scholarly journals Treatment responses to Azithromycin and Ciprofloxacin in uncomplicated Salmonella Typhi infection: A comparison of Clinical and Microbiological Data from a Controlled Human Infection Model

2019 ◽  
Vol 13 (12) ◽  
pp. e0007955 ◽  
Author(s):  
Celina Jin ◽  
Malick M. Gibani ◽  
Shaun H. Pennington ◽  
Xinxue Liu ◽  
Alison Ardrey ◽  
...  
Keyword(s):  
Salmonella Typhi ◽  
Human Infection ◽  
Infection Model ◽  
Treatment Responses ◽  
Microbiological Data

scholarly journals IgA and IgG1 Specific to Vi Polysaccharide of Salmonella Typhi Correlate With Protection Status in a Typhoid Fever Controlled Human Infection Model

2019 ◽  
Vol 10 ◽  
Author(s):  
Lindsay C. Dahora ◽  
Celina Jin ◽  
Rachel L. Spreng ◽  
Frederick Feely ◽  
Ryan Mathura ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Salmonella Typhi ◽  
Human Infection ◽  
Infection Model

scholarly journals An Outpatient, Ambulant-Design, Controlled Human Infection Model Using Escalating Doses of Salmonella Typhi Challenge Delivered in Sodium Bicarbonate Solution

2014 ◽  
Vol 58 (9) ◽  
pp. 1230-1240 ◽  
Author(s):  
Claire S. Waddington ◽  
Thomas C. Darton ◽  
Claire Jones ◽  
Kathryn Haworth ◽  
Anna Peters ◽  
...  
Keyword(s):  
Sodium Bicarbonate ◽  
Sodium Bicarbonate Solution ◽  
Salmonella Typhi ◽  
Human Infection ◽  
Infection Model

scholarly journals Homologous and heterologous re-challenge with Salmonella Typhi and Salmonella Paratyphi A in a randomised controlled human infection model

2020 ◽  
Vol 14 (10) ◽  
pp. e0008783
Author(s):  
Malick M. Gibani ◽  
Celina Jin ◽  
Sonu Shrestha ◽  
Maria Moore ◽  
Lily Norman ◽  
...  
Keyword(s):  
Salmonella Typhi ◽  
Human Infection ◽  
Infection Model ◽  
Randomised Controlled

scholarly journals A Salmonella Typhi Controlled Human Infection Study for Assessing Correlation between Bactericidal Antibodies and Protection against Infection Induced by Typhoid Vaccination

2021 ◽  
Vol 9 (7) ◽  
pp. 1394
Author(s):  
Elizabeth Jones ◽  
Celina Jin ◽  
Lisa Stockdale ◽  
Christina Dold ◽  
Andrew J. Pollard ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Salmonella Typhi ◽  
Human Infection ◽  
Infection Model ◽  
Conjugate Vaccines ◽  
Serum Bactericidal Activity ◽  
Iga Antibodies ◽  
Protection Against Infection ◽  
Infection Study

Vi-polysaccharide conjugate vaccines are efficacious against typhoid fever in children living in endemic settings, their recent deployment is a promising step in the control of typhoid fever. However, there is currently no accepted correlate of protection. IgG and IgA antibodies generated in response to Vi conjugate or Vi plain polysaccharide vaccination are important but there are no definitive protective titre thresholds. We adapted a luminescence-based serum bactericidal activity (SBA) for use with S. Typhi and assessed whether bactericidal antibodies induced by either Vi tetanus toxoid conjugate (Vi-TT) or Vi plain polysaccharide (Vi-PS) were associated with protection in a controlled human infection model of typhoid fever. Both Vi-PS and Vi-TT induced significant increase in SBA titre after 28 days (Vi-PS; p < 0.0001, Vi-TT; p = 0.003), however higher SBA titre at the point of challenge did not correlate with protection from infection or reduced symptom severity. We cannot eliminate the role of SBA as part of a multifactorial immune response which protects against infection, however, our results do not support a strong role for SBA as a mechanism of Vi vaccine mediated protection in the CHIM setting.

scholarly journals Salmonella Typhi Bactericidal Antibodies Reduce Disease Severity but Do Not Protect against Typhoid Fever in a Controlled Human Infection Model

2018 ◽  
Vol 8 ◽  
Author(s):  
Helene B. Juel ◽  
Helena B. Thomaides-Brears ◽  
Thomas C. Darton ◽  
Claire Jones ◽  
Elizabeth Jones ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Disease Severity ◽  
Salmonella Typhi ◽  
Human Infection ◽  
Infection Model ◽  
Reduce Disease Severity

scholarly journals Rhinovirus induces MUC5AC in a human infection model and in vitro via NF- B and EGFR pathways

2010 ◽  
Vol 36 (6) ◽  
pp. 1425-1435 ◽  
Author(s):  
C. A. Hewson ◽  
J. J. Haas ◽  
N. W. Bartlett ◽  
S. D. Message ◽  
V. Laza-Stanca ◽  
...  
Keyword(s):  
Human Infection ◽  
Infection Model

scholarly journals A pneumococcal controlled human infection model in Malawi: Transfer of an established pneumococcal carriage model from Liverpool, UK to Blantyre, Malawi – A feasibility study

2020 ◽  
Vol 5 ◽  
pp. 25
Author(s):  
Ben Morton ◽  
Sarah Burr ◽  
Kondwani Jambo ◽  
Jamie Rylance ◽  
Marc Y.R. Henrion ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Feasibility Study ◽  
Invasive Disease ◽  
Community Acquired Pneumonia ◽  
Human Infection ◽  
Infection Model ◽  
Endpoint Detection ◽  
Pneumococcal Carriage ◽  
Sampling Protocols ◽  
Classical Culture

Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement and demonstrate reduced effectiveness against mucosal colonisation.  As asymptomatic colonisation of the human nasopharynx is a prerequisite for pneumococcal disease, this is proposed as a marker for novel vaccine efficacy. Our team established a safe and reproducible pneumococcal controlled human infection model at Liverpool School of Tropical Medicine (LSTM). This has been used to test vaccine induced protection against nasopharyngeal carriage for ten years in over 1000 participants. We will transfer established standardised operating procedures from LSTM to Malawi and test in up to 36 healthy participants. Primary endpoint: detection of the inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: confirmation of robust clinical and laboratory methods for sample capture and processing. Tertiary endpoints: participant acceptability of study and methods. We will test three doses of pneumococcal inoculation (20,000, 80,000 and 160,000 colony forming units [CFUs] per naris) using a parsimonious study design intended to reduce unnecessary exposure to participants. We hypothesise that 80,000 CFUs will induce nasal colonisation in approximately half of participants per established LSTM practice. The aims of the feasibility study are: 1) Establish Streptococcus pneumoniae experimental human pneumococcal carriage in Malawi; 2) Confirm optimal nasopharyngeal pneumococcal challenge dose; 3) Confirm safety and measure potential symptoms; 4) Confirm sampling protocols and laboratory assays; 5) Assess feasibility and acceptability of consent and study procedures. Confirmation of pneumococcal controlled human infection model feasibility in Malawi will enable us to target pneumococcal vaccine candidates for an at-risk population who stand the most to gain from new and improved vaccine strategies.

scholarly journals EnterotoxigenicE. colivirulence gene regulation in human infections

2018 ◽  
Vol 115 (38) ◽  
pp. E8968-E8976 ◽  
Author(s):  
Alexander A. Crofts ◽  
Simone M. Giovanetti ◽  
Erica J. Rubin ◽  
Frédéric M. Poly ◽  
Ramiro L. Gutiérrez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Virulence Factor ◽  
Virulence Gene ◽  
Human Infection ◽  
Anaerobic Growth ◽  
Infection Model ◽  
Low Oxygen ◽  
Virulence Gene Expression ◽  
Factor Expression

EnterotoxigenicEscherichia coli(ETEC) is a global diarrheal pathogen that utilizes adhesins and secreted enterotoxins to cause disease in mammalian hosts. Decades of research on virulence factor regulation in ETEC has revealed a variety of environmental factors that influence gene expression, including bile, pH, bicarbonate, osmolarity, and glucose. However, other hallmarks of the intestinal tract, such as low oxygen availability, have not been examined. Further, determining how ETEC integrates these signals in the complex host environment is challenging. To address this, we characterized ETEC’s response to the human host using samples from a controlled human infection model. We found ETEC senses environmental oxygen to globally influence virulence factor expression via the oxygen-sensitive transcriptional regulator fumarate and nitrate reduction (FNR) regulator. In vitro anaerobic growth replicates the in vivo virulence factor expression profile, and deletion offnrin ETEC strain H10407 results in a significant increase in expression of all classical virulence factors, including the colonization factor antigen I (CFA/I) adhesin operon and both heat-stable and heat-labile enterotoxins. These data depict a model of ETEC infection where FNR activity can globally influence virulence gene expression, and therefore proximity to the oxygenated zone bordering intestinal epithelial cells likely influences ETEC virulence gene expression in vivo. Outside of the host, ETEC biofilms are associated with seasonal ETEC epidemics, and we find FNR is a regulator of biofilm production. Together these data suggest FNR-dependent oxygen sensing in ETEC has implications for human infection inside and outside of the host.

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