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,
Manuscript received: December 3, 2002, Initial review completed: January 24, 2003; Revision accepted: May 5, 2003.
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.
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
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
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.
Competing interests: None stated.