Evaluation of Binax Now Streptococcus Pneumoniae Urinary Antigen Test in Children in a Community With a High Carriage Rate of Pneumococcus

Pneumococcal antigen was present in urine from 49 of 102 well Gambian children. Eighty-nine of the 102 were nasopharyngeal carriers of pneumococci. The positive predictive value for carriage was 96%, and the negative predictive value was 22%. The test is not useful for predicting etiology of disease in populations with a high rate of nasopharyngeal carriage of pneumococci. Streptococcus pneumoniae is a major cause of mortality and disability in young children worldwide 1 and is the leading bacterial cause of community-acquired pneumonia. 2 Most children in developing countries carry the pneumococcus in their nasopharynx. Diagnostic methods for invasive pneumococcal disease are at present inadequate, and the true burden of disease remains unknown in many developing countries. 3 A new urine antigen detection kit, Binax NOW Streptococcus pneumoniae Urinary Antigen Test (Binax Inc., Portland, ME) has been developed recently and tested in a small number of subjects with pneumococcal bacteremia in the US with promising results as indicated in the test kit procedure booklet. The US Food and Drug Administration has approved Binax NOW for use in the US since August, 1999. However, the test has not been evaluated in communities with high carriage rates of pneumococci. In these communities a false positive might result from the presence of antigen from carriage rather than from pneumococcal disease. The purpose of this study was to determine whether this test detects pneumococcal antigen in urine samples obtained from children colonized with S. pneumoniae in the nasopharynx. Methods. The protocol for this study was approved by the Gambia Government and Medical Research Council Ethics Committee. Nasopharyngeal swabs were taken from 102 children (mean age, 46 months; minimum 44.7, maximum 48.6; sd 0.93) during a pneumococcal carriage study undertaken in the Upper River Division of The Gambia. The children enrolled had had no antibiotics in the previous month and had no history of a recent illness compatible with pneumococcal disease. In the Gambia children have an infant welfare card that contains details of all immunization records, clinical illness and clinical consultations. It was thus possible during this study to exclude children who have had a recent history (within 3 months) of an illness compatible with otitis media, acute lower respiratory infection or hospitalization for possible invasive pneumococcal disease. In addition children who had within the same period been treated for any ailments with antimicrobials that could possibly impact nasopharyngeal colonization by pneumococci, such as trimethoprim-sulfamethoxazole, ampicillin or penicillin were excluded. Nasopharyngeal swabs collected by Calcium Alginate Applicator (Fisher Scientific Co., distributed by Curtin Matheson Scientific, Houston, TX) were placed in skim milk-tryptone-glucose-glycerol transport media, immersed in dry ice in the field and plated in the laboratory on sheep blood agar supplemented with 5 μg/ml gentamicin (Totexmedica GmbH, Tritten, Germany) for specific isolation of S. pneumoniae. Semiquantitation of isolates was done by plating out a known volume of diluted nasopharyngeal swab in skim milk-tryptone-glucose-glycerol within 4 h of collection. S. pneumoniae isolates were identified by colony morphology, susceptibility to optochin (Unipath, Basingstoke, UK) and capsular type by latex agglutination using antisera from the Statens Serumsinstitut (Copenhagen, Denmark) as described previously. 4 Urine sam-ples (at least 1 ml each) were obtained at the time of collection of the swab, or soon after, with the use of sterile universal containers and were coded and stored at −20°C before testing. The urine antigen tests were performed according to the manufacturer’s instructions by a laboratory technician who had no involvement with the pneumococcal carriage study or knowledge of the culture results. Results. Eighty-nine of 102 children studied (87%) carried S. pneumoniae. Urine samples obtained from 49 of the 89 children (55%) tested positive in the Binax NOW test (Table 1). In addition urine samples from 2 other children who were not carriers of S. pneumoniae were positive. The sensitivity and specificity of the test for detection of nasopharyngeal carriage of S. pneumoniae in our study population were 55 and 85%, respectively. The test had a positive predictive value of 96% for the detection of carriage and a negative predictive value of only 22%. Colony-forming units (CFU) varied widely from 1 × 10 2 CFU/ml to 2.38 × 10 7 CFU/ml irrespective of the intensity of the color line on the positive tests.Table 1: Detection of urinary antigen by Binax NOW in children with nasopharyngeal carriage of Streptococcus pneumoniaeDiscussion. The detection of urinary antigen in more than one-half of the children colonized by S. pneumoniae indicates that a positive result from this test does not necessarily imply active disease in children. Thus when used in a community with high pneumococcal carriage, a positive result from Binax NOW test must be interpreted with caution. The two “false positive” tests in our study may indeed have been true positives because the presence of pneumococcal antigen resulting from colonization is intermittent and pneumococcal antigen could be excreted in urine after the disappearance of S. pneumoniae from the nasopharynx. Alternatively carriage might be present at a level of colonization that is undetectable by culture. In The Gambia, as in many other developing countries, nasopharyngeal carriage of S. pneumoniae begins in the first few weeks of life, and >80% of children are colonized by the age of 1 year, 5 decreasing to ∼20% in adults. 6 Therefore the Binax NOW test would likely be of limited value for detection of childhood pneumococcal pneumonia in our study population. In a recent study of the etiology of pneumonia in Beijing, China, the Binax NOW test was no more likely to be positive among children with radiographically confirmed pneumonia than among control children, and it was more likely to be positive among children who were colonized by S. pneumoniae. 7 The test may also be of limited use in the diagnosis of adult pneumonia because of the relatively high carriage rates of S. pneumoniae in Gambian adults. This requires further investigation. There was no correlation between the magnitude of nasopharyngeal carriage and the intensity of the color line in positive tests. Acknowledgments. Binax NOW kits were provided by Binax Inc., Portland, ME, and technical assistance was provided by Osman Secka and Mark Saaka.