Brucellosis 1989). A granulomatous inflammatory process may

Brucellosis is a severe acute febrile disease caused by Brucella
species, which is a gram-negative
bacterium of the genus Brucella (Haag
et al., 2010; Bruce., 1887). It is a
zoonotic disease remaining among the worldwide distributed zoonotic diseases (Corbel.,
1997; Olsen and Staff, 2005).

Brucellosis manifests flu-like symptoms with an undulant fever, rarely
resulting in human death. However, it can pose a significant economic loss to
owners of domesticated animals due to loss of progeny, reduced milk yield, and
infertility. In animals, brucellosis causes epididymitis in males and abortion
in females (Xavier et al., 2009; Silva et al., 2011).

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Brucellosis results in abortion of fetuses which is the most obvious
manifestation of Brucellosis (Merck Veterinary Manual, 2016); mostly abortion
is associated with the last trimester of gestation, producing weak newborn
calves and infertility in cattle (Enright et al., 1984; Poester et al., 2005).
Additionally, in
pregnant cows, development of local lymphadenopathy at the site of infection
that progresses to acute lymphadenitis can be observed (Schlafer.,2007). In
bulls, orchitis is the most significant lesion induced by Brucella abortus (Lambert et al., 1963; Trichard et al., 1982). As
a result of chronic orchitis and fibrosis of the testicular parenchyma,
affected bulls may develop permanent infertility which leads to major loss of
progeny in a herd (Campero et al., 1990).

Histopathologically, the lesions of Brucellosis consist of necrotic
placentitis and interstitial mastitis in pregnant cows, and fibrinous pleuritis
with interstitial pneumonia in aborted fetuses and newborn calves (Alcina V et
al, 2009). Trophoblastic cells are swollen and filled with coccobacilli. There is usually neutrophilic and
histiocytic inflammatory infiltration, associated with necrosis, oedema, fibrin deposition, and in some cases
vasculitis (Xavier et al., in press). The inflammatory reaction is associated
with multifocal erosions or superficial ulcerations of the luminal epithelium
(Payne, 1959; Meador et al., 1988). Lymphoid hyperplasia in lymph nodes that
may be associated with a neutrophilic infiltrates which may progress to a
granulomatous lymphadenitis (Payne, 1959; Meador et al., 1988, 1989). A
granulomatous inflammatory process may be eventually seen in the liver, spleen,
and kidney (Meador et al., 1988; Hong et al., 1991), and rarely the central
nervous system may be affected with multifocal or diffuse histiocytic
meningitis (Hong et al., 1991).Whereas, in the spleen descriptions of
pathological changes in the organ includes giant cells and increased numbers of
phagocytic cells in the sinusoids (Rothenberg R,1933).

There are a few critical
steps that Brucella species undergoes
to cause infection, firstly invading the host animal’s epithelia cells,
allowing infection through mucosal surfaces (Ackermann al, 1988, Paixão al,
2009), Resistance to intracellular bacterial pathogens mostly does rely on
cell-mediated immunity (Hong et al., 1991), which involves activation of the
bactericidal mechanisms of antigen-presenting cells (macrophages and dendritic
cells) and the subsequent expansion of antigen-specific CD4+ and CD8+ T-cell
clones (Baldwin and Winter, 1994; Liautard et al., 1996) Brucella antigens induce the production of T helper type 1 (Th1)
cytokines, and an adequate Th1 immune response is critical for the clearance of
Brucella infection. Activation of IFN- y producing CD4+ Th1 immune is necessary
for the control of Brucella infection. (P. Skendros, 2013). BLS  has been
reported to elicit mixed Th1-Th2 pathway response critical for humoral and
cell-mediated immune defence (Velikovsky et al., 2002). PrpA is linked with
chronicity of Brucella infections by potentiating splenocyteic and B-cell
stimulantion (Spera et al., 2006). Therefore, immunization with PrpA would not
only have immunomodulatory effects but would also reduce the chronicity of
Brucella infection. Omp19 elicits adaptive interleukin (IL)-17 cytokine
production which is necessary for mucosal immunity and also confers protection
when used as a subunit vaccine platform (Pasquevich et al., 2011). SOD induces
a diverse immune responses (Onate et al., 1999)

Diagnosis of
brucellosis is based on direct or indirect laboratory methods, direct methods
would include; bacterial culture which
has high specificity and has been used as one of the gold standards of
diagnosis  as it allows biotyping of the
isolate (Poester et al., 2005; Navarro et al., 2004). Enzyme
Linked immunosorbent assay (ELISA) is most popular serological assay as it is
standard for the diagnosis of brucellosis measuring IgG, IgA and IgM antibodies.
ELISA can be used for both acute and chronic phases of disease also detecting
Brucella-specific IgG subclasses (Ajah.,2010; Agasthya et al.,2012).

is an alternative technique for direct diagnosis as in-situ Specific Brucella abortus antigens have been
identified in formalin fixed, paraffin-embedded tissues of cows, goats, and
mice using polyclonal antibodies prepared in hyper
immunized rabbits as a form of diagnosis (Meador VP et al., 1986; Palmer
MV et al., 1996).

Studies do
depict the use of real-time polymerase chain reaction assays for antigen
detection associated with infectious disease spread (Smythe et al., 2002;
Reischl et al., 2003; Peters et al., 2004). Brucella
spp. has been identified by amplification of a specific region of its genome,
as have other closely related bacteria, to examine their cross-reactivity
(Redkar et al., 2001; Newby et al., 2003). The IS711
region of the Brucella genome has
been used to identify B. abortus, B. melitensis
and B. suis
biovar 1. Similar primers and probes exploiting the IS711 repetitive element
were used by Newby et al. (2003) for real-time detection.


It is important to control Brucellosis in animal
population and thus immunization play a very critical role, Brucella abortus
S19 and Brucella melitensis Rev.
1 vaccines have been widely used in developed countries. However, both the
vaccines have been reported to have induced abortions in pregnant animals and
are virulent for humans; Moreover, they elicit anti-Brucella antibodies
that interfere with serodiagnosis. Furthermore, S19 is only used in calves, as
adult vaccination results in orchitis in male, prolonged infection and possible
abortion complications in pregnant female cattle. Whereas, Rev 1 is
streptomycin resistant, an important antibiotic used to treat the disease
(Muñoz-Montesino et al,.2004). At immunological critical sites an intracellular
pathogen such as attenuated Salmonella strain can be licensed as a vector to
deliver Brucella antigens. Salmonella strain due to
its likeness in infection exhibits natural infection as does Brucella, this similarity makes Salmonella a pragmatic choice for an
anti-Brucella vaccine delivery platform. The Salmonella Typhimurium delivery system –based Brucella vaccine used in this study was developed and tried in mice,
it proved to be a suitable vectored Brucella
vaccine in different routes of immunization. Its protective efficiency was
improved by use of heterogous antigens of Brucella
which included SOD, BLS, PrpA and Omp19 proteins (used in this study) and
further purified LPS was included in the cocktail which coffered immunization
results at par with reference RB51vaccination (not done in this study) ( Kim et al., 2016; Lalsianmthara
et al., 2017). Nevertheless, livestock animal vaccine trial was not attempted in
their study as mice was used. Although, large animal experimental trials are
uncommon due to limited resources, it is important to characterize the
equivalent immune responses in livestock hosts (natural host) in order to
consider the commercializing of the developed vaccine. Studying the vaccine
efficacy in goats would give an understanding of its safety in the natural
hosts. To reduce economic losses from brucellosis; accurate,
safe and sensitive diagnostic methods equally play a central role in the
control and eradication of brucellosis in both animals and humans. This present
study also explores the use of histopathological changes, Elisa Quantitation of
Goat IgG, bacteriology, immunohistochemistry and real-time polymerase chain
reaction as parallel tools in studying the efficacy and safety (host safety
issues) of the ST-system against (Brucella
abortus strain 544) in caprine.