Diagnosis of Pneumococcal Disease Limitations of Surveillance for Invasive Disease David Murdoch University of Otago, Christchurch New Zealand
Key Points We are still reliant on culture-based methods for diagnosing pneumococcal disease These methods have major limitations which impact on surveillance and epidemiologic research There is a need for newer diagnostics
S. pneumoniae Identification Bile solubility negative positive
Advantages of Culture-Based Methods for Diagnosing Invasive Pneumococcal Disease Can be implemented world-wide High diagnostic accuracy Provide serotype data Provide antimicrobial susceptibility data Potentially stable marker over time
Why do Culture-Base Methods Lack Sensitivity for Diagnosing Invasive Pneumococcal Disease? 1) Many laboratories have difficulty isolating S. pneumoniae
Why do Culture-Base Methods Lack Sensitivity for Diagnosing Invasive Pneumococcal Disease? 2) Issues with sample type
Pneumococcal Meningitis Traditional microscopy and culture of CSF samples can be highly sensitive and specific Gram stain smear of CSF 1 sensitivity of 84% Specificity 98% 1 Rev Infect Dis 1980;2:725-45
Pneumococcal Pneumonia
Pneumococcal Pneumonia Respiratory samples are problematic Often unobtainable from children Sputum culture can be difficult to interpret
Pneumococcal Pneumonia Yields from blood cultures are generally low in invasive pneumococcal disease Positivity rates: Adult pneumonia 3-8% Pneumococcal meningitis >50%
Why do Culture-Base Methods Lack Sensitivity for Diagnosing Invasive Pneumococcal Disease? 3) Prior antibiotic use may affect recovery of S. pneumoniae
Yield of pneumococci in cases of pneumonia: Pre-antibiotic era 80% 1950s 40-70% Currently <30%
Implications for Surveillance and Epidemiologic Research Need other approaches in order to obtain accurate burden data (e.g. vaccine probe studies, modeling) Need large sample sizes in order to obtain sufficient statistical power in epidemiologic studies Differences between bacteraemic and non-bacteraemic disease
Newer Diagnostic Methods for Pneumococcal Disease
NOW S. pneumoniae Urinary Antigen Test +ve -ve
NOW S. pneumoniae Urinary Antigen Test 420 Urine samples from adults with pneumonia 169 Urine samples from adult patients without pneumonia 120 (29%) positive 0 positive J Clin Microbiol 2001;39:3495-8
Performance of NOW test ~80% sensitivity compared to blood cultures Less affected by prior antimicrobial use Remains positive for several weeks after acute illness Useful for testing CSF samples in suspected pneumococcal meningitis
Use of NOW test for the Diagnosis of Pneumococcal Meningitis Samra et al (N=519, all ages) 1 22 cases of pneumococcal meningitis 95% sensitivity, 100% specificity Direct CSF smear 68% sensitivity Saha et al (N=450, children) 2 122 cases of pneumococcal meningitis 100% sensitivity, 100% specificity 1 Diagn Microbiol Infect Dis 2003;45:237-40 2 Pediatr Infect Dis J 2005;24:1093-8
Performance of NOW test Problems: Detects carriage in children Relatively expensive
S. pneumoniae PCR Most studies have only tested blood samples for occult pneumococcal bacteraemia Sensitivity compared to blood cultures: Adults 29-100% Children 57-100% Variable rate of positive results from control patients High sensitivity and specificity for testing CSF samples
Pneumococcal Diagnostics Future Prospects Nucleic acid detection Quantitative assays Antigen detection assays e.g. pneumolysin Novel approaches e.g. breath analysis
Immediate Activities Emphasis on establishing and maintaining high quality laboratory diagnostics for culturing pneumococcus Enhanced capacity Staff training Adequate supplies Quality control systems Funding Explore utilising improved diagnostic tools for pneumococcal meningitis Encourage research on pneumococcal diagnostics