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Missed pertussis diagnosis during co-infection with Bordetella holmesii

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Abstract

The purpose of this study is to identify predictive factors associated with missed diagnosis of B. pertussis–B. holmesii co-infection by assessing the analytical performance of a commercially available multiplexed PCR assay and by building a prediction model based on clinical signs and symptoms for detecting co-infections. This is a retrospective study on the electronic health records of all clinical samples that tested positive to either B. pertussis or B. holmesii from January 2015 to January 2018 at Geneva University Hospitals. Multivariate logistic regression was used to build a model for co-infection prediction based on the electronic health record chart review. Limit of detection was determined for all targets of the commercial multiplexed PCR assay used on respiratory samples. A regression model, developed from clinical symptoms and signs, predicted B. pertussis and B. holmesii co-infection with an accuracy of 82.9% (95% CI 67.9–92.8%, p value = .012), for respiratory samples positive with any of the two tested Bordetella species. We found that the LOD of the PCR reaction targeting ptxS1 is higher than that reported by the manufacturer by a factor 10. The current testing strategy misses B. pertussis and B. holmesii co-infections by reporting only B. holmesii infections. Thus, we advocate to perform serological testing for detecting a response against pertussis toxin whenever a sample is found positive for B. holmesii. These findings are important, both from a clinical and epidemiological point of view, as the former impacts the choice of antimicrobial drugs and the latter biases surveillance data, by underestimating B. pertussis infections during co-infections.

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Data availability

The datasets generated and analyzed during the current study are not publicly available due to confidentiality issues but are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to acknowledge Pre Claire-Anne Siegrist and the Laboratory of Vaccinology of the Geneva University Hospitals for their help in diagnosing the case of Bordetella co-infection that led to our study.

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Authors and Affiliations

  1. Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland

    Mikaël de Lorenzi-Tognon & Jacques Schrenzel

  2. Bacteriology Laboratory, Division of Laboratory Medicine, Department of Diagnostics, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1211, Geneva 14, Switzerland

    Mikaël de Lorenzi-Tognon, Gesuele Renzi & Jacques Schrenzel

  3. Genomic Research Laboratory, Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Yannick Charretier & Jacques Schrenzel

  4. Division of General Medicine, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland

    Anne Iten, Catherine Hafner & Sarah Rosset-Zufferey

  5. Service of Vaccinology, Faculty of Medicine, Geneva, Switzerland

    Barbara Lemaitre

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  1. Mikaël de Lorenzi-Tognon
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  2. Yannick Charretier
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  3. Anne Iten
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  4. Catherine Hafner
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  5. Sarah Rosset-Zufferey
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  7. Gesuele Renzi
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  8. Jacques Schrenzel
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Contributions

All authors contributed to the study conception and design. Material preparation and data collection were performed by Yannick Charretier, Catherine Hafner, Sarah Rosset-Zufferey, Barbara Lemaitre, Gesuele Renzi, Mikaël de Lorenzi-Tognon, and Jacques Schrenzel. Data analyses were performed by Mikaël de Lorenzi-Tognon. The first draft of the manuscript was written by Mikaël de Lorenzi-Tognon and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mikaël de Lorenzi-Tognon.

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Ethics approval and consent to participate

The project was approved by the Geneva Ethical Committee and registered as study n°2020–02072 and a consent was waived due to the retrospective aspect of the study.

Competing interests

The authors declare no competing interests.

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de Lorenzi-Tognon, M., Charretier, Y., Iten, A. et al. Missed pertussis diagnosis during co-infection with Bordetella holmesii. Eur J Clin Microbiol Infect Dis 41, 1227–1235 (2022). https://doi.org/10.1007/s10096-022-04488-3

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