The role of influenza in the severity and transmission of respiratory bacterial disease

Abstract

Infections with influenza viruses and respiratory bacteria each contribute substantially to the global burden of morbidity and mortality. Simultaneous or sequential infection with these pathogens manifests in complex and difficult-to-treat disease processes that need extensive antimicrobial therapy and cause substantial excess mortality, particularly during annual influenza seasons and pandemics. At the host level, influenza viruses prime respiratory mucosal surfaces for excess bacterial acquisition and this supports increased carriage density and dissemination to the lower respiratory tract, while greatly constraining innate and adaptive antibacterial defences. Driven by virus-mediated structural modifications, aberrant immunological responses to sequential infection, and excessive immunopathological responses, co-infections are noted by short-term and long-term departures from immune homoeostasis, inhibition of appropriate pathogen recognition, loss of tolerance to tissue damage, and general increases in susceptibility to severe bacterial disease. At the population level, these effects translate into increased horizontal bacterial transmission and excess use of antimicrobial therapies. With increasing concerns about future possible influenza pandemics, the past decade has seen rapid advances in our understanding of these interactions. In this Review, we discuss the epidemiological and clinical importance of influenza and respiratory bacterial co-infections, including the foundational efforts that laid the groundwork for today’s investigations, and detail the most important and current advances in our understanding of the structural and immunological mechanisms underlying the pathogenesis of co-infection. We describe and interpret what is known in sequence, from transmission and phenotypic shifts in bacterial dynamics to the immunological, cellular, and molecular modifications that underlie these processes, and propose avenues of further research that might be most valuable for prevention and treatment strategies to best mitigate excess disease during future influenza pandemics.

Influenza A Virus Infection Predisposes Hosts to Secondary Infection with Different Streptococcus pneumoniae Serotypes with Similar Outcome but Serotype-Specific Manifestation

“…In line with this, infections with 19F are most commonly found in children and immunocompromised patients (36). Furthermore, our findings are consistent with reports that bacterial-strain-specific differences are surpassed and mortality does not correlate with the incidence of bacteremia during the acute phase of IAV infection (37,38). In fact, mortality was proportional to the uncontrolled bacterial outgrowth in the LRT and not bacteremia, as the coinfected animals that succumbed to the infection showed high vari- ability in the extent of bacteremia.…”

Burden of Influenza in Less Than 5-Year-Old Children Admitted to Hospital with Pneumonia in Developing and Emerging Countries: A Descriptive, Multicenter Study

“…1 The literature shows that the clinical characteristics of children with lower respiratory tract infections are dependent on the carriage of specific pathogens in the nasopharynx. 2,18 Streptococcus pneumoniae was detected more frequently in blood samples from influenza-related cases, with a high detection rate (70.9%) of viral-bacterial cocolonizations found. As previously mentioned in the literature, it suggests that influenza viruses may be considered as precursors of bacterial pneumonia or as etiological agents of pneumonia.…”

Identification of Rare PB2-D701N Mutation from a Patient with Severe Influenza: Contribution of the PB2-D701N Mutation to the Pathogenicity of Human Influenza

“…The dose-dependent invasive ability of pneumococci was solely dependent on the number and phagocytic ability of resident macrophages initially present (Smith and McCullers, 2014). In addition, virus-mediated patches of desquamated epithelium allow bacteria to adhere and invade with increase vigor (reviewed in Mina and Klugman, 2014). Thereby, infection with a particularly virulent influenza strain would exacerbate these processes that together with the respiratory tract damage may enhance the subsequent opportunistic bacterial infections.…”