1

BRUCELLOSIS: A NEGLECTED ZOONOSIS1

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SUMMARY3

Brucellosis is a bacterial disease mainly of domestic animals. The infection is transmitted to humans by animals4

through breaks in the skin by contact with infected materials like aborted foetuses, placenta or indirectly by5

ingestion of animal products and by inhalation of airborne agents. Brucellosis is the most important zoonosis6

worldwide which accounts for about 500, 000 reported human cases annually around the globe particularly among7

agricultural and pastoral populations. It results in serious economic losses in animals as a result of abortion, reduced8

fertility, birth of weak offsprings and reduced productivity; and in humans, it results in chronic debilitation resulting9

in low work output and subsequent negative economic implication. The paper reviews brucellosis in different10

species of animals. It highlights the aetiology, morphology, host range, pathophysiology, clinical signs, pathology11

and epidemiology of the disease in various species. Preventive and control measures against the disease, economic12

and public health implications have been also examined. It is concluded that, the eradication of brucellosis in13

animals may be achieved by long-term investment in surveillance programmes, including testing and culling of14

positive reactors and vaccination, culminating in eradication of the disease the human population.15

Key words: Brucellosis, zoonosis16

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18

INTRODUCTION19

Brucellosis is a highly contagious and one of the most important and prevalent zoonoses worldwide which is caused20

by bacteria of the genus Brucella (Foster et al., 2009). The burden of the disease is enoumous but yet remains21

under-prioritised globally especially amongst the pastoralists and small-scale livestock farmers (Plum et al., 2013).22

Humans can be infected by the ingestion of food products such as milk and its products contaminated with the23

organism or by direct interaction with an infected animal or aerosol inhalation (Christopher, 2010; Rust, 2012). It is24

mainly an occupational disease affecting veterinarians, abattoir workers, farmers and laboratory workers, working25

with the organism. It is therefore recommended that all laboratory work involving this organism should be carried26

out under biosafety level 3 (Poiester et al., 2010). There are four species of Brucella incriminated in human27

brucellosis, which are B. melitensis, B. suis, B. abortus and B. canis in order of importance (CDC, 2004; Yongqun,28

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2006). The synonyms of the disease in humans are: Undulant fever, Constantinople fever as well as fevers of Malta,29

Naples, Cyprus, Crete, Crimea, Levant, Syria, Mediterranean, Gilbraltar, Gastric, milk, Remittent, Relapsing and30

Rock (Megid et al., 2010; Rust, 2012). The disease in cattle is also known as infectious abortion, “slinking of calf”,31

contagious abortion, epizootic abortion and Bang’s disease in tribute to the pioneer of the study of the disease in this32

species (Abdulkadir, 1989; Megid et al., 2010).33

34

AETIOLOGY35

The organisms of the genus Brucella are part of the α-2 subgroup of the Proteobacteriaceae. They show close36

genetic bond with some plant pathogens and symbionts of the genera Agrobacterium and Rhizobium, and also with37

animal pathogens (Bartonella) and opportunistic or soil bacteria (Ochrobactrum) (OIE Terrestrial Manual, 2009).38

Brucella organisms are Gram-negative, facultative intracellular bacteria (Young, 2000; Alton and Forsyth, 2004).39

They are strictly aerobic, non-encapsulated, and catalase- and oxidase-positive (Young, 1995). They are non-40

carbohydrate fermenters and have variable urease activity. The Brucella organisms have a lipopolysaccharide coat41

that is much less pyrogenic than other Gram-negative organisms, which explains the reason for the rare presence of42

high fever in brucellosis (Gerald and Faaem, 2009; Rust, 2012). There are six well-known and documented species43

of the genus which include B. abortus, B. melitensis, B. ovis, B. canis, B. neotome and B. suis and they are further44

divided into biotypes (Alton et al., 1975). However, recently, a marine species was identified and was first classified45

as B. maris which was later divided into two species: B. ceti and B. pinnipedialis, denoting isolates from cetaceans46

and seals, respectively (Foster et al., 2007). Furthermore, a new Brucella species was first isolated in 2008 from47

systemically-infected common voles (Microtus arvalis) in South Moravia, Czech Republic, which was named B.48

microti (Scholz et al. 2008). The organism was similarly isolated from mandibular lymph nodes of wild red foxes49

(Vulpes vulpes) in Austria. The latest species described is B. inopinata, which was isolated from infected human50

breast implant (De, 2008; Scholz et al., 2010). However, the reservoir of this species of Brucella is not known. An51

unnamed strain (Brucella spp. NVSL 07-0026) has also been isolated lately from a baboon (Schlabritz-Loutsevitch,52

2009). Consequently, this shows that there is more information to be explored with respect to the genus Brucella and53

its host range.54

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Morphology58

Brucella organisms are small measuring about 0.5-0.7 by 0.6-1.5µm, non-motile, non-spore forming, non-59

encapsulated, coccobacilli, which occur singly or occasionally in a group of short chains or clusters (Ryan and Ray,60

2004). Likewise, they do not have flagella or pilli and do not show bipolar staining. The cellular and colonial61

morphology of the species of Brucella are similar in most respect (Deyoe, 1981). All Brucella species possess62

smooth lipopolysaccharide (SLPS) in their outer cell wall with the exception of B. ovis and B. canis, which have the63

rough lipopolysaccharide (RLPS) and protein antigens (Blasco, 1990). Smooth lipopolysaccharide contains an64

immunodominant O polysaccharide (OPS) which has been chemically defined as a homopolymer of 4, 6-dideoxy-4-65

formamide-alpha-D mannose linked via glycosidic linkages (Bundle et al., 1987).66

HOST RANGE67

Verger et al. (1987) reported that, in spite of more than 94% similarity amongst members of the genus Brucella, the68

causative agents have inclinations for different hosts. It has also been advocated that Brucella melitensis can69

represent members of the genus with multiple biovars. The primary host plays an important role in the maintenance70

of the disease in nature, as most of them are reservoirs of infection for each particular species (Ko and Splitter,71

2003). The alpine ibex in Italy and chamois in the French Alps have been found to be infected with Brucella72

organism. However, there is no evidence that these animals serve as reservoir hosts for livestock (OIE, 2009).73

Sheep and goats are mainly infected by three biovars of Brucella melitensis (OIE, 2009). Most breeds of goats are74

readily infected, but the susceptibility in breeds of sheep is variable. Brucella melitensis, the least species-specific75

species of Brucella, has been reported occasionally in cattle, camels and dogs, but rarely in horses and pigs.76

Infections in sheep and goats can spill over into wild ruminants. Sheep have a relative resistance for infections with77

B. abortus (Collier and Molello, 1964; Allsup, 1974). They can, however, assume a carrier state, capable of78

excreting the organism for up to 40 months post- infection (Luchsinger and Anderson, 1967). The occurrence of79

natural infection with B. abortus is low in goats, thus making this animal species less important as a host. (Mathur,80

1967).81

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Cattle are the preferential host for B. abortus. However, infections with this species of Brucella can occur in82

buffaloes, camels, deer, dogs, horses, goats, sheep, and man (Manthei, 1950; Kudi et al., 1997; Megid et al., 2010).83

Turkeys, pigeons, pheasant, duck, goose, and chicken have also been reported to be susceptible (Emmel, 1930;84

Adesiyun and Abdu, 1984).85

Horses are susceptible to B. abortus and less frequently to B. suis. The organism has a preference for bursae,86

tendons, muscles and joints, where they cause arthritis, intermittent lameness and swelling of the carpal joint.87

However, it is normally found as secondary invaders in cases of “fistulous withers” and “poll evil”, which is88

inflammation of the supra-spinatous and supra-atlantal bursa, respectively (Hall, 1977, Megid et al., 2010).89

90

Systemic infection leading to reproductive involvements in pigs is usually caused only by Brucella suis, biovars 1, 291

and 3 have been identified as an important re-emerging disease of domestic and wild pigs (Fretin et al., 2008).92

However, this pathogen may also affect other animal species such as cattle, horses, rabbits, hares, reindeers, dogs,93

and humans (Rust, 2012). Brucella suis biovars 1 and 3, have been shown to have pathogenic potential for humans94

(Frye, 1991). Furthermore, biovars 4 and 5 are specifically associated with reindeer and rodents, respectively95

(Corbel, 2006). Self-limiting infections can occur in pigs infected with other Brucella species (OIE, 2009a).96

Dogs can be infected by four of the six species of Brucella, namely B. canis, B. abortus, B. melitensis and B. suis,97

excluding B. ovis and B. neotomae (Hollet, 2006). Canine brucellosis caused by B. canis, usually affect domestic98

dogs, wild carnivores, and seldom other domestic animals and man (Carmichael, 1990). The disease could be99

presented as asymptomatic to mild, despite an on-going systemic infection (Shin and Carmichael, 1999).100

The Office International des Epizooties (2009) reported that camels are not known to be primary host for any101

species of Brucella organisms. However, they are susceptible to both B. abortus and B. melitensis. Brucella102

neotomae is known to infect only the desert wood rat under natural conditions and has not been reported to infect103

other species of animals (Stoenner and Leckman, 1957).104

The marine strain of Brucella has been isolated from various species of marine mammals, which include: seal105

(Phoca vitulina), dolphins (Tursiops truncatus, Delphinus delphis, Lagenorhynchus acutus and Stenella106

coeruleoalba), whale (Balaenoptera acutorostrata, Balaenoptera physalus, Orcinus orca) (Ewalt et al., 1994; Ross107

et al., 1994; Foster et al., 1996).108

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Brucella melitensis, B. suis and B. abortus are the major Brucella species responsible for human brucellosis. These109

species have ruminants, pigs, and cattle as preferential hosts, respectively (Godfroid et al., 2005). However, B.110

melitensis is incriminated as the principal cause of brucellosis in humans with a few organisms, ranging from 10 to111

100 being sufficient to set off an incapacitating chronic infection (Fugier et al., 2007). Two recently-identified112

Brucella species isolated from marine mammals, B. ceti and B. pinnipedialis, may cause human brucellosis (Foster113

et al., 2007).114

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PATHOPHYSIOLOGY117

Members of the genus Brucella are intracellular pathogens that localize in lympho-reticular cells of the body and118

have a special affinity for sugar-rich organs such as the pregnant uterus and udder or the testicles and accessory sex119

glands of the female and male hosts, respectively (Ghaffar, 2010; Olsen et al. 2010). After ingestion, the Brucella120

organism penetrates the mucosal epithelium of the gastro-intestinal tract, from where it is transported free or within121

phagocytic cells to regional lymph nodes (Poole et al., 1972). In a pregnant uterus, multiplication of the bacteria is122

favoured by the presence of the sugar alcohol, erythritol, which is a foetal product concentrated in the chorion and123

cotyledons. Furthermore, the interaction of the bacteria with placental trophoblasts suggests that its ability to acquire124

iron is vital as the brucellae enter their acute replicative stage (Cutler et al., 2005). Mutants of Brucellae, unable to125

utilize erythritol, are severely attenuated in ruminant hosts. In vitro data suggest that Brucella metabolizing126

erythritol have a heightened requirement also for iron, scavenged through siderophores such as 2, 3-127

dihydroxybenzoic acid or brucebactin. This may be linked with the requirement for effective iron acquisition for128

virulence in ruminant hosts. The absence of erithritol in human placenta and foetus may explain the reason for lack129

of spontaneous abortion in humans (Gonzalez Carrero et al., 2002; Parent et al., 2002). In a more advanced phase,130

B. melitensis can colonize the udder of lactating goats, resulting in acute mastitis with the production of clotted and131

watery milk and reduced milk yield (Enright, 1990).132

The long-term survival and replication of Brucella spp. is enhanced by their ability to modify the endosomal133

compartment of phagocytic cell. This they do by employing various mechanisms to make the host environment134

suitable. It was also reported by Xavier et al (2010) that the Brucella organisms have the ability to persist and135

replicate within phagocytic cells of the reticulo-endothelial system as well as in non-phagocytic cells such as136

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dendritic cells macrophages and trophoblasts. In these cells, they form an important source of the organisms for137

periodic re-infection. The major virulence factor for the organism is cell wall lipopolysaccharide, which is essential138

for the functional and structural integrity of the outer membrane of Gram-negative bacteria. Normal serum factors,139

including complement, are involved in opsonisation of the organisms to allow phagocytosis, polymorphonuclear140

leucocytes have limited ability to kill bacteria within phagocytes. Thus, Brucella organisms that escape are further141

ingested by macrophages, where they become localised and undergo multiplication within organs of the reticulo-142

endothelial system. There could be an involvement of any or multiple organs and systems of the body (Lapaque et143

al., 2005). There is a surge in the level of humoural antibodies directed against lipopolysaccharide soon after an144

infection and other cell wall antigens are produced. However, the ability of the body to mount cell-mediated145

immunity is the major mechanism of recovery from the illness. Survival of Brucella organisms in the host may be146

due to the production of adenine and guanine monophosphate. The production inhibits phagosomal fusion and147

oxidative burst activity by inhibiting the degranulation of peroxidase-containing granules and, consequently, the148

myeloperoxidase-peroxide-halide system of bacterial killing (Ghaffar, 2010; Wafa, 2011).149

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INCUBATION PERIOD151

There is a significant variation in the incubation period in infection with members of the genus Brucella. The period152

is mainly influenced by gestation, exposure dose, age, and vaccination status (Nicoletti, 1980). The length of the153

incubation period is inversely proportional to the stage of gestation at the time of exposure and could range between154

53-251 days (Thomsen, 1950).155

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CLINICAL SIGNS OF BRUCELLOSIS158

Brucellosis is a multi-systemic disease. The nature, degree of the infection, animal host and the infecting Brucella159

species are determinants of the manifestation of clinical signs (Megid et al., 2010).160

Cattle161

In cows, the disease usually becomes apparent, causing abortion occurring from the 5 th to the 8th month of gestation.162

However, abortion was observed in a three-month pregnant heifer 56 days after being fed with the cotyledons from163

an aborting cow as observed by Bang in 1906 (Megid et al., 2010). According to Acha and Szyfres (2003), abortion164

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in pregnant females usually occurs once, after which immunity is acquired. Subsequently as an alternative to165

abortion, birth of premature foetuses, still-born or birth of weak calves may occur. Placental retention, which may166

follow abortion, may lead to metritis, which in turn may cause permanent or momentary infertility. Some infected167

cows do not show any symptoms of the disease and may give birth to normal calves (Nicoletti, 1980). Brucellosis in168

bulls mainly affects the reproductive tract, leading to orchitis, epididymitis, ampullitis and seminal vesiculitis.169

Orchitis is usually unilateral, but there is a possibility that both testicles may become affected. The period of170

incubation of brucellosis in the bull has not been fully determined (Plant et al., 2008).171

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Pigs173

The most common manifestation of brucellosis in the sow is abortion, occurring at any time during gestation (OIE,174

2009a). Vaginal discharge is often absent in chronically infected sows. The most economically important sequel of175

the disease is infertility rather than abortion. Deyoe (1986) and Megid et al. (2010) reported that abortion rate is176

higher in sows and gilts exposed to B. suis via the genital tract at the time of breeding, and that abortions are177

influenced more by the time of exposure to the B. suis rather than by the stage of gestation. Furthermore, embryonic178

resorptions have been witnessed as early as 17 days following natural mating by boars, disseminating B. suis179

through their semen. Abortions in early pregnancy usually occur with little or no vaginal discharge. Affected sows180

rarely abort more than once and those infected before sexual maturity hardly ever abort (Acha and Szyfres, 2003).181

Brucellosis could turn out to be more persistent causing lesions in the reproductive tract that often result in either182

temporary or permanent interference with sexual activities (OIE, 2009a). Furthermore, the organism can be183

discharged in the semen of infected boars without any apparent abnormality in the sex organs or interference with184

sexual activity. In both sexes, infection may result in swollen joints and tendon sheaths, which may subsequently185

manifest as lameness and, seldom, posterior paralysis (Deyoe and Manthei, 1975; Holyoake, 2010). There could also186

be abscesses of various sizes in organs and tissues (Acha and Szyfres, 1989). Boars that do not develop a genital187

infection seldom recover from the disease (Deyoe, 1986). However, infections in accessory sex glands are very188

common in boars, but do not always affect fertility. Infection of the genital organs is usually short-lived in sows189

(Acha and Szyfres, 2003).190

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Sheep and Goats193

There has not been evidence that involvement of different biovars of Brucella melitensis results in varying clinical194

signs in sheep and goats (Fensterbank et al., 1987). The principal clinical feature of B. melitensis infection in ewes195

and does are late term abortion, placental retention, and birth of weak offspring, who usually die during the196

peripartum period (Aldomy et al., 1992). Alton (1990) observed that abortion in female goats occurred between 3197

and 4 weeks after experimental infection with high doses of B. melitensis. However, abortion in ewes occurred 4 to198

12 weeks after experimental infection with the same organism, which is an indication that ewes are relatively more199

resistant. Most acute natural infections with Brucella melitensis in does during pregnancy lead to colonisation of the200

udder, which lead to shedding of the organism in milk during subsequent lactations. Intermittent shedding of the201

organism in milk also occurs in animals with persistent udder infection, resulting in inflammation of the udder with202

subsequent reduction in milk production (The European Commission, 2001).203

Acute phase of brucellosis in the ram results in epididymitis, which can be severe, with sperm stasis and secondary204

spermatocele formation, resulting in infertility (Enright, 1990). This phase is characterised by poor semen quality205

and distension of the scrotal sac by either haemorrhagic or fibrino-purulent exudates (Enright, 1990). The principal206

clinical findings are palpable lesions in the epididymis and tunicae. However, lesions usually ensue after the acute207

syndrome has resolved and the latent period has elapsed. The chronic phase in infected bucks could, however, be208

characterised by hygromas and joint inflammation. It is worthy of note in infection with Brucella ovis that some209

infected rams, showing palpable lesions at one examination may be clinically normal a few weeks later, and that not210

all infected rams develop lesions in their external genital organs (Jones and Marly, 1975).211

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Horses213

In horses, brucellosis can pass un-noticed or may be associated with clinical signs for as long as two years post-214

exposure (Cvetnic et al., 2005). Infection in this species most often involves Brucella abortus. Furthermore, the215

disease is mainly recognised as an inflammation of the supraspinous and supra-atlantal bursae. The syndromes are216

known as “fistulous withers” and “poll evil”, respectively. The bursal sac becomes obviously distended by a clear,217

viscous, straw-coloured exudate and develops a thickened wall. It may rupture, resulting in a secondary point of218

infection by other invading organisms. Excretion of the organism in vaginal discharges seems to be short-lived in219

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mares. Other clinical signs reported in horses due to B. abortus infection are arthritis, intermittent lameness, lethargy220

and swelling of the carpal joint (Ocholi et al., 2004).221

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Dogs223

Shin and Carmichael (1999) reported that infection with B. canis results in variable clinical signs associated with the224

reproductive system. This infection can be asymptomatic to mild, despite an on-going systemic infection, with high225

morbidity and low mortality. The characteristic sign of brucellosis in the canine species as in most species of226

animals is late-term abortion, which can occur between 30-57 days of gestation. It is more common from 45 to 55227

days of gestation in about 75% of the cases. Abortions are followed by mucoid, sero-sanguineous, brownish or grey228

vaginal discharge that persists for up to six weeks. The pattern of oestrus and breeding does not change in bitches229

with brucellosis (Hollet, 2006). The disease in the bitch can result in repeated abortions or birth of sick puppies that230

often die during the post-partum period. Resorption or early embryonic death within 2 to 3 weeks after breeding can231

also occur. Subsequently in the disease, birth of apparently normal offsprings can occur (Shin and Carmichael, 1999;232

Hollett, 2006).233

Clinical signs of Brucella abortus infection in dogs vary from mild fever to orchitis and testicular atrophy with234

shedding of the organisms in the urine (Neiland and Miller, 1981). Mantur et al. (2007) reported that dogs235

experimentally infected with B. suis were found to be afebrile and asymptomatic and do not present gross lesions. It236

was further reported that under natural conditions, weakness of the hind-limbs along with large and firm237

epididymitis could be associated with oligospermia and increased number of neutrophils in semen, similar to what is238

observed in infection with Brucella canis. Failure to achieve intromission due to pain, unwillingness to ejaculate or239

successful internal ties without pregnancy has been reported (Robles et al., 1998; Hollett, 2006). Brucella canis240

infection targets androgen-dependent organs, causing severe epididymitis, orchitis and prostatitis. Epididymitis241

usually begins at about five weeks after infection, and can be detected on physical examination by an acute onset of242

inflammation, pain and swelling. There is the development of scrotal dermatitis as a result of constant licking of the243

scrotum. This may subsequently lead to oedema, which could further be contaminated by non-haemolytic244

staphylococci (Hollett, 2006).245

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Camels248

Camels are not known to be major host for any Brucella species (Musa and Shigidi, 2001) .However, camels may be249

infected with B. abortus and B. melitensis when they are pastured together with goats, cattle and sheep. In such250

cases, they shed the organisms in milk, thus posing a serious public health problem (Musa et al., 2008; Gwida,251

2012). Camels are silent carriers of the disease as clinical signs of brucellosis in camels seem to be very rare.252

253

Humans254

Human brucellosis is a chronic, debilitating and life-threatening disease that may be presented with variable clinical255

signs (Colmenero et al., 1990). Although the clinical presentations of the disease are variable, the most common256

clinical sign is undulant fever in which the temperature can vary from 37ºC in the morning to 40ºC in the afternoon.257

Other signs include night sweats with a peculiar odour, chills, arthralgia, myalgia and weakness (Megid et al., 2010).258

Furthermore, malaise, insomnia, anorexia, headache, constipation, sexual impotence, nervousness, and depression259

are also common presentations. Depending on the internal organs affected, complications like spondylitis, arthritis,260

endocarditis, orchitis and prostatitis could be noticed (Acha and Szyfres, 2003). Neurological complications like261

meningitis, encephalitis, meningo-encephalitis, brain abscess, chorea, facial palsy, meningo-myeloencephalo-262

spondylosis, and ischaemic attacks have also been reported to occur during the onset of the disease, during the263

recuperation period or even well after recovery from an acute infection (Tikare and Mantur, 2008). Though the264

illness can be debilitating and chronic, brucellosis is seldom fatal in humans, except for few untreated cases due to265

endocarditis (Madkour, 2001).266

267

A prolonged course of illness, often associated with suppurative destructive lesions, is associated with B. suis268

infections. Brucella abortus is associated with mild-to-moderate sporadic disease that rarely causes complications.269

Brucella canis infection has a disease course that is indistinguishable from B. abortus infection. Brucella canis270

infection has an insidious onset, causing frequent relapses, and does not commonly cause chronic disease in humans.271

Brucella pinnipediae and B. cetaceae have been recently reported to cause mainly neuro-brucellosis in humans272

(Wafa, 2011).273

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PATHOLOGY DUE TO BRUCELLOSIS277

General pathology278

Pathology due to brucellosis is usually generalized because various organs are affected, though they are mostly279

encountered in the reproductive system (Meador et al., 1989). The pathology may depend on the infecting Brucella280

species and the organs or tissues involved. Aborted foetuses may appear normal, autolysed or may have different281

degrees of subcutaneous oedema along with blood-stained fluid in their body cavities (Xavier et al., 2009).282

Abortions in brucellosis are typically accompanied by placentitis and the cotyledons may appear red, yellow, normal283

or necrotic. In cattle and small ruminants, the intercotyledonary region is characteristically leathery, appearing wet284

with focal thickening and exudates on the surface (OIE, 2009). Histological findings in brucellosis infection are285

mainly lymphocytic infiltrations, granulomas with necrosis (Jackson and Pankay, 1967).286

In adult animals, the reproductive tract, mammary gland, supramammary lymph nodes, other lymphoid tissues,287

bones, joints, and other tissues and organs may show granulomatous to purulent lesions. Mild to severe endometritis288

may be observed after an abortion (AHA, 2005). In bulls, B. abortus results in swelling of the testicles that may not289

be obvious. The pressure induced owing to the swelling, may result in necrotic foci that coalesce and lead to entire290

necrosis of the testicules with sequestration by inflammatory thickening of the tunica. It was reported by Nicoletti291

(1986) that the accessory sex glands may be infected by B. abortus, and that the organism may also localize in the292

carpal and other bursae, where hygromas containing large number of bacteria may be found.293

294

In sows, B. suis biovar 2 infections are associated with nodules of varying sizes in internal organs, particularly seen295

more in the reproductive organs (OIE, 2009a). The lesions can also be seen in the spleen, liver, lungs, and most296

other organs, including the skin and subcutaneous tissues. Nodules often become purulent, but regardless of the297

presence of the nodules, the sow’s body condition may remain good. In addition, cattarhal metritis is common and298

that abscess can frequently be found in the testes or seminal vesicles of the boar (Meirelles-Bartolli et al., 2012).299

Histologic findings in brucellosis usually include mixed inflammatory infiltration with lymphocytic predominance,300

granulomas (in up to 55% of cases) and necrosis.301

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Pathology due to Brucella melitensis infection304

Aborted foetuses due to B. melitensis usually have a normal gross appearance. However, there can be305

bronchopneumonia, haemorrhagic fluid in the thoracic cavity, enlarged lymph nodes, liver and spleen (Alton, 1990).306

Granulomatous inflammatory lesions are often found in lymphoid tissues and organs such as the reproductive307

organs, udder and supramammary lymph node and sometimes joints and synovial membranes in animals infected308

with B. melitensis. However, the lesions when present are not pathognomonic. There can also be an acute mastitis309

with palpable nodules and the production of clotted and watery milk in the udder of infected animals (EC, 2001).310

311

Pathology due to Brucella ovis infection312

Lesions caused by B. ovis are generally restricted to the epididymis and accessory sex glands (Cameron and313

Leuerman, 1976; Bulgin, 1990). The epididymal enlargement can be unilateral or bilateral, and the tail of the314

epididymis is more often affected than the head or body. There is usually a fibrous atrophy of the testis, the tunica315

vaginalis is also often thickened and fibrous and can have extensive adhesions. Semen of infected rams is usually of316

poor quality as characterized by decreased sperm concentration, and contains inflammatory cells (Buckrell et al.,317

1985). Although placentitis is uncommon, it is occasionally seen in infected ewes (OIE, 2009).318

319

Pathology due to Brucella canis infection320

The lymph nodes are often enlarged in affected species. The retropharyngeal and inguinal lymph nodes are often321

involved, but generalized lymphadenitis also occurs. The spleen is frequently enlarged, and may be firm and322

nodular. Hepatomegaly may also be seen. Scrotal oedema and scrotal dermatitis, epididymitis, orchitis, prostatitis,323

testicular atrophy and fibrosis may occur in some infected males, while metritis and vaginal discharge may be seen324

in infected females. Less commonly reported lesions include discospondylitis, meningitis, focal non-suppurative325

encephalitis, osteomyelitis, uveitis, and abscesses in various internal organs (Hollett, 2006). Lesions from aborted326

foetus in the canine species are not obvious, however the organism can be isolated from the lungs and liver (Brennan327

et al., 2008). Carmichael and Joubert (1988) reported that semen from infected dogs usually contains large numbers328

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of abnormal sperm and inflammatory cells, especially during the first three months following infection and329

chronically infected males may have azospermia, or reduced numbers of immature sperm cells.330

331

Pathology due to Brucella neotome infection332

Lesions due to brucellosis in marine animals occur only in a few species, and they include meningoencephalitis,333

subcutaneous abscesses, placentitis, abortion, epididymitis, chronic purulent or granulomatous orchitis,334

lymphadenitis, mastitis, spinal discospondylitis, peritonitis, and a mineralized lung granuloma (Foster et al., 1996).335

Others are hepatic abscesses, hepatic and splenic necrosis. There is also the presence of macrophage and or336

histiocytic cell infiltrations in the liver, spleen and lymph nodes. The lesions in dolphins with meningo-encephalitis337

are usually severe, chronic and widespread along with non-suppurative meningitis, which is most severe in the338

brainstem. The meningitis is usually accompanied by periventricular encephalitis (Gonzalez et al., 2002; Hernandez-339

Mora et al., 2008).340

341

EPIDEMIOLOGY OF BRUCELLOSIS342

Distribution of Brucellosis343

Brucella organisms have a worldwide distribution, but brucellosis is more common in countries having poorly344

standardized or ineffective animal and public health programmes (Capasso, 2002). Rust (2006) reported that345

brucellosis is a zoonotic infectious illness to which humans became exposed as a result of domestication of animals346

and the establishment of animal husbandry as an important element following civilisation. The prevalence of347

zoonotic disease globally is usually and also a reflection of indigenous cultures in husbandry systems. The348

epidemiology of brucellosis is, therefore, dynamic as changes in the causative agent, host or environment may affect349

the complex interrelationship that exists between them thereby influencing the epidemiology of the disease. Thus,350

measures have been difficult in the control of this disease because of the involvement of livestock and humans in its351

spread (WHO/MZCP, 1998). The Mediterranean countries of Europe, Northern and Eastern Africa, Near East352

countries, India, Central Asia, Mexico, and Central and South America are especially affected by this disease353

(Donev, 2010). Brucellosis was not suspected in Nigeria until contageous abortion was reported in newly established354

stock farms (Earnshaw and O’Brien, 1928). Since then, the existence of the disease as a zoonosis acquired through355

sheep and goats have been reported by various researchers in Nigeria (Halle and Ajogi, 1997; Kaltungo et al., 2013).356

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The herding of different species of livestock together significantly promotes interspecies transmission of brucellosis357

(Ocholi et al., 1993). It was reported by Esuruoso (1974) that generally, brucellosis is more prevalent in358

government-owned farms than in nomadic herds due to intensive system of management. Similarly, it was reported359

that the prevalence of the disease could result in variations, which may be attributed to some factors like sampling360

technique, diagnostic method used, vaccination status of the animals, climatic conditions, geography, species, sex361

and age (Gul and Khan, 2007). The nature of the brucellosis in Nigeria, where people still consume unpasteurized362

milk and milk products is not clear (Cadmus et al., 2006). Studies in various parts of Nigeria show that the disease is363

widespread, particularly in ranches, livestock breeding centres, and dairy farms, where the prevalence of the364

infection in cattle ranges between 3.7% and 48.8% (Esuruoso and Hill, 1971; Esuruoso and Van Black, 1972;365

Esuruoso, 1974). Infection rates in nomadic herds have been shown to be between 0.4% and 26.0% (Nuru and366

Dennis, 1975; Ocholi et al., 1996). There was also a report of prevalence ranging from 0.4% to 8.6%, based on367

abattoir surveys (Chukwu, 1987). Kaltungo et al. (2013) reported a prevalence of 2.5% in goats in Kaduna North368

Senatorial District of Kaduna State, Nigeria.369

370

Of the nine known Brucella species, Brucella melitensis is the least species-specific and is the major cause of human371

brucellosis (Reguera et al., 2003). It is one of the most important zoonoses worldwide, accounting for an annual372

incidence of more than half a million cases (Pappas et al., 2006, Saleem, 2010). The risk of infection is proportional373

to the degree of contact with Brucella-infected animals, their excreta, or their edible by-products, particularly milk374

or cheese. Pasteurisation of milk and care in the slaughtering of animals for meat and assurance of adequate cooking375

of meat are of great importance in preventing human brucellosis. Brucellosis occurs worldwide, except in those376

countries where it has been eradicated after a long and expensive eradication campaign. Eradication is usually377

defined as the absence of any reported cases for at least five years. These countries include Australia, Canada,378

Cyprus, Denmark, Finland, the Netherlands, New Zealand, Norway, Sweden and the United Kingdom (OIE, 2002).379

The fact that brucellosis is considered a re-emerging problem for countries like Israel, Kuwait, Saudi Arabia, Brazil380

and Colombia is of great concern (Sleem, 2010).381

382

383

384

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Susceptibility to Brucella organisms385

All domesticated animals have been reported to be susceptible to Brucella organisms, except the cat (FAO/WHO,386

1986). Ko and Splitter (2003) reported that the primary host is an important agent in the maintenance of the disease387

as most of the other hosts serve as reservoirs of the infection for each particular species. There is the possibility for388

cross infection among animal species, especially when they are kept in close contact. Adult animals are considerably389

more susceptible to infection by Brucella spp. than younger ones. Such adults may be infected and may not show390

any clinical sign, but generally show only a weak and transient serological response (Corbel, 2006). Furthermore,391

young animals are often resistant, though it should be noted that latent infections can occur and such animals may be392

hazardous when mature. Susceptibility increases during pregnancy, and animals get more susceptible with the393

advancement of pregnancy due to the presence of erythritol in the uterus. Bulls are relatively more resistant than394

sexually mature heifers and they are less resistant than sexually immature heifers (Megid et al., 2010). Conversely,395

in the swine industry, boars are more likely to be sources for introducing Brucella organisms into a herd (Acha and396

Szyfres, 2003).397

398

Corbel and Brinley-Morgan (1984) reported that dairy breeds of sheep appear more susceptible than those kept for399

meat production. It has been reported that, other than natural immunity, management is also a key factor that could400

possibly account for the lower incidence of brucellosis in males than in females. This is because, most dairy cows401

and many beef bulls are maintained separately from the general herd and their exposure to infection is, therefore,402

lessened (Manthei et al., 2010).403

404

Resistance of Brucella organisms to environmental factors and chemicals405

Ability of members of the genus to persist outside the mammalian hosts is relatively high, compared to most other406

non-sporing pathogenic bacteria and can survive for a long time in both hot and cold environments, particularly with407

high moisture content. Brucella organisms can survive in tap water for several months at 4 to 8 0C, they can also408

survive for 2.5 years at 00C, and several years in frozen tissues or medium (FAO, 2005). Brucellae can also survive409

for up to 60 days in damp soil, and for up to 144 days at 20 0C, 40% relative humidity and at pH greater than 4. They410

can survive freezing and thawing and also for several weeks in non-fermented milk (Merchant and Packer, 1975).411

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This accounts for the persistence of infection in tropical Africa where husbandry and management practices are poor412

and tend to encourage the survival of the organism.413

Brucellae can survive for 30 days in urine, 75 days in aborted foetuses and more than 200 days in uterine exudates.414

They are however destroyed at 56 - 610C within 4-5 hours in beddings contaminated with infected faecal material,415

(King, 1957). Brucella species are susceptible to dyes like thionin, basic fuschin methylviolet, pyronin, and safranin-416

O at standard concentration of 20 g/ml, and the susceptibility varies between biovars (European Commission, 2001).417

They grow in a minimal medium containing sodium chloride, sodium thiosulphate, ammonium sulphate, glucose,418

nicotinic acid, thiamine, panthotenic acid and biotin (Plommet, 1991). Their growth can be improved by the addition419

of serum or blood, while susceptibility to dyes varies between species and biovars, the fact which has been used for420

routine typing tests for members of the genus (European Commission, 2001).421

422

Hollet (2006) reported that Brucella species are readily killed by most commonly available disinfectants, including423

hypochlorite solutions, 70% ethanol, isopropanol, iodophores, phenolic disinfectants, formaldehyde, glutaraldehyde424

and xylene. However, organic matter and low temperatures decrease the efficacy of the disinfectants. Sodium425

hypochlorite at 2.5%, 2-3% caustic soda, 20% freshly slaked lime suspension, and 2% formaldehyde solution are426

capable of destroying Brucella on contaminated surfaces following one hour of exposure.427

428

Effects of management practices429

The system of husbandry greatly influences the spread of infection due to Brucella species. Animals on institutional430

farms that abort due to brucellosis have high chances of infecting other animals within the flock than free range431

nomadic type of husbandry animals, which have less chances of remaining or returning to the contaminated432

environment (Bale, 1980). However, a more accepted view is that, the prevalence is higher in pastoral production433

systems, where there is free mixing of large number of animals of different species and lowest for the confined434

farms (Emslie and Nel, 2002; Samartino, 2002; Megersa et al., 2011; Racloz et al., 2013). Lambing or kidding in435

dark and crowded enclosures favours the spread of the organism, while open-air parturition in a dry environment436

results in decreased transmission (AHA, 2005).437

438

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Transmission of brucellosis439

Most infections due to members of the genus Brucella result from ingestion of the organism, from diseased animals,440

contaminated feedstuffs and drinking points. Aborted foetuses, placental membranes or fluids, and other vaginal441

discharges, present after an infected animal has aborted or parturated are very rich sources of the organism. The442

habit of feeding aborted materials to dogs and also burning of such materials by pastoralists favour transmission of443

the disease (Kaltungo, 2013). Infection by aerosol, which makes it a potential biological weapon and contamination444

of abraded skin and mucosal surfaces have been reported (Pappas, 2006).445

Natural breeding can result in infection in swine and dogs and, to a lesser extent, sheep and goats (Corbel, 2006).446

Generally, brucellosis is carried from one herd to another by an infected or exposed animal. However, transplacental447

transmission can be possible occasionally (USDA 2000). The purchase of animals from unscreened sources, sharing448

of male breeding stock and extensive system of management, which permits indiscriminate matting are means by449

which susceptible animals can be exposed to infection.450

The use of pooled colostra for feeding newborn calves may also be responsible for the transmission of the infection451

(Corbel, 2006). It has been established that brucellosis in bulls does not always result in infertility, although semen452

quality may be affected. Bulls that remain fertile and functionally active will shed Brucella organisms in the semen453

during the acute phase of the disease and can therefore serve to spread the disease (FAO, 2005). Shedding, however,454

may cease or become intermittent (McCaughey and Purcell, 1973). In contrast to artificial insemination, bulls used455

in natural service may fail to spread the infection, as the infected semen is not deposited in the uterus (Ray, 1979).456

457

In small ruminants, Brucella infection is usually transmitted by contact with the placenta, foetus, foetal fluids,458

aborted materials and vaginal discharges from infected animals. Small ruminants are capable of shedding the459

organism after either abortion or full-term parturition (OIE, 2009). Furthermore, goats usually shed B. melitensis in460

vaginal discharges for at least 2 to 3 months, though shedding usually ends within three weeks in sheep. It was also461

reported by the OIE (2009) that B. mellitensis can be found in milk and semen and that infected ewes and does may462

shed the organism in milk and semen for prolonged periods, leading to infection in lambs and kids. Furthermore,463

infection in sheep occurs mainly through the nasopharyngeal route and can also be transmitted from dam to kid/lamb464

in uterus or via the colostrum or milk.465

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Transmission of brucellosis in pigs occurs by both venereal and through the oral routes, with B. suis being secreted466

in large numbers for long periods especially in afterbirth as well as in uterine discharges and milk in females or in467

semen from infected boars (Alton, 1990).468

Brucella ovis transmission can occur by direct contact between rams kept in the same premises, when they sniff at469

one another or through ewes that have mated with an infected ram prior to a susceptible one during the same mating470

season. They thus serve as mechanical transmitters (Hughes, 1972; Brown et al. 1973). In ewes, B. ovis can471

uncommonly cause abortion associated with placentitis beginning at 30 days of gestation. Infected ewes may give472

birth to weak lambs and there may be high neonatal mortality rate (Meinershagen et al., 1974). Ewes do not play an473

important role in the transmission of Brucella ovis, since they do not remain permanent carriers of the disease.474

Transmission of brucellosis in dogs usually occurs by breeding, sniffing or ingestion of contaminated placental475

tissues, aborted foetuses or vaginal secretions from infected bitches. Brucella canis may be shed for long periods in476

semen or vaginal secretion post-abortion (Carmichael and Kenny, 1970).477

478

Garner et al. (1997) reported that the means by which Brucella spp are transmitted among marine mammals is479

poorly understood. However, the almost exclusive localisation of these bacteria within the intestinal lumen and/or480

uterus of the lungworm (Parafi laroides, Phocoena) in the pulmonary systems of an infected Pacific harbour seal481

and harbour porpoise suggests the strong possibility that these may play a role in transmission of Brucella species.482

However, Foster et al. (2002) reported that transmission of brucellosis in marine animals may occur through mucosa483

and injured skin, direct contact, or by the oral route due to ingestion of other infected marine mammals. Vertical or484

horizontal transmission to the foetus is a possible means of infection since Brucella organisms have been isolated485

from foetal tissues and in milk of dolphins (Hernandez-Mora et al., 2008). Additionally, it was reported by Rhyan et486

al. (2001) that experimental infection of cattle with marine species of Brucella is possible.487

488

Brucellosis is primarily a disease of animals in which man is an accidental host (AAP, 2003). Transmission of this489

disease in humans could thus be occupational through the mucus membrane or abraded skin. Farmers, shepherds,490

hunters, butchers, laboratory workers, veterinarians, and slaughterhouse workers are at a greater risk of contracting491

the disease (Cutler et al., 2005; CDC, 2007). The non-occupational sources of exposure include ingestion of infected492

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19

meat and contaminated dairy products (Cutler et al., 2005; Pappas et al., 2005; Beheshti, 2010). In addition to the493

food-borne and occupational infection, brucellosis is linked to travel and bioterrorism, Brucella is considered as a494

biological weapon in the category B pathogen (Young 1995; Greenfield et al., 2002). Recently, other routes of495

transmission have been identified to include infection through breast milk (Tikare and Mantur, 2008), sexual496

intercourse (Ruben and Band, 1991) and blood transfusion (Magoffin and Kabler, 1949). The role of flies and ticks497

in the transfer of Brucella organisms from infected to uninfected herd/flock has not been established (AHA, 2005).498

499

Immune response to Brucella infection500

Pathogens have developed adaptative measures for survival and multiplication within their hosts. They include the501

ability to control phagocyte apoptosis, while another is to affect the expression of cytokines, which is necessary for a502

normal protective function of the immune response (Dornand et al., 2002). Antibody response to B. abortus will be503

used as an example because it has been most studied in detail (Nielsen and Yu, 2010). Brucella infection in cattle504

consists of early IgM isotype which usually appears 5-15 days post-exposure, but may sometimes be delayed.505

Appearance of this antibody depends on the route of exposure, infecting dose of the bacteria and the immune status506

of the host animal (Beh, 1973). Production of IgM isotype is followed shortly by production of IgG1 isotype and507

subsequently IgG2 and IgA in little quantities (Corbel, 1972; Beh, 1974). Indicator of exposure, therefore, depends508

on identification of IgM antibody isotype. However, a number of other microorganisms contain antigens with509

similar epitopes to those of Brucella, and the main antibody response to these cross reacting antigens is IgM.510

Therefore, measurement of IgM antibody isotype sometimes results in false positive reactions in serological tests511

leading to low assay specificity (Nielsen and Yu, 2010). Production of IgG2 and IgA isotypes occurs later in512

infection and so measurement of these antibodies would generally lower assay sensitivity. Therefore, the most useful513

antibody measurement for serological tests for brucellosis is IgG1 (Nielsen et al., 1984). In addition to cross514

reactions, vaccinal antibodies sometimes cause diagnostic problems due to false positive reactors.515

Brucella abortus S19 is a widely used vaccine which is antigenically indistinguishable from pathogenic strains of B.516

abortus (Nielsen and Yu, 2010). However, administration of the vaccine to young animals, usually between 3 and 8517

months of age (calfhood vaccination), generally allows the antibody response to wane sufficiently to eliminate some518

diagnostic problems at sexual maturity (Nicoletti, 1990; Adone and Pasquali, 2013). Some mature animals have519

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20

residual antibody, leading to higher antibody levels in vaccinated animals which could also lead to diagnostic520

difficulties.521

522

TREATMENT OF BRUCELLOSIS523

Brucella species are intracellular Gram negative pathogens that infect host macrophages. This fact makes their524

contact with antimicrobial agents difficult. Therefore for any antibiotic to be effective in the treatment of brucellosis,525

it must have the ability to adequately penetrate macrophages of the host animal and act in the acidic intracellular526

environment. (Peppas et al., 2005; Kaya et al., 2012). There is a general need for combined treatment, since all527

monotherapies are characterized by unacceptably high relapse rates. Concurrent treatment with chlortetracycline and528

streptomycin has effected some level of cure in sheep, though it is usually not economically feasible except in529

valuable rams (Cynthia, 2005, Peppas et al., 2005). It has been reported that fertility may remain low, even if the530

organism is eliminated. Treatment of the disease in cattle is generally unsuccessful because of the intracellular531

sequestration of the organisms in lymph nodes, the mammary gland and the reproductive organs. Generally, failure532

in treatment of brucellosis in animals has been attributed to reasons like the use of incorrect dose of antibiotics,533

inadequate duration of treatment, high cost of medication, and failure to cure udder infection which, could lead to a534

relapse (Radwan et al., 1992). Long term treatment regimen, leads to antibiotics residue in milk and meat of treated535

animals which could be passed onto the food chain of humans.536

537

PREVENTION AND CONTROL OF BRUCELLOSIS538

The fact that brucellosis is a disease of major economic and zoonotic importance, a strategy for its control in539

animals, especially livestock, is vital in endemic areas. The primary focus of the control strategy should be the540

reduction of the infection in animal population to such a level that the impact of the disease on human heal th and541

animal production is minimized. The B. abortus S19 and B. melitensis Rev. 1 vaccines are the cornerstones of542

control programme in cattle and small ruminants, respectively (Smith, 2013). In the absence of a human brucellosis543

vaccine, prevention of human brucellosis depends on the control of the disease in animals.544

Prevention and control of brucellosis in animals essentially include test and culling of positive reactors, quarantine,545

zoning and tracing.546

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Test and culling of positive reactors547

Serological testing of livestock should be routinely carried out using approved serological tests. All animals reacting548

positively to the tests should be destroyed or consigned for immediate slaughter at an approved abattoir following549

strict hygienic procedures. Tissues like mammary, medial and internal iliac, retropharyngeal, parotid and550

prescapular lymph nodes and spleen from such animals should be submitted for Brucella culture (AHA, 2005).551

Furthermore, there is a limitation to eradication by test and slaughter as some cases of latently-infected young552

animals remain serologically negative to standard tests until late into their first pregnancy. It has also been reported,553

that, time of quarantine should be long enough to ensure that all breeding animals complete gestation without554

evidence of infection.555

556

Corbel (2006) reported that the prevalence of B. ovis can be decreased by examining and culling rams with palpable557

abnormalities before breeding. However, it is worthy of note that palpable lesions are not always found in all558

infected rams and, therefore, laboratory testing of rams should also be considered.559

560

561

Quarantine and movement controls562

In case of any suspicion of brucellosis, quarantine must be immediately imposed on the affected herd or flock to563

ensure the containment of any infection after which such herds/flocks will require repeated sero-surveillance to564

confirm their status. Movement of latently-infected animals presents the greatest risk, and the potential for565

movement of infected material by dogs or birds should not be ignored. In a brucellosis endemic country, clear566

demarcation of diseased and disease-free zones should be established. Thereafter, tight control on the movement of567

animals between these zones should be enforced. When an infection is suspected or confirmed, trace-back and trace-568

forward of animal movements is essential to identify the index case and other potentially infected or exposed herds569

to forestall future spread of the disease (FAO, 1999).570

571

Surveillance572

Surveillance should be carried out in neighbouring herd/flock to identify any infected herd/flock, not already573

identified by tracing. This will guarantee that the infection has not spread to the immediate neighbourhood.574

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Surveillance for evidence of antibodies to Brucella spp in livestock by Rose Bengal plate test and Milk Ring test and575

other serological testing of high-risk herds is the preferred approach. On-farm activities also include examination of576

production records for evidence of abortions and/or infertility. Surveillance has also been reported to be an effective577

tool in monitoring the progress and effectiveness of the control programme, after the cessation of vaccination578

(Smiths, 2013).579

580

Depopulation of infected animals581

Infected animals at term or having a vaginal discharge pose a disease risk to personnel and in contact animals. They582

should, therefore, preferably be depopulated immediately by burning and/or buried. It has been reported that the583

level of infection is at its peak 4 days to calving or abortion, and 14 days afterwards in cattle (Parkinson, 2009).584

However, depopulation has serious economic impacts such as the availability of compensation from government,585

which is an important incentive to ensure that owners promptly report any evidence of infection.586

587

Decontamination588

Decontamination of equipment and environment can be achieved with the aid of sunlight, high temperatures, wiping589

down contaminated surfaces with a freshly-made (less than 7 days old) 1:10 aqueous dilution of household bleach590

and a range of chemicals (CDC, 2004). Furthermore, other measures to reduce the likelihood of environmental591

survival of infective bacteria include draining wet areas and ploughing of the soil to improve the rate of desiccation592

of the organism.593

594

Vaccination595

Vaccination is an extremely important and effective facet of most control strategies of brucellosis infection, but has596

the disadvantage that its use may confuse diagnosis by stimulating the production of hypersensitivity or antibodies,597

notably IgG1, which is detectable by some serological tests. Thus antibody titres may persist for a prolonged period598

in a small proportion of vaccinated animals and this proportion increases with age at vaccination (Corbel, 1996).599

However, it has been reported that live vaccines have until now proved superior to inactivated products for the600

prevention of animal brucellosis (Nicoletti, 1990). Brucella abortus S19 and B. melitensis Rev.1 vaccines have601

proven effective against B. abortus in cattle and against B. melitensis and B. ovis in sheep and goats, respectively602

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(Elberg, 1996; Nicoletti, 1990). Both vaccines are capable of causing abortion in a proportion of pregnant animals,603

and of being pathogenic for humans in case of accidental injection. Furthermore, Brucella melitensis Rev.1 has also604

been evaluated for the vaccination of cattle in countries, where B. melitensis infection in sheep and goats is605

widespread. Experimental studies have shown that B. melitensis Rev.1 vaccine provided immunity to B. melitensis606

equal to or superior than the immunity induced by B. abortus S19 with a lower vaccine dose in cattle. Despite the607

promising results, the use of B. melitensis Rev.1 in this species of animals has been very limited (Nicoletti, 1990).608

609

Xie Xin (1986) reported that since 1971, a live-attenuated smooth strain of B. suis biovar 1 strain 2 has been used as610

an oral vaccine to control brucellosis in cattle, sheep, goats and pigs in China. The vaccine is safe when611

administered orally, and does not induce persistent antibody titres.612

613

Although the S2 strain of B. abortus also gave a satisfactory protection rate in cattle (Nicoletti, 1990a), its efficacy614

against experimental B. melitensis infection in pregnant ewes or against B. ovis infection in rams was inferior to that615

of B. melitensis Rev.1 vaccine (Blasco, 1990; Verger et al., 1995). It was also reported that, currently, the live-616

attenuated B. melitensis Rev.1 vaccine appears to be the most generally effective vaccine strain available for617

prevention of animal brucellosis. Brucella abortus strain 45/20 vaccine is normally administered as two doses, given618

6 to 12 weeks apart, followed by an annual booster (CDC, 2005). There have been reports that, the new attenuated619

vaccine, Brucella strain RB51, licensed by the United States Department of Agriculture, Animal and Plant Health620

Inspection Service for use in cattle in the USA does not stimulate the production of antibodies detectable in standard621

diagnostic tests. However, it stimulates the production of other antibodies that can be detected with a special assay622

that indicates that the animal has been previously vaccinated. Vaccination against B. ovis is being practiced in some623

parts of the world. Successful vaccines have been difficult to develop for pigs. It seems that pigs are generally not624

vaccinated, except in China. Furthermore, no vaccines have been developed for dogs and there also seem not to be625

any successful vaccine developed for the prevention of fistulous withers or poll evil in horses (Corbel, 2006).626

627

Wild animal control628

Feral animals, including buffalo and deer, may become infected with brucellosis, if they graze in the same area as629

domestic animals. They should, therefore, be controlled by mustering or field destruction (Corbel, 2006).630

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Control of brucellosis in other species631

Control of brucellosis in other species of animals is similar to that for livestock. Housing of dogs in individual cages632

can help in reducing the spread of the organism. Repeated testing and the removal of seropositive or culture-positive633

animals, combined with quarantine and testing of newly-added dogs, have been used to eradicate brucellosis from634

some kennels (Corbel, 2006).635

It was also reported that, specific control methods have not been established for brucellosis in marine mammals, but636

the general principles of infection control in such animals include isolation, disinfection, and practice of good637

hygiene. Prevention of brucellosis in humans, however, still depends on the eradication or control of the disease in638

animal hosts. The exercise of hygienic precautions to limit exposure to infection through occupational activities, and639

the effective heating of dairy products and other potentially contaminated foods like meat should be adequately640

considered (Corbel, 1997).641

642

Re-stocking of depopulated herd/flock643

Restocking of a decontaminated herd/flock should be done after 30 days during the hot season and slightly longer644

during the cold season (AHA, 2005). This measure assures minimal risk of re-infection because Brucella organisms645

are rapidly inactivated or killed by sunlight as a result of desiccation. Corbel (2006) reported that replacement646

animals should come from brucellosis-free areas or accredited herds/flock. Furthermore, animals from other sources647

should be isolated and screened before adding them to herds/flocks.648

649

Public awareness650

Farmers should be enlightened through the media or public campaigns on the importance of inspecting susceptible651

animals regularly and reporting abortions, birth of weak or dead fetuses, or infertility to appropriate authorities. An652

abortion investigation programme that relieves the farmer of the costs of investigation is a useful strategy. Details of653

any imposed movement controls need to be readily available and clearly explained to the farmers. Given the654

important zoonotic implications of brucellosis, people at risk must be advised on appropriate occupational health655

and safety requirements and health authorities alerted to the potential for human infection (Maxwell and Bill, 2008).656

657

658

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ECONOMIC IMPLICATIONS OF BRUCELLOSIS659

In developed counties, the economic implications associated with brucellosis are as a result of slaughter of660

herds/flocks infected with Brucella, while in developing countries, it is due to actual abortion of foetus and resulting661

in decreased milk production, birth of weak offspring that most often do not survive the neonatal days, placental662

retention and subsequent infertility. Furthermore, it is very difficult to estimate the financial loss incurred by human663

brucellosis, but it is definitely substantial. The economic losses encompass both public health costs in terms of664

treatment cost and long term debilitation that renders the individual unproductive. Others are loss of livestock665

production through loss of milk and meat, and restrictions in international livestock trade and by diminished animal666

working power (Gul and Khan, 2007). The disease can have an effect on exports and constrain efforts to introduce667

exotic livestock breeds, which are more susceptible to the disease (Saleem et al., 2010).668

669

PUBLIC HEALTH IMPLICATION OF BRUCELLOSIS670

Infection of livestock with Brucella spp poses a significant health risk for transmission to humans by direct contact671

with infected animals, materials with skin abrasions, inhalation of aerosols or from consumption of unpasteurized672

milk and other dairy and food products (Olsen and Samartino, 2009; Christopher et al., 2010)). The disease in man is673

highly debilitating, though not considered to be fatal, except in complicated cases (Falade, 1974). Most human cases674

are occupational and occur in farmers, veterinarians, slaughter-house workers and butchers (Yagupsky and Baron,675

2005). Although there has been great progress in controlling the disease in many countries, there remain some676

regions where the infection persists in domestic animals and, consequently, transmission to the human population677

frequently occurs. The expansion of animal industries and urbanisation along with lack of hygienic measures in678

animal husbandry and in food handling can partly account for brucellosis remaining as a public health hazard. The679

expansion of international travels, which stimulate the taste for exotic dairy goods such as fresh cheeses which may680

be contaminated with Brucella spp, and the importation of such foods into Brucella-free regions, may contribute to681

the ever-increasing concern over human brucellosis (Corbel, 2006).682

683

684

685

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26

Concluding Remarks686

Brucellosis is an important zoonotic disease affecting a wide range of animals and a neglected disease, with no687

official policy on its eradication in most developing countries. The eradication of brucellosis may be achieved688

through surveillance programmes in humans and animals, which require comprehensive approaches and long-term689

investments. The programmes include: vaccination, serologic testing with isolation and culling of infected animals690

(test and slaughter), public awareness, health education activities, and providing sufficient financial resources for691

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