title: Assessing pneumococcal meningitis association with viral respiratory infections and antibiotics: insights from statistical and mathematical models.
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.
authors.affiliation: Unité de Pharmaco-épidémiologie et Maladies Infectieuses PhEMI, Institut Pasteur, 75015 Paris, France. lulla.opatowski@pasteur.fr
authors.forename: Lulla
authors.initials: L
authors.lastname: Opatowski
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Varon
authors.forename: Claire
authors.initials: C
authors.lastname: Dupont
authors.forename: Laura
authors.initials: L
authors.lastname: Temime
authors.forename: Sylvie
authors.initials: S
authors.lastname: van der Werf
authors.forename: Laurent
authors.initials: L
authors.lastname: Gutmann
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Boëlle
authors.forename: Laurence
authors.initials: L
authors.lastname: Watier
authors.forename: Didier
authors.initials: D
authors.lastname: Guillemot
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D005602:France / Q000453:epidemiology; D006801:Humans; D008586:Meningitis, Pneumococcal / Q000188:drug therapy / Q000453:epidemiology*; D015233:Models, Statistical; D008962:Models, Theoretical; D015999:Multivariate Analysis; D010406:Penicillins; D012141:Respiratory Tract Infections / Q000453:epidemiology*; D013296:Streptococcus pneumoniae / Q000472:pathogenicity
chemical_list: D000900:Anti-Bacterial Agents; D010406:Penicillins
keywords: Streptococcus pneumonia meningitis; antibiotic resistance fitness cost; influenza; mathematical model; statistical model; virus–bacteria interaction