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 FeverAnimal DiseaseBang’s DiseaseEnzootic AbortionEpizootic AbortionSlinking of CalvesRam EpididymitisContagious Abortion
History
History of Malta Fever450 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 DiseasesPhysician 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 detailJeffery Allen Marston
Sir David Bruce (1855-1931)
British Army physician and microbiologist Discovered Micrococcus melitensisProfessor 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 goatsProfessor 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 melitensisTransmission
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 meatTransmission 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 monthsTransmission in Animals
Ingestion of infected tissues or body fluids Contact with infected tissues or body fluids Mucous membranes, injections Venereal Swine, sheep, goats, dogs FomitesEpidemiology
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% seroprevalenceB. abortus
Worldwide Some countries have eradicated it Notifiable diseasein 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 AfricaB. 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 EuropeB. ovis
Most sheep-raising regions Australia New Zealand North America South America South Africa Many European countriesB. canis
Poorly understood 1-19% prevalence in United States Rarely causes disease in humansIncidence of Brucellosis in USA
Brucellosis in U.S.: 1975-2006
BrucellosisUnited 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 lesionsClinical Presentation of Human Brucellosis
Human Brucellosis & Associated Species
SevereHuman 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 dysfunctionHuman 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 acceptedHuman Disease
Congenitally infected infants Low birth weight Failure to thrive Jaundice Hepatomegaly Splenomegaly Respiratory difficulty General signs of sepsis (fever, vomiting) AsymptomaticDiagnosis 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 PCRTreatment 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 valvesPrognosis
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. melitensisPrognosis
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, swinePrevention and Control
Prevention and ControlEducation 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 animalsBrucellosis 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 movementBrucella 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 impactSummery
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 damagePlate 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