Cargando…

Asymptomatic Bordetella pertussis infections in young African infants and their mothers identified within a longitudinal cohort

Despite long-standing vaccination programs, pertussis incidence has increased in numerous countries; transmission by asymptomatic individuals is a suspected driver of this resurgence. However, unequivocal evidence documenting asymptomatic infections in adults and children is lacking due, in part, to...

Descripción completa

Detalles Bibliográficos
Autores principales: Gill, CJ, Gunning, CE, MacLeod, W, Mwananyanda, L, Thea, D, Pieciak, R, Kwenda, G, Mupila, Z, Rohani, P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685339/
https://www.ncbi.nlm.nih.gov/pubmed/33236026
http://dx.doi.org/10.1101/2020.11.18.20231423
_version_ 1783613164903989248
author Gill, CJ
Gunning, CE
MacLeod, W
Mwananyanda, L
Thea, D
Pieciak, R
Kwenda, G
Mupila, Z
Rohani, P
author_facet Gill, CJ
Gunning, CE
MacLeod, W
Mwananyanda, L
Thea, D
Pieciak, R
Kwenda, G
Mupila, Z
Rohani, P
author_sort Gill, CJ
collection PubMed
description Despite long-standing vaccination programs, pertussis incidence has increased in numerous countries; transmission by asymptomatic individuals is a suspected driver of this resurgence. However, unequivocal evidence documenting asymptomatic infections in adults and children is lacking due, in part, to the cross-sectional nature of most pertussis surveillance studies. In addition, modern pertussis surveillance relies on quantitative PCR (qPCR) using fixed diagnostic thresholds to identify cases. To address this gap, we present a longitudinal analysis of 17,442 nasopharyngeal samples collected from a cohort of 1,320 Zambian mother/infant pairs. Using full-range cycle threshold (CT) values from IS481 qPCR assays, we document widespread asymptomatic infections among mothers and also, surprisingly, among young infants. From an initial group of eight symptomatic infants who tested positive by qPCR, we identify frequent contemporaneous subclinical infections in mothers. Within the full cohort, we observe strong temporal correlation between low- and high-intensity qPCR signals. We compute a single time-averaged score for each individual summarizing the evidence for pertussis infection (EFI), and show that EFI strongly clusters within mother/infant pairs, and is strongly associated with clinical symptomatology and antibiotic use. Overall, the burden of pertussis here is substantially underestimated when restricting diagnostic criteria to IS481 CT≤35. Rather, we find that full-range CT values provide valuable insights into pertussis epidemiology in this population, and illuminate the infection arc within individuals. These findings have significant implications for quantifying asymptomatic pertussis prevalence and its contribution to overall transmission. Our results also expose limitations of threshold-based interpretations of qPCR assays in infectious disease surveillance.
format Online
Article
Text
id pubmed-7685339
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Cold Spring Harbor Laboratory
record_format MEDLINE/PubMed
spelling pubmed-76853392020-11-25 Asymptomatic Bordetella pertussis infections in young African infants and their mothers identified within a longitudinal cohort Gill, CJ Gunning, CE MacLeod, W Mwananyanda, L Thea, D Pieciak, R Kwenda, G Mupila, Z Rohani, P medRxiv Article Despite long-standing vaccination programs, pertussis incidence has increased in numerous countries; transmission by asymptomatic individuals is a suspected driver of this resurgence. However, unequivocal evidence documenting asymptomatic infections in adults and children is lacking due, in part, to the cross-sectional nature of most pertussis surveillance studies. In addition, modern pertussis surveillance relies on quantitative PCR (qPCR) using fixed diagnostic thresholds to identify cases. To address this gap, we present a longitudinal analysis of 17,442 nasopharyngeal samples collected from a cohort of 1,320 Zambian mother/infant pairs. Using full-range cycle threshold (CT) values from IS481 qPCR assays, we document widespread asymptomatic infections among mothers and also, surprisingly, among young infants. From an initial group of eight symptomatic infants who tested positive by qPCR, we identify frequent contemporaneous subclinical infections in mothers. Within the full cohort, we observe strong temporal correlation between low- and high-intensity qPCR signals. We compute a single time-averaged score for each individual summarizing the evidence for pertussis infection (EFI), and show that EFI strongly clusters within mother/infant pairs, and is strongly associated with clinical symptomatology and antibiotic use. Overall, the burden of pertussis here is substantially underestimated when restricting diagnostic criteria to IS481 CT≤35. Rather, we find that full-range CT values provide valuable insights into pertussis epidemiology in this population, and illuminate the infection arc within individuals. These findings have significant implications for quantifying asymptomatic pertussis prevalence and its contribution to overall transmission. Our results also expose limitations of threshold-based interpretations of qPCR assays in infectious disease surveillance. Cold Spring Harbor Laboratory 2020-11-19 /pmc/articles/PMC7685339/ /pubmed/33236026 http://dx.doi.org/10.1101/2020.11.18.20231423 Text en https://creativecommons.org/licenses/by-nd/4.0/This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Gill, CJ
Gunning, CE
MacLeod, W
Mwananyanda, L
Thea, D
Pieciak, R
Kwenda, G
Mupila, Z
Rohani, P
Asymptomatic Bordetella pertussis infections in young African infants and their mothers identified within a longitudinal cohort
title Asymptomatic Bordetella pertussis infections in young African infants and their mothers identified within a longitudinal cohort
title_full Asymptomatic Bordetella pertussis infections in young African infants and their mothers identified within a longitudinal cohort
title_fullStr Asymptomatic Bordetella pertussis infections in young African infants and their mothers identified within a longitudinal cohort
title_full_unstemmed Asymptomatic Bordetella pertussis infections in young African infants and their mothers identified within a longitudinal cohort
title_short Asymptomatic Bordetella pertussis infections in young African infants and their mothers identified within a longitudinal cohort
title_sort asymptomatic bordetella pertussis infections in young african infants and their mothers identified within a longitudinal cohort
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685339/
https://www.ncbi.nlm.nih.gov/pubmed/33236026
http://dx.doi.org/10.1101/2020.11.18.20231423
work_keys_str_mv AT gillcj asymptomaticbordetellapertussisinfectionsinyoungafricaninfantsandtheirmothersidentifiedwithinalongitudinalcohort
AT gunningce asymptomaticbordetellapertussisinfectionsinyoungafricaninfantsandtheirmothersidentifiedwithinalongitudinalcohort
AT macleodw asymptomaticbordetellapertussisinfectionsinyoungafricaninfantsandtheirmothersidentifiedwithinalongitudinalcohort
AT mwananyandal asymptomaticbordetellapertussisinfectionsinyoungafricaninfantsandtheirmothersidentifiedwithinalongitudinalcohort
AT thead asymptomaticbordetellapertussisinfectionsinyoungafricaninfantsandtheirmothersidentifiedwithinalongitudinalcohort
AT pieciakr asymptomaticbordetellapertussisinfectionsinyoungafricaninfantsandtheirmothersidentifiedwithinalongitudinalcohort
AT kwendag asymptomaticbordetellapertussisinfectionsinyoungafricaninfantsandtheirmothersidentifiedwithinalongitudinalcohort
AT mupilaz asymptomaticbordetellapertussisinfectionsinyoungafricaninfantsandtheirmothersidentifiedwithinalongitudinalcohort
AT rohanip asymptomaticbordetellapertussisinfectionsinyoungafricaninfantsandtheirmothersidentifiedwithinalongitudinalcohort