The Controlled Human Infection Model for Enterotoxigenic Escherichia coli

Porter, Chad K.; Talaat, Kawsar R.; Isidean, Sandra D.; Kardinaal, A.F.M.; Chakraborty, Subhra; Gutiérrez, Ramiro L.; Sack, David A.; Bourgeois, A. Louis

doi:10.1007/82_2021_242

Cited by 3 publications

(3 citation statements)

References 148 publications

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“…In this study, we used the E. coli infection challenge model to study the effects of the intervention on infection and diarrhea as a model to evaluate whether the WPC might offer protection against infection in infants. A limitation of this study is that this type of inoculation can only be performed in healthy adults with a well-functioning immune system [ 51 ]. This population does not represent a vulnerable infant population with a high disease burden.…”

Section: Discussionmentioning

confidence: 99%

A Double-Blind, Randomized Intervention Study on the Effect of a Whey Protein Concentrate on E. coli-Induced Diarrhea in a Human Infection Model

et al. 2022

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Infectious diseases are a major cause of morbidity and mortality worldwide. Nutritional interventions may enhance resistance to infectious diseases or help to reduce clinical symptoms. Here, we investigated whether a whey protein concentrate (WPC) could decrease diarrheagenic Escherichia coli-induced changes in reported stool frequency and gastrointestinal complaints in a double-blind, parallel 4-week intervention study. Subjects were randomly assigned to a whey hydrolysate placebo group, a low-dose WPC group or a high-dose WPC group. After 2 weeks of consumption, subjects (n = 121) were orally infected with a high dose of live but attenuated diarrheagenic E. coli (strain E1392/75-2A; 1E10 colony-forming units). Subjects recorded information on stool consistency and the frequency and severity of symptoms in an online diary. The primary outcome parameters were a change in stool frequency (stools per day) and a change in Gastrointestinal Symptom Rating Scale (GSRS) diarrhea score between the first and second days after infection. Neither dose of the whey protein concentrate in the dietary treatment affected the E. coli-induced increase in stool frequency or GSRS diarrhea score compared to placebo treatment. The composition of the microbiota shifted between the start of the study and after two weeks of consumption of the products, but no differences between the intervention groups were observed, possibly due to dietary guidelines that subjects had to adhere to during the study. In conclusion, consumption of the whey protein concentrate by healthy adults did not reduce diarrhea scores in an E. coli infection model compared to a whey hydrolysate placebo control.

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Section: Discussionmentioning

confidence: 99%

A Double-Blind, Randomized Intervention Study on the Effect of a Whey Protein Concentrate on E. coli-Induced Diarrhea in a Human Infection Model

et al. 2022

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“…The ETEC strain was H10407 (LT + ST + CFA/I + ) [ 21 , 22 , 23 ]. The inoculum was freshly prepared from vials (Lot #0519) produced under cGMP conditions at the Walter Reed Army Institute of Research Pilot Bioproduction Facility.…”

Section: Methodsmentioning

confidence: 99%

“…Subjects were admitted to the inpatient facility at the Center for Immunization Research at the JHU Bayview Campus the day prior to challenge and evaluated for continued eligibility and had baseline samples collected. All subjects initiated an overnight fast and were challenged the next day with a target inoculum of 2 × 10 7 CFU of ETEC strain H10407 [ 21 , 22 , 23 , 24 ]. Subjects were monitored for diarrhea and other signs of enteric illness.…”

Section: Methodsmentioning

confidence: 99%

Efficacy Evaluation of an Intradermally Delivered Enterotoxigenic Escherichia coli CF Antigen I Fimbrial Tip Adhesin Vaccine Coadministered with Heat-Labile Enterotoxin with LT(R192G) against Experimental Challenge with Enterotoxigenic E. coli H10407 in Healthy Adult Volunteers

Gutiérrez,

Porter,

Harro

et al. 2024

Microorganisms

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Background. Enterotoxigenic E. coli (ETEC) is a principal cause of diarrhea in travelers, deployed military personnel, and children living in low to middle-income countries. ETEC expresses a variety of virulence factors including colonization factors (CF) that facilitate adherence to the intestinal mucosa. We assessed the protective efficacy of a tip-localized subunit of CF antigen I (CFA/I), CfaE, delivered intradermally with the mutant E. coli heat-labile enterotoxin, LTR192G, in a controlled human infection model (CHIM). Methods. Three cohorts of healthy adult subjects were enrolled and given three doses of 25 μg CfaE + 100 ng LTR192G vaccine intradermally at 3-week intervals. Approximately 28 days after the last vaccination, vaccinated and unvaccinated subjects were admitted as inpatients and challenged with approximately 2 × 107 cfu of CFA/I+ ETEC strain H10407 following an overnight fast. Subjects were assessed for moderate-to-severe diarrhea for 5 days post-challenge. Results. A total of 52 volunteers received all three vaccinations; 41 vaccinated and 43 unvaccinated subjects were challenged and assessed for moderate-to-severe diarrhea. Naïve attack rates varied from 45.5% to 64.7% across the cohorts yielding an overall efficacy estimate of 27.8% (95% confidence intervals: −7.5–51.6%). In addition to reducing moderate–severe diarrhea rates, the vaccine significantly reduced loose stool output and overall ETEC disease severity. Conclusions. This is the first study to demonstrate protection against ETEC challenge after intradermal vaccination with an ETEC adhesin. Further examination of the challenge methodology is necessary to address the variability in naïve attack rate observed among the three cohorts in the present study.

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Health risk assessment and removal efficiency of typical opportunistic pathogens by advanced reclaimed water treatment process

Sun

Hao

et al. 2022

Preprint

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In this study, two combined processes of coagulation sedimentation-NaClO disinfection and coagulation sedimentation-Ultrafiltration(UF)-NaClO disinfection were used as deep treatment processes. To explore the removal effect and mechanism of the combined process on Legionella, Pseudomonas aeruginosa, Mycobacterium avium and Escherichia coli in the secondary effluent. Taking Beijing Olympic Forest Park as the evaluation scene of reclaimed water landscape reuse, the health risk assessment were carried out on the opportunistic pathogens. The results showed that the combined process of coagulation sedimentation-UF-NaClO had a good removal effect on Legionella, Pseudomonas aeruginosa, Mycobacterium avium and Escherichia coli, the removal rates were 99.8%, 98.6%, 99.4% and 99.1%, respectively. There was a significant positive correlation between the concentration of Escherichia coli in the secondary effluent and the three opportunistic pathogens, but the correlation between the concentration of Escherichia coli in the effluent and the three opportunistic pathogens was no longer significant after the two combination processes. After secondary effluent coagulation and sedimentation-UF-NaClO disinfection and reuse for urban landscape leisure activities, the single exposure infection probability of the three opportunistic pathogens is the lowest, and the safety rate of human health can reach from 70.9–100.0%.

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The Controlled Human Infection Model for Enterotoxigenic Escherichia coli

Cited by 3 publications

References 148 publications

A Double-Blind, Randomized Intervention Study on the Effect of a Whey Protein Concentrate on E. coli-Induced Diarrhea in a Human Infection Model

A Double-Blind, Randomized Intervention Study on the Effect of a Whey Protein Concentrate on E. coli-Induced Diarrhea in a Human Infection Model

Efficacy Evaluation of an Intradermally Delivered Enterotoxigenic Escherichia coli CF Antigen I Fimbrial Tip Adhesin Vaccine Coadministered with Heat-Labile Enterotoxin with LT(R192G) against Experimental Challenge with Enterotoxigenic E. coli H10407 in Healthy Adult Volunteers

Health risk assessment and removal efficiency of typical opportunistic pathogens by advanced reclaimed water treatment process

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