# Acute Rheumatic Fever Diagnostic Network (ARC Network) clinical recruitment protocol

**Authors:** Ndate Fall, Asha Clare Bowen, Samantha Buonfiglio, Joshua Reginald Francis, Christopher Gorman, Renata Fonseca Mendoza, Ela Fernandes, Nicole J Moreland, Maria Carmo Pereira Nunes, Craig Sable, Masood Sadiq, Casey P Shannon, Tom Parks, Anna Ralph, Amy Sanyahumbi, Rachel Sarnacki, Scott Tebbutt, Rachel Webb, Jonathan Carapetis, Andrea Zawacki Beaton

PMC · DOI: 10.1136/bmjopen-2025-114968 · BMJ Open · 2026-03-25

## TL;DR

This paper outlines a global study to develop a diagnostic test for acute rheumatic fever by collecting data and biospecimens from children and adolescents.

## Contribution

The study introduces a standardized, multicenter recruitment protocol for ARF biomarker discovery in low- and middle-income countries.

## Key findings

- The ARC Network uses standardized procedures to recruit children aged 3–18 with suspected ARF and controls across four countries.
- Biospecimens and data collected will support future biomarker discovery for diagnosing acute rheumatic fever.
- Centralized training and quality control ensure high-quality, globally representative data collection.

## Abstract

Rheumatic heart disease, a major cause of morbidity and mortality in low- and middle-income countries, results from acute rheumatic fever (ARF), for which no diagnostic test currently exists. The ARF Diagnosis Collaborative Network (ARC Network) was established to address this gap by recruiting a rigorously phenotyped, globally representative cohort of children and adolescents with ARF and controls to support biomarker discovery. This paper describes the ARC Network’s multicentre recruitment strategy and standardised procedures for classifying ARF cases and controls, enabling robust development of novel, accessible diagnostics.

The ARC Network recruits children and adolescents aged 3–18 years with suspected ARF and matched controls across four countries. Clinical, laboratory and echocardiographic data are collected using standardised protocols. Echocardiographic and clinical core teams provide rigorous standardised case review. Biospecimens are processed locally following harmonised procedures and shipped to a central biobank for long-term storage and future biomarker studies. Centralised training, quality control and a research database ensure high-quality, globally representative data to support ARF biomarker discovery.

The ARC Network follows Institutional Review Board protocols with local ethical approval and informed consent, and oversees clinical data and biobank use for ARF research.

## Linked entities

- **Diseases:** acute rheumatic fever (MONDO:0017767), rheumatic heart disease (MONDO:0006955)

## Full-text entities

- **Genes:** CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, ARC (activity regulated cytoskeleton associated protein) [NCBI Gene 23237] {aka Arg3.1, hArc}, GAST (gastrin) [NCBI Gene 2520] {aka GAS}
- **Diseases:** GAS infections (MESH:D007239), autoimmune complication (MESH:D020274), cardiac symptoms (MESH:D006331), rash (MESH:D005076), carditis (MESH:D009205), cardiovascular condition (MESH:D002318), RHD (MESH:D012214), cardiomyopathy (MESH:D009202), chorea (MESH:D002819), joint pain (MESH:D018771), pericardial effusion (MESH:D010490), movement disorder (MESH:D009069), acute post-streptococcal glomerulonephritis (MESH:D013313), fever (MESH:D005334), pharyngitis (MESH:D010612), infectious (MESH:D003141), ARF (MESH:D012213), inflammation (MESH:D007249), congenital heart disease (MESH:D006330), valvular lesions (MESH:D006349)
- **Chemicals:** ethylenediaminetetraacetic acid (MESH:D004492)
- **Species:** Streptococcus pyogenes (species) [taxon 1314], Homo sapiens (human, species) [taxon 9606], Streptococcus sp. 'group A' (species) [taxon 36470]
- **Mutations:** 39INSP

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13034315/full.md

## References

23 references — full list in the complete paper: https://tomesphere.com/paper/PMC13034315/full.md

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Source: https://tomesphere.com/paper/PMC13034315