Group A Streptococcus, Acute Rheumatic Fever and Rheumatic Heart Disease: Epidemiology and Clinical Considerations

Curr Treat Options Cardio Med (2017) 19:15 DOI 10.1007/s11936-017-0513-y Valvular Heart Disease (J Dal-Bianco, Section Editor) Group A Streptococcus, Acute Rheumatic Fever and Rheumatic Heart Disease: Epidemiology and Clinical Considerations Liesl J. Zühlke, MB ChB DCH FCPaeds Cert Card MPH FESC PhD1,2,3,* Andrea Beaton, MD4 Mark E. Engel, BSc(MED) Hons MPH PhD3 Christopher T. Hugo-Hamman, MBChB DCH FCPaeds MA1,5 Ganesan Karthikeyan, MBBS DM MSc6 Judith M. Katzenellenbogen, BSc (Occ Ther) BSc Hons (Epidemiol) M Sc PhD7,8,9 Ntobeko Ntusi, BSc(hons) MBChB FCP(SA) DPhil10 Anna P. Ralph, BMedSci MBBS (Hons) MPH DTMH FRACP PhD11,12 Anita Saxena, MBBS MD DM FACC FCS6 Pierre R. Smeesters, MD PhD13,14,15,16 David Watkins, MD MPH MD PHD1,17 Peter Zilla, MD PhD18,19 Jonathan Carapetis, BMedSc MBBS FRACP FAFPHM FAHMS PhD7,8,20 Address 1 Department of Paediatric Cardiology, Faculty of Health Sciences, Red Cross War Memorial Childrens Hospital, University of Cape Town, Cape Town, South Africa *,2 Institute of Child Health, Red Cross War Memorial Childrens Hospital, Room 2.17 2nd floor, Klipfontein Road, Mowbray, Cape Town, 7700, South Africa Email: 3 Department of Medicine, Faculty of Health Sciences, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa 4 Children’s National Health System, 111 Michigan Avenue NW, Washington, DC, 20010, USA 5 Ministry of Health and Social Services, Windhoek, Namibia 6 Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India 7 Telethon Kids Institute, Roberts Road, Subiaco, Perth, Australia 8 University of Western Australia, Crawley, Australia 15 Page 2 of 23 Curr Treat Options Cardio Med (2017) 19:15 9 School of Population Health, University of Western Australia, Crawley, Perth, WA, Australia 10 Division of Cardiology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa 11 Global and Tropical Health, Menzies School of Health Research, Darwin, NT, Australia 12 Department of Medicine, Royal Darwin Hospital, Darwin, NT, Australia 13 Paediatric Department, Academic Children Hospital Queen Fabiola, Université Libre de Bruxelles, Brussels, Belgium 14 Molecular Bacteriology Laboratory, Université Libre de Bruxelles, Brussels, Belgium 15 Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia 16 Group A Streptococcus research group, Murdoch Children’s Research Institute, Parkville, VIC, Australia 17 Division of General Internal Medicine, University of Washington, Seattle, WA, USA 18 Christiaan Barnard Division of Cardiothoracic Surgery, Faculty of Health Sciences, University of Cape Town, 7925 Obsrvatory, Cape Town, South Africa 19 Cardiovasular Research Unit, University of Cape Town, Anzio Road, 7925, Cape Town, South Africa 20 Princess Margaret Hospital for Children, Perth, WA, Australia * The Author(s) 2017. This article is published with open access at Springerlink.com This article is part of the Topical Collection on Valvular Heart Disease Keywords Group A streptococcus I Acute rheumatic fever I Pathogenesis I Global burden of disease I Echocardiography Acronyms AR Aortic regurgitation I ARF Acute rheumatic fever I CMR Cardiovascular magnetic resonance I GAS Group A β-hemolytic Streptococcus I LMIC Low- and middle-income countries I MR Mitral regurgitation I MS Mitral stenosis I RHD Rheumatic heart disease I WHF World Heart Federation I WHO World Health Organization Opinion statement Early recognition of group A streptococcal pharyngitis and appropriate management with benzathine penicillin using local clinical prediction rules together with validated rapi-strep testing when available should be incorporated in primary health care. A directed approach to the differential diagnosis of acute rheumatic fever now includes the concept of low-risk versus medium-to-high risk populations. Initiation of secondary prophylaxis and the establishment of early medium to long-term care plans is a key aspect of the management of ARF. It is a requirement to identify high-risk individuals with RHD such as those with heart failure, pregnant women, and those with severe disease and multiple valve involvement. As penicillin is the mainstay of primary and secondary prevention, further research into penicillin supply chains, alternate preparations and modes of delivery is required. Curr Treat Options Cardio Med (2017) 19:15 Page 3 of 23 15 Introduction Acute rheumatic fever (ARF) and its sequel, rheumatic heart disease (RHD), cause significant morbidity and mortality in developing countries, yet they are underrecognized as global health problems [1]. A recent surge in the scientific exploration of ARF and RHD has resulted in alternate hypotheses regarding the pathogenesis of ARF, new global burden of disease estimates and revised diagnostic criteria. These scientific advances have been mirrored by the declaration of their commitment to end ARF/RHD on the part of international agencies, such as the World Heart Federation (WHF) [2], the World Health Organization (WHO) [3], and the African Union (AU) [4]. This review summarizes these findings and provides a clinical perspective on ARF/RHD pathogenesis, epidemiology, diagnosis, prevention, management and control. Pathophysiology Although epidemiological and immunological studies have clearly identified group A β-hemolytic streptococcus (GAS) as the etiologic agent triggering ARF in a susceptible host, the molecular pathways linking GAS to ARF are still poorly understood. Molecular mimicry and autoimmunity probably play a pivotal role in the pathogenesis of ARF and carditis [5] since it was shown that the streptococcal M protein shares an α-helical coiled structure with cardiac proteins such as myosin and that antibodies isolated from ARF patients cross-react with both M protein and heart tissue. Elevated in patients with valvular involvement, these antibodies are significantly reduced after surgical removal of inflamed valves and they correlate with poor prognosis [6]. Moreover, heart-M protein cross-reactive T cells have been isolated from the myocardium and the valves of RHD patients suggesting their involvement in the pathophysiology of the disease [7, 8]. However, the role of collagen should not be underestimated, as shown by recent studies demonstrating pathological findings in subendothelial and perivascular connective tissue in ARF [9]. It has been demonstrated that a streptococcal M protein domain called PARF (peptide associated with rheumatic fever) binds to the CB3 region of collagen type IV resulting in an antibody response to the collagen with consequent inflammation [10]. However, a recent study in New Zealand (NZ) has shown that among 74 GAS strains associated with ARF, only one GAS isolate contained the PARF motif, thus suggesting that additional and/or complementary mechanisms are likely to be involved with ARF pathogenesis [11]. At the clinical level, chronic RHD characteriz (...truncated)