Understanding Paratyphoid Infection
Condition: Enteric Fever Caused by Salmonella Enterica Serovar Paratyphi A
MeSH terms: Typhoid Fever
Study type: Interventional

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.
    


Intervention name(s): Salmonella enterica serovar Paratyphi A (strain NVGH308)
Intervention type(s): Biological
Intervention description(s): Ingestion of 1-5x10³ to 1-5x10⁵ colony forming units (CFU) of the challenge strain after bicarbonate buffer solution.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Enteric fever; Paratyphoid; Salmonella Paratyphi; Challenge study; Human model of infection