8 results on '"LaRocque, Regina C."'
Search Results
2. Cholera toxin and O-specific polysaccharide immune responses after oral cholera vaccination with Dukoral in different age groups of Bangladeshi participants.
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Dash, Pinki, Hakim, Al, Akter, Aklima, Al Banna, Hasan, Kaisar, M. Hasanul, Aktar, Amena, Jahan, Sultana Rownok, Ferdous, Jannatul, Basher, Salima Raiyan, Kamruzzaman, Mohammad, Chowdhury, Fahima, Akter, Afroza, Tauheed, Imam, Weil, Ana A., Charles, Richelle C., Calderwood, Stephen B., Ryan, Edward T., LaRocque, Regina C., Harris, Jason B., and Bhuiyan, Taufiqur Rahman
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- 2024
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3. Clinical and Genomic Characterization of a Cohort of Patients With Klebsiella pneumoniae Bloodstream Infection.
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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
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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]
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- 2024
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4. Knowledge, attitudes and practices regarding the use of mobile travel health apps.
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Machoko, Munashe M P, Dong, Yinan, Grozdani, Andonaq, Hong, Hung, Oliver, Elizabeth, Hyle, Emily P, Ryan, Edward T, Colubri, Andrés, and LaRocque, Regina C
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NAVIGATION & travel mobile apps ,SCIENTIFIC literature ,TRAVEL hygiene ,MOBILE hospitals ,MEDICAL care costs ,HEALTH facilities - Abstract
This article discusses the knowledge, attitudes, and practices of US international travelers regarding the use of mobile travel health apps. The study collected data from 261 participants through an electronic survey, which assessed their smartphone usage habits, internet accessibility while traveling, concerns about personal health, and preferences for features in a travel health app. The majority of participants reported always carrying a smartphone during international travel and expressed interest in receiving health information through a travel health app. Preferred features for the app included real-time alerts about local outbreaks, information about nearby medical facilities, and COVID-19 travel-related restrictions. However, some participants had concerns about data security and privacy. The study provides insights into travelers' perspectives on mobile health apps and supports further development in this area. [Extracted from the article]
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- 2024
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5. Vibrio cholerae O1 experiences mild bottlenecks through the gastrointestinal tract in some but not all cholera patients.
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Lypaczewski P, Chac D, Dunmire CN, Tandoc KM, Chowdhury F, Khan AI, Bhuiyan TR, Harris JB, LaRocque RC, Calderwood SB, Ryan ET, Qadri F, Shapiro BJ, and Weil AA
- Abstract
Vibrio cholerae O1 causes the diarrheal disease cholera, and the small intestine is the site of active infection. During cholera, cholera toxin is secreted from V. cholerae and induces a massive fluid influx into the small intestine, which causes vomiting and diarrhea. Typically, V. cholerae genomes are sequenced from bacteria passed in stool, but rarely from vomit, a fluid that may more closely represents the site of active infection. We hypothesized that V. cholerae O1 population bottlenecks along the gastrointestinal tract would result in reduced genetic variation in stool compared to vomit. To test this, we sequenced V. cholerae genomes from 10 cholera patients with paired vomit and stool samples. Genetic diversity was low in both vomit and stool, consistent with a single infecting population rather than coinfection with divergent V. cholerae O1 lineages. The amount of single-nucleotide variation decreased from vomit to stool in four patients, increased in two, and remained unchanged in four. The variation in gene presence/absence decreased between vomit and stool in eight patients and increased in two. Pangenome analysis of assembled short-read sequencing demonstrated that the toxin-coregulated pilus operon more frequently contained deletions in genomes from vomit compared to stool. However, these deletions were not detected by PCR or long-read sequencing, indicating that interpreting gene presence or absence patterns from short-read data alone may be incomplete. Overall, we found that V. cholerae O1 isolated from stool is genetically similar to V. cholerae recovered from the upper intestinal tract., Importance: Vibrio cholerae O1, the bacterium that causes cholera, is ingested in contaminated food or water and then colonizes the upper small intestine and is excreted in stool. Shed V. cholerae genomes from stool are usually studied, but V. cholerae isolated from vomit may be more representative of where V. cholerae colonizes in the upper intestinal epithelium. V. cholerae may experience bottlenecks, or large reductions in bacterial population sizes and genetic diversity, as it passes through the gut. Passage through the gut may select for distinct V. cholerae mutants that are adapted for survival and gut colonization. We did not find strong evidence for such adaptive mutations, and instead observed that passage through the gut results in modest reductions in V. cholerae genetic diversity, and only in some patients. These results fill a gap in our understanding of the V. cholerae life cycle, transmission, and evolution.
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- 2024
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6. Modeling approaches to inform travel-related policies for COVID-19 containment: a scoping review and future directions.
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Koiso S, Gulbas E, Dike L, Mulroy NM, Ciaranello AL, Freedberg KA, Jalali MS, Walker AT, Ryan ET, LaRocque RC, and Hyle EP
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Background: Travel-related strategies to reduce the spread of COVID-19 evolved rapidly in response to changes in the understanding of SARS-CoV-2 and newly available tools for prevention, diagnosis, and treatment. Modeling is an important methodology to investigate the range of outcomes that could occur from different disease containment strategies., Methods: We examined 43 articles published from December 2019 through September 2022 that used modeling to evaluate travel-related COVID-19 containment strategies. We extracted and synthesized data regarding study objectives, methods, outcomes, populations, settings, strategies, and costs. We used a standardized approach to evaluate each analysis according to 26 criteria for modeling quality and rigor., Results: The most frequent approaches included compartmental modeling to examine quarantine, isolation, or testing. Early in the pandemic, the goal was to prevent travel-related COVID-19 cases with a focus on individual-level outcomes and assessing strategies such as travel restrictions, quarantine without testing, social distancing, and on-arrival PCR testing. After the development of diagnostic tests and vaccines, modeling studies projected population-level outcomes and investigated these tools to limit COVID-19 spread. Very few published studies included rapid antigen screening strategies, costs, explicit model calibration, or critical evaluation of the modeling approaches., Conclusion: Future modeling analyses should leverage open-source data, improve the transparency of modeling methods, incorporate newly available prevention, diagnostics, and treatments, and include costs and cost-effectiveness so that modeling analyses can be informative to address future SARS-CoV-2 variants of concern and other emerging infectious diseases (e.g., mpox and Ebola) for travel-related health policies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)
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- 2024
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7. Antibody responses in Klebsiella pneumoniae bloodstream infection: a cohort study.
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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
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8. Diversity of Vibrio cholerae O1 through the human gastrointestinal tract during cholera.
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Lypaczewski P, Chac D, Dunmire CN, Tandoc KM, Chowdhury F, Khan AI, Bhuiyan T, Harris JB, LaRocque RC, Calderwood SB, Ryan ET, Qadri F, Shapiro BJ, and Weil AA
- Abstract
Vibrio cholerae O1 causes the diarrheal disease cholera, and the small intestine is the site of active infection. During cholera, cholera toxin is secreted from V. cholerae and induces a massive fluid influx into the small intestine, which causes vomiting and diarrhea. Typically, V. cholerae genomes are sequenced from bacteria passed in stool, but rarely from vomit, a fluid that may more closely represents the site of active infection. We hypothesized that the V. cholerae O1 population bottlenecks along the gastrointestinal tract would result in reduced genetic variation in stool compared to vomit. To test this, we sequenced V. cholerae genomes from ten cholera patients with paired vomit and stool samples. Genetic diversity was low in both vomit and stool, consistent with a single infecting population rather than co-infection with divergent V. cholerae O1 lineages. The number of single nucleotide variants decreased between vomit and stool in four patients, increased in two, and remained unchanged in four. The number of genes encoded in the V. cholerae genome decreased between vomit and stool in eight patients and increased in two. Pangenome analysis of assembled short-read sequencing demonstrated that the toxin-coregulated pilus operon more frequently contained deletions in genomes from vomit compared to stool. However, these deletions were not detected by PCR or long-read sequencing, indicating that interpreting gene presence or absence patterns from short-read data alone may be incomplete. Overall, we found that V. cholerae O1 isolated from stool is genetically similar to V. cholerae recovered from the upper intestinal tract.
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- 2024
- Full Text
- View/download PDF
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