title: Interaction of Vaccination and Reduction of Antibiotic Use Drives Unexpected Increase of Pneumococcal Meningitis.
abstract: Antibiotic-use policies may affect pneumococcal conjugate-vaccine effectiveness. The reported increase of pneumococcal meningitis from 2001 to 2009 in France, where a national campaign to reduce antibiotic use was implemented in parallel to the introduction of the 7-valent conjugate vaccine, provides unique data to assess these effects. We constructed a mechanistic pneumococcal transmission model and used likelihood to assess the ability of competing hypotheses to explain that increase. We find that a model integrating a fitness cost of penicillin resistance successfully explains the overall and age-stratified pattern of serotype replacement. By simulating counterfactual scenarios of public health interventions in France, we propose that this fitness cost caused a gradual and pernicious interaction between the two interventions by increasing the spread of nonvaccine, penicillin-susceptible strains. More generally, our results indicate that reductions of antibiotic use may counteract the benefits of conjugate vaccines introduced into countries with low vaccine-serotype coverages and high-resistance frequencies. Our findings highlight the key role of antibiotic use in vaccine-induced serotype replacement and suggest the need for more integrated approaches to control pneumococcal infections.
authors.affiliation: 1] Institut Pasteur, Unité de Pharmaco-Épidémiologie et Maladies Infectieuses, F-75015 Paris, France [2] INSERM, U1181, F-75015 Paris, France [3] Univ. Pierre et Marie Curie, Cellule Pasteur UPMC, F-75005 Paris, France [4] Univ. Versailles Saint Quentin, UFR des Sciences de la Santé Simone-Veil, EA 4499, F-78180 Montigny-le-Bretonneux, France.
authors.forename: Matthieu Domenech
authors.initials: MD
authors.lastname: de Cellès
authors.affiliation: 1] Institut Pasteur, Unité de Pharmaco-Épidémiologie et Maladies Infectieuses, F-75015 Paris, France [2] INSERM, U1181, F-75015 Paris, France [3] Univ. Pierre et Marie Curie, Cellule Pasteur UPMC, F-75005 Paris, France [4] Univ. Versailles Saint Quentin, UFR des Sciences de la Santé Simone-Veil, EA 4499, F-78180 Montigny-le-Bretonneux, France.
authors.forename: Margarita
authors.initials: M
authors.lastname: Pons-Salort
authors.affiliation: 1] AP-HP, Hôpital Européen Georges-Pompidou, Laboratoire de Bactériologie, F-75015 Paris, France [2] Centre National de Référence des Pneumocoques, F-75015 Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Varon
authors.affiliation: 1] Institut Pasteur, Unité de Pharmaco-Épidémiologie et Maladies Infectieuses, F-75015 Paris, France [2] INSERM, U1181, F-75015 Paris, France [3] Univ. Pierre et Marie Curie, Cellule Pasteur UPMC, F-75005 Paris, France.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Vibet
authors.affiliation: 1] Institut Pasteur, Unité de Pharmaco-Épidémiologie et Maladies Infectieuses, F-75015 Paris, France [2] INSERM, U1181, F-75015 Paris, France [3] Univ. Versailles Saint Quentin, UFR des Sciences de la Santé Simone-Veil, EA 4499, F-78180 Montigny-le-Bretonneux, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ligier
authors.affiliation: cole Centrale Paris, Laboratoire de Mathématiques Appliquées aux Systèmes, F-92290 Châtenay-Malabry, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Letort
authors.affiliation: 1] Institut Pasteur, Unité de Pharmaco-Épidémiologie et Maladies Infectieuses, F-75015 Paris, France [2] INSERM, U1181, F-75015 Paris, France [3] Univ. Versailles Saint Quentin, UFR des Sciences de la Santé Simone-Veil, EA 4499, F-78180 Montigny-le-Bretonneux, France.
authors.forename: Lulla
authors.initials: L
authors.lastname: Opatowski
authors.affiliation: 1] Institut Pasteur, Unité de Pharmaco-Épidémiologie et Maladies Infectieuses, F-75015 Paris, France [2] INSERM, U1181, F-75015 Paris, France [3] Univ. Versailles Saint Quentin, UFR des Sciences de la Santé Simone-Veil, EA 4499, F-78180 Montigny-le-Bretonneux, France [4] AP-HP, Hôpital Raymond-Poincaré, Unité Fonctionnelle de Santé Publique, F-92380 Garches, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Guillemot
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D005602:France / Q000453:epidemiology; D000069443:Heptavalent Pneumococcal Conjugate Vaccine / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D057970:Inappropriate Prescribing / Q000706:statistics & numerical data*; D008586:Meningitis, Pneumococcal / Q000453:epidemiology* / Q000276:immunology / Q000635:transmission; D008962:Models, Theoretical; D010403:Penicillin Resistance; D010406:Penicillins / Q000627:therapeutic use; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000276:immunology; D014611:Vaccination / Q000706:statistics & numerical data*; D018074:Vaccines, Conjugate / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D010406:Penicillins; D018074:Vaccines, Conjugate