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Professor David Moranz discusses the concept of viral-bacterial co-pathogenesis and its relevance to sepsis, septic shock, and death from bacterial disease, using early 20th-century pandemics as a lens.
Key points:
- The idea that sepsis, septic shock, and death can be downstream events prompts examination of upstream events and progression to prevent outcomes.
- Co-pathogenesis, involving simultaneous infection with a virus and a bacterium, was recognized in the early 1900s. Ellis Island health officers noted higher mortality in children with viral infections like measles when co-infected with bacteria such as streptococci or diphtheria.
- During World War I, crowded army camps experienced massive measles outbreaks and secondary bacterial pneumonia deaths. A notable study tracked soldiers with measles: those who were colonized with group A beta-hemolytic streptococcus (Strep pyogenes) had all complications and deaths among colonized individuals, while non-colonized soldiers fared better.
- With influenza in 1918, pathology from the Armed Forces Institute of Pathology showed that death was associated with severe bacterial pneumonia in all 58 autopsies studied. Across 173 autopsy studies from 15 countries (over 8,000 individuals), 95% had pneumopathogens cultured from the lungs; 80.4% of pleural effusions contained pneumopathogens; 70% of those with pre-death blood cultures had one or more positive cultures.
- The principal pneumopathogens identified were Streptococcus pneumoniae (pneumococcus), Streptococcus pyogenes (Group A beta-hemolytic strep), and Staphylococcus, though other pathogens occurred as well, including meningococcus in some outbreaks of fatal influenza-associated pneumonia.
- Pathology commonly showed bronchopneumonia, with viral lesions characterized by infection of apical cells of the bronchiolar and bronchial epithelium. The virus disrupts the protective epithelial layer, enabling bacteria to colonize the basal layer and cause pneumonia. This is why bronchopneumonia was prevalent in both measles- and influenza-associated deaths.
- The proximate cause of death often involved hypoxia from damaged pulmonary tissue or alveolar edema; sepsis and multi-organ failure were also cited in some cases, alongside heart or renal failure in others.
- Notable interpretation by contemporaries: French physician quote that influenza condemns secondary infections; William McCallum remarked he never autopsied a flu death without finding bacteria. He viewed these events as epidemics of severe bacterial pneumonia precipitated by the two viruses.
- In modern research, experimental models (mostly mice, sometimes primates) show that adding influenza (or similar viruses) to a bacterial infection like pneumococcus results in markedly worse pathology and faster death, illustrating the continuing relevance of viral-bacterial co-pathogenesis.
The talk links historical observations to current inquiry, describing how colonization by pneumopathogens in crowded settings, followed by a cytolytic viral infection that damages the respiratory epithelium, creates conditions for severe bacterial pneumonia and respiratory compromise.