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ISRA MEDICAL JOURNAL Volume 3 Issue 3 Dec 2011
Humaira Zafar, Kiran Tauseef Bukhari
Rheumatic fever (RF) and Rheumatic Heart Disease (RHD) continues to be a global health problem since
long. Moreover, it is a leading cause of morbidity and mortality especially in younger age group i.e. 3–18
RF is a non suppurative complication of Group A Streptococcus Pyogenes (GASP) pharyngeal infection
observed in post streptococcus sequelae. The reason for this is the negligence of diagnosis and improper
treatment. While if diagnosed early and treated well within 10 days of onset of pharyngitis, occurrence of this
life threatening condition can be prevented.
Apart from many virulent factors produced by GASP, the most important ones for the pathogenesis are the M
proteins i.e. antigens and the Streptolysin O. Only M proteins of GASP have the strong rheumatogenic
potential while the rises in Streptolysin O titer levels are suggestive of recent GASP pharyngeal infection.
The significant level of ASO titer is >200.
The current review article will provide update information regarding early diagnosis of GASP pharyngeal
infection by ASO titers in different ages. Thus, by initiating early treatment, the morbidity and mortality rates
due to RF and RHD can be reduced in under developed countries like ours.
KEY WORDS: Group A Streptococcus Pyogenes, Rheumatic fever, Rheumatic Heart Disease, ASO Titer
include tonsillopharyngeal abscesses, cellulitis, otitis media, sinusitis, necrotizing fasciitis, streptococcus Rheumatic fever continues to be a global health bacteremia, meningitis and brain abscesses. While problem since long and it remains a major cause of the non suppurative ones includes acute rheumatic morbidity and mortality both in developed and in fever, acute glomrulonephritis and Streptococcal under developed countries. It is usually observed as a complication following Group A Beta Hemolytic The pathogenic factors include the presence of protein antigens i.e. M antigens or protein and T Streptococcus pyogenes was first discovered by antigens or protein. M protein is a macromolecule Billroth, in 1874 amongst the patients with wound having hyper variable terminal regions, a conserved infection. In 1883 Fehleisen isolated chain forming, C terminal region and A, B and C repeat regions on organism in a pure culture from peri erysipelas lesion. the basis of peptide sequence periodicity. The M Rosebach, named the organism Streptococcus protein are the helical coiled structures and appears pyogenes, in 1884. In 1903 J H Brown and Schott like hair projection on the cell wall. The M type Mueller, studied and described different patterns of specific strain of group A beta hemolytic streptococci hemolysis as alpha, beta and gamma hemolysis. A streptococcus pyogenes are believed to cause later development was the Lancefield Classification, streptococcus pharyngitis which if untreated can lead of beta hemolytic Streptococcus by serotyping on the to the development of Rheumatic Fever in it's post streptococcal sequelae. M protein is the major
The epidemiological studies in 1900's help establish virulent factor that can resist phagocytosis, traverses a relationship of Group A Streptococcal Pyogenes i.e. and penetrates bacterial cell wall, multiply rapidly in GASP infection with acute rheumatic fever and acute human tissues and ultimately initiates disease. These M proteins are also believed to have GASP leads to two types of diseases i.e. suppurative rheumatogenic potential and hence also called the and the non-suppurative. The suppurative ones Rheumatogenic Proteins.
Apart from these antigenic protein production, GASP
Correspondence to:
also produces many important hemolytic toxins, out Dr. Humaira Zafar
of which the most important ones are the streptolysin O and S. They function to cause damage to many cells including polymorphonuclear leucocytes, Isra University, Islamabad Campus, Pakistan platelets and tissue culture cells. The rise in Anti Streptolysin O titers are suggestive of recent GAS GABHS, M types were the most common pathogenic In patients with acute pharyngitis bacterial detection strains and most common age group of 3-18 years. is limited to a search of group A beta hemolytic In Brazil 20,000 new cases are diagnosed per year Streptococcus pyogenes (GABHSP) because it is the which has decreased in last 5 years to 500 cases per only bacteria which can lead to the development of year with the mean age group of 5-18 years. In complications like Rheumatic Fever (RF) and Acute Hawaii, 69 patients out of total 85 were positive for Glomerulonephritis (AGN). Thus leading to increase specific M types of GABHS. In Grenada, morbidity morbidity and mortality rates, while if treated well and caused by RF and RHD has been quite extensive early with antimicrobials like penicillin macrolides, fluoroquinolones, tetracycline, doxycyclines etc. can RF if untreated can develop recurrence and thus The infecting streptococci must be eradicated from leads to new valve damage made evident by the pharynx as it is the only specific type which can echocardiography for the patients with pure 14, 15, 16
cause RF in its post streptococcal sequelae.
Syndeham's Chorea, (especially in patients having subclinical valvulitis). So longer duration of LITERATURE REVIEW
secondary prophylaxis is recommended in RF RF usually occurs in 3-4% of untreated children Early diagnosis of infection by taking throat swabs for especially in first 10 days of onset of pharyngitis. culture and ASO titer estimation will be helpful for Rheumatic Heart Diease usually develops 4-8 weeks isolating bacteria. While early treatment with after GASP pharyngitis in 30-45% of individuals with p e n i c i l l i n , m a c r o l i d e s , f l u o r o q u i n o l o n e s , untreated Rheumatic fever. Jones Criteria tetracyclines, doxycycline etc can prevent describes the specific features of RF. It includes the major and the minor criteria. Major criteria includes; carditis, polyarthitis, syndeham's chorea, CONCLUSION
subcutaneous nodules, erythema marginatum and prolong PR interval while minor criteria includes Rheumatic Fever is a non suppurative complication raised ESR, leucocytosis > 15000, increased ASO of Group A Streptococcus Pyogenes pharyngeal titer, anaemia, epistaxis and abdominal pain. For infection observed in post streptococcus sequelae. diagnosis of RF two major or one major and two The early/accurate diagnosis of GASP pharyngeal minor manifestations of Jones criteria plus the infection by ASO titers and provision of specific evidence of preceeding GASP pharyngeal infection m a n a g e m e n t w i t h p e n i c i l l i n , m a c r o l i d e s , must be there to diagnose RF . Most important fluoroquinolones, tetracyclines, doxycycline etc can clinical features of GAS pharyngeal infection includes prevent the occurrence of Rheumatic fever. Thus, (a) >101°F fever, (b) Tonsillar exudates, (c) lack of
reducing the morbidity and mortality rates in under cough, (d) Anterior cervical lymphadenopathy, (e) at developed countries like the one of ours.
least 10 days history of sore throat, (f) Raised ASO titers (g) positive throat cultures .
The pathogenesis of RF is still not completely defined. New measures should be adopted for its affected age groups are between 3-18 years, and in WHO, Geneva, 1988, Technical Report Series addition unhygienic conditions, low socio economic conditions, seasonal variation i.e. common in winter and spring, (children with) underlying medical [ illnesses, environmental factors and recurrent sore esources/trs923/en/] Retrieved on 18 October throat, all contributes in predisposition Depending upon these all factors, this preventable Sharma S. Strep. Group A Infection. Med. Scap disease is still highly prevalent in Pakistan J o u r n a l . 2 0 0 6 ; 5 . We b s i t e : [ w w w. e - Irrefutable studies by Wannamaker in early 1950's showed that early diagnosis and treatment i.e. primary prophylaxis can prevent occurrence of Rf . Carapetis JR. Epidemiology and prevention of The national surveillance data of the year 2003 and Group A Streptococcus infection: acute resp. 2004 in France showed only two positive cases out of tract infection, skin infection and their squeal at 100,000 inhabitants. While National surveillance of the close of twentieth century. Clin Infect Dis. North America showed 45% children positive for ISRA MEDICAL JOURNAL Volume 3 Issue 3 Dec 2011
esources/trs923/en/] Retrieved on 18 October infection. Clin Microbiol Rev. 2000; 13: 470- Nunthapisud P, Sirilertapanrana S, Tatiyakavee SK, Chumderpedelsuk S. The colonization rate microbiology and molecular pathogenesis. of Group A Streptococcus in throat of low New York, Oxford University Press. 2000: 102- socioeconomic. School going children in G. Proft T. Identification and Characterization of Infection. Zbl Bakt. 1992; 22: 50-51.
Pyogenes. J Exp Med. 1999; 189: 89-101.
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Steer AC, Danchin MH, Carapetis JR. Group A Determination of the relationship between Streptococcal infection in Children. J Pediatr Group A Streptococcal genome content, M type Child Health. 2007; 43 (4): 2003-2213.
and Toxic Shock Syndrome by a mixed genome microarray. Infect Immune. 2007; 75: 2603- Prophylaxis of Acute RF by treatment of the Narula J. Rheumatic fever. Am Regist Pathol. amounts of penicillin. Am J Med. 1951; 10: Bisno Al. Acute Pharyngitis: etiology and Mihaila L, Loufinoun J, Chirouze C, Galtch N. diagnosis. Paediatr. 1996, 97(6): 949- 954.
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Shulman ST, Robert T, Kobat W. Four year Gerber MA, Stabd FT. Rapid diagnosis of GAS Group A Streptococcus pharyngitis serotype Infection. Clin Microbiol Rev. 2004; 17 (3): 571- surveillance in North America. 2003–2004. Bassetti M, Manno G, Collida A, Ferrado A, Barros R, Alencar F, Higa F. Identification of Gatti G, Ugolotti e, et al. Erythromycin GABHS strains in Brazil. Lancet. 2005 114.
Resistance In Streptococcus Pyogenes In Italy. Joint WHO/ISFC meeting on RF/RHD control with emphasis on Primary Prevention, Geneva, Windward Islands Research and Educational Foundation (WINDREF). Research Institute, WebSite:[ A n n u a l R e p o r t 2 0 0 3 ( R F & R H D ) . g/cienteng/sweng/swc6003i/inordet1/inordet1.
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Respiratory Tract Carrier State An Engina. J Panamonta M, Chaikitpinyo A, Aurichayapal N, Weraarchakul. Evolution of valve damage in S. Barros SF, Alencsar R, Higa F, Alcantaser F. Syndeham's chorea during recurrence of acute Identification of group A beta hemolytic RF. Int J Cardiol. 2007; 119(1): 73-79.
streptococcus strains in Brazil. Lancet. 2005; Group A Streptococcal Infection 2007/2008, Seasonal update. Health Protection Report. Jones TD. Diagnosis of Rheumatic Fever. J Am Green, N. M., Beres, .B., Graviss, E.A., Allison, J.E., Mc Geer A. J, Musser J. M. Group A Prevention of RF/RHD. Report of a consultation Streptococcus Strain causinf invasive infection to review progress and develop future activities and pharyngitis. J Clin Microbiol.2005; 43: G e n e v a , W H O , 2 0 0 0 . W e b S i t e : [


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Russian Chemical Reviews 71 (1) 71 ± 83 (2002) # 2002 Russian Academy of Sciences and Turpion LtdPeptide nucleic acids: structure, properties, applications, strategiesIII. Applications of peptide nucleic acidsIV. Basic principles of chemical synthesis of peptide nucleic acidsV. Factors determining the efficiency of condensation in the synthesis of peptide nucleic acidsVI. The main strategi

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