Infection and immunity in the simulation tool 4Flu


4Flu simulates the spread of the four influenza strains A(H1N1), A(H3N2), B/Yamagata and B/Victoria on a dynamically evolving contact network of individuals. As it is not possible to start the simulations with a realistic age-dependent immunity pattern, the simulations have to be initialized for some time (default: 20 years) during which demographic turnover, vaccinations and infections occur.

Infection and natural history

Infected individuals pass through a latent period before becoming infectious. The duration of infectiousness is different for children and for adults. Infected individuals can pass on their infection to some others who are in contact with them, but usually not all susceptible contacts will be infected. The average value of the probability of infection is calibrated such that for the model with German demography and German contact matrix, the annual infection incidence of young adults is 10.6% (Williams et al. "Seasonal influenza risk in hospital healthcare workers is more strongly associated with household than occupational exposures: results from a prospective cohort study in Berlin, Germany, 2006/07", 2010; BMC Infectious Diseases 10: 8). This value fluctuates seasonally with a peak which is 43% higher than average around Christmas and a minimum in summer (Vynnycky et al. "Estimating the impact of childhood influenza vaccination programmes in England and Wales", Vaccine 2008; 26: 5321-5330). Due to the low transmission in summer, infections regularly go extinct during the summer months, but new infections are introduced throughout the simulation year at a very low rate.
Infection and immunity graph

Dynamic of specific and unspecific immunity

After recovering from infection, individuals become immune against the influenza virus with which they were infected. In case of an influenza B infection, they may furthermore acquire protection against the other B lineage ("B lineage cross protection"). Each individual's immunity is lost after some time, but it may be boostered by later infections or vaccinations. Furthermore, the user has the possibility to activate a non-specific ("inferferon") immunity which protects an infected individual against all other infections for a specified time.

Drift variants

In random years, circulating influenza variants are replaced by newly occurring drift variants. The user can specify for each one of the 4 influenza strains, how long it takes on average until a circulating variant is replaced by a new one. Only a percentage of the individuals who were protected against the old variant are also protected against the new drift variant. This further shortens the duration of immunity. In some of the years when a new drift variant occurs, the vaccine is not well matched against this new drift variant, which reduces the vaccine efficacy (i.e. the percentage of vaccinees who become immune).