA ,SEQUENCE analysis ,CONFIDENCE intervals ,MANN Whitney U Test ,ACQUISITION of data ,KLEBSIELLA infections ,RISK assessment ,HOSPITAL mortality ,T-test (Statistics) ,GENOMES ,SYMPTOMS ,RESEARCH funding ,DESCRIPTIVE statistics ,CHI-squared test ,MEDICAL records ,DRUG resistance in microorganisms ,DATA analysis software ,ODDS ratio ,LOGISTIC regression analysis ,MICROBIAL virulence - Abstract
Background The clinical and microbial factors associated with Klebsiella pneumoniae bloodstream infections (BSIs) are not well characterized. Prior studies have focused on highly resistant or hypervirulent isolates, limiting our understanding of K. pneumoniae strains that commonly cause BSI. We performed a record review and whole-genome sequencing to investigate the clinical characteristics, bacterial diversity, determinants of antimicrobial resistance, and risk factors for in-hospital death in a cohort of patients with K. pneumoniae BSI. Methods We identified 562 patients at Massachusetts General Hospital with K. pneumoniae BSIs between 2016 and 2022. We collected data on comorbid conditions, infection source, clinical outcomes, and antibiotic resistance and performed whole-genome sequencing on 108 sequential BSI isolates from 2021 to 2022. Results Intra-abdominal infection was the most common source of infection accounting for 34% of all BSIs. A respiratory tract source accounted for 6% of BSIs but was associated with a higher in-hospital mortality rate (adjusted odds ratio, 5.4 [95% confidence interval, 2.2–12.8]; P <.001 for comparison with other sources). Resistance to the first antibiotic prescribed was also associated with a higher risk of death (adjusted odds ratio, 5.2 [95% confidence interval, 2.2–12.4]; P <.001). BSI isolates were genetically diverse, and no clusters of epidemiologically and genetically linked cases were observed. Virulence factors associated with invasiveness were observed at a low prevalence, although an unexpected association between O-antigen type and the source of infection was found. Conclusions These observations demonstrate the versatility of K. pneumoniae as an opportunistic pathogen and highlight the need for new approaches for surveillance and the rapid identification of patients with invasive antimicrobial-resistant K. pneumoniae infection. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
5. Multiplexed real-time PCR for the detection and differentiation of Klebsiella pneumoniae O-antigen serotypes.
- Author
-
Slater D, Hutt Vater K, Sridhar S, Hwang W, Bielawski D, Turbett SE, LaRocque RC, and Harris JB
- Subjects
- Humans, Multiplex Polymerase Chain Reaction methods, Whole Genome Sequencing, Klebsiella pneumoniae genetics, Klebsiella pneumoniae isolation & purification, Klebsiella pneumoniae classification, Klebsiella pneumoniae immunology, O Antigens genetics, O Antigens immunology, O Antigens analysis, Klebsiella Infections diagnosis, Klebsiella Infections microbiology, Real-Time Polymerase Chain Reaction methods, Feces microbiology, Serogroup, Serotyping methods
- Abstract
Klebsiella pneumoniae has emerged as a global health threat due to its role in the spread of antimicrobial resistance and because it is a frequent cause of hospital-acquired infections and neonatal sepsis. Capsular and lipopolysaccharide (LPS) O-antigen polysaccharide surface antigens are major immunogens that are useful for strain classification and are candidates for vaccine development. We have developed real-time PCR reagents for molecular serotyping, subtyping, and quantitation of the most prevalent LPS O-antigen types (i.e., O1, O2, O3, and O5) of Klebsiella pneumoniae . We describe two applications for this O-typing assay: for screening culture isolates and for direct typing of Klebsiella pneumoniae present in stool samples. We find 100% concordance between the results of the O-typing assay and whole-genome sequencing of 81 culture isolates, and >90% agreement in O-typing performed directly on specimens of human stool, with disagreement arising primarily from a lack of sensitivity of the culture-based comparator method. Additionally, we find evidence for mixed O-type populations at varying levels of abundance in direct tests of stool from a hospitalized patient population. Taken together, these results demonstrate that this novel O-typing assay can be a useful tool for K. pneumoniae epidemiologic and vaccine studies.IMPORTANCE Klebsiella pneumoniae is an important opportunistic pathogen. The gastrointestinal (GI) tract is the primary reservoir of K. pneumoniae in humans, and GI carriage is believed to be a prerequisite for invasive infection. Knowledge about the dynamics and duration of GI carriage has been hampered by the lack of tools suitable for detection and strain discrimination. Real-time PCR is particularly suited to the higher-throughput workflows used in population-based studies, which are needed to improve our understanding of carriage dynamics and the factors influencing K. pneumoniae colonization., Competing Interests: The authors declare no conflict of interest.
- Published
- 2024
- Full Text
- View/download PDF
6. Antibody responses in Klebsiella pneumoniae bloodstream infection: a cohort study.
- Author
-
Hwang W, Wantuch PL, Bernshtein B, Zhiteneva J, Slater D, Vater KH, Sridhar S, Oliver E, Roach DJ, Rao S, Turbett SE, Knoot CJ, Harding CM, Amin MN, Cross AS, LaRocque RC, Rosen DA, and Harris JB
- Abstract
Background: Klebsiella pneumonia (Kpn) is the fourth leading cause of infection-related deaths globally, yet little is known about human antibody responses to invasive Kpn. In this study, we sought to determine whether the O-specific polysaccharide (OPS) antigen, a vaccine candidate, is immunogenic in humans with Kpn bloodstream infection (BSI). We also sought to define the cross-reactivity of human antibody responses among structurally related Kpn OPS subtypes and to assess the impact of capsule production on OPS-targeted antibody binding and function., Methods: We measured plasma antibody responses to OPS (and MrkA, a fimbrial protein) in a cohort of patients with Kpn BSI and compared these with controls, including a cohort of healthy individuals and a cohort of individuals with Enterococcus BSI. We performed flow cytometry to measure the impact of Kpn capsule production on whole cell antibody binding and complement deposition, utilizing patient isolates with variable levels of capsule production and isogenic capsule-deficient strains derived from these isolates., Findings: We enrolled 69 patients with Kpn BSI. Common OPS serotypes accounted for 57/69 (83%) of infections. OPS was highly immunogenic in patients with Kpn BSI, and peak OPS-IgG antibody responses in patients were 10 to 30-fold higher than antibody levels detected in healthy controls, depending on the serotype. There was significant cross-reactivity among structurally similar OPS subtypes, including the O1v1/O1v2, O2v1/O2v2 and O3/O3b subtypes. Physiological amounts of capsule produced by both hyperencapsulated and non-hyperencapsulated Kpn significantly inhibited OPS-targeted antibody binding and function., Interpretation: OPS was highly immunogenic in patients with Kpn BSI, supporting its potential as a candidate vaccine antigen. The strong cross-reactivity observed between similar OPS subtypes in humans with Kpn BSI suggests that it may not be necessary to include all subtypes in an OPS-based vaccine. However, these observations are tempered by the fact that capsule production, even in non-highly encapsulated strains, has the potential to interfere with OPS antibody binding. This may limit the effectiveness of vaccines that exclusively target OPS., Funding: National Institute of Allergy and Infectious Diseases at the National Institutes of Health., Research in Context: Evidence before this study: Despite the potential of O-specific polysaccharide (OPS) as a vaccine antigen against Klebsiella pneumoniae (Kpn), the immunogenicity of OPS in humans remains largely unstudied, creating a significant knowledge gap with regard to vaccine development. A search of PubMed for publications up to March 18, 2024, using the terms " Klebsiella pneumoniae " and "O-specific polysaccharide" or "O-antigen" or "lipopolysaccharide" revealed no prior studies addressing OPS antibody responses in humans with Kpn bloodstream infections (BSI). One prior study
1 evaluated antibody response to a single lipopolysaccharide (which contains one subtype of OPS) in humans with invasive Kpn infection; however, in this study OPS typing of the infecting strains and target antigen were not described. Added value of this study: Our investigation into OPS immunogenicity in a human cohort marks a significant advance. Analyzing plasma antibody responses in 69 patients with Kpn BSI, we found OPS to be broadly immunogenic across all the types and subtypes examined, and there was significant cross-reactivity among structurally related OPS antigens. We also demonstrated that Kpn capsule production inhibit OPS antibody binding and the activation of complement on the bacterial surface, even in classical Kpn strains expressing lower levels of capsule. Implications of all the available evidence: While the immunogenicity and broad cross-reactivity of OPS in humans with Kpn BSI suggests it is a promising vaccine candidate, the obstruction of OPS antibody binding and engagement by physiologic levels of Kpn capsule underscores the potential limitations of an exclusively OPS-antigen based vaccine for Kpn. Our study provides insights for the strategic development of vaccines aimed at combating Kpn infections, an important antimicrobial resistant pathogen.- Published
- 2024
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.