Brucellosis

Dr.T.V.Rao MD

Dr.T.V.Rao MD 1
Brucellosis an Important
Zoonotic Disease

Dr.T.V.Rao MD 2
 Brucellosis,
• Brucellosis, also called Bang's disease,
Crimean fever, Gibraltar fever, Malta
fever, Maltese fever, Mediterranean
fever, rock fever, or undulant fever, is a
highly contagious zoonosis caused by
ingestion of unsterilized milk or meat
from infected animals or close contact
with their secretions.
Dr.T.V.Rao MD 3
 Brucellosis
Brucellosis is a zoonotic infection
transmitted to humans contact
with fluids from infected animals
(sheep, cattle, goats, pigs, or
other animals) derived food
products such as unpasteurized
milk and cheese . The disease is
rarely, if ever, transmitted
between humans.Dr.T.V.Rao MD 4
 Zoonosis
• Brucellosis: Disease of domestic
and wild animals (zoonosis):
Transmittable to humans. It has
different non-specific symptoms and
signs “
• 1886, Bruce isolated Brucella
Melitensis from spleens of malta
fever victims.
Dr.T.V.Rao MD 5
 Brucellosis in humans
• Brucellosis in humans is usually
associated with the consumption of
unpasteurized milk and soft cheeses
made from the milk of infected animals,
primarily goats, infected with Brucella
melitensis and with occupational
exposure of laboratory workers,
veterinarians, and slaughterhouse
workers. Dr.T.V.Rao MD 6
Major Transmission of Brucellosis

Dr.T.V.Rao MD 7
 Other names for Brucellosis

Undulant fever
Malta fever
Gibraltar fever
Mediterranean fever.
Dr.T.V.Rao MD 8
 Bacteriology
Gm - ve cocci, coccobacilli, bacilli.
Strict aerobic, nonmotile, nonspore
forming.
B. ovis, B. abortus --CO2
supplementation.
Grow in regular media -- prolonged
incubation > 4 weeks.
Dr.T.V.Rao MD 9
 Characteristics of Bacteria
• Brucella spp are small gram-negative
aerobic coccobacilli lacking a capsule,
flagella, endospores, or native plasmids.
• Oxidase and catalase tests are positive
for most members of the genus Brucella.
• Some species require CO2 enrichment
for primary isolation in the laboratory.

Dr.T.V.Rao MD 10
 Identification of Bacteria
• Other methods for the identification
and speciation of Brucella include:
production of urease and H2S
sensitivity to dyes, basic fuchsin,
thionin, and thionin blue
use of specific antisera

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 B. abortus
B. abortus
• Bacteria is excreted in genital secretions
(including semen), milk, colostrum.
• Sources of Human Infection:
• Survival time:
Raw milk and products /Direct contact
Cheese at 4oC: 180 days !!!
Water at 25oC: 50 days • Portal of entry: oral mucosa, nasopharynx and
conjunctivae, genital then X in regional lymph
Meat and salted meat: 65 days node and spread to RES (nodes of udder, uterus,
Manure at 12oC: 250 days !!!! erythritol...). Placentitis with endometritis. Fetus
die with edema /congestion of lung, dissimenated
• Widespread: Cattle, Bison, Elk, Deer, Moose, Horse,
hemorrhages of epicardium and splenic capsule.
Sheep, Goat, Swine, Donkey, Dogs, Birds, Hares, Fox, Rats,
Bacteria in lung and digestive tract of the fetus.
mice, Camels and Human.

B. suis
• Wild pigs, Rats, Swine.
B. melitensis • Abortion,metritis,
bursitis, spondylitis
(Lumbar and sacral),
• Goat (1886), Sheep, arthritis, orchitis,
Cow (1905 in paralysis.
Malta), Swine, Brucella canis
Hares, Camels,
Buffalo, Impala. • Brucella canis was first described as a cause of
abortion in beagles in the USA
• It was subsequently shown to infect dogs in many
other countries, irrespective of breed
Dr.T.V.Rao MD 12
• An occasional cause of brucellosis in humans
 Brucella melitensis*

• Principal hosts - goats and sheep

• Most pathogenic in humans
• Sporadic cases in humans in the U.S.
occur related to consumption of
unpasteurized dairy products from
countries where the disease is present.

Dr.T.V.Rao MD 13
 Brucella abortus

• Principal host - cattle

• Eradication of B.
abortus from cattle is
nearly complete in the
U.S., but the disease
still occurs in some wild
bison and elk herds in
the western U.S.

Dr.T.V.Rao MD 14
 Brucella suis
• Principal host - swine
• Since B. suis is
normally found in
pigs, wild hog (feral
swine) hunters are at
risk of becoming
infected when they
field dress infected
pigs.
Dr.T.V.Rao MD 15
 Brucella canis
• Principal host - dog
• Individuals who are in
close contact with
dogs, or
breeders/veterinary
staff who assist with
birthing are at risk of
becoming infected.
• CDC does not currently
perform serological
testing for Brucella Dr.T.V.Rao MD 16
canis
 Epidemiology
Brucellosis occurs worldwide; major endemic areas
include countries of the Mediterranean basin, Arabian
Gulf, the Indian subcontinent, and parts of
Mexico, Central and South America
Human Infection. melitensis is the species that infects
humans most frequently.
The incubation period ranges from a few days to a few
months.
The disease is manifested as fever accompanied by a wide
array of other symptoms.

Dr.T.V.Rao MD 17
 Methods of transmission
• Direct inoculation through cuts and skin abrasions
from handling animal carcasses, placentas, or contact
with animal vaginal secretions
• Direct Conjunctival inoculation
• Inhalation of infectious aerosols
• Ingestion of contaminated food such as raw
milk, cheese made from unpasteurized (raw) milk, or
raw meat
• Venereal transmission has been suggested, but the
data are not conclusive

Dr.T.V.Rao MD 18
 Incubation period
• Acute or sub acute disease follows an incubation
period which can vary from 1 week to 6 or more
months.
• In most patients for whom the time of exposure
can be identified, the incubation period is between
2 and 6 weeks
• The length of the incubation period may be
influenced by many factors
– virulence of the infecting strain
– size of the inoculum
– route of infection
– resistance of the host
Dr.T.V.Rao MD 19
 Portals of entry
• Oral entry - most common route
– Ingestion of contaminated animal products
(often raw milk or its derivatives)
– contact with contaminated fingers
• Aerosols
– Inhalation of bacteria
– Contamination of the conjunctivae
• Percutaneous infection through skin
abrasions or by accidental inoculation
Dr.T.V.Rao MD 20
 Clinical Manifestation
• Fever
• Night sweats
• Malaise
• Anorexia
• Arthralgia
• Fatigue
• Weight loss
• Depression. Dr.T.V.Rao MD 21
 Clinical Manifestations
• The presentation of brucellosis is characteristically variable
• The onset may be insidious or abrupt
• Influenza-like with fever reaching 38 to 40oC
– Limb and back pains are unusually severe, night
sweating and fatigue are marked.
– Anorexia, weakness, severe fatigue and loss of
weight, depression
– Headache
• The leukocyte count tends to be normal or reduced, with a
relative lymphocytosis
– Relative leukopenia
• On physical examination, splenomegaly may be the only
finding.
Dr.T.V.Rao MD 22
 Clinical features
Often fits one of the three pattern:
febrile illness resembling typhoid, less
severe
fever & acute monoarthritis
(hip/knee),young child
long lasting fever,LBA,hip pain,older man
• Travel to an endemic area
• Occupation
• Consumption of unpasteurized milk
Dr.T.V.Rao MD 23
 Physical Examination
Physical manifestations may be absent.
• If present,
Focal Features:
Musculoskeletal pain
Osteomyelitis
Septic Arthritis
Minimal lymphadenopathy
Hepatosplenomegaly occasionally.

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 Systemic Infections with Brucellosis
• Osteoarticular disease, especially sacroileitis — 20 to
30 percent and vertebral spondylitis. Large joints are
affected most commonly in children
• Genitourinary disease, especially epididymo-orchitis
— 2 to 40 percent of males
• Neurobrucellosis, usually presenting as meningitis —
1 to 2 percent.
• Less common neurologic complications include
papilledema, optic
neuropathy, radiculopathy, stroke, and intracerebral
hemorrhage
Dr.T.V.Rao MD 25
 Complications and Brucella
 Endocarditis — 1 percent.Most cases of
endocarditis are left-sided, and about two-
thirds occur on previously damaged valves.
 Hepatic abscess — 1 percent
 Other less common complications include
pneumonitis, pleural effusion, empyema,, or
abscess involving the spleen, thyroid, or
epidural space, uveitis.
 A few cases of Brucella infection involving
prosthetic devices such as pacemaker wires
and prosthetic joints have been reported
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 Differential Diagnosis
•Tuberculosis
•Toxoplasmosis
•CMV
•HIV infection
Dr.T.V.Rao MD 27
 Chronic Brucellosis
• Patients with undiagnosed and
untreated brucellosis can be
symptomatic for months. In
addition, previously treated
patients may present with
relapsed infection.
Dr.T.V.Rao MD 28
 Chronic Brucellosis
• The presence of granulomatous
hepatitis, hepatic micro
abscesses, bone marrow
granulomas, and/or
hemophagocytosis should prompt
further diagnostic evaluation for
brucellosis.
• Relapse — About 10 percent of
patients relapse after therapy
Dr.T.V.Rao MD 29
 Relapse
• About 10 percent of patients relapse after
therapy.
• Most relapses occur within three months
following therapy and almost all occur within
six months.
• Risk factors for relapse include inadequate
initial therapy, duration of the initial illness of
less than 10 days, male sex, bacteremia, and
thrombocytopenia
Dr.T.V.Rao MD 30
Laboratory Diagnosis

Dr.T.V.Rao MD 31
Dr.T.V.Rao MD 32
 Investigations
• Total counts-Normal/reduced
• Thrombocytopenia
• ESR/CRP-Normal/Increased
• CSF/Body fluid analysis-Lymphocytosis,
low glucose levels, elevated ADA
• Biopsied samples of lymph node, liver-
non caveating granuloma without acid
fast bacilli.
Dr.T.V.Rao MD 33
 Serological Tests
• Most serological studies for diagnosis of
Brucellosis are based on antibody detection
These include:
• Serum agglutination (standard tube
agglutination)
• ELISA Rose Bengal agglutination
• Complement fixation
• Indirect Coombs
• Immunecapture-agglutination (Brucellacapt
Dr.T.V.Rao MD 34
• Serology
– Main laboratory method of diagnosis
– Serum agglutination test - most widely used
• measures agglutination for IgG, IgM, IgA
• 2ME - break sulf-hydrile bonds in IgM polymer -
no agglutination
• which level is diagnostic ??
1 : 160 - non endemic area
1 : 320 - endemic area
• SAT - false negative
– Prozone
– Blocking antibodies
– Other tests: coombs, ELISA,
Dr.T.V.Rao MD CFT, FTA 35
 Serum agglutination
• It is generally agreed that a titer of
>1:160 in the presence of a compatible
illness supports the diagnosis of
brucellosis.
• Demonstration of a fourfold or greater
increase or decrease in agglutinating
antibodies over 4 to 12 weeks provides
even stronger evidence for the diagnosis.
Dr.T.V.Rao MD 36
 ELISA
• ELISA is probably the second most common
serologic method.
• The sensitivity of the ELISA was 100 percent
when compared with blood culture but only
44 percent compared with serologic tests
other than ELISA
• The Specificity was >99 percent.
• In a study including 75 patients with
brucellosis, five patients with positive ELISA
had a negative tube agglutination test
Dr.T.V.Rao MD 37
 PCR an Emerging Tool
• Polymerase chain reaction (PCR) shows
promise for rapid diagnosis of Brucella
spp 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
Dr.T.V.Rao MD 38
 Imaging
• Patients with spine symptoms MRI
examination to rule out spinal cord
compromise.
• Plain radiographs, radionuclide bone
scintigraphy, CT scanning, and joint
sonography.

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 Radiology of Spine
can differentiate Tuberculosis from Brucellosis

Dr.T.V.Rao MD 40
 Management
• The World Health Organization recommends
the following for adults and children older than
8 years:
– Doxycycline 100 mg PO bid and rifampin 600-900
mg/d PO: Both drugs are to be given for 6 weeks
(more convenient but probably increases the risk of
relapse).
– Doxycycline 100 mg PO bid for 6 weeks and
streptomycin 1 g/d IM daily for 2-3 weeks: This
regimen is believed to be more effective, mainly in
preventing relapse.
Dr.T.V.Rao MD 41
 Treatment
Drugs against Brucella
• Tetracycline's
• Aminoglycosides
– Streptomycin since 1947
– Gentamicin
– Netilmicin
• Rifampicin
• Quinolones - ciprofloxacin
• ?3rd generation cephalosporins

Dr.T.V.Rao MD 42
 Treatment
Antibiotic Therapy
There are two major regimens:
Regimen A: Doxycycline 100 mg orally
twice daily for 6 weeks +
Streptomycin 1 gram intramuscularly
once daily for the first 14 to 21 days

Dr.T.V.Rao MD 43
 Treatment
• Regimen B:
Doxycycline 100 mg orally
twice daily plus
rifampin 600 to 900 mg (15
mg/kg) orally once daily for
six weeks. Dr.T.V.Rao MD 44
 Focal Disease
• Patients with focal disease have a
less favorable prognosis. In a study
of 530 patients (including 170
patients with focal disease); those
with focal disease had a greater
likelihood of therapeutic failure,
relapse, or death.

Dr.T.V.Rao MD 45
 Indications for Surgery
• Endocarditis where valve replacement or valve
debridement is required
• Drainage or excision of abscesses, especially
those that have not responded to
antimicrobials
• Spinal epidural abscess
• Removal of infected foreign bodies, eg,
pacemaker wires, prosthetic joints

Dr.T.V.Rao MD 46
 Need for Surgery
• Resection of mycotic aneurysms
• Procurement of tissue for diagnostic
purposes
• Chronic hepatosplenic suppurative
brucellosis may require surgery in
addition to antibiotics to achieve
cure
Dr.T.V.Rao MD 47
 Osteoarticular Disease
• Patients with Brucella spondylitis
appear to respond better to
doxycycline-streptomycin or a three-
drug regimen (doxycycline-
streptomycin-rifampin) than to
doxycycline-rifampin.

Dr.T.V.Rao MD 48
 Neurobrucellosis
• Doxycycline,
• Rifampin
• Trimethoprim-Sulphmethoxazole .
• The duration of therapy is generally prolonged
individualized according to clinical signs and
symptoms
• Continued until cerebrospinal fluid
parameters have returned to normal
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 Endocarditis
• Antimicrobial therapy alone may be
attempted absence of heart failure,
valvular destruction, abscess, or a
prosthetic valve.
• A combination of three or four
antimicrobials, eg, a tetracycline,
rifampin, and an aminoglycoside plus or
minus trimethoprim-Sulphmethoxazole.
Dr.T.V.Rao MD 50
 Needs longer duration of Treatment

• Therapy is usually given for six

weeks to six months.
• The aminoglycoside component is
usually administered for two to
four weeks in an effort to avoid
toxicity
Dr.T.V.Rao MD 51
 Relapse
• Relapse should prompt assessment for a
focal lesion, especially hepatosplenic
abscess
• Most relapses can be treated successfully
with a repeat course of a standard
regimen.
• Should resistance or a second or third
relapse occur, an alternative regimen
should be devised.
Dr.T.V.Rao MD 52
 Pregnancy and Brucellosis
• Premature labor and fetal wastage
• Rifampin — 900 mg once daily for six
weeks
• Rifampin — 900 mg once daily plus
trimethoprim-Sulphmethoxazole(TMP-
SMX; 5 mg/kg of the
trimethoprim component twice daily) for
four weeks
Dr.T.V.Rao MD 53
 Prevention
–Control of disease in domestic
animals
• immunization using B. abortus strain 19
and B. melitensis strain Rev 1
–Routine pasteurization of milk
–In labs strict biosafety precautions
Dr.T.V.Rao MD 54
• Programme Created by Dr.T.V.Rao MD
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Dr.T.V.Rao MD 55