Ralph, Anna

Webb, Rachel

Moreland, Nicole J

McGregor, Reuben

Bosco, Anthony

Broadhurst, David

Lassmann, Timo

Barnett, Timothy C

Benothman, Rym

Yan, Jennifer

Remenyi, Bo

Bennett, Julie

Wilson, Nigel

Mayo, Mark

Pearson, Glenn

Kollmann, Tobias

Carapetis, Jonathan R

2021-09-15

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.

Global and Tropical Health, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia anna.ralph@menzies.edu.au.

Royal Darwin Hospital, Darwin, Northern Territory, Australia.

KidzFirst Hospital, Counties Manukau District Health Board, Auckland, New Zealand.

Starship Children's Hospital, Auckland, New Zealand.

Department of Paediatrics; Child and Youth Health, University of Auckland, Auckland, New Zealand.

School of Medical Sciences and Maurice Wilkins Centre, The University of Auckland, Auckland, New Zealand.

Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia.

Centre for Integrative Metabolomics and Computational Biology, Edith Cowan University, Perth, Western Australia, Australia.

Global and Tropical Health, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.

Department of Public Health, University of Otago, Wellington, New Zealand.

Department of Infectious Diseases, Perth Children's Hospital, Perth, Western Australia, Australia.

School of Medicine, University of Western Australia, Perth, Western Australia, Australia.

BMJ Open. 2021 Sep 15;11(9):e053720. doi: 10.1136/bmjopen-2021-053720.

0000-0002-2253-5749

https://pubmed.ncbi.nlm.nih.gov/34526345/?otool=iaurydwlib

https://hdl.handle.net/10137/11881

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Searching for a technology-driven acute rheumatic fever test: the START study protocol.

Journal Article

Publication