Exploring the nasopharyngeal microbiota composition in infants with whooping cough: A test-negative case-control study.

Muntsa Rocafort,Desiree Henares,Pere Godoy,Carmen Muñoz-Almagro,Irene Barrabeig,Pedro Brotons,Marta Valenciano,Angela Domínguez,Cristian Launes,Lore Merdrignac,Daniela Flavia Hozbor

doi:10.1371/journal.pone.0259318

Abstract

PurposeThe purpose of this study was to characterize the nasopharyngeal microbiota of infants with possible and confirmed pertussis compared to healthy controls.MethodsThis prospective study included all infants <1 year with microbiologically confirmed diagnosis of pertussis attended at a University Hospital over a 12-month period. For each confirmed case, up to 2 consecutive patients within the same age range and meeting the clinical case definition of pertussis but testing PCR-negative were included as possible cases. A third group of asymptomatic infants (healthy controls) were also included. Nasopharyngeal microbiota was characterized by sequencing the V3-V4 region of the 16S rRNA gene. Common respiratory DNA/RNA viral co-infection was tested by multiplex PCR.ResultsTwelve confirmed cases, 21 possible cases and 9 healthy controls were included. Confirmed whooping cough was primarily driven by detection of Bordetella with no other major changes on nasopharyngeal microbiota. Possible cases had limited abundance or absence of Bordetella and a distinctive microbiota with lower bacterial richness and diversity and higher rates of viral co-infection than both confirmed cases and healthy controls. Bordetella reads determined by 16S rRNA gene sequencing were found in all 12 confirmed cases (100%), 3 out of the 21 possible cases (14.3%) but in any healthy control.ConclusionThis study supports the usefulness of 16S rRNA gene sequencing for improved sensitivity on pertussis diagnosis compared to real-time PCR and to understand other microbial changes occurring in the nasopharynx in children <1 year old with suspected whooping cough compared to healthy controls.

Highlights

Whooping cough, known as pertussis, is a highly transmissible acute respiratory infection mainly caused by the bacterium Bordetella pertussis
This study supports the usefulness of 16S rRNA gene sequencing for improved sensitivity on pertussis diagnosis compared to real-time polymerase chain-reaction (PCR) and to understand other microbial
Proportion of infants with their mother vaccinated with B. pertussis was 41.7% among confirmed cases and 95.2% among possible cases (p-value = 0.0002)

Summary

Introduction

Known as pertussis, is a highly transmissible acute respiratory infection mainly caused by the bacterium Bordetella pertussis. Other Bordetella species such as B. parapertussis, B. holmesii and B. bronchiseptica have been associated with pertussis-like illness [1]. Despite initial symptomatology resembles that of a common cold, whooping-cough characteristic manifestations usually appear after 10 to 15 days [2]. Pertussis affects all population ages, but while adolescents and adults usually develop mild symptoms, the disease can be especially life-threatening in unvaccinated and incompletely vaccinated young infants (

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