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Yr 2 - Clinical Pathology > Infection in the Immunocompromised > Flashcards

Infection in the Immunocompromised Flashcards

1
Q

What are innate defenses?

A

Innate immunity involves barriers that keep harmful materials from entering your body. These barriers form the first line of defence in the immune response

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2
Q

Examples of innate defenses?

A

Skin (barrier, sebum, normal flora) – e.g. burns

Mucous membranes (tears, urine flow, phagocytes)

Lungs (goblet cells, muco-ciliary escalator. Cystic fibrosis)

Interferons, complement, lysozyme, acute phase proteins

Normal commensal flora in gut – antibiotic treatment alters flora e.g. C. difficile, Candida spp.

(Extremes of age, pregnancy, malnutrition)

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3
Q

What is the body’s second line of defence?

A

Neutrophils are very important after initial breach of innate defences

i.e. less neutrophils = more infection

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4
Q

What can neutrophil dysfunction be divided into?

A

Quantitative and qualitative disorders

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5
Q

What characterises a qualitative neutrophil disorder?

A

Defect in cellular function e.g. lose ability to kill or chemotaxis

E.g. inadequate signalling

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6
Q

What characterises a quantitative neutrophil disorder?

A
  • Inadequate number of mature neutrophils
  • More common

E.g. cancer treatment, bone marrow malignancy, aplastic anaemia - drugs

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7
Q

What is an example of a qualitative neutrophil disorder?

A

Chronic Granulomatous Disease (CGD)

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8
Q

What is CGD?

Pathogenesis?

Why do granulomas form?

A

WHAT: Rare, inherited immunodeficiency

PATHOGENESIS:

1) Defect in gp91^phox gene that encodes the NADPH oxidase enzyme complex which is formed at the surface of the phagolysosome.
2) Phagocytes are unable to produce hydrogen peroxide to fight specific kinds of bacteria and fungi.
3) Phagocytes can recognise infection but not kill it, resulting in granulomas (collection of macrophages) due to cytokine release

RESULT: Susceptible to certain bacterial and fungal infections.

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9
Q

What is the classic bacteria that CGD patients are most at risk of?

A

Staph. aureus infections

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10
Q

What is neutropenia?

A

An abnormally low concentration of neutrophils (a type of white blood cell) in the blood

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11
Q

In general, what is neutropenia classified as?

A

<0.5x10^9/L

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12
Q

In neutropenic patients, what infections are most serious?

A

Pseudomonal infections

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13
Q

Treatment for neutropenic patients?

A

The two primary treatments for neutropenia are;
1) antibiotics to fight infection; broad spectrum antibiotics e.g. Antipseudomonal penicillin +/- gentamicin

2) drugs that help the bone marrow make neutrophils e.g. G-CSF

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14
Q

What common bacterial infections do neutropenic patients get?

A
  • E. coli, S. aureus
  • Often normal flora e.g. Coag neg staph

These patients often have lines put in, which can lead to these infections

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15
Q

What common fungal infections do neutropenic patients get?

A

Candida spp., Aspergillus spp.

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16
Q

What is given to neutropenic patients that help the bone marrow make neutrophils?

A

Granulocyte colony-stimulating factor (G-CSF) is a blood growth factor that stimulates the bone marrow to produce more infection-fighting white blood cells called neutrophils.

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17
Q

What is T cell deficiency?

A

A deficiency of T cells, caused by decreased function of individual T cells, it causes an immunodeficiency of cell-mediated immunity.

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18
Q

What causes congenital T cell deficiencies?

A

T helper dysfunction +/- hypogammaglobulinaemia

rare

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19
Q

What is hypogammaglobulinemia?

A

A problem with the immune system that prevents it from making enough antibodies called immunoglobulins.

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20
Q

What causes acquired T cell deficincies?

A
  • Drugs e.g. ciclosporin after transplantation
  • Steroids
  • Viruses e.g. HIV
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21
Q

In patients with T cell deficiencies, which bacteria are they susceptible to?

A

Listeria monocytogenes, Mycobacteria

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22
Q

In patients with T cell deficiencies, which viruses– transplants are they susceptible to?

A
  • Herpes viruses: HSV, CMV, VZV.
  • Transplants

Serological testing, prophylaxis and treatment with e.g. aciclovir and ganciclovir

23
Q

In patients with T cell deficiencies, which fungal infections are they susceptible to?

A

Candida spp., Cryptococcus spp.

24
Q

Patients with T cell deficiencies are also susceptible to protozoan and parasitic infections.

One of these is cryptosporidium parvum. What is this?

A

One of several species that cause cryptosporidiosis, a parasitic disease of the mammalian intestinal tract.

  • Oocysts shed by cattle/humans
  • Faecal oral route
25
Q

How can cryptosporidium parvum affect patients with T cell deficiencies?

A

Most patients recover after prolonged illness of up to 3 wks. May take much longer in T-cell deficients.

26
Q

Symptoms of cryptosporidium parvum?

A

Acute, watery, and non bloody diarrhoea.

Can be detrimental in T cell deficients.

27
Q

Hypogammaglobulinaemias can be acquired or congenital.

How can they be acquired?

A

Multiple myeloma, burns

28
Q

What type of bacteria tend to cause problems in patients with hypogammaglobulinaemias?

A

Usually encapsulated bacteria e.g. S. pneumoniae

29
Q

What is treatment for hypogammaglobulinaemias?

A

Immunoglobulin therapy (to replace them)

30
Q

What is complement deficiency?

A

an immunodeficiency of absent or suboptimal functioning of one of the complement system proteins.

31
Q

What are patients with complement deficiency at risk of?

A

Although complement undoubtedly plays a role in host defence against many microbial pathogens, it appears most important in protection against encapsulated bacteria, especially N. meningitidis but also S. pneumoniae, H. influenzae, and, to a lesser extent, N. gonorrhoeae.

32
Q

What can C5-8 deficiency of the complement system lead to?

A

Neisseria infections (particularly Neisseria meningitidis)

33
Q

What is a splenectomy?

A

surgery to remove the entire spleen

34
Q

What is the role of the spleen?

A

source of complement and antibody producing B-cells, removes opsonised bacteria from blood.

35
Q

What can cause a splenectomy to be needed?

A

traumatic, surgical or functional e.g. sickle cell anaemia

36
Q

What is functional asplenia?

A

Functional asplenia occurs when splenic tissue is present but does not work well (e.g. sickle-cell disease, polysplenia)

37
Q

After a splenectomy, which organisms are patients at risk of?

A

S. pneumoniae, Haemophilus influenzae type B, N. meningitidis, malaria

38
Q

What are biologic drugs?

A

Drugs made from proteins and other substances produced by the body.

Used for some long-term medical conditions, including rheumatoid arthritis, Crohn’s disease, psoriasis

39
Q

How do biologics work?

A

Inhibit inflammatory cytokine signals e.g. tumour necrosis factor or TNF, inhibiting T-cell activation, or depleting B-cells.

40
Q

What can biologics put you at risk of?

A

Risk of tuberculosis, herpes zoster, Legionella pneumophila, and Listeria monocytogenes

41
Q

What are the 2 main types of transplants?

A
  1. Solid organ transplant

2. Stem cells in haematological malignancy (bone marrow transplant)

42
Q

What do anti-rejection treamtments do after transplants?

A

Anti-rejection treatment suppresses cell mediated immunity to stop effects of cytotoxic and natural killer cells.

43
Q

What does the degree of immunosuppression required after transplant depend on?

A

Degree of immunosuppression varies on how closely the donor and recipient are matched and organ involved.

44
Q

Example of diary of infections in transplantation

A
  1. The initial disease e.g. HBV
  2. Surgery and hospital admission e.g. S. aureus wound infection
  3. Organ receipt e.g. Toxoplasmosis, CMV
  4. Opportunistic infection during initial immunosuppression (initial 3/12, e.g. CMV, Aspergillus)
  5. Later opportunistic infection (after 3/12, e.g. Zoster, Listeria)
45
Q

General principles of infections in immunocompromised patients:

A

Treat the known infection – empirical, need specimens from likely site of infection to guide therapy

E.g. remove catheters

Reverse defect if possible/stop immunosuppression

Prevention most important

46
Q

In which patients should live vaccines be avoided?

A

in T-cell deficient

47
Q

Clinical Case 1:

  • 19 yo student, bruising, fever
  • Diagnosed with acute myeloid leukaemia (AML). Chemotherapy started
  • First 2 courses uneventful
  • Few days into final course chemo, febrile neutropenic. Blood cultures E. coli. Given piperacillin/tazobactam.

Where could the focus be?

A

What can cause neutropenia?
- Chemo

E coli may have come from:

  • Ulcers in gut caused by chemo
  • UTI
  • Hospital acquired pneumonia
48
Q

For nosocomial pneumonia and bacterial infections in neutropenic patients, what should be given straight away?

A

Piperacillin with tazobactam

49
Q

Clinical Case 1:

One week later blood cultures have yeast – Candida albicans

Treatment?

A

Candida albicans likely to have come from a line infection

Treatment:

  • Take line out
  • Antifungal therapy (broadspectrum) –> Liposomal amphotericin B, followed by fluconazole treatment
50
Q

What is fluconazole?

A

Fluconazole is an antifungal medicine

51
Q

What gene is affected in CGD?

A

pg91^phox

52
Q

What complex is affected in CGD?

A

NAPDH oxidase complex

53
Q

Why are males more affected by CGD?

A

Gp91^phox is encoded by the X chromosome (females are normally carriers)

Yr 2 - Clinical Pathology (80 decks)

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