Observational studyClinical infectious diseases : an official publication of the Infectious Diseases Society of America2014
An outpatient, ambulant-design, controlled human infection model using escalating doses of Salmonella Typhi challenge delivered in sodium bicarbonate solution.
Observational study in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 4 of them syntheses that pooled it.
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Who cites it
101 citing papers in PubMed, 4 syntheses or guidelines pooled it, 152 citations in OpenAlex.
- A consensus immune dysregulation framework for sepsis and critical illnesses.Nature medicine · 2025Guideline
- Associations among Water, Sanitation, and Hygiene, and Food Exposures and Typhoid Fever in Case-Control Studies: A Systematic Review and Meta-Analysis.The American journal of tropical medicine and hygiene · 2020Pooled it
- Incubation period of typhoidal salmonellosis: a systematic review and meta-analysis of outbreaks and experimental studies occurring over the last century.BMC infectious diseases · 2018Pooled it
- A systematic review and meta-analysis on the incubation period of Campylobacteriosis.Epidemiology and infection · 2017Pooled it
- Molecular correlates of vaccine-induced protection against typhoid fever.The Journal of clinical investigation · 2023Trial
- Vi-specific serological correlates of protection for typhoid fever.The Journal of experimental medicine · 2021Trial
- Homologous and heterologous re-challenge with Salmonella Typhi and Salmonella Paratyphi A in a randomised controlled human infection model.PLoS neglected tropical diseases · 2020Trial
- Treatment responses to Azithromycin and Ciprofloxacin in uncomplicated Salmonella Typhi infection: A comparison of Clinical and Microbiological Data from a Controlled Human Infection Model.PLoS neglected tropical diseases · 2019Trial
- IgA and IgG1 Specific to Vi Polysaccharide ofFrontiers in immunology · 2019Trial
- Efficacy and immunogenicity of a Vi-tetanus toxoid conjugate vaccine in the prevention of typhoid fever using a controlled human infection model of Salmonella Typhi: a randomised controlled, phase 2b trial.Lancet (London, England) · 2017Trial
- Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a.PLoS neglected tropical diseases · 2016Trial
- Interferon-driven alterations of the host's amino acid metabolism in the pathogenesis of typhoid fever.The Journal of experimental medicine · 2016Trial
- Trial
- EnhancedInfection and immunity · 2026Article
- Evaluation of mdh, dld, tcfA, and folE gene markers for detection of enteric fever using real-time PCR.Scientific reports · 2026Article
- Controlled human infection with Mycobacterium tuberculosis: practical considerations for clinical trials.The Lancet. Microbe · 2026Review
- Phase II multicentre double-blind randomised controlled trial of a Bivalent VaccInation againstBMJ open · 2026Article
- Sexually transmitted enteric infections in men who have sex with men.Clinical microbiology reviews · 2025Review
- Leveraging paired serology to estimate the incidence of typhoidal Salmonella infection in the STRATAA study.PLoS neglected tropical diseases · 2025Article
- Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundTyphoid fever is a major global health problem, the control of which is hindered by lack of a suitable animal model in which to study Salmonella Typhi infection. Until 1974, a human challenge model advanced understanding of typhoid and was used in vaccine development. We set out to establish a new human challenge model and ascertain the S. Typhi (Quailes strain) inoculum required for an attack rate of 60%-75% in typhoid-naive volunteers when ingested with sodium bicarbonate solution.
methodsGroups of healthy consenting adults ingested escalating dose levels of S. Typhi and were closely monitored in an outpatient setting for 2 weeks. Antibiotic treatment was initiated if typhoid diagnosis occurred (temperature ≥38°C sustained ≥12 hours or bacteremia) or at day 14 in those remaining untreated.
resultsTwo dose levels (10(3) or 10(4) colony-forming units) were required to achieve the primary objective, resulting in attack rates of 55% (11/20) or 65% (13/20), respectively. Challenge was well tolerated; 4 of 40 participants fulfilled prespecified criteria for severe infection. Most diagnoses (87.5%) were confirmed by blood culture, and asymptomatic bacteremia and stool shedding of S. Typhi was also observed. Participants who developed typhoid infection demonstrated serological responses to flagellin and lipopolysaccharide antigens by day 14; however, no anti-Vi antibody responses were detected.
conclusionsHuman challenge with a small inoculum of virulent S. Typhi administered in bicarbonate solution can be performed safely using an ambulant-model design to advance understanding of host-pathogen interactions and immunity. This model should expedite development of diagnostics, vaccines, and therapeutics for typhoid control.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.