Modelling seasonal variations in the age and incidence of Kawasaki disease to explore possible infectious aetiologies

Abstract

The average age of infection is expected to vary during seasonal epidemics in a way that is predictable from the epidemiological features, such as the duration of infectiousness and the nature of population mixing. However, it is not known whether such changes can be detected and verified using routinely collected data. We examined the correlation between the weekly number and average age of cases using data on pre-vaccination measles and rotavirus. We show that age -incidence patterns can be observed and predicted for these childhood infections. Incorporating additional information about important features of the transmission dynamics improves the correspondence between model predictions and empirical data. We then explored whether knowledge of the age -incidence pattern can shed light on the epidemiological features of diseases of unknown aetiology, such as Kawasaki disease (KD). Our results indicate KD is unlikely to be triggered by a single acute immunizing infection, but is consistent with an infection of longer duration, a non-immunizing infection or co-infection with an acute agent and one with longer duration. Age -incidence patterns can lend insight into important epidemiological features of infections, providing information on transmission-relevant population mixing for known infections and clues about the aetiology of complex paediatric diseases.

Temporally Varying Relative Risks for Infectious Diseases

“…Another way to summarize the changing age-profile of infection during the course of an epidemic is by the correlation between mean age in a given week and incidence in that week, which we refer to as the age-incidence pattern [30]. By examining the correlation coefficient between the weekly incidence of observed cases and the average age of such cases at different lags, it was shown that determining whether this correlation is highest at negative versus positive lags (i.e.…”

“…By examining the correlation coefficient between the weekly incidence of observed cases and the average age of such cases at different lags, it was shown that determining whether this correlation is highest at negative versus positive lags (i.e. whether the average age is greatest before or after the epidemic peak) helps to identify which age groups are more likely to be infected early on in the epidemic [30]. …”

“…It is the leading cause of acquired heart disease in children from high-income countries, and there is genetic variation in susceptibility [41]. A model was constructed to examine how the age-incidence pattern for Kawasaki disease hospitalizations in the United States would vary depending on assumptions about characteristics of the pathogen(s) involved, such as the duration of infection and the presence or absence of lifelong immunity to reinfection [30]. …”

Kawasaki disease and soy: potential role for isoflavone interaction with Fcγ receptors

“…Thus, prevailing theories regarding infectious etiology assume that KD results from an abnormal immune response to a first infection in predisposed individuals (32). The rarity of the disease over the first few months of life suggests that maternal passive immunity plays a protective role against the inciting The relationship between Kawasaki disease (Kd) incidence for children <5 y (boxes) or <18 y (diamonds) and adult soy consumption per day for three major ethnic groups in hawaii (Caucasian in white, native hawaiian in gray, and Japanese in black).…”

Finding Kawasaki Disease

“…Epidemiologic tools have traditionally been used to determine the etiology of infectious diseases, but, 50 years later, the application of these approaches to the study of KD has only yielded limited insights. [12] Although KD is the most common cause of acquired heart disease in children in countries where rheumatic heart disease has waned, the etiology remains a mystery. [3] The current paradigm is that KD is an immunologic reaction to an environmental trigger in genetically susceptible children.…”