Clinical Trial: Scrub Typhus Pediatric Immunology Study

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: The Natural Immune Response In Pediatric Scrub Typhus In Chiangrai

Brief Summary: This is an observational study of the natural immune response to scrub typhus in patients recruited from Chiangrai Prachanukroh Hospital, N-Thailand. Febrile patients with a positive IgM rapid diagnostic test will be asked if they wish to take part in a study to improve the understanding of how the body responds to scrub typhus. Blood samples will be collected from each participant ("STP", n=60) at baseline (the day of presentation to hospital), 2 weeks later in hospital, 12 weeks after baseline at the clinic visit and 1 year later. Data on clinical presentation and relapses will be recorded. Control subjects are scrub typhus exposed patients from a rural village in the caption area of Prachanukroh Hospital ("STE", n=80; approx. 40 children and 40 adults), and healthy adults blood donors from Bangkok ("STH" n=30) - these subjects will be enrolled for one single blood sample. The study team will also collect eschar swab specimens from STP group and a non-invasive specimen of the dark crust on the day of enrollment.

Detailed Summary:

Primary Objective:

o To measure and characterize the memory and effector T-cell responses, as well as the humoral response in young patients with acute scrub typhus and to compare theseThese acute responses will be compared to responses in the convalescent phase of the same individuals at 2, 12 and 52 weeks later, as well as to scrub typhus-exposed controls and to healthy controls.

Secondary Objectives:

  • To establish ELISpot and flow cytometer based immunology assays using human samples collected in rural areas of high scrub typhus endemicity.
  • To set up a prospective cohort study of paediatric scrub typhus in a region of high endemicity

Description of the Study Sites and Population Chiangrai Prachanukroh Hospital in Chiangrai province, N-Thailand is ideally suited for this study. We have a well-established collaboration, due to a previously completed multi-year fever study and an excellent relationship with local senior doctors, staff and the hospital-based laboratory. There is a very high rate of scrub typhus cases admitted to the infectious diseases ward and the recent establishment of a MORU (Mahidol Oxford Tropical Medicine Research Unit) satellite laboratory within the hospital facilities, make this study site unique and highly suited for performing this research project. This study will contribute significantly towards the long-term aim of developing the Chiangrai study site towards an immunogenicity monitoring field site for vaccine trials.

The 'scrub typhus' patients (STP) are febrile children recruited from the ID and/or pediatric wards at Prachanukroh hospital during an acute hospitalization du
Sponsor: University of Oxford

Current Primary Outcome: Cellular immune response to Orientia tsutsugamushi [ Time Frame: 2 years ]

Characterize the cellular immune response to Orientia tsutsugamushi, based on immune cell phenotyping and quantitation of effector, memory & regulatory T cell functions.


Original Primary Outcome: Immune response [ Time Frame: 2 years ]

Current Secondary Outcome:

  • T-cell subsets during the scrub typhus infection [ Time Frame: 2 years ]
    Identification of T-cell subsets affected by apoptosis during the course of acute scrub typhus.
  • Antibody isotypes during the scrub typhus infection [ Time Frame: 2 years ]
    Determination of the antibody isotypes and their dynamics involved in natural scrub typhus infection.
  • Adaptive immune response to Orientia tsutsugamushi [ Time Frame: 2 years ]
    Characterisation of the adaptive immune response to Orientia tsutsugamushi, measured by ex vivo interferon-gamma ELISPOT in spot forming cells per million peripheral blood mononuclear cells (SFC/106PBMC), using four Orientia antigens (whole cell antigen, 56kDa, 47kDa and scaC) in samples of acute disease and long term follow up.


Original Secondary Outcome:

  • T-cell subsets during the scrub typhus infection [ Time Frame: 2 years ]
  • Antibody isotypes during the scrub typhus infection [ Time Frame: 2 years ]
  • Adaptive immune response to Orientia tsutsugamushi [ Time Frame: 2 years ]


Information By: University of Oxford

Dates:
Date Received: February 27, 2015
Date Started: July 2015
Date Completion: July 2017
Last Updated: August 31, 2016
Last Verified: August 2016