Int. J. Adv. Res. Biol. Sci. (2020).

7(9): 9-31

International Journal of Advanced Research in Biological Sciences

ISSN: 2348-8069
www.ijarbs.com
DOI: 10.22192/ijarbs Coden: IJARQG (USA) Volume 7, Issue 9 -2020
Review Article

DOI: http://dx.doi.org/10.22192/ijarbs.2020.07.09.002

A Review on Zoonotic importance of a Brucellosis.

Wondimu Hailu Enaro

Arbaminch Univeresity, College of Agricultural Science.

Abstract
Brucella is facultative intracellular gram negative, aerobic, catalase-positive, non-motile, non-spore forming and rod shaped
(coccobacilli). The Brucella genus is composed of 12 recognized species after isolation and identification of novel species from
mandibular lymph nodes of the red fox. Brucellosis is one of the most important zoonotic diseases of public health implications
causingsocio-economic impacts on the livelihoods of the poor rural pastoralist communities and the urban population worldwide.
It is a bacterial disease, caused by members of the genus Brucella; and in small ruminants Brucellamelitensisis the most common
species in developing countries and is associated with clinically apparent disease in humans. Brucellosis also known as “undulant
fever”, “Mediterranean fever” or “Malta fever” is a highly contagious zoonosis caused by ingestion of unpasteurized milk or
undercooked meat from infected animals, or close contact with their secretions. Brucellosis has been an emerging disease since
the discovery of Brucellamelitensis by Bruce in 1887, and it causes a systemic infection with clinical manifestations as fever,
sweats, fatigue and joint pain. Because each type has distinctive epidemiologic features, with each new type, the complexity of
the interaction with humans has increased. Because new strains may emerge and existing types adapt to changing social and
agricultural practices, the picture remains incomplete. Treatment of the disease is difficult because its symptom is complex, it can
cause flu and malaria like symptoms. The control of brucellosis requires collaboration of different discipline through one health
approach. Especially, in developing country Ethiopia, since the eradication of brucellosis is difficult, its control is very important.

Keywords: Brucellosis, Epidemiology, Zoonotic importance, Transmission.

Introduction
Brucellosis is one of the most common widespread domestic animals worldwide; especially so in
zoonoses throughout the world, mainly caused by developing countries where disease controls programs
Brucella abortus, Brucella melitensis or Brucellasuis, are either non-existent or inadequate. The disease also
and is transmitted to people from various animal occurs in wild animals, thus posing a danger of
species (WHO,2006). Brucellosis due to Brucella transmission between domestic and wild animals in
abortus, Brucella melitensis and Brucellasuis were interface areas.Brucella species that cause disease in
included in the second category (List B) of domestic and wildlife include Brucella abortus,
communicable diseases (Litaet al., 2016). Despite its Brucella melitensis, Brucella ovis, Brucella suis and
widespread distribution, it is considered to be a Brucella canis(Shirima,2005). The disease poses a
neglected zoonosis because, in many endemic areas, it
is not regarded as a priority by national and
international health systems (Adone and Pasquali,
2013). It is a major socio-economic importance in
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barrier to trade of animals and animal products, and been reported to cause disease in humans (Shirima,
can causes a public health hazard, and is an 2005). Humans can be infected by consuming
impediment to free animal movement (Zinsstag et al., contaminated food (mainly raw milk and dairy
2011). products) (Sintayehu et al., 2015). In addition, it can
also infected by contact of the skin, even apparently
Brucellosis is an infectious bacterial disease caused by healthy skin or the digestive, conjunctival or
members of the genus Brucella, and that characterized nasopharyngeal mucous membranes with infected
by late abortion, retained foetal membranes, and to a animals or matter produced by them (mainly genital
lesser extent,orchitis and infection of the accessory sex secretions, aborted foetuses or placentas, but also
glands in males and impaired fertility. The disease infected organs such as the liver, spleen or udder in
primarily affects cattle, buffalo, bison, pigs, goats, particular, or contaminated manure or wool) (“FAF,
sheep, dogs, elk, and camels and occasionally horses EOHS,”2014).
(Walker,2005; Kahn, 2005;Zinsstaget al.,2011). It is
essentially a disease of sexually mature animals, the In human, Brucellosis is an acute or sub-acute febrile
predilection sites being the reproductive tracts of illness usually marked by an intermittent or remittent
males and female. If the animal is not pregnant, a fever accompanied by malaise, anorexia and
chronic disease results without symptom and perhaps prostration, and which, in the absence of specific
negative serology. However, if such an animal treatment, may persist for weeks or months (WHO,
becomes pregnant the production of simple 2006).
carbohydrate eryhritol in the fetus and its membranes
cases enormous multiplication of bacteria in the uterus The disease is economically important as it is
and this are likely to end in abortion (Tesfaye et al., associated with abortion storms in newly infected
2017) herds, a high level of retained placenta and hence
endometritis or metritis resulting in reduced milk
Animals become infected by ingesting contaminated production, infertility. In addition, the zoonotic nature
pastures, feedstuffs and water or licking infected of the disease has a serious impact on public health
placentae, foeti or the genitalia of infected female (Radostitis et al.,2007).According to Mangen et
animals soon after abortion or delivery (Shirima, al.(2002) the economic losses due to brucellosis
2005). The clinical findings are dependent upon the summarized as :1) Losses due to abortion in the
immune status of the herd. Among highly susceptible, affected animal population; 2) Diminished milk
non-vaccinated pregnant cattle, abortion after the 5th production, Brucella mastitis and contamination of
month of pregnancy is the typical feature of the milk;3) Cull and condemnation of infected animals
disease. In subsequent pregnancies the fetus is usually due to breeding failure;4) Endangering animal export
carried to full term although second or even third trade of a nation;5) Human brucellosis causing
abortions may occur in the same cow; and retention of reduced work capacity through sickness of the affected
the placenta and metritis are common sequelae to people;6) Government costs on research and
abortion (Radostitis et al., 2007). eradication schemes;7) Losses of financial
investments.
According to Aworh et al (2013), Brucellosis is more
prevalent in developing countries and considered to be Despite the advances made in surveillance and control,
a serious health problem due to lack of effective public the prevalence of Brucellosis is increasing in many
health measures, domestic animal health programs, developing countries due to various sanitary, socio-
and appropriate diagnostic facilities. Furthermore, the economic and political factors (Mohammed et al.,
situation is also worsened by the resemblance of the 2016). Many countries have made considerable
disease with other diseases leading to misdiagnosis progress with their eradication programs but in
and underreporting (Regea, 2017).It was eradicated in countries like Africa brucellosis is considered to be
several countries through test and slaughter, one of the most serious disease problems facing the
vaccination and restriction of animal movements veterinary profession (Tesfaye et al., 2017).
(Shirima, 2005).
In Ethiopia, different study has been conducted in
Brucella abortus, Brucella melitensis, Brucella suis different areas that reported sero prevalence of
and Brucella canis can all cause human brucellosis, brucellosis study demonstrated that the overall
whereas Brucella ovis and Brucella neotomae have not seroprevalence of small- ruminant brucellosis in and

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around Bahir Dar to be 1.2% by the RBPT and 0.4%

by CFT. More than half of the sera which tested 2 Literature review and Discussion
positive for RBPT, tested negative for CFT. This
could be due to cross-reactions between Brucella and 2.1Epidemiology
other bacteria which share similar epitopes. This
prevalence is lower than prevalences recorded in The epidemiology of the disease in livestock and
previous studies carried out in different parts of the humans as well as appropriate preventive measures is
country; 4.8% in Afar (Ashenafi Feyissa et al., 2007); not well understood, and in particular such
9.7% in Afar and Somali (TeshaleSori et al., 2007); information is inadequate in sub-Saharan Africa
1.5% in sheep and 1.3% in goats in central highlands (McDermott and Arimi, 2002). Despite endemic
of Ethiopia (TekeleyeBekele and Kassali, 1990); 16% nature of brucellosis in many developing countries the
in Afar Region (Yibeltal, Muhie 2005) and 3.37%, disease remains under diagnosed and under-reported
0.11%, 3.94% and 0.49% from Afar Region, Somali (Regea, 2017).
Region, Borena Zone and South Omo Zone,
respectively (MelesseBalcha et al., 2006). The The epidemiology of cattle brucellosis is complex and
difference in the prevalence of brucellosis between the influenced by several factors. These can be broadly
current and previous studies might be attributed to the classified into factors associated with the transmission
differences in geographical location, sample size and of the disease between herds, and factors influencing
management systems. In Afar and Somali Region, the maintenance and spread of infection within herds.
large numbers of different species of animals are Routes of transmission from animal to human include:
raised on communal pastures under limited watering 1- direct contact with infected animals, 2- inhalation of
areas, where as the livestock management in the contaminated aerosols, and 3- ingestion of
northwestern Ethiopia is characterized by mixed unpasteurized dairy products. The climatic and agro-
farming, in which fewer animals are raised separately. ecological diversities of Ethiopia may allow a wide
Limited financial resources, political instability and range of livestock production systems, and therefore,
lack of commitment by local and regional different management systems, multiple livestock
governments, as well as the presence of other serious species per holding, stock density and social
livestock diseases (that ispeste des petits ruminants, organizations to handle livestock may account for the
Rift Valley fever, foot and mouth disease, contagious widespread risk factors for maintenance and
caprinepleuro pneumonia, lumpy skin disease and transmission of cattle brucellosis (Megersaet al.,2011).
African swine fever), in many African countries have
diverted attention from important zoonotic diseases 2.1.1 Etoilogy
such as tuberculosis and brucellosis. There is no
strategic control and eradication plan against According to Schelling et al(2003), Brucellosis is an
brucellosis in Ethiopia under implementation economically important and widespread zoonosis in
(Sintayehu et al., 2015). Therefore, the objective this the world caused by bacteria of the genus Brucella,
review was; which tend to infect specific animal species; in which
cattle is usually infected by Brucella abortus, sheep
 To assess the review on the cause of and goats by Brucella melitensis, and swine by
brucellosis both in animals and humans. Brucella suis (Awah-Ndukum, 2018).
 To review the epidemiology of brucellosis
both in animals and humans. Brucella is the agent responsible for brucellosis, a
 To review the zoonotic importance of contagious infectious animal disease with global
brucellosis. distribution that can infect humans (“FAF,
 To review mode of transmission, treatment, EOHS,”2014). Brucella is characterized as small,
control and prevention of brucellosis. facultative intracellular, gram negative, aerobic,
capnophilic, catalase-positive, non-motile, non-spore
forming and rod shaped (coccobacilli) bacteria that
can infect many species of animals, including humans.
Apart from Brucella ovis and Brucella neotomae, all
brucella species are oxidase positive; as well as all are
urease-positive except Brucella ovis (Quinn et al.,
2002).

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The Brucella genus is composed of 12 recognized suis, B. ovis, B. canis, B. neotomae, and B. microti,
species after isolation and identification of novel and two that affect marine animals are, B. ceti and B.
species from mandibular lymph nodes of the red fox pinnipedialis. The first three species are called
(Scholz et al., 2016).There are six ‘classical’ species: classical Brucella and within these species, seven
Brucella abortus, Brucella melitensis, Brucella suis, biovars are recognized for B. abortus, three for B.
Brucella ovis, Brucella canis and Brucella neotomae, melitensis and five for B.suis (Schellinget al., 2003).
andthe first three of these are subdivided into biovars
based on cultural and serological properties (OIE, In general, brucella have a predilection for both female
2013). They affect many animal species, but especially and male reproductive organs in sexually mature
of those that produce food: sheep (especially milk animals and each Brucella species tends to infect a
Producing), goats, cattle and pigs and, on a more particular animal species. The target organs and
localized scale, camels, buffaloes, yaks and reindeer tissues of Brucella species are placenta, mammary
(WHO, 2006). glands, and epididymis in animal reservoir host
(Quinn et al., 2002). Persistent (lifelong) infection is a
Brucellosis is an important zoonotic disease caused by characteristic of its facultative intracellular organism,
infection with bacteria of the Genus Brucella. It was with shedding in reproductive and mammary
first isolated by Bruce in 1887 from the spleens of secretions (Radostitiset al., 2007).Brucella survives in
soldiers dying of Mediterranean fever on the island of freezing and thawing, and under proper environmental
Malta. Bruce called it Micrococcus melitensis. The condition, they survive for up to 4 months in milk,
origin of the disease remained a mystery for nearly 20 urine, water, and damp soil. Most disinfectants active
years until it was discovered that goats were the source against other gram-negative bacteria kill Brucella, and
of infection for human populations. Nine Brucella pasteurization also effectively killbrucella in
species are currently recognized. Seven of them that milk(Walker, 1999).
affect the terrestrial are, B. abortus, B. melitensis, B.

Table 1: The table below summarizes Brucella species, hosts and transmission mode
(http://www.ansci.wisc.edu/jjp1/ansci_repro/misc/syllabus, 2002)

Strain Symptoms Principle Host Other Hosts S y m p t o m s Transmission Human Disease

Brucellaabortus C a t t l e Sheep, goats, pigs, horses, Abortion after 5 months Ingestion, some undulant fever-control
dogs, humans, wild ungulates venereal with antibiotics

Brucellamelitensis Sheep, goats. cattle, pigs, dogs, humans, Later term abortion, Ingestion Malta fever: can be fatal in human
buffalo camels weak young, mastitis (goats)

Brucellaovis S h e e p most often effects rams, rare abortions

Brucellasuis P i g cattle, horses dogs, humans Abortion and infertility ingestion and venereal extremely deadly in
reindeer, caribou humans
Brucellacanis D o g s H u m a n s abortions at 40-60 days Venereal mild disease in humans

2.1.2 Mode of disease transmission which are either pregnant, that have recently delivered,
or aborted (Shirima, 2005). The risk posed to
Brucellosis occurs in animals of all age groups, but susceptible animals following parturition of infected
persists commonly in sexually mature animals. cattle depends on three factors: 1) the number of
Infection is frequently introduced into clean herds or organisms excreted, 2) the survival of these organisms
flocks through the introduction of infected animals under the existing environmental conditions, and 3)

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the probability of susceptible animals being exposed to People working in direct contact with infected
enough organisms to establish infection (World Health animals: breeders, veterinarians, Artificial
Organization, 2006). Brucellas are disseminated by insemination technicians, slaughterhouse worker and
direct or indirect contact with infected animals. rendering plant personnel are those most highly
Natural transmission occurs by ingestion organisms, exposed to infection; and also one of the agents most
most common routes of entry, although exposure often responsible for contamination in laboratories,
through the skin, conjunctiva, genital mucosa, and often through aerosolisation. A few rare cases of
respiratory routes occurs. The major source for infection were observed during handling of vaccine
exposure Brucellaabortus in cattle and strains (spattering on lips or in the eye, accidental
Brucellamelitensis in sheep and goats is through inoculation), and transmission between humans, and
aborted fetuses, fetal membranes, and post abortion sexual transmission in particular has never actually
uterine discharge (Walker, 1999). been proven (“French Agency for Food, Environment
and occupational Health and Safety,”2014).
Venereal transmission by infected bulls to susceptible
cows appears to be rare. Transmission may occur by Brucellosis is an infection primarily of animals that
artificial insemination when Brucella contaminated causes infertility and late-term abortion. Rarely,
semen is deposited in the uterus but, reportedly, not brucellosis occurs in humans as a zoonosis causing a
when deposited in the midcervix (Kahn, 2005). Intra broad spectrum of symptoms. The ultimate control of
herd spread occurs by both vertical and horizontal human brucellosis will depend on the elimination of
transmission. Horizontal transmission is usually by the disease in animals; therefore human cases may act
direct contamination and, although the possibility of as a marker of animal disease.
introduction of infection by flies, dogs, rats, ticks,
infected boots, fodder, and other inanimate objects Brucella bacteria are found in the blood, urine, semen,
exists, it is not significant relative to control measures. vaginal discharges, placentas, milk and aborted
The organism is ingested by the face fly but is rapidly foetuses of infected animals. It may also be found in
eliminated and there is no evidence for a role in the saliva, and nasal, ocular and joint fluids of infected
natural transmission (Radostitiset al., 2007). animals.

The reservoirs of Brucella species comprise cattle, Humans usually become exposed by contact with
goats, sheep and some wildlife (Lita et al., 2016). The bacteria contaminated fluids from infected animals
disease is transmitted to man mainly by direct contact through abraded skin or mucous membranes or by
with infected livestock and or through consumption of ingestion of infected animal products. In laboratories
raw or uncooked animal products (Radostitis et al., and during butchering of infected animals, Brucella
2007). Human infections may occur through breaks in may be transmitted in aerosols. It can also be
the skin when handling infected animal tissues (Regea, transmitted on fomites as it withstands drying and can
2017). Usually the main source of brucellosis for survive in contaminated dust and soil. Survival may be
urban populations is ingestion of fresh milk or dairy prolonged in conditions of low temperature, high
products prepared from unheated milk. Cow, sheep, humidity and no sunlight. Brucella species are also
goat or camel milk contaminated with Brucella considered potential bioterrorism agents.
melitensis is particularly hazardous as it is drunk in
fairly large volume and may contain large numbers of Person-to-person transmission of brucellosis is very
organisms (WHO, 2006). Common sources for rare. Congenital infection may occur through the
infection are aborted fetuses, fetal membranes, and placenta, during breast feeding or due to contact with
post abortion uterine discharge, all of which contain the mother's blood, urine or faeces during delivery.
large numbers of organisms. Brucella melitensisis There have also been rare reports of transmission after
considered the most virulent species for human blood transfusions, bone marrow transplant and sexual
followed by Brucella abortus, and Brucella suis; and contact.
Brucella canis, Brucella ovis and Brucella neotomae
do no infect humans (Walker, 1999). Live animal vaccines for brucellosis are known to be
pathogenic to humans however they are not currently
in use in Australia.

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Figure 1: Transmission mode of brucellosis within its host range (Garin-Bastuji, 2014).

2.1.3Host range Brucellosis in cattle is usually caused by biovars of

Brucella abortus. In some countries, particularly in
According to Seifert (1996), Brucellae can be affects southern Europe and western Asia, where cattle are
domestic animals such as cattle, sheep, goats, camels kept in close association with sheep or goats, infection
and pigs, and creates a serious economic problem for can also be caused by Brucella melitensis, and
both the intensive and extensive livestock production occasionally, Brucella suis may cause a chronic
systems in the tropics, and also affect wild animals, infection in the mammary gland of cattle, but it has not
rodents, sea mammals and even fresh water fish (as been reported to cause abortion or spread to other
cited in Degefu et al., 2011). animals. The disease is usually asymptomatic in non-
pregnant females (OIE, 2013). Susceptibility of cattle
The severity of the disease depends upon many factors to Brucella abortus infection is influenced by the age,
such as previous vaccination, age, sex and sex, and reproductive status of the individual animal.
management such as herd or flock size and density. Sexually mature, pregnant cattle are more susceptible
Abortions are more prevalent in unvaccinated animals to infection with the organism than sexually immature
and numbers of organisms shed are much greater. The cattle of either sex. Abortions occur most commonly
bacteria are found in tissues and fluids associated with in outbreaks in unvaccinated heifers after the fifth
pregnancy, the udder and the lymph nodes which drain month of pregnancy, and affected bulls shows orchitis,
the relevant areas (World Health Organization, 2006). epididymitis, and seminal vesiculitis (Radostitis et al.,
2007).
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Small ruminant brucellosis is most commonly caused The two main causes for spontaneous abortion in
by Brucella meltensi, and also Brucella ovisis an animals are erythritol, which can promote infections in
important cause of orchitis and epididymitis in sheep the fetus and placenta, and the lack of anti-Brucella
but it is not recognized as a cause of natural infection activity in the amniotic fluid. Males can also harbor
in goat(Kahn, 2005). the bacteria in their reproductive tracts, namely
seminal vesicles, ampullae, testicles, and epididymes
Brucellosis has been reported in the one-humped
camel (Camelus dromedarius) and in the two-humped Brucella melitensis in sheep and goats represents, by
camel(Camelus bactrianus), and in the South far, the most important source of brucellosis in
American camelids, llama (Lama glama), alpaca humans. This species of Brucella is not enzootic in the
(Lama pacos), guanaco (Lamaguinicoe), and vicuna United States, Canada, northern Europe, Australasia or
(Vicugnevicugne) related to contact with large and South East Asia. It is prevalent in Latin America, the
small ruminants infected with Brucella abortus or Mediterranean area, Central Asia and, especially, in
Brucella melitensis(OIE,2013). the countries around the Arabian Gulf. Humans are
principally infected by the handling of parturient
Porcine brucellosis is an infection caused by biovar 1, animals and the consumption of raw milk and milk
2 or 3 of Brucella suis. It occurs in many countries products, especially fresh soft cheeses. In many cases
where pigs are raised. Generally, the prevalence is the vehicle of infection is uncertain and bacteria-laden
low, but in some areas, such as South America and dust is suspected.
South-East Asia, the prevalence is much higher.
Porcine brucellosis may be a serious, but presently 2.1.3.2 Brucellosis in Humans
unrecognized, problem in some countries (Pérez-
Sancho et al., 2015). The most common manifestation The first recognized human case of brucellosis in the
of brucellosis in female pigs is abortion, occurring USA was in 1898 in an army officer who contracted
very early or at any time during gestation (OIE,2013). the disease in Puerto Rico (Radostitis et al., 2007).
Brucellosis remains one of the most common zoonotic
Brucellosis in horses is caused by Brucellaabortus or diseases worldwide, with more than 500,000 human
Brucellasuis. Suppurative bursitis, most commonly cases reported annually, particularly from developing
recognized as fistulous withers or poll evil, is the most countries (Gumi et al., 2013).
common condition associated with brucellosis in
horses (Kahn, 2005). Brucellosis in human also known as “undulant fever”,
“Mediterranean fever” or “Malta fever” is a zoonosis
2.1.3.1 Brucellosis in Livestock and the infection is almost invariably transmitted by
direct or indirect contact with infected animals or their
Species infecting domestic livestock are B. abortus products. It affects people of all age groups and of
(cattle, bison, and elk), B. canis (dogs), B. melitensis both sexes. Although there has been great progress in
(goats and sheep), B. ovis (sheep), and B. suis (caribou controlling the disease in many countries, there still
and pigs). Brucella species have also been isolated remain regions where the infection persists in
from several marine mammal species (cetaceans and domestic animals and, consequently, transmission to
pinnipeds). the human population frequently occurs. It is an
important human disease in many parts of the world
B. abortus is the principal cause of brucellosis in especially in the Mediterranean countries of Europe,
cattle. The bacteria are shed from an infected animal at north and east Africa, the Middle East, south and
or around the time of calving or abortion. Once central Asia and Central and South America and yet it
exposed, the likelihood of an animal becoming is often unrecognized and frequently goes unreported
infected is variable, depending on age, pregnancy (WHO, 2006).
status, and other intrinsic factors of the animal, as well
as the number of bacteria to which the animal was Human beings are susceptible to infection with
exposed (Wyatt, H. Vivian (2014). The most common Brucella abortus, Brucella melitensis, Brucellasuis
clinical signs of cattle infected with B. abortus are biovars, and rarely Brucella canis; however, B.
high incidences of abortions, arthritic joints, and melitensis causes serious infection and is responsible
retained placenta. for the most of worldwide morbidity. It is a systemic
disease characterized by acute or insidious onset of

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continued, intermittent, undulant or irregular fever of nomadism; communities grazing by livestock, and
variable duration, headache, profuse sweating, chills, modern changes to wards larger animal populations
weakness, generalized aching, and joint pain (Quinn et and increased commerce. Importation of high
al., 2002). producing livestock due to demands for additional
animal protein and trend toward intensification of
Brucellosis is a widespread zoonosis mainly animal productionfavors the spread and transmission
transmitted from cattle, sheep, goats, pigs and camels of the infection (Tesfaye et al., 2017).Brucellosis in
through direct contact with blood, placenta, fetuses or livestock and humans is still common in the Middle
uterine secretions or through consumption of East, Asia, Africa, South and Central America, the
contaminate draw animal products (especially Mediterranean Basin and the Caribbean. Brucella
unpasteurized milk and soft cheese). In endemic areas, melitensis is particularly common in the
human brucellosis has serious public health Mediterranean basin, and it has also been reported
consequences. Worldwide, Brucellamelitensisis the from Africa, India and Mexico(CFSPH2009). Only a
most prevalent species causing human brucellosis, few world regions are brucellosis-free with regard to
owing in part to difficulties in immunizing free- domestic animals (except for rare accidental outbreaks
ranging goats and sheep. In countries where in free-range pig farms), and these regions include
eradication in animals (through vaccination and/or Northern, Central and Eastern Europe, Australia,
elimination of infected animals) is not feasible, Canada, Japan and New Zealand (“French Agency for
prevention of human infection is primarily based on Food, Environment and occupational Health and
raising awareness, food-safety measures, occupational Safety,”2014). Also it is considered as a re-emerging
hygiene and laboratory safety. In most countries, problem in many countries such as Israel, Kuwait,
brucellosis is a notifiable disease(Gumi et al., 2013). Saudi Arabia, Brazil and Colombia, where there is an
increasing incidence of Brucella melitensis or Brucella
2.1.4 Geographic distribution suis biovar1 infection in cattle. In Ethiopia, brucellosis
is endemic and the disease is highly prevalent in cattle,
Occurrence of brucellosis is increasing in tropical and camels and small ruminants in pastoral and agro-
subtropical regions because of practices such as pastoral areas (Regea, 2017).

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Figure 2: Geographical distribution of Brucella species (Garin-Bastuji, 2014).

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2.1.5 Risk Factors bacteraemic phase, bones, joints, eyes and brain can be
infected, but the bacteria are most frequently isolated
Animal risk factors: Susceptibility of cattle to B. from supra-mammary lymph nodes, milk, iliac lymph
abortus infection is influenced by the age, sex and nodes, spleen and uterus. In bulls, the predilection
reproductive status of the individual animal. Sexually sites for infection are also the reproductive organs and
mature pregnant cattle are more susceptible to the associated lymph nodes. During the acute phase of
infection with the organism than sexually immature infection, the semen contains large number of Brucella
cattle of either sex. Susceptibility increases as stage of but as the infection becomes chronic, the number of
gestation increases(Radostitset al,2006). Brucella excreted decreases. However, it may also
continue to be excreted for years or just become
Pathogen risk factor: B. abortus is a facultative intermittent (Acha&Szyfres, 2001).After the Brucella
intracellular organism capable of multiplication and organisms spread through the hematogenous route in
survival within the host phagosome. The organisms females then also reach the placenta and finally to the
are phagocytised by poly morphonuclar leucocytes in fetus. The preferential localization to the reproductive
which some survive and multiply. The organism is tract of the pregnant animal is due to the presence of
able to survive within macrophages because; it has the the allantoic fluid factors that would stimulate the
ability to survive phagolysosome. The bacterium growth of Brucella. Erythritol (four-carbon alcohol) is
possesses an unconvenential non-endotoxin considered to be one of the factors, which are elevated
lipopolysaccaride, which confers resistance to in the placenta and fetal fluid from about the fifth
antimicrobial attacks and modulates the host immune month of gestation. An initial localization within
response. These properties make lipopolysaccharide erythrophagostictrophoblsates of the placentome
an important virulence factor for Brucella survival and adjacent to chorio-allntoic membrane results in rupture
replication in the host(Radostitset al, 2006). of the cells and ulceration of the membrane. The
damage to placental tissue together with foetal
Occupational risk factors: Laboratory workers infection and foetal stress inducing maternal hormonal
handling Brucella cultures are at high risk of acquiring changes may cause abortion (Radostitset al., 2000).
brucellosis trough accidents, aresolization and/or B. abortus has predilection in the pregnant uterus,
inadequate laboratory procedures. In addition to this, udder, testicle and accessory male sex glands,
abattoir workers, farmers and veterinarians are at high lymphnodes, joint capsule and bursa. After initial
risk of acquiring the infection(Colibaliy&Yamego, invasion of the body, localization occurs initially in
2000). the lymph nodes. B. abortus is phogocytized by
macrophages and neutrophils in an effort by the host
Managemental risk factors: The spread of the to eliminate the organism. However, once inside
disease from one herd to the other and from one area phagocyte, B. abortus is able to survive and replicate.
to another is almost always due to the movement of an The phagocyte migrates via the lymphatic system to
infected animal from infected herd in to a non-infected the draining lymph node where Brucella infection
susceptible herd. A case-control study of brucellosis in causes cell lysis and eventual lymph node hemorrhage
Canada indicates that, herds located close to other 2-3 weeks following exposure. Because of vascular
infected herds and those herds whose owners made injury some of the bacteria inter to the blood streams
frequent purchase of cattle had an increased risk of and subsequent bacteremia occurs, which disseminates
acquiring brucellosis. Once infected, the time required the pathogen throughout the body. If the infected
to become free of brucellosis was increased by large animals are pregnant, B. abortus will colonize and
herd size, active abortion and by loss replicate in high number in the chronic trophoblasts
housing(Radostitset al, 2006). ofthe developing fetus. The resulting tissue necrosis of
the fetal membrane follows transmission of bacteria to
2.1.6Pathogenesis the fetus. The net effect of chorionic and fetal
colonization is abortion during the last trimester of
Invading Brucella usually localize in the lymph pregnancy. In fetus, naturally and experimentally
nodes, draining the invasion site, resulting in infected with B. abortus, the tissue changes include
hyperplasia of lymphoid and reticulo-endothelial lymphoid hyperplasia in multiple lymph nodes,
tissue and the infiltration of inflammatory cells. lymphoid depletion in thymic cortex, adrenal cortical
Survival of the first line of defense by the bacteria hyperplasia and disseminated inflammatory foci
results in local infection and the escape of Brucella composed mainly of large mononuclear leukocytes. In
from the lymph nodes in to the blood. During cattle abortion occurs principally in the last three
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 Int. J. Adv. Res. Biol. Sci. (2020). 7(9): 9-31

months of pregnancy, while in dogs occur around 50 demyelization and meningo-vascular syndromes
days of gestation. Abortion in swine can occur at any (Wiley,2005).
time in gestation(Radostits et al., 2006).
Cardiovascular involvement; endocarditis occurs in
2.1.7 Clinical Sign less than 2% of cases, but it accounts for the majority
of brucellosis-related deaths. Genitourinary
Clinical findings of brucellosis such as fever, complications; interstitial nephritis, pyelonephritis,
headache, back pain, sweats, malaise, and anorexia are glomerulonephritis, and immunoglobulin nephropathy
usually non-specific. The onset of clinical have been reported.
manifestations can be insidious or acute, beginning
within 2 to 4 weeks following infection. Compared Epididymo-orchitis occurs in up to 10% of men with
with the symptoms, there are often few signs in the brucellosis (Harrison’s principles of internal medicine
physical examination (Jundishapur J Microbiol. 2011). 16th ed. 2005). Hematological complications;
Mild lymph-adenopathy and splenomegaly or hematologic manifestations of brucellosis include
hepatomegaly may be seen in a portion of patients anemia, leukope-nia, thrombocytopenia, and clotting
(BMC Infect Dis. 2003). Recurrence of symptoms disorders. Ocular complications; uveitis is generally a
after therapy may or may not be associated with late complication, consisting variably of chronic
relapse of the disease. Bacteriologic relapse usually iridocyclitis, nummular keratitis, multi focal
appears within 3 to 6 months after discontinuing drug choroiditis, and optic neuritis (PLoS Med. 2007).
treatment and is not usually caused by antibiotic
resistance (Antimicrob Agents Chemother. 1986). In In highly susceptible non vaccinated pregnant cow,
chronic brucellosis, symptoms can recur after a long abortion occurs after the 5thmonths of pregnancy; in
period of time and are associated with fever which is bull, orchitis and epididmytis are cardinal signs. In
one of the most objective signs of infection. An case of horse, it is usually associated B.abortus with
important laboratory finding is the persistence of high chronic bursal enlargement of the neck and withers,
titers of IgG antibodies (BMC Infect Dis. 2003). In and abortion in mares. Brucellosis in swine has acute
some patients persistent nonspecific symptoms may be symptoms like abortion, infertility and birth of weak
seen without elevated titers of IgG. The reason for this piglets, orchitis, epididymitis and arthritis. Sheep and
condition is not clear, but some investigators believe goats have similar to that observed in other species of
that it may be due to exacerbation of pre-existing animals. Abortion in goats occurs most frequently in
psychoneurosis by the infection(Rev Infect Dis. 1991). the third or fourth months of pregnancy. In case of dog
and cats, infertility either in male or female, abortion
2.1.7.1 Clinical Sign in Animals and still birth or weak puppies are common
manifestations (Radostits et al., 2006).
In some cases patients with brucellosis present with a
range of complications. The most important 2.1.7.2 Clinical Signs in Humans
complications of brucellosis (Wiley; 2005) are as
follows; gastrointestinal symptoms - anorexia, nausea, The most common symptoms of brucellosis include
vomiting, pain, diarrhea, and constipation, which are undulant fever in which the temperature can vary from
observed in 70% of brucellosis cases. Hepatobiliary 37.80c in the morning to 400c in the afternoon; night
system; hepatic involvement is common in brucellosis. sweets with peculiar odder and weakness. Common
Skeletal complications; osteoarticular complications symptoms also include insomnia, anorexia, headache,
are the most common focal forms of the disease and constipation, sexual impotence, nervousness,
have been reported in 10% to 80% of cases depending encephalitis, spondilitis, arthritis, endocarditis, orchitis
on the series, the ages of the patients, and the infecting and depression. Spontaneous abortion mostly in the
Brucella spp. Nervous system; depression and lack of first and second trimesters of pregnancy, are seen in
concentration are common symptoms in brucellosis, pregnant women infected with Brucella. Lack of
however direct invasion of the central nervous system appropriate therapy during the acute phases may result
occurs in less than 5% of cases. Neurological in localization of Brucella in various tissues and
syndromes in brucellosis include; meningitis, organs and lead to sub -acute or chronic disease which
encephalitis, myelitis-radiculoneuronitis, brain is very hard to treat(Mantur&Mangalgi2007).
abscess, epidural abscess, granuloma, and

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 Int. J. Adv. Res. Biol. Sci. (2020). 7(9): 9-31

2.2Diagnosis A definite diagnosis requires the isolation of brucellae

from the blood, bone marrow or other tissues (Wiley;
Diagnosis of brucellosis is based on clinical findings 2005). How-ever, cultural examinations are time
(nonspecific), history (including occupation, travel to consuming, hazardous and not sensitive. Thus,
an endemic area and ingestion of unpasteurized dairy clinicians often rely on indirect proof of infection.
products) and laboratory tests such as serology or A variety of serological tests have been developed, but
bacterial isolation. Although modern diagnostic at least two serological tests should be combined to
techniques such as nucleic acid amplification have con-firm an active infection. Usually, the standard
been introduced, they are not yet widely available tube agglutination (STA) test (Wright) is used first and
especially in areas with restricted resources. Blood and the 2mercap-toetanole (2ME) test will confirm its
tissue based polymerase chain reactions (PCR) can results (with 97.1% sensitivity and 100% specificity)
detect brucellosis, although PCR is more sensitive and (Jundishapur, 2011). In the absence of a bacteriologic
quicker than blood culture (Harrisons principles of examination an initial diagnosis is made by showing
internal medicine 16th ed. 2005). high titers of IgG- antibodies against Brucella in the
serum. (Jundishapur,2011). According to the National
Diagnosis of brucellosis is the corner stone of any Program against Brucellosis (NPB) diagnosis is based
control and eradication programmes of the disease. on serological tests (Wright > 1/80 and 2 ME > 1/20)
Especially in humans due to its heterogeneous and in the presence of clinical findings suggestive of
poorly specific clinical symptoms, the diagnosis of brucellosis (Ghasemi, 2008). Other techniques such as
brucellosis always requires laboratory conformation. It polymerase chain reaction (PCR) have been used to
is made possible by direct demonstration of the causal diagnose brucellosis (Wiley, 2005). Khosraviet al,
organism using staining, immunoflorecent antibody, (2006). reported that the high degree of sensitivity of a
culture, and directly demonstration of antibodies using PCR assay, together with its speed, versatility in
serological techniques (Walker, 1999). sample handling, and risk reduction for laboratory
personnel, make this technique a very useful tool for
For the diagnosis of brucellosis, the organism may be the diagnosis of brucellosis, compared with
recovered from a variety of materials which usually conventional culture method (Pak, 2006).
depends on the presenting clinical signs (OIE, 2009).
In animals, the placenta is the most infective and 2.2.1 Culture Technique and Microscopic
contains the greatest concentration of bacteria; this is Examination
followed by the lymph nodes and milk; and from
blood in humans (Poiester et al., 2010). Furthermore, Specimen of fetal stomach, lung, liver, placenta,
other materials rich in the organism include: Stomach cotyledon and vaginal discharges are stained with
contents, spleen and lungs from aborted foetuses, Gram stain and modified ZiehlNeelsen stains. Brucella
vaginal swabs, semen, and arthritis or hygroma fluids appears as small red-colored, coccobacili in clumps.
from adult animals. From animal carcasses, the Blood or bone marrow samples can be taken cultured
preferred tissues for culture are the mammary gland, in 5-10% blood agar is used .To check up bacterial and
supramammary, medial and internal iliac, fungal contamination; Brucella selective media are
retropharyngeal, parotid and prescapular lymph nodes often used. The selective media are nutritive media,
and spleen (OIE, 2009; Ahmed et al., 2010). All blood agar based with 5% seronegative equine or
specimens must be packed separately, cooled and bovine serum. On primary isolation it usually requires
transported immediately to the laboratory in leak proof the addition of 5 -10% carbon dioxide and takes 3-5
containers. For humans, blood for culture is the days incubation at 37cofor visible colonies to
material of choice, but specimens need to be obtained appear(Maquire, 2002).
early in the disease. The samples should be frozen
until required for culture (OIE, 2009). There is no Marin et al. (1996) reported that a presumptive
ideal tissue for the isolation of Brucella from marine bacteriological diagnosis of Brucellacan be made by
mammals, unlessgrosslesions are found in the tissues. means of the microscopic examination of smears from
However, the recommended tissues for the recovery of vaginal swabs, placentas or aborted foetuses, stained
Brucella in marine mammals are the spleen, the with the Stamp modification of the Ziehl-Neelsen
mammary gland, the mandibular, gastric, external and staining method. However, morphologically-related
internal iliac and colorectal lymph nodes, the testes micro-orga-nisms, such as Chlamydophilaabortus,
and blood (Foster et al., 2002). Chlamydia psittaci and Coxiellaburnettican mislead

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 Int. J. Adv. Res. Biol. Sci. (2020). 7(9): 9-31

the diagnosis because of their superficial similarity for reaction to take place (McCaughey, 1972; Hubber
(Marin et al., 1996; Poiesteret al., 2010). Accordingly, and Nicoletti, 1986). Immunoglobulins present in the
the isolation of B. melitensis on appropriate culture milk will, in part, be attached to fat globules via the Fc
media such as Farrell’s selective media is portion of the fat molecule (Poiesteret al., 2010). The
recommended for an accurate diagnosis (Farrell, immunoglobulinsdetected by MRT areIgM and IgA.
1974). Vaginal swabs and milk samples are the best This test may be applied to individual animals or to
samples to use in isoating B. melitensis from sheep pooled milk samples using a larger volume of milk,
and goats (Marin et al., 1996). relative to the pool size (MacMillan et al., 1990). The
milk ring test is prone to false reactions caused by
Guinea pigs are the most sensitive laboratory animals. abnormal milk due to mastitis, presence of colostrum
Two guinea pigs are intramuscularly inoculated 0.5- and milk from the late lactation (Al-Maririand Haj-
1ml of suspected tissue homogenate and sacrificed at Mahmoud, 2010). False negatives may also occur in
three and six weeks post inoculation and serum is milk with a low concentration of lacteal antibodies or
taken along with spleen and other abnormal tissue for lacking fat-clustering factors (Bercovich, 1998). In
serology and bacteriological examination, respectively spite of these problems, the MRT has been found to be
(Maquire, 2002). extremely effective, and is usually the method of
choice in dairy herds, and may be used as an
2.2.2 Serological Examination inexpensive screening test in conjunction with other
tests (Corbel, 2006).
Body fluids such as serum, uterine discharge, vaginal
mucus, milk, or semen plasma from a suspected Serum Agglutination Test
animal may contain different quantities of antibodies
of the M, G1, G2, and A isotypes directed against This test is based on the reactivity of antibodies
Brucella(Beh, 1974). Infected animals may not always against the smooth lipopolysaccharide of Brucella.
produce all antibody isotypes in detectable quantities; Excess of antibodies resulting in false negative
therefore, results from several serological tests should reaction due to prozone effect can be overcome by
be used as a presumptive evidence of infection (FAO, applying a serial dilution of 1:2 through 1:64 of the
2005). In addition, depending on the sensitivity and serum samples thus increasing the test specificity
specificity, serological tests can be used to screen for, (Afify et al., 2013). The test is performed at a near
or confirm brucellosis. neutral pH, which makes it more efficient in detecting
IgM antibody. Hence, it is best used to detect acute
Traditionally, screening tests are inexpensive, fast and infections. It is less effective for IgG, resulting in low
highly sensitive, but most of the time, lack specificity. assay specificity (Corbel, 1972; Nielsen et al., 1984).
However, confirmatory tests are required to be both Due to this fact, the SAT, despite being sensitive, is
sensitive and specific, thereby eliminating some false generally not used as a single test, but rather it is used
positive reactions. Most confirmatory tests are more in combination with other tests. Other short comings
complicated and more expensive to perform than the of the test include false positive and false negative
screening tests (Diaz et al., 2011). The commonly used results (Poiester et al., 2010). For this reason, the test
serological tests include milk ring test (MRT), serum is only suitable for herd testing, rather than for testing
agglutination test (SAT), standard plate agglutination individual animals.
test (SPAT), complement fixation test (CFT), 2-
mercapto-ethanol test (2-MET), buffered antigen test Rose Bengal Plate Test (RBPT)
(BPAT), and rose Bengal plate test (RBPT). Others
include the card test (CARD), Rivanol test, Coombs The RBPT is a spot agglutination technique which is
test, indirect immune-flourescent test (IFAT), heat also known as the card test or buffered Brucella
inactivation test (HIT), skin test, immune-assay and antigen test (Stemshorn et al., 1985). It uses a
molecular biology technique(Beh, 1974). suspension of B. abortus smooth cells stained with the
Rose Bengal dye, buffered to pH 3.65. At neutral pH,
Milk Ring Test (Mrt) this test can measure the presence of IgM, IgG1 and
IgG2. However, IgM appears to be the most active. At
The MRT is basically a rapid agglutination test carried the buffered pH of 3.65, RBPT, prevents agglutination
out on whole milk or cream. Haematoxylin stained with IgM, and apparently, measures only IgG1
Brucella cells are added to whole milk and incubated (Corbel, 1972). It was considered that while the test

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 Int. J. Adv. Res. Biol. Sci. (2020). 7(9): 9-31

gave few false negative results, it gave many false Enzyme-Linked Immune Sorbent Assay (ELISA)
positives, possibly due, in significant part, to reaction
with IgM in animals with previous vaccination. In The ELISA tests offer excellent sensitivity and
situations where vaccination is not routinely specificity whilst being robust, fairly simple to
conducted, the use of this test can give a good record perform with a minimum of equipment and readily
of exposure of animals to Brucella organisms. available from a number of commercial sources in kit
form. They are more suitable than the CFT for use in
It is an internationally recommended test for the smaller laboratories and ELISA technology is now
screening of brucellosis in small ruminants, but lacks used for diagnosis of a wide range of animal and
standardization of the antigen. Low pH of the antigen human diseases. Although in principle ELISAs can be
enhances the specificity of the test, while the used for the tests of serum from all species of animal
temperature of the antigen and the ambient and man, results may vary between laboratories
temperature at which the reaction takes place may depending on the exact methodology used. Not all
influence the sensitivity and specificity of the test standardization issues have yet been fully addressed.
(Alton, 1981; Macmillan et al., 1990). Corbel (1972) For screening, the test is generally carried out at a
observed that the sensitivity of the test was associated single dilution. It should be noted, however, that
with fractions containing immuno-globulinIgG, although the ELISAs are more sensitive than the
especially the IgG1. RBPT, sometimes they do not detect infected animals
which are RBPT positive. It is also important to note
Complement Fixation Test (CFT) that ELISAs are only marginally more specific than
RBPT or CFT (WHO, 1997). There are also other
The CFT detects mainly the IgG1isotype antibody, as serological diagnostic tests that use for diagnosis of
the IgMisotypes are partially destroyed during the brucellosis such as SAT, PCR, and so on
inactivation process. Since antibodies of the IgG1 type (Epameinondas, 2005).
usually appear after antibodies of the IgM type,
control and surveillance of this disease is best done 2.2.3 Differential Diagnosis
with SAT and CFT (WHO/MZCP, 1998). The test
shows good correlations with the recovery of Brucella The diagnosis of the cause of abortion in a single
organisms from artificial recovery or naturally- animal or in a group of cattle is difficult because of the
infected animals (Madsen, 1994).Although the test is multiplicity of causes that may be involved. When an
fast and accurate, it does not allow for discrimination abortion problem is under investigation, a systemic
between antibodies due to infection from vaccinal approach should be used. This includes a complete
antibodies (Nielsen, 2002; Poiesteret al., 2010). Other laboratory evaluation and follow-up inquiries into
problems include large number of reagents and each herd. The following procedure is recommended:
controls needed to carry out the test. Furthermore,
each time the assay is set up, a large number of  Ascertain the age of the fetus by inspection
titrations are needed, and interpretation of the results is and from the breeding records
subjective due to differences in techniques (Madsen,  Take blood samples for serological tests for
1994). Occasionally, there is direct activation of brucellosis and leptospirosis
complement by serum (anti-complementary activity)  Examine uterine fluids and the contents of the
and the inability of the test to be amenable for use with fetal abomasum at the earliest opportunity for
haemolysed serum samples. The laborious nature of trichomonads, and subsequently by cultural methods
this test and the requirement of highly- trained for B. abortus, Campylobacter fetus, trichomonads,
personnel and suitable laboratory facilities make the Listeria spp., and fungi
CFT less suitable for use in developing countries  Supplement these tests by examination of
(FAO, 2005). The CFT may also test false negative, urine for leptospires, and of the placenta or uterine
when antibodies of the IgG2 type hinder complement fluid for bacteria and fungi, especially if the fetus is
fixation (Nielsen et al., 1988; MacMillan et al., 1990). not available
Despite these inherent problems, the CFT is a widely  Examine placenta fixed in formalin for
used test, and has been regarded as the most specific evidence of placentitis.
and accepted serological test for diagnosis of In the early stages of the investigation, the herd history
brucellosis. Thus, it is a recommended test for may be of value in suggesting the possible etiological
international trade (OIE, 2009). agent. For example, in brucellosis, abortion at 6

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months or later is the major complaint, whereas in making the diagnosis and in
trichomoniasis and vibriosis, failure to conceive and treating patients. The primary diagnostic pitfall is failu
prolongation of the diestrual period is the re to consider possible Brucella infection in a patient
usualhistory(Microbiol, 2005). with history that suggests a possible source of
infection (eg, a farmer, a traveler to an endemic
The protean character of this disease makes it difficult region, or a veterinarian).
to differentiate. Syndromes that need differentiation
include: 2.2.4 Necropsy Finding

 Abortion and infertility in sows In the acute stage, there is inflammatory edema in the
 Posterior paresis diseases of spinal cord loose scrotal fascia, exudate in the tunica vaginalis and
 Mortality in young pigs is also caused by early granulation tissue formation. In the chronic
many agents and the important entities are listed under stage, the tunics of the testes become thickened and
disease of the newborn. ETEC is the most common fibrous and develop adhesions. There are
cause of PWD in pigs. This pathotype is characterized circumscribed indurations in the epididymis and these
by the production of enterotoxins and adhesins, both granulomata may also be present in the testicle. In
essential for disease development. Enterotoxins advanced stages they undergo caseation necrosis. As
produced by ETEC may be heat stable [STa, STb, or the epididymis enlarges the testicle becomes
enteroaggregative E. coli heat stable enterotoxin 1 atrophied. B. avis can usually be isolated from the
(EAST1)] or heat labile (LT). Enterotoxin genes are genital organs, especially the tail of the epididymis,
on plasmids of ETEC bacteria and act on the intestinal and rarely from internal organs and lymph nodes.
epithelium of pigs.Thecritically ill neonates depends
on many factors, including the nature and severity of The abortus is characterized by thickening and edema,
the disease, facilities available for care and the sometimes restricted to only a part of the placenta,
expertise of the personnel caring for the with firm, elevated yellow-white plaques in the inter
neonate(Amezcua,etal2002). cotyledonary areas and varying degrees of
cotyledonary necrosis. Microscopically, organisms are
Many rams with abnormalities of intrascrotal tissues visible within the cytoplasm of trophoblasts of the
do not have brucellosis(Genetzky, 1995). Most are inflamed placenta. A vasculitis is often present. The
cases of epididymitis and need to be organism can be isolated from the placenta and the
differentiatedwithBorder disease, Salmonellosis, stomach and lungs of the lamb
Toxoplasmosis, etc.Abortion in ewes may be
associated with a number of infectious diseases. Some Samples for confirmation of diagnosis
of the diseases that need to be differentiated with
animal brucellosis are summarized as; Bacteriology -epididymal granuloma, seminal vesicle,
inguinal lymph node/fetal lung, stomach content,
 Leptospirosis placenta (CULT -has special growth requirements,
 Infectious bovine rhino-tracheitis CYTO -Stamp's Or Kosters'stain on placental smear)
 Mycoses Histology -formalin-fixed epididymis, testicle,
 Trichomonosis inguinal lymph node/placenta, fetal lung, liver, spleen,
 Neosporosis kidney, heart, brain
 Vibriosis
 Epizootic bovine abortion Necrotizing placentitis and disseminated inflammatory
 Bovine virus diarrhea reactions in aborted fetal tissues are the characteristic
 Enzootic abortion of ewes changes. Adult animals are seldom necropsied.
 Salmonellosis Findings in bovine fetuses infected with B. abortus
 Toxoplasmosis usually include serohemorrhagic fluid in the body
 Rift Valley fever cavities and subcutis, and apneumonia. Often
 Tick borne fever2 granulomatous lesions and focal necrosis are noted in
several fetal organs and a granulomatous
The signs and symptoms of brucellosis can be leptomeningitis may also occur. Pneumonia is not a
nonspecific and can mimic those of many other consistent finding and its character may vary. The
diseases; therefore, meticulous attention is needed in placenta is usually edematous. There may be leathery

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plaques on the external surface of the chorion and Treatment protocols may differ in children less than
there is necrosis of the cotyledons. The key microscopi eight yearsand pregnant women because of adverse
c feature of this inflamedchorioallantois is the presenc effects of some medications including inhibition of
e of intra cytoplasmic coccobacilli within chorionic tro bone growth due to tetracycline treatment in children
phoblasts (Searson1986). and teratogenic potential of some drugs, such
asStreptomycin (WHO 2006).
2.3Treatment
Treatment is unsuccessful because of the intracellular
Brucellosis is treated with antibiotics, although the sequestration of the organisms in lymph nodes, the
most effectiveantibiotic regimens and treatment mammary gland, and reproductive organs and the
durations are unclear (Cisneros1990; Karabay bacteria are facultative intracellular bacteria that can
2004). There are some limitations in choosingthe best survive and multiply within the cells of the
regimen: there is a limited choice of antibiotics that macrophage system. Treatment failures are considered
actintracellularly (eg doxycycline and streptomycin) to be due not to the development of antimicrobial
(Agalar 1999); and the prolonged treatment needed to resistance but rather to the inability of the drug to
prevent relapse may increase the occurrence of penetrate the cell membrane barrier (Radostitiset
adverse events (including gastric discomfort, al.,2007). Though the complex nature of brucellosis
hepatotoxicity (liver toxicity), nephrotoxicity (kidney makes it harder to treat, long-term treatment with an
toxic-ity), and allergic reactions) and reduce adherence antibiotic is thought to be beneficial. In most cases,
to the treatment. Regimens that combine two or more antibiotics in combination are found to be more
antibiotics are now recommended by most experts due effective against the infection; however, the state of
to high relapse rates with treatmentwith one type of the disease still does not lose its importance. Several
antibiotic (monotherapy) (Agalar 1999; Pappas2005b). conventional antibiotics including tetracycline, trimeth
'In 1971, the World Health Organization (WHO) oprim sulfamethoxazole, aminoglycosides, rifampicin,
suggested a 21-day regimen of tetracycline this quinolones, chloramphenicol, doxycycline, and strept
regimen was successful in reducing the early omycin are commonly used in clinics. In several cases,
symptoms, it failed totreat the disease completely, and the application of antibiotics in a specific order has
immediate relapses were seen insome patients (Ariza given best results. Likewise, a case reported that
1985; Cisneros 1990). Accordingly, in 1986the Joint treatment with doxycycline for six months, followed
Food and Agriculture Organization of the United by streptomycin for three weeks was found very
Nations (FAO)/World Health Organization (WHO) effective against brucellosis in human.
Expert Committee on Brucellosis proposed two new
regimens: rifampicin (600to 900 mg/day orally) plus Due to the intracellular localization of Brucella and its
doxycycline (200 mg/day orally) forsix weeks; and ability to adapt to the environmental conditions
doxycycline (100 mg/day orally) for 45 days encountered in its replicative niche e.g. macrophage
plusstreptomycin (1 g/day intramuscularly) for two to (Seleem et al., 2008), treatment of domestic animals
three weeks(WHO 1986). The rifampicin−doxycycline with antibiotics is not usually successful. Even though,
regimen is the mostpopular treatment, possibly treatment failure and relapse rates are also high in
because it is cheap and easily available(Pappas humans, treatment depend on the drug combination of
2005b), while streptomycin requires parenteral doxycycline with streptomycin which is currently the
administration in a hospital setting or in an best therapeutic option with less side effects and less
appropriately set-up primarycare network, both of relapses, especially in cases of acute and localized
which are restricted in lower income countries (Pappas forms of brucellosis (Seleemet al., 2009). Neither
2005a). The above-mentioned combinations streptomycin nor doxycycline alone can prevent
werereplicated in the 2006 WHO recommendations multiplication of intracellular Brucella (Shashaet al.,
(WHO 2006).Other antibiotic formulations, including 1994). Although the doxycycline streptomycine
quinolones (e.g. ciprofloxacin and ofloxacin) and regimen is considered as the golden standard
trimethoprim/sulfamethoxazole (co-trimoxazole), have treatment, it is less practical because the streptomycin
been used (Pappas 2005b; WHO 2006). However, must be administered parentrally for 3 weeks. A
questions remain about their effectiveness (Pappas combination of doxycycline treatment (6 weeks
2006;WHO 2006). duration) with parentrally administered gentamicin (5
mg/kg) for 7 days is also considered an acceptable
alternate regimen (Glynn & Lynn, 2008).

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Measures to prevent and control brucellosis rely upon Organization, 2006). To lower your risk of getting
direct approaches, aimed at minimizing the risk of brucellosis from a natural source: Avoid eating or
spreading infection among animals. Collectively, these drinking unpasteurized milk, cheese, or ice cream
measures reduce the exposure of animals to (including queso fresco), uncooked meat thoroughly,
Brucellaspecies, and increase resistance to infection in and use disinfects in the area where the animals are
susceptible animals(Adone and Pasquali, 2013). aborted (Regea, 2017).

Approaches at Control and Prevention of brucellosis Application of vaccines in the control and eradication
depend on the animal species involved, Brucella of brucellosis in humans has shown unsatisfactory
species, management practices, and availability and results. The use of live vaccines has often provoked
efficacy of vaccines. Approaches used to brucellosis unacceptable reactions in individuals. The recent
includes 1) immunization alone 2) testing and attempt of developing analogue mutants of another
removing of infected animals in conjunction with an Brucella species and the use of Brucella nucleic acid
immunization program, and 3) testing and removing of in the production of animal and human vaccines offers
infected animals without immunization(Walker,1999). hope in the control of the disease (Shirima, 2005).
Vaccination of young heifers, a strategic measure
2.4Prevention and Control Strategies during the early years of eradication schemes, is
discontinued when the prevalence of brucellosis
As the ultimate source infected animals or their reaches low levels that result to predominantly cell-
products, prevention must be based on elimination of mediated immunity. Three types of vaccines are used
human brucellosis is direct or indirect exposure to of in cattle attenuated strain 19(S19) vaccine, adjuvanted
such contact (WHO, 2006). In addition, prevention of 45/20 vaccine and the more recent RB51 vaccine:
human brucellosis depends mainly on programmes to
control and eradicate the disease in farm animals in 1. S19 vaccine is administered to female calves
order to reduce the prevalence of infection in herds up to 5 months of age, and vaccination of mature
through implementation of health control and/or animals leads to persistent antibody titres.
medical measures (animal vaccination), and when 2. 45/20 bacterin, although less effective, has
possible to attain eradication of the disease, initially been is some national eradication schemes, and even
farm by farm, and then on a regional and national level when administered to adult animal, the vaccine does
(“FAF, EOHS”2014). Every case of human brucellosis not induce persistent antibody titres
is directly or indirectly linked with infected animals or 3. RB51 strain is stable, rough mutants who
their products. So, the control of human brucellosis induce good protection against abortion and does not
depends on minimizing/ controlling disease burden in result persistent antibody titres (Quinn et al., 2002).
animals and reducing animal to human transmission For brucellosis prevention, the following measures can
(Zinsstag et al., 2011). be used as alternatives, it includes:

Methods of prevention include health education to  Careful selection of replacement animals.

reduce occupational and food-borne risks, including These, whether purchased or produced from existing
pasteurization of all dairy products. However, stock, should originate from Brucella-free herds or
education campaigns have never resulted in fully flocks. Pre-purchase tests are necessary unless the
eliminating the risks of infection, and the ultimate replacements are from populations in geographically
prevention of human infection remains elimination of circumscribed areas that are known to be free of the
the infection among animals (Regea, 2017). disease.
 Isolation of purchased replacements for at
The control of the disease in humans is impaired by least 30 days and in addition a serological test prior to
the lack of available vaccines, thus leaving the control commingling is necessary.
of animal brucellosis as the most effective strategy to  Prevention of contacts and commingling with
prevent human infection (Pérez-Sancho et al., 2015). herds or flocks of unknown status or those with
In many situations there is little alternative but to brucellosis.
attempt to minimize impact of the disease and to  If possible, laboratory assistance should be
reduce the risk of infection by personal hygiene, utilized to diagnose causation of abortions, premature
adoption of safe working practices, protection of the births, or other clinical signs. Suspect animals should
environment and food hygiene (World Health be isolated until a diagnosis can be made.

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 Int. J. Adv. Res. Biol. Sci. (2020). 7(9): 9-31

 Herds and flocks should be included in committees or even by collection of diagnostic

surveillance measures such as periodic milk ring tests samples or immunization. Several audiovisual aids are
in cattle (at least four times per year), and testing of available which could be used in conjunction with
slaughtered animals with simple screening serological lectures or group discussion with great advantage.
procedures such as the RBT. Others, such as posters and wall pictures, can be used
 Proper disposal (burial or burning) of on work premises to remind workers of various
placentas and non-viable fetuses, and disinfection of dangers or of precautions they have to take in handling
contaminated areas should be performed potentially infected animals or products. It is
thoroughly(WHO,2006). important to enlist the aid of community leaders in the
education campaign.

3 Conclusion and Recommendation The development of delayed hypersensitivity to

intradermally administered Brucella-specific antigens
Brucellosis is one of the most widespread zoonoses, is an indication of past exposure to infection but does
mainly caused by Brucellaabortus, Brucella melitensis not indicate its current significance. Although used in
or Brucella suis, and is transmitted to people from the past in some countries, the intradermal test is not
various animal species that mainly by direct contact recommended for diagnosis. The use of undefined and
with infected livestock or through consumption of raw unstandardized antigen preparations may also provoke
or uncooked animal products. In human, Brucellosis is antibodies which interfere with subsequent serological
always caused by B. melitensis(cause Undulant or tests.With increasing use of live Brucella vaccines to
Malta fever) followed by B. suis, B. abortus and B. immunize cattle (B. abortus strain 19 and RB 51) and
canis, and it causes a systemic infection with clinical sheep and goats (B. melitensis strain Rev 1), the
manifestations as fever, sweats, fatigue and joint pain . problem of accidental self-inoculation by veterinarians
is widespread.
The disease primarily affect cattle, buffalo, bison,
pigs, goats, sheep ,dogs, elk, camels and occasional The essential element in the treatment of all forms of
horses, and it can be late abortion, retained foetal human brucellosis is the administration of effective
membranes, and to a lesser extent, orchitis and antibiotics for an adequate length of time. Antibiotic
infection of the accessory sex glands in males and treatment should be implemented at as early a stage as
impaired fertility. Aborted fetuses, placental possible, even in patients who appear to be showing a
membranes or fluids, and other vaginal discharges spontaneous improvement. In those patients with
present after an infected animal has aborted or calved complications, additional treatment, including in some
are all highly contaminated with infectious Brucella cases surgical intervention, will be necessary.
organisms. It causes considerable economic losses in
livestock production due to abortion, infertility and As the ultimate source of human brucellosis is direct
reduction in milk production, and in addition, the or indirect exposure to infected animals or their
zoonotic nature of the disease has a serious impact on products, prevention must be based on elimination of
public health. such contact. The obvious way to do this elimination
of the disease from animals is often beyond the
Since people working in direct contact with infected financial and human resources of many developing
animals: breeders, veterinarians, artificial insemination countries. The technical and social difficulties
technicians, slaughterhouse worker, laboratories involved in eradicating B. melitensis from small
worker and rendering plant personnel are those most ruminants have even taxed the resources of some
highly exposed to infection; these people must be developed countries.
awareness on transmission of disease. Education of
people in order to avoid consuming unpasteurized Vaccination is an extremely important and effective
milk and milk derivatives, and careful handling and facet of most control strategies but has the
disposal of afterbirths, especially in cases of abortion disadvantage that its use may confuse diagnosis by
is important. stimulating the production of hypersensitivity or
antibodies detectable by serological tests. Antibody
Small discussion groups and lectures are extremely titres may persist for a prolonged period in a small
useful means of communication and could be followed proportion of vaccinated animals and this proportion
immediately by such actions as formation of action increases with age at vaccination.

26
 Int. J. Adv. Res. Biol. Sci. (2020). 7(9): 9-31

Farm workers and animal attendants in particular, unlikely to be successful in cattle if the remainder of
should wear adequate protective clothing when contact the herd is unvaccinated, especially in large
with infected animals is probable or if the environment populations.
is likely to have been contaminated by excreta,
abortions or parturition products from animals with The goal in the application of hygiene methods to the
brucellosis.Farm implements used for handling control of brucellosis is reduction of exposure of
contaminated material should be disinfected after use susceptible animals to those that are infected, or to
by immersion in a suitable disinfectant (iodophor, their discharges and tissues. This is a classical
phenolic soap or dilute caustic soda). procedure in disease control. Factors such as the
methods of animal husbandry (e.g. commingling of
Brucellosis is a zoonosis with a strong correlation herds or flocks), patterns of commerce, prevalence of
between animal and human diseases. While public clinical signs, type of facilities, and degree of
health measures such as pasteurisation and education dedication of the owners of animals, will also
have varying degrees of success, it remains primarily a determine success. Owners are often poorly informed
veterinary responsibility to control brucellosis, about disease transmission and recommendations,
including application of principles of epidemiology such as separation of parturient animals, can be
and animal husbandry.Careful selection of difficult or impossible to implement.
replacement animals. These, whether purchased or
produced from existing stock, should originate from Brucellosis may be avoided by using proper sanitation
Brucella-free herds or flocks. Pre-purchase tests are methods. Proper herd management strategies can also
necessary unless the replacements are from aid in the avoidance of the disease. These include:
populations in geographically circumscribed areas that Maintaining closed herds, recording individual animal
are known to be free of the disease. identification and maintaining accurate records,
isolating and testing purchased additions as well as
The aim of an animal control programme is to reduce cattle re-entering the herd and arranging diagnostic
the impact of a disease on human health and the workups and necropsies for potentially or suspected
economic consequences. The elimination of the brucellosis infected cattle.
disease from the population is not the objective of a
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