Infections in the Immunocompromised Host

Question 1

What is the definition of the immunocompromised host?

Answer 1

Disruption of specific defence of an organ/system. Humoral/cellular.

Question 2

What are the common features of infections in the immunocompromised?

Answer 2

• Can often predict the infection if you know the underlying disease and immune deficit
• Often organsims of low pathogenicity/opportunistic infections

Question 3

What innate defences may be disrupted?

Answer 3

• Skin (barrier, sebum, normal flora) – iv or urinary catheters, surgery and burns
• Interferons, complement, lysozyme, acute phase proteins
• Mucous membranes (tears, urine flow, phagocytes)
• E.g. Lungs – goblet cells, muco-ciliary escalator. Cystic fibrosis
• Normal commensal flora in gut – antibiotic treatment alters flora e.g. C. difficile, Candida spp.

Question 4

How are immunodeficiencies classified?

Answer 4

• Congenital or primary

- Acquired or secondary

Question 5

Which cell presents the 2nd line of defence?

Answer 5

• Neutrophils (NE) very important after initial breach of innate defences
• Less NE – increasing infection

Question 6

What are the possible neutrophil defects that may be present?

Answer 6

• Qualitative defects (e.g. lose ability to kill or chemotaxis) or
• Quantitative defects (less present)

Question 7

What are the features of qualitative neutrophil defects?

Answer 7

– Chemotaxis – rare, congenital, inadequate signalling, abnormality in receptors or NE movement
–Killing power - inherited, Chronic Granulomatous Disease. NE fail to mount a respiratory burst in phagocytosis. Deficient in NADPH oxidase so hydrogen peroxide not formed. At risk of Staph. aureus infections

Question 8

What are the features of quantitative neutrophil defects?

Answer 8

eg - cancer treatment, bone marrow malignancy, aplastic anaemia caused by drugs
“Neutropenic”
Esp. imp. when 50% will develop an infection. Highly lethal if not treated quickly with correct antibiotics – empirical therapy, >50% those with Pseudomonal infections will die in 24hrs if not treated

Question 9

What sort of infections might you see in neutropenic patients?

Answer 9

• Bacterial infections – Gram negative bacilli (e.g E. coli), Gram positive cocci (e.g. S. aureus ) - often normal flora. E.g. Coagulase negative staph
• Fungal infections – Candida spp. , Aspergillus spp.

Question 10

What treatment is given for infections in neutropenic patients?

Answer 10

Broad spectrum. An aminoglycoside and an antipseudomonal penicillin, 2nd line treatment e.g. a carbapenem, then antifungals, remember viruses

Question 11

What are the potential T cell deficiencies?

Answer 11

• Congenital – rare
• Acquired – drugs e.g. ciclosporin after transplantation (decreases graft versus host disease and rejection), steroids
• Acquired – viruses e.g. HIV

Question 12

What kind of infections might you see in patients who are T cell deficient?

Answer 12

• May be intracellular
• BACTERIAL – Listeria monocytogenes (food), mycocteria – MTB, MAI
• VIRAL – e.g. leukaemia and transplanted pnts - HSV, CMV (pre–emptive treatment), VZV. Serological testing, prophylaxis and treatment with e.g. aciclovir and ganciclovir
• FUNGAL – e.g. Candida spp., Cryptococcus spp.
• PARASITIC - Cryptosporidium, symptomatic treatment only. Toxoplasma. Strongyloides - may get gram -ve sepsis as larvae move.

Question 13

What are hypogammaglobulinaemias?

Answer 13

• Antibody problems
• Congenital - rare
• Acquired – multiple myeloma, chronic lymphocytic leukaemia, burns

Question 14

What sort of infections do you see in patients with hypogammaglobulinaemias?

Answer 14

Usually encapsulated bacteria e.g. S. pneumoniae in the resp. tract or e.g. Giardia lamblia or Cryptosporidium in GIT

Question 15

What kind of infections would you see in complement deficiency?

Answer 15

• Encapsulated bacteria. Need complement to help kill organisms. Earlier defect in pathway then greater no. of organisms may infect.
• Classical and Alternative
• e.g. C5-8 then Neisseria meningitidis is important – lysis not achieved via membrane attack complex as MAC not formed. 50-60% pnts will have 1 episode of disease in life
• Frequent, serious S. pneumoniae infections as poor quality opsonisation
• Hereditary and very rare

Question 16

What are the potential consequences of a splenectomy?

Answer 16

• Spleen - source of complement and antibody producing B-cells, removes opsonised bacteria from blood.
• Streptococcus pneumoniae, Haemophilus influenzae type B, N. meningitidis, malaria
• High mortality, vaccination, prophylactic penicillin, education – seek help if unwell

Question 17

What are biologics?

Answer 17

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

Question 18

What are the immunological risks of biologics?

Answer 18

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

Question 19

What are the consequences of organ transplantation?

Answer 19

Anti-rejection treatment suppresses cell mediated immunity to stop effects of cytotoxic and natural killer cells. Degree of immunosuppression varies on how closely the donor and recipient are matched.

Question 20

What infections are possible in organ transplantation?

Answer 20

1. The initial disease (e.g. HBV, liver transplant)
2. Surgery and hospital admission (e.g. ventilator acquired pneumonia, S. aureus wound infection)
3. Organ receipt (e.g. Toxoplasmosis, CMV), patient matching
4. Opportunistic infection during initial immunosuppression (initial 3/12, e.g. CMV, Aspergillus)
5. Later opportunistic infection (after 3/12, e.g. Zoster, Listeria)

Question 21

Which patients need to avoid live vaccines?

Answer 21

T cell deficient