ISRA MEDICAL JOURNAL Volume 3 Issue 3 Dec 2011 REVIEW ARTICLE STRATEGIES FOR THE PREVENTION OF RHEUMATIC FEVER AND ITS COMPLICATIONS Humaira Zafar, Kiran Tauseef Bukhari ABSTRACT
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 years. 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 INTRODUCTION
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
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,
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 . REFERENCES
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.
consideration for children with invasive group A
Shulman ST. Streptococcal infection, clinical
Streptococcal infection. J Clin Pediatr. 2007;
pathogenesis. New York, Oxford University
Martin JM, Green M, Barbadora KA, Wald ER.
Group A Streptococcus infection among school
age children. Clinical Characterization and
Group A Streptococcal Infection in Ontario,
their carrier state. Paediatr. 2004; 114 (5):
Canada. New Eng J Med. 1996; 335: 547-554.
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.
Infection due to Streptococcus pyogenes in
Cheesbrough M. Microbiological Test. ASO
France in 2003–2004. Lancefield 2005; 82.
Antibody Titer Test. Volume II; Page161.
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,
A n n u a l R e p o r t 2 0 0 3 ( R F & R H D ) .
2003.pdf] Retrieved on 18 October 2011.
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 :
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
Official Company Communication: Pharmanex Product Testing Statement Pharmanex knows that dietary supplements play an important role in helping many athletes achieve peak performance. However, readily available supplements all too frequently contain substances, which not only are prohibited in competitive sports, but are also detrimental to health. Athletes who use supplements may in