Estimating the Force of Infection

➢Serological surveys is one of the most common ways to investigate the

epidemiology of infectious diseases and to estimate parameters such as the force
of infection.

➢The force of infection (FOI) can be easily derived from the sero-prevalence
under assumptions including time homogeneity and life long immunity.

➢In terminology of survival analysis, the FOI is nothing else than the hazard
function.
 Age-Dependent Force of Infection
General expressions for the force of infection according to different
link functions in a GLM framework
Using a so-called catalytic model with log link (𝑖. 𝑒. , 𝜋(𝑎) = 1 − 𝑒 𝜂(𝑎) ) leads to a
simple interpretation of the first derivative of the linear predictor. Indeed,𝜂(𝑎) is the
cumulative hazard and hence the force of infection is simply the first derivative of
the linear predictor:

𝜋′(𝑎) 𝜂′(𝑎)𝑒 −𝜂𝑎

𝜆(𝑎) = = −𝜂𝑎
= 𝜂′(𝑎).
𝜋(𝑎) 𝑒

In general, when the link function is not restricted to be the log link, FOI can still be
derived analogously. Basic calculus shows that for a GLM based FOI can be
expressed as a product of two functions:

𝜆(𝑎) = 𝜂′(𝑎)𝛿(𝜂(𝑎)).
 Modeling Issues
➢A first issue is the definition of antibody activity levels as they truly reflect natural
infection, rather than maternal antibodies (inherited immunity) or vaccine induced
activity (vaccine immunity).
➢A second issue is the decay of the antibody activity some (longer) time after
infection, and related to that, the assumption of lifelong immunity.
➢A third issue concerns the already mentioned possibility of misclassifying an
individual as susceptible or being infected together with the deletion of the
equivocal cases.
➢The fourth issue brings us in a seamless way to the fifth issue: the choice of a
model for the predictor function η(a). Moreover, a too restricted model might not
be able to indicate multiple peaks in the force of infection.
➢A final sixth issue concerns the paradigm for inference.
Parametric Approaches to Model the
Prevalence and Force of Infection
 Fractional Polynomial Models
The motivation to model the force of infection with fractional polynomials is to
extend the family of polynomial models, allowing for
(1) more flexibility in combination with
(2) improved behavior at the extremes of the observed age range.
For the Hepatitis A data from Belgium anno 1993–1994 , we consider two
generalized linear models with logit and complementary log–log link functions. For
the logit model the linear predictor is 𝜂(𝑎) = 𝛽0 + 𝛽1 𝑎 + 𝛽2 𝑎3 .
This model has a deviance of 82.74 on with 83 degrees of freedom. For the
complementary log–log model 𝜂(𝑎) = log(𝛽0 )+ 𝛽1 𝑎2 + 𝛽2 𝑎3 , the deviance is 81.41,
also on with 83 degrees of freedom. The force of infection of these models can be
derived from Table.
Parametric models for the prevalence from literature, represented as fractional
polynomials, and their corresponding force of infection
Royston and Altman (1994) introduced the family of fractional polynomials as a
generalization of the conventional polynomial class of functions. In the context of
binary responses, a fractional polynomial (FP) of degree m for the linear predictor is
defined as
η𝑚 (𝑎, 𝛽, 𝑝1 , 𝑝2 , 𝑝3 , … , 𝑝𝑚 ) = σ𝑚
𝑖=0 𝛽𝑖 𝐻𝑖 (𝑎),

where 𝑚 is an integer, 𝑝1 , 𝑝2 , 𝑝3 , … , 𝑝𝑚 is a sequence of powers, and 𝐻𝑖 (𝑎), is a

transformation given by
𝑎 𝑝𝑖 if 𝑝𝑖 ≠ 𝑝𝑖−1
𝐻𝑖 (𝑎) = {
𝐻𝑖−1 𝑎 log 𝑎 if 𝑝𝑖 = 𝑝𝑖−1

with 𝑝0 = 0 and 𝐻𝑖 ≡ 1, and 𝑎𝑝𝑖 = log(a) if 𝑝𝑖 = 0

Semiparametric Approaches to Model the
Prevalence and Force of Infection
 B-Splines
In semiparametric regression, the parametric analysis is extended by including
segment-wise parametric functions that are able to follow deviations from the
overall trend in the data. One typically imposes continuity and differentiability up to
a certain order by constraining these segment-wise functions in the knots, i.e., the
points where two adjacent segments join. This approach is known as spline
smoothing (de Boor 1978).

Eilers and Marx (1996) used B-splines of which the basis functions are defined as
differences of truncated polynomials of degree p (de Boor 1978). They proposed to
use m-order difference penalties on the coefficients of adjacent B-spline basis
functions to control the smoothness of the curve and consequently used the term “P-
splines” (penalized splines).
 References
▪ Anderson R, May R (1991) Infectious diseases of humans: dynamics and control.
Oxford University Press, Oxford.
▪ N. Hens et al., Modeling Infectious Disease Parameters Based on Serological and
Social Contact Data, Statistics for Biology and Health 63, DOI 10.1007/978-1-
4614-4072-7, © Springer Science+Business Media New York 2012.
▪ Bollaerts K, Aerts M, Hens N, Shkedy Z, Faes C, Van Damme P, Beutels P (2012)
Estimating the force of infection directly from antibody levels. Technical report,
Center for Statistics, Hasselt University. In press by Statistical Modelling.
▪ Eilers PHC, Marx BD (1996) Flexible smoothing with B-splines and penalties
(with discussion). Stat Sci 89:89–121.
▪ Niel Hens ,Ziv Shkedy , Marc Aerts et al. Modeling Infectious Disease Parameters
Based on Serological and Social Contact Data, A Modern Statistical Perspective.