general overview of the pathogen, species and host relationship, pathogenesis, clinical symptoms, diagnosis, laboratory diagnosis or screening methods, epidemiology of the diseases, prevention and control, treatment

1. BRUCELLA
 By abdi kidane
@university of addis ababa
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2. Introduction
 Brucellae are intracellular bacteria that cause brucellosis, a chronic
disease of domestic and wild animals and humans. The ability of these
bacteria to invade, survive for long periods of time and multiply within
host cells is critical for disease causation.
 Brucellosis is a worldwide zoonosis caused by infection with the
bacterial genus Brucella.
 It causes more than 500,000 infections per year worldwide.
 The heaviest disease burden lies in countries of the Mediterranean
basin and Arabian Peninsula.
 The annual number of reported cases in United States (now
approximately 100 cases) has dropped significantly because of
aggressive animal vaccination programs and milk pasteurization.
 The facultative intracellular parasitism characteristic of Brucella spp.
evolved through evolutionary selection to avoid the host immune
system. Target cells and tissues include trophoblasts, fetal lung,
macrophages, and the male and female reproductive organs.
Subsequently, fetal viscera and placenta become heavily infected, and
placentitis and abortions occur, with devastating economic effects on
livestock production.
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3. 1. General overview of pathogen
 Brucella is a genus of Gram-negative bacteria, named
after David Bruce (1855–1931). They are small (0.5 to 0.7 by
0.6 to 1.5 µm), non encapsulated, non motile, facultative
intracellular coccobacilli.
 They survive extremes in temperature, pH, and humidity, and in
frozen and aborted materials. They infect many species, but
with some specificity.
 The different species of Brucella are genetically very similar,
although each has slightly different host specificity.
 The many names of brucellosis include (human disease/animal
disease):
○ Malta fever/Bang's disease
○ Undulant fever/enzootic abortion
○ Mediterranean fever/epizootic abortion
○ Rock fever of Gibraltar/slinking of calves
○ Gastric fever/ram epididymitis
○ Contagious abortion/spontaneous abortion
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4. Species and host relationship
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Species Host
B. melitensis goats and sheep
B. abortus cattle
B. canis dogs
B. suis pigs
B. ovis sheep
B. neotomae desert woodrat (Neotoma lepida)
B. pinnipedialis seal
B. ceti dolphin, porpoise, whale
B. microti common vole (Microtus arvalis)
B. inopinata Unknown
B. papionis baboon
B. vulpis red fox (Vulpes vulpes)

5. The traditional classification of Brucella
species is based largely on the preferred
hosts.
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Geographic
Distribution
Animal ReservoirOrganism
Mediterranean, Asia,
Latin America, parts of
Africa and some
southern European
countries
Goats, sheep, camelsB melitensis
Worldwide
Cows, buffalo, camels,
yaks
B abortus
South America,
Southeast Asia, United
States
Pigs (biotype 1-3)B suis
CosmopolitanCaninesBrucella canis

6. Pathogenesis of disease
 Following exposure, Brucella penetrates infected mucosal
surfaces. The epithelium covering the ileum, Peyer’s patches
are the preferential site for entry. Peyer's patches (or aggregated
lymphoid nodules) are organized lymphoid nodules, named
after the 17th-century Swiss anatomist Johann Conrad Peyer.
They are aggregations of lymphoid tissue that are usually found
in the lowest portion of the small intestine, the ileum and they
differentiate the ileum from the duodenum and jejunum. The
duodenum can be identified by Brunner's glands. The jejunum
has neither Brunner's glands nor Peyer's Patches.
 Following entry, Brucella organisms either in free in
intracellular environment or in phagocytic cells localize in the
regional lymph nodes. There they proliferate and infect other
cells or are killed and infection is terminated. Some cattle
appear to be innately resistant to infection and this is related to
the macrophage’s ability to contain the organisms.
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7. Cont,,,
 From the regional lymph nodes, Brucella disseminates hematogenously
and localize in the reticuloendothelial system and the reproductive tract.
 There is preferential localization to the pregnant uterus. Unknown factors
in gravid uterus, collectively referred to as allantoic fluid factors, stimulate
the growth of Brucella. Erythritol, a four carbon alcohol, is considered as
one of these factors. Infection of the uterus results in abortion.
 The exact mechanism of abortion is unclear. However, likely possibilities
are that abortion results from:
 Interference with fetal circulation due to the existing placentitis.
 The effect of Endotoxin and /or
 Fetal stress resulting from inflammatory response in fetal tissue
 Immunity in brucellosis is mainly cell mediated.
 Activated macrophages can kill the bacteria.
 Tissue reaction to brucella consists of granuloma formation.
 The brucellae spread from the initial site of infection through
lymphatic channel to the local lymph glands.
 Then they disseminate throughout the body through blood stream.
 They have a predilection for the placenta.
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8. Clinical symptoms
 Subclinical brucellosis
 Acute or subacute brucellosis
 Chronic brucellosis
 Localized brucellosis.
 Relapsing brucellosis
 Fever is the most common symptom which is associated with chills.
 Constitutional symptoms of brucellosis including anorexia, asthenia, fatigue,
weakness, and malaise (>90% of cases).
 Bone and joint symptoms include arthralgias, low back pain, spine and joint pain,
and, rarely, joint swelling.
 Neuropsychiatric symptoms of brucellosis are common including Headache,
depression, and fatigue.
 Gastrointestinal symptoms include abdominal pain, constipation, diarrhea, and
vomiting.
 Neurologic symptoms of brucellosis can include weakness, dizziness, unsteadiness
of gait and urinary retention.
 Cough and dyspnea develop in up to 19% of persons with brucellosis; however,
these symptoms are rarely associated with active pulmonary involvement.
 Fever which is associated with relative bradycardia.
 Hepatosplenomegaly (or isolated hepatomegaly or splenomegaly).
 Osteoarticular findings can include tenderness and swelling over affected joints,
bursitis, decreased range of motion, and joint effusion (rare).
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9. Cont,,,,
 Neurologic findings vary according to the presentation of neurologic
disease, as follows:
 Acute meningoencephalitis (most common neurological
manifestation) - Depressed level of consciousness, meningeal
irritation, cranial nerve involvement, coma, seizure, and
respiratory depression
 Peripheral polyradiculoneuropathy - Hypotonia and are flexia in
most cases, paraparesis, and an absence of sensory involvement
 Diffuse CNS involvement - Spasticity, hyperreflexia, clonus, extensor
plantar response, sensorineural hearing loss, cranial nerve
involvement, and cerebellar signs.
 Cutaneous manifestations including erythema nodosum,
papulonodular eruption, impetigo or vasculitic lesions.
 Ocular findings can include uveitis, keratoconjunctivitis, optic
neuritis or cataract.
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10. Diagnosis
 Brucella is isolated from a blood culture on Castaneda medium or
from bone marrow. Prolonged incubation (up to six weeks) may be
required, as they are slow-growing, but on modern automated
machines, the cultures often show positive results within 7 days.
On Gram stain, they appear as dense clumps of Gram-negative
coccobacilli and are exceedingly difficult to see.
Bacteriological
 Milk samples, vaginal swabs and aborted fetus are useful for
recovering the organisms antemortem .
 Samples collected at necropsy include multiple lymph nodes,
spleen, udder, pieces of uterus and testicular tissue.
 Staining with Gram-negative stain , biochemical tests .
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11. Cont,,..
 Polymerase chain reaction (PCR) shows promise for rapid diagnosis of Brucella species in
human blood specimens. Positive PCR at the completion of treatment is not predictive of
subsequent relapse.
 PCR testing for fluid and tissue samples other than blood has also been described. A history of
animal contact is pivotal; in endemic area, it should be in the diagnosis of any nonspecific
febrile illness.
 Some of this diagnosis including.
○ Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy
○ Cryptococcosis
○ Hepatitis, Viral
○ Histoplasmosis
○ Infectious Mononucleosis
○ Infective Endocarditis
○ Leptospirosis
○ Tuberculosis
○ Influenza
○ Tuberculosis of the Genitourinary System
○ Malaria
○ Typhoid Fever
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12. Laboratory Diagnosis or screening methods
 CBC shows leukopenia, relative lymphocytosis or pancytopenia.
 LFT shows slight elevation
 Blood culture has sensitivity of 60% and subcultures are still
advised for at least 4 weeks.
 Bone marrow culture has sensitivity of 80-90%.
 Serology
1. Serum tube agglutination test.
2. Tray agglutination test
 Titers of more than 1:160 in conjunction with compatible
clinical presentation is considered highly suggestive of
infection. Titers of more than 1:320 are considered to be
more specific, especially in endemic areas.
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13. Cont…
 ELISA
○ It measures IgM,IgG and IgA allowing for better interpretation.
 PCR
○ It is used for rapid and accurate diagnosis of brucellosis.
 Histological findings:
○ It includes mixed inflammatory infiltrates with lymphocytic
predominance and granulomas (in up to 55% of cases) with
necrosis.
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14. Cont….
 milk ring test-
 A sample of whole milk is mixed well with a drop of the stained
brucella antigen.
 Brucella antigen ( a concentrated suspension of killed Br.
abortus stained with hematoxylin)
 The mixture of whole milk and stained brucella antigen are
incubated in a water bath at 70oC for 40-50 minutes.
 If antibodies are present in the milk, the bacilli are agglutinated
and rise with the cream to form a blue ring at the top, leaving
the milk unstained.
 If antibodies are absent, no colored ring is formed and the milk
remains uniformly blue.
 The whey agglutination test is another useful method for
detecting the antibodies in milk.
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15. Epidemiology of the disease
 Worldwide, brucellosis remains a major source of disease in
humans and domesticated animals. Although reported
incidence and prevalence of the disease vary widely from
country to country, bovine brucellosis caused mainly by B.
abortus is still the most widespread form.
 The disease has a limited geographic distribution, but
remains a major problem in the Mediterranean region,
western Asia, and parts of Africa and Latin America. Recent
reemergence in Malta and Oman indicates the difficulty of
eradicating this infection.
 B. ovis has not been demonstrated to cause overt disease in
humans, although it is widespread in sheep.
 B. canis can cause disease in humans, although this is rare
even in countries where the infection is common in dogs.
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16. Prevention and control
 Test and isolation/slaughter- to eliminate animals infected with Brucella
 The isolation of test-positive animals is essential, especially during and after parturition.
Hygiene (sanitation)-to reduce/prevent disease transmission
 Proper disposal (burial or burning) of placentas and non-viable fetuses.
 Disinfection of contaminated areas should be performed thoroughly
Control of animal movement
Vaccination-to reduce herd susceptibility
 There is general agreement that the most successful and economical means of control of
brucellosis in animals is through vaccination.
 It is often recommended that vaccination with strains 19 and Rev.1 should be limited to sexually
immature female animals.
 Avoid consumption of raw dairy products.
 Immunize in areas of high prevalence.
 Calves with live attenuated B. abortus strain 19
 Young goats and sheep with B. melitensis Rev-1
 No human vaccine
 Eradicate reservoir
 Identify, segregate, and/or cull infected animals
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17. Treatment
 No practical treatment is available for brucellosis.
 Usually not economically feasible.
 Fertility may remain low even if the organism is
eliminated.
 Oxytetracycline in valuable rams
 Treat with – – Rifampicin & – Doxycycline for 6 wks
 Tetracycline for 6 wks with – Streptomycin for initial
2-3 wks
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