Proceedings of the 10th International Colloquium on Paratuberculosis

#50
Assessment <strong>of</strong> <strong>the</strong> age at occurrence <strong>of</strong> MAP infection, adjusting for <strong>the</strong> latent
infection period, in Danish dairy cattle
Kostoulas P a,1 , Nielsen SS b , Browne WJ c , Leontides L a
aLaboratory
<strong>of</strong> Epidemiology, Biostatistics and Animal Health Economics, University <strong>of</strong> Thessaly,
Trikalon 224, GR-43100, Karditsa, Greece.
b
Department <strong>of</strong> Large Animal Sciences, Faculty <strong>of</strong> Life Sciences, University <strong>of</strong> Copenhagen,
Grønnegårdsvej 8, 1870 Frederiksberg C, Denmark.
c
School <strong>of</strong> Clinical Veterinary Sciences, University <strong>of</strong> Bristol, BS40 5DU, U.K.
ABSTRACT
Detection <strong>of</strong> Mycobacterium avium subspecies paratuberculosis (MAP) infection is
considerably delayed due to <strong>the</strong> long latent infection period. We developed and applied a
Bayesian Weibull regression model to make inferences about <strong>the</strong> risk <strong>of</strong> MAP infection from
<strong>the</strong> analysis <strong>of</strong> data from tests that detected infection with delay. Milk and fecal samples were
collected (11 and 4 times/year, respectively) for 1912 cows from 8 naturally infected Danish
dairy herds and tested by an indirect milk ELISA and LJ or HEYM, respectively. We used (I)
a standard Weibull survival model to assess <strong>the</strong> association between age at milk
seroconversion and MAP shedding and (II) <strong>the</strong> proposed model, which adjusted for <strong>the</strong> latent
period <strong>of</strong> MAP infection, to assess <strong>the</strong> association between age at induction <strong>of</strong> MAP infection
and MAP shedding. Estimated median infection times under (II) revealed that animals getting
infected earlier in <strong>the</strong>ir lives were more likely to become MAP shedders, while <strong>the</strong>re was no
difference between shedding levels. Importantly, <strong>the</strong> proposed model captured <strong>the</strong> inverse
relationship between <strong>the</strong> incidence rate <strong>of</strong> seroconversion and that <strong>of</strong> infection with time. The
observed incidence rate <strong>of</strong> milk seroconversion increases, while that <strong>of</strong> infection decreases
with age. Young calves are more susceptible to MAP infection and susceptibility to infection
decreases with time. Ignoring <strong>the</strong> latent infection period severely affects survival estimates;
<strong>the</strong>refore, <strong>the</strong> proposed model can be particularly useful in <strong>the</strong> case <strong>of</strong> chronic infections, like
paratuberculosis, that have a long latent infection period.
INTRODUCTION
Standard diagnostics for Mycobacterium avium subspecies paratuberculosis (MAP) infection
– although highly specific – lack sensitivity, hampering control <strong>of</strong> paratuberculosis in
domestic ruminants. In <strong>the</strong> absence <strong>of</strong> sensitive tests, detection <strong>of</strong> MAP infection is delayed
depending on <strong>the</strong> duration <strong>of</strong> <strong>the</strong> latent infection period. To infer <strong>the</strong> time-to-infection based
on time-to-detection <strong>of</strong> infection data, survival analysis models should adjust for <strong>the</strong> latent
infection period.
Few studies considering survival analysis models adjust for <strong>the</strong> measurement error
on survival times and most <strong>of</strong> <strong>the</strong>m concern retrospectively collected socioeconomic data
(e.g. unemployment time), where respondents round up or <strong>of</strong>f <strong>the</strong>ir recall times (“heaping”).
These models, however, mainly consider errors that are symmetrically distributed around
zero (Augustin and Wolff, 2004), which are, <strong>the</strong>refore, not applicable to infectious diseases
because detection <strong>of</strong> infection is systematically delayed with non-zero mean. O<strong>the</strong>r models
considering multiplicative errors (Skinner and Humphreys, 1999) would not be appropriate
because <strong>the</strong> latent infection period is not expected to be proportional to <strong>the</strong> age at infection.
For example, a multiplicative error model would assume that a cow infected with MAP at <strong>the</strong>
age <strong>of</strong> three would have a latent infection period three times that for a one year old cow.
We developed and applied a Bayesian Weibull survival model that adjusted for <strong>the</strong>
latent period <strong>of</strong> MAP infection. We initially analyzed <strong>the</strong> data (I) ignoring <strong>the</strong> latent period to
assess <strong>the</strong> association between age at milk seroconversion and shedding level.
1 pkost@vet.uth.gr
151
1