2. WHO comments:
– “More than any other infectious disease,
pneumonia remains the number one
killer worldwide.”
– Streptococcus pneumoniae and Haemophilus influenzae
are the top two bacterial causes of acute respiratory infections.
– Both viral and bacteria respiratory infections present the same
clinical symptoms and can often only be distinguished by
laboratory tests
– 80% of pneumonia patients may unnecessarily
be given antibiotics - contributing to
antibiotic resistance
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3. Case Review
• Respiratory Tract Infection (RTI) cases
– very large cases
– several diseases with similar symptoms
• Target cases
– Community-acquired pneumonia
– Nosocomial pneumonia cases
– Acute ‘Flu-like’ cases
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4. Community - Acquired
Pneumonia
~12 million cases treated annually
worldwide
S. pneumoniae is the leading cause of
bacterial pneumonia -
up to 65% of cases in some studies
Legionella also a leading cause of community-acquired
pneumonia - up to 15%
S. pneumoniae and Legionella pneumonia have high
mortality rates - as high as 30%
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5. Acute ‘Flu-like’ Cases
• Clinical symptoms of lower RTI diseases
(pneumonia, acute influenza and acute
bronchitis) similar
• Bacterial pneumonia can be a complication of
acute influenza or acute bronchitis
• Significantly increases overall case potential
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7. Causative Agents of
Community-Acquired Pneumonia
Bacterial Viral
Streptococcus pneumoniae Influenza A & B
Legionella pneumohila RSV
Haemophilus influenza type B Adenovirus
Non typable Haemophilus Para Influenza
Staphlococcus aureus
Moraxella catarrhalis
Pseudomonas aeruginosa
Chlymydia pneumonia
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Mycoplasma pneumonia 7
8. Community-Acquired Pneumonia
CAP
• S. pneumoniae is the leading cause of bacterial
pneumonia and CAP - up to 65% of all cases in
some studies
• Legionella also a leading cause of community-acquired
pneumonia - up to 15%
• S. pneumoniae and Legionella pneumonia have high
mortality rates - as high as 30%
• Bacterial infections can occur as a complication
of influenza
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9. Community-Acquired Pneumonia
• Transmission: person to person by direct contact
with infectious secretions
• Risk groups • Symptoms
– elderly – fever, chills
– children under 2 and / – chest pain, pleurisy,
or attending day care difficulty breathing
– patients with – blood-tinged sputum
underlying illness – headache
– immunocompromised – cough (often non-
patients productive)
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10. Community-Acquired Pneumonia
• Treatment
– Pathogen-specific diagnosis -
• help direct the most cost-effective treatment
• minimizes the risk of increasing antibiotic resistance
– Empirical treatment
• may not always be the most cost-effective treatment
• increases the risk of antibiotic resistance
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11. Community-Acquired Pneumonia
• many strains of S. pneumoniae have intermediate
sensitivity and resistance to penicillin and
resistance to single or multiple broad-spectrum
antibiotics (Goldstein and Acar, 1996)
• accurate diagnosis required allowing specific
antibiotic therapy
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14. Diagnostics
• Blood Culture
– Advantages
• positive = confirmation patient is bacteremic
• allows for drug susceptibility testing
– Disadvantages
• only 10-30% of all pneumonia cases are
bacteremic - positive culture result in only 25%
of cases (Musher, 1992)
• potential errors by technician
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15. Diagnostics
• Blood Culture
– Disadvantages
• can also be positive in patients with meningitis,
otitis media, septic arthritis, etc
• 24-48 hours incubation
• requires experienced technicians to perform and
interpret results
• expensive
– technician time
– instrumentation (incubators)
• invasive for the patient
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16. Diagnostics
• Sputum Culture
– Advantages
• supplies and reagents relatively inexpensive
• non-invasive for the patient
• allows for drug susceptibility testing
– Disadvantages
• samples must be taken prior to antibiotic therapy
• sample required from lower respiratory tract;
difficult to obtain (non-productive cough, children,
elderly)
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17. Diagnostics
• Sputum Culture
– Disadvantages
• samples must be processed immediately
– delays reduce isolation rates of the organism
– high false positive rates (carrier)
– low sensitivity and specificity
• normally 48 hours for positive identification
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18. Diagnostics
• Sputum Culture
– Disadvantages
• expensive
– technician time
– equipment
– experienced personnel are needed to perform and
interpret results
• Difficult to identify infecting organism
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19. Diagnostics
• Sputum Gram Stain
– Advantages
• inexpensive reagents and supplies
• non-invasive for the patient
• rapid test time
– Disadvantages
• requires sample from lower respiratory tract;
difficult to obtain
• samples must be processed immediately
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20. Diagnostics
• Sputum Gram Stain
– Disadvantages
• high false positive rate
• low sensitivity and specificity; large numbers of
organisms must be present
• does not allow for drug susceptibility testing
• requires experienced personnel
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21. Diagnostics
• PCR / DFA
– Advantages
• same day results
• specificity
– Disadvantages
• requires sample from lower respiratory tract;
difficult to obtain
• expensive - equipment, skilled technician
• sensitivity
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22. Diagnostics
• NOW® ICT Urinary Antigen
– Technology
• detects antigen, which is a common component of
the cell wall within the species
– S. pneumoniae - C-polysaccharide antigen, common to
all serotypes within the species
– Legionella - lipopolysaccharide portion of the serogroup
1 cell wall
• rabbit anti-species antibody as capture component
• rabbit anti-species antibody conjugated to colloidal
gold as detection component
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23. Technology
• Absorbent
• Control Line--Goat
anti-rabbit IgG
• Sample Line--Rabbit
anti-S. pneumoniae
antibody
• Conjugate Pad
• Sample Pad
( patent No. 91/214051).
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24. Intellectual Property
• 12 Issued Patents
– 4 ICT platform
– 7 Magnetic particles
– 1 Meningitis test
• 11 Patents Applied For
– respiratory, meningitis, and bacteria screen area
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25. Diagnostics
• NOW® ICT Urinary Antigen
– Advantages
• rapid results - 15 minutes
• non-invasive sample - urine
• easy test to run and interpret results
• accurate
– Limitations
• Susceptibility cannot be performed
• Single bacteria test
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28. Diagnostics
Comparison of Streptococcus pneumoniae Test Methods
Methods Sample Type Sensitivity Specificity Time
1 1
Binax NOW® Urine 86% 94% 15 mins
PCR Blood 52% 100% 4 hrs
2
Blood Culture Blood 10-30% >95% 48 hrs
Sputum Culture Sputum 50-60% 50-80% 48 hrs
Sputum Gram Stain Sputum 50-60% 50-80% 15 mins
1-Retrospective study data -- blood culture used as reference method.
2-Numbers reflect percent of pneumonia patient population estimated to be bacteremic.
Note: Sensitivity and specificity data on blood culture, sputum culture, and sputum Gram stain taken from various
published studies. References available upon request.
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29. Positioning
• NOW® ICT Features
– Easy to run
– Rapid test - only 15 minute tests for
S. pneumoniae and Legionella available
– Uses non-invasive sample
– No special equipment needed
– Easy to interpret resul
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30. – Accurate results
– U.S. FDA cleared products
– Multiple applications for S. pneumoniae
test - pneumonia, CSF and otitis media
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31. NOW® ICT S. pneumoniae
additional applications
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32. CSF application
• Anti-microbial therapy often initiated empirically because
causative agent not identified in advance
• Sensitivity of CSF gram staining is 75% - decreases to 50% in
patients given anti-microbial therapy
• Latex bacterial antigen assays have low sensitivity in CSF
• Streptococcus pneumoniae is typically the second most
common causative agent of community-acquired acute
bacterial meningitis
• Increasing rates of pneumococcal resistance to penicillin and
third generation cephalosporins
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33. CSF application
• NOW® ICT S. pneumoniae test
– 100% sensitivity and specificity with CSF sample
– published studies
• New Rapid Antigen Test for Diagnosis of Pneumococcal
Meningitis.
Marcos et al, The Lancet 357: 1499-1500, 2001.
• Using the NOW test in Cerebrospinal Fluid for the Rapid
Diagnosis of Pneumococcal meningitis.
Samrai et al, ASM: 114, 2001.
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34. CSF application
• NOW® ICT S. pneumoniae test
– additional application to support bringing the test into a
hospital lab
– only accurate rapid test for detection of a critical
pathogen for bacterial meningitis
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35. Otitis Media application
• NOW® ICT S. pneumoniae test
– Rapid Detection of S. pneumoniae in the Airways of Children
with Acute Otitis Media.
Faden et al, ASM: 113, 2001.
• Sensitivity – 90.0% (18/20) versus culture positive
nasopharangeal samples
• Specificity – 86.9% (21/23) versus culture negative
nasopharangeal samples
– one of three leading causes of otitis media
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36. Reference
• Published Studies - S. pneumoniae
– Evaluation of a Rapid Immunochromatographic Test for the
Detection of Streptococcus pneumoniae Antigen in Urine
Samples from Adults with Community-Acquired Pneumonia
Murdoch et al, ASM: 112, 2001
– Detection of Streptococcus pneumoniae Antigen by a Rapid
Immunochromatographic Assay in Urine Specimens
Dominguez et al: Chest, 119: 243-249, 2001
– Diagnostic Utility of a Rapid Urine Pneumococcal Antigen
Assay
Neuman et al, 2001 Pediatric Academic Societies Meeting
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37. • Published Studies - S. pneumoniae
– Evaluation of Binax NOW®, an Assay for the Detection of
Pneumococcal Antigen in Urine Samples, Performed among
Pediatric Patients
Dowell et al, Clinical Infectious Diseases, 32: 2001
– New Rapid Test for Detecting S. pneumoniae in Lower
Respiratory Tract Infections
Lienhard et al, Clinical Microbiology and Infection 7: 101
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38. Detection of Streptococcus pneumoniae Antigen by a
Rapid Immunochromatogrphic Assay in Urine Samples
CHEST, 119: 243-249, 2001
J.Dominguez et al
♦ Conclusions
(1) Now® S. pneumoniae test is sensitive and specific
(2) Now® S. pneumoniae test is a valuable tool for diagnosing
pneumococcal pneumonia cases, especially nonbacteremic cases,
which are often not diagnosed.
(3) Blood culture is only useful in approximately 25% of
pneumococcal pneumonia cases (i.e. that is the percent of the
population that is bacteremic).
(4) Sputum cultures only provide a probable diagnosis due to
difficulties associated with methodology (obtaining reliable
samples, etc.) and samples for culture are rarely taken
invasively due to concerns with the techniques that must be used.
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39. Evaluation of a Rapid Immunochromatographic Test
for the Detection of Streptococcus pneumoniae Antigen
in Urine Samples from Adults with Community-
Acquired Pneumonia
ASM: 112, 2001
Murdoch et al,
The authors conclude :
“ The Now® S. pneumoniae antigen test is a useful
adjunct to culture for determining the etiology of
community-acquired pneumonia in adults.”
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