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1

T/F: Brucella is the most common zoonotic disease in the world

True

-500,000 new cases annually

-Increasing prevalence w/ rise in tourism

2

How is Brucella transmitted to humans?

-Direct contact with fluid from infected animals

-Consumption-can be passed by food products (i.e. unpasteurized milk and cheese)

-Inhalation

-Aerosol

3

Identify the 6 Brucella species and the most commonly associated reservoir

1. B.melitensis (small ruminant-goats and sheep)

2. B. abortus (cattle)

3. B. suis (swine)

4. B. canis (dogs)

5. B. neotomae (desert wood rats)- not pathogenic to humans

6. B. ovis (sheep) -not pathogenic to humans

4

T/F: All six Brucella species cause disease in humans.

False

Only four are pathogenic to humans (melitensis, abortus, suis, and canis)

5

What are the microbiology characteristics of Brucella (morphology, gram negative/positive, etc)?

-Gram negative coccobacilli (rods)

-No spores, capsules or flagella

-Facultative intracellular aerobe

6

How does pasteurization prevent brucellosis?

-eliminates the organism

-reduces number of human cases

7

T/F: David Bruce detected Brucella in goat’s milk after British Soldiers became sick while in Malta.

True

8

Majority of worldwide cases of Brucella are attributed to B. _____________

Melitensis

9

What two strains of Brucella are more virulent to humans?

-B. melitensis

-B. suis

10

What regions have a high prevalence of Brucella?

-Mediterranean Basin

-Arabian peninsula

-Indian subcontinent

-Parts of Mexico

-Central and South America.

11

What strain of Brucella has been discovered in breast implants?

B. inopinata

-not zoonotic, but interesting and rare

12

What occupations are at an increased risk for Brucellosis?

-Shepard’s

-veterinarians

-dairy-industry professionals

-micro lab personnel



13

How might a Brucella infection cause spontaneous abortions in cattle?

-Brucella has an affinity for tissues rich in erythritol (i.e animal uterus, breast, and placenta)

-the organism will multiply in the uterus

14

What is the most common Brucella species in the United States? Where are most reported cases of Brucellosis in the US?

-B. abortus

-California, Florida, Texas, and Virginia

15

Brucella __________ is the most widespread cause of infection, but rarely causes human disease.

abortus

16

Brucella ___________ is the most common type seen with disease and is the most prevalent

melitensis

17

List the four pathogenic Brucella species in order of severity (1= most severe, 4=least severe)

1. B. melitensis
2. B. suis
3. B. abortus
4. B. canis

18

Contaminated sheep and goat milk with Brucella _______ seems to be the leading source of human brucellosis worldwide.

melitensis

19

What two countries are most affected by Brucella?

Mongolia and Syria

20

Up until 2002, the highest burden of Brucella was in what two states?

Texas and Hawaii

21

T/F: Person-to-person transmission of Brucella is common.

False

Extremely rare, a few cases from direct tissue transplantation

22

How is Brucella transmitted in the environment?

-Contaminated by birth products/abortions of infected animals

-Can be spread by inhalation of contaminated dust

-Can survive for long periods of time in dust, dug, slurry, water, soil, carcasses

23

___________ transmission is the most common cause of Brucella exposure to humans. _______ products are more common than meat products to cause infection.

Foodborne

Dairy (i.e soft cheeses, fresh milk and dairy products)

24

Brucella is an intracellular parasite of the ____________ system that does NOT produce an exotoxin.

-reticuloendothelial system (macrophages and phagocytic cells in the lymph nodes and bone marrow)

25

How does Brucella cause disease?

1. Macrophages phagocytose Brucella.

2. Phagocytosed Brucella reproduce and inhibit cells critical for life functions

3. Phagocytosed bacteria travel in the blood to organs (ex. Spleen, liver, bone marrow, kidneys, and lymph nodes)

4. Bacteria secretes proteins which elicits an immune response causing granuloma formation

5. Granuloma formations destroy tissue and cause destructive disease

26

Describe the acute presentation of Brucellosis

-Invariable, Undulant Fever (most common symptom)

-Rigors if bacteremic

-Malodorous perspiration (wet hay-like odor)

-Constitutional symptoms (fevers, chills, night sweats, weight loss)

-Chronic fatigue symptoms may develop

-Nonspecific physical exam may see swelling of particular organs (ex. lymphadenopathy, hepatomegaly/splenomegaly)

27

What are the most common symptoms of acute Brucellosis?

-Fever

-Chills

-Sweats

28

T/F: About 50% of Brucellosis cases are acute

True

29

What is the incubation period for Brucellosis?

Usually 5-60 days

1-2 months common

30

In subacute cases, why might a person not seek treatment?

-The onset is insidious and subacute infection presents with nonspecific symptoms (malaise, fevers, chills, fatigue, night sweats, weight loss, headache,etc.).

-Individuals may confuse the infection with a cold that the immune system clears without intervention.

31

______________ disease is the most common presentation of focal brucellosis usually seen in acute infection. Peripheral arthritis and _________ are the most common subclassifications seen. Complications are linked to the __________ serotype, which may express presentations around the bones of the spine.

-Osteoarticular

-sacrolititis

-HLA-B39

32

T/F: Osteoarticular disease can present as peripheral arthritis, sacroliitis, and spondylitis.

True

Peripheral arthritis: most common, non-erosive, involves knees, ankles, wrists, and hips, seen in acute infection

Sacroiliitis: inflammation of bones around the sacrum (lower back) seen in acute infection


Spondylitis: inflammation of space between vertebral discs propensity for lumbar spine, difficult to treat

33

____________ system is the most common site of focal brucellosis, which carries a potential risk for _________.

-Reproductive system


-Spontaneous abortion

34

What are the clinical presentations of Brucellosis in various body systems?

1. Bones: osteoarticulitis (peripheral arthritis, sacroiliitis, spondylitis)

2. Reproductive system: epididymoorchitis in men, spontaneous abortion

3. Liver: hepatitis (tranaminasemia, abscesses and jaundice-rare)

4. CNS: Meningitis, encephalitis, meningoencephalitis, meningovascular disease, brain abscess, demyelinating syndromes

5. Cardiovascular: endocarditis

35

Endocarditis is the principal cause of mortality associated with Brucella. How does the disease progress and lead to fatality?

-overtime the heart forms infective vegetation’s on the valve (usually aortic) that leads to physical changes and decreased functionality

1. Bacteria stick onto a valve of the heart

2. Accumulate more bacteria and thrombotic material (plateletes, fibrin, etc.) that creates a vegetation on a valve


3.Bactetria produce materials (chemicals like chemokines and proteins) with resistance factors against treatment (i.e. antibiotics)

4. Valvular dysfunction (pressure changes, valves stop working, inefficient blood flow)

5. Physical changes in heart that can lead to heart failure

36

Brucella endocarditis is _____ and effects 1-5% of infected individuals. Patients with endocarditis likely have/had underlying cardiac conditions. Most frequently the ______ valve is affected. _______ ventricular failure is most common.

-rare

-aortic

-Left

37

How does Brucella affect animals?

-usually infects animals in endemic areas

-asymptomatic with initial infection

-localized reproductive tract (epididymus and orchitis in M and placentitis in F)

-may cause spontaneous abortions and still births

38

Sheep and goat Brucella infections are highly contagious because of _________ of B. Melitensis and the proximity of herd members.

Pathogenicity (how severe)

39

With brucellosis Ig_ against the LPS appears during the first week of infection. Ig_ appears during the second week of infection. Both peek at 4 weeks. IgM persists at _______ levels than IgG after 6 months. If Ig_ and Ig_ persist for longer than 6 months then a person has chronic brucellosis.

-IgM (acute factor)

-IgG (chronic factor)

-higher

-IgA and IgG

40

What is the gold standard of for Brucellosis diagnosis and why

-Blood culture (isolation of bacterium from blood or tissue sample) or Bone marrow culture (harder to obtain)

-Propensity for reticuloendothelium

-takes long period of time

41

Titers> _________ plus history of clinical presentation with Brucella are necessary for diagnosis.

1:160

42

What are some drawbacks to agglutination test (aka milk ring test)?

-can’t detect B. canis***

-crops reactions possible

-Lack of seroconversion: false negative if patient doesn’t make antibodies

43

What prevents seroconversion when performing diagnostic testing for Brucellosis?

1. May too early in the course of infection for the body to produce IgM and IgG

2. Presence of blocking antibodies => “Prozone” phenomenon: prevents agglutination due to excess antigen, excess of non-specific serum factors => false negative

44

Describe the prozone effect. (Brucella)

-The body of the infected host produces high amounts of (blocking) antibody that prevents natural Brucella antibodies from binding.

Produces a false negative result upon diagnostic testing due (not detecting antibody of interest)

45

What is the treatment for Brucellosis?

Doxycycline (bacteriostatic) and rifampin for 6 weeks

-Combination is ideal

46

What are general control measures that could be implemented for Brucella?

-Safe farming and good personal hygiene

-PPE (gloves, protective clothing, sanitary tools)

-safe disposal of aborted fetus

-food safety (store soft cheese for 6 months, food acidification to pH<3.5, pasteurize milk (80-85 C) especially if in an area where brucellosis is high, cook meats)

47

What are animal control measures that could be implemented for Brucella?

-choose animals from Brucella free herds, isolate new animals for 30d

-diagnose abortion causation, premature births, and other clinical signs w/ lab assistance

-routine surveillance of herds and flocks (milk ring test)

-vaccination (most successful method for prevention and control)

48

What is the best Brucella surveillance for the four main reservoirs?

Cattle: milk ring test (dairy), blood sample (beef)

Pigs, Sheep, Goats: blood sample


49

What is the milk ring test (MRT)?

-simple and effective, but only works for cows

-drop of hematoxylin-stained antigen into a sample of cow’s milk

If Brucella antibody is present, a blue ring of cream will appear at the top of the tube/glass

50

How did the US Department of Agriculture Cooperative State-Federal Brucellosis Eradication Program try to eliminate Brucella? What is the prevalence of Brucella in domestic herds now?

-Tested animals for Brucella

-Slaughtered any positive animals or animals exposed to positive animals, traced back exposure, vaccinated animals

-Surveillance: MRT, market cattle identification (blood test)

-No longer found in domestic herds in the US

51

What organism causes Q Fever

Coxiella burnetii

52

How is Q fever distributed across the globe?

Worldwide except Antarctica and New Zealand

53

How does Q fever infect a host?

-Using a passive mechanism, the bacteria survives within the phagolysosome of a macrophage

-Produces spores to withstand harsh environments

-Antigenic variation/phase variation (phase I highlight infectious)

54

What are Q-fever reservoir species?

-Goats, sheep and cattle (main reservoirs)

-Cats

-Rabbits

-Birds

- Ticks

55

How is Q Fever transmitted to humans?

-organism excreted in urine, feces, milk, and birth fluids

-inhalation of the organism from contaminated environments (most common, only need 1-10 organism to be infected)

-raw milk (occasionally)

56

T/F: Coxiella (Q Fever) is one of the most infective species in the world

True

-Only takes 1-10 organisms

-70% morbidity

-potential bioterrorism (especially w, ability to form spores)

57

Q. Fever has an incubation period of ________

Most commonly: 20 days (range of 14-39 days)

58

What are the symptoms of Q. Fever?

-Nonspecific symptoms (headache, fatigue, malaise, chills, fevers, night sweats)

-retro-orbital pain

-self-limited febrile illness (2-14d)

-most are asymptomatic

59

What are the severe complications of chronic Q-fever?

-endocarditis

-osteomyelitis

-Neuro complications

60

What is the general course of disease for Q fever?

1. Exposure

2. Acute Q Fever (primary infection)

3. Chronic infection (if pregnancy: abortion or chronic carriage, endocarditis, cancer)

61

T/F: Most individuals with Q fever are asymptomatic.

True

The infection may self resolve

62

T/F: Chronic Q fever will more commonly lead to endocarditis.

True; it’s the main consequence of chronic infection

63

Over the years, the number of Q Fever cases have ______ due to _______ diagnosis and reporting. People of ________ age are more likely to present symptoms. While it may seem like _____ are more at risk, their immune systems are stronger and able to fight off infection..

-increased

-better/more

-older

-children

64

T/F: There is high incidence of Q Fever in urban areas.

False

High incidence in rural areas (farming, sheep and goats)

65

How is Q fever detected?

Serology to determine antigenic phase

66

What are the antigenic phases of Q fever and how do they relate to the course of disease?

Phase I: acute infectious phase

Phase II: less virulent, susceptible

Chronic infection: High Phase I and Phase II Ab

Acute: high phase II Ab

67

T/F: Phase II antibodies present before phase I in Q Fever.

True

-Phase II is detectable during acute Q fever, whereas high levels of phase I antibodies are detectable during chronic Q fever


-acute is antiphase II IgG >/= 200 and IgM >/= 50

68

What is the treatment for Q Fever?

Doxycycline for 2 weeks