3. Dr.T.V.RaoMD
3
• 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.
4. Dr.T.V.RaoMD
4
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.
5. Zoonosis
Dr.T.V.RaoMD
5
• 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.
7. Other names for Brucellosis
Dr.T.V.RaoMD
7
Undulant fever
Malta fever
Gibraltar fever
Mediterranean fever.
8. Bacteriology
Dr.T.V.RaoMD
8
Gm - ve cocci, coccobacilli, bacilli.
Strict aerobic, nonmotile,nonspore
forming.
B. ovis, B. abortus --CO2
supplementation.
Grow in regular media -- prolonged
incubation > 4 weeks.
9. Characteristics of Bacteria
Dr.T.V.RaoMD
9
• Brucella spp are small gram-negative
aerobic coccobacilli lacking a capsule,
flagella, endospores, or nativeplasmids.
• Oxidase and catalase tests are positive
for most members of the genus Brucella.
• Some species require CO2 enrichment
for primary isolation in thelaboratory.
10. B. abortus
• Sources of Human Infection:
Raw milk and products /Directcontact
• Portal of entry: oral mucosa, nasopharynx and
conjunctivae, genital then X in regional lymph
node and spread to RES (nodes of udder, uterus,
erythritol...). Placentitis with endometritis. Fetus
die with edema /congestion of lung,dissimenated
hemorrhages of epicardium and splenic capsule.
Bacteria in lung and digestive tract of the fetus.
B. abortus
• Bacteria is excreted in genital secretions
(including semen), milk, colostrum.
• Survival time:
Cheese at 4oC: 180 days!!!
Water at 25oC: 50 days
Meat and salted meat: 65days
Manure at 12oC: 250 days!!!!
• Widespread: Cattle, Bison, Elk, Deer, Moose, Horse,
Sheep, Goat, Swine, Donkey, Dogs, Birds, Hares, Fox,Rats,
mice, Camels and Human.
B. melitensis
• Goat (1886),Sheep,
Cow (1905 in
Malta), Swine,
Hares, Camels,
Buffalo, Impala.
B. suis
• Wild pigs, Rats, Swine.
• Abortion,metritis,
bursitis, spondylitis
(Lumbar and sacral),
arthritis, orchitis,
paralysis.
Brucella canis
• 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
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occasionalcause of brucellosis in humans
12
11. Brucella melitensis*
Dr.T.V.RaoMD 11
• 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.
12. Brucella abortus
Dr.T.V.RaoMD 12
• 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.
13. Brucella suis
Dr.T.V.RaoMD 13
• 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.
14. 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.RaoMD
canis
16
15. Epidemiology
Dr.T.V.RaoMD 15
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.
16. Methods of transmission
Dr.T.V.RaoMD 16
• 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
17. 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 hosDrt.T.V.Rao MD 19
18. 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.RaoMD 20
20. Dr.T.V.RaoMD 20
Chronic Brucellosis
• Patients with undiagnosed and
untreated brucellosis can be
symptomatic for months. In
addition, previously treated
patients may present with
relapsed infection.
21. 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 relapseDr.
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eD
r therapy 29
22. Relapse
Dr.T.V.RaoMD 22
• 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
25. Investigations
Dr.T.V.RaoMD 25
• 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.
26. Serological Tests
Dr.T.V.RaoMD 26
• 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
27. ELISA
Dr.T.V.RaoMD 27
• 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
28. PCR an Emerging Tool
Dr.T.V.RaoMD 28
• 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 beendescribed
29. Imaging
Dr.T.V.RaoMD 29
• Patients with spine symptoms MRI
examination to rule out spinal cord
compromise.
• Plain radiographs, radionuclide bone
scintigraphy, CT scanning, and joint
sonography.
30. Management
Dr.T.V.RaoMD 30
• 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.
32. Treatment
Dr.T.V.RaoMD 32
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