Evaluation of the Clinical and Microbiological Response to Salmonella Paratyphi A Infection in the First Paratyphoid Human Challenge Model
| Autor: | Dobinson, H.C., Gibani, M.M., Jones, C., Thomaides-Brears, H.B., Voysey, M., Darton, T.C., Waddington, C.S., Campbell, D., Milligan, I., Zhou, L., Shrestha, S., Kerridge, S.A., Peters, A., Stevens, Z., Podda, A., Martin, L.B., D'Alessio, F., Thanh, D.P., Basnyat, B., Baker, S., Angus, B., Levine, M.M., Blohmke, C.J., Pollard, A.J. |
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| Přispěvatelé: | Baker, Stephen [0000-0003-1308-5755], Apollo - University of Cambridge Repository |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Time Factors Immunology enteric fever Bacteremia Microbiology Feces Young Adult FEVER DESIGN Paratyphoid Fever Major Article Humans paratyphoid infection 11 Medical and Health Sciences OUTPATIENT Science & Technology Temperature 06 Biological Sciences Middle Aged bacterial infections and mycoses immune responses Healthy Volunteers Editor's Choice Salmonella enterica paratyphi A Infectious Diseases Blood Salmonella paratyphi A ENTERICA SEROVAR PARATYPHI bacteria ORAL TYPHOID VACCINE human challenge study Female BURDEN Life Sciences & Biomedicine |
| Zdroj: | Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America |
| ISSN: | 1058-4838 |
| DOI: | 10.17863/cam.38620 |
| Popis: | Summary The safe establishment of a protocol for a human challenge model for Salmonella Paratyphi A can be used to expedite the evaluation of novel vaccine candidates and provides insight into the clinical and immune response to paratyphoid infection. Background. To expedite the evaluation of vaccines against paratyphoid fever, we aimed to develop the first human challenge model of Salmonella enterica serovar Paratyphi A infection. Methods. Two groups of 20 participants underwent oral challenge with S. Paratyphi A following sodium bicarbonate pretreatment at 1 of 2 dose levels (group 1: 1–5 × 103 colony-forming units [CFU] and group 2: 0.5–1 × 103 CFU). Participants were monitored in an outpatient setting with daily clinical review and collection of blood and stool cultures. Antibiotic treatment was started when prespecified diagnostic criteria were met (temperature ≥38°C for ≥12 hours and/or bacteremia) or at day 14 postchallenge. Results. The primary study objective was achieved following challenge with 1–5 × 103 CFU (group 1), which resulted in an attack rate of 12 of 20 (60%). Compared with typhoid challenge, paratyphoid was notable for high rates of subclinical bacteremia (at this dose, 11/20 [55%]). Despite limited symptoms, bacteremia persisted for up to 96 hours after antibiotic treatment (median duration of bacteremia, 53 hours [interquartile range, 24–85 hours]). Shedding of S. Paratyphi A in stool typically preceded onset of bacteremia. Conclusions. Challenge with S. Paratyphi A at a dose of 1–5 × 103 CFU was well tolerated and associated with an acceptable safety profile. The frequency and persistence of bacteremia in the absence of clinical symptoms was notable, and markedly different from that seen in previous typhoid challenge studies. We conclude that the paratyphoid challenge model is suitable for the assessment of vaccine efficacy using endpoints that include bacteremia and/or symptomatology. Clinical Trials Registration. NCT02100397. |
| Databáze: | OpenAIRE |
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