Acta Clinica Belgica

International Journal of Clinical and Laboratory Medicine

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THE CLINICAL-DIAGNOSTIC ROLE OF

ANTISTREPTOLYSIN O ANTIBODIES

I Geerts, N De Vos, J Frans & A Mewis

To cite this article: I Geerts, N De Vos, J Frans & A Mewis (2011) THE CLINICAL-DIAGNOSTIC
ROLE OF ANTISTREPTOLYSIN O ANTIBODIES, Acta Clinica Belgica, 66:6, 410-415

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 410 THE CLINICALDIAGNOSTIC ROLE OF ANTISTREPTOLYSIN O ANTIBODIES
Original Article
THE CLINICALDIAGNOSTIC ROLE OF
ANTISTREPTOLYSIN O ANTIBODIES
Geerts I1*, De Vos N2*, Frans J1, Mewis A3
1
Laboratory Medicine, Imelda Hospital, Bonheiden, Belgium, 2Laboratory Medicine, Heilig Hart
Hospital, Mol, Belgium and 3Laboratory Medicine, Jessa Hospital, Campus Virga Jesse, Hasselt, Belgium
*
Both authors equally contributed to this work
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Correspondence and offprint requests to: Inge Geerts, E-mail: inge.geerts@imelda.be
ABSTRACT
The antistreptolysin O antibody (ASLO) test is often
requested in a clinical setting with limited evidence for its
usefulness. For this reason, the diagnostic scenario in
which ASLO plays an evidence-based role and the analyti-
cal performance of the test are critically appraised, taking
into account the clinical need and the direct medical cost.
Little or no scientific evidence was found for the use of
ASLO in patients with pharyngitis, post-streptococcal glo-
merulonephritis and in adults with rheumatoid arthritis.
The clinical relevance of ASLO is restricted to paediatrics,
where it contributes to fulfil the diagnosis of acute rheu-
matic fever (ARF) as per Jones criteria. The standardization
of current automated ASLO-latex assays is limited. Atten-
tion should be paid to inaccurate reference values and
many circumstances causing false positive and false nega-
tive results. Because of a low prevalence of ARF in the
Western world, a high negative predictive value is obtained
for the ASLO test (> 99%). In clinical practice, the result of
the test is not urgent. To reduce overconsumption, the
clinical laboratory should drive the request behaviour of
physicians by a strategic lay-out of the application form.
The health insurance/government also contributed by
introducing a diagnostic rule for reimbursement.
Key words: antistreptolysin O, Group A Streptococcus, Strepto-
coccus pyogenes, acute rheumatic fever, ASLO
INTRODUCTION
Antistreptolysin O is an exotoxin of Group A Streptococ-
cus (GAS) or Streptococcus pyogenes. After an infection with
Acta Clinica Belgica, 2011; 66-6
95083_ACB6_02-(OA 2902 R1).indd 410
beta-haemolytic Streptococci, the host produces antistrep-
tolysin O antibodies (ASLO). This immunologic reaction may
trigger rare but serious non-suppurative complications, like
acute rheumatic fever (ARF) [and its chronic sequel rheumatic
heart disease (RHD)] and acute post-streptococcal glomeru-
lonephritis (AGN). ASLO is the leading serological marker to
indicate an antecedent beta-haemolytic Streptococcus infec-
tion. This review will answer the question in which clinical-
diagnostic scenario the ASLO test is evidence-based. We
examine the clinical relevance of ASLO in the Western world.
Furthermore, we check the financial impact of the ASLO test
and we discuss some suggestions to attain a more selective
request behaviour. The decision-making strategy is built in
parallel with Price’s items for evidence-based laboratory med-
icine (1).
LITERATURE SEARCH STRATEGY
Guidelines, reviews, clinical trials, original articles and ref-
erence works were identified through a search in the data-
bases of PubMed MEDLINE (1966-2009), EMBASE (1966-2009),
Cochrane Library (Issue 3, 2009), SUMSearch (Last update of
interface: 04-17-2008), the National Institute for Health and
Clinical Excellence (NICE NHS Evidence, 2009) and UpToDate
version 17.1 (1992-2009). The following Medical Subject
Headings (MeSH) or EMTREE terms were used: “Antistreptoly-
sin”, “Antistreptolysin” AND “Sensitivity and Specificity”, “Antist-
reptolysin” AND “Reference Values”, “Rheumatic Fever”, “Rheu-
matic Fever” AND “Antistreptolysin”, “Rheumatic Fever” AND
“Rheumatic Heart Disease” AND “Jones criteria”, “Glomerulo-
nephritis”, “Glomerulonephritis” AND “Antistreptolysin”, “Strep-
tococcus pyogenes”. The quality of scientific literature about
ASLO is poor. A PubMed search for antistreptolysin gave only
2 recent reviews, published in the last 10 years. A PubMed
search for rheumatic fever, on the contrary, revealed more
recent reviews.
doi: 10.2143/ACB.66.6.2062604
2/12/11 11:39
 THE CLINICALDIAGNOSTIC ROLE OF ANTISTREPTOLYSIN O ANTIBODIES
ANALYTICAL PERFORMANCE
Important pre-analytical factors influencing ASLO serology
are the site of primary beta-haemolytic Streptococcus infection
and the moment of sample collection. The assay response is
optimal post-pharyngitis, but limited after pyoderma, because
cholesterol in the skin neutralizes the antistreptolysin O mol-
ecule (2). Consequently, half of the sera will be ASLO negative
in pyoderma patients (2, 3). Serial sample collection during
acute and convalescent phase aims to show a rising ASLO titre,
to differentiate between infected patients and GAS carriers (3).
Patients often present many days after the onset of infection
or too late during convalescence, which hampers the demon-
stration of a rising titre (3-5). Because ASLO kinetics are variable
between subjects, the correct moment for sample collection
cannot be advised. For example, one case already reached the
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plateau at day 8, while in another case, the ASLO titre contin-
ued to increase up to 18 days after the clinical onset of infec-
tion (6). Generally, the ASLO titre begins to rise approximately
1 week after infection, reaching a peak after 3 to 6 weeks (7).
The extent of the titre is not related to disease severity, and the
rate of decline is not related to the course of disease (8). For this
reason, ASLO is of limited use for follow-up.
The ASLO reference values are often inaccurate. They vary
geographically, in relation to the local frequency of Strepto-
coccus infections. They are known to be higher in children
than in adults, with the highest values in the group aged
9-12 years (4, 7). Nevertheless, Roche’s product insert of
Cobas Integra 400/800 proposes a lower reference value for
children (< 150 IU/ml) than for adults (< 200 IU/ml). Reference
values in Siemens’ product insert of BN ProSpec are only
established in an adult population, which is irrelevant. Each
laboratory should determine its own reference values in a
correct reference population of children without antecedent
beta-haemolytic Streptococcus infection, but this is not
always ethically justifiable. In the literature, the only available
paediatric reference values are in old Todd Units or WHO I.U.,
based on the reciprocal of the dilution obtained with the
obsolete ASLO neutralization assay (4, 9). The ‘upper limit of
normal’ (ULN) used to calculate these reference values cannot
be compared between studies, because of various definitions
of ULN depending on the author (3, 4, 9). Another study men-
tions no units at all (3). The WHO I.U. of 1961 is traceable to
the Todd Unit, with an error of 5% (10). The reference values
in WHO I.U. are not useful for the current automated ASLO-
latex assays expressed in I.U./ml.
The traditional ASLO neutralization assay is well-standard-
ized, but the newer latex agglutination, automated nephelo-
metric or turbidimetric assays are not (4). Because of the lim-
ited standardization, consecutive samples should be analyzed
in the same laboratory.
For the interpretation of the ASLO result, physicians
should consider multiple circumstances causing false positive
and false negative results (Table 1). Literature concerning the
analytical performance of ASLO is ambiguous.
DIAGNOSTIC PERFORMANCE
The measurement of ASLO is not useful to diagnose a GAS
pharyngitis (Recommendation B-III) (11). For the diagnosis of
95083_ACB6_02-(OA 2902 R1).indd 411
411
Table 1: Circumstances causing false positive and false
negative ASLO results
False positive result False negative result
– Lipemic samples – Sample collected during latency
– Bacterial contaminated samples period
– Aspecific antibodies in healthy – Sample collected late in convales-
subjects cence
– Infection with Lancefield group C – Post-pyoderma (e.g., post-
& G Streptococcus streptococcal glomerulonephritis)
– Tuberculosis – Corticosteroids and other immu-
– Active viral hepatitis nosuppressiva
– Monoclonal gammopathy – Early administration of antibiotics
References: Siemens’ product insert BN ProSpec, Roche’s product insert
Cobas Integra 400/800 and (2, 4, 8).
GAS pharyngitis, a throat culture remains recommended (7).
The throat culture can differentiate between the Lancefield
groups, in contrast to ASLO, which is generated by GAS as
well as Group C and G Streptococcus. Another reason for per-
forming throat culture is to detect other pathogens like
Arcanobacterium haemolyticum. Transient GAS colonisation
of the oropharynx appears in 3% to 15%, depending on the
endemicity of acute infections (12). Thus, a part of the posi-
tive throat swabs are falsely indicative of acute infection. The
diagnostic differentiation between GAS pharyngitis and GAS
colonisation has to be made in correlation with the clinical
symptoms.
The Jones criteria were formulated to diagnose the initial
attack of ARF (13). They include clinical and laboratory find-
ings and require the evidence of an antecedent beta-haemo-
lytic Streptococcus infection (Table 2). In patients with a pre-
suming ARF, the determination of an elevated ASLO titre is
appropriate for the confirmation of an antecedent beta-
haemolytic Streptococcus infection. A rising ASLO titre,
proven by consecutive measurements between acute and
convalescent serology, emphasizes the diagnostic role of
ASLO. The ASLO titer most often peaks when the first symp-
toms of ARF occur, while at that time the throat culture is
negative in 75% of patients (13).
Although the relationship between post-streptococcal
reactive arthritis and ARF remains unresolved, patients who
fulfil the Jones criteria should be considered to have ARF.
Migratory arthritis without evidence of other major Jones cri-
teria, if supported by two minor manifestations, still must be
considered ARF, especially in children. They should be treated
as ARF, and appropriate antibiotic prophylaxis should be pre-
scribed (14).
The role of ASLO is more dubious in the diagnosis of
AGN, especially because ASLO has no impact on the treat-
ment of AGN. In case of pyoderma-associated AGN, the
immune response is often weak (15). Immunogenicity is
weak because the GAS strains causing pyoderma are less
rheumatogenic.
ASLO has no diagnostic value in adults (13, 16). The ASLO
test is inadequate to differentiate between self-limiting
arthritis and persistent rheumatoid arthritis in an adult pop-
ulation, as shown by an insufficient area under the curve
(AUC) of 0.52 on the receiver operating characteristic (ROC)
curve (16). The traditional ASLO neutralization assay (ASL-kit
bioMérieux, France) shows a specificity (95% C.I.) of 93.2%
(84.7%-97.5%) and a sensitivity of 72.7% (64.2%-77.0%) to
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 412 THE CLINICALDIAGNOSTIC ROLE OF ANTISTREPTOLYSIN O ANTIBODIES

Table 2: Jones criteria 1992 and diagnostic categories of WHO 2002-2003 (13).
The Jones Criteria (1992 update)
Major manifestations Carditis
Polyarthritis
Chorea
Erythema marginatum
Subcutaneous nodules
Minor manifestations Clinical: arthralgia
fever
Laboratory: elevated acute phase reactants (ESR, leukocyte count)
ECG: prolonged PR interval
Evidence of antecedent beta-haemolytic Streptococcus infection Elevated or rising streptococcal antibody titres (ASLO or anti-DNase B titre)
Positive throat culture or rapid streptococcal antigen test
Recent scarlet fever
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Diagnostic categories of WHO (2002-2003) using above criteria

Primary episode of ARF
Recurrent attack of ARF in a patient without established RHD
Recurrent attack of ARF in a patient with established RHD
Rheumatic chorea insidious onset Rheumatic carditis
Chronic valve lesions of RHD
ESR: Erythrocyte Sedimentation Rate; ECG: electrocardiogram
2 major manifestations or 1 major and 2 minor manifestations
PLUS evidence of antecedent beta-haemolytic Streptococcus infection
2 minor manifestations
PLUS evidence of antecedent beta-haemolytic Streptococcus infection
2 major manifestations or 1 major and 2 minor manifestations
PLUS evidence of antecedent beta-haemolytic Streptococcus infection
Other major manifestations or evidence of antecedent beta-haemolytic
Streptococcus infection not required
Do not require any other criteria to be diagnosed as having RHD

Table 3: A simulation of the diagnostic performance of the antistreptolysin O neutralization assay for the detection of
post-streptococcal disease in a Belgian paediatric population (< 15 years).
ARF Total Positive predictive value (PPV) = 0.32%

Positive Negative Negative predictive value (NPV) = 99.99%

ASLO test Positive 395§ 123.004 123.399 Pre-test probability = 0.3/1000
Negative 148 1.685.885§§ 1.686.033 Positive likelihood ratio = 11
Total 543** 1.808.889 1.809.432* Post-test probability = 3/1000
* The population data are based on the information of the Belgian government (FOD Economie, Algemene Directie Statistiek en Economische Informatie):
in December 2007 there were 10.666.866 Belgian citizens; the age group under 15 years was calculated = 1.809.432 children.
** The prevalence of RHD in high-income countries is 0.3/1000 children aged 5-14 years (17).
§
For post-streptococcal disease, the § sensitivity is 72.7% and the §§ specificity is 93.2% with the antistreptolysin O neutralization test (3).

detect post-streptococcal disease in children (3). These data
were collected in a population aged 3 to 14 years with
mainly post-streptococcal glomerulonephritis and a minor-
ity of ARF. For the automated ASLO-latex assays, no specific-
ity and sensitivity percentages are available in scientific lit-
erature nor in the product inserts of Cobas Integra 400/800
(Roche) and BN ProSpec (Siemens). For this reason, a simula-
tion of the diagnostic performance characteristics of ASLO
to detect post-streptococcal disease is only possible for the
antistreptolysin O neutralization assay (Table 3). The simula-
tion starts from a clinical scenario of carditis. Table 3 shows
a very low positive predictive value (PPV) of 0.32%. How-
ever, the inclusion of ASLO in the Jones criteria to diagnose
an antecedent beta-haemolytic Streptococcus infection pre-
sumes an acceptable PPV (11). The post-test probability of
3/1000 indicates that only 3 patients truly have antecedent
beta-haemolytic Streptococcus infection with probable
evolution to RHD, in a group of 1000 patients who test pos-
itive for ASLO. Decision-making based on the ASLO results
can only rely on the high negative predictive value (NPV).
The NPV of 99% means that a normal ASLO titre rules out an
antecedent beta-haemolytic Streptococcus infection.
CLINICAL IMPACT / EPIDEMIOLOGY
GAS may trigger an auto-immune reaction one week to
one month after initial infection. The pathophysiology is
probably based on molecular mimicry between streptococcal
antigens and human tissue. The post-streptococcal syn-
dromes ARF and AGN are paediatric diseases, prevalent in
developing countries, but less common in the Western world.
Hence, literature concerning post-streptococcal complica-
tions in the Western world is scarce. Because epidemiological

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 THE CLINICALDIAGNOSTIC ROLE OF ANTISTREPTOLYSIN O ANTIBODIES 413

Table 4: Epidemiological characteristics of acute rheumatic fever (ARF) and acute post-streptococcal glomerulonephritis (AGN)
ARF AGN

After pharyngitis After pharyngitis After pyoderma

Population Precondition 5-10% (2) 25% (2)
Age 4-15 y (12,15) Early school age Infant, preschool age
(5-6 y) (18) (2-5 y) (18)
Season (15, 18) Less in summer Winter and spring Late summer and early fall
Appearance (15) Continuous & outbreaks Especially outbreaks
Latency (14, 18) 19 d (1-5 w) 10 d (1-3 w) 3 w (3-6 w)
Attack rate (18, 21) Low (0.4- 0.9%) High (10-15%)
Incidence Worldwide 19/100000/y (24) No data
Western world 0.5/100000/y (24) Between < 1/1000000/y (26) and
to 10/100000/y (17) 0.3/100000/y (37)
Less developed countries 13-54/100000/y* (17) Children: 24.3/100000/y (17)
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Adults: 2/100000/y (17)

Prevalence Worldwide RHD=1.3/1000 (17) No data
Western world Between RHD=0.3/1000 (17) and
RHD=0.5/1000 (19)
Less developed countries RHD=3.2/1000 (17)
Recurrence (15, 18) Frequent Rare
Prophylaxis (15) Effective Useless
Mortality Western world High Limited (17)
RHD= 0.5-8/100000/y (23)
d = day; w = week; y = year
*Middle East, North Africa, Latin America and Asia

data are often extrapolated, outdated and weak, they have to
be interpreted cautiously (Table 4).
ARF is most frequently found among children aged 4 to
15 years, because it is a complication of GAS pharyngitis, which
occurs mainly in school-aged children (14, 15). GAS is the etio-
logic agent in 15 to 30% of children with acute pharyngitis (7,
20). After untreated GAS pharingitis or tonsillitis, the attack rate
of ARF is 3% in a closed community, but considerably lower in
open communities namely less than 0.9% (15, 21). ARF causes
acute inflammation of the joints (migratory arthritis), the soft
tissues (subcutaneous nodules), the heart valves and the cen-
tral nervous system. In 80% of the cases, migratory arthritis is
the first symptom (22). The incidence of ARF is 100 times higher
in developing countries than in the Western world, where only
5/1000000 Western school-aged children are affected every
year (23, 24). The Centre for Disease Control stopped the active
surveillance of ARF in 1994, because they registered continu-
ously low ARF incidences (25). Nevertheless, ARF must be con-
sidered in case of fever of unknown origin or arthritis, because
of its serious complication: recurrent ARF episodes may lead to
RHD ten to twenty years later. RHD can be chronic or progres-
sive, causing severe cardiac failure and death. Annual mortality
rates for RHD vary from 0.5 to 8/100000 (23). No incidence data
of RHD are described in the literature. The prevalence of RHD
is approximately 3/10000 in the Western world (17).
In AGN, the auto-immune reaction attacks renal glomer-
uli, leading to inflammation of the kidneys. Compared to
developing countries, where AGN is frequently a complica-
tion of GAS pyoderma, the incidence of pyoderma-associated
AGN is negligible in the Western world (< 1/million per year)
(26). AGN is mostly subclinical and is self-limiting. Exception-
ally, severe irreversible renal failure may occur in less than 1%
of AGN patients (15, 27).
IMPACT OF PREVENTION AND THERAPY
ARF can be prevented by careful treatment of GAS phar-
yngitis with oral penicillin V 250 mg twice a day during at
least 10 days (or erythromycin 20 mg/kg twice a day in case
of penicillin allergy) (15, 28, 29). The antibiotic treatment aims
to protect against the complications of GAS pharyngitis in
suspected children. In the Western world the incidence of
ARF is so low that the risks of antibiotic use are outweighed
against the potential benefits (30). The very high Number
Needed to Treat (NNT = 4000) raises the question whether the
antibiotic use is cost-effective in the Western world (30, 31,
32). Before one patient can be saved from the development
of ARF, 4000 patients with GAS pharyngitis will have to be
treated. Controversy about the use of antibiotics in GAS phar-
yngitis is strengthened due to the limited impact of the anti-
biotics on pharyngitis itself: antibiotics shorten the sympto-
matic period by only 16 hours. The NHG Standard, BAPCOC
and the Sanford Guide specify which populations must be
treated (Table 5) (29, 33, 34).
Table 5: Indications for antibiotic treatment in GAS infection
(29, 33, 34)
Severe throat infection
Frequent relapse of throat infection
(≥ 5 episodes of pharyngitis per year or 2 years in a row)
Peritonsillar infiltrate
Immunocompromised patient with throat infection
History of ARF
Epidemic of GAS in a closed community

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 414 THE CLINICALDIAGNOSTIC ROLE OF ANTISTREPTOLYSIN O ANTIBODIES
ARF patients need secondary prophylaxis (oral penicillin
V 250 mg twice a day). The duration of prophylaxis must be
tailored to each individual situation, but in most cases
prophylaxis until the age of 21 is recommended to prevent
RHD (7). According to the AHA Guidelines of 2009, endocar-
ditis prophylaxis is only necessary in patients with pros-
thetic valves (7).
In AGN, the impact of primary antibiotic prophylaxis is
nihil. No difference in clinical severity is demonstrated
between patients with or without antibiotic treatment (15).
Because relapses of AGN are uncommon, the secondary
prophylaxis is not indicated.
COST ANALYSIS
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From a laboratory perspective, the ASLO assay performed
in Belgian laboratories shows financial deficit. The total cost
of the test, depending on reagents, materials and technicians,
exceeds the reimbursement. A calculation of the costs was
made in two separate clinical laboratories for the analysis of
17 to 35 samples per month on automated analysers (Cobas
Integra 400/800 from Roche and BN ProSpec from Siemens)
using an ASLO-latex assay (35, 36). Material and reagents,
including general laboratory costs and quality controls, cost
approximately € 1.55 to € 2.40 per test. The cost for techni-
cians was calculated to be € 0.22 to € 3.78 per test. In total
one ASLO test costs between € 1.97 and € 6.18. The maximal
reimbursement (B-value: B80), as recorded in the Belgian
nomenclature, is € 2.46 per test. We observed mainly ASLO
requests for ambulatory patients, which further diminishes
the reimbursement to 25% of the B-value (i.e. € 0.62 per test).
Since a few years, it was unclear whether ASLO should be
kept in the Belgian nomenclature for reimbursement. For this
reason, the Scientific Institute of Public Health (ISP/WIV)
stopped the external quality assurance program for ASLO
since 2003 [Personal communication with the expert K. Ver-
nelen MD, WIV Clinical Biology, 27th of July 2009]. In 2009, the
spending expenditure of the Belgian national insurance insti-
tute for disease-invalidity (INAMI/RIZIV) was € 153695 for all
ASLO tests, which is considerable [RIZIV data, obtained from
M. Moens MD, BVAS].
DECISION / CONCLUSION
Acute joint pain in children is a common complaint in the
ambulatory practice and emergency department of a hospi-
tal and ARF is part of the differential diagnosis. In the Western
world ARF is a rare immunological complication of GAS phar-
yngitis, with an ARF incidence of 0.5/100000 [24]. Recurrent
ARF episodes can evolve to RHD many years later with a high
mortality rate of 0.5-8/100000 (23). Antibiotic prophylaxis to
prevent ARF recurrence is recommended in well-defined
cases (Table 5) (29, 33, 34). The Jones criteria of 1992 to diag-
nose ARF mention the use of the ASLO test: the clinical rele-
vance of ASLO is the detection of an antecedent beta-haemo-
lytic Streptococcus infection in view of ARF. This assumes an
acceptable PPV. Critical appraisal of the diagnostic perfor-
mance of the ASLO assay indicates a PPV of < 1% in Western
world, which does not meet the requirements. As a result of
Acta Clinica Belgica, 2011; 66-6
95083_ACB6_02-(OA 2902 R1).indd 414
the high NPV > 99%, ASLO can only be used to rule out an
antecedent beta-haemolytic Streptococcus infection. Despite
this ambiguous diagnostic performance of the ASLO test,
it still remains a criterion to fulfil Jones criteria. Although
the evidence is limited, ASLO will continue to play a clinical-
diagnostic role, as long as there are no better diagnostic tests
for an antecedent beta-haemolytic Streptococcus infection
and as long as there is not enough recent literature to recon-
sider the Jones criteria.
A better standardization of ASLO-latex assays could be
realized by organizing proficiency testing.
A more selective request behaviour of physicians is
strongly recommended for ASLO. The laboratory should incite
a substantial reduction of the current overconsumption of
ASLO by a strategic position of ASLO on the application form;
e.g. not in line with infectious serology, but rather intended
under the section of rheumatologic markers. In December
2009, the Belgian study group of microbiology/committee of
clinical biology submitted a proposal for a diagnostic rule
based on the ‘Critically Appraised Topics’ about ASLO (35, 36).
In October 2010, the health insurance/government intro-
duced the proposed diagnostic rule for reimbursement
namely “ASLO is restricted to patients, younger than 18 years,
clinically suspected of ARF following streptococcal pharyngi-
tis or post-streptococcal reactive arthritis”. The total budget
per year after introduction of the diagnostic rule is estimated
at € 23054 and the possible cost savings per year are esti-
mated at € 130641.
REFERENCES
1. Price CP. Evidence-based laboratory medicine: supporting decision-making. Clin
Chem 2000; 46: 1041-1050.
2. Burton DR. Group A streptococcus: Virulence factors and pathogenic mecha-
nisms. UpToDate 2009.
3. Blyth CC, Robertson PW. Anti-streptococcal antibodies in the diagnosis of acute
and poststreptococcal disease: streptokinase versus streptolysin O and deoxy-
ribonuclease B. Pathol 2006; 38: 152-156.
4. Shet A, Kaplan EL. Clinical use and interpretation of group A streptococcal anti-
body tests: a practical approach for the pediatrician or primary care physician.
Pediatr Infect Dis J 2002; 21: 420-426.
5. Powell C, Parks D. Anti-Streptolysin O Microtitration. In: Isenberg HD. Clinical
Microbiology Procedures handbook, 2nd ed. Washington: American Society for
Microbology Press. 1992: 9.4.1.
6. Uçkay I, Ferry T, Stern R, et al. Use of serum antistreptolysin O titers in the micro-
bial diagnosis of orthopedic infections. Int J Infect Dis 2009; 13: 421-424.
7. Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of Rheumatic Fever and
Diagnosis and Treatment of Acute Streptococcal Pharyngitis: a scientific state-
ment from the American Heart Association Rheumatic Fever, Endocarditis, and
Kawasaki Disease Committee of the Council on Cardiovascular Disease in the
Young, the Interdisciplinary Council on Functional Genomics and Translational
Biology, and the Interdisciplinary Council on Quality of Care and Outcomes
Research. Circulation 2009; 119: 1541-1551.
8. Wallach J. Antistreptococcal Antibody Titers – Acute Rheumatic Fever. In: Wal-
lach J. Interpretation of diagnostic tests, 8th ed.philadelphia: Wolters Kluwer.
Lippincott Williams & Wilkins. 2007; 37-40 and 115.
9. Sethi S, Kaushik K, Mohandas K, Sengupta C, Singh S, Sharma M. Anti-
Streptolysin O titers in normal healthy children of 5-15 years. Indian Pediatr
2003; 40: 1068-1071.
10. Spaun J, Bentzon MW, Olesen Larsen S, Hewitt LF. International Standard for
Antistreptolysin-O. Bull Wld Hlth Org 1961; 24: 271-279.
11. Scottish Intercollegiate Guidelines Network (SIGN). Management of Sore Throat
and Indications for Tonsillectomy: A National Clinical Guideline. SIGN Publica-
tion Number 34; January 1999.
12. Cimolai N. Streptococcus pyogenes is alive and well. BC Medical Journal 2009;
51: 122-127.
13. Special Writing Group of the committee on Rheumatic Fever, Endocarditis, and
Kawasaki Association. Guidelines for the diagnosis of rheumatic fever: Jones
criteria, 1992 update. JAMA 1992; 268: 2069-2073.
14. Gibofsky A, Zabriskie JB. Clinical manifestations and diagnosis of acute rheu-
matic fever. UpToDate 2009.
2/12/11 11:39
 THE CLINICALDIAGNOSTIC ROLE OF ANTISTREPTOLYSIN O ANTIBODIES
15. Bisno AL. Nonsuppurative Poststreptococcal Sequelae: Rheumatic Fever and
Glomerulonephritis. In: Mandell G, Bennett JE, Dolin R, eds. Principles and prac-
tice of infectious diseases. Philadelphia: Elsevier Churchill Livingstone, 6th ed.
2000: 2380-2392.
16. Visser H, Speyer I, Ozcan B, Breedveld FC, van Ogtrop ML, Hazes JM. The diag-
nostic value of streptococcal serology in early arthritis: a prospective cohort
study. Rheumatol 2000; 39: 1351-1356.
17. Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of Group A
streptococcal disease. Lancet Infect Dis 2005; 5: 685-694.
18. Wannamaker LW. Differences between streptococcal infections of the throat
and of the skin. N Eng J Med 1970; 282: 23-31.
19. Carapetis JR, McDonald M, Wilson NJ. Acute Rheumatic Fever. Lancet 2005; 366:
155-168.
20. IDSA guideline. Bisno AL, Gerber MA, Gwaltney JM et al. Practice guidelines for
the diagnosis and management of group A streptococcal pharyngitis. CID 2002;
35: 113-125.
21. Siegel AC, Johnson EE, Stollerman GH. Controlled studies of streptococcal phar-
yngitis in a pediatric population: factors related to the attack rate of rheumatic
fever. N Eng J Med 1961; 265: 559-566.
22. Carapetis JR, Currie JB. Rheumatic fever in a high incidence population: the impor-
tance of monoarthritis and low grade fever. Arch Dis Child 2001; 85: 223-227.
Downloaded by [University of Nebraska, Lincoln] at 01:46 31 May 2016
23. WHO. Rheumatic Fever and Rheumatic Heart Disease: report of a WHO Expert
Consultation, Geneva: World Health Organization, 2004.
24. Altamimi S, Khalil A, Khalaiwi KA, Milner R, Pusic MV, Al Othman MA. Short
versus Standard duration antibiotic therapy for acute streptococcal pharyngitis
in children. Cochrane Database Syst Rev 2009, 1: CD004872.
25. Ressel G. Center for Disease Control and Prevention (CDC). Practice guidelines:
principles of appropiate antibiotic use: part IV. Acute pharyngitis. Am Fam Phy-
sician 2001.
95083_ACB6_02-(OA 2902 R1).indd 415
415
26. IDSA guideline. Stevens DL, Bisno AL, Chambers HF et al. Practice guidelines for
the diagnosis and management of skin and soft-tissue infections. CID 2005; 41:
1373-1830.
27. Steer AC, Danchin MH, Carapetis JR. Group A Streptococcal infections in Chil-
dren. J. Paediatr Child Health 2007; 43: 203-113.
28. Gibofsky A, Zabriskie JB. Treatment and prevention of acute rheumatic fever.
UpToDate 2009.
29. Nederlands Huisartsen Genootschap. NHG-standaard M11: Acute keelpijn,
2007.
30. Robertson KA, Volmink JA, Mayosi BM. Antibiotics for the primary prevention
of acute rheumatic fever: a meta-analysis. BMC Cardiovas Disord 2005; 5: 11.
31. Del Mar C, Glasziou PP, Spinks A. Antibiotics for sore throat. Cochrane Database
Syst Rev 2006, 4: CD000023.
32. Ehrlich JE, Demopoulos BP, Daniel KR, Ricarte MC, Glied S. Critically appraised
economic evaluation. NHS Economic Evaluation Database. 2009 (2). Cost-
effectiveness of treatment options for prevention of rheumatic heart disease
from group A streptococcal pharyngitis in pediatric population. Preventive
Medicine 2002; 35: 250-257.
33. De Meyere M, Matthys J, Cox T. Acute keelpijn. Aanbeveling voor goed gebruik
van antibiotica. Brussel: BAPCOC/ WVVH, 2001.
34. Sanford JP, Gilbert DN, Moellering RC, Merle A, Eliopoulos GM. In: The Sanford
guide to antimicrobial therapy 2008-2009, 21th ed.
35. Geerts I, Frans J. Anti-Streptolysine O antistoffen anno 2009: nog nuttig? Criti-
cally appraised topic 2009; http://w1.uzleuven.be/labo/Leermodule/EBLM_CAT/
content.html.
36. De Vos N, Mewis A. Rheumatologie: zijn antistreptolysine O antilichamen &
Waaler-Rose obsoleet? Critically appraised topic 2009; http://w1.uzleuven.be/
labo/Leermodule/EBLM_CAT/content.html.
37. Niaudet P. Poststreptococcal Glomerulonephritis. UpToDate 2010 version 18.3.
Acta Clinica Belgica, 2011; 66-6
2/12/11 11:39