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Detection of antibody responses against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis proteins in children with community-acquired pneumonia: effects of combining pneumococcal antigens, pre-existing antibody levels, sampling interval, age, and duration of illness

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Abstract

We evaluated the effects of combining different numbers of pneumococcal antigens, pre-existing antibody levels, sampling interval, age, and duration of illness on the detection of IgG responses against eight Streptococcus pneumoniae proteins, three Haemophilus influenzae proteins, and five Moraxella catarrhalis proteins in 690 children aged <5 years with pneumonia. Serological tests were performed on acute and convalescent serum samples with a multiplexed bead-based immunoassay. The median sampling interval was 19 days, the median age was 26.7 months, and the median duration of illness was 5 days. The rate of antibody responses was 15.4 % for at least one pneumococcal antigen, 5.8 % for H. influenzae, and 2.3 % for M. catarrhalis. The rate of antibody responses against each pneumococcal antigen varied from 3.5 to 7.1 %. By multivariate analysis, pre-existing antibody levels showed a negative association with the detection of antibody responses against pneumococcal and H. influenzae antigens; the sampling interval was positively associated with the detection of antibody responses against pneumococcal and H. influenzae antigens. A sampling interval of 3 weeks was the optimal cut-off for the detection of antibody responses against pneumococcal and H. influenzae proteins. Duration of illness was negatively associated with antibody responses against PspA. Age did not influence antibody responses against the investigated antigens. In conclusion, serological assays using combinations of different pneumococcal proteins detect a higher rate of antibody responses against S. pneumoniae compared to assays using a single pneumococcal protein. Pre-existing antibody levels and sampling interval influence the detection of antibody responses against pneumococcal and H. influenzae proteins. These factors should be considered when determining pneumonia etiology by serological methods in children.

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Acknowledgments

We thank Sanofi Pasteur (Lyon, France) for supplying PcpA and PhtD; Prof. Elaine Tuomanen at St. Jude Children’s Research Hospital (Memphis, TN, USA) for supplying Ply, CbpA, PspA 1; Profs. Susan Hollingshead, David Briles, and Pat Coan at University of Alabama (Birmingham, AL, USA) for supplying PspA 2; and Valneva Austria GmbH (Vienna, Austria) for supplying SP1732-3, SP2216-1, NTHi Protein D, NTHi0371-1, NTHi0830, MC Omp CD, MC_RH4_2506, MC_RH4_1701, MC_RH4_3729-1, and MC_RH4_4730. We also thank Camilla Virta and Leena Saarinen for their help in the laboratory and thank Ângela G. Vasconcellos, MD, PhD student, for her technical assistance with the ROC curve analysis.

This work was supported by: Bahia State Agency for Research Funding (FAPESB), Brazil; Brazilian Council for Scientific and Technological Development (CNPq), Brazil; and, in part, by National Institute for Health and Welfare, Finland. Profs. Aldina Barral, Maria Regina A. Cardoso, and Cristiana M. Nascimento-Carvalho are investigators at CNPq.

Conflict of interest

Andreas Meinke is an employee of Valneva Austria GmbH.

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Authors and Affiliations

  1. Postgraduate Programme in Health Sciences, Federal University of Bahia School of Medicine, Praça XV de Novembro, s/n - Largo do Terreiro de Jesus, Salvador, Bahia, 40025-010, Brazil

    I. C. Borges, D. C. Andrade, A.-L. Vilas-Boas, A. Barral & C. M. Nascimento-Carvalho

  2. Department of Paediatrics, Federal University of Bahia School of Medicine, Salvador, Bahia, Brazil

    M.-S. H. Fontoura & C. M. Nascimento-Carvalho

  3. National Institute for Health and Welfare, Helsinki, Finland

    H. Laitinen, N. Ekström & H. Käyhty

  4. DST/NRF Vaccine Preventable Diseases, MRC Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa

    P. V. Adrian

  5. Valneva Austria GmbH, Campus Vienna Biocenter 3, Vienna, Austria

    A. Meinke

  6. Department of Epidemiology, University of São Paulo School of Public Health, São Paulo, Brazil

    M.-R. A. Cardoso

  7. Department of Pathology, Federal University of Bahia School of Medicine and Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil

    A. Barral

  8. Department of Paediatrics, Turku University and University Hospital, Turku, Finland

    O. Ruuskanen

Authors
  1. I. C. Borges
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  2. D. C. Andrade
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  3. A.-L. Vilas-Boas
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  4. M.-S. H. Fontoura
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  5. H. Laitinen
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  6. N. Ekström
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  7. P. V. Adrian
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  8. A. Meinke
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  9. M.-R. A. Cardoso
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  10. A. Barral
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  11. O. Ruuskanen
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  12. H. Käyhty
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  13. C. M. Nascimento-Carvalho
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Corresponding author

Correspondence to I. C. Borges.

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Borges, I.C., Andrade, D.C., Vilas-Boas, AL. et al. Detection of antibody responses against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis proteins in children with community-acquired pneumonia: effects of combining pneumococcal antigens, pre-existing antibody levels, sampling interval, age, and duration of illness. Eur J Clin Microbiol Infect Dis 34, 1551–1557 (2015). https://doi.org/10.1007/s10096-015-2385-y

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  • DOI: https://doi.org/10.1007/s10096-015-2385-y

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