Dataset Information

Rheumatic Fever in Large Cohort of Adolescents in Israel.

ABSTRACT: Background: Acute rheumatic fever (ARF) remains a major worldwide healthcare problem, despite its progressive decline in developed countries. The aims of our study were to estimate the prevalence of ARF among adolescents in Israel and to investigate risk factors. Methods: The study population consisted of 113,671 consecutive conscripts 16-19 years old, born during 1971-1993, who completed the medical profiling as part of the recruitment process to the IDF. ARF was diagnosed according to Jones criteria at time of illness, with confirmation relying on medical documentation and cardiologist evaluation including echocardiography. Results: The general prevalence rate of ARF was 0.12%. A downward trend was observed, from 0.19% among those born during 1971-1980 to 0.07% among those born during 1981-1993. Differences in prevalence of ARF were noted in sub-populations based on country of birth and origin-Israel, Ethiopia and the former soviet union (FUSSR). The prevalence rates of valvar disease among ARF+ and ARF- recruits were 15.7% and 0.95%, respectively. In multivariable logistic regression analyses, 4 variables were negatively associated with ARF: later birth year group, female gender, rural residence, youngest child; and 3 were positively associated with ARF: young parents, above normal BMI and valvar disease. Conclusion: Our study provides support for the documented decline in ARF prevalence and describes socio-demographic and anthropometric risk factors including the association with valvar disease and novel risk factors including above normal BMI and young parents, both warranting further investigation which might help in developing societal level prevention strategies.

SUBMITTER: Machluf Y

PROVIDER: S-EPMC6992586 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Rheumatic Fever in Large Cohort of Adolescents in Israel.

Machluf Yossy Y Chaiter Yoram Y Farkash Rivka R Sebbag Anat A Fink Daniel Lyon DL

Frontiers in medicine 20200124

<b>Background:</b> Acute rheumatic fever (ARF) remains a major worldwide healthcare problem, despite its progressive decline in developed countries. The aims of our study were to estimate the prevalence of ARF among adolescents in Israel and to investigate risk factors. <b>Methods:</b> The study population consisted of 113,671 consecutive conscripts 16-19 years old, born during 1971-1993, who completed the medical profiling as part of the recruitment process to the IDF. ARF was diagnosed accordi ...[more]

PMID: 32039216

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Project description:BackgroundAcute rheumatic fever (ARF) is a serious sequela of Group A Streptococcus (GAS) infection associated with significant global mortality. Pathogenesis remains poorly understood, with the current prevailing hypothesis based on molecular mimicry and the notion that antibodies generated in response to GAS infection cross-react with cardiac proteins such as myosin. Contemporary investigations of the broader autoantibody response in ARF are needed to both inform pathogenesis models and identify new biomarkers for the disease.MethodsThis study has utilised a multi-platform approach to profile circulating autoantibodies in ARF. Sera from patients with ARF, matched healthy controls and patients with uncomplicated GAS pharyngitis were initially analysed for autoreactivity using high content protein arrays (Protoarray, 9000 autoantigens), and further explored using a second protein array platform (HuProt Array, 16,000 autoantigens) and 2-D gel electrophoresis of heart tissue combined with mass spectrometry. Selected autoantigens were orthogonally validated using conventional immunoassays with sera from an ARF case-control study (n=79 cases and n=89 matched healthy controls) and a related study of GAS pharyngitis (n=39) conducted in New Zealand.ResultsGlobal analysis of the protein array data showed an increase in total autoantigen reactivity in ARF patients compared with controls, as well as marked heterogeneity in the autoantibody profiles between ARF patients. Autoantigens previously implicated in ARF pathogenesis, such as myosin and collagens were detected, as were novel candidates. Disease pathway analysis revealed several autoantigens within pathways linked to arthritic and myocardial disease. Orthogonal validation of three novel autoantigens (PTPN2, DMD and ANXA6) showed significant elevation of serum antibodies in ARF (p < 0.05), and further highlighted heterogeneity with patients reactive to different combinations of the three antigens.ConclusionsThe broad yet heterogenous elevation of autoantibodies observed suggests epitope spreading, and an expansion of the autoantibody repertoire, likely plays a key role in ARF pathogenesis and disease progression. Multiple autoantigens may be needed as diagnostic biomarkers to capture this heterogeneity.

Dataset Information

Rheumatic Fever in Large Cohort of Adolescents in Israel.

Publications

Rheumatic Fever in Large Cohort of Adolescents in Israel.

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