Searching for a technology-driven acute rheumatic fever test: the START study protocol
David Broadhurst,
Bo Remenyi,
Timothy C Barnett,
Jonathan R Carapetis,
Jennifer Yan,
Anna P Ralph,
Glenn Pearson,
Mark Mayo,
Rachel Webb,
Nicole J Moreland,
Reuben McGregor,
Anthony Bosco,
Timo Lassmann,
Rym Benothman,
Julie Bennett,
Nigel Wilson,
Tobias Kollmann
Affiliations
David Broadhurst
Centre for Integrative Metabolomics and Computational Biology, Edith Cowan University, Perth, Western Australia, Australia
Bo Remenyi
Global and Tropical Health, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia
Timothy C Barnett
Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia
Jonathan R Carapetis
Department of Infectious Diseases, Perth Children`s Hospital, Nedlands, Western Australia, Australia
Jennifer Yan
3 Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia
Anna P Ralph
Global and Tropical Health, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia
Glenn Pearson
Indigenous Health, The Kids Research Institute Australia, Perth, WA, Australia
Mark Mayo
Global and Tropical Health, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia
Rachel Webb
Starship Children’s Hospital, Auckland, New Zealand
Nicole J Moreland
Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand
Reuben McGregor
School of Medical Sciences and Maurice Wilkins Centre, The University of Auckland, Auckland, New Zealand
Anthony Bosco
Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia
Timo Lassmann
Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia
Rym Benothman
Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia
Julie Bennett
Department of Public Health, University of Otago Wellington, Wellington, New Zealand
Nigel Wilson
Green Lane Paediatric and Congenital Cardiac Services, Starship Children`s Health, Te Whatu Ora – Health New Zealand, Te Toka Tumai Auckland, Auckland, New Zealand
Tobias Kollmann
Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia
Introduction The absence of a diagnostic test for acute rheumatic fever (ARF) is a major impediment in managing this serious childhood condition. ARF is an autoimmune condition triggered by infection with group A Streptococcus. It is the precursor to rheumatic heart disease (RHD), a leading cause of health inequity and premature mortality for Indigenous peoples of Australia, New Zealand and internationally.Methods and analysis ‘Searching for a Technology-Driven Acute Rheumatic Fever Test’ (START) is a biomarker discovery study that aims to detect and test a biomarker signature that distinguishes ARF cases from non-ARF, and use systems biology and serology to better understand ARF pathogenesis. Eligible participants with ARF diagnosed by an expert clinical panel according to the 2015 Revised Jones Criteria, aged 5–30 years, will be recruited from three hospitals in Australia and New Zealand. Age, sex and ethnicity-matched individuals who are healthy or have non-ARF acute diagnoses or RHD, will be recruited as controls. In the discovery cohort, blood samples collected at baseline, and during convalescence in a subset, will be interrogated by comprehensive profiling to generate possible diagnostic biomarker signatures. A biomarker validation cohort will subsequently be used to test promising combinations of biomarkers. By defining the first biomarker signatures able to discriminate between ARF and other clinical conditions, the START study has the potential to transform the approach to ARF diagnosis and RHD prevention.Ethics and dissemination The study has approval from the Northern Territory Department of Health and Menzies School of Health Research ethics committee and the New Zealand Health and Disability Ethics Committee. It will be conducted according to ethical standards for research involving Indigenous Australians and New Zealand Māori and Pacific Peoples. Indigenous investigators and governance groups will provide oversight of study processes and advise on cultural matters.
