250 F. Olea-Popelka et al.
species in national bovine TB control pro-
grammes. With regard to the potential zoonotic
transmission from these domestic species, the
risk profile should, in principle, be based primar-
ily on utilization of milk and meat and, to a
smaller extent, on close contact, indicating that
these species should clearly be considered in
future strategies to prevent and control zoonotic
TB when local conditions and socio-cultural
practices favour the transmission of M. bovis
from these domestic species to humans.
16.3 Diagnosis and ImmunologyCurrent approaches to diagnosing TB in the live
animal rely on an immunological readout. This
introduces the possibility that animals that have
been exposed to the infection but have subse-
quently cleared it successfully will be killed
unnecessarily. Indeed, we may unwittingly be
removing animals with a degree of immunologi-
cal resistance to infection. This could be avoided
if there was a suitably accurate and cost- effective
means of detecting bacilli within bodily excre-
tions. This would also focus control on those ani-
mals at risk of infecting others. However, as
pointed out by Waters in Chapter 12, agent-
based strategies for the detection of tuberculous
cattle are currently unreliable for use as ante-
mortem tests, possibly due to the paucibacillary
nature of the disease resulting in a transient and
low level of bacterial shedding.
Although the existing immunological
means of diagnosis, including the intradermal
tuberculin test, remain the cornerstone of diag-
nosis and control for bovine TB, there is still a
requirement for novel and improved ante-
mortem tests and testing algorithms to be devel-
oped and implemented. These might be based on
immunological and/or molecular markers iden-
tified in circulating T cells and/or monocytes in
infected animals differentiating them from unin-
fected or even vaccinated animals. As discussed
by Wanzala and Sreevatsan in Chapter 13, while
the pipeline for new bovine TB diagnostics has
shown some interesting new developments,
‘improvements in standardization and valida-
tion procedures to increase reproducibility and
accuracy and promote adoption of these bio-
markers’ is required. Emerging technologies
developed for improved diagnosis of human
M. tuberculosis infection, such as the GeneXpert
(Stevens et al., 2017), circulating nucleic acid
(Miotto et al., 2013) or breath analysis
( McNerney et al., 2010) will likely prove useful
in time for the discovery and application of bio-
markers of diagnostic relevance for bovine TB.
Underpinning the development of new or
improved means of immunodiagnosis is an
increased understanding of the immune
response to vaccination and infection. The host
immune response on exposure to mycobacteria
is complex, as emphasized by Salguero in Chap-
ter 9 and Hope and Werling in Chapter 11, and
more work is needed to tease apart the nature of
protective immunity from immune responses
that are detrimental to the host together with
information on the major bacterial antigens or
combinations of antigens that stimulate these
responses. It is likely that these differences are
quantitative as well as qualitative, including a
strong temporal component. While much has
been learnt about the immune response of cattle
to infection, supported by an increasing array of
specific reagents with which to study it, the same
cannot be said for other species.
The immune response of the host during
mixed infection is also likely to become a major
topic for further investigation, and this has
implications not only for immunological diagno-
sis, but also for vaccination. We have seen in
Chapters 11 and 12 that co-infection with
Fasciola hepatica can confuse the response to
M. bovis. M. avium subsp. paratuberculosis (MAP)
is another pathogen causing a chronic infection
in which an initial Th1 response can modulate
to a Th2 response. This could also profoundly
affect the response to M. bovis. The high preva-
lence of MAP in some countries suggests that
this could be a real problem that will require
addressing.
Tuberculins, including purified protein
derivatives (PPDs), are a poorly defined and com-
plex mix of proteins, lipids and carbohydrates of
inherently poor specificity as many of the com-
pounds within PPDs are antigenically cross-
reactive amongst the various mycobacterial
species. Efforts to replace tuberculin with defined
proteins or peptides for immunodiagnosis are
generating promising results, as reviewed by
Waters in Chapter 12. It is hoped that advances
in computational methods to predict which