Abstract
Background: Bovine tuberculosis (bTB; Mycobacterium bovis) remains a significant problem in a number of countries, and is often found where M. avium subsp. paratuberculosis (MAP) is also present. In the United Kingdom, bTB has been difficult to eradicate despite long-term efforts. Co-infection has been proposed as one partial mechanism thwarting eradication.Methods: A retrospective case-control study of 4,500 cattle herds in Northern Ireland, where serological testing of cattle for MAP, was undertaken (2004–2015). Blood samples were ELISA tested for MAP; infection of M. bovis was identified in herds by the comparative tuberculin test (CTT) and through post-mortem evidence of infection. Case-herds were those experiencing a confirmed bTB breakdown; control-herds were not experiencing a breakdown episode at the time of MAP testing. A second model included additional testing data of feces samples (culture and PCR results) to better inform herd MAP status. Multi-level hierarchical models were developed, controlling for selected confounders. A sensitivity analysis of the effect of MAP sample numbers per event and the prior timing of tuberculin-testing was undertaken.Results: 45.2% (n = 250) of case observations and 36.0% (3,480) of control observations were positive to MAP by ELISA (45.8% and 36.4% when including ancillary fecal testing, respectively). Controlling for known confounders, the adjusted odds ratio (aOR) for this association was 1.339 (95%CI:1.085–1.652; including ancillary data aOR:1.356;95%CI:1.099–1.673). The size-effect of the association increased with the increasing number of samples per event used to assign herd MAP status (aOR:1.883 at >2 samples, to aOR:3.863 at >10 samples), however the estimated CI increased as N decreased. 41.7% of observations from chronic herds were MAP serology-positive and 32.2% from bTB free herds were MAP positive (aOR: 1.170; 95%ci: 0.481–2.849).Discussion: Cattle herds experiencing a bTB breakdown were associated with increased risk of having a positive MAP status. Chronic herds tended to exhibit higher risk of a positive MAP status than bTB free herds, however there was less support for this association when controlling for repeated measures and confounding. MAP co-infection may be playing a role in the success of bTB eradiation schemes, however further studies are required to understand the mechanisms and to definitively establish causation.
Highlights
Chronic mycobacterial infections are some of the most challenging pathogens to eradicate at national and international scales, requiring large-scale long-term coordinated eradication efforts [1,2,3]
This study identified a robust association between confirmed bovine TB breakdown episodic risk and herd M. avium subsp. paratuberculosis (MAP) status, based primarily on MAP serum ELISA testing with some supplementary fecal testing
We have found robust associations between bTB herd breakdown episode risk and concurrent MAP infections at the herd level
Summary
Chronic mycobacterial infections are some of the most challenging pathogens to eradicate at national and international scales, requiring large-scale long-term coordinated eradication efforts [1,2,3]. A further complication is the presence of a known wildlife reservoir species that can harbor widespread and high levels of infection [11, 12], and which cull trials have provided evidence to suggest are involved in the risk of infection within cattle herds [13, 14]. Despite these issues, modeling studies suggest that the mean reproductive number of the system (R0), which determines whether infection will be maintained in populations in perpetuity, is only slightly above 1 [15,16,17]. Co-infection has been proposed as one partial mechanism thwarting eradication
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