124 F.J. Salguero
lymph nodes with possible spread to other
organs (Terefe, 2014).
Detection of tuberculosis by slaughter sur-
veillance requires that the infected animal have
visible lesions at inspected sites. A detailed
post-mortem examination in the abattoir or
post-mortem room is crucial to identify
tuberculosis- like lesions in a variety of organs,
including the liver, spleen, kidney, mammary
gland, etc. Several studies have reported that the
detection of tuberculosis infection in the abat-
toir increases with enhanced meat inspection
procedures, such as multiple slicing of organs
and tissues (Corner, 1994; Whipple et al., 1996).
Macroscopic detection of granulomatous lesions
can produce a tentative diagnosis of bovine
tuberculosis. Histopathological examination of
the lesions may increase the confidence of the
diagnosis, but the bacteriological isolation of
M. bovis is the final answer to a definitive diagno-
sis ( Corner, 1994). The inspection and culture of
lymph nodes are crucial for the diagnosis of
bovine tuberculosis and there is a recent hypoth-
esis proposing tuberculosis to be a lymphatic dis-
ease with a pulmonary portal (Behr and Waters,
2013).
9.3 The Hallmark Microscopic
Lesion of Bovine Tuberculosis:
The GranulomaThe microscopic lesion observed in tuberculosis,
regardless of the tissue and the host, is the
granuloma. The granuloma is a distinctive mor-
phological lesion typical of a chronic inflamma-
tory reaction with abundant epithelial-like
(epithelioid) macrophages (Palmer et al., 2015).
Lymphocytes, plasma cells, neutrophils and
Langhans-type multi-nucleated giant cells
(MNGCs), formed through the fusion of multiple
macrophages, are also observed within the
granuloma. These cell types are often observed
surrounding a caseous necrotic core.
Following mycobacterial infection, mono-
cytes, lymphocytes, neutrophils and tissue-
resident macrophages are recruited, mediated
by cytokines and chemokines (Mattila et al.,
2013) in an attempt to control the infection,
forming cellular aggregates (Aranday-Cortés
et al., 2013). Granulomas in cattle show
different stages of formation, suggesting dissem-
ination from primary foci as described in human
tuberculosis (van Rhijn et al., 2008).
The granuloma structure has been
described as a physical barrier to mycobacterial
growth and spread (Aranday-Cortés et al.,
2013). Experimental infection in cattle has
allowed the qualitative classification of granulo-
mas during the course of bovine tuberculosis
infection (Wangoo et al., 2005; Johnson et al.,
2006; Palmer et al., 2007; Aranday-Cortés et al.,
2013). Microscopically, the granulomas are
classified into four different stages of develop-
ment (Wangoo et al., 2005) (Fig. 9.2). Early
lesions, categorized as stage I (‘initial’) small
granulomas are formed by an accumulation of
neutrophils, epithelioid macrophages, a small
number of lymphocytes and a few Langhans-
type multi-nucleated giant cells. Necrosis is
absent in stage I granulomas. The lesion will
progress to stage II (‘solid’) granulomas with a
similar structure to stage I, but with a central
infiltrate of neutrophils and lymphocytes
together with a thin capsule surrounding the
lesion. The lesion will start to form a central area
of caseous necrosis and progress to stage III
(‘necrotic’) granuloma where the central
caseous necrosis is surrounded by multiple epi-
thelioid cells, multi-nucleated giant cells and
lymphocytes. Stage III granulomas exhibit a
complete fibrous capsule with a central area of
necrosis and occasionally minimal mineraliza-
tion. The necrotic core is surrounded by epitheli-
oid macrophages and MNGCs, and a peripheral
zone of macrophages, clustered lymphocytes
and isolated neutrophils (Aranday-Cortés et al.,
2013). Finally, stage IV (‘mineralized’) granulo-
mas are completely surrounded by a relatively
thick capsule of fibrous tissue and display obvi-
ous central areas of necrosis with extensive min-
eralization. Necrotic cores are surrounded by
macrophages and MNGCs and a peripheral zone
of macrophages and dense clusters of lympho-
cytes just inside the fibrotic capsule. Stage IV
granulomas may be multi-centric with several
granulomas coalescing to form one very large
granuloma displaying multiple necrotic cores.
Large stage IV granulomas are often surrounded
by a small amount of ‘satellite’ stage I and stage
II granulomas (Aranday-Cortés et al., 2013).
The presence of acid-fast bacilli (AFB) in tis-
sue sections with the Ziehl-Neelsen stain show a