TY - JOUR
T1 - Searching for a technology-driven acute rheumatic fever test
T2 - The START study protocol
AU - Ralph, Anna P.
AU - Webb, Rachel
AU - Moreland, Nicole J.
AU - McGregor, Reuben
AU - Bosco, Anthony
AU - Broadhurst, David
AU - Lassmann, Timo
AU - Barnett, Timothy C.
AU - Benothman, Rym
AU - Yan, Jennifer
AU - Remenyi, Bo
AU - Bennett, Julie
AU - Wilson, Nigel
AU - Mayo, Mark
AU - Pearson, Glenn
AU - Kollmann, Tobias
AU - Carapetis, Jonathan R.
N1 - Funding Information:
Funding The study is funded by the Australian National Health and Medical Research Council (NHMRC) grant #1147531. AR is supported by NHMRC fellowship #1142011. TCB is supported by the Western Australia Department of Health and a Career Development Fellowship from Improving Health Outcomes in the Tropical North (NHMRC #1131932).
PY - 2021/9/15
Y1 - 2021/9/15
N2 - 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 Mā ori and Pacific Peoples. Indigenous investigators and governance groups will provide oversight of study processes and advise on cultural matters.
AB - 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 Mā ori and Pacific Peoples. Indigenous investigators and governance groups will provide oversight of study processes and advise on cultural matters.
KW - diagnostic microbiology
KW - immunology
KW - paediatric rheumatology
KW - valvular heart disease
UR - http://www.scopus.com/inward/record.url?scp=85115261133&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2021-053720
DO - 10.1136/bmjopen-2021-053720
M3 - Article
C2 - 34526345
AN - SCOPUS:85115261133
SN - 2044-6055
VL - 11
JO - BMJ Open
JF - BMJ Open
IS - 9
M1 - e053720
ER -
