Influenza transmission in households during the 1918 pandemic

Abstract

Analysis of historical data has strongly shaped our understanding of the epidemiology of pandemic influenza and informs analysis of current and future epidemics. Here, the authors analyzed previously unpublished documents from a large household survey of the "Spanish" H1N1 influenza pandemic, conducted in 1918, for the first time quantifying influenza transmissibility at the person-to-person level during that most lethal of pandemics. The authors estimated a low probability of person-to-person transmission relative to comparable estimates from seasonal influenza and other directly transmitted infections but similar to recent estimates from the 2009 H1N1 pandemic. The authors estimated a very low probability of asymptomatic infection, a previously unknown parameter for this pandemic, consistent with an unusually virulent virus. The authors estimated a high frequency of prior immunity that they attributed to a largely unreported influenza epidemic in the spring of 1918 (or perhaps to cross-reactive immunity). Extrapolating from this finding, the authors hypothesize that prior immunity partially protected some populations from the worst of the fall pandemic and helps explain differences in attack rates between populations. Together, these analyses demonstrate that the 1918 influenza virus, though highly virulent, was only moderately transmissible and thus in a modern context would be considered controllable.

Figure 1.

A) Sizes of the households included in a canvass of influenza cases in Baltimore, Maryland, 1918. We analyzed data from 6,753 households with a mean of 4.26 inhabitants per household. B) Distribution of the 7,140 recorded influenza cases within these households. For each household size, the bars show the proportion of households recording 0, 1, 2, or more cases, highlighted in colors ranging from cold (white/blue) to warm (red/black). The yellow diamonds show the attack rate for each household size (the overall attack rate was 24.7%), while the open triangles show the secondary attack rate (i.e., the attack rate for remaining persons after the introduction of 1 infected case); the overall mean was 32.5%. Data from households containing more than 12 people were sparse and are not shown. C) Graph equivalent to that in part B, showing the best-fitting basic Reed-Frost model. D) Predictions of the best-fitting extended model (which included the effects of prior immunity, variable infectiousness, and transmission rates scaling with household size).

Figure 2.

A) Susceptible-infectious transmission probability for the 1918 influenza pandemic, by household size. In addition to results from the Baltimore, Maryland, study, which are shown in red (squares, nonparametric; line, parametric), results are also shown for a study of 2009 H1N1 pandemic influenza (22) (orange circles) and 2 further studies of seasonal influenza transmission (green diamonds, Epigrippe Study (21); blue triangles, Tecumseh Study (20)). The studies used different methods, so estimates are not exactly comparable; the comparison with the Tecumseh Study (20) may be the most valid, since we analyzed serologically confirmed infections in initially seronegative households. The 2 other studies were also comparable, since they were based on follow-up of symptomatic cases after an index case (21, 22). All of the studies show evidence of declining susceptible-infectious transmission probability in larger households, but this is less pronounced for the 1918 Frost and Sydenstricker study (19) than for the others, perhaps because of secular changes in the nature of the household (see Web Appendix). Bars, 95% confidence interval. B) Characterization of a measure of interperson variability in infectiousness by means of a plot of the proportion of transmission attributable to the X% most infectious individuals. The brown line corresponds to homogeneity (when all infected persons have identical infectiousness); the lower red line shows the best-fitting model. The upper red line corresponds to the estimate from a different but plausible model with misreporting (see Web Appendix), and thus the red shaded area corresponds to estimates with model uncertainty. The curves were compared with a previous analysis of several infectious diseases (34): The blue line shows the most variable of the infectious diseases studied (severe acute respiratory syndrome (SARS)) and the green line the least (pneumonic plague). C) Predicted number of secondary cases attributable to within-household transmission (blue bars) and between-household transmission (orange bars) for an index case living in a household of size 5, in the absence of prior immunity or public health interventions. An index case infects an average of 0.69 persons in his or her household and 1.22 persons outside of it. The distributions are highly overdispersed. D) Distribution of immune individuals within households of different sizes predicted by the best-fitting model, using the same color scheme as in Figure 1. The yellow diamonds show the average proportion of immune individuals.

Figure 3.

Time series of incident symptomatic influenza cases in a 1918 Baltimore, Maryland, canvass (19) (green bar chart). Estimates of the effective reproduction number R (how many people each infected person infects; the blue shaded area is the 95% confidence interval) and of the effective household reproduction number R^* (how many households each infected household infects; the pink shaded area is the 95% confidence interval) are shown. Inset: estimates of the generation time distribution for individuals (blue line; gamma distribution with mean 2.85 days (standard deviation (SD), 0.93)) and for households with no prior immunity (purple line; mean = 5.01 days (SD, 2.83)) or households with prior immunity (red line; mean = 4.68 days (SD, 2.69)). For clarity, the household generation time distribution is not normalized in the plot.