356 results on '"Ryan ET"'
Search Results
2. Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: the Global Burden of Disease Study 1990-2016
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Khalil, IA, Troeger, C, Blacker, BF, Rao, PC, Brown, A, Atherly, DE, Brewer, TG, Engmann, CM, Houpt, ER, Kang, G, Kotloff, KL, Levine, MM, Luby, SP, Maclennan, CA, Pan, WK, Pavlinac, PB, Platts-Mills, JA, Qadri, F, Riddle, MS, Ryan, ET, Shoultz, DA, Steele, AD, Walson, JL, Sanders, JW, Mokdad, AH, Murray, CJL, Hay, SI, and Reiner, RC
- Published
- 2018
3. In the clinic. Travel medicine.
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Schwartz BS, Larocque RC, Ryan ET, Schwartz, Brian S, Larocque, Regina C, and Ryan, Edward T
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PREVENTION of bites & stings ,ENVIRONMENTALLY induced diseases ,TRAFFIC safety ,PREVENTION of communicable diseases ,COUNSELING ,HEALTH status indicators ,IMMUNIZATION ,INSECTS ,PATIENT education ,RESEARCH funding ,RISK assessment ,TRAVEL hygiene ,PREVENTION - Published
- 2012
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4. Immune responses to cholera in children.
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Leung DT, Chowdhury F, Calderwood SB, Qadri F, Ryan ET, Leung, Daniel T, Chowdhury, Fahima, Calderwood, Stephen B, Qadri, Firdausi, and Ryan, Edward T
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Cholera is a severe acute dehydrating diarrheal disease caused by Vibrio cholerae O1 or O139 infection, and is associated with significant mortality and morbidity globally. Although young children bear a high burden of the disease, currently available oral vaccines give a lower efficacy and shorter duration of protection in this group than in adults. According to the studies of natural infection, young children achieve comparable systemic anti-V. cholerae antigen-specific antibody, gut-homing antibody-secreting cell and memory B-cell responses as adults. Studies on innate and cell-mediated immune responses are lacking in children, and may offer important insights into differences in vaccine efficacy. The impact of host factors such as malnutrition, genetics and coinfection with other pathogens also remains to be fully defined. [ABSTRACT FROM AUTHOR]
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- 2012
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5. Case records of the Massachusetts General Hospital. Case 38-2011. A 34-year-old man with diarrhea and weakness.
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Ryan ET, Cronin CG, Branda JA, Ryan, Edward T, Cronin, Carmel G, and Branda, John A
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- 2011
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6. Case records of the Massachusetts General Hospital. Case 20-2011. A 30-year-old man with diarrhea after a trip to the Dominican Republic.
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Ryan ET, Madoff LC, and Ferraro MJ
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- 2011
7. Pre-travel health advice-seeking behavior among US international travelers departing from Boston Logan International Airport.
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Larocque RC, Rao SR, Tsibris A, Lawton T, Anita Barry M, Marano N, Brunette G, Yanni E, Ryan ET, LaRocque, Regina C, Rao, Sowmya R, Tsibris, Athe, Lawton, Thomas, Barry, M Anita, Marano, Nina, Brunette, Gary, Yanni, Emad, and Ryan, Edward T
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Background: Globally mobile populations are at higher risk of acquiring geographically restricted infections and may play a role in the international spread of infectious diseases. Despite this, data about sources of health information used by international travelers are limited.Methods: We surveyed 1,254 travelers embarking from Boston Logan International Airport regarding sources of health information. We focused our analysis on travelers to low or low-middle income (LLMI) countries, as defined by the World Bank 2009 World Development Report.Results: A total of 476 survey respondents were traveling to LLMI countries. Compared with travelers to upper-middle or high income (UMHI) countries, travelers to LLMI countries were younger, more likely to be foreign-born, and more frequently reported visiting family as the purpose of their trip. Prior to their trips, 46% of these travelers did not pursue health information of any type. In a multivariate analysis, being foreign-born, traveling alone, traveling for less than 14 days, and traveling for vacation each predicted a higher odds of not pursuing health information among travelers to LLMI countries. The most commonly cited reason for not pursuing health information was a lack of concern about health problems related to the trip. Among travelers to LLMI countries who did pursue health information, the internet was the most common source, followed by primary care practitioners. Less than a third of travelers to LLMI countries who sought health information visited a travel medicine specialist.Conclusions: In our study, 46% of travelers to LLMI countries did not seek health advice prior to their trip, largely due to a lack of concern about health issues related to travel. Among travelers who sought medical advice, the internet and primary care providers were the most common sources of information. These results suggest the need for health outreach and education programs targeted at travelers and primary care practitioners. [ABSTRACT FROM AUTHOR]- Published
- 2010
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8. Management of travellers' diarrhoea.
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Hill DR and Ryan ET
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- 2008
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9. Case records of the Massachusetts General Hospital. Case 29-2007. A 51-year-old man with gastric cancer and lung nodules.
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Ryan ET, Aquino SL, Kradin RL, Ryan, Edward T, Aquino, Suzanne L, and Kradin, Richard L
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- 2007
10. Infectious diseases of severe weather-related and flood-related natural disasters.
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Ivers LC and Ryan ET
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- 2006
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11. Case records of the Massachusetts General Hospital. Case 39-2005. A 63-year-old woman with a positive serologic test for syphilis and persistent eosinophilia.
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Ryan ET, Felsenstein D, Aquino SL, Branda JA, Morgan JG, Ryan, Edward T, Felsenstein, Donna, Aquino, Suzanne L, Branda, John A, and Morgan, John G
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- 2005
12. Illness after international travel.
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Ryan ET, Wilson ME, Kain KC, Ryan, Edward T, Wilson, Mary E, and Kain, Kevin C
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- 2002
13. Cholera vaccines.
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Ryan ET, Calderwood SB, Ryan, E T, and Calderwood, S B
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- 2001
14. Clostridium difficile-associated diarrhea: a review.
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Mylonakis E, Ryan ET, and Calderwood SB
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- 2001
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15. Assessing Impacts of Unconventional Natural Gas Extraction on Microbial Communities in Headwater Stream Ecosystems in Northwestern Pennsylvania
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Ryan eTrexler, Caroline eSolomon, Colin J Brislawn, Justin R Wright, Abigail eRosenberger, Erin E McClure, Alyssa M Grube, Mark P Peterson, Mehdi eKeddache, Olivia eMason, Terry C Hazen, Christopher J Grant, and Regina eLamendella
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next generation sequencing ,16S rRNA gene sequencing ,beta diversity ,methanotrophs ,fracking ,marcellus shale ,Microbiology ,QR1-502 - Abstract
Hydraulic fracturing and horizontal drilling have increased dramatically in Pennsylvania Marcellus shale formations, however the potential for major environmental impacts are still incompletely understood. High-throughput sequencing of the 16S rRNA gene was performed to characterize the microbial community structure of water, sediment, bryophyte, and biofilm samples from 26 headwater stream sites in northwestern Pennsylvania with different histories of fracking activity within Marcellus shale play. Further, we describe the relationship between microbial community structure and environmental parameters measured. Approximately 3.2 million 16S rRNA gene sequences were retrieved from a total of 58 samples. Microbial community analyses showed significant reductions in species richness as well as evenness in sites with Marcellus shale activity (MSA+). Beta diversity analyses revealed distinct microbial community structure between sites with and without Marcellus shale activity (MSA-). For example, OTUs within the Acetobacteracea, Methylocystaceae, Acidobacteriaceae, and Phenylobacterium were greater than three log-fold more abundant in MSA+ sites as compared to MSA- sites. Further, several of these OTUs were strongly negatively correlated with pH and positively correlated with the number of wellpads in a watershed. It should be noted that many of the OTUs enriched in MSA+ sites are putative acidophilic and/or methanotrophic populations. This study revealed apparent shifts in the autochthonous microbial communities and highlighted potential members that could be responding to changing stream conditions as a result of nascent industrial activity in these aquatic ecosystems.
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- 2014
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16. Smarter vaccine design will circumvent regulatory T cell-mediated evasion in chronic HIV and HCV infection
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Anne Searls De Groot, Leonard eMoise, Frances eTerry, Andres H. Gutierrez, Ryan eTassone, Phyllis eLosikoff, Stephen H. Gregory, Chris eBailey-Kellogg, and William D Martin
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HIV ,HLA-DR Antigens ,Immune Evasion ,Vaccines ,immunoinformatics ,regulatory T cells ,Microbiology ,QR1-502 - Abstract
Despite years of research, vaccines against HIV and HCV are not yet available, due largely to effective viral immunoevasive mechanisms. A novel escape mechanism observed in viruses that cause chronic infection is suppression of viral-specific effector CD4+ and CD8+ T cells by stimulating regulatory T cells (Tregs) educated on host sequences during tolerance induction. Viral class II MHC epitopes that share a TCR-face with host epitopes may activate Tregs capable of suppressing protective responses. We designed an immunoinformatic algorithm, JanusMatrix, to identify such epitopes and discovered that among human-host viruses, chronic viruses appear more human-like than viruses that cause acute infection. Furthermore, an HCV epitope that activates Tregs in chronically infected patients, but not clearers, shares a TCR-face with numerous human sequences. To boost weak CD4+ T cell responses associated with persistent infection, vaccines for HIV and HCV must circumvent potential Treg activation that can handicap efficacy. Epitope-driven approaches to vaccine design that involve careful consideration of the T cell subsets primed during immunization will advance HIV and HCV vaccine development.
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- 2014
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17. Trends and Future Challenges in Sampling the Deep Terrestrial Biosphere
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Michael J Wilkins, Rebecca eDaly, Paula J Mouser, Ryan eTrexler, Kelly C Wrighton, Shikha eSharma, David R Cole, Jennifer F Biddle, Elizabeth eDenis, Jim K Fredrickson, Thomas L. Kieft, Tullis C Onstott, Lee ePetersen, Susan M Pfiffner, Tommy J Phelps, and Matthew O Schrenk
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deep subsurface ,deep biosphere ,contamination ,shale ,drilling ,deep life ,Microbiology ,QR1-502 - Abstract
Research in the deep terrestrial biosphere is driven by interest in novel biodiversity and metabolisms, biogeochemical cycling, and the impact of human activities on this ecosystem. As this interest continues to grow, it is important to ensure that when subsurface investigations are proposed, materials recovered from the subsurface are sampled and preserved in an appropriate manner to limit contamination and ensure preservation of accurate microbial, geochemical, and mineralogical signatures. On February 20th, 2014, a workshop on Trends and Future Challenges in Sampling The Deep Subsurface was coordinated in Columbus, Ohio by The Ohio State University and West Virginia University faculty, and sponsored by The Ohio State University and the Sloan Foundation’s Deep Carbon Observatory. The workshop aims were to identify and develop best practices for the collection, preservation, and analysis of terrestrial deep rock samples. This document summarizes the information shared during this workshop.
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- 2014
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18. Emerging role of endosomal Toll-like receptors in rheumatoid arthritis
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Ryan eThwaites, Giselle eChamberlain, and Sandra eSacre
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Autoimmunity ,Inflammation ,Therapeutics ,Rheumatoid arthritis ,Toll-like receptor ,autoimmunity models ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Toll-like receptors (TLRs) and their downstream signalling pathways have been comprehensively characterised in innate immunity. In addition to this function, these receptors have also been suggested to be involved in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). Murine in vivo models and human in vitro tissue models of RA have provided a wealth of information on the potential activity of TLRs and components of the downstream signalling pathways. Whilst most early work investigated the cell surface TLRs, more recently the focus has moved to the endosomal TLRs 3, 7, 8 and 9. These receptors recognise endogenous and exogenous double-stranded RNA, single-stranded RNA and DNA. The development of therapeutics to inhibit the endosomal TLRs or components of their signalling cascades may represent a way to target inflammation upstream of cytokine production. This may allow for greater specificity than existing therapies including cytokine blockade. Here, we review the current information suggesting a role for the endosomal TLRs in RA pathogenesis and the efforts to target these receptors therapeutically.
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- 2014
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19. Central regulation of metabolism by protein tyrosine phosphatases
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Ryan eTsou and Kendra eBence
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Obesity ,energy balance ,Pten ,mouse models ,insulin signaling ,protein tyrosine phosphatase ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Protein tyrosine phosphatases (PTPs) are important regulators of intracellular signaling pathways via the dephosphorylation of phosphotyrosyl residues on various receptor and non-receptor substrates. The phosphorylation state of central nervous system (CNS) signaling components underlies the molecular mechanisms of a variety of physiological functions including the control of energy balance and glucose homeostasis. In this review, we summarize the current evidence implicating PTPs as central regulators of metabolism, specifically highlighting their interactions with the neuronal leptin and insulin signaling pathways. We discuss the role of a number of PTPs (PTP1B, SHP2, TCPTP, RPTPe, and PTEN), reviewing the findings from genetic mouse models and in vitro studies which highlight these phosphatases as key central regulators of energy homeostasis.
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- 2013
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20. Clinical Implications of Human Population Differences in Genome-wide Rates of Functional Genotypes
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Ali eTorkamani, Phillip ePham, Ondrej eLibiger, Vikas eBansal, Guangfa eZhang, Ashley A Scott-Van Zeeland, Ryan eTewhey, Eric J. Topol, and Nicholas eSchork
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Genomics ,Population Genetics ,diversity ,Human Disease ,functional variant ,variant annotation ,Genetics ,QH426-470 - Abstract
There have been a number of recent successes in the use of whole genome sequencing and sophisticated bioinformatics techniques to identify pathogenic DNA sequence variants responsible for individual idiopathic congenital conditions. However, the success of this identification process is heavily influenced by the ancestry or genetic background of a patient with an idiopathic condition. This is so because potential pathogenic variants in a patient’s genome must be contrasted with variants in a reference set of genomes made up of other individuals’ genomes of the same ancestry as the patient. We explored the effect of ignoring the ancestries of both an individual patient and the individuals used to construct reference genomes. We pursued this exploration in two major steps. We first considered variation in the per-genome number and rates likely functional derived (i.e., non-ancestral, based on the chimp genome) single nucleotide variants and small indels in 52 individual whole human genomes sampled from 10 different global populations. We took advantage of a suite of computational and bioinformatics techniques to predict the functional effect of over 24 million genomic variants, both coding and non-coding, across these genomes. We found that the typical human genome harbors ~5.5-6.1 million total derived variants, of which ~12,000 are likely to have a functional effect (~5000 coding and ~7000 non-coding). We also found that the rates of functional genotypes per the total number of genotypes in individual whole genomes differ dramatically between human populations. We then created tables showing how the use of comparator or reference genome panels comprised of genomes from individuals that do not have the same ancestral background as a patient can negatively impact pathogenic variant identification. Our results have important implications for clinical sequencing initiatives.
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- 2012
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21. Familial aggregation of Vibrio cholerae-associated infection in Matlab, Bangladesh.
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Rahman KM, Duggal P, Harris JB, Saha SK, Streatfield PK, Ryan ET, Calderwood SB, Qadri F, Yunus M, LaRocque RC, Rahman, Kazi Mizanur, Duggal, Priya, Harris, Jason B, Saha, Sajal Kumar, Streatfield, Peter Kim, Ryan, Edward T, Calderwood, Stephen B, Qadri, Firdausi, Yunus, Mohammad, and LaRocque, Regina C
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Vibrio cholerae is a major cause of diarrhoeal illness in endemic regions, such as Bangladesh. Understanding the factors that determine an individual's susceptibility to infection due to V. cholerae may lead to improved prevention and control strategies. Increasing evidence suggests that human genetic factors affect the severity of V. cholerae-associated infection. This study, therefore, sought to characterize the heritable component of susceptibility to infection due to V. cholerae using the Matlab Health and Demographic Surveillance System database of the International Centre for Diarrhoeal Disease Research, Bangladesh. In total, 144 pedigrees that included a cholera patient and 341 pedigrees without a cholera patient were evaluated during 1 January-31 December 1992. The odds of the sibling of a patient being admitted with cholera were 7.67 times the odds of the sibling of an unaffected individual being admitted with cholera [95% confidence interval (CI) 2.40-24.5, p < 0.001], after adjustment for gender, age, socioeconomic status, and hygiene practices. Although exposure to environmental reservoirs is essential in the epidemiology of cholera, household-specific factors, such as familial relatedness to an index case, may also be important determinants of risk of cholera. Further analysis of human genetic factors that contribute to susceptibility to cholera may be productive. [ABSTRACT FROM AUTHOR]
- Published
- 2009
22. Bacteremia, fever, and splenomegaly caused by a newly recognized bartonella species.
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Eremeeva ME, Gerns HL, Lydy SL, Goo JS, Ryan ET, Mathew SS, Ferraro MJ, Holden JM, Nicholson WL, Dasch GA, Koehler JE, Eremeeva, Marina E, Gerns, Helen L, Lydy, Shari L, Goo, Jeanna S, Ryan, Edward T, Mathew, Smitha S, Ferraro, Mary Jane, Holden, Judith M, and Nicholson, William L
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Bartonella species cause serious human infections globally, including bacillary angiomatosis, Oroya fever, trench fever, and endocarditis. We describe a patient who had fever and splenomegaly after traveling to Peru and also had bacteremia from an organism that resembled Bartonella bacilliformis, the causative agent of Oroya fever, which is endemic to Peru. However, genetic analyses revealed that this fastidious bacterium represented a previously uncultured and unnamed bartonella species, closely related to B. clarridgeiae and more distantly related to B. bacilliformis. We characterized this isolate, including its ability to cause fever and sustained bacteremia in a rhesus macaque. The route of infection and burden of human disease associated with this newly described pathogen are currently unknown. [ABSTRACT FROM AUTHOR]
- Published
- 2007
23. Case records of the Massachusetts General Hospital. Case 19-2005. A 17-year-old girl with respiratory distress and hemiparesis after surviving a tsunami.
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Kao AY, Munandar R, Ferrara SL, Systrom DM, Sheridan RL, Cash SS, Ryan ET, Kao, Ann Y, Munandar, Rus, Ferrara, Stephen L, Systrom, David M, Sheridan, Robert L, Cash, Sydney S, and Ryan, Edward T
- Published
- 2005
24. Development of a Shigella conjugate vaccine targeting Shigella flexneri 6 that is immunogenic and provides protection against virulent challenge.
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Kelly M, Janardhanan J, Wagh C, Verma S, Charles RC, Leung DT, Kamruzzaman M, Pansuriya RK, Chowdhury F, Vann WF, Kaminski RW, Khan AI, Bhuiyan TR, Qadri F, Kováč P, Xu P, and Ryan ET
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Immunity protective against shigella infection targets the bacterial O-specific polysaccharide (OSP) component of lipopolysaccharide. A multivalent shigella vaccine would ideally target the most common global Shigella species and serotypes such as Shigella flexneri 2a, S. flexneri 3a, S. flexneri 6, and S. sonnei. We previously reported development of shigella conjugate vaccines (SCVs) targeting S. flexneri 2a (SCV-Sf2a) and 3a (SCV-Sf3a) using a platform squaric acid chemistry conjugation approach and carrier protein rTTHc, a 52 kDa recombinant protein fragment of the heavy chain of tetanus toxoid. Here we report development of a SCV targeting S. flexneri 6 (SCV-Sf6) using the same platform approach. We demonstrated that SCV-Sf6 was recognized by serotype-specific monoclonal antibodies and convalescent sera of humans recovering from shigellosis in Bangladesh, suggesting correct immunological display of OSP. We vaccinated mice and found induction of serotype-specific OSP and LPS IgG and IgM responses, as well as rTTHc-specific IgG responses. Immune responses were increased when administered with aluminum phosphate adjuvant. Vaccination induced bactericidal antibody responses against S. flexneri 6, and vaccinated animals were protected against lethal challenge with virulent S. flexneri 6. Our results assist in the development of a multivalent vaccine protective against shigellosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert Kaminski reports a relationship with Latham BioPharm Group that includes: employment. Edward T Ryan has patent ##9,616,139 issued to Massachusetts General Hospital., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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25. 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
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- Humans, Cholera Toxin genetics, Diarrhea microbiology, Phylogeny, Cholera microbiology, Vibrio cholerae O1 genetics, Vibrio cholerae O1 isolation & purification, Feces microbiology, Gastrointestinal Tract microbiology, Genome, Bacterial genetics, Genetic Variation
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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., Competing Interests: The authors declare no conflict of interest.
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- 2024
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26. Determinants of immune responses predictive of protection against shigellosis in an endemic zone: a systems analysis of antibody profiles and function.
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Bernshtein B, Kelly M, Cizmeci D, Zhiteneva JA, Macvicar R, Kamruzzaman M, Bhuiyan TR, Chowdhury F, Khan AI, Qadri F, Charles RC, Xu P, Kováč P, Clarkson KA, Kaminski RW, Alter G, and Ryan ET
- Abstract
Background: Shigella is the third leading global cause of moderate or severe diarrhoea among children younger than 5 years globally, and is the leading cause in children aged 24-59 months. The mechanism of protection against Shigella infection and disease in endemic areas is uncertain. We aimed to compare the Shigella-specific antibody responses in individuals living in Shigella-endemic and non-endemic areas, and to identify correlates of protection in a Shigella-endemic location., Methods: We applied a systems approach to retrospectively analyse serological responses to Shigella across endemic and non-endemic populations. We profiled serum samples collected from 44 individuals from the USA without previous exposure to Shigella and who were experimentally challenged with Shigella sonnei (non-endemic setting), and serum samples collected from 55 Peruvian army recruits (endemic setting). In the endemic setting, a subset of 37 samples collected from individuals infected with culture-confirmed Shigella flexneri 2a were divided into two groups: susceptible, which included individuals infected within 90 days of entering the camp (n=29); or resistant, which included individuals infected later than 90 days after entering the camp (n=8). We analysed Shigella-specific antibody isotype, subclass, and Fc receptor binding profiles across IpaB, IpaC, IpaD, and lipopolysaccharide from S flexneri 2a, 3a, and 6, and S sonnei, and O-specific polysaccharide (OSP) from S flexneri 2a and 3a and S sonnei. We also evaluated antibody-mediated complement deposition and innate immune cell activation. The main outcome of interest was the detection of antibody markers and functionality associated with protection against shigellosis in a high-burden endemic setting., Findings: Adults with endemic exposure to Shigella possessed broad and functional antibody responses across polysaccharide, glycolipid, and protein antigens compared with individuals from non-endemic regions. In a setting with high Shigella burden, elevated levels of OSP-specific Fcα receptor (FcαR) binding antibodies were associated with resistance to shigellosis, whereas total OSP-specific IgA was not, suggesting a potentially unique functionality. OSP-specific FcαR binding IgA found in resistant individuals activated bactericidal neutrophil functions including phagocytosis, degranulation, and production of reactive oxygen species. Moreover, IgA depletion from resistant serum significantly reduced binding of OSP-specific antibodies to FcαR and antibody-mediated activation of neutrophils and monocytes., Interpretation: Our findings suggest that OSP-specific functional IgA responses contribute to protective immunity against Shigella infection in a high-burden setting. These findings will assist in the development and evaluation of Shigella vaccines., Funding: US National Institutes of Health., Competing Interests: Declaration of interests GA is an employee of Moderna Therapeutics and holds equity in Leyden Labs and Systems Seromyx. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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27. Coding-complete genomes of 18 SARS-CoV-2 Omicron JN.1, JN.1.4, and JN.1.11 sub-lineages in Bangladesh.
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Tahsin A, Hasan M, Rahman S, Jubair M, Afrad MH, Khan MH, Alam MS, Begum MN, Karim MY, Mukta SA, Habib MT, Alam AN, Chowdhury EK, Rahman MR, Ryan ET, Shirin T, Rahman M, and Qadri F
- Abstract
We report 18 coding-complete genome sequences of emerging SARS-CoV-2 Omicron sub-lineages JN.1, JN.1.4, and JN.1.11 from Bangladesh. Nasopharyngeal swab samples were obtained from individuals with COVID-19 symptoms between December 2023 and January 2024. Whole genome sequencing was performed following the ARTIC Network-based protocol using Oxford Nanopore Technology., Competing Interests: The authors declare no conflict of interest.
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- 2024
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28. 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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29. 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 P, Hakim A, Akter A, Banna HA, Kaisar MH, Aktar A, Jahan SR, Ferdous J, Basher SR, Kamruzzaman M, Chowdhury F, Akter A, Tauheed I, Weil AA, Charles RC, Calderwood SB, Ryan ET, LaRocque RC, Harris JB, Bhuiyan TR, and Qadri F
- Subjects
- Adult, Child, Humans, Adolescent, Child, Preschool, Aged, Infant, Newborn, Cholera Toxin, O Antigens, Immunoglobulin M, Antibodies, Bacterial, Immunoglobulin A, Vaccination, Antibody Formation, Immunoglobulin G, Cholera Vaccines, Cholera prevention & control, Vibrio cholerae O1
- Abstract
Vaccination is important to prevent cholera. There are limited data comparing anti-O-specific polysaccharide (OSP) and anti-cholera toxin-specific immune responses following oral whole-cell with cholera toxin B-subunit (WC-rBS) vaccine (Dukoral, Valneva) administration in different age groups. An understanding of the differences is relevant because young children are less well protected by oral cholera vaccines than older children and adults. We compared responses in 50 adults and 49 children (ages 2 to <18) who were administered two doses of WC-rBS at a standard 14-day interval. All age groups had significant IgA and IgG plasma-blast responses to the OSP and cholera toxin B-subunit (CtxB) antigens that peaked 7 days after vaccination. However, in adults and older children (ages 5 to <18), antibody responses directed at the OSP antigen were largely IgA and IgG, with a minimal IgM response, while younger children (ages 2 to <5) mounted significant increases in IgM with minimal increases in IgA and IgG antibody responses 30 days after vaccination. In adults, anti-OSP and CtxB memory B-cell responses were detected after completion of the vaccination series, while children only mounted CtxB-specific IgG memory B-cell responses and no OSP-memory B-cell responses. In summary, children and adults living in a cholera endemic area mounted different responses to the WC-rBS vaccine, which may be a result of more prior exposure to Vibrio cholerae in older participants. The absence of class-switched antibody responses and memory B-cell responses to OSP may explain why protection wanes more rapidly after vaccination in young children compared to older vaccinees.IMPORTANCEVaccination is an important strategy to prevent cholera. Though immune responses targeting the OSP of V. cholerae are believed to mediate protection against cholera, there are limited data on anti-OSP responses after vaccination in different age groups, which is important as young children are not well protected by current oral cholera vaccines. In this study, we found that adults mounted memory B-cell responses to OSP, which were not seen in children. Adults and older children mounted class-switched (IgG and IgA) serum antibody responses to OSP, which were not seen in young children who had only IgM responses to OSP. The lack of class-switched antibody responses and memory B-cell responses to OSP in younger participants may be due to lack of prior exposure to V. cholerae and could explain why protection wanes more rapidly after vaccination in young children., Competing Interests: The authors declare no conflict of interest.
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- 2024
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30. Case 4-2024: A 39-Year-Old Man with Fever and Headache after International Travel.
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Ryan ET, Succi MD, Paras ML, and Klontz EH
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- Adult, Humans, Male, Travel, Internationality, Fever etiology, Headache etiology, Travel-Related Illness
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- 2024
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31. 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
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32. Knowledge, attitudes and practices regarding the use of mobile travel health apps.
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Machoko MMP, Dong Y, Grozdani A, Hong H, Oliver E, Hyle EP, Ryan ET, Colubri A, and LaRocque RC
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- Humans, Health Knowledge, Attitudes, Practice, Knowledge, Mobile Applications, Telemedicine
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- 2024
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33. Appearance of tolerance-induction and non-inflammatory SARS-CoV-2 spike-specific IgG4 antibodies after COVID-19 booster vaccinations.
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Akhtar M, Islam MR, Khaton F, Soltana UH, Jafrin SA, Rahman SIA, Tauheed I, Ahmed T, Khan II, Akter A, Khan ZH, Islam MT, Khanam F, Biswas PK, Ahmmed F, Ahmed S, Rashid MM, Hossain MZ, Alam AN, Alamgir ASM, Rahman M, Ryan ET, Harris JB, LaRocque RC, Flora MS, Chowdhury F, Khan AI, Banu S, Shirin T, Bhuiyan TR, and Qadri F
- Subjects
- Humans, ChAdOx1 nCoV-19, SARS-CoV-2, Vaccination, Antibodies, Viral, RNA, Messenger, Immunoglobulin G, COVID-19 prevention & control
- Abstract
Background: Understanding the characteristics of the humoral immune responses following COVID-19 vaccinations is crucial for refining vaccination strategies and predicting immune responses to emerging SARS-CoV-2 variants., Methods: A longitudinal analysis of SARS-CoV-2 spike receptor binding domain (RBD) specific IgG antibody responses, encompassing IgG subclasses IgG1, IgG2, IgG3, and IgG4 was performed. Participants received four mRNA vaccine doses (group 1; n=10) or two ChAdOx1 nCoV-19 and two mRNA booster doses (group 2; n=19) in Bangladesh over two years., Results: Findings demonstrate robust IgG responses after primary Covishield or mRNA doses; declining to baseline within six months. First mRNA booster restored and surpassed primary IgG responses but waned after six months. Surprisingly, a second mRNA booster did not increase IgG levels further. Comprehensive IgG subclass analysis showed primary Covishield/mRNA vaccination generated predominantly IgG1 responses with limited IgG2/IgG3, Remarkably, IgG4 responses exhibited a distinct pattern. IgG4 remained undetectable initially but increased extensively six months after the second mRNA dose, eventually replacing IgG1 after the 3rd/4th mRNA doses. Conversely, initial Covishield recipients lack IgG4, surged post-second mRNA booster. Notably, mRNA-vaccinated individuals displayed earlier, robust IgG4 levels post first mRNA booster versus Covishield counterparts. IgG1 to IgG4 ratios decreased with increasing doses, most pronounced with four mRNA doses. This study highlights IgG response kinetics, influenced by vaccine type and doses, impacting immunological tolerance and IgG4 induction, shaping future vaccination strategies., Conclusions: This study highlights the dynamics of IgG responses dependent on vaccine type and number of doses, leading to immunological tolerance and IgG4 induction, and shaping future vaccination strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Akhtar, Islam, Khaton, Soltana, Jafrin, Rahman, Tauheed, Ahmed, Khan, Akter, Khan, Islam, Khanam, Biswas, Ahmmed, Ahmed, Rashid, Hossain, Alam, Alamgir, Rahman, Ryan, Harris, LaRocque, Flora, Chowdhury, Khan, Banu, Shirin, Bhuiyan and Qadri.)
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- 2023
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34. Development of a prediction model for the acquisition of extended spectrum beta-lactam-resistant organisms in U.S. international travellers.
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Brown DG, Worby CJ, Pender MA, Brintz BJ, Ryan ET, Sridhar S, Oliver E, Harris JB, Turbett SE, Rao SR, Earl AM, LaRocque RC, and Leung DT
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- Humans, Enterobacteriaceae, beta-Lactams, Prospective Studies, beta-Lactamases, Risk Factors, Anti-Bacterial Agents therapeutic use, Enterobacteriaceae Infections drug therapy
- Abstract
Background: Extended spectrum beta-lactamase producing Enterobacterales (ESBL-PE) present a risk to public health by limiting the efficacy of multiple classes of beta-lactam antibiotics against infection. International travellers may acquire these organisms and identifying individuals at high risk of acquisition could help inform clinical treatment or prevention strategies., Methods: We used data collected from a cohort of 528 international travellers enrolled in a multicentre US-based study to derive a clinical prediction rule (CPR) to identify travellers who developed ESBL-PE colonization, defined as those with new ESBL positivity in stool upon return to the United States. To select candidate features, we used data collected from pre-travel and post-travel questionnaires, alongside destination-specific data from external sources. We utilized LASSO regression for feature selection, followed by random forest or logistic regression modelling, to derive a CPR for ESBL acquisition., Results: A CPR using machine learning and logistic regression on 10 features has an internally cross-validated area under the receiver operating characteristic curve (cvAUC) of 0.70 (95% confidence interval 0.69-0.71). We also demonstrate that a four-feature model performs similarly to the 10-feature model, with a cvAUC of 0.68 (95% confidence interval 0.67-0.69). This model uses traveller's diarrhoea, and antibiotics as treatment, destination country waste management rankings and destination regional probabilities as predictors., Conclusions: We demonstrate that by integrating traveller characteristics with destination-specific data, we could derive a CPR to identify those at highest risk of acquiring ESBL-PE during international travel., (© International Society of Travel Medicine 2023. Published by Oxford University Press.)
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- 2023
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35. Comparison of O-specific polysaccharide responses in patients following infection with Vibrio cholerae O139 versus vaccination with a bivalent (O1/O139) oral killed cholera vaccine in Bangladesh.
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Kaisar MH, Kelly M, Kamruzzaman M, Bhuiyan TR, Chowdhury F, Khan AI, LaRocque RC, Calderwood SB, Harris JB, Charles RC, Čížová A, Mečárová J, Korcová J, Bystrický S, Kováč P, Xu P, Qadri F, and Ryan ET
- Subjects
- Humans, Child, O Antigens, Lipopolysaccharides, Bangladesh epidemiology, Vaccines, Inactivated, Antibodies, Bacterial, Immunoglobulin A, Immunoglobulin M, Vaccination, Cholera prevention & control, Cholera Vaccines, Vibrio cholerae O139, Vibrio cholerae O1, Blood Group Antigens
- Abstract
Cholera caused by Vibrio cholerae O139 emerged in the early 1990s and spread rapidly to 11 Asian countries before receding for unclear reasons. Protection against cholera is serogroup-specific, which is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS). V. cholerae O139 also expresses the OSP-capsule. We, therefore, assessed antibody responses targeting V. cholerae O139 OSP, LPS, capsule, and vibriocidal responses in patients in Bangladesh with cholera caused by V. cholerae O139. We compared these responses to those of age-gender-blood group-matched recipients of the bivalent oral cholera vaccine (OCV O1/O139). We found prominent OSP, LPS, and vibriocidal responses in patients, with a high correlation between these responses. OSP responses primarily targeted the terminal tetrasaccharide of OSP. Vaccinees developed OSP, LPS, and vibriocidal antibody responses, but of significantly lower magnitude and responder frequency (RF) than matched patients. We separately analyzed responses in pediatric vaccinees born after V. cholerae O139 had receded in Bangladesh. We found that OSP responses were boosted in children who had previously received a single dose of bivalent OCV 3 yr previously but not in vaccinated immunologically naïve children. Our results suggest that OSP-specific responses occur during cholera caused by V. cholerae O139 despite the presence of capsules, that vaccination with bivalent OCV is poorly immunogenic in the short term in immunologically naïve individuals, but that OSP-specific immune responses can be primed by previous exposure, although whether such responses can protect against O139 cholera is uncertain. IMPORTANCE Cholera is a severe dehydrating illness in humans caused by Vibrio cholerae serogroups O1 or O139. Protection against cholera is serogroup-specific, which is defined by the O-specific polysaccharide (OSP) of V. cholerae LPS. Yet, little is known about immunity to O139 OSP. In this study, we assessed immune responses targeting OSP in patients from an endemic region with cholera caused by V. cholerae O139. We compared these responses to those of the age-gender-blood group-matched recipients of the bivalent oral cholera vaccine. Our results suggest that OSP-specific responses occur during cholera caused by V. cholerae O139 and that the OSP responses primarily target the terminal tetrasaccharide of OSP. Our results further suggest that vaccination with the bivalent vaccine is poorly immunogenic in the short term for inducing O139-specific OSP responses in immunologically naïve individuals, but OSP-specific immune responses can be primed by previous exposure or vaccination., Competing Interests: The authors declare no conflict of interest.
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- 2023
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36. Coding-complete genomes of XBB.1.16, XBB.2.3, FL.4 (alias of XBB.1.9.1.4), and XBB.3 of SARS-CoV-2 Omicron isolated from Bangladesh.
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Rahman S, Habib MT, Afrad MH, Hasan M, Tahsin A, Jubair M, Khan MH, Alam AN, Chowdhury EK, Rahman M, Ryan ET, Shirin T, and Qadri F
- Abstract
We announce the coding-complete genomes of four different strains of SARS-CoV-2 Omicron lineages, XBB.1.16, XBB.2.3, FL.4 (alias of XBB.1.9.1.4), and XBB.3. These strains were obtained between October 2022 and May 2023 from nasopharyngeal swabs of four Bangladeshi individuals, while one of them had a travel history. Genomic data were produced by implementing ARTIC Network-based amplicon sequencing using the Oxford Nanopore Technology., Competing Interests: The authors declare no conflict of interest.
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- 2023
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37. Vaccination of Rabbits with a Cholera Conjugate Vaccine Comprising O-Specific Polysaccharide and a Recombinant Fragment of Tetanus Toxin Heavy Chain Induces Protective Immune Responses against Vibrio cholerae O1.
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Kelly M, Jeon S, Yun J, Lee B, Park M, Whang Y, Lee C, Charles RC, Bhuiyan TR, Qadri F, Kamruzzaman M, Cho S, Vann WF, Xu P, Kováč P, Ganapathy R, Lynch J, and Ryan ET
- Subjects
- Child, Rabbits, Humans, Animals, Mice, Child, Preschool, O Antigens, Tetanus Toxin, Vaccines, Conjugate, Immunoglobulin M, Vaccination, Antibody Formation, Disease Models, Animal, Antibodies, Bacterial, Cholera Toxin, Cholera prevention & control, Vibrio cholerae O1, Cholera Vaccines
- Abstract
There is a need for next-generation cholera vaccines that provide high-level and durable protection in young children in cholera-endemic areas. A cholera conjugate vaccine (CCV) is in development to address this need. This vaccine contains the O-specific polysaccharide (OSP) of Vibrio cholerae O1 conjugated via squaric acid chemistry to a recombinant fragment of the tetanus toxin heavy chain (OSP:rTTHc). This vaccine has been shown previously to be immunogenic and protective in mice and found to be safe in a recent preclinical toxicological analysis in rabbits. We took advantage of excess serum samples collected as part of the toxicological study and assessed the immunogenicity of CCV OSP:rTTHc in rabbits. We found that vaccination with CCV induced OSP-, lipopolysaccharide (LPS)-, and rTTHc-specific immune responses in rabbits, that immune responses were functional as assessed by vibriocidal activity, and that immune responses were protective against death in an established virulent challenge assay. CCV OSP:rTTHc immunogenicity in two animal model systems (mice and rabbits) is encouraging and supports further development of this vaccine for evaluation in humans.
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- 2023
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38. Gut microbiome perturbation, antibiotic resistance, and Escherichia coli strain dynamics associated with international travel: a metagenomic analysis.
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Worby CJ, Sridhar S, Turbett SE, Becker MV, Kogut L, Sanchez V, Bronson RA, Rao SR, Oliver E, Walker AT, Walters MS, Kelly P, Leung DT, Knouse MC, Hagmann SHF, Harris JB, Ryan ET, Earl AM, and LaRocque RC
- Subjects
- United States, Humans, Travel, Metagenome, Travel-Related Illness, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Drug Resistance, Microbial, beta-Lactamases genetics, DNA, Escherichia coli genetics, Gastrointestinal Microbiome genetics
- Abstract
Background: Culture-based studies have shown that acquisition of extended-spectrum β-lactamase-producing Enterobacterales is common during international travel; however, little is known about the role of the gut microbiome before and during travel, nor about acquisition of other antimicrobial-resistant organisms. We aimed to identify (1) whether the gut microbiome provided colonisation resistance against antimicrobial-resistant organism acquisition, (2) the effect of travel and travel behaviours on the gut microbiome, and (3) the scale and global heterogeneity of antimicrobial-resistant organism acquisition., Methods: In this metagenomic analysis, participants were recruited at three US travel clinics (Boston, MA; New York, NY; and Salt Lake City, UT) before international travel. Participants had to travel internationally between Dec 8, 2017, and April 30, 2019, and have DNA extractions for stool samples both before and after travel for inclusion. Participants were excluded if they had at least one low coverage sample (<1 million read pairs). Stool samples were collected at home before and after travel, sent to a clinical microbiology laboratory to be screened for three target antimicrobial-resistant organisms (extended-spectrum β-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, and mcr-mediated colistin-resistant Enterobacterales), and underwent DNA extraction and shotgun metagenomic sequencing. We profiled metagenomes for taxonomic composition, antibiotic-resistant gene content, and characterised the Escherichia coli population at the strain level. We analysed pre-travel samples to identify the gut microbiome risk factors associated with acquisition of the three targeted antimicrobial resistant organisms. Pre-travel and post-travel samples were compared to identify microbiome and resistome perturbation and E coli strain acquisition associated with travel., Findings: A total of 368 individuals travelled between the required dates, and 296 had DNA extractions available for both before and after travel. 29 travellers were excluded as they had at least one low coverage sample, leaving a final group of 267 participants. We observed a perturbation of the gut microbiota, characterised by a significant depletion of microbial diversity and enrichment of the Enterobacteriaceae family. Metagenomic strain tracking confirmed that 67% of travellers acquired new strains of E coli during travel that were phylogenetically distinct from their pre-travel strains. We observed widespread enrichment of antibiotic-resistant genes in the gut, with a median 15% (95% CI 10-20, p<1 × 10
-10 ) increase in burden (reads per kilobase per million reads). This increase included antibiotic-resistant genes previously classified as threats to public health, which were 56% (95% CI 36-91, p=2 × 10-11 ) higher in abundance after travel than before. Fluoroquinolone antibiotic-resistant genes were aquired by 97 (54%) of 181 travellers with no detected pre-travel carriage. Although we found that visiting friends or relatives, travel to south Asia, and eating uncooked vegetables were risk factors for acquisition of the three targeted antimicrobial resistant organisms, we did not observe an association between the pre-travel microbiome structure and travel-related antimicrobial-resistant organism acquisition., Interpretation: This work highlights a scale of E coli and antimicrobial-resistant organism acquisition by US travellers not apparent from previous culture-based studies, and suggests that strategies to control antimicrobial-resistant organisms addressing international traveller behaviour, rather than modulating the gut microbiome, could be worthwhile., Funding: US Centers for Disease Control and Prevention and National Institute of Allergy and Infectious Diseases., Competing Interests: Declaration of interests SET is a Committee Member for the American Society of Transplantation Consensus Conference on Novel Infectious Disease Diagnostics in Solid Organ Transplant, Subgroup Leader on the Rapid Antimicrobial Resistance Detection Methods Subgroup, and received funding within the past 36 months from the Massachusetts General Hospital Vickery-Colvin Grant. DTL is a councillor on Clinical Group, Member of the Scientific Program Committee for American Society of Tropical Medicine and Hygiene, and received authorship royalties from UpToDate. JBH provided editorial services for UpToDate. RCL received payments for editorial services from UpToDate and the US Centers for Disease Control and Prevention Foundation. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2023
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39. Influenza: seasonality and travel-related considerations.
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Kakoullis L, Steffen R, Osterhaus A, Goeijenbier M, Rao SR, Koiso S, Hyle EP, Ryan ET, LaRocque RC, and Chen LH
- Subjects
- Humans, Vaccination, Immunization Schedule, Travel-Related Illness, Seasons, Influenza, Human prevention & control, Influenza Vaccines, Air Travel
- Abstract
Rationale for Review: This review aims to summarize the transmission patterns of influenza, its seasonality in different parts of the globe, air travel- and cruise ship-related influenza infections and interventions to reduce transmission., Key Findings: The seasonality of influenza varies globally, with peak periods occurring mainly between October and April in the northern hemisphere (NH) and between April and October in the southern hemisphere (SH) in temperate climate zones. However, influenza seasonality is significantly more variable in the tropics. Influenza is one of the most common travel-related, vaccine-preventable diseases and can be contracted during travel, such as during a cruise or through air travel. Additionally, travellers can come into contact with people from regions with ongoing influenza transmission. Current influenza immunization schedules in the NH and SH leave individuals susceptible during their respective spring and summer months if they travel to the other hemisphere during that time., Conclusions/recommendations: The differences in influenza seasonality between hemispheres have substantial implications for the effectiveness of influenza vaccination of travellers. Health care providers should be aware of influenza activity when patients report travel plans, and they should provide alerts and advise on prevention, diagnostic and treatment options. To mitigate the risk of travel-related influenza, interventions include antivirals for self-treatment (in combination with the use of rapid self-tests), extending the shelf life of influenza vaccines to enable immunization during the summer months for international travellers and allowing access to the influenza vaccine used in the opposite hemisphere as a travel-related vaccine. With the currently available vaccines, the most important preventive measure involves optimizing the seasonal influenza vaccination. It is also imperative that influenza is recognized as a travel-related illness among both travellers and health care professionals., (© International Society of Travel Medicine 2023. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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40. Travel Medicine.
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Rolfe RJ, Ryan ET, and LaRocque RC
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- Female, Pregnancy, Humans, Ambulatory Care Facilities, Awareness, Chemoprevention, Travel Medicine, Medicine
- Abstract
International travel can cause new illness or exacerbate existing conditions. Because primary care providers are frequent sources of health advice to travelers, they should be familiar with destination-specific disease risks, be knowledgeable about travel and routine vaccines, be prepared to prescribe chemoprophylaxis and self-treatment regimens, and be aware of travel medicine resources. Primary care providers should recognize travelers who would benefit from referral to a specialized travel clinic for evaluation. Those requiring yellow fever vaccination, immunocompromised hosts, pregnant persons, persons with multiple comorbid conditions, or travelers with complex itineraries may warrant specialty referral., Competing Interests: Disclosures: All relevant financial relationships have been mitigated. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-0801.
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- 2023
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41. Mass photometry: A powerful tool for carbohydrates-proteins conjugation monitoring and glycoconjugates molecular mass determination.
- Author
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Wu D, Xu P, Kelly M, Ryan ET, Kováč P, and Piszczek G
- Subjects
- Carbohydrates chemistry, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods, Glycoconjugates chemistry, Vaccines
- Abstract
Glycoconjugate vaccines are important additions to the existing means for prevention of diseases caused by bacterial and viral pathogens. Conjugating carbohydrates to proteins is a crucial step in the development of these vaccines. Traditional mass spectrometry techniques, such as MALDI-TOF and SELDI-TOF, have difficulties in detecting glycoconjugates with high molecular masses. Mass photometry (MP) is a single-molecule technique that has been recently developed, which allows mass measurements of individual molecules and generates mass distributions based on hundreds to thousands of these measurements. In this study, we evaluated the performance of MP in monitoring carbohydrate-protein conjugation reactions and characterization of conjugates. Three different glycoconjugates were prepared from carrier protein BSA, and one from a large protein complex, a virus capsid with 3.74 MDa molecular mass. The masses measured by MP were consistent with those obtained by SELDI-TOF-MS and SEC-MALS. The conjugation of BSA dimer to carbohydrate antigen was also successfully characterized. This study shows that the MP technique is a promising alternative to methods developed earlier for monitoring glycoconjugation reactions and characterization of glycoconjugates. It measures intact molecules in solution and it is highly accurate over a wide mass range. MP requires only a very small amount of sample and has no specific buffer constraints. Other MP advantages include minimal cost of consumables and rapid data collection and analysis. Its advantages over other methods make it a valuable tool for researchers in the glycoconjugation field., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
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- 2023
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42. Development of Shigella conjugate vaccines targeting Shigella flexneri 2a and S. flexneri 3a using a simple platform-approach conjugation by squaric acid chemistry.
- Author
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Kelly M, Mandlik A, Charles RC, Verma S, Calderwood SB, Leung DT, Biswas R, Islam K, Kamruzzaman M, Chowdhury F, Khanam F, Vann WF, Khan AI, Bhuiyan TR, Qadri F, Vortherms AR, Kaminski R, Kováč P, Xu P, and Ryan ET
- Subjects
- Humans, Child, Animals, Mice, Child, Preschool, Shigella flexneri, Vaccines, Conjugate, Lipopolysaccharides, O Antigens, Antibodies, Bacterial, Immunoglobulin G, Shigella Vaccines, Dysentery, Bacillary prevention & control, Shigella
- Abstract
There is a need for vaccines effective against shigella infection in young children in resource-limited areas. Protective immunity against shigella infection targets the O-specific polysaccharide (OSP) component of lipopolysaccharide. Inducing immune responses to polysaccharides in young children can be problematic, but high level and durable responses can be induced by presenting polysaccharides conjugated to carrier proteins. An effective shigella vaccine will need to be multivalent, targeting the most common global species and serotypes such as Shigella flexneri 2a, S. flexneri 3a, S. flexneri 6, and S. sonnei. Here we report the development of shigella conjugate vaccines (SCV) targeting S. flexneri 2a (SCV-Sf2a) and 3a (SCV-Sf3a) using squaric acid chemistry to result in single point sun-burst type display of OSP from carrier protein rTTHc, a 52 kDa recombinant protein fragment of the heavy chain of tetanus toxoid. We confirmed structure and demonstrated that these conjugates were recognized by serotype-specific monoclonal antibodies and convalescent sera of humans recovering from shigellosis in Bangladesh, suggesting correct immunological display of OSP. We vaccinated mice and found induction of serotype-specific OSP and LPS IgG responses, as well as rTTHc-specific IgG responses. Vaccination induced serotype-specific bactericidal antibody responses against S. flexneri, and vaccinated animals were protected against keratoconjunctivitis (Sereny test) and intraperitoneal challenge with virulent S. flexneri 2a and 3a, respectively. Our results support further development of this platform conjugation technology in the development of shigella conjugate vaccines for use in resource-limited settings., 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 © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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43. Intrinsic Resistance to Colistin in the Genus Hafnia .
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Turbett SE, Bronson RA, Worby CJ, McGrath GEG, Hodgkins E, Becker M, Belford B, Kogut L, Oliver E, Ryan ET, LaRocque RC, Earl AM, and Pierce VM
- Subjects
- Humans, Colistin pharmacology, Enterobacteriaceae, Microbial Sensitivity Tests, Anti-Bacterial Agents pharmacology, Hafnia genetics, Anti-Infective Agents
- Abstract
A bacterial species is considered to be intrinsically resistant to an antimicrobial when nearly all of the wild-type isolates (i.e., those without acquired resistance) exhibit minimum inhibitory concentration (MIC) values that are sufficiently high such that susceptibility testing is unnecessary, and that the antimicrobial should not be considered for therapy. Accordingly, knowledge of intrinsic resistance influences both the selection of treatment regimens and the approach to susceptibility testing in the clinical laboratory, where unexpected results also facilitate the recognition of microbial identification or susceptibility testing errors. Previously, limited data have suggested that Hafnia spp. may be intrinsically resistant to colistin. We evaluated the in vitro activity of colistin against 119 Hafniaceae that were isolated from human samples: 75 (63%) from routine clinical cultures and 44 (37%) from stool samples of travelers undergoing screening for antimicrobial resistant organisms. Broth microdilution colistin MICs were ≥4 μg/mL for 117 of 119 (98%) isolates. Whole-genome sequencing of 96 of the isolates demonstrated that the colistin-resistant phenotype was not lineage-specific. 2 of the 96 (2%) isolates harbored mobile colistin resistance genes. Compared to whole-genome sequencing, VITEK MS matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and VITEK 2 GN ID failed to consistently distinguish between Hafnia alvei, Hafnia paralvei, and Obesumbacterium proteus. In conclusion, using a reference antimicrobial susceptibility testing method and a genetically diverse collection of isolates, we found Hafnia spp. to be intrinsically resistant to colistin. The recognition of this phenotype will help inform rational approaches by which to perform antimicrobial susceptibility testing and therapy for patients with infections that are caused by Hafnia spp., Competing Interests: The authors declare a conflict of interest. S.E.T., R.C.L., and V.M.P. receive royalties from UpToDate. R.C.L. also received payments for editorial services from the CDC Foundation. V.M.P. is a member of the Clinical and Laboratory Standards Institute Subcommittee on Antimicrobial Susceptibility Testing.
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- 2023
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44. Shigella O-specific polysaccharide functional IgA responses mediate protection against shigella infection in an endemic high-burden setting.
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Bernshtein B, Kelly M, Cizmeci D, Zhiteneva JA, Macvicar R, Kamruzzaman M, Bhuiyan TR, Chowdhury F, Khan AI, Qadri F, Charles RC, Xu P, Kováč P, Kaminski RW, Alter G, and Ryan ET
- Abstract
Shigella is the second leading cause of diarrheal disease-related death in young children in low and middle income countries. The mechanism of protection against shigella infection and disease in endemic areas is uncertain. While historically LPS-specific IgG titers have been associated with protection in endemic settings, emerging deeper immune approaches have recently elucidated a protective role for IpaB-specific antibody responses in a controlled human challenge model in North American volunteers. To deeply interrogate potential correlates of immunity in areas endemic for shigellosis, here we applied a systems approach to analyze the serological response to shigella across endemic and non-endemic populations. Additionally, we analyzed shigella-specific antibody responses over time in the context of endemic resistance or breakthrough infections in a high shigella burden location. Individuals with endemic exposure to shigella possessed broad and functional antibody responses across both glycolipid and protein antigens compared to individuals from non-endemic regions. In high shigella burden settings, elevated levels of OSP-specific FcαR binding antibodies were associated with resistance to shigellosis. OSP-specific FcαR binding IgA found in resistant individuals activated bactericidal neutrophil functions including phagocytosis, degranulation and reactive oxygen species production. Moreover, IgA depletion from resistant serum significantly reduced binding of OSP-specific antibodies to FcαR and antibody mediated activation of neutrophils and monocytes. Overall, our findings suggest that OSP-specific functional IgA responses contribute to protective immunity against shigella infection in high-burden settings. These findings will assist in the development and evaluation of shigella vaccines.
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- 2023
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45. Predicting Vibrio cholerae infection and symptomatic disease: a systems serology study.
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Wiens KE, Iyer AS, Bhuiyan TR, Lu LL, Cizmeci D, Gorman MJ, Yuan D, Becker RL, Ryan ET, Calderwood SB, LaRocque RC, Chowdhury F, Khan AI, Levine MM, Chen WH, Charles RC, Azman AS, Qadri F, Alter G, and Harris JB
- Subjects
- Child, Humans, Antibodies, Bacterial, Bangladesh epidemiology, Diarrhea epidemiology, Cholera epidemiology, Cholera prevention & control, Vibrio cholerae
- Abstract
Background: Vibriocidal antibodies are currently the best characterised correlate of protection against cholera and are used to gauge immunogenicity in vaccine trials. Although other circulating antibody responses have been associated with a decreased risk of infection, the correlates of protection against cholera have not been comprehensively compared. We aimed to analyse antibody-mediated correlates of protection from both V cholerae infection and cholera-related diarrhoea., Methods: We conducted a systems serology study that analysed 58 serum antibody biomarkers as correlates of protection against V cholerae O1 infection or diarrhoea. We used serum samples from two cohorts: household contacts of people with confirmed cholera in Dhaka, Bangladesh, and cholera-naive volunteers who were recruited at three centres in the USA, vaccinated with a single dose of CVD 103-HgR live oral cholera vaccine, and then challenged with V cholerae O1 El Tor Inaba strain N16961. We measured antigen-specific immunoglobulin responses against antigens using a customised Luminex assay and used conditional random forest models to examine which baseline biomarkers were most important for classifying individuals who went on to develop infection versus those who remained uninfected or asymptomatic. V cholerae infection was defined as having a positive stool culture result on days 2-7 or day 30 after enrolment of the household's index cholera case and, in the vaccine challenge cohort, was the development of symptomatic diarrhoea (defined as two or more loose stools of ≥200 mL each, or a single loose stool of ≥300 mL over a 48-h period)., Findings: In the household contact cohort (261 participants from 180 households), 20 (34%) of the 58 studied biomarkers were associated with protection against V cholerae infection. We identified serum antibody-dependent complement deposition targeting the O1 antigen as the most predictive correlate of protection from infection in the household contacts, whereas vibriocidal antibody titres ranked lower. A five-biomarker model predicted protection from V cholerae infection with a cross-validated area under the curve (cvAUC) of 79% (95% CI 73-85). This model also predicted protection against diarrhoea in unvaccinated volunteers challenged with V cholerae O1 after vaccination (n=67; area under the curve [AUC] 77%, 95% CI 64-90). Although a different five-biomarker model best predicted protection from the development of cholera diarrhoea in the challenged vaccinees (cvAUC 78%, 95% CI 66-91), this model did poorly at predicting protection against infection in the household contacts (AUC 60%, 52-67)., Interpretation: Several biomarkers predict protection better than vibriocidal titres. A model based on protection against infection among household contacts was predictive of protection against both infection and diarrhoeal illness in challenged vaccinees, suggesting that models based on observed conditions in a cholera-endemic population might be more likely to identify broadly applicable correlates of protection than models trained on single experimental settings., Funding: National Institute of Allergy and Infectious Diseases and National Institute of Child Health and Human Development, National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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46. Distinguishing Severe Acute Respiratory Syndrome Coronavirus 2 Persistence and Reinfection: A Retrospective Cohort Study.
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Turbett SE, Tomkins-Tinch CH, Anahtar MN, Dugdale CM, Hyle EP, Shenoy ES, Shaw B, Egbuonu K, Bowman KA, Zachary KC, Adams GC, Hooper DC, Ryan ET, LaRocque RC, Bassett IV, Triant VA, Siddle KJ, Rosenberg E, Sabeti PC, Schaffner SF, MacInnis BL, Lemieux JE, and Charles RC
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- Humans, COVID-19 Testing, Reinfection diagnosis, Retrospective Studies, SARS-CoV-2 genetics, RNA, COVID-19 diagnosis
- Abstract
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection is poorly understood, partly because few studies have systematically applied genomic analysis to distinguish reinfection from persistent RNA detection related to initial infection. We aimed to evaluate the characteristics of SARS-CoV-2 reinfection and persistent RNA detection using independent genomic, clinical, and laboratory assessments., Methods: All individuals at a large academic medical center who underwent a SARS-CoV-2 nucleic acid amplification test (NAAT) ≥45 days after an initial positive test, with both tests between 14 March and 30 December 2020, were analyzed for potential reinfection. Inclusion criteria required having ≥2 positive NAATs collected ≥45 days apart with a cycle threshold (Ct) value <35 at repeat testing. For each included subject, likelihood of reinfection was assessed by viral genomic analysis of all available specimens with a Ct value <35, structured Ct trajectory criteria, and case-by-case review by infectious diseases physicians., Results: Among 1569 individuals with repeat SARS-CoV-2 testing ≥45 days after an initial positive NAAT, 65 (4%) met cohort inclusion criteria. Viral genomic analysis characterized mutations present and was successful for 14/65 (22%) subjects. Six subjects had genomically supported reinfection, and 8 subjects had genomically supported persistent RNA detection. Compared to viral genomic analysis, clinical and laboratory assessments correctly distinguished reinfection from persistent RNA detection in 12/14 (86%) subjects but missed 2/6 (33%) genomically supported reinfections., Conclusions: Despite good overall concordance with viral genomic analysis, clinical and Ct value-based assessments failed to identify 33% of genomically supported reinfections. Scaling-up genomic analysis for clinical use would improve detection of SARS-CoV-2 reinfections., Competing Interests: Potential conflicts of interest. M. N. A. is an equity holder and consultant to Day Zero Diagnostics (company does not work on SARS-CoV-2). P. C. S. is a co-founder of, shareholder in, and scientific advisor to Sherlock Biosciences, Inc (2019–present); she is also a Board member of and shareholder in Danaher Corporation (2019–present), and co-founder and consultant to Delve Bio (2022–present). P. C. S. has filed IP related to genome sequencing and analysis. P. C. S. also reports that Sherlock Biosciences has licensed technology from the author and her lab on CRISPR-based diagnostics and has received consulting fees from the same; stock or stock options with Polaris Genomics (investor and future scientific advisory board [SAB] member) and NextGen Jane (former SAB member and investor). I. V. B. reports an unrelated NIH grant number R01AI042006-24S1. E. S. S. reports unrelated grants or contracts from CDC, Assistant Secretary for Preparedness and Response, MIT/Quanta; payment or honoraria as a writer for Up To Date (2022 to current) and for a single lecture on COVID Infection Prevention to Vertex Pharmaceuticals, 2020; roles as President of Massachusetts Infectious Diseases Society, Vice-Chair of Public Policy and Government Affairs Committee, Society for Healthcare Epidemiology of America, and Member of Boston Biosafety Committee, Boston Public Health Commission. K. A. B, reports NIH training grant 5T32 AI007387-32, unrelated to this work. C. M. D. reports grants paid to institution (NIH/National Institute of Child Health and Human Development [NICHD] grant number K08 HD101342; Harvard University Center for AIDS Research [CFAR]; and MGH Executive Committee on Research), payments to institution from CDC; and contracts to institution from International AIDS Vaccine Initiative and NIH/IMPAACT Network. R. C. L. reports grant from CDC: U01-CK000633; UpToDate: Royalties for Authorship; payment or honoraria from CDC Foundation: Editorial Services; a leadership or fiduciary role on the board of Greater Boston Physicians for Social Responsibility. J. E. L. reports consulting fees 2019–2020 from Sherlock Biosciences; and honorarium from Virology Education. E. R. reports participation as PPD member of the Moderna Clinical Endpoint Adjudication Committee. S. E. T. reports royalties from UpToDate; travel support for attending Duke Clinical Research Institute meeting on preparing for the next pandemic; and reports that her husband is a partner and has equity in an economic consulting firm (Analysis Group Inc.) that provides consulting services for life science companies among many others. E. P. H. reports grants or contracts unrelated to this work and paid to institution from NIH and MGH; royalties paid to author from UpToDate. All other authors report no conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2023
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47. Travel-associated extensively drug-resistant typhoid fever: a case series to inform management in non-endemic regions.
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Posen HJ, Wong W, Farrar DS, Campigotto A, Chan T, Barker KR, Hagmann SHF, Ryan ET, LaRocque RC, Earl AM, Worby CJ, Castelli F, Fumadó VP, Britton PN, Libman M, Hamer DH, and Morris SK
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- Humans, Travel, Azithromycin, Anti-Bacterial Agents, Salmonella typhi, Carbapenems, Pakistan epidemiology, Typhoid Fever epidemiology, Anti-Infective Agents
- Abstract
Background: Extensively drug-resistant (XDR) typhoid fever is a threat to travelers to Pakistan. We describe a multicontinental case series of travel-acquired XDR typhoid fever to demonstrate the global spread of the problem and encourage preventive interventions as well as appropriate empiric antimicrobial use., Methods: Cases were extracted from the GeoSentinel database, microbiologic laboratory records of two large hospitals in Toronto, Canada, and by invitation to TropNet sites. All isolates were confirmed XDR Salmonella enterica serovar Typhi (Salmonella typhi), with resistance to ampicillin, ceftriaxone, ciprofloxacin and trimethoprim-sulfamethoxazole., Results: Seventeen cases were identified in Canada (10), USA (2), Spain (2), Italy (1), Australia (1) and Norway (1). Patients under 18 years represented 71% (12/17) of cases, and all patients travelled to Pakistan to visit friends or relatives. Only one patient is known to have been vaccinated. Predominant symptoms were fever, abdominal pain, vomiting and diarrhoea. Antimicrobial therapy was started on Day 1 of presentation in 75% (12/16) of patients, and transition to a carbapenem or azithromycin occurred a median of 2 days after blood culture was drawn. Antimicrobial susceptibilities were consistent with the XDR S. typhi phenotype, and whole genome sequencing on three isolates confirmed their belonging to the XDR variant of the H58 clade., Conclusions: XDR typhoid fever is a particular risk for travelers to Pakistan, and empiric use of a carbapenem or azithromycin should be considered. Pre-travel typhoid vaccination and counseling are necessary and urgent interventions, especially for visiting friends and relatives travelers. Ongoing sentinel surveillance of XDR typhoid fever is needed to understand changing epidemiology., (© International Society of Travel Medicine 2022. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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48. Long-term sialidase-specific immune responses after natural infection with cholera: Findings from a longitudinal cohort study in Bangladesh.
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Chowdhury F, Akter A, Bhuiyan TR, Biswas R, Firoj MG, Tauheed I, Harris JB, Larocque RC, Ross AG, McMillan NAJ, Charles RC, Ryan ET, Calderwood SB, and Qadri F
- Subjects
- Adult, Child, Humans, Neuraminidase, Longitudinal Studies, Bangladesh, B-Lymphocytes, Immunologic Memory, Immunoglobulin G, Antibodies, Bacterial, Lipopolysaccharides, Cohort Studies, Cholera Toxin, Immunoglobulin M, Immunoglobulin A, Cholera, Coinfection
- Abstract
Background: Immune responses that target sialidase occur following natural cholera and have been associated with protection against cholera. Sialidase is a neuraminidase that facilitates the binding of cholera toxin (CT) to intestinal epithelial cells. Despite this, little is known about age-related sialidase-specific immune responses and the impact of nutritional status and co-infection on sialidase-specific immunity., Methods: We enrolled 50 culture-confirmed Vibrio cholerae O1 cholera cases presenting to the icddr,b Dhaka hospital with moderate to severe dehydration. We evaluated antibody responses out to 18 months (day 540) following cholera. We assessed immune responses targeting sialidase, lipopolysaccharide (LPS), cholera toxin B subunit (CtxB), and vibriocidal responses. We also explored the association of sialidase-specific immune responses to nutritional parameters and parasitic co-infection of cases., Results: This longitudinal cohort study showed age-dependent differences in anti-sialidase immune response after natural cholera infection. Adult patients developed plasma anti-sialidase IgA and IgG responses after acute infection (P<0.05), which gradually decreased from day 30 on. In children, no significant anti-sialidase IgA, IgM, and IgG response was seen with the exception of a late IgG response at study day 540 (p=0.05 compared to adults). There was a correlation between anti-sialidase IgA with vibriocidal titers, as well as anti-sialidase IgA and IgG with anti-LPS and anti-CtxB antibody responses in adult patients, whereas in children, a significant positive correlation was seen only between anti-sialidase IgA and CtxB IgA responses. Stunted children showed significantly lower anti-sialidase IgA, IgG, and IgM antibody responses and higher LPS IgG and IgM antibody responses than healthy children. The anti-sialidase IgA and IgG responses were significantly higher in cases with concomitant parasitic infection., Conclusion: Our data suggest that cholera patients develop age-distinct systemic and mucosal immune responses against sialidase. The stunted children have a lower anti-sialidase antibody response which may be associated with gut enteropathy and the neuraminidase plays an important role in augmented immune response in cholera patients infected with parasites., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chowdhury, Akter, Bhuiyan, Biswas, Firoj, Tauheed, Harris, Larocque, Ross, McMillan, Charles, Ryan, Calderwood and Qadri.)
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- 2022
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49. Identifying Recent Cholera Infections Using a Multiplex Bead Serological Assay.
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Jones FK, Bhuiyan TR, Muise RE, Khan AI, Slater DM, Hutt Vater KR, Chowdhury F, Kelly M, Xu P, Kováč P, Biswas R, Kamruzzaman M, Ryan ET, Calderwood SB, LaRocque RC, Lessler J, Charles RC, Leung DT, Qadri F, Harris JB, and Azman AS
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- Humans, Cross-Sectional Studies, Antibodies, Bacterial, Immunoglobulin G, Immunoglobulin A, Bangladesh epidemiology, Cholera epidemiology, Vibrio cholerae O1
- Abstract
Estimates of incidence based on medically attended cholera can be severely biased. Vibrio cholerae O1 leaves a lasting antibody signal and recent advances showed that these can be used to estimate infection incidence rates from cross-sectional serologic data. Current laboratory methods are resource intensive and challenging to standardize across laboratories. A multiplex bead assay (MBA) could efficiently expand the breadth of measured antibody responses and improve seroincidence accuracy. We tested 305 serum samples from confirmed cholera cases (4 to 1083 d postinfection) and uninfected contacts in Bangladesh using an MBA (IgG/IgA/IgM for 7 Vibrio cholerae O1-specific antigens) as well as traditional vibriocidal and enzyme-linked immunosorbent assays (2 antigens, IgG, and IgA). While postinfection vibriocidal responses were larger than other markers, several MBA-measured antibodies demonstrated robust responses with similar half-lives. Random forest models combining all MBA antibody measures allowed for accurate identification of recent cholera infections (e.g., past 200 days) including a cross-validated area under the curve (cvAUC
200 ) of 92%, with simpler 3 IgG antibody models having similar accuracy. Across infection windows between 45 and 300 days, the accuracy of models trained on MBA measurements was non-inferior to models based on traditional assays. Our results illustrated a scalable cholera serosurveillance tool that can be incorporated into multipathogen serosurveillance platforms. IMPORTANCE Reliable estimates of cholera incidence are challenged by poor clinical surveillance and health-seeking behavior biases. We showed that cross-sectional serologic profiles measured with a high-throughput multiplex bead assay can lead to accurate identification of those infected with pandemic Vibrio cholerae O1, thus allowing for estimates of seroincidence. This provides a new avenue for understanding the epidemiology of cholera, identifying priority areas for cholera prevention/control investments, and tracking progress in the global fight against this ancient disease.- Published
- 2022
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50. Longevity of memory B cells and antibodies, as well as the polarization of effector memory helper T cells, are associated with disease severity in patients with COVID-19 in Bangladesh.
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Akhtar M, Basher SR, Nizam NN, Kamruzzaman M, Khaton F, Banna HA, Kaisar MH, Karmakar PC, Hakim A, Akter A, Ahmed T, Tauheed I, Islam S, Ahmmed F, Mahamud S, Hasnat MA, Sumon MA, Rashed A, Ghosh S, Calderwood SB, Harris JB, Charles RC, LaRocque RC, Ryan ET, Banu S, Shirin T, Chowdhury F, Bhuiyan TR, and Qadri F
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- Humans, Bangladesh epidemiology, Memory B Cells, SARS-CoV-2, Immunoglobulin G, Antibodies, Viral, Patient Acuity, Th17 Cells, COVID-19
- Abstract
The longevity of immune responses induced by different degrees of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides information important to understanding protection against coronavirus disease 2019 (COVID-19). Here, we report the persistence of SARS-CoV-2 spike receptor-binding domain (RBD) specific antibodies and memory B cells recognizing this antigen in sequential samples from patients in Bangladesh with asymptomatic, mild, moderate and severe COVID-19 out to six months following infection. Since the development of long-lived memory B cells, as well as antibody production, is likely to be dependent on T helper (Th) cells, we also investigated the phenotypic changes of Th cells in COVID-19 patients over time following infection. Our results show that patients with moderate to severe COVID-19 mounted significant levels of IgG antibodies out to six months following infection, while patients with asymptomatic or mild disease had significant levels of IgG antibodies out to 3 months following infection, but these then fell more rapidly at 6 months than in patients with higher disease severity. Patients from all severity groups developed circulating memory B cells (MBCs) specific to SARS-CoV-2 spike RBD by 3 months following infection, and these persisted until the last timepoint measured at 6 months. A T helper cell response with an effector memory phenotype was observed following infection in all symptomatic patients, while patients with asymptomatic infection had no significant increases in effector Th1, Th2 and Th17 effector memory cell responses. Our results suggest that the strength and magnitude of antibody and memory B cells induced following SARS-CoV-2 infection depend on the severity of the disease. Polarization of the Th cell response, with an increase in Th effector memory cells, occurs in symptomatic patients by day 7 following infection, with increases seen in Th1, Th2, Th17 and follicular helper T cell subsets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Akhtar, Basher, Nizam, Kamruzzaman, Khaton, Banna, Kaisar, Karmakar, Hakim, Akter, Ahmed, Tauheed, Islam, Ahmmed, Mahamud, Hasnat, Sumon, Rashed, Ghosh, Calderwood, Harris, Charles, LaRocque, Ryan, Banu, Shirin, Chowdhury, Bhuiyan and Qadri.)
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- 2022
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