Mathematical modeling of postcoinfection with influenza A virus and Streptococcus pneumoniae, with implications for pneumonia and COPD-risk assessment

Yi Hsien Cheng, Shu Han You, Yi Jun Lin, Szu Chieh Chen*, Wei Yu Chen, Wei Chun Chou, Nan Hung Hsieh, Chung Min Liao

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background: The interaction between influenza and pneumococcus is important for understanding how coinfection may exacerbate pneumonia. Secondary pneumococcal pneumonia associated with influenza infection is more likely to increase respiratory morbidity and mortality. This study aimed to assess exacerbated inflammatory effects posed by secondary pneumococcal pneumonia, given prior influenza infection. Materials and methods: A well-derived mathematical within-host dynamic model of coinfection with influenza A virus and Streptococcus pneumoniae (SP) integrated with dose-response relationships composed of previously published mouse experimental data and clinical studies was implemented to study potentially exacerbated inflammatory responses in pneumonia based on a probabilistic approach. Results: We found that TNFα is likely to be the most sensitive biomarker reflecting inflammatory response during coinfection among three explored cytokines. We showed that the worst inflammatory effects would occur at day 7 SP coinfection, with risk probability of 50% (likely) to develop severe inflammatory responses. Our model also showed that the day of secondary SP infection had much more impact on the severity of inflammatory responses in pneumonia compared to the effects caused by initial virus titers and bacteria loads. Conclusion: People and health care workers should be wary of secondary SP infection on day 7 post-influenza infection for prompt and proper control-measure implementation. Our quantitative risk-assessment framework can provide new insights into improvements in respiratory health especially, predominantly due to chronic obstructive pulmonary disease (COPD).

Original languageEnglish
Pages (from-to)1973-1988
Number of pages16
JournalInternational Journal of COPD
Volume12
DOIs
StatePublished - 5 Jul 2017

Keywords

  • Chronic obstructive pulmonary disease
  • Coinfection
  • Influenza
  • Modeling
  • Pneumonia
  • Risk assessment

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