Brucellosis

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www.indiandentalacademy.com INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com

Overview:

www.indiandentalacademy.com Overview Organism History Epidemiology Transmission Disease in Humans Disease in Animals Prevention and Control

The Organism:

The Organism

Brucella spp.:

www.indiandentalacademy.com Brucella spp. Gram negative, coccobacilli bacteria Facultative, intracellular organism Environmental persistence Temp, pH, humidity Frozen and aborted materials Multiple species

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www.indiandentalacademy.com Species Biovar/Serovar Natural Host Human Pathogen B. abortus 1-6, 9 cattle yes B.melitensis 1-3 goats, sheep yes B. suis 1, 3 swine yes 2 hares yes 4 reindeer, caribou yes 5 rodents yes B. canis none dogs, other canids yes B. ovis none sheep no B. neotomae none Desert wood rat no B. maris marine mammals ?

The Many Names of Brucellosis:

www.indiandentalacademy.com The Many Names of Brucellosis Human Disease Malta Fever Undulant Fever Mediterranean Fever Rock Fever of Gibraltar Gastric Fever Animal Disease Bang’s Disease Enzootic Abortion Epizootic Abortion Slinking of Calves Ram Epididymitis Contagious Abortion

History:

History

History of Malta Fever:

www.indiandentalacademy.com History of Malta Fever 450 BC: Described by Hippocrates 1905: Introduction into the U.S. 1914: B. suis Indiana, United States 1953: B. ovis New Zealand, Australia 1966: B. canis in dogs, caribou and reindeer

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www.indiandentalacademy.com Sir William Burnett (1779-1861) Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical Diseases Physician General to the Navy Differentiated the various fevers affecting soldiers

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www.indiandentalacademy.com Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical Diseases Contracted Malta fever Described his own case in great detail Jeffery Allen Marston

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www.indiandentalacademy.com Sir David Bruce (1855-1931) British Army physician and microbiologist who discovered Micrococcus melitensis Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical Diseases

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www.indiandentalacademy.com Bernhard Bang (1848-1932) Danish physician and veterinarian Discovered Bacterium abortus could infect cattle, horses, sheep and goats Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical Diseases

History:

www.indiandentalacademy.com History Alice Evans, American bacteriologist Credited with linking the organisms Similar morphology and pathology between: Bang’s Bacterium abortus Bruce’s Micrococcus melitensis Nomenclature today credited to Sir David Bruce Brucella abortus and Brucella melitensis

Transmission:

Transmission

Transmission to Humans:

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

Transmission to Humans:

www.indiandentalacademy.com Transmission to Humans Inhalation of infectious aerosols Pens, stables, slaughter houses Inoculation with vaccines B. abortus strain 19, RB-51 B. melitensis Rev-1 Conjunctival splashes, injection Person-to-person transmission is very rare Incubation varies 7-21 days to several months

Transmission in Animals:

www.indiandentalacademy.com Transmission in Animals Ingestion of infected tissues or body fluids Contact with infected tissues or body fluids Mucous membranes, injections Venereal Swine, sheep, goats, dogs

Epidemiology:

Epidemiology

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Who is at Risk?:

www.indiandentalacademy.com Who is at Risk? Occupational Disease Cattle ranchers/ dairy farmers Veterinarians Abattoir workers Meat inspectors Lab workers Hunters Travelers

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www.indiandentalacademy.com Consumers of unpasteurized dairy products are also at risk

B. melitensis :

www.indiandentalacademy.com B. melitensis Latin America, Middle East, Mediterranean, eastern Europe, Asia, and parts of Africa Accounts for most human cases In the Mediterranean and Middle East Up to 78 cases/100,000 people/year Arabic Peninsula 20% seroprevalence Recent emergence in cattle on Middle Eastern intensive dairy farms

B. abortus:

www.indiandentalacademy.com B. abortus Worldwide Some countries have eradicated Notifiable disease in many countries Poor surveillance and reporting due to lack of recognition Fever of Unknown Origin (FUO)

B. suis:

www.indiandentalacademy.com B. suis Biovars 1 and 3 Worldwide problems where swine are raised Free United Kingdom, Canada Eradicated Holland, Denmark Low Incidence Middle East, North Africa

B. suis:

www.indiandentalacademy.com B. suis Low Levels United States and Australia Persistent problem in feral swine Biovar 1 Established in cattle in Brazil and Columbia Biovar 2 Enzootic in wild hares in Europe

B. canis:

www.indiandentalacademy.com B. canis Poorly understood 1-19% prevalence in United States Rarely causes disease in humans

Brucellosis in U.S.: 1972-2002:

www.indiandentalacademy.com Brucellosis in U.S.: 1972-2002 1972 1977 1982 1987 1992 1997 2002 Year 350 300 250 200 150 100 50 0 Reported Cases

Brucellosis:

www.indiandentalacademy.com Brucellosis United States Approximately 100 cases per year Less than 0.5 cases/100,000 people Mostly California, Florida, Texas, Virginia Many cases associated with consumption of foreign cheeses

Disease in Humans:

Disease in Humans

Human Disease:

www.indiandentalacademy.com Human Disease Can affect any organ or organ system All patients have a cyclical fever Variability in clinical signs Headache, weakness, arthralgia, depression, weight loss, fatigue, liver dysfunction

Human Disease:

www.indiandentalacademy.com Human Disease 20-60% of cases Osteoarticular complications Arthritis, spondylitis, osteomyelitis Hepatomegaly may occur Gastrointestinal complications 2-20% of cases Genitourinary involvement Orchitis and epididymitis most common

Human Disease:

www.indiandentalacademy.com Human Disease Neurological Depression, mental fatigue Cardiovascular Endocarditis resulting in death Chronic brucellosis is hard to define Length, type and response to treatment variable Localized infection Blood donations of infected should not be accepted

Diagnosis in Humans:

www.indiandentalacademy.com Diagnosis in Humans Isolation of organism Blood, bone marrow, other tissues Serum agglutination test Fourfold or greater rise in titer Samples 2 weeks apart Immunofluorescence of organism in clinical specimen PCR

Treatment of Choice:

www.indiandentalacademy.com Treatment of Choice Combination therapy has the best efficacy Doxycycline for six weeks in combination with streptomycin for 2-3 weeks or rifampin for 6 weeks CNS cases treat 6-9 months Same for endocarditis cases plus surgical replacement of valves

Prognosis:

www.indiandentalacademy.com Prognosis May last days, months or years Recovery is common Disability is often pronounced About 5% of treated cases relapse Failure to complete the treatment regimen Sequestered infection requiring surgical drainage Case-fatality rate: <2% ( untreated) Endocarditis caused by B. melitensis

Animals and Brucellosis:

Animals and Brucellosis

Clinical Signs: Cattle & Bison:

www.indiandentalacademy.com Clinical Signs: Cattle & Bison Third trimester abortions with B. abortus Retained placenta Once expelled will have a leathery appearance Endometritis Birth of dead or weak calves Respiratory distress and lung infections Low milk yield

Clinical Signs: Sheep & Goats:

www.indiandentalacademy.com Clinical Signs: Sheep & Goats B. melitensis causing late term abortions Retained placenta Birth of dead or weak lambs/kids Goats - articular and periarticular hygroma localizations B. ovis causing abortions, fertility problems Orchitis, epididymitis Abnormal breeding soundness exam Organisms present in semen

Clinical Signs: Swine:

www.indiandentalacademy.com Clinical Signs: Swine B. suis Prolonged bacteremia Abortion, early or late gestation Fertility problems Sows temporary Boars, unilateral or bilateral orchitis Lameness, posterior paralysis, spondylitis, metritis, abscesses

Clinical Signs: Horses:

www.indiandentalacademy.com Clinical Signs: Horses B. abortus most common Susceptible to B. suis Fistulous Withers or Poll Evil Inflammation of the supraspinous bursa Exudative process Fills with clear viscous liquid Can eventually rupture

Clinical Signs: Dogs:

www.indiandentalacademy.com Clinical Signs: Dogs Susceptible to B. melitensis, B. abortus, and B. suis B. canis causes abortions Last trimester of pregnancy Prolonged vaginal discharge Bacteremia Failure to conceive, stillbirths, prostatitis, epididymitis

Clinical Signs: Wildlife:

www.indiandentalacademy.com Clinical Signs: Wildlife Elk Abortions, no retained placenta Moose Weakness, debilitated Predators not clinical but are vectors Coyotes, crows, vultures, bears Aid in disease spread by carrying infected tissues away from abortion site

Diagnosis in Animals:

www.indiandentalacademy.com Diagnosis in Animals Isolation of organism Blood, semen, other tissues Serology Brucellosis card test, ELISA Brucella milk ring test Demonstration by fluorescent antibody of organism in clinical specimen Placenta, fetus

Treatment of Animals:

www.indiandentalacademy.com Treatment of Animals Combination antibiotic therapy has the best efficacy Surgical drainage plus antibiotics Often expensive High rate of failure Indemnity program from government

Prognosis:

www.indiandentalacademy.com Prognosis Disease may last days, months, or years Eradication program in the United States often leads to slaughter of certain species Cattle, bison, horses, sheep, goats, swine

Yellowstone National Park:

www.indiandentalacademy.com Yellowstone National Park

Bison in Yellowstone:

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

Elk in Yellowstone:

www.indiandentalacademy.com Elk in Yellowstone Exposed to B. abortus via winter feeding grounds Isolate themselves at calving Clean the area Remain separate from herd for a few days Less disease transmission between herdmates

Prevention and Control:

Prevention and Control

Prevention and Control:

www.indiandentalacademy.com Prevention and Control Education about risk of transmission Farmer, veterinarian, abattoir worker, butcher, consumer, hunter, public Wear proper attire if dealing with infected animals/ tissues Gloves, masks, goggles Avoid consumption of raw dairy products

Prevention and Control:

www.indiandentalacademy.com Prevention and Control Immunize in areas of high prevalence Young goats and sheep with Rev-1 Calves with RB51 No human vaccine Eradicate reservoir Identify, segregate, and/or cull infected animals

Prevention and Control:

www.indiandentalacademy.com Prevention and Control B. suis, ovis, and canis Veneral transmission Separate females at birthing to reduce transmission on the farm or in kennel

RB51:

www.indiandentalacademy.com RB51 Approved for use February 1996 for calves Able to differentiate “wild type” exposure from immunization 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

U.S. Eradication Program:

www.indiandentalacademy.com U.S. Eradication Program U.S. Department of Agriculture 1934: Cooperative State-Federal Brucellosis Eradication Program Removal of diseased cattle due to drought 1951: APHIS became involved 1957: 124,000 positive herds Approach Test, slaughter, trace back, investigate, and vaccinate

U.S. Eradication Program:

www.indiandentalacademy.com U.S. Eradication Program Target date for eradication was December 31, 1998 Surveillance Brucellosis ring test Pooled milk Market Cattle Identification Blood test, individual Indemnity for whole herd depopulation $250 nonregistered cattle/bison $750 or 95% of value minus salvage value for registered cattle

U.S. Eradication Program:

www.indiandentalacademy.com 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

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

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www.indiandentalacademy.com http://www.aphis.usda.gov/vs/nahps/brucellosis/status_rpt/figure05.jpg

Brucellosis Classes:

www.indiandentalacademy.com 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 tested twice before and once after export.

Brucellosis Today:

www.indiandentalacademy.com Brucellosis Today                                                              USDA/APHIS

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www.indiandentalacademy.com                                                                  USDA/APHIS

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www.indiandentalacademy.com                                                            USDA/APHIS

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www.indiandentalacademy.com USDA/APHIS

B. abortus Exposure:

www.indiandentalacademy.com B. abortus Exposure 1997: Kansas State University 14 month old heifer admitted to hospital with calving complications Vaccinated with RB51 at 8 months 10 times the dose for known pregnant cattle 9 humans exposed Treated with doxycycline No clinical signs

Brucellosis as a Biological Weapon:

www.indiandentalacademy.com Brucellosis as a Biological Weapon Aerosolized B. melitensis City of 100,000 people Inhale 1,000 cells (2% decay per min) Case-fatality rate of 0.5% 50% hospitalized for 7 days Outpatients required 14 visits 5% relapsed Results 82,500 cases requiring extended therapy 413 deaths $477.7 million in economic impact

Internet Resources :

www.indiandentalacademy.com 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.htm WHO Fact Sheet Brucellosis www.who.int/inf-fs/en/fact173.html Brunet Publication progress.box.co.il/brunet/public_sub2_pl.html

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Acknowledgments Development of this presentation was funded by a grant from the Centers for Disease Control and Prevention to the Center for Food Security and Public Health at Iowa State University.

Acknowledgments:

www.indiandentalacademy.com Acknowledgments Author: Co-author: Reviewers: Radford Davis, DVM, MPH Danelle Bickett-Weddle, DVM, MPH Stacy Holzbauer, DVM Jean Gladon, BS

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Thank You www.indiandentalacademy.com Leader in continuing dental education www.indiandentalacademy.com

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