Modeling directly from antibody levels

library(serosv)

Mixture model

Proposed model

Two-component mixture model for test result \(Z\) with \(Z_j (j = \{I, S\})\) being the latent mixing component having density \(f_j(z_j|\theta_j)\) and with \(\pi_{\text{TRUE}}(a)\) being the age-dependent mixing probability can be represented as

\[ f(z|z_I, z_S,a) = (1-\pi_{\text{TRUE}}(a))f_S(z_S|\theta_S)+\pi_{\text{TRUE}}(a)f_I(z_I|\theta_I) \]

The mean \(E(Z|a)\) thus equals

\[ \mu(a) = (1-\pi_{\text{TRUE}}(a))\mu_S+\pi_{\text{TRUE}}(a)\mu_I\]

From which the true prevalence can be calculated by

\[ \pi_{\text{TRUE}}(a) = \frac{\mu(a) - \mu_S}{\mu_I - \mu_S} \]

Force of infection can then be calculated by

\[ \lambda_{TRUE} = \frac{\mu'(a)}{\mu_I - \mu(a)} \]

Fitting data

To fit the mixture data, use mixture_model function

df <- vzv_be_2001_2003[vzv_be_2001_2003$age < 40.5,]
df <- df[order(df$age),]
data <- df$VZVmIUml
model <- mixture_model(antibody_level = data)
model$info
#> 
#> Parameters:
#>       pi    mu  sigma
#> 1 0.1088 2.349 0.6804
#> 2 0.8912 6.439 0.9437
#> 
#> Distribution:
#> [1] "norm"
#> 
#> Constraints:
#>    conpi    conmu consigma 
#>   "NONE"   "NONE"   "NONE"
plot(model)

sero-prevalence and FOI can then be esimated using function estimate_from_mixture

est_mixture <- estimate_from_mixture(df$age, data, mixture_model = model, threshold_status = df$seropositive, sp=83, monotonize = FALSE)
plot(est_mixture)
#> Warning: No shared levels found between `names(values)` of the manual scale and the
#> data's fill values.