Cutting Edge Issues in Rheumatic Fever

Division of Allergy, Asthma and Immunology, Thomas Jefferson University, Nemours/A.I. Dupont Children's Hospital, 1600 Rockland Road, Wilmington, DE 19803, USA.
Clinical Reviews in Allergy & Immunology (Impact Factor: 5.46). 05/2011; 42(2):213-37. DOI: 10.1007/s12016-011-8271-1
Source: PubMed


Although the incidence of acute rheumatic fever and rheumatic heart disease has decreased significantly in regions of the world where antibiotics are easily accessible, there remains a high incidence in developing nations as well as in certain regions where there is a high incidence of genetic susceptibility. These diseases are a function of poverty, low socioeconomic status, and barriers to healthcare access, and it is in the developing world that a comprehensive prevention program is most critically needed. Development of group A streptococcal vaccines has been under investigation since the 1960s and 50 years later, we still have no vaccine. Factors that contribute to this lack of success include a potential risk for developing vaccine-induced rheumatic heart disease, as well as difficulties in covering the many serological subtypes of M protein, a virulence factor found on the surface of the bacterium. Yet, development of a successful vaccine program for prevention of group A streptococcal infection still offers the best chance for eradication of rheumatic fever in the twenty-first century. Other useful approaches include continuation of primary and secondary prevention with antibiotics and implementation of health care policies that provide patients with easy access to antibiotics. Improved living conditions and better hygiene are also critical to the prevention of the spread of group A streptococcus, especially in impoverished regions of the world. The purpose of this article is to discuss current and recent developments in the diagnosis, pathogenesis, and management of rheumatic fever and rheumatic heart disease.

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    • "Rheumatic fever (RF) and its most severe sequel chronic rheumatic heart disease (RHD) are chronic inflammations occurring in genetically predisposed children and teenagers, resulting from oropharynx infection by -hemolytic Streptococcus group A. It affects the heart, joints, nervous system and skin and may progress to rheumatic heart disease, with stenosis of valve tissue and permanent heart damage (Chang, 2012). MBL and Ficolin-2 promote complement deposition on the streptococcal cell wall through binding to GlcNAc (Neth et al., 2000) and lipoteichoic acid (Lynch et al., 2004), respectively. "
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    ABSTRACT: The lectin pathway of the complement system has a pivotal role in the defense against infectious organisms. After binding of mannan-binding lectin (MBL), ficolins or collectin 11 to carbohydrates or acetylated residues on pathogen surfaces, dimers of MBL-associated serine proteases 1 and 2 (MASP-1 and MASP-2) activate a proteolytic cascade, which culminates in the formation of the membrane attack complex and pathogen lysis. Alternative splicing of the pre-mRNA encoding MASP-1 results in two other products, MASP-3 and MAp44, which regulate activation of the cascade. A similar mechanism allows the gene encoding MASP-2 to produce the truncated MAp19 protein. Polymorphisms in MASP1 and MASP2 genes are associated with protein serum levels and functional activity. Since the first report of a MASP deficiency in 2003, deficiencies in lectin pathway proteins have been associated with recurrent infections and several polymorphisms were associated with the susceptibility or protection to infectious diseases. In this review, we summarize the findings on the role of MASP polymorphisms and serum levels in bacterial, viral and protozoan infectious diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Molecular Immunology 04/2015; 67(1). DOI:10.1016/j.molimm.2015.03.245 · 2.97 Impact Factor
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    ABSTRACT: South Asia (SA) is both the most populous and the most densely populated geographical region in the world. The countries in this region are undergoing epidemiological transition and are facing the double burden of infectious and non-communicable diseases. Heart failure (HF) is a major and increasing burden all over the world. In this review, we discuss the epidemiology of HF in SA today and its impact in the health system of the countries in the region. There are no reliable estimates of incidence and prevalence of HF (heart failure) from this region. The prevalence of HF which is predominantly a disease of the elderly is likely to rise in this region due to the growing age of the population. Patients admitted with HF in the SA region are relatively younger than their western counterparts. The etiology of HF in this region is also different from the western world. Untreated congenital heart disease and rheumatic heart disease still contribute significantly to the burden of HF in this region. Due to epidemiological transition, the prevalence of hypertension, diabetes mellitus, obesity and smoking is on the rise in this region. This is likely to escalate the prevalence of HF in South Asia. We also discuss potential developments in the field of HF management likely to occur in the nations in South Asia. Finally, we discuss the interventions for prevention of HF in this region
    Current Cardiology Reviews 04/2013; 9(2). DOI:10.2174/1573403X11309020003
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    ABSTRACT: Acute rheumatic fever is an inflammatory sequelae of Group A Streptococcal pharyngitis that affects multiple organ systems. The incidence of acute rheumatic fever has been declining even before the use of antibiotics became widespread, however the disease remains a significant cause of morbidity and mortality in children, particularly in developing countries and has been estimated to affect 19 per 100,000 children worldwide. Acute rheumatic fever is a clinical diagnosis, and therefore subject to the judgment of the clinician. Because of the variable presentation, the Jones criteria were first developed in 1944 to aid clinicians in the diagnosis of acute rheumatic fever. The Jones criteria have been modified throughout the years, most recently in 1992 to aid clinicians in the diagnosis of initial attacks of acute rheumatic fever and to minimize overdiagnosis of the disease. Diagnosis of acute rheumatic fever is based on the presence of documented preceding Group A Streptococcal infection, in addition to the presence of two major manifestations or one major and two minor manifestations of the Jones Criteria. Without documentation of antecedent Group A Streptococcal infection, the diagnosis is much less likely except in a few rare scenarios. Carditis, polyarthritis and Sydenham's chorea are the most common major manifestations of acute rheumatic fever. However, despite the predominance of these major manifestations of acute rheumatic fever, there can be significant overlap with other disorders such as Lyme disease, serum sickness, drug reactions, and post-Streptococcal reactive arthritis. This overlap between disease processes has led to continued investigation of the pathophysiology as well as development of new biomarkers and laboratory studies to aid in the diagnosis of acute rheumatic fever and distinction from other disease processes.
    Autoimmunity reviews 01/2014; 13(4-5). DOI:10.1016/j.autrev.2014.01.036 · 7.93 Impact Factor
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