Understanding Paratyphoid Infection

• Research type

  Research Study

• Full title

  Development of a Human Model of Salmonella enterica serovar Paratyphi A challenge in Healthy Adult Volunteers

• IRAS ID

  142635

• Contact name

  Andrew Pollard

• Contact email

  andrew.pollard@paediatrics.ox.ac.uk

• Sponsor organisation

  University of Oxford

• Clinicaltrials.gov Identifier

  NCT02100397

• Research summary

  Research Summary
  Enteric fever is responsible for over 20 million illnesses and 200,000 deaths each year. S. Paratyphi A accounts for a substantial and increasing proportion of these cases, as high as 90% in some regions of Asia. There are currently no vaccines directed against S. Paratyphi A, although there some candidates in preclinical and phase 1 trials.
  Paratyphoid is a human-restricted infection, for which there are currently no small animal models available. In order to further our understanding of the host-pathogen interactions, this study will develop a novel human challenge model in which to investigate this infection, using a recent successful typhoid challenge model as its template.
  Anticipating the development of a successful live challenge model through this study, there will be the possibility of evaluating novel paratyphoid vaccines that are currently in early clinical testing. This serves an important function because field trials in endemic areas are expensive and time consuming. Speeding up this process using our model will be of great benefit to endemic areas.
  We will recruit potential participants from the Oxfordshire area. Healthy subjects will ingest S. Paratyphi after drinking a bicarbonate buffer solution. Follow up over 14 days will establish whether each participant meets clearly defined criteria for diagnosis of paratyphoid infection. Statistical analysis will be performed on this outcome will determine if it consistently gives an attack rate of 60 to 75%. Descriptive clinical and laboratory data collected from participant observations, samples of blood, faeces, urine and saliva will allow insights into the disease and the host response. A maximum of 80 participants will be enrolled. Total follow up will be over one year.
  The study is funded by the European Vaccine Initiative and the Gates Foundation.

  Summary of Results
  Please see following Publications.
  Primary; Understanding paratyphoid infection: study protocol for the development of a human model of Salmonella enterica serovar Paratyphi A challenge in healthy adult volunteers - PubMed (nih.gov)
  Microbiological;https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbQne05VVe0UaW9iiRd6kqFqtWutHnJcHr7ictnJmUHPRmqlx6JJhYRinb8ad536rmA-3D-3DNptH_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YId0UPdP-2Fn-2F6EitAAQdL68IQyNSjpeqGnr9KIG08aVjUnUjVRLo0VPGjVYbqGvZjXr0YQIYo43czhvkSa0RJGhMvp4jGvK78v0-2F2XUnIk-2Fi7qFzVSxr0mnGqiaJCdtfP9CYSfno394eYe8O7n2Jc-2FlcNBSud9oFnKdJN6bGn09N-2FQ2QLvDu4Y3pQoNxyTIffus-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C6854052e1a764fee984308da01d08507%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637824292334387778%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=q4r65KevjnGwbBF42Huf01sYyLHXc2fvnfAtKvvMbUw%3D&reserved=0
  Shedding: https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbYmQsGrKhqntA-2FbTU5g6kdE6pqOzJoqNpZfOObG9-2BsBz_9Jh_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YId0UPdP-2Fn-2F6EitAAQdL68I5JNBqi4OPd4QjvgvR-2BCrXmsiys2U0lR0Pw-2BVKEBzPQ4X920TU5sE2tVzEwJpgYhHR0vFkXmZjFG-2Bt6p3IIk1vE-2Fw-2Fm2fNfa7Tdg-2BmDZQy79iNlw1HcxXGew01s-2FB9XZHipXbrCc4zm2zeivaP9-2BnWvGCVXNMsfALsi1ScAApmy0-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C6854052e1a764fee984308da01d08507%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637824292334387778%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=hlpOc0cS5Nm32C1MdPZ66t7nesm4%2F9dTD0S0DcMrbU8%3D&reserved=0
  Mucosal: https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbVwF9GF26HVDCRt-2Fvvs6f3H9l0jmOliTvYvmgNXXM2g1otBDd50yCDrWGY8YYt5pjw-3D-3DGqc1_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YId0UPdP-2Fn-2F6EitAAQdL68IrboiXQOq7Oh6-2BMH9VlIlzO7dHUXEBSHxIVc-2BFafwXi0yQLTcbJ1XFYF3TiIS-2BIyE8IsVg6ZhfkMgqyAYVkZsC9Q9Us-2FjpFaIcZKAz7n7WNq3I2nWe3gPqzFg9CLhOA-2BkFzpJ-2FZXAJCptfocpFm2A0VUhB03Hhh7W550dO24UVVM-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C6854052e1a764fee984308da01d08507%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637824292334387778%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=0hyu4NGb1ueiCJbbw5GmEdVEilMEniOdylxqxizRdbE%3D&reserved=0
  Diagnostics: https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbQne05VVe0UaW9iiRd6kqFoQK1SWXGGVBhlj2jxEY4wTrOWnrigNVKm3dwYritd9rg-3D-3DDFPx_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YId0UPdP-2Fn-2F6EitAAQdL68IElFvjKn0MUUSC6TTeihOPmbLzqv9T-2FX66ZBZyFmqGwAFG-2FZT0pglU7QDgES6pqIT0usZY81NutxJh-2FmWrCE4DsxiRShX35p47UHqmQQ0Qg2HAR9s-2BkKx-2FyaZvNWFkDAv93JQV3TeMzCZ45hcBQA6uHmn04sCP3jch0N5SWdrhj0-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7C6854052e1a764fee984308da01d08507%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637824292334387778%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=cKf%2FUAkPyjMtLDQ%2BkDKa1RUTCFir838PSD%2FVVWk3fB8%3D&reserved=0

• REC name

  South Central - Oxford A Research Ethics Committee

• REC reference

  14/SC/0004

• Date of REC Opinion

  20 Feb 2014

• REC opinion

  Further Information Favourable Opinion