Abstract
Mycobacterium avium subsp. paratuberculosis (MAP) causes a chronic infection in cattle. MAP infected cattle with humoral immune (HI) reactions with IgG antibodies are usually those where latency of infection has ceased and their infection is progressing towards reduced milk yield, weight loss and significant bacterial excretion in feces. The proportion of detectable infections among all infected animals that will develop disease is often referred to as ‘the tip of the iceberg’. The purpose of this study was to estimate this proportion. Test-records from 18,972 Danish dairy cows with MAP specific IgG antibodies on their final test-record were used to estimate age-specific sensitivities (Se). These cows were the infected ones considered to develop disease in a population with a representative age-distribution and were defined as cases. The specificity (Sp) of the test was estimated based on test-results from 166,905 cows, which had no MAP IgG antibodies in their final four test-records. The Sp, age-specific Se and maximum Se were used to estimate the probability of having HI at a given age resulting in the proportion of infected cows with HI at a given age. For cows 2 years of age, the proportion of detectable cases was 0.33, while it was 0.94 for cows 5 years of age. Thus, there was a significant shift in the tip of the iceberg with aging. This study provided a model for estimating the proportion of latent chronic infections that would progress to disease, and the results can be used to model infection dynamics.
Highlights
Paratuberculosis is a chronic infection of cattle and other ruminants, caused by Mycobacterium avium subsp. paratuberculosis (MAP) [1]
MAP infections are presumed to occur in calfhood with a subsequent latent infection, where pro-inflammatory immune responses are thought to keep the infection under control [2], [3]
The infection evolves before 2 years of age, but from 2 to 6 years of age, a large proportion of infected animals appears to develop anti-inflammatory immune responses characterized by IgG antibodies [4], [5]
Summary
Paratuberculosis is a chronic infection of cattle and other ruminants, caused by Mycobacterium avium subsp. paratuberculosis (MAP) [1]. A population may consist of three groups of animals: 1) non-infected or potentially latently infected animals where infection will never evolve; 2) MAP infected animals with a latent infection that will evolve within the expected life-time; and 3) MAP infected animals where the infection is progressing with a predominant antiinflammatory or humoral immune response (HI) The size of these three groups is of interest when disease progression should be predicted, for example in mathematical infection models [11], [12], and the proportion of those with HI among all infected, where the infection will develop, is often referred to as ‘‘the tip of the iceberg’’. This proportion would most likely depend on the age-distribution in the population, because the infection is chronic
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