Topic 102 - Bovine tuberculosis (RED) Flashcards

1
Q

What is bovine tuberculosis?

A

A chronic bacterial disease

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2
Q

Occurrence of bovine tuberculosis:

A

It is widespread !

We differentiate between:
1. Tuberculosis-free countries
2. Infected countries

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3
Q

What is special with the tuberculosis-free countries?

A

We can still find the disease in wild living ruminants, wild boars and badgers, all of these are reservoirs !

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4
Q

Causative agent of bovine tuberculosis:

A

Mycobacterium bovis
AND
Mycobacterium caprae

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5
Q

How is the bovine tuberculosis shed?

A

Shed by carrier animals via:
- Tracheal discharge ⭢ Most importantly in cattle
- Milk
- Faces
- Urine
- Semen

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6
Q

How susceptible is cattle to bovine tuberculosis?

A

VERY !!

Only need 10 bacteria to infect via aerosol

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7
Q

How does bovine tuberculosis infect?

A
  1. Most commonly via inhalation

But also:
2. Per os ⭢ Especially in calves

Rare forms:
3. Intra uterine
4. Per cutaneous

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8
Q

In case of bovine tuberculosis, we see different lesions. What are the nature of them influenced by?

A
  1. Agent, the bacterium itself
  2. Host resistance: Cellular and specific immunity
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9
Q

Which type of lesions can we see in case of bovine tuberculosis? And why?

A
  1. Tubercules ⭢ There is a balance between resistance and bacteria
  2. Proliferative lesions ⭢ Resistance of host is high
  3. Exudative lesions ⭢ Resistance of host is low, which makes and immediate reaction
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10
Q

Pathogenesis until tubercule formation in case of bovine tuberculosis:

A
  1. Bacilli and phagocyted by macrophages and dendritic cells
  2. The cells reaches the lymph nodes in order to eliminate the bacteria
  3. They are facultative bacteria, meaning they can replicate intracellularly
  4. Fusion of lysome with the phagosome is inhibited by the antiphagotic materials in the cell wall.
  5. Mycobacteria is released from dead macrophages and different mediators will be releases and this is the signal for the cellular immune reaction
  6. There is a tubercule formation
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11
Q

Pathogenesis of tubercule formation in case of bovine tuberculosis:

A
  1. The bacteria replicates in the macrophages, reaching a certain number
  2. The macrophages and dendritic cells are lysed.
  3. As a result of the cell lysis different mediators will be released attracting different inflammatory cells: histiocytes, lymphocytes, giant cells
  4. They will be collected around the bacteria
  5. There will be several layers of the tuberculum, and we can find plasma infiltrated in the middle
  6. Due to the plasma infiltration, coagulation necrosis happens, and different cells will encapsulated the necrosis
  7. Granulation tissue and fibrinocytes will be collected around and this will isolate the forming the tuberculum.
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12
Q

Name the mediators released due to the lysis:

A

ɣ-IFN = Gamma-interferon
TNF = Tumour necrosis factor

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13
Q

Timeline of pathogenesis of tuberculum in case of bovine tuberculosis:

A

1st week: 1st form of tubercule formation, the inflammation cells appear
2nd week: The 2nd layer of the tubercule is formed, coagulation necrosis happens
3rd week: Complete granulation tissue is formed
7th week: Calcification can happen. Calcium salt can be deposited and it can be examined post mortem

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14
Q

There are 3 different outcomes of pathogenesis of bovine tuberculosis, name them:

A
  1. Tubercule formation = Cellular immune response
  2. Exudative lesions
  3. Proliferative lesions
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15
Q

Pathogenesis of bovine tuberculosis, where the outcome is exudative lesions:

A
  1. The host has a poor cellular immune response.
  2. As the bacteria replicated, the host will try to prevent the spread and an immediate reaction is needed
  3. The area is infiltrated with plasma which contains high amount of lymphovytes.
  4. As a result of the plasma infiltration, there is a necrosis, due to the cells dying
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16
Q

Pathogenesis of bovine tuberculosis, where the outcome is proliferative lesions:

A
  1. The immunity of the host is better, and copes with the bacteria.
  2. There is a strong infiltration with cellular infiltration
  3. A strong granulation tissue will be produced and mainly proliferative lesions are seen
  4. There is NO plasma, NO necrosis and NO calcification
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17
Q

What is the pathogenesis of bovine tuberculosis influenced by?

A
  1. The immune state of the host
  2. If it is a first of a repeated infecion
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18
Q

The infection of bovine tuberculosis can change, there can be discontinous pathogenesis with different phases. Name them:

A
  1. Primary focus
  2. Early generalisation
  3. Post primary phase
  4. Exhaust phase Also called: Late generalisation
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19
Q

Pathogenesis of primary focus of bovine tuberculosis:

A

We find lesions at the site of entry and lesions in the regional lymph nodes.
The site of entry in cattle = Lungs
The site of entry ins pigs = alimentary tract

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20
Q

Pathogenesis of primary focus of bovine tuberculosis, outcome:

A
  1. If resistance is high = inactive state
  2. If resistance is low = early generalisation
    ⭢ There is a lympho-haematogenic dissemination, the bacteria gets into the lymphatic and blood system. The bacteria reaches all organs and we have the early generalisation
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21
Q

Pathogenesis of early generalisation of bovine tuberculosis:

A
  1. If resistance is good, we see tubercule formation
  2. If resistance is weak, we see mainly exudaive lesions
  3. The lesions can be: Acute or protracted tuberculosis
    ⭢ Acute = Miliary tuberculosis, where several small tubercules will be formed
    ⭢ Protracted tuberculosis = Fever, but larger tuberculi will be formed
  4. We also see lesions in the lymph nodes
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22
Q

Pathogenesis of early generalisation of bovine tuberculosis, outcome:

A

The balance between the host and the agent is not stable, so the outcome can vary

  1. Can recover
  2. A longer or shorter inactive state can be reached
  3. Animal can die
  4. Progression can happen ⭢ animal enters 3rd phase
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23
Q

Pathogenesis of Post primary phase of bovine tuberculosis:

A
  1. There is a second spread of the bacteria, can come from a previous lesion or it can be exogenous = Post primary phase
  2. The animal is an allergic state, due to the early generalisation, and the immune system have already “met” the bacteria
  3. There is an immune response, preventing the inhibited spread of the bacteria.
  4. They can spread in the lungs, but not spread through the blood, not reaching the lymph nodes !!
  5. It replicates and can cause lesions in the lungs, but only through airborne infection - Causing infection via intra canalicular spread
  6. It is called organic tuberculosos, because this phase is limited to reacting in organs only
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24
Q

Pathogenesis of Post primary phase of bovine tuberculosis, outcome:

A
  1. Large lesions, frequently the resistance is low enough and extend the lesions
  2. We see necrotic and caseous lesions, and caverns are seen
  3. the original structure of the organs are sometimes unrecognisable and the outcome is late generalisation
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25
Q

Pathogenesis of Late generalisation of bovine tuberculosis:

A
  1. The resistance of the immune system is exhausted
  2. The immune system is not able to inhibit the generalisation of the agent and there is a lymphogenic spread
  3. The bacteria reaches the organs and standard lesions will develop
  4. The bacteria will reach the lymph nodes and fresh lesions is seen
  5. The animal will die
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26
Q

Incubation time for bovine tuberculosis:

A

Months, sometimes years
= because the replication is long

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27
Q

Clinical signs of bovine tuberculosis:

A

Not typical, especially not in the beginning.

There are different clinical signs in the different phases:

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28
Q

Clinical signs for bovine tuberculosis in primary focus:

A

= 1st phase

No clinical signs

29
Q

Clinical signs for bovine tuberculosis in early generalisation:

A

Not very typical !!

  1. Fever
  2. Enlarged lymph nodes
  3. ⭣ in milk production
30
Q

Clinical signs for bovine tuberculosis in prost primary phase:

A

We see organic tuberculosis.

  1. Enlarged lymph nodes
  2. Organic clinical signs, depending on where the lesions are: Lungs, intestines, udder, kidney, genitals, CNS, bones
31
Q

Clinical signs for bovine tuberculosis in lungs:

A

= Pulmonary tuberculosis

We see respiratiry signs:
1. Returning cough, progressing severity. First dry, later wet
2. Rubbing noise, from pleuritis
3. Tympany. Due to the enlargement of the mediastinal lymph nodes compressing the esophagus

32
Q

Clinical signs for bovine tuberculosis in intestines:

A
  1. Diarrhoea
  2. Enlarged mesenterial lymph nodes
33
Q

Clinical signs for bovine tuberculosis in udder:

A

Quite typical!

We see tuberculum formation and the skin is uneven, often connected with enlarged lymph nodes.
The consistency of milk is changed

34
Q

Clinical signs for bovine tuberculosis in kidneys:

A

= Renal tuberculosis

  1. Protein in the urine
  2. Abdominal pain - The animal has a hunched back
35
Q

Clinical signs for bovine tuberculosis in the male genitals:

A

We see nodules, the surface of the testicles are uneven

36
Q

Clinical signs for bovine tuberculosis in the female genitals:

A
  1. Vaginal discharge
  2. Irregular cycle
  3. Infertility
37
Q

Which phases of bovine tuberculosis can post mortem lesions be seen?

A

Typically seen in phase 2, 3 and 4

PM lesions are very informative

38
Q

Which PM lesions can we see in the second phase of bovine tuberculosis?

A

Small tubercules
Calcification in older tuberculum
Lesions in the lymph nodes !!

39
Q

Which PM lesions can we see in the third phase of bovine tuberculosis?

A

Also called organic tuberculosis

  1. Acinonodular pneumonia
  2. NO fresh lesions in the lymph nodes !!
40
Q

Which PM lesions can we see in the fourth phase of bovine tuberculosis?

A
  1. Fresh miliary tubercules
  2. Caseous lesions
  3. Fresh lesions in the lymph nodes !!
41
Q

How can we diagnose bovine tuberculosis, which approaches?

A

We use two approaches:

  1. Diagnosis of the disease
  2. Diagnosis of the infection - Examining the immune response
42
Q

How can we diagnose the disease of bovine tuberculosis?

A
  1. Evaluate the epidemiology, the clinical signs and the lesions A good veterinarian can diagnose based on this
  2. With histology we can reach a definite diagnosis
  3. We need to detect the bacterium, since bovine tuberculosis is notifiable, we need laboratory confirmation
43
Q

How can we diagnose the disease of bovine tuberculosis, bu detection of the bacterium?

A
  1. Microscopical examination with Ziehl-Neelsen
  2. Isolation BUT: takes too long
  3. PCR and staining is used today
    4.
44
Q

How can we diagnose the infection of bovine tuberculosis?

A

We use 3 methods:

  1. Allergic tests, by using tuberculin tests
  2. We test the cellular immune response
  3. We test the humoral immune response
45
Q

How can we diagnose the infection of bovine tuberculosis, by testing the cellular immune response?

A
  1. Mostly used is the gamma interferin test
  2. We also have lymphocyte proliferation test
46
Q

How can we diagnose the infection of bovine tuberculosis, by testing the humoral immune response?

A

Less important. Not used in cattle, but rather used in wild animals - Because the sensibility of the test is low and therefore is is only done as an additional test, not a primary test

47
Q

How can we diagnose the infection of bovine tuberculosis, by testing the tuberculin test?

A

We use tuberculin, which is an antigen extract made from the bacterium.
Today we use PPD = Purified Protein Derivate, this derivate is made from the old tuberculum where the tuberculoproteins are precipitated partially from the bacteria and the product.

48
Q

How many types of tuberculin do we have?

A

2 types:
1. M.bovis
2. M. avium subsp. avium

49
Q

How many different tests use the tuberculin test, name them.

A

2

  1. Thermal test
  2. Skin intradermal test, SID ⭢ Mostly used today
50
Q

How is “thermal test” performed?

A

We measure the basic temperature. Every 2nd hour we measure it and if the temperature increase exceeds 1.5 = positive test

51
Q

How is “SID” performed?

A
  1. Clean the skin
  2. Measure the skin fold
  3. 0.1 ml is injected into clipped skin OR into the caudal fold of the tail
  4. Then we read the test after 72 hours, in older animals we read again the test after 96 hours (4days)
52
Q

When can a SID be repeated?

A

It can be repeated after 60-90 days, in some places after 42 days… But important to keep in mind: the test can give a false negative at this point

53
Q

Type of hypersensitivity of SID, as well as sensitivity and specificity.

A

Type 4 hypersensititivy

90-95% sensitivity, pracitcally is a 100%

High specificty on a genus level, meaning we can identity the mycobacterium, BUT not the serovar of it.

54
Q

How can we measure the positive/negative tuberculin test?

A

We examine 2 reactions:
1. Increased thickness of the skin fold
2. The local reaction

Can also do a comparative tuberculin test, using mammal and avian at the same time ⭢ Injected with a 20cm space between them and we compare the reaction between them

55
Q

What type of instrument is used to measure the SID?

A

A reading calliper

56
Q

Reading the SID, tuberculin test. What does it read, when positive

A

The increase is equal to or more than 4mm
OR
We see local reactions

57
Q

Reading the SID, tuberculin test. What does it read, when inconclusive

A

An increase of between 2-4mm
AND
We see no local reactions

58
Q

Reading the SID, tuberculin test. What does it read, when negative

A

The increase is less than 2mm
AND
We see no local reactions

59
Q

Which factors can give the SID a false negative?

A

1. Pre-allergy ⭢ 1-3 weeks after infection, the animal can show false reaction
2. Old, isolated infection ⭢ Old animals do not react
3. Anergy ⭢ The immune response is exhaust, it cannot give a response
4. Immunosuppression ⭢ Can cause a reaction to not happen

60
Q

Which factors can give the SID a false positive?

A

1. Parallergy ⭢ Other mycobacterium than M.bovis causing the infection
2.Antigen relationship ⭢ the antigens are related

61
Q

To differentiate between a parallergy and an anctual infection with M.bovis, how can we examine it?

A
  1. epidemiological analysis
  2. were animals introduced into the herd?
  3. contact with wild living animals
  4. is tuberculosis present in the wild living animals locally?
  5. pasture and water source shared with wild living animals

(Based on 3 pilars)

62
Q

What are the 3 pilars that we base the difference of parallergy and an anctual infection with M.bovis on?

A
  1. Comparative tuberculin test
  2. Slaughterhouse control: With PM examination, histology, culture, PCR
  3. Gamma-interferon test
63
Q

If a suspected herd is confirmed positive with M.bovis, what do we do?

A

1. close the herd
2. Introduce movement restrictions
3. isolation of reacting or inconclusive animals
4. diagnostics, with comparative SIT, slaughterhouse control and gamma-interferon test
5. Elimination of repeated reactors or stamping out the whole herd

64
Q

How would you treat a farm animal that has tested positive for tuberculosis?

A

Antibiotic treatment is PROHIBITED !!
IF we would treat with AB, the long term treatment of AB would cause a risk of AB resistance.

The eradication and maintenance of the free status is the aim

65
Q

How would you treat a zoo animal that has tested positive for tuberculosis?

A

AB can be used with special authorization.

66
Q

What would you do as preventative measures for bovine tuberculosis?

A
  1. General epidemiological rules
  2. Prevention of infection
  3. Vaccines
  4. The main aim = eraditaction
67
Q

Which preventative measure would you do to prevent infection of bovine tuberculosis?

A
  1. Quarantine with a negative tuberculin test
  2. Isolation form wild living animals
  3. Vaccination
68
Q

Type of vaccination used against bovine tuberculosis

A

Vaccination cannot prevent the disease, but both live and inactivated strains exist

69
Q

Eradication measures in case of bovine tuberculosis

A

we use 3 methods:
1. Selection (test and slaughter)
2. Generation shift ⭢ widely used
3. Herd replacement