Abstract Background Recently, the promise of a new universal long-term flu vaccine has become more tangible than ever before. Such a vaccine would protect against very many seasonal and pandemic flu strains for many years, making annual vaccination unnecessary. However, due to complacency behavior, it remains unclear whether the introduction of such vaccines would maintain high and stable levels of vaccination coverage year after year. Findings To predict the impact of universal long-term flu vaccines on influenza epidemics we developed a mathematical model that linked human cognition and memory with the transmission dynamics of influenza. Our modeling shows that universal vaccines that provide short-term protection are likely to result in small frequent epidemics, whereas universal vaccines that provide long-term protection are likely to result in severe infrequent epidemics. Conclusions Influenza vaccines that provide short-term protection maintain risk awareness regarding influenza in the population and result in stable vaccination coverage. Vaccines that provide long-term protection could lead to substantial drops in vaccination coverage and should therefore include an annual epidemic risk awareness programs in order to minimize the risk of severe epidemics.

Abstract Background Current measures of the clinical efficacy of antiretroviral therapy (ART) in the treatment of HIV include the change in HIV RNA in the plasma and the gain in CD4 cells. Methods We propose new measures for evaluating the efficacy of treatment that is based upon combinations of non-nucleoside and nucleoside reverse transcriptase inhibitors. Our efficacy measures are: the CD4 gain per virion eliminated , the potential of CD4 count restoration and the viral reproduction number (R0) . These efficacy measures are based upon a theoretical understanding of the impact of treatment on both viral dynamics and the immune reconstitution. Patient data were obtained from longitudinal HIV clinical cohorts. Results We found that the CD4 cell gain per virion eliminated ranged from 10-2 to 600 CD4 cells/virion, the potential of CD4 count restoration ranged from 60 to 1520 CD4 cells/μl, and the basic reproduction number was reduced from an average of 5.1 before therapy to an average of 1.2 after one year of therapy. There was substantial heterogeneity in these efficacy measures among patients with detectable viral replication. We found that many patients who achieved viral suppression did not have high CD4 cell recovery profiles. Our efficacy measures also enabled us to identify a subgroup of patients who were not virally suppressed but had the potential to reach a high CD4 count and/or achieve viral suppression if they had been switched to a more potent regimen. Conclusion We show that our new efficacy measures are useful for analyzing the long-term treatment efficacy of combination reverse transcriptase inhibitors and argue that achieving a low R0 does not imply achieving viral suppression.