The 1918 influenza pandemic killed 20–40 million people worldwide1, and is seen as a worst-case scenario for pandemic planning. Like other pandemic influenza strains, the 1918 A/H1N1 strain spread extremely rapidly. A measure of transmissibility and of the stringency of control measures required to stop an epidemic is the reproductive number, which is the number of secondary cases produced by each primary case2. Here we obtained an estimate of the reproductive number for 1918 influenza by fitting a deterministic SEIR (susceptible-exposed-infectious-recovered) model to pneumonia and influenza death epidemic curves from 45 US cities: the median value is less than three. The estimated proportion of the population with A/H1N1 immunity before September 1918 implies a median basic reproductive number of less than four. These results strongly suggest that the reproductive number for 1918 pandemic influenza is not large relative to many other infectious diseases2. In theory, a similar novel influenza subtype could be controlled. But because influenza is frequently transmitted before a specific diagnosis is possible and there is a dearth of global antiviral and vaccine stores, aggressive transmission reducing measures will probably be required.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Patterson, K. D. & Pyle, G. F. The geography and mortality of the 1918 influenza pandemic. Bull. Hist. Med. 65, 4–21 (1991)
Anderson, R. M. & May, R. M. Infectious Diseases of Humans: Dynamics and Control (Oxford Univ. Press, Oxford, 1991)
Webby, R. J. & Webster, R. G. Are we ready for pandemic influenza? Science 302, 1519–1522 (2003)
Nicholson, K., Webster, R. G. & Hay, A. J. Textbook of Influenza (Blackwell Science, Malden, Massachusetts, 1998)
Webster, R. G., Bean, W. J., Gorman, O. T., Chambers, T. M. & Kawaoka, Y. Evolution and ecology of influenza A viruses. Microbiol. Rev. 56, 152–179 (1992)
Simonsen, L. et al. Pandemic versus epidemic influenza mortality: a pattern of changing age distribution. J. Infect. Dis. 178, 53–60 (1998)
Frost, W. H. Statistics of influenza morbidity with special reference to certain factors in case incidence and case fatality. Public Health Rep. 35, 584–597 (1920)
Longini, I. M. Jr, Halloran, M. E., Nizam, A. & Yang, Y. Containing pandemic influenza with antiviral agents. Am. J. Epidemiol. 159, 623–633 (2004)
Gog, J. R., Rimmelzwaan, G. F., Osterhaus, A. D. & Grenfell, B. T. Population dynamics of rapid fixation in cytotoxic T lymphocyte escape mutants of influenza A. Proc. Natl Acad. Sci. USA 100, 11143–11147 (2003)
Spicer, C. C. & Lawrence, C. J. Epidemic influenza in Greater London. J. Hyg. (Lond.) 93, 105–112 (1984)
Rvachev, L. A. & Longini, I. M. Jr A mathematical model for the global spread of influenza. Math. Biosci. 75, 3–22 (1985)
Fraser, C., Riley, S., Anderson, R. M. & Ferguson, N. M. Factors that make an infectious disease outbreak controllable. Proc. Natl Acad. Sci. USA 101, 6146–6151 (2004)
Jordan, E. O. Epidemic Influenza; a Survey (American Medical Assn, Chicago, 1927)
Wolbach, S. B. Comments on the pathology and bacteriology of fatal influenza cases, as observed at Camp Devens, Mass. Johns Hopkins Hosp. Bull. 338, 104–109 (1919)
MacCallum, W. G. Johns Hopkins Hospital Reports (Johns Hopkins Press, Baltimore, 1921)
Klotz, O. Studies on Epidemic Influenza 207–293 (Pittsburgh Univ. School of Medicine, Pittsburgh, 1919)
Collins, S. D., Frost, W. H., Gover, M. & Sydenstricker, E. Mortality from Influenza and Pneumonia in 50 Large Cities of the United States 1910–1929. Public Health Rep. 45, 2277–2328 (1930)
Bureau of the Census, Mortality Rates 1910–1920 with Population of the Federal Censuses of 1910 and 1920 and Intercensal Estimates of Population (Govt Print. Off., Washington, 1923)
Bureau of the Census. Population of the 100 largest urban places: 1920. 〈http://www.census.gov/population/documentation/twps0027/tab15.txt〉 (1998).
Bureau of the Census. Population of the 100 largest urban places: 1910. 〈http://www.census.gov/population/documentation/twps0027/tab14.txt〉 (1998).
Pearl, R. Influenza studies: further data on the correlation of explosiveness of outbreak of the 1918 epidemic. Public Health Rep. 36, 273–298 (1921)
Frost, W. H. The epidemiology of influenza. J. Am. Med. Assoc. 73, 313–318 (1919)
Olson, D. R., Simonsen, L., Edelson, P. J. & Morse, S. S. 4th Int. Conf. on Emerging Infectious Diseases [Abstract] (CDC, Atlanta, 2004)
Stanley, L. L. Influenza at San Quentin Prison, California. Public Health Rep. 34, 996–1008 (1919)
Hill, A. N. & Longini, I. M. Jr The critical vaccination fraction for heterogeneous epidemic models. Math. Biosci. 181, 85–106 (2003)
Riley, S. et al. Transmission dynamics of the etiological agent of SARS in Hong Kong: impact of public health interventions. Science 300, 1961–1966 (2003)
Lipsitch, M. et al. Transmission dynamics and control of severe acute respiratory syndrome. Science 300, 1966–1970 (2003)
Wallinga, J. & Teunis, P. Different epidemic curves for severe acute respiratory syndrome reveal similar impacts of control measures. Am. J. Epidemiol. 160, 509–516 (2004)
We thank J. Wallinga and D. Olson for discussions and C. Raviola for data procurement. This work was supported in part by the National Defense Science and Engineering Graduate Fellowship (C.E.M.), the Medical Scientist Training Program Fellowship (C.E.M.), NIAID (J.M.R. and M.L.) and the Ellison Medical Foundation (M.L.).
The authors declare that they have no competing financial interests.
This file includes Supplementary Data, Methods, Discussion and Figure Legends. (DOC 100 kb)
Histogram of the proportion of infected hosts assumed to be infectious between 1 and 8 days post infection in the model. (PDF 15 kb)
Histogram of the proportion of all deaths occurring on each day in the five weeks following infection. (PDF 15 kb)
Transmission rate ratio, the adult:child CFP ratio (m) and the number of serial intervals required for the exponential growth rate to reflect the magnitude of R. (PDF 213 kb)
Spreadsheet of the weekly excess pneumonia and influenza mortality data originally published in Collins, S. D., Frost, W. H., Gover, M. & Sydenstricker, E. Mortality from Influenza and Pneumonia in 50 Large Cities of the United States 1910-1929. Public Health Reports 45, 2277-2328 (1930). (XLS 23 kb)
About this article
The Journal of Infectious Diseases (2019)
Mathematical Methods in the Applied Sciences (2019)
Synthesis and SAR Study of Carbamoyl Pyridone Bicycle Derivatives as Potent Inhibitors of Influenza Cap-dependent Endonuclease
Journal of Medicinal Chemistry (2019)
Computational and Structural Biotechnology Journal (2019)
A practical generation-interval-based approach to inferring the strength of epidemics from their speed