Individual-level Association of Influenza Infection With Subsequent Pneumonia: A Case-control and Prospective Cohort Study

Abstract

Background Pneumonia is a leading cause of mortality worldwide. Influenza may result in primary pneumonia or be associated with secondary bacterial pneumonia. While the association with secondary pneumonia has been established ecologically, individual-level evidence remains sparse and the risk period for pneumonia following influenza poorly defined. Methods We conducted a matched case-control study and a prospective cohort study among Nicaraguan children aged 0-14 years from 2011-2018. Physicians diagnosed pneumonia cases based on Integrated Management for Childhood Illness (IMCI) guidelines. Cases were matched with up to 4 controls on age (months) and study week. We fit conditional logistic regression models to assess the association between influenza subtype and subsequent pneumonia development, and a Bayesian non-linear survival model to estimate pneumonia hazard following influenza. Results Participants with influenza had greater risk of developing pneumonia in the 30 days following onset compared to those without influenza (matched odds ratio [mOR]: 2.7, 95% CI: 1.9, 3.9). Odds of developing pneumonia were highest for participants following A(H1N1)pdm09 illness (mOR: 3.7, 95% CI: 2.0, 6.9), followed by influenza B, and A(H3N2). Participants’ odds of pneumonia following influenza were not constant, showing distinct peaks 0-6 days (mOR: 8.3, 95% CI: 4.8, 14.5) and 14-20 (mOR: 2.5, 95% CI: 1.1, 5.5) days post influenza infection. Conclusions Influenza is a significant driver of both primary and secondary pneumonia among children. Distinct periods of elevated pneumonia risk in the 30 days following influenza supports multiple etiological pathways.

Incidence and seasonality of respiratory viruses among medically attended children with acute respiratory infections in an Ecuador birth cohort, 2011–2014

“…Indeed, almost all children aged 12–23 months had MAARIs, and more than one in five tested positive for RSV and one in 10 for influenza. The incidence of respiratory viruses among this young age group is important because younger children are also at highest risk of viral 14 and bacterial pneumonias 15 and subsequent hospitalizations 16 . Such a burden suggests the value of continued investment in Ecuador's pharmaceutical and nonpharmaceutical interventions to prevent respiratory illnesses, which were associated with an annual productivity loss of US$152 million 17 …”

Influenza Virus Infection Increases Host Susceptibility To Secondary Infection with Pseudomonas aeruginosa, and This Is Attributed To Neutrophil Dysfunction through Reduced Myeloperoxidase Activity

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“…In this regard, it is important to remember that influenza represents a major cause of morbidity and mortality in older people [42]. Moreover, influenza is an important cause of other medical conditions in older subjects such as stroke and cardiovascular diseases [43], disability [44], pneumonia [45], and finally mortality. Vaccination against influenza in older people is highly effective in preventing all these conditions and therefore highly recommended [46].…”