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ISRA MEDICAL JOURNAL
Volume 3 Issue 3 Dec 2011
STRATEGIES FOR THE PREVENTION OF RHEUMATIC FEVER
AND ITS COMPLICATIONS
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
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
Apart from these antigenic protein production, GASP
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,
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
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conditions, seasonal variation i.e. common in winter
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Depending upon these all factors, this preventable
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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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