Incidence, Clinical Manifestations and Risk Factors of Acute Rheumatic Fever: A Systematic Review and Meta-Analysis of the Global Perspective

Abstract

Acute Rheumatic Fever (ARF) is a system-wide disease in which chronic, wide spread inflammatory changes occur in response to a group A streptococcal (GAS) infection that most often affects children and adolescents and those from developing countries. The aim of this study is to calculate the global incidence of ARF and identify the frequencies of major and clinical manifestations and risk factors globally to provide a better indication of the burden of disease and additional information on the dispersion of manifestations and risk factors. A meta-analysis was conducted by pooling cross-sectional and cohort studies, and Morbidity and Mortality Weekly Reports (MMWRs) that were English, full-text, peer-reviewed articles published after 1990 that included ARF cases of any race or nationality that were aged 0 to 19 years at the time of evaluation. Measures of interest included incidence rates and frequencies of clinical and major manifestation of ARF. In total, 27 studies met all inclusion criteria; twelve (44.4%) were crosssectional and another 12 (44.4%) were cohort studies. A linear mixed effects model was used to calculate a pooled risk ratio; however, heterogeneity was found to be significantly high across all articles. When exploring heterogeneity of the effect by study region and age, those from the Americas (β = -4.880, p <0.001) and Africa (β = -2.919, p = 0.021), and those that included children under the age of 5 (β = -2.103, p = 0.006) had incidence estimates that were significantly lower compared to their respective stratifications, indicating that characteristics of these populations may be introducing bias. Clinical and major manifestations were unable to be explored due to the way that these variables were presented. Although substantial heterogeneity existed between studies, the results provide evidence of where gaps exist regarding ARF research on a global scale. Properly describing the characteristics of this disease is the first step towards creating adequate criteria and guidelines that will lead to better health outcomes for those suffering from ARF, reduce the economic burden of this disease, and improve the quality of life of these individuals.