Systematic analysis of infectious disease outcomes by age shows lowest severity in school-age children

Abstract

The COVID-19 pandemic has ignited interest in age-specific manifestations of infection but surprisingly little is known about relative severity of infectious disease between the extremes of age. In a systematic analysis we identified 142 datasets with information on severity of disease by age for 32 different infectious diseases, 19 viral and 13 bacterial. For almost all infections, school-age children have the least severe disease, and severity starts to rise long before old age. Indeed, for many infections even young adults have more severe disease than children, and dengue was the only infection that was most severe in school-age children. Together with data on vaccine response in children and young adults, the findings suggest peak immune function is reached around 5-14 years of age. Relative immune senescence may begin much earlier than assumed, before accelerating in older age groups. This has major implications for understanding resilience to infection, optimal vaccine scheduling, and appropriate health protection policies across the life course.

Fig. 1

Severity of infectious disease by age for polio, typhoid, tuberculosis, smallpox, chickenpox, measles, infectious mononucleosis and HIV. The 95% confidence intervals on the estimates are shown where they are known or could be calculated. (a) Polio in England and Wales 1947–50, notified deaths/notified cases (23,143 cases); (b) Typhoid in small towns in New York State, US, 1915–24, notified deaths/notified cases; (c) Pulmonary TB in Denmark, 1925–34, percent of notified cases dying by 31^st December 1934; (d) Measles in England and Wales, 1970–88, notified deaths/notified cases; (e) Smallpox in London Smallpox Hospital, UK, 1836–51, case fatality rate among unvaccinated patients; (f) Chickenpox in France 1997–9, estimated hospitalisation rates based on national databases and surveillance; (g) Infectious mononucleosis in Rochester, Minnesota, US, 1950–69, percent hospitalised; (h) HIV in Europe, North America and Australia, 1983–1996, percent dying within 10 years, mother-to-child infections excluded (12,910 cases, survival estimated from graph).

Fig. 2

Severity of infectious disease by age for influenza, pertussis, Salmonellosis, yellow fever, typhus, scarlet fever, Ebola, and Meningococcal meningitis. The 95% confidence intervals on the estimates are shown where they are known or could be calculated. (a) Influenza in Maryland, US, 1918–19, case fatality rate from household surveys; (b) Pertussis in small towns in New York State, US, 1915–24, notified deaths/notified cases; (c) Salmonellosis in Spain 1997–2006, case fatality rate among hospitalised patients (numbers estimated from graph and population data); (d) Yellow fever in New Orleans, US, 1878, case fatality rate; (e) Typhus in London Fever Hospital 1848–57, case fatality rate; (f) Scarlet fever in Pennsylvania, US, 1907–12, notified deaths/notified cases; (g) Ebola in Guinea, Liberia and Sierra Leone, 2013–15. case fatality rate; (h) Meningococcal meningitis in Cyprus, 1908–9, case fatality rate.

Fig. 3

Severity of infectious disease by age for Japanese encephalitis, cholera, Lassa fever, brucellosis, hepatitis B, plague, hepatitis A, and SARS The 95% confidence intervals on the estimates are shown where they are known or could be calculated. (a) Japanese encephalitis in Korea, 1955–66, notified deaths/notified cases; (b) Cholera in Munich, Germany, 1873–4, notified deaths/notified cases; (c) Lassa fever in Nigeria, 2018, case fatality rate in laboratory confirmed cases; (d) Brucellosis in Malta, 1936, case fatality rate; (e) Hepatitis B in Alaska, 1971–6, proportion of new infections with symptomatic hepatitis; (f) Plague in 75 villages in Jalandhar District, India, 1897–8, notified deaths/notified cases; (g) Hepatitis A in England and Wales, 1979–85, notified deaths/notified cases; (h) SARS in Hong Kong, 2003, case fatality rate (numbers estimated from incidence and population data).

Fig. 4

Severity of infectious disease by age for COVID-19, MERS-CoV, St Louis encephalitis, Western equine encephalitis, diphtheria, Escherichia coli, and dengue. The 95% confidence intervals on the estimates are shown where they are known or could be calculated. (a) COVID-19 in Spain 2020, notified deaths/notified confirmed cases, as of 11 May 2020; (b) MERS-CoV in Saudi Arabia June 2012-July 2014 and 2017–18, case fatality rate^,; (c) S Louis encephalitis in St Louis, US, 1933, case fatality rate, (d) Campylobacter in Canada, 2001–4, percent hospitalised; (e) Western equine encephalitis in Mannitoba, Canada, 1941, case fatality rate; (f) Diphtheria in London, UK, 1894–1903, notified deaths/notified cases; (g) E coli 0104/H4 Hamburg, Germany, 2011, proportion developing haemolytic uraemic syndrome; (h) Dengue in Brazil 2000–2014, proportion haemorrhagic, with any complications, and hospitalised.