presents the overall illness attack rates and numbers of cases of influenza illness expected during a single influenza season in the US population under the baseline scenario for each value of R
in 0.1 increments from 1.1 to 2.4. On the basis of estimates derived from past influenza seasons, a seasonal influenza outbreak with R
ranging from 1.1 to 1.6 would correspond to a mild, moderate, or severe seasonal outbreak. A pandemic influenza outbreak with R
ranging from 1.5 to 1.8 would likely be considered a moderate pandemic, and a pandemic influenza outbreak with an R
of 1.8–2.4 would be severe (23
). Our model indicates that approximately 19.3–59.2 million cases of influenza (a 6.3%–19.4% illness attack rate) would occur among the 305.5 million people in the United States during a mild seasonal influenza outbreak (R
1.1–1.2) at baseline. These numbers are consistent with previous estimates. For example, Molinari et al. (28
) estimated that 24.7 million cases occur annually in a typical influenza season (an 8.5% illness attack rate based on the 2003 US population). Under a severe pandemic scenario, if R
2.4, nearly 160 million cases would be expected in the United States (a 52.2% illness attack rate) based on our model.
Baseline influenza illness attack rates (AR, %) and number of cases (millions) based on the model and a US population of 305.5 million people for reproductive number (R) values ranging from 1.1 to 2.4.
The higher the vaccine coverage in children, the greater the reduction in the overall attack rate, the age-specific attack rates, and the number of cases for a given value of R
, regardless of whether the vaccine is well matched or poorly matched to the circulating strain ( and , and ). The relation between increasing values of R
and the absolute difference between illness attack rates for a given level of vaccine coverage compared with baseline is nonmonotonic. The greatest absolute difference in overall attack rates due to vaccination compared with baseline occurs at low to moderate values of R
1.2–1.5). Within this range, as vaccination coverage increases, the greatest absolute benefit of vaccination occurs at slightly higher values of R
. If the vaccines are well matched to the circulating influenza strain, vaccinating 70% of children could prevent as many as 98.7 million cases during a severe seasonal influenza outbreak or a moderate pandemic, depending on the transmission intensity (; 70% vaccination coverage, LAIV, R
1.6). If the vaccines are poorly matched, vaccinating 70% of children could prevent as many as 78.7 million cases during a severe seasonal influenza outbreak, depending on the transmission intensity (; 70% vaccination coverage, LAIV, R
Homologous Vaccine: Comparison of Numbers of Influenza Cases (Millions)a Under 6 Different Vaccination Strategies as the Reproductive Number (R) Ranges From 1.1 to 2.4
Heterologous Vaccine: Comparison of Numbers of Influenza Cases (Millions)a Under 6 Different Vaccination Strategies as the Reproductive Number (R) Ranges From 1.1 to 2.4
Influenza illness attack rates, at baseline and after 70% of children are vaccinated, for a range of values of the reproductive number (R) for both homologous and heterologous vaccine.
Age-specific influenza illness attack rates for adults and children, at baseline and after 70% of children are vaccinated, for a range of values of the reproductive number (R) when the vaccine is homologous.
There is also a nonmonotonic relation between the value of R
and the absolute difference in the reduction in the number of cases when comparing vaccinating children with LAIV and with TIV. Again, the greatest difference in the number of cases prevented when comparing the 2 vaccines was observed at intermediate values of R
for all scenarios. For example, if the vaccines are poorly matched to the circulating influenza strain and vaccine coverage is high (70%), LAIV could prevent an additional 22.1 million influenza cases in the population beyond the number of cases prevented by TIV alone (Table 3; R
= 1.5), given the efficacies modeled. In our model, LAIV, compared with TIV, was assigned higher VESP
, and VEI
values based on our best guesses for these efficacies from previous work (8
). The higher the vaccine efficacies, the greater the numbers of influenza cases that can be prevented.
Regardless of transmission intensity, children have higher attack rates than adults at baseline (). Vaccinating 70% of children with a well-matched influenza vaccine substantially reduces the attack rates for both children and adults at low to moderate levels of transmission intensity (R
1.1−1.5). The difference between the baseline attack rates and the age-specific attack rates at higher levels of transmission intensity is greater for children than for adults. Children experience a greater reduction in age-specific attack rates with the intervention modeled because they benefit from the direct protection of vaccination and the indirect effects, whereas the reduction in the attack rates for adults results from only the indirect effects of vaccinating children. The age-specific illness attack rates at lower vaccination coverage levels are qualitatively similar to those at higher coverage levels, but the rise in the attack rates occurs at lower values of R
for lower vaccination coverage levels and increases more rapidly (results not shown).
Finally, we observed strong indirect, total, and overall effects of influenza vaccination at lower values of R
with high vaccination coverage (). The indirect effects in both adults and children were similar regardless of transmission intensity. The indirect vaccine effects in both groups declined rapidly after R
1.2−1.6, depending on the coverage, indicating that as the level of transmission increased, the unvaccinated were not as well protected indirectly. At values of R
≥ 2.0, the intensity of transmission effectively overwhelms the ability of the vaccine to protect indirectly, given the greater level of exposure to infection. The value of R
at which the indirect effects began to decline depends on the vaccination coverage. With lower vaccination coverage in children, the decline in indirect vaccine effects occurs at lower values of R
. This shift in the decline of the indirect effects in adults is illustrated for all 3 levels of vaccine coverage when both LAIV and TIV are well matched to the circulating influenza strain (). The indirect effects of TIV were slightly lower than the VEIndirect
observed for LAIV regardless of transmission intensity, but the shape of the trends was qualitatively similar.
Indirect, overall, and total vaccine effects (VE) for adults and children when 70% of children are vaccinated with live, attenuated vaccine for a range of values of the reproductive number (R) when the vaccine is homologous.
Indirect vaccine effects (VE) for adults after vaccinating children with influenza vaccine for a range of values of the reproductive number (R) when the vaccine is homologous.
The total effect of vaccination in children remained relatively high regardless of the severity of the outbreak or the coverage level when the vaccines were well matched to the influenza strain. Both the VEOverall in children and the VEOverall in the entire population decreased as R increased, with the initial decline occurring at lower levels of transmission intensity for lower levels of vaccination coverage. The overall and total effects were higher than the indirect effects because they account for the direct effect of the vaccine in the vaccinated children in the population as well as the indirect effects of the vaccination intervention.
When the vaccines were poorly matched to the circulating influenza strains, the same qualitative trends were observed. However, the decline in indirect, total, and overall vaccine effects occurred at lower levels of transmission intensity and decreased more rapidly compared with the well-matched scenario (results not shown).