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Brucellosis, also called undulant

fever, undulating fever, or Malta


Brucellosis fever, is a zoonosis (infectious
disease transmitted from animals to
humans) caused by bacteria of the
Pengendalian Vektor genus Brucella. It is primarily a
Penyakit disease of domestic animals (goats,
pigs, cattle, dogs, etc) and humans
and has a worldwide distribution,
mostly now in developing countries.
Center for Food Security and Public Health
Iowa State University - 2004

Overview
Organism
History
Epidemiology Organisme
Transmission
Human Disease
Animal Disease
Prevention and Control

Center for Food Security and Public Health


Iowa State University - 2004

Brucella spp. Species Biovar/


Serovar
Natural Host Human
Pathogen
B. abortus 1-6, 9 cattle yes
Gram negatif, coccobacilli bacteria B.melitensis 1-3 goats, sheep yes

Facultatif, intraselular organisme B. suis 1, 3 swine yes


Persistensi di Lingkungan 2 hares yes
4 reindeer, caribou yes
Temp, pH, kelembaban
5 rodents yes
Material aborsi dan dibekukan B. canis none dogs, other yes
Multiple species canids
B. ovis none sheep no
B. neotomae none Desert wood rat no
B. maris marine mammals ?

Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

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The Many Names of Brucellosis

Penyakit pada Penyakit pada


Manusia Binatang
Malta Fever Bangs Disease
History
Undulant Fever Enzootic Abortion
Mediterranean Fever Epizootic Abortion
Rock Fever of Slinking of Calves
Gibraltar Ram Epididymitis
Gastric Fever Contagious Abortion
Center for Food Security and Public Health
Iowa State University - 2004

History of Malta Fever Sir William Burnett


(1779-1861)
450 BC: Described by Hippocrates
1905: Introduction into the U.S. Physician General to
1914: B. suis Indiana, United States the Navy
1953: B. ovis New Zealand, Australia Differentiated the
various fevers
1966: B. canis in dogs, caribou and affecting soldiers
reindeer

Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical


Center for Food Security and Public Health Diseases Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical


Diseases

Jeffery Allen
Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical
Diseases

Marston Sir David Bruce


(1855-1931)

Contracted Malta British Army


fever physician and
microbiologist who
Described his own
discovered
case in great detail
Micrococcus
melitensis

Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

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Bernhard Bang
History
(1848-1932)
Alice Evans, American bacteriologist
Credited with linking the organisms
Danish physician
and veterinarian Similar morphology and pathology
Discovered between:
Bacterium abortus Bangs Bacterium abortus
could infect cattle,
Bruces Micrococcus melitensis
horses, sheep and
goats Nomenclature today credited to
Sir David Bruce
Brucella abortus and Brucella melitensis
Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical
Diseases Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

Transmission to Humans
Conjunctiva or broken skin
contacting infected tissues
Transmission Blood,
urine, vaginal discharges,
aborted fetuses, placentas
Ingestion
Raw milk & unpasteurized dairy
products
Rarely through undercooked meat

Center for Food Security and Public Health


Iowa State University - 2004

Transmission to Humans Transmission in Animals


Inhalation of infectious aerosols Ingestion of infected tissues
Pens, stables, slaughter houses or body fluids
Inoculation with vaccines Contact with infected tissues
B. abortus strain 19, RB-51
or body fluids
B. melitensis Rev-1
Mucous membranes, injections
Conjunctival splashes, injection

Person-to-person transmission is very rare Venereal


Incubation varies Swine, sheep, goats, dogs
7-21 days to several months

Center for Food Security and Public Health Center for Food Security and Public Health
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Epidemiology

Center for Food Security and Public Health


Iowa State University - 2004

Who is at Risk?
Occupational Disease Consumers of
Cattle ranchers/ dairy farmers unpasteurized
Veterinarians dairy products are
Abattoir workers also at risk
Meat inspectors
Lab workers

Hunters
Travelers

Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

B. melitensis B. abortus
Latin America, Middle East, Worldwide
Mediterranean, eastern Europe,
Asia, and parts of Africa Some countries have
Accounts for most human cases eradicated
Inthe Mediterranean and Middle Notifiable disease in many
East countries
Up to 78 cases/100,000
people/year Poor surveillance and
Arabic Peninsula 20% reporting due to lack of
seroprevalence
recognition
Recent emergence in cattle on
Middle Eastern intensive dairy Fever of Unknown Origin
farms Center for Food Security and Public Health
(FUO) Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

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B. suis B. suis
Biovars 1 and 3 Low Levels
Worldwide problems where swine are United States and Australia
raised
Persistent problem in feral swine
Free
Biovar 1
United Kingdom, Canada
Established in cattle in Brazil and
Eradicated
Columbia
Holland, Denmark
Biovar 2
Low Incidence
Enzootic in wild hares in Europe
Middle East, North Africa
Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

B. canis Brucellosis in U.S.: 1972-2002


350
Poorly understood
300
1-19% prevalence in
United States
250
Reported Cases

200
Rarely causes disease
in humans
150

100

50

0
1972 1977 1982 1987 1992 1997 2002
Year
Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

Brucellosis
United States
Approximately 100 cases per year
Less than 0.5 cases/100,000 people Disease in Humans
Mostly California, Florida, Texas,
Virginia
Many cases associated
with consumption of
foreign cheeses

Center for Food Security and Public Health


Iowa State University - 2004

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Human Disease Human Disease
Can affect any organ or organ 20-60% of cases
system Osteoarticular complications
All patients have a cyclical fever Arthritis, spondylitis, osteomyelitis

Variability in clinical signs Hepatomegaly may occur


Headache, weakness, Gastrointestinal complications
arthralgia, depression, 2-20% of cases
weight loss, fatigue,
Genitourinary involvement
liver dysfunction
Orchitis and epididymitis most common

Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

Human Disease Diagnosis in Humans


Neurological Isolation of organism
Depression, mental fatigue Blood, bone marrow, other tissues
Cardiovascular Serum agglutination test
Endocarditis resulting in death Fourfold or greater rise in titer
Chronic brucellosis is hard to define Samples 2 weeks apart
Length, type and response to treatment
variable Immunofluorescence of organism in
Localized infection clinical specimen
Blood donations of infected should PCR
not be accepted Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

Treatment of Choice Prognosis


Combination therapy has the best May last days, months or years
efficacy Recovery is common
Doxycycline for six weeks in Disability is often pronounced
combination with streptomycin for 2-3
weeks or rifampin for 6 weeks About 5% of treated cases relapse
Failure to complete the treatment regimen
CNS cases treat 6-9 months
Sequestered infection requiring surgical
Same for endocarditis cases plus drainage
surgical replacement of valves
Case-fatality rate: <2% ( untreated)
Endocarditis caused by B. melitensis
Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

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Clinical Signs: Cattle & Bison
Third trimester abortions
with B. abortus
Animals and Retained placenta
Brucellosis Once expelled will have a
leathery appearance
Endometritis
Birth of dead or weak calves
Respiratory distress and lung infections
Low milk yield
Center for Food Security and Public Health
Iowa State University - 2004

Clinical Signs: Sheep & Goats Clinical Signs: Swine


B. melitensis causing late term abortions B. suis
Retained placenta
Prolonged bacteremia
Birth of dead or weak lambs/kids
Abortion, early or late gestation
Goats - articular and periarticular
hygroma localizations Fertility problems
B. ovis causing abortions, fertility Sows temporary
problems Boars, unilateral or bilateral orchitis
Orchitis, epididymitis
Lameness, posterior paralysis,
Abnormal breeding soundness exam
Organisms present in semen
spondylitis, metritis, abscesses
Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

Clinical Signs: Horses Clinical Signs: Dogs


B. abortus most common Susceptible to
Susceptible to B. suis B. melitensis, B. abortus, and B. suis
Fistulous Withers or Poll Evil B. canis causes abortions
Inflammation of the supraspinous bursa Last trimester of pregnancy
Exudative process Prolonged vaginal discharge
Fills with clear viscous liquid Bacteremia
Can eventually rupture Failure to conceive, stillbirths,
prostatitis, epididymitis

Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

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Clinical Signs: Wildlife Diagnosis in Animals
Elk Isolation of organism
Abortions, no retained Blood, semen, other tissues
placenta Serology
Moose Brucellosis card test, ELISA
Weakness, debilitated Brucella milk ring test
Predators not clinical but are vectors Demonstration by fluorescent
Coyotes, crows, vultures, bears
antibody of organism in clinical
specimen
Aid in disease spread by carrying infected
tissues away from abortion site Placenta, fetus
Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

Treatment of Animals Prognosis


Combination antibiotic therapy has Disease may last days, months, or
the best efficacy years
Surgical drainage plus antibiotics Eradication program in the United
Often expensive States often leads to slaughter of
High rate of failure certain species
Cattle, bison, horses, sheep, goats,
Indemnity program from government swine

Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

Yellowstone
Bison in Yellowstone
National Park
Goal = Brucellosis
free by 2010
Can leave the park
to winter feed in
Wyoming
Up to 50% sero-
positive
Congregate at
calving

Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

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Elk in Yellowstone
Exposed to B. abortus via winter
feeding grounds
Prevention and
Isolate themselves at
calving Control
Clean the area
Remain separate from
herd for a few days
Less disease transmission between
herdmates
Center for Food Security and Public Health
Iowa State University - 2004

Prevention and Control Prevention and Control


Education about risk of transmission Immunize in areas of
Farmer, veterinarian, abattoir worker, high prevalence
butcher, consumer, hunter, public Young goats and sheep with Rev-1
Wear proper attire if dealing with Calveswith RB51
infected animals/ tissues No human vaccine
Gloves, masks, goggles Eradicate reservoir
Avoid consumption of raw dairy Identify, segregate, and/or cull
products infected animals

Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

Prevention and Control RB51


B. suis, ovis, and canis Approved for use February 1996 for calves
Veneral transmission Able to differentiate wild type exposure
Separate females at birthing to reduce
from immunization
transmission on the farm or in kennel Lacks LPS-O antigen that causes antibody
response on serologic or milk tests
Infectious to humans
Serologically negative upon testing exposure
CDC registry of human exposures
32 documented exposures as of 1998

Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

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U.S. Eradication Program U.S. Eradication Program
U.S. Department of Agriculture Target date for eradication
1934: Cooperative State-Federal was December 31, 1998
Brucellosis Eradication Program Surveillance
Removal of diseased cattle due to drought Brucellosis ring test
1951: APHIS became involved Pooled milk

1957: 124,000 positive herds Market Cattle Identification


Blood test, individual
Approach
Indemnity for whole herd depopulation
Test,slaughter, trace back, $250 nonregistered cattle/bison
investigate, and vaccinate
$750 or 95% of value minus salvage value for
registered cattle
Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

U.S. Eradication Program


Fiscal Year 2001
4.7 million calves vaccinated
9.9 million cattle tested under the
Market Cattle Identification program
3 brucellosis herds depopulated
Indemnity paid = $211,153
An additional $47,700 for purchase of
animals or diagnostic purposes

http://www.aphis.usda.gov/vs/nahps/brucellosis/status_rpt/figure11.jpg

Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

Brucellosis Classes
Free
A
No more than 0.25% infection rate and cattle
must be tested before export
B
Infection rate of no more than 1.5% and must
be tested before interstate movement
C
Infection rate >1.5% and herds must be
http://www.aphis.usda.gov/vs/nahps/brucellosis/status_rpt/figure05.jpg
tested twice before and once after export.
Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

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Brucellosis Today

USDA/APHIS
USDA/APHIS Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

USDA/APHIS USDA/APHIS
Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

Brucellosis
B. abortus Exposure
as a Biological Weapon
1997: Kansas State University Aerosolized B. melitensis
City of 100,000 people
14 month old heifer admitted to hospital
Inhale 1,000 cells (2% decay per min)
with calving complications
Case-fatality rate of 0.5%
Vaccinated with RB51 at 8 months 50% hospitalized for 7 days
10 times the dose for known pregnant cattle Outpatients required 14 visits
5% relapsed
9 humans exposed

Results
Treated with doxycycline
82,500 cases requiring extended therapy
No clinical signs
413 deaths
$477.7 million in economic impact

Center for Food Security and Public Health Center for Food Security and Public Health
Iowa State University - 2004 Iowa State University - 2004

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Internet Resources
USDA APHIS VS Status Report
www.aphis.usda.gov/vs/nahps/brucellosis/bruc_erad.
html
USDA APHIS Cattle and Bison
www.aphis.usda.gov:80/vs/nahps/Brucellosis/cattle.h
tm
WHO Fact Sheet Brucellosis
www.who.int/inf-fs/en/fact173.html
Brunet Publication
progress.box.co.il/brunet/public_sub2_pl.html

Center for Food Security and Public Health


Iowa State University - 2004

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