1. Assessing pneumococcal meningitis association with viral respiratory infections and antibiotics: insights from statistical and mathematical models
- Author
-
Emmanuelle Varon, Didier Guillemot, Laurent Gutmann, Sylvie van der Werf, Laura Temime, Laurence Watier, Pierre-Yves Boëlle, Claire Dupont, Lulla Opatowski, Department of Infectious Disease Epidemiology [London] (DIDE), Imperial College London, Pharmacoépidémiologie et maladies infectieuses (PhEMI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre National de Référence des Pneumocoques (CNRP), Assistance Publique - Hôpitaux de Paris, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Fonctionnelle de Santé Publique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Génétique moléculaire des virus à ARN ((U-Pasteur_ 2 / UMR_3569)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), L.O. was supported by a joint grant from the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Sante Et de la Recherche Médicale (INSERM) and the Institut National de la Recherche en Informatique et Automatique (INRIA). L.O. was also supported by a Sanofi-Aventis grant. This study has received funding from the French government's Investissement d'Avenir programme, Laboratoire d'Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR-10-LABX-62-IBEID), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital Raymond Poincaré [Garches], CHU Saint-Antoine [APHP], and ANR-10-LABX-0062/10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
- Subjects
medicine.drug_class ,Antibiotics ,Penicillins ,Streptococcus pneumonia meningitis ,Biology ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Antibiotic resistance ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Streptococcus pneumoniae ,medicine ,Humans ,030212 general & internal medicine ,Respiratory Tract Infections ,Research Articles ,General Environmental Science ,0303 health sciences ,Models, Statistical ,General Immunology and Microbiology ,Respiratory tract infections ,030306 microbiology ,Meningitis, Pneumococcal ,statistical model ,General Medicine ,antibiotic resistance fitness cost ,Models, Theoretical ,medicine.disease ,Virology ,3. Good health ,Anti-Bacterial Agents ,Vaccination ,Pneumococcal infections ,Immunology ,Multivariate Analysis ,virus-bacteria interaction ,Respiratory virus ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,France ,General Agricultural and Biological Sciences ,influenza ,Meningitis ,mathematical model - Abstract
Pneumococcus is an important human pathogen, highly antibiotic resistant and a major cause of bacterial meningitis worldwide. Better prevention requires understanding the drivers of pneumococcal infection incidence and antibiotic susceptibility. Although respiratory viruses (including influenza) have been suggested to influence pneumococcal infections, the underlying mechanisms are still unknown, and viruses are rarely considered when studying pneumococcus epidemiology. Here, we propose a novel mathematical model to examine hypothetical relationships between Streptococcus pneumoniae meningitis incidence (SPMI), acute viral respiratory infections (AVRIs) and antibiotic exposure. French time series of SPMI, AVRI and penicillin consumption over 2001–2004 are analysed and used to assess four distinct virus–bacteria interaction submodels, ascribing the interaction on pneumococcus transmissibility and/or pathogenicity. The statistical analysis reveals strong associations between time series: SPMI increases shortly after AVRI incidence and decreases overall as the antibiotic-prescription rate rises. Model simulations require a combined impact of AVRI on both pneumococcal transmissibility (up to 1.3-fold increase at the population level) and pathogenicity (up to threefold increase) to reproduce the data accurately, along with diminished epidemic fitness of resistant pneumococcal strains causing meningitis (0.97 (0.96–0.97)). Overall, our findings suggest that AVRI and antibiotics strongly influence SPMI trends. Consequently, vaccination protecting against respiratory virus could have unexpected benefits to limit invasive pneumococcal infections.
- Published
- 2013
- Full Text
- View/download PDF