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Brucellosis

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

The Many Names of Brucellosis

Human Disease Malta Fever Undulant Fever Mediterranean Fever Rock Fever of Gibraltar Gastric Fever
Animal DiseaseBang’s DiseaseEnzootic AbortionEpizootic AbortionSlinking of CalvesRam EpididymitisContagious Abortion

History

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

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

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

Contracted Malta fever Described his own case in great detail
Jeffery Allen Marston

Sir David Bruce (1855-1931)

British Army physician and microbiologist Discovered Micrococcus melitensis
Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical Diseases

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

Alice Evans, American bacteriologistCredited with linking the organismsSimilar morphology and pathology between:Bang’s Bacterium abortus Bruce’s Micrococcus melitensisNomenclature today credited to Sir David BruceBrucella abortus and Brucella melitensis

Transmission

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

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 5-21 days to three months

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 Fomites

Epidemiology

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

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


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

B. suis

Worldwide problems where swine are raised Free United Kingdom, Canada Eradicated Holland, Denmark Low Incidence Middle East, North Africa

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. ovis

Most sheep-raising regions Australia New Zealand North America South America South Africa Many European countries

B. canis

Poorly understood 1-19% prevalence in United States Rarely causes disease in humans

Incidence of Brucellosis in USA

Brucellosis in U.S.: 1975-2006

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

Acute disease often develops with initial nonspecific symptoms of malaise, chills, fatigue, weakness, myalgias (muscles), weight loss, arthralgias (joint), and nonproductive cough Mild disease with rare suppurative complications Chronic disease and recurrence are common because it can survive in phagocytic cells and multiply to high concentrations May also take the form of destructive lesions
Clinical Presentation of Human Brucellosis

Human Brucellosis & Associated Species

Severe

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
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

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 persons should not be accepted

Human Disease

Congenitally infected infants Low birth weight Failure to thrive Jaundice Hepatomegaly Splenomegaly Respiratory difficulty General signs of sepsis (fever, vomiting) Asymptomatic

Diagnosis in Humans

Isolation of organism Blood, bone marrow, other tissues Serum agglutination test Four-fold or greater rise in titer Samples 2 weeks apart Immunofluorescence Organism in clinical specimens PCR

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

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

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

Prevention and Control

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

Immunize in areas of high prevalence Young goats and sheep No human vaccine Eradicate reservoir Identify, segregate, and/or cull infected animals

Brucellosis Classes

Free Feb 1, 2008 – U.S. class-free in cattleA: No more than 0.25% infection rate and cattle must be tested before exportB: Infection rate of no more than 1.5% and must be tested before interstate movement

Brucella 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 economic impact



Summery

Brucella Infections (cont.)

Animals are natural reservoir Cattle, goats, sheep, swine, bison, elk, dogs, foxes, coyotes 500,000 human cases per year worldwide Less than 100 annual cases in the U.S. due to successful control of the disease in livestock and the animal reservoir Transmission via i) ingestion of contaminated milk or cheese, or ii) direct contact with infected animals or animal products Because it can be transmitted to humans, brucellosis is one of the most regulated diseases of cattle in the U.S.
Epidemiology of Brucellosis

Brucellosis in Humans

Reportable disease Human brucellosis = Bang's disease, named for Bernhard Bang & Sir David Bruce who discovered Brucella Facultative intracellular pathogens of mononuclear-phagocyte system (formerly reticuloendothelial system which is involved in immune defense against microbial infection and removal of worn-out blood cells) Bacteria are phagocytosed by macrophage or polymorphonuclear leukocyte Survive intracellularly by inhibiting killing Carried to spleen, liver, bone marrow, lymph nodes, kidneys Form granulomas (mass of granulation tissue produced in response to chronic infections, inflammation, or foreign bodies) and cause destructive tissue damage


Plate agglutination test (a.k.a., Brucella ring test) diagnosing Brucella Drop of serum mixed with drop of Brucella antigen Clumping indicates infection If the mixture remains clear, the result is negative. Treated with combination of tetracycline and doxycycline For infants, tetracycline is toxic, so children are treated with trimethoprim-sulfamethoxazole.
Diagnosis & Treatment of Human Brucellosis


In 1934, the U.S. Department of Agriculture (USDA) established the National Brucellosis Eradication Effort which is managed by Animal, Plant, and Health Inspection Service (APHIS) APHIS certifies states as brucellosis-free, classes A, B, or C of which all states are currently classified A Serology & confirmatory bacterial culture to identify infected animals
Control & Prevention of Brucellosis






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