Association of Nonpharmaceutical Interventions During the COVID-19 Pandemic With Invasive Pneumococcal Disease, Pneumococcal Carriage, and Respiratory Viral Infections Among Children in France

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Key Points

Question

Was the implementation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic associated with changes in the incidence of invasive pneumococcal disease (IPD) and associated pneumococcal carriage and respiratory viral infections (RSVs) in children in France?

Findings

In this cohort study using interrupted time series analysis of data from multiple national surveillance systems involving 11 944 children, the incidence of pediatric IPD decreased after implementation of NPIs during the COVID-19 pandemic. This decrease was associated with decreases in influenza and RSV cases, but the pneumococcal carriage rate remained stable.

Meaning

These results suggest that the established association between pneumococcal carriage and IPD was modified after viral epidemiological changes associated with NPIs, suggesting that interventions targeting respiratory viruses may help prevent a large proportion of pediatric IPD cases.

Abstract

Importance

An association between pneumococcal nasopharyngeal carriage and invasive pneumococcal disease (IPD) has been previously established. However, it is unclear whether the decrease in IPD incidence observed after implementation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic was associated with concomitant changes in pneumococcal carriage and respiratory viral infections.

Objective

To assess changes in IPD incidence after the implementation of NPIs during the COVID-19 pandemic and examine their temporal association with changes in pneumococcal carriage rate and respiratory viral infections (specifically respiratory syncytial virus [RSV] and influenza cases) among children in France.

Design, Setting, and Participants

This cohort study used interrupted time series analysis of data from ambulatory and hospital-based national continuous surveillance systems of pneumococcal carriage, RSV and influenza-related diseases, and IPD between January 1, 2007, and March 31, 2021. Participants included 11 944 children younger than 15 years in France.

Exposures

Implementation of NPIs during the COVID-19 pandemic.

Main Outcomes and Measures

The estimated fraction of IPD change after implementation of NPIs and the association of this change with concomitant changes in pneumococcal carriage rate and RSV and influenza cases among children younger than 15 years. The estimated fraction of change was analyzed using a quasi-Poisson regression model.

Results

During the study period, 5113 children (median [IQR] age, 1.0 [0.6-4.0] years; 2959 boys [57.9%]) had IPD, and 6831 healthy children (median [IQR] age, 1.5 [0.9-3.9] years; 3534 boys [51.7%]) received a swab test. Data on race and ethnicity were not collected. After NPI implementation, IPD incidence decreased by 63% (95% CI, −82% to −43%; P < .001) and was similar for non–13-valent pneumococcal conjugate vaccine serotypes with both high disease potential (−63%; 95% CI, −77% to −48%; P < .001) and low disease potential (−53%; 95% CI, −70% to −35%; P < .001). The overall pneumococcal carriage rate did not significantly change after NPI implementation (−12%; 95% CI, −37% to 12%; P = .32), nor did the carriage rate for non-PCV13 serotypes with high disease potential (−26%; 95% CI, −100% to 52%; P = .50) or low disease potential (−7%; 95% CI, −34% to 20%; P = .61). After NPI implementation, the estimated number of influenza cases decreased by 91% (95% CI, −74% to −97%; P < .001), and the estimated number of RSV cases decreased by 74% (95% CI, −55% to −85%; P < .001). Overall, the decrease in influenza and RSV cases accounted for 53% (95% CI, −28% to −78%; P < .001) and 40% (95% CI, −15% to −65%; P = .002) of the decrease in IPD incidence during the NPI period, respectively. The decrease in IPD incidence was not associated with pneumococcal carriage, with carriage accounting for only 4% (95% CI, −7% to 15%; P = .49) of the decrease.

Conclusions and Relevance

In this cohort study of data from multiple national continuous surveillance systems, a decrease in pediatric IPD incidence occurred after the implementation of NPIs in France; this decrease was associated with a decrease in viral infection cases rather than pneumococcal carriage rate. The association between pneumococcal carriage and IPD was potentially modified by changes in the number of RSV and influenza cases, suggesting that interventions targeting respiratory viruses, such as immunoprophylaxis or vaccines for RSV and influenza, may be able to prevent a large proportion of pediatric IPD cases.

Abstract

This cohort study uses data from national continuous surveillance systems to examine the association between nonpharmaceutical interventions for COVID-19 and the incidence of invasive pneumococcal disease, pneumococcal carriage, and respiratory viral infections among children in France.

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Most cited references 37

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Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000–15

Brian Wahl, Katherine L O'Brien, Adena Greenbaum … (2018)

Summary Background Pneumococcal conjugate vaccine (PCV) and Haemophilus influenzae type b (Hib) vaccine are now used in most countries. To monitor global and regional progress towards improving child health and to inform national policies for disease prevention and treatment, we prepared global, regional, and national disease burden estimates for these pathogens in children from 2000 to 2015. Methods Using WHO and Maternal and Child Epidemiology Estimation collaboration country-specific estimates of pneumonia and meningitis mortality and pneumonia morbidity from 2000 to 2015, we applied pneumococcal and Hib cause-specific proportions to estimate pathogen-specific deaths and cases. Summary estimates of the proportion of pneumonia deaths and cases attributable to these pathogens were derived from four Hib vaccine and six PCV efficacy and effectiveness study values. The proportion of meningitis deaths due to each pathogen was derived from bacterial meningitis aetiology and adjusted pathogen-specific meningitis case–fatality data. Pneumococcal and Hib meningitis cases were inferred from modelled pathogen-specific meningitis deaths and literature-derived case–fatality estimates. Cases of pneumococcal and Hib syndromes other than pneumonia and meningitis were estimated using the ratio of pathogen-specific non-pneumonia, non-meningitis cases to pathogen-specific meningitis cases from the literature. We accounted for annual HIV infection prevalence, access to care, and vaccine use. Findings We estimated that there were 294 000 pneumococcal deaths (uncertainty range [UR] 192 000–366 000) and 29 500 Hib deaths (18 400–40 700) in HIV-uninfected children aged 1–59 months in 2015. An additional 23 300 deaths (15 300–28 700) associated with pneumococcus and fewer than 1000 deaths associated Hib were estimated to have occurred in children infected with HIV. We estimate that pneumococcal deaths declined by 51% (7–74) and Hib deaths by 90% (78–96) from 2000 to 2015. Most children who died of pneumococcus (81%) and Hib (76%) presented with pneumonia. Less conservative assumptions result in pneumococcccal death estimates that could be as high as 515 000 deaths (302 000–609 000) in 2015. Approximately 50% of all pneumococcal deaths in 2015 occurred in four countries in Africa and Asia: India (68 700 deaths, UR 44 600–86 100), Nigeria (49 000 deaths, 32 400–59 000), the Democratic Republic of the Congo (14 500 deaths, 9300–18 700), and Pakistan (14 400 deaths, 9700–17 000]). India (15 600 deaths, 9800–21 500), Nigeria (3600 deaths, 2200–5100), China (3400 deaths, 2300–4600), and South Sudan (1000 deaths, 600–1400) had the greatest number of Hib deaths in 2015. We estimated 3·7 million episodes (UR 2·7 million–4·3 million) of severe pneumococcus and 340 000 episodes (196 000–669 000) of severe Hib globally in children in 2015. Interpretation The widespread use of Hib vaccine and the recent introduction of PCV in countries with high child mortality is associated with reductions in Hib and pneumococcal cases and deaths. Uncertainties in the burden of pneumococcal disease are largely driven by the fraction of pneumonia deaths attributable to pneumococcus. Progress towards further reducing the global burden of Hib and pneumococcal disease burden will depend on the efforts of a few large countries in Africa and Asia. Funding Bill & Melinda Gates Foundation.

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Streptococcus pneumoniae: transmission, colonization and invasion

Daniela M. Ferreira, James Paton, Jeffrey Weiser (2018)

Streptococcus pneumoniae as a complex relationship with its obligate human host. On the one hand, the pneumococci are highly adapted commensals, and their main reservoir on the mucosal surface of the upper airways of carriers enables transmission. On the other hand, they can cause severe disease when bacterial and host factors allow them to invade essentially sterile sites, such as the middle ear spaces, lungs, bloodstream and meninges. Transmission, colonization and invasion depend on the remarkable ability of S. pneumoniae to evade or take advantage of the host inflammatory and immune responses. The different stages of pneumococcal carriage and disease have been investigated in detail in animal models and, more recently, in experimental human infection. Furthermore, widespread vaccination and the resulting immune pressure have shed light on pneumococcal population dynamics and pathogenesis. Here, we review the mechanistic insights provided by these studies on the multiple and varied interactions of the pneumococcus and its host.

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Segmented regression analysis of interrupted time series studies in medication use research.

A K Wagner, S B Soumerai, F Zhang … (2002)

Interrupted time series design is the strongest, quasi-experimental approach for evaluating longitudinal effects of interventions. Segmented regression analysis is a powerful statistical method for estimating intervention effects in interrupted time series studies. In this paper, we show how segmented regression analysis can be used to evaluate policy and educational interventions intended to improve the quality of medication use and/or contain costs.

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Author and article information

Journal

Journal ID (nlm-ta): JAMA Netw Open

Journal ID (iso-abbrev): JAMA Netw Open

Title: JAMA Network Open

Publisher: American Medical Association

ISSN (Electronic): 2574-3805

Publication date (Electronic): 28 June 2022

Publication date Collection: June 2022

Publication date PMC-release: 28 June 2022

Volume: 5

Issue: 6

Electronic Location Identifier: e2218959

Affiliations

[1 ]Association Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France

[2 ]Association Française de Pédiatrie Ambulatoire, Saint-Germain-en-Laye, France

[3 ]Assistance Publique–Hôpitaux de Paris, Service d'Accueil des Urgences Pédiatriques, Université de Paris, Paris, France

[4 ]Assistance Publique–Hôpitaux de Paris, Robert Debré University Hospital, Epidémiologie Clinique–Évaluation Économique Appliqué aux Populations Vulnérables, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1123, Université de Paris, Paris, France

[5 ]Université Paris Est, Institut Mondor de Recherche Biomédicale, Groupe d'Etude de Maladies Infectieuses Néonatales et Infantiles, Créteil, France

[6 ]Groupe de Pathologie Infectieuse Pédiatrique, Paris, France

[7 ]Clinical Research Center, Centre Hospitalier Intercommunal de Créteil, Créteil, France

[8 ]Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Unité Mixte de Recherche Scientifique 1138, Université de Paris, Paris, France

[9 ]Assistance Publique–Hôpitaux de Paris, Service de Pédiatrie Générale, Robert Debré University Hospital, Université de Paris, Paris, France

[10 ]Direction des Maladies Infectieuses, Santé Publique France, Saint-Maurice, France

[11 ]Centre National de Référence des Infections Respiratoires, Institut Pasteur, Paris, France

[12 ]Assistance Publique–Hôpitaux de Paris, Service de Microbiologie, Robert Debré University Hospital, Université de Paris, Paris, France

[13 ]Infection Antimicrobials Modelling Evolution, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1137, Université de Paris, Paris, France

[14 ]Service de Pédiatrie Médicale, Centre Hospitalier Universitaire Caen-Normandie, Caen, France

[15 ]Chirurgie Générale, Digestive et de l'Obésité, Centre Hospitalier Intercommunal de Créteil, Créteil, France

[16 ]Institut National de la Santé et de la Recherche Médicale, L’Institut Mondor de Recherche Biomédicale, Unité 955, Université Paris-Est Créteil, Créteil, France

[17 ]Assistance Publique–Hôpitaux de Paris, Centre d’Investigation Clinique 1426, Robert Debré University Hospital, Université de Paris, Paris, France

[18 ]Néonatalogie et Réanimation Néonatale, Centre Hospitalier Intercommunal de Créteil, Créteil, France

[19 ]Microbiologie et Centre National de Référence du Pneumocoque, Centre Hospitalier Intercommunal de Créteil, Créteil, France

[20 ]Service des Maladies Infectieuses Pédiatriques, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Québec, Canada

Author notes

Article Information

Accepted for Publication: April 21, 2022.

Published: June 28, 2022. doi:10.1001/jamanetworkopen.2022.18959

Corresponding Author: Naïm Ouldali, PhD, Assistance Publique–Hôpitaux de Paris, Department of General Pediatrics, Pediatric Infectious Disease and Internal Medicine, Robert Debré University Hospital, Université de Paris, 48 Bd Serrurier, 75019 Paris, France ( naim.ouldali@ 123456aphp.fr ).

Author Contributions: Drs Rybak and Ouldali had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Rybak, Levy, Angoulvant, Levy-Bruhl, Faye, Cohen, Ouldali.

Acquisition, analysis, or interpretation of data: Rybak, Levy, Angoulvant, Auvrignon, Gembara, Danis, Vaux, van der Werf, Béchet, Bonacorsi, Assad, Lazzati, Michel, Kaguelidou, Varon, Ouldali.

Drafting of the manuscript: Rybak, Gembara, Béchet, Cohen.

Critical revision of the manuscript for important intellectual content: Rybak, Levy, Angoulvant, Auvrignon, Danis, Vaux, Levy-Bruhl, van der Werf, Bonacorsi, Assad, Lazzati, Michel, Kaguelidou, Faye, Varon, Ouldali.

Statistical analysis: Rybak, Angoulvant, Danis, Béchet, Assad, Ouldali.

Obtained funding: Levy, Cohen.

Administrative, technical, or material support: Levy, Gembara, Béchet, Assad, Lazzati, Michel, Kaguelidou, Varon.

Supervision: Levy, Angoulvant, Danis, Michel, Kaguelidou, Varon, Ouldali.

Conflict of Interest Disclosures: Dr Rybak reported receiving grants from the Association Française de Pédiatrie Ambulatoire and travel funding from AstraZeneca and Pfizer outside the submitted work. Dr Levy reported receiving grants from Pfizer (via ACTIV) during the conduct of the study; grants from GlaxoSmithKline, Merck Sharp & Dohme, Pfizer, and Sanofi; personal fees from Merck Sharp & Dohme and Pfizer; and nonfinancial support from Merck Sharp & Dohme and Pfizer outside the submitted work. Dr Angoulvant reported receiving grants from Pfizer outside the submitted work. Dr van der Werf reported receiving grants from Sante Publique France during the conduct of the study and a provisional patent on SARS-CoV-2 diagnostics and a research grant from Sanofi Pasteur on an unrelated subject outside the submitted work. Dr Assad reported receiving travel funding from Bastide le Confort Médical and Novartis outside the submitted work. Dr Lazzati reported receiving personal fees from Johnson & Johnson, Medtronic, and W. L. Gore & Associates outside the submitted work. Dr Cohen reported receiving grants (via ACTIV) and personal fees from GlaxoSmithKline, Merck Sharp & Dohme, Pfizer, and Sanofi outside the submitted work. Dr Varon reported receiving grants (via the National Reference Center for Pneumococci, Centre Hospitalier Intercommunal de Créteil) from the Santé Publique France during the conduct of the study and grants (via the National Reference Center for Pneumococci, Centre Hospitalier Intercommunal de Créteil) from Merck Sharp & Dohme and Pfizer outside the submitted work. Dr Ouldali reported receiving travel funding from GlaxoSmithKline, Pfizer, and Sanofi outside the submitted work. No other disclosures were reported.

Funding/Support: This work was supported by funding from Pfizer (via ACTIV) for the pneumococcal carriage study, funding from the French Institute for Public Health Surveillance (via the National Reference Center for Pneumococci) for the invasive pneumococcal disease study, and a 2021-2023 fellowship award from the European Society of Pediatric Infectious Diseases (Dr Ouldali).

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank the following team members of ACTIV (Créteil, France) for their technical assistance: Michel Boucherat, MD, Isabelle Ramay, Marine Borg, Aurore Prieur, and Elsa Sobral. We also thank the following team members from the Laboratory of Medical Biology and the National Reference Centre for Pneumococci, Intercommunal Hospital of Créteil (Créteil, France) for their technical assistance: Cécile Culeux, Assiya El Mniai, and Jameel Batah, MD. We thank all of the following pediatricians (affiliated with ACTIV) who participated in the carriage study: Catherine Abt-Nord, MD, Marie-José Aim-Mille, MD, Marie-Hélène Akou’ou, MD, Daniel Allain, MD, Michel Amzallag, MD, Patrick André, MD, Marie-Constance Anthoine-Milhomme, MD, Isabelle Aubier, MD, Anne Auvrignon, Pierre Bakhache, MD, Joelle Baron, MD, Béatrice Baszanger, MD, Christophe Batard, MD, Gérard Beley, MD, Mohammed Benani, MD, Catherine Bensoussan-Ambacher, MD, Eric Billard, MD, Louis Billet, MD, Jean-Paul Blanc, MD, Marie-José Bodin, MD, Eric Boez, MD, Bernard Bohe, MD, Jacky Bouglé, MD, Fabrice Bouillot, MD, Bénédicte Broussin, MD, Jean-Louis Cabos, MD, Fabienne Cahn-Sellem, MD, Patrice Camier, MD, Françoise Ceccato, MD, Anne Chevé, MD, Daniele Clavel, MD, Claire Claverie, MD, Robert Cohen, MD, Lucette Coicadan, MD, François Corrard, MD, Liliane Cret, MD, Gwenaelle D’Acremont, MD, Nadia D’Ovidio-Panis, MD, Véronique Dagrenat, MD, Brigitte de Brito, MD, Françoise De Grenier, MD, Patrice Deberdt, MD, Isabelle Defives, MD, Anne Delatour, MD, Jean-François Delobbe, MD, Véronique Derkx, MD, Roxane Desandes, MD, Véronique Desvignes, MD, Michel Dogneton, MD, Isabelle Donikian-Pujol, MD, Catherine Douer-Fernando, MD, Michel Dubosc, MD, Jocelyne Ducellier, MD, Catherine Dumont, MD, Annie Elbez, MD, Jacques Elbhar, MD, Nadim Elkhoury, MD, Catherine Ferté-Devin, MD, Jean-Michel Fiorini, MD, Denis Garel, MD, Jean-Luc Gasnier, MD, Annabella Gasser, MD, Béatrice Gaudin, MD, Nathalie Gelbert-Baudino, MD, Piotr Gembara, MD, Catherine Georgeot, MD, Martine Gerardin, MD, Marc Giorno, MD, Marie Goldrey, MD, Stéphanie Gorde-Grosjean, MD, René Gorge, MD, Juliette Gosselin, MD, Cécile Guiheneuf, MD, Jean-Louis Guillon, MD, Jean-François Hassan, MD, André Hayat, MD, Henri Hollenberg, MD, Pascale Huguet, MD, Priscille Hugot, MD, Michel Hunin, MD, Ara Kalindjian, MD, Kai Kassmann, MD, Zalfa Klink, MD, Marc Koskas, MD, Chantal Lastmann-Lahmi, MD, Fanny Le Mouel, MD, Hélène Le Scornet, MD, Marie-Claude Lemarchand, MD, Jean-Claude Lévêque, MD, Joel Levy, MD, Marc Levy, MD, Daniel Livon, MD, Murielle Louvel, MD, Nassira Maamri-Belaroussi, MD, Christine Magendie, MD, Ilda Martins, MD, Marie-Odile Mercier-Oger, MD, Claude Messica, MD, Françoise Meunier, MD, Anne-Sylvestre Michot, MD, Jacques Miclot, MD, Pascaline Migault, MD, Isabelle Nave, MD, Michel Navel, MD, Jean-François Nicolas, MD, Marie-Odile Oger, MD, Joseph Ohayon, MD, Jean-Claude Oilleau, MD, Annie Pappo, MD, France Paratte, MD, Jacques Peguet, MD, Christian Perrin, MD, Corinne Petit, MD, Brigitte Pinçant, MD, Odile Pinard, MD, Anne Piollet, MD, Jean-François Pujol, MD, Marie-Thérèse Pujol, MD, Nathalie Ramos, MD, Sophie Ravilly, MD, Yves Regnard, MD, Marc Robert, MD, Olivier Romain, MD, Stéphanie Romano, MD, Marie-Charlotte Rondeau, MD, Gaëlle Roques, MD, Bechara Saade, MD, Jean-François Salaün, MD, Catherine Salinier-Rolland, MD, Catherine Schlemmer, MD, Aurélie Sellam, MD, Elisa Seror, MD, Geneviève Sivelle, MD, David Somerville, MD, Nathalie Temam-Basse, MD, Emilie Thomas, MD, Jean-Michel Thiron, MD, François Thollot, MD, Jonathan Toledano, MD, Robert Touitou, MD, Catherine Turberg-Romain, MD, Josette Vaugeois, MD, François Vie Le Sage, MD, Jean-Luc Vuillemin, MD, Andreas Werner, MD, Rose Wisnewsky, MD, Alain Wollner, MD, Claudie Wollner, MD, and Christophe Ythier, MD. The investigators of the carriage study received financial compensation for each swab test performed. We thank all of the microbiology laboratories that participated in invasive pneumococcal disease surveillance (more than 400 laboratories throughout France, for which no compensation was provided). We thank Laura Smales, MSW, of BioMedEditing (Canada) for assistance with language editing (compensation provided). Dr Rybak personally thanks Olivia Nguyen, MD, of Hôpital Saint-Joseph (Paris, France) for her technical support (no compensation provided).

Article

Publisher ID: zoi220547

DOI: 10.1001/jamanetworkopen.2022.18959

PMC ID: 9240903

PubMed ID: 35763298

SO-VID: 76aef0c0-e3e0-499b-8884-1c26d26a3d31

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This is an open access article distributed under the terms of the CC-BY License.

Association of Nonpharmaceutical Interventions During the COVID-19 Pandemic With Invasive Pneumococcal Disease, Pneumococcal Carriage, and Respiratory Viral Infections Among Children in France

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Key Points

Question

Findings

Meaning

Abstract

Importance

Objective

Design, Setting, and Participants

Exposures

Main Outcomes and Measures

Results

Conclusions and Relevance

Abstract

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 37

Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000–15

Streptococcus pneumoniae: transmission, colonization and invasion

Segmented regression analysis of interrupted time series studies in medication use research.

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