Understanding Paratyphoid Infection

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. This study is funded by the European Vaccine Initiative and the Bill and Melinda Gates Foundation. 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.

Healthy subjects to ingest a dose of Salmonella enterica serovar Paratyphi A, strain NVGH308, after drinking a bicarbonate buffer. Intensive 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%. If this is not reached with the first cohort of 20 participants, the dose will be escalated and the process repeated. A maximum of 80 participants will be enrolled. Total follow up will be over the course of one year. 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. These insights will forward our knowledge of paratyphoid disease and may help discover or develop diagnostic methods.

This study is funded by the European Vaccine Initiative and the Bill and Melinda Gates Foundation. 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.

Healthy subjects will ingest a dose of Salmonella enterica serovar Paratyphi A, strain NVGH308, after drinking a bicarbonate buffer. Intensive 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%. If this is not reached with the first cohort of 20 participants, the dose will be escalated and the process repeated. A maximum of 80 participants will be enrolled. Total follow up will be over the course of one year. 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. These insights will forward our knowledge of paratyphoid disease and may help discover or develop diagnostic methods. 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 phase 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.

Conditions

• Enteric Fever Caused by Salmonella Enterica Serovar Paratyphi A

Interventions

BIOLOGICAL

Salmonella enterica serovar Paratyphi A (strain NVGH308)

Ingestion of 1-5x10³ to 1-5x10⁵ colony forming units (CFU) of the challenge strain after bicarbonate buffer solution.

Sponsors & Collaborators

• University of Oxford

  lead OTHER

Principal Investigators

• Andrew Pollard, MBBS · Oxford Vaccine Group

Study Design

Allocation

NA

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-03-31

Primary Completion

2016-01-31

Completion

2022-03-09

Countries

• United Kingdom

Study Locations