Infection Diseases / Infections / Viral Infection

The prevalence of death from infection in unvaccinated humans is generally driven by age.
Abel & Casanova 2024 Immunity 57(7): 1457-1465

Bacterial infection occurs through Toll pathway and Immune deficiency (IMD) pathway
Royet et al. 2011

There is enormous individual clinical variation in the course of any infection
Casanova & Abel 2021a Annu. Rev. Pathol. 16: 23-50

No more than a dozen known microbes can kill more than 10% of infected individuals, even without medical prevention and treatment. Fewer than 100 microbes can kill more than 1% of infected individuals. Most of the remaining 3,000 known pathogens are less virulent and cause life-threatening disease in <1% of infected individuals. The observed infection-fatality ratio is probably the best estimate of human microbial virulence.
Abel & Casanova 2024 Immunity 57(7): 1457-1465

Microbes considered highly virulent, such as the plague pathogen Yersinia pestis, have infected more people than initially thought.
Ratsitorahina et al. 2000 Trop. Med. Int. Health 5: 94-98
Li et al. 2005 Emerg. Infect. Dis. 11: 1494-1496

Although data on infection fatality are lacking, it is generally believed that the outcome of an infection is determined primarily by qualitative (pathogenicity) and quantitative (inoculum) microbial factors.
Abel & Casanova 2024 Immunity 57(7): 1457-1465

The "infection puzzle" refers to the significant variability in clinical outcomes observed among individuals with infections. Geneticists propose that the root cause of death from infections lies in the host's determinants, which can be inherited or acquired, overt or covert. Death from infection indicates an underlying immunodeficiency. Immunodeficiencies can be:

• Inherited (rare or common)


• Acquired (due to external factors like immunosuppressants or HIV, or internal factors like autoimmunity or immunosenescence)
  Incomplete penetrance means not every individual with an immunodeficiency will develop the disease. Genetic modifiers may influence the presence of immunological abnormalities.
  Casanova & Abel 2021a Annu. Rev. Pathol. 16: 23-50
  Casanova & Abel 2022 Cell 185: 3086-3103

Age-Dependence of Death from Infection

• Most infectious diseases show a strong age-dependence in mortality.


• Primary infections typically occur in childhood, with young children being the most vulnerable.


• Adolescents and young adults are the least susceptible.


• Older individuals generally show increased susceptibility to death, forming a U-shaped prevalence curve.


• Some infections, like malaria, show an L-shaped curve where the risk does not increase in the elderly.


• The 1918 influenza pandemic exhibited a unique W-shaped curve, severely affecting people aged 25-34.


• The COVID-19 pandemic follows a J-shaped curve, with the risk of death doubling every 5 years from childhood onward.


• Endemic and pandemic infections follow distinct, non-overlapping patterns.
  De Schryver & Meheus 1990 Bull. World Health Organ. 68: 639-654
  Taubenberger & Morens 2006 Emerg. Infect. Dis. 12: 15-22
  Alcaı¨s et al. 2010 Ann. N. Y. Acad. Sci. 1214: 18-33
  O’Driscoll et al. 2021 Nature 590: 140-145
  Megli & Coyne 2022 Nat. Rev. Microbiol. 20: 67-82