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Comparative Study
. 2021 Sep 1;224(12 Suppl 2):S209-S217.
doi: 10.1093/infdis/jiab073.

Comparison of Culture, Antigen Test, and Polymerase Chain Reaction for Pneumococcal Detection in Cerebrospinal Fluid of Children

Md Hasanuzzaman  1   2 , Senjuti Saha  1 , Roly Malaker  1 , Hafizur Rahman  1 , Mohammad S I Sajib  1 , Rajib C Das  1 , Maksuda Islam  1 , Davidson H Hamer  3   4   5 , Gary L Darmstadt  6 , Samir K Saha  1   7   8
Affiliations
Comparative Study

Comparison of Culture, Antigen Test, and Polymerase Chain Reaction for Pneumococcal Detection in Cerebrospinal Fluid of Children

Md Hasanuzzaman et al. J Infect Dis. .

Abstract

Background: Sensitivity of culture for the detection of Streptococcus pneumoniae is limited by prior antibiotic exposure. Immunochromatographic test (ICT) is highly sensitive and specific for pneumococcal antigen detection in the cerebrospinal fluid (CSF) of meningitis cases. We determined the specificity and sensitivity of culture, ICT, and polymerase chain reaction (PCR) and the effect of antibiotic exposure on their performance.

Methods: CSF specimens from suspected meningitis cases admitted to Dhaka Shishu Hospital, Bangladesh, were tested using culture, ICT and PCR. Additionally, 165 specimens collected from 69 pneumococcal cases after antibiotic treatment were tested.

Results: Of 1883 specimens tested, culture detected 9, quantitative PCR (qPCR) detected 184, and ICT detected 207 pneumococcal cases (including all culture and qPCR positives). In comparison to ICT, sensitivity of culture was 4.4% and of qPCR was 90.6%; both were 100% specific. After antibiotic exposure, culture sensitivity plummeted rapidly; conventional PCR and qPCR sensitivity disappeared after day 6 and 20, respectively. ICT detected pneumococcal antigen for >10 weeks.

Conclusions: While culture provides the most information about bacterial characteristics, in high antibiotic exposure settings, ICT exhibits maximum sensitivity. We recommend culture and ICT as mainstay for pneumococcal diagnosis and surveillance; qPCR can generate additional molecular data where possible.

Keywords: ICT; antibiotic exposure; diagnostic; meningitis; pneumococcal vaccine; pneumococcus; surveillance; vaccine preventable.

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Figures

Figure 1.
Figure 1.
Selection, characteristics, and pathogens detected in the cerebrospinal fluid samples used in the study. A, Flow diagram of the diagnostic tests used in the study and results attained. B, The total number of pneumococcus detected using each method. *These positives also include the 9 samples detected by culture. #The total of 1558 and 203 samples (1761) included in specificity and sensitivity calculations. Abbreviations: CSF, cerebrospinal fluid; Hi, Haemophilus influenzae; ICT, immunochromatographic test; Nmen, Neisseria meningitidis; QNS, quantity not sufficient; qPCR, quantitative polymerase chain reaction; Spn, Streptococcus pneumoniae.
Figure 2.
Figure 2.
Time of collection and mode of pneumococcal detection of the 165 longitudinal samples from 69 patients with confirmed pneumococcal meningitis. The exact start date of antibiotic treatment was known for patients 1–30. The start date was estimated for patients 31–69 using lytA cycle threshold value (see “Methods”). Abbreviations: cPCR, conventional polymerase chain reaction; ICT, immunochromatographic test; qPCR, quantitative polymerase chain reaction.
Figure 3.
Figure 3.
Sensitivity of culture, immunochromatographic test, cPCR, and qPCR for detection of pneumococcus after antibiotic treatment initiation. Abbreviations: cPCR, conventional polymerase chain reaction; ICT, immunochromatographic test; qPCR, quantitative polymerase chain reaction.
See this image and copyright information in PMC

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