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Brief Reports

Indian Pediatrics 2003; 40:1068-1071 

Anti-Streptolysin O Titers in Normal Healthy Children of 5-15 Years

 

Sunil Sethi, Kirti Kaushik, Kavya Mohandas, Caesar Sengupta, Surjit Singh* and Meera Sharma

From the Departments of Medical Microbiology and Pediatrics*, Post Graduate Institute of Medical Education and Research, Chandigarh 160 012, India.

Correspondence to : Dr. Sunil Sethi, Assistant Professor, Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research, Chandigarh 160 012, India.
E-mail: sunilsethi10@hotmail.com

Manuscript received: December 3, 2002, Initial review completed: January 24, 2003; Revision accepted: May 5, 2003.

Abstract:

Antistreptolysin O (ASO) levels vary with age group of the study population and geographical locations. The present study was undertaken to determine the upper limit of normal of ASO in 200 normal children of 5-15 years of age with no history of recent sore throat infection. The standard tube dilution method (WHO) was used for estimating ASO titers. It was found that 239 IU was the upper limit of normal in the study population, which can be considered as the baseline ASO titer. This can provide useful guidelines for physicians in the interpretation of elevated ASO titers in cases of suspected acute rheumatic fever.

Key words: Antistreptolysin O titers, Children, Acute rheumatic fever.

Acute rheumatic fever (ARF) is an important non-suppurative sequelae of Group-A streptococcal (GAS) infection of the throat. Diagnosis of ARF, according to the Jones criteria requires evidence of antecedent GAS infection(1). Positive throat cultures are obtained only in about 11% at the time of presentation of ARF(2). Moreover, mere presence of the organism in the throat can also indicate a carrier state which is seen in 2.5-35.4% of individuals(3). However, the appearance of antibody to Streptolysin O (Antistreptolysin O or ASO) in serum of a patient or an increase in the ASO titer is usually indicative of recent streptococcal infection(4). This is especially true when considering the diagnosis of non-suppurative sequelae of GAS infection. Although ASO titer has provided a useful guideline to physicians this has been shown to vary with age(2), geographical location and site of infection. Clinical microbiology laboratories often use interpretative criteria suggested by manufacturers of commercial antibody test kits. Because such ‘normal’ levels may only reflect appropriate titer for adults correct interpretation of titer in children can be problematic. Moreover, it is not often feasible to obtain acute and convalescent sera. Thus, the absolute value of ASO is of diagnostic importance. Hence, this study was undertaken to determine the upper limit of normal (ULN) of ASO, in normal children between the ages 5-15 years.

Subjects and Methods

Blood samples (2-3 mL) from 200 normal school going children (5-15 years) with no history of any recent throat infection were collected. Sera were separated and stored at –20ºC till further use. Written informed consent was obtained for enrollment.

Each serum sample was subjected to ASO neutralization test(5). The antigen was prepared in the laboratory using the standard strain, Streptococcus pyogenes C203S obtained from the WHO collaborating refer-ence and research center on streptococcus, Prague, Czech Republic. The standard neutralization test was performed as recommended by WHO(5). The highest dilution of serum showing no hemolysis was considered the ASO titer for the subject. Geometric mean titer (GMT) of ASO in the study population was calculated and ULN was calculated as geometric mean +2 standard deviation. Control sera (known positive and negative) were included in each test run.

Results

The children were categorized into two groups. Group I included 131 children of age group 5-10 years. Group II included 69 children of age group 11-15 years. ASO titer of all children as determined by neutralization test is depicted in Table I. Out of 200 children, 89 (44.5%) children had ASO titer less than 100 IU, whereas number of children showing ASO titer 100, 125, 150 and 195 IU were 16 (8%), 27 (13.5%), 18 (9%), 43 (21.5%) respectively. However, 7 children (3.5%) showed highest ASO titer of 244 IU.

TABLE I

ASO Titres of the Study Population by Standard Neutralization Test
  Sera
tested

ASO titers (IU)

Study groups <100 100 125 156 195 244
Group I (5-10 years)
131
63 (48.0%)
9 (6.8%)
14 (10.6%)
10 (7.6%)
29(22.1%)
6 (4.5%)
Group II (11-15 years)
69
26 (19.8%)
7 (5.3%)
13 (9.9%)
8 (6.1%)
14 (10.6%)
1 (0.7%)
Total
200
89 (67.9%)
16 (12.2%)
27 (20.6%)
18 (13.7%)
43 (32.8%)
7 (5.3%)

 

The geometrical mean titer and upper limit of normal of study population is shown in Table II. The ULN of two study groups was 230.62 IU and 242.87 IU respectively. The difference between them was not statistically significant (P >0.05).

TABLE II

Geometric Mean Titers and Upper Limit of Normal of Study Population
Study groups
 
Sera
tested
Geometric
mean titers
Upper limit
of normal
Group I
(5-10 years)
131
113.72
230.62
Group II
(11-15 years)
69
110.32
242.87
Total
200
111.63
238.59

 

Discussion

Anti-streptolysin O test, an internationally standardized test(5) is widely used in detection of group A streptococcal infections and their sequelae(6,7). Elevated or rising titers of ASO are seen in 80% or more of the cases with acute rheumatic lever(7). Acute and convalescent sera should be obtained and tested simultaneously to decide a rising ASO titer but this is not always feasible. Hence, a single specimen when available requires to be compared with a pre-determined base line value or an upper limit of normal.

ASO titers can vary depending on the geographic location, age group of the study population, and the climatic conditions. ASO titers more than 333 Todd units are generally considered elevated in children(8). However, this was found to be 239 IU in our study population. The study by Kaplan, et al.(9) also showed that GMT and the ULN for the entire group of children were 89 IU and 240 IU respectively. The geometric mean and upper limit of normal in our study group was also greater in children of age group 11-15 years, though the difference was not statistically significant. In a study from Chennai(10), out of 124 children, antistreptolysin O and C-reactive protein levels were reported to be higher in 11- 15 years old children than in 5-10 year old children. However, in this study group, 89.5% of children indicated history of repeated sore throat as compared to our study population, who had no history of recent sore throat infection. The relatively higher ASO values in this group may be that children face attacks of GAS infection many times till reaching this age group.

Gharagozolo, et al.(11) reported that the same study population showed greater ASO levels during the winter season than in summer. This study was conducted from November to March, i.e., winter to early spring, when streptococcal infections are at peak, to compensate for any seasonal variation.

However, it must he recognized that these values are for children in and around Chandigarh. Because specific ULN and GMT may vary for children living elsewhere, establishment of values in other areas will require additional studies.

Having establishment the upper limit of normal in school age children in our population, we can consider this (239 IU) as baseline ASO titer. This would prove helpful in the interpretation of elevated ASO titers in cases of suspected ARF. This value is likely representative of the pediatric population in and around Chandigarh and should be of clinical value to physicians, epidemiologists and clinical laboratory personnel who can misinterpret streptococcal antibody titers because of a failure to realize that children will on an average, have higher titers than the adult values listed as ‘normal’ in manufacturer’s inserts.

Contributors: SS designed the study. CS was responsible for analysis and interpretation of data. KM and SS drafted and revised the article. KK was responsible for quality control and technical performance. MS helped in the study design.

Funding: None.

Competing interests: None stated.

Key Messages

• Antistreptolysin O titers of 239 IU can be considered as the upper limit of normal in children population (age 5-15 years) in and around Chandigarh for the diagnosis of group A streptococal infection or its sequelae like acute rheumatic fever.

 

 References


 

1. Special writing group of the committee on rheumatic fever, endocarditis and Kawasaki disease of the council on cardiovascular disease in the young of the American Heart Association: Guidelines for the diagnosis of rheumatic fever. Jones criteria, 1992 update. Jama 1992, 268: 2069-2073.

2. Kaplan EL. Rheumatic fever. In: Fauci AS, Brawnwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, Hauser SL, Longo DL eds. Harrison’s Principle of Internal Medicine. 14th edn. New York: McGraw-Hill; 2001; p 1340-1343.

3. Pichichero ME, Marsocci SM, Murphy ML, Hoeger W, Green JL, Sorrento A. Incidence of streptococcal carriers in private practice. Arch Pediatr Adolesc Med 1999; l53: 624-628.

4. Gooder H. Antistreptolysin O: Its interaction with streptolysin O, its titration and a comparison of some standard preparations. Bull WHO 1961; 25: 173-183.

5. Dawson KP, Ameen AS, Nsanze H, Bin-oyhman S, Mustafa N. The prevalence of Group A streptococcal throat carriage in AL-Ain, United Arab Emirates. Ann Trop pediatr 1996; 16: 123-127.

6. Klein GC, Baker CN and Jones WL. Upper limits of normal–antistreptolysin O and anti deoxyribonuclease B titers. Applied Microbio 1971; 21: 999-1000.

7. Stollerman GH, Lewis AT, Sehultz I, Taranta A. Relationship of immune response to group A streptococci to the course of acute, chronic and recurrent rheumatic fever. Am J Met 1956; 20: 163-169.

8. Report of the Adhoc committee to revise the Jones criteria (modified) of the council on rheumatic fever and congenital heart disease of the American Heart Association. Circulation 1965; 32: 664-668.

9. Kaplan EL, Rothemel CD, Johnson DR. Antostreptolysin O and anti deoxyribonuclease B titers; normal values for children age 2 to 12 in the US. Pediatrics 1998; 101; 86-88.

10. Rajkumar S, Krishnamurthy R. Isolation of group A beta hemolytic streptococci in the tonsillopharynx of social children in Madras city and correlation with their clinical features. Jpn J Infect Dis 2001; 54: 137-139.

11. Gharagozolo R, Gharamian P. The range of ASO titers among 3129 healthy individual in summer and winter in Tehran, Iran. Pahlavi Med J 1976: 7; 323-333.

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