Bovine tuberculosis

Mycobacterium bovis Molecular Typing and Surveillance 59

geographical regions (Hershberg et al., 2008;
Wirth et al., 2008). This consistent observation
has significant implications for control ( Gagneux
and Small, 2007) and despite sharing >99.95%
nucleotide identity the MTC resolves into a series
of ‘ecotypes’, each with its own non-absolute
host-preference (Smith et al., 2006a; Whelan
et al., 2010). It is biologically untenable that
genetic variation in both the host and the patho-
gen does not influence the outcome of exposure,
infection, disease and infectivity (Allen et al.,
2010). Phylogenetic analysis of the MTC shows
that the animal-adapted strains are found in a
single major lineage marked by the deletion
of chromosomal region of difference 9 (RD9-
deleted) (Brosch et al., 2002). This important
work has since been extended (Smith et al.,
2006a, 2006b; Smith and Upton, 2012) to pre-
dict the most likely genotype in a series of
inferred ancestors for modern animal-adapted
MTC bacteria.

5.4 Epidemiology

Classical epidemiology attempts to identify those
factors that determine disease distribution in
time and space within and across populations.
Furthermore, epidemiology is concerned with
the mechanism(s) that determine disease trans-
mission, manifestation and progression. The epi-
demiology of bovine TB worldwide is notoriously
complex (Drewe et al., 2014), with current evi-
dence indicating both cattle and wildlife infec-
tion sources in a number of ecosystems, the
relative significance of which is uncertain and
will vary amongst species, across regions and
over time. Factors such as the adequacy of cattle
control measures, the infection pressure in wild-
life populations and the interaction between
cattle and wildlife species are important (Skuce
et al., 2012).

5.4.1 Molecular epidemiology

As a sub-specialism of epidemiology and driven
by rapid advances in genome analyses and com-
parative genomics (Loman and Pallen, 2015),
molecular epidemiology is the application of
molecular taxonomy, phylogeny or population

genetics techniques to epidemiologic problems.

Molecular techniques further stratify data for

epidemiologic activities, including disease sur-

veillance, outbreak investigations, identifying

transmission patterns and risk factors amongst

apparently unconnected cases, characterizing

host-pathogen interactions and assessing rela-

tive pathogen virulence.

Rapid improvements in the performance

and scalability of pathogen molecular typing

and access to meta-data are revolutionizing and

modernizing disease control and surveillance in

human health (Aarestrup et al., 2012). They are

predicted to have a similarly transforming

impact on animal health. This relatively new

discipline provides an opportunity to revisit the

received wisdom about infectious disease

dynamics and has become an essential compo-

nent of most modern infectious disease investi-

gations (Muellner et al., 2011, 2015). Here we

discuss how M. bovis molecular epidemiology

has already improved our limited understanding

of bovine TB ecology, evolution and epidemiol-

ogy and the opportunities and limitations pre-

sented by the impending pathogen genomics

revolution (Kwong et al., 2015). Molecular typ-

ing should not be seen as an end in itself; it

should add value to, and is no replacement for,

sound epidemiological design and implementa-

tion. The benefits of deployment should flow

from the policy decisions that are informed by

the evidence and estimates provided by rational

molecular epidemiology studies.

The development and application of molec-

ular epidemiology to more fully understand dis-

ease ecology and epidemiology is particularly

well demonstrated in the highly related patho-

gen M. tuberculosis (Schurch and van Soolingen,

2012; Jagielski et al., 2016). While there have

been significant methodological and data

advances over recent years, these methods have

been used effectively to monitor and investigate

TB transmission dynamics, to detect laboratory

cross-contamination, to differentiate relapse

from re-infection, to evaluate those risk factors

that place TB cases in a cluster of the same

molecular type and to investigate emerging drug

resistance. These methods have also revolution-

ized our understanding of the evolution and

phylogeography of this important human

pathogen (Comas and Gagneux, 2011; Pepperell

et al., 2011). Molecular surveillance (Muellner