Stages of Paratuberculosis

Paratuberculosis infection has been described in four stages: silent, subclinical, clinical and advanced clinical (Tiwari et al., 2006). Of note, a recently proposed reclassification suggests that the silent and the subclinical stages can be binned together, as these first two stages both represent MAP infection without any noticeable clinical signs.

Animals in the silent stage have been in­fected with MAP but do not shed the bacteria, nor do they have a detectable immune response. Therefore, diagnosis is based on tissue culture/ histology/polymerase chain reaction (PCR) (Whittington et al., 2017). Animals in the sub- clinical stage may be detected through diagnos­tic tests that detect presence of the organism, but these methods often yield a high proportion of false-negative test results, due to intermittent shedding of low amounts of MAP. Enzyme- linked immunosorbent assays (ELISAs) can also be used at the subclinical stage but have lower sensitivity; however, sensitivity improves as the animal approaches the clinical stage (Tiwari et al., 2006). Subclinically affected animals have decreased milk production that is positively as­sociated with ELISA status and test optical den­sity (OD) (Sorge et al., 2011). The clinical stage is characterized by decrease in body condition despite a normal or increased appetite, inter­mittent to persistent diarrhoea with increased thirst, decreased milk production and reduced fertility. Diagnostic tests evaluating antibody responses are most reliable for animals in the clinical stage of infection (Tiwari et al., 2006). Reduced productivity plus other clinical signs (diarrhoea, weight loss) often prompt the re­moval of these animals from the herd before they enter the final stage. Animals entering the advanced clinical stage of infection are of­ten weak, lethargic and emaciated with ‘pipe stream' diarrhoea. Eventually they may develop mandibular oedema (bottle jaw) from enteric protein loss and the subsequent loss of oncotic pressure (Tiwari et al., 2006).

Often paratuberculosis is referred to as a disease that exhibits the iceberg phenomenon: for every advanced clinical case, there are one or two clinical cases, four to eight subclinical cases and 10-14 in the silent stage of MAP infection. However, based on models by Magombedze et al. (2013), the proportion of silent infections may be greatly overestimated. They reported that the calculated ratio was highly dependent on how long the disease had been present on the farm, but in all instances, the number of animals in the silent stage was much less than that in the subclinical stage. This could possibly be due to past studies misclassifying subclinical animals as silent infections (Magombedze et al., 2013). This has implications for disease modelling and control, in that the iceberg ratio has been used to provide a rough estimate of disease burden and disease risk. With misclassification of sub- clinical shedding animals into a silent stage of disease, we underestimate the risk for disease spread. More recently, two distinct types of shed­ding patterns of paratuberculosis have been described, progressive and non-progressive (Schukken et al., 2015; Beaver et al., 2017). These non-progressive shedders shed low num­bers of MAP in their faeces intermittently and do not mount any appreciable humoral immune response, in contrast to progressive shedders, which slowly increase the amount of MAP shed in their faeces and have seroconversion of im­munoglobulins. Proportions of these progressive and non-progressive shedders within an infected herd may be important in future paratuberculo­sis research and control programmes.

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