Volume 94, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Prior antibiotic use, contamination, limited blood volume, and processing delays reduce yield of blood cultures for detection of . We performed immunochromatographic testing (ICT) on broth from incubated blood culture bottles and real-time polymerase chain reaction (PCR) on broth and whole blood and compared findings to blood culture in patients with suspected bacteremia. We selected 383 patients in Mali and 586 patients in Thailand based on their blood culture results: 75 and 31 were positive for pneumococcus, 100 and 162 were positive for other pathogens, and 208 and 403 were blood culture negative, respectively. ICT and PCR of blood culture broth were at least 87% sensitive and 97% specific compared with blood culture; whole blood PCR was 75–88% sensitive and 96–100% specific. Pneumococcal yields in children < 5 years of age increased from 2.9% to 10.7% in Mali with > 99% of additional cases detected by whole blood PCR, and from 0.07% to 5.1% in Thailand with two-thirds of additional cases identified by ICT. Compared with blood culture, ICT and PCR on cultured broth were highly sensitive and specific but their ability to improve pneumococcal identification varied by site. Further studies of these tools are needed before widespread implementation.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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  1. Rudan I, Boschi-Pinto C, Biloglav Z, Mulholland K, Campbell H, , 2008. Epidemiology and etiology of childhood pneumonia. Bull World Health Organ 86: 408416.[Crossref] [Google Scholar]
  2. Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, Jha P, Campbell H, Walker CF, Cibulskis R, Eisele T, Liu L, Mathers C, , 2010. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet 375: 19691987.[Crossref] [Google Scholar]
  3. Hansen J, Black S, Shinefield H, Cherian T, Benson J, Fireman B, Lewis E, Ray P, Lee J, , 2006. Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than 5 years of age for prevention of pneumonia: updated analysis using World Health Organization standardized interpretation of chest radiographs. Pediatr Infect Dis J 25: 779781.[Crossref] [Google Scholar]
  4. Klugman KP, Madhi SA, Huebner RE, Kohberger R, Mbelle N, Pierce N, , 2003. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. N Engl J Med 349: 13411348.[Crossref] [Google Scholar]
  5. Cutts FT, Zaman SM, Enwere G, Jaffar S, Levine OS, Okoko JB, Oluwalana C, Vaughan A, Obaro SK, Leach A, McAdam KP, Biney E, Saaka M, Onwuchekwa U, Yallop F, Pierce NF, Greenwood BM, Adegbola RA, , 2005. Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial. Lancet 365: 11391146.[Crossref] [Google Scholar]
  6. Vuori E, Peltola H, Kallio MJ, Leinonen M, Hedman K, , 1998. Etiology of pneumonia and other common childhood infections requiring hospitalization and parenteral antimicrobial therapy. SE-TU Study Group. Clin Infect Dis 27: 566572.[Crossref] [Google Scholar]
  7. Forgie IM, O'Neill KP, Lloyd-Evans N, Leinonen M, Campbell H, Whittle HC, Greenwood BM, , 1991. Etiology of acute lower respiratory tract infections in Gambian children: II. Acute lower respiratory tract infection in children ages one to nine years presenting at the hospital. Pediatr Infect Dis J 10: 4247.[Crossref] [Google Scholar]
  8. Forgie IM, O'Neill KP, Lloyd-Evans N, Leinonen M, Campbell H, Whittle HC, Greenwood BM, , 1991. Etiology of acute lower respiratory tract infections in Gambian children: I. Acute lower respiratory tract infections in infants presenting at the hospital. Pediatr Infect Dis J 10: 3341.[Crossref] [Google Scholar]
  9. Isaacman DJ, Karasic RB, Reynolds EA, Kost SI, , 1996. Effect of number of blood cultures and volume of blood on detection of bacteremia in children. J Pediatr 128: 190195.[Crossref] [Google Scholar]
  10. Mtunthama N, Gordon SB, Kusimbwe T, Zijlstra EE, Molyneux ME, French N, , 2008. Blood culture collection technique and pneumococcal surveillance in Malawi during the four year period 2003–2006: an observational study. BMC Infect Dis 8: 137.[Crossref] [Google Scholar]
  11. Rhodes J, Hyder JA, Peruski LF, Fisher C, Jorakate P, Kaewpan A, Dejsirilert S, Thamthitiwat S, Olsen SJ, Dowell SF, Chantra S, Tanwisaid K, Maloney SA, Baggett HC, , 2010. Antibiotic use in Thailand: quantifying impact on blood culture yield and estimates of pneumococcal bacteremia incidence. Am J Trop Med Hyg 83: 301306.[Crossref] [Google Scholar]
  12. Madhi SA, Kuwanda L, Cutland C, Klugman KP, , 2005. The impact of a 9-valent pneumococcal conjugate vaccine on the public health burden of pneumonia in HIV-infected and -uninfected children. Clin Infect Dis 40: 15111518.[Crossref] [Google Scholar]
  13. 2005. Binax NOW Streptococcus pneumoniae Package Insert. Portland, ME: Binax. [Google Scholar]
  14. Faden H, Heimerl M, Varma C, Goodman G, Winkelstein P, , 2002. Urinary excretion of pneumococcal cell wall polysaccharide in children. Pediatr Infect Dis J 21: 791793.[Crossref] [Google Scholar]
  15. Adegbola RA, Obaro SK, Biney E, Greenwood BM, , 2001. Evaluation of Binax NOW Streptococcus pneumoniae urinary antigen test in children in a community with a high carriage rate of pneumococcus. Pediatr Infect Dis J 20: 718719.[Crossref] [Google Scholar]
  16. Dowell SF, Garman RL, Liu G, Levine OS, Yang YH, , 2001. Evaluation of Binax NOW, an assay for the detection of pneumococcal antigen in urine samples, performed among pediatric patients. Clin Infect Dis 32: 824825.[Crossref] [Google Scholar]
  17. Hamer DH, Egas J, Estrella B, MacLeod WB, Griffiths JK, Sempertegui F, , 2002. Assessment of the Binax NOW Streptococcus pneumoniae urinary antigen test in children with nasopharyngeal pneumococcal carriage. Clin Infect Dis 34: 10251028.[Crossref] [Google Scholar]
  18. Esposito S, Bosis S, Colombo R, Carlucci P, Faelli N, Fossali E, Principi N, , 2004. Evaluation of rapid assay for detection of Streptococcus pneumoniae urinary antigen among infants and young children with possible invasive pneumococcal disease. Pediatr Infect Dis J 23: 365367.[Crossref] [Google Scholar]
  19. Dominguez J, Blanco S, Rodrigo C, Azuara M, Gali N, Mainou A, Esteve A, Castellvi A, Prat C, Matas L, Ausina V, , 2003. Usefulness of urinary antigen detection by an immunochromatographic test for diagnosis of pneumococcal pneumonia in children. J Clin Microbiol 41: 21612163.[Crossref] [Google Scholar]
  20. Samra Z, Shmuely H, Nahum E, Paghis D, Ben Ari J, , 2003. Use of the NOW Streptococcus pneumoniae urinary antigen test in cerebrospinal fluid for rapid diagnosis of pneumococcal meningitis. Diagn Microbiol Infect Dis 45: 237240.[Crossref] [Google Scholar]
  21. Diez-Domingo J, Cantarino MV, Torrenti JM, Sansano MI, Rosich AJ, Merino AH, de Miguel AG, Gonzalez JB, Marcos MD, , 2010. A randomized, multicenter, open-label clinical trial to assess the immunogenicity of a meningococcal C vaccine booster dose administered to children aged 14 to 18 months. Pediatr Infect Dis J 29: 148152.[Crossref] [Google Scholar]
  22. Saha SK, Darmstadt GL, Yamanaka N, Billal DS, Nasreen T, Islam M, Hamer DH, , 2005. Rapid diagnosis of pneumococcal meningitis: implications for treatment and measuring disease burden. Pediatr Infect Dis J 24: 10931098.[Crossref] [Google Scholar]
  23. Moisi JC, Saha SK, Falade AG, Njanpop-Lafourcade BM, Oundo J, Zaidi AK, Afroj S, Bakare RA, Buss JK, Lasi R, Mueller J, Odekanmi AA, Sangare L, Scott JA, Knoll MD, Levine OS, Gessner BD, , 2009. Enhanced diagnosis of pneumococcal meningitis with use of the Binax NOW immunochromatographic test of Streptococcus pneumoniae antigen: a multisite study. Clin Infect Dis 48 (Suppl 2): S49S56.[Crossref] [Google Scholar]
  24. Petti CA, Woods CW, Reller LB, , 2005. Streptococcus pneumoniae antigen test using positive blood culture bottles as an alternative method to diagnose pneumococcal bacteremia. J Clin Microbiol 43: 25102512.[Crossref] [Google Scholar]
  25. Baggett HC, Rhodes J, Dejsirilert S, Salika P, Wansom T, Jorakate P, Kaewpan A, Olsen SJ, Maloney SA, Peruski LF, , 2012. Pneumococcal antigen testing of blood culture broth to enhance the detection of Streptococcus pneumoniae bacteremia. Eur J Clin Microbiol Infect Dis 31: 753756.[Crossref] [Google Scholar]
  26. Saha S, Darmstadt G, Naheed A, Arifeen S, Islam M, Fatima K, Breiman R, Sack D, Hamer D, , 2011. Improving the sensitivity of blood culture for Streptococcus pneumoniae . J Trop Pediatr 57: 192196.[Crossref] [Google Scholar]
  27. Zhang Y, Isaacman DJ, Wadowsky RM, Rydquist-White J, Post JC, Ehrlich GD, , 1995. Detection of Streptococcus pneumoniae in whole blood by PCR. J Clin Microbiol 33: 596601. [Google Scholar]
  28. Carvalho MG, Tondella ML, McCaustland K, Weidlich L, McGee L, Mayer LW, Steigerwalt A, Whaley M, Facklam RR, Fields B, Carlone G, Ades EW, Dagan R, Sampson JS, , 2007. Evaluation and improvement of real-time PCR assays targeting lytA, ply, and psaA genes for detection of pneumococcal DNA. J Clin Microbiol 45: 24602466.[Crossref] [Google Scholar]
  29. Kee C, Palladino S, Kay I, Pryce TM, Murray R, Rello J, Gallego M, Lujan M, Munoz-Almagro C, Waterer GW, , 2008. Feasibility of real-time polymerase chain reaction in whole blood to identify Streptococcus pneumoniae in patients with community-acquired pneumonia. Diagn Microbiol Infect Dis 61: 7275.[Crossref] [Google Scholar]
  30. Rello J, Lisboa T, Lujan M, Gallego M, Kee C, Kay I, Lopez D, Waterer GW, , 2009. Severity of pneumococcal pneumonia associated with genomic bacterial load. Chest 136: 832840.[Crossref] [Google Scholar]
  31. Peters RP, de Boer RF, Schuurman T, Gierveld S, Kooistra-Smid M, van Agtmael MA, Vandenbroucke-Grauls CM, Persoons MC, Savelkoul PH, , 2009. Streptococcus pneumoniae DNA load in blood as marker of infection in patients with community-acquired pneumonia. J Clin Microbiol 47: 33083312.[Crossref] [Google Scholar]
  32. Pai R, Gertz RE, Beall B, , 2006. Sequential multiplex PCR approach for determining capsular serotypes of Streptococcus pneumoniae isolates. J Clin Microbiol 44: 124131.[Crossref] [Google Scholar]
  33. Morais L, Carvalho MG, Roca A, Flannery B, Mandomando I, Soriano-Gabarro M, Sigauque B, Alonso P, Beall B, , 2007. Sequential multiplex PCR for identifying pneumococcal capsular serotypes from south-Saharan African clinical isolates. J Med Microbiol 56: 11811184.[Crossref] [Google Scholar]
  34. Azzari C, Moriondo M, Indolfi G, Massai C, Becciolini L, de Martino M, Resti M, , 2008. Molecular detection methods and serotyping performed directly on clinical samples improve diagnostic sensitivity and reveal increased incidence of invasive disease by Streptococcus pneumoniae in Italian children. J Med Microbiol 57: 12051212.[Crossref] [Google Scholar]
  35. Resti M, Moriondo M, Cortimiglia M, Indolfi G, Canessa C, Becciolini L, Bartolini E, de Benedictis FM, de Martino M, Azzari C, , 2010. Community-acquired bacteremic pneumococcal pneumonia in children: diagnosis and serotyping by real-time polymerase chain reaction using blood samples. Clin Infect Dis 51: 10421049.[Crossref] [Google Scholar]
  36. Azzari C, Cortimiglia M, Moriondo M, Canessa C, Lippi F, Ghiori F, Becciolini L, de Martino M, Resti M, , 2011. Pneumococcal DNA is not detectable in the blood of healthy carrier children by real-time PCR targeting the lytA gene. J Med Microbiol 60: 710714.[Crossref] [Google Scholar]
  37. Rouphael N, Steyn S, Bangert M, Sampson JS, Adrian P, Madhi SA, Klugman KP, Ades EW, , 2011. Use of 2 pneumococcal common protein real-time polymerase chain reaction assays in healthy children colonized with Streptococcus pneumoniae . Diagn Microbiol Infect Dis 70: 452454.[Crossref] [Google Scholar]
  38. Pimenta FC, Roundtree A, Soysal A, Bakir M, du Plessis M, Wolter N, von Gottberg A, McGee L, Carvalho M da G, Beall B, , 2013. Sequential triplex real-time PCR assay for detecting 21 pneumococcal capsular serotypes that account for a high global disease burden. J Clin Microbiol 51: 647652.[Crossref] [Google Scholar]
  39. da Gloria Carvalho M, Pimenta FC, Jackson D, Roundtree A, Ahmad Y, Millar EV, O'Brien KL, Whitney CG, Cohen AL, Beall BW, , 2010. Revisiting pneumococcal carriage by use of broth enrichment and PCR techniques for enhanced detection of carriage and serotypes. J Clin Microbiol 48: 16111618.[Crossref] [Google Scholar]

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  • Received : 12 Jun 2015
  • Accepted : 18 Sep 2015
  • Published online : 03 Feb 2016

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