Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness

Early and aggressive treatment, including antibiotics and intensive care, could save most patients with severe influenza-associated pneumonia.

“suggests that early and aggressive treatment, including antibiotics and intensive care, could save most patients [84, 85]”

The extent of bacterial coinfection in influenza patients has not been systematically examined.

“Despite the long historical understanding of the risk posed by bacterial coinfections in influenza patients,2 the extent of coinfection has not been systematically examined.55”

Streptococcus pneumoniae was the most frequent bacterial coinfection.

“Consistent with the prior literature,55, 62 we found that S. pneumoniae was the most frequent bacterial coinfection; however, both S. aureus and other bacterial coinfections were also quite common.”

Staphylococcus aureus and other bacterial coinfections were also quite common.

“Consistent with the prior literature,55, 62 we found that S. pneumoniae was the most frequent bacterial coinfection; however, both S. aureus and other bacterial coinfections were also quite common.”

The 1918-1919 H1N1 influenza pandemic resulted in more than 50 million deaths, with many caused by bacterial super-infection leading to secondary pneumonia.

“the so-called “Spanish Flu” pandemic of H1N1 influenza A virus from 1918 to 1919 resulted in more than 50 million deaths, with many caused by bacterial super-infection leading to secondary pneumonia”

Over a period of 2 months in 1918 at 37 large American army camps, secondary bacterial infection occurred in approximately 17% of those diagnosed with influenza, of which approximately 35% were fatal.

“Over a period of 2 months in 1918 at 37 large American army camps, secondary bacterial infection occurred in approximately 17% of those diagnosed with influenza of which approximately 35% were fatal.”

In the US military, the mean influenza attack rate during the 1918/1919 pandemic was 23%, the mean percentage of influenza cases that developed pneumonias was 16%, and the mean percentage of pneumonia cases that were fatal was 34%.

“Overall, it has been estimated that in the US military, the mean influenza attack rate during the course of the 1918/1919 pandemic was 23%, the mean percentage of influenza cases that developed pneumonias was 16% and the mean percentage of pneumonia cases that were fatal was 34%.”

S pneumoniae is the most frequently isolated pathogen associated with influenza.

“S pneumoniae is the most frequently isolated pathogen associated with influenza”

S. pneumoniae is the most common bacterium found in viral secondary bacterial infections and is particularly associated with high mortality and morbidity during influenza epidemics and pandemics.

“Streptococcus pneumoniae is the most common bacteria found in viral secondary bacterial infections, and is particularly associated with causing high mortality and morbidity during influenza epidemics and pandemics (Brundage, 2006; Joseph et al., 2013).”

Influenza infection causes decreased mucociliary activity, dysfunction of immune cells, and reduced phagocytosis, which reduces clearance of the virus from host airways and the host's ability to fight the virus.

“Virally induced decreased mucociliary activity, the dysfunction of immune cells and the reduction of phagocytosis reduces clearance of the virus from the host airways and the host’s ability to fight the virus (Brundage, 2006; Wu et al., 2011; Cauley and Vella, 2015).”

H. influenzae has been associated with complication of disease during influenza pandemics.

“and has been associated with the complication of disease during influenza pandemics (Abrahams et al., 1919; Spooner et al., 1919; Brundage, 2006; Palacios et al., 2009).”

H. influenzae is commonly found to co/secondarily infect viral infection.

“Haemophilus influenzae is another bacteria commonly found to co/secondarily infect viral infection”

The 1918 pandemic infected 50% of the world's population and resulted in approximately 40-50 million deaths worldwide.

“It is considered the most devastating influenza pandemic ever recorded, infecting 50% of the world’s population and resulting in approximately 40–50 million deaths worldwide.”

India alone suffered 7 million deaths during the 1918 pandemic.

“India alone suffered 7 million deaths (Potter, 2001; Hilleman, 2002; Brundage, 2006; Michaelis et al., 2009).”

Out of 20 tested sputum specimens from a British army camp in north France, 90% presented with H. influenzae, 65% with S. pneumoniae, 25% with other Streptococcus spp., and 15% with Staphylococcus spp.

“Out of 20 tested sputum specimens from a British army camp based in north France, 90% presented with H. influenzae, 65% presented with S. pneumoniae, 25% with other Streptococcus spp. and 15% with Staphylococcus spp.”

At Camp Devens, of those infected with influenza, 17% developed pneumonia, of which 35% were fatal.

“Of those infected, 17% developed pneumonia, of which 35% of cases were fatal.”

At Camp Logan, post-mortems found S. pneumoniae in the lungs of 44% and heart blood of 33%.

“Post-mortems found S. pneumoniae in the lungs of 44% and heart blood of 33% (Hall et al., 1918; Brundage, 2006).”

At Camp Custer, sputum cultures proved presence of S. pneumoniae in 26% of cases, and 28% of lung and blood cultures were positive for S. pneumoniae.

“Sputum cultures proved the presence of S. pneumoniae in 26% of cases. Further investigation found 28% of lung and blood cultures were positive for S. pneumoniae, again acting as supporting evidence of the invasive potential of such co-infections (Blanton and Irons, 1918; Brundage, 2006).”

At Camp Custer, 21% of influenza cases progressed to pneumonia, of which 28% died.

“At Camp Custer, 21% of influenza cases progressed to pneumonia, of which 28% died.”

In 1919 re-examination of lung tissue from 1918 fatalities, S. pyogenes longus was found in 36%, S. pneumoniae in 29%, and H. influenzae in 25%.

“Further lung tissue from fatalities of this pandemic were re-examined in 1919; S. pyogenes longus was found in 36% of cases, S. pneumoniae in 29% of cases and H. influenzae in 25% (Abrahams et al., 1919; Brundage, 2006).”

At Camp Logan, 2,487 influenza-associated hospitalizations were recorded, 17% acquired pneumonia, and 4% of pneumonia cases were fatal.

“Here 2,487 influenza-associated hospitalizations were recorded, 17% acquired pneumonia with 4% of these cases being fatal.”

Influenza with secondary bacterial infection of S. pneumoniae, H. influenzae and/or Staphylococcus sp. was associated with major outbreaks of purulent bronchitis in 1916 and 1917.

“Influenza with secondary bacterial infection of S. pneumoniae (and other Streptococcus sp.), H. influenzae and/or Staphylococcus sp. was associated with major outbreaks of purulent bronchitis in 1916 and 1917 (Brundage, 2006; Joseph et al., 2013).”

At Camp Devens, blood culture revealed 65% had S. pneumoniae, 2.5% had H. influenzae, and 1.3% had S. aureus.

“Blood culture revealed 65% had S. pneumoniae, 2.5% had H. influenzae and 1.3% had S. aureus (Spooner et al., 1919; Brundage, 2006).”

At Camp Devens, out of 37 autopsies, 43% were positive for pure growth of H. influenzae in at least one lobe of the lung.

“Out of 37 autopsies performed, 43% were positive for pure growth of H. influenzae in at least one lobe of the lung.”

Among specimens positive for H. influenzae, many exhibited simultaneous H. influenzae and S. pneumoniae co-infection, with H. influenzae identified as the primary bacterial infector.

“Out of the specimens positive for H. influenzae, many exhibited simultaneous H. influenzae and S. pneumoniae co-infection; with H. influenzae identified as the primary bacterial infector.”

At Camp Devens in 1918, a quarter of all troops were diagnosed with influenza within a 1-month period.

“Within a 1-month period in 1918 at the military Camp Devens, a quarter of all troops were diagnosed with influenza.”

At Camp Jackson, 17% of influenza cases progressed to pneumonia, and 31% of pneumonia cases were fatal.

“At Camp Jackson, 17% of influenza cases progressed to pneumonia with a further 31% of pneumonia cases proving fatal.”

At Camp Jackson, autopsies found S. pneumoniae to be the bacterial co-infection most associated with pneumonia, and 155 of 312 lung cultures were positive for S. aureus.

“Autopsies found S. pneumoniae to be the bacterial co-infection most associated with pneumonia, however, 155 of 312 lung cultures were positive for S. aureus (Michael, 1942; Brundage, 2006).”

Viral-induced immunosuppression can allow bacterial superinfection.

“Viral induced immunosuppression can allow for a bacterial super infection”

During influenza infection, impaired immunologic cells can suppress host immune responses and immune cell dysfunction can reduce the host's ability to fight bacteria.

“host immune responses can be suppressed when immunologic cells are impaired during influenza infection and immune cell dysfunction can reduce the host’s ability to fight bacteria”