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Composition of Populations and Durations of Persistence of Bordetella pertussis Bacteria in Patients with Whooping Cough and Contact Persons

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Abstract

Whooping cough still occupies a leading position in the group of controlled infectious diseases, despite worldwide mass vaccination. In recent decades, there has been a significant increase in the incidence of whooping cough and the spread of atypical forms among adolescents and adults. It has been proposed that the formation of an anthropogenic source of infection evolves due to Bordetella pertussis bacteria with reduced or completely lost virulence that are capable of long-term persistence in the human body and restoration of infectivity under certain conditions. The persistence mechanisms of the causative agent of whooping cough have not yet been studied completely. We hypothesize that one of the mechanisms may be a change of the bvgAS operon, which regulates the expression of all virulence genes of B. pertussis bacteria because of the integration of IS-elements. Mobile IS-elements are known to have the ability to both embed into the host genome sites and be cut out of them with the restoration of impaired functions. The purpose of this study was to evaluate the duration of persistence and to analyze the population composition of B. pertussis bacteria in children with whooping cough and contact persons in family foci. In this study, 80 children with confirmed diagnosis of pertussis and 116 people from 59 family foci of pertussis in contact with those children were examined. Patients were included in the study after they signed an informed consent. To detect B. pertussis DNA in nasopharyngeal swabs and to register IS-element integrations, the PCR-RT-IS test-system developed at the Gamaleya Research Institute was used along with nested PCR and sequencing. It has been shown to be possible to detect the causative agent of whooping cough in patients at different stages of the disease and in family members who have been in contact with patients for a long period. It has been found that, in the period of convalescence from whooping cough, the formation of insertional avirulent mutants of B. pertussis in the upper respiratory tract, which are capable of long-term persistence in the human body, is observed in 25% of patients. The appearance of avirulent mutants has been registered at a lower frequency (15%) in contact persons from family foci. The long-term detection of the causative agent of whooping cough and the registration of B. pertussis bvg-mutants containing the integration of IS-elements in bacterial carriers confirm the hypothesis that bacterial transition to persistence because of the insertional inactivation of bvgAS operon is possible. Identifying persistent B. pertussis bacteria and studying the mechanisms of their formation is important for creating new vaccination strategies and improvement of pertussis vaccines.

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Authors and Affiliations

  1. Gamaleya National Research Center of Epidemiology and Microbiology, 123098, Moscow, Russia

    A. Yu. Medkova, E. G. Semin, S. V. Kulikov, L. N. Sinyashina & G. I. Karataev

  2. Pediatric Research and Clinical Center for Infectious Diseases, 197022, St. Petersburg, Russia

    Yu. V. Nesterova & I. V. Babachenko

Authors
  1. A. Yu. Medkova
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  2. E. G. Semin
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  3. S. V. Kulikov
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  4. Yu. V. Nesterova
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  5. I. V. Babachenko
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  6. L. N. Sinyashina
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  7. G. I. Karataev
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Correspondence to A. Yu. Medkova.

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This article does not contain any studies involving animals performed by any of the authors.

Statement of Compliance with Standards of Research Involving Humans as Subjects

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.

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Translated by E. Larina

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Medkova, A.Y., Semin, E.G., Kulikov, S.V. et al. Composition of Populations and Durations of Persistence of Bordetella pertussis Bacteria in Patients with Whooping Cough and Contact Persons. Mol. Genet. Microbiol. Virol. 38, 61–69 (2023). https://doi.org/10.3103/S0891416823020064

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