Study objectives and outcomes
| Objective(s) | Outcome/end point(s) | |
|---|---|---|
| Primary | To determine the dose (in colony forming units) of Salmonella Paratyphi A, challenge strain NVGH308, needed to produce a 60–75% attack rate when ingested with sodium bicarbonate solution in healthy adult volunteers | Clinically or microbiologically proven paratyphoid infection following oral challenge with S. Paratyphi A, strain NVGH308, delivered with sodium bicarbonate solution |
| Secondary | (1) To describe the human physiological response to S. Paratyphi A challenge, and in those developing or not developing infection | Description of the clinical course after challenge using, for example, participant symptom profiles, temperature measurements and other recorded clinical and laboratory observations |
| (2) To evaluate the sensitivity of the predefined criteria for paratyphoid infection, using subsequent clinical, microbiological and laboratory outcomes | Determination of the challenge dose/kg (dose/surface area) actually ingested by those developing and those not developing paratyphoid infection at each dose level. Analysis of the attack rate using alternative criteria including, for example, passive field surveillance definitions, alternative temperature thresholds and adjunctive microbiological and laboratory diagnostic assays | |
| (3) To describe the characteristics of bacterial dynamics after challenge, including onset and duration of bacteraemia, bacterial burden at diagnosis and stool shedding | Microbiological assays to detect and characterise S. Paratyphi after challenge in blood, stool and urine | |
| (4) To describe the human immune response to challenge, including the innate, humoral, cell-mediated and mucosal responses | Immunological laboratory assays to measure innate, humoral, cell-mediated and mucosal responses to challenge | |
| (5) To determine genetic features affecting host–pathogen responses, alteration of those responses through epigenetic changes, control of gene expression and post-translational modifications | Laboratory and high-throughput assays to measure genetic factors affecting susceptibility, gene expression and protein translation | |
| (6) To discover, develop and evaluate novel diagnostic methods for S. Paratyphi A infection | Exploratory analysis of blood, faeces, saliva and urine samples using experimental assays and diagnostics | |
| (7) To explore the factors, influences and motivation affecting volunteers’ decision to participate in human challenge studies and their experiences of the study process | Participant responses using questionnaires during the course of the study |