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Spectrum and inoculum size effect of a rapid antigen detection test for group A streptococcus in children with pharyngitis.

ABSTRACT: BACKGROUND: The stability of the accuracy of a diagnostic test is critical to whether clinicians can rely on its result. We aimed to assess whether the performance of a rapid antigen detection test (RADT) for group A streptococcus (GAS) is affected by the clinical spectrum and/or bacterial inoculum size. METHODS: Throat swabs were collected from 785 children with pharyngitis in an office-based, prospective, multicenter study (2009-2010). We analysed the effect of clinical spectrum (i.e., the McIsaac score and its components) and inoculum size (light or heavy GAS growth) on the accuracy (sensitivity, specificity, likelihood ratios and predictive values) of a RADT, with laboratory throat culture as the reference test. We also evaluated the accuracy of a McIsaac-score-based decision rule. RESULTS: GAS prevalence was 36% (95CI: 33%-40%). The inoculum was heavy for 85% of cases (81%-89%). We found a significant spectrum effect on sensitivity, specificity, likelihood ratios and positive predictive value (p<0.05) but not negative predictive value, which was stable at about 92%. RADT sensitivity was greater for children with heavy than light inoculum (95% vs. 40%, p<0.001). After stratification by inoculum size, the spectrum effect on RADT sensitivity was significant only in patients with light inoculum, on univariate and multivariate analysis. The McIsaac-score-based decision rule had 99% (97%-100%) sensitivity and 52% (48%-57%) specificity. CONCLUSIONS: Variations in RADT sensitivity only occur in patients with light inocula. Because the spectrum effect does not affect the negative predictive value of the test, clinicians who want to rule out GAS can rely on negative RADT results regardless of clinical features if they accept that about 10% of children with negative RADT results will have a positive throat culture. However, such a policy is more acceptable in populations with very low incidence of complications of GAS infection.

SUBMITTER: Cohen JF

PROVIDER: S-EPMC3387167 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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Project description:BACKGROUND: Pharyngitis management guidelines include estimates of the test characteristics of rapid antigen streptococcus tests (RAST) using a non-systematic approach. OBJECTIVE: To examine the sensitivity and specificity, and sources of variability, of RAST for diagnosing group A streptococcal (GAS) pharyngitis. DATA SOURCES: MEDLINE, Cochrane Reviews, Centre for Reviews and Dissemination, Scopus, SciELO, CINAHL, guidelines, 2000-2012. STUDY SELECTION: Culture as reference standard, all languages. DATA EXTRACTION AND SYNTHESIS: Study characteristics, quality. MAIN OUTCOME(S) AND MEASURE(S): Sensitivity, specificity. RESULTS: We included 59 studies encompassing 55,766 patients. Forty three studies (18,464 patients) fulfilled the higher quality definition (at least 50 patients, prospective data collection, and no significant biases) and 16 (35,634 patients) did not. For the higher quality immunochromatographic methods in children (10,325 patients), heterogeneity was high for sensitivity (inconsistency [I(2)] 88%) and specificity (I(2) 86%). For enzyme immunoassay in children (342 patients), the pooled sensitivity was 86% (95% CI, 79-92%) and the pooled specificity was 92% (95% CI, 88-95%). For the higher quality immunochromatographic methods in the adult population (1,216 patients), the pooled sensitivity was 91% (95% CI, 87 to 94%) and the pooled specificity was 93% (95% CI, 92 to 95%); however, heterogeneity was modest for sensitivity (I(2) 61%) and specificity (I(2) 72%). For enzyme immunoassay in the adult population (333 patients), the pooled sensitivity was 86% (95% CI, 81-91%) and the pooled specificity was 97% (95% CI, 96 to 99%); however, heterogeneity was high for sensitivity and specificity (both, I(2) 88%). CONCLUSIONS: RAST immunochromatographic methods appear to be very sensitive and highly specific to diagnose group A streptococcal pharyngitis among adults but not in children. We could not identify sources of variability among higher quality studies. The present systematic review provides the best evidence for the wide range of sensitivity included in current guidelines.

Project description:Antibiotic treatment of Group A Streptococcus (GAS) pharyngitis is important in acute rheumatic fever (ARF) prevention, however clinical guidelines for prescription vary. GAS carriers with acute viral infections may receive antibiotics unnecessarily. This review assessed the prevalence of GAS pharyngitis and carriage in different settings.A random-effects meta-analysis was performed. Prevalence estimates for GAS+ve pharyngitis, serologically-confirmed GAS pharyngitis and asymptomatic pharyngeal carriage were generated. Findings were stratified by age group, recruitment method and country income level. Medline and EMBASE databases were searched for relevant literature published between 1 January 1946 and 7 April 2017. Studies reporting prevalence data on GAS+ve or serologically-confirmed GAS pharyngitis that stated participants exhibited symptoms of pharyngitis or upper respiratory tract infection (URTI) were included. Included studies reporting the prevalence of asymptomatic GAS carriage needed to state participants were asymptomatic.285 eligible studies were identified. The prevalence of GAS+ve pharyngitis was 24.1% (95% CI: 22.6-25.6%) in clinical settings (which used 'passive recruitment' methods), but less in sore throat management programmes (which used 'active recruitment', 10.0%, 8.1-12.4%). GAS+ve pharyngitis was more prevalent in high-income countries (24.3%, 22.6-26.1%) compared with low/middle-income countries (17.6%, 14.9-20.7%). In clinical settings, approximately 10% of children swabbed with a sore throat have serologically-confirmed GAS pharyngitis, but this increases to around 50-60% when the child is GAS culture-positive. The prevalence of serologically-confirmed GAS pharyngitis was 10.3% (6.6-15.7%) in children from high-income countries and their asymptomatic GAS carriage prevalence was 10.5% (8.4-12.9%). A lower carriage prevalence was detected in children from low/middle income countries (5.9%, 4.3-8.1%).In active sore throat management programmes, if the prevalence of GAS detection approaches the asymptomatic carriage rate (around 6-11%), there may be little benefit from antibiotic treatment as the majority of culture-positive patients are likely carriers.

Project description:Group A Streptococcus (GAS) infections account for an estimated 500,000 deaths every year. This bacterial pathogen is responsible for a variety of mild and life-threatening infections and the triggering of chronic autoimmune sequelae. Pharyngitis caused by group A Streptococcus (GAS), but not asymptomatic GAS carriage, is a prerequisite for acute rheumatic fever (ARF). Repeated bouts of ARF may trigger rheumatic heart disease (RHD), a major cause of heart failure and stroke accounting for 275,000 deaths annually. A vaccine that prevents pharyngitis would markedly reduce morbidity and mortality from ARF and RHD. Nonhuman primates (NHPs) have been utilized to model GAS diseases, and experimentally infected rhesus macaques develop pharyngitis. Here we use an NHP model of GAS pharyngitis to evaluate the efficacy of an experimental vaccine, Combo5 (arginine deiminase [ADI], C5a peptidase [SCPA], streptolysin O [SLO], interleukin-8 [IL-8] protease [SpyCEP], and trigger factor [TF]), specifically designed to exclude GAS components potentially linked to autoimmune complications. Antibody responses against all Combo5 antigens were detected in NHP serum, and immunized NHPs showed a reduction in pharyngitis and tonsillitis compared to controls. Our work establishes the NHP model as a gold standard for the assessment of GAS vaccines.IMPORTANCE GAS-related diseases disproportionally affect disadvantaged populations (e.g., indigenous populations), and development of a vaccine has been neglected. A recent strong advocacy campaign driven by the World Health Organization and the International Vaccine Institute has highlighted the urgent need for a GAS vaccine. One significant obstacle in GAS vaccine development is the lack of a widely used animal model to assess vaccine efficacy. Researchers in the field use a wide range of murine models of infection and in vitro assays, sometimes yielding conflicting results. Here we present the nonhuman primate pharyngeal infection model as a tool to assess vaccine-induced protection against colonization and clinical symptoms of pharyngitis and tonsillitis. We have tested the efficacy of an experimental vaccine candidate with promising results. We believe that the utilization of this valuable tool by the GAS vaccine research community could significantly accelerate the realization of a safe and effective GAS vaccine for humans.

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Spectrum and inoculum size effect of a rapid antigen detection test for group A streptococcus in children with pharyngitis.

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