Animal tuberculosis: impact of disease heterogeneity in transmission, diagnosis, and control

Abstract

Animal tuberculosis (TB) in terrestrial mammals is mainly caused by Mycobacterium bovis. This pathogen is adapted to a wide range of host species, representing a threat to livestock, wildlife and human health. Disease heterogeneity is a hallmark of multi‐host TB and a challenge for control. Drivers of animal TB heterogeneity are very diverse and may act at the level of the causative agent, the host species, the interface between mycobacteria and the host, community of hosts, the environment and even policy behind control programmes. In this paper, we examine the drivers that seem to contribute to this phenomenon. We begin by reviewing evidence accumulated to date supporting the consensus that a complex range of genetic, biological and socio‐environmental factors contribute to the establishment and maintenance of animal TB, setting the grounds for heterogeneity. We then highlight the complex interplay between individual, species‐specific and community protective factors with risk/maintenance variables that include animal movements and densities, co‐infection and super‐shedders. We finally consider how current interventions should seek to consider and explore heterogeneity in order to tackle potential limitations for diagnosis and control programmes, simultaneously increasing their efficacy.

Cell-Mediated Immunological Biomarkers and Their Diagnostic Application in Livestock and Wildlife Infected With Mycobacterium bovis

“…The most used cytokine biomarker for TB diagnostic assays is IFN-γ, a critical Th1 cytokine produced upon lymphocyte activation in defense against M. bovis (43). This cytokine is also vital for the formation and function of granulomas, a hallmark of the response to M. bovis in host species (94,120). Compared with other cytokine assays to date, IGRAs are robust and comparatively easy to standardize, and the development of new IGRAs for multiple non-bovine species has been suggested for bTB screening and control (13,120).…”

“…This cytokine is also vital for the formation and function of granulomas, a hallmark of the response to M. bovis in host species (94,120). Compared with other cytokine assays to date, IGRAs are robust and comparatively easy to standardize, and the development of new IGRAs for multiple non-bovine species has been suggested for bTB screening and control (13,120). The increasingly widespread use of IGRAs (such as Bovigam R ) in cattle, due to US-and EUapproval as a TST adjunct for parallel testing in bTB eradication programs to increase Se, may also explain interest in its use for wildlife species.…”

“…Although IFN-γ has proved invaluable for several species as a biomarker of M. bovis infection, in other species, including lions and warthogs (Phacochoerus africanus), it does not appear to be as useful (83,98). It has also been observed that depending on the infection phase, IGRAs (and the SICTT) may fail to detect M. bovis-infected animals, which could be due to either very early infection (when a response detectable by the IGRA is still forming) or a depressed (anergic) immune state occurring in the later stages of bTB (119,120). In addition, there may be individual or species differences in immune responses, resulting in failure of IGRAs to detect infection.…”

“…Moreover, IGRA results can be confounded by co-infections with environmental strains, vaccination (in some domestic species) and, although contended, possible interference by previous testing including the SICTT (13,69). The host immune response to mycobacteria is naturally linked to disease progression yet bTB generally presents with extended and advanced, poorly described disease stages, posing an additional challenge for the extension of IFN-γ-based diagnostics to distinguish infection from active disease (120,122). However, correlations between IFN-γ and M. bovis pathology have been preliminarily detected in badgers and buffaloes (72,74).…”

Estimates of the global and continental burden of animal tuberculosis in key livestock species worldwide: A meta-analysis study

“…The performance of both tests can be influenced by host intrinsic factors. Standard application conditions and result interpretation are normally described for cattle, requiring optimization when transposed to other species [ 14 , 15 ]. The post mortem evaluation by gross pathology, histopathology and bacteriological techniques are the reference diagnostic methods for animal TB [ 13 ].…”