Infection in the immunocompromised host

Question 1

What are examples of innate defences?

Answer 1

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

Question 2

What are the classifications of immunodeficiencies?

Answer 2

Congenital or primary

Acquired or secondary

Question 3

What is the ‘2nd line of defence’?

Answer 3

Neutrophils (NE) very important after initial breach of innate defences

Question 4

What defects can occur in the second line of defence (NE)

Answer 4

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

Question 5

What are examples of qualitative defects in neutrophils to do with chemotaxis?

Answer 5

Chemotaxis – rare, congenital, inadequate signalling, abnormality in receptors or NE movement

Question 6

What are examples of qualitative defects in neutrophils to do with killing power?

Answer 6

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 7

What are causes of quantitative defects in neutrophils?

Answer 7

• cancer treatment, bone marrow malignancy, aplastic anaemia caused by drugs

Question 8

> 50% those with ________ infections will die in 24hrs if not treated

Answer 8

Pseudomonal

Question 9

What infections are neutropenic patients most susceptible to?

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

How are infections in neutropenic patients treated?

Answer 10

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

Question 11

What are the causes of 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 are the common opportunistic pathogens in T cell deficiencies?

Answer 12

BACTERIAL – Listeria monocytogenes (food), Mycobacteria – 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.

Question 13

What protozoan/parasitic infection are most common in T cell deficient patients?

Answer 13

Cryptosporidium parvum – Sporozoa

Toxoplasma gondii

Strongyloides stercoralis.

Question 14

What are Hypogammaglobulinaemias?

Answer 14

Antibody problems
Congenital - rare
Acquired – multiple myeloma, chronic lymphocytic leukaemia, burns
Usually encapsulated bacteria e.g. S. pneumoniae in the resp. tract or e.g. Giardia lamblia or Cryptosporidium in GIT

Question 15

What are the features of complement deficiency?

Answer 15

Hereditary, rare
Encapsulated bacteria. Need complement to help kill organisms.
Earlier the defect in pathway, then greater no. of orgs may infect.
Classical and Alternative pathways

e.g. C5-8 then Neisseria meningitidis is important – lysis not achieved via membrane attack complex as MAC not formed.

50-60% pts will have 1 episode of disease in life

Frequent, serious S. pneumoniae infections as poor quality opsonisation

Question 16

What are the features of a splenectomy?

Answer 16

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

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

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.

E.g. Rheumatoid arthritis

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

Question 18

What does anti-rejection treatment do?

Answer 18

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 19

What are the opportunities for infection in organ transplantation?

Answer 19

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 20

What are the general principles of management of infection in transplant patients?

Answer 20

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

Question 21

What investigations are done when infection suspected in immunocompromised patients?

Answer 21

History and examination

Urgent diagnosis and treatment

Blood cultures. Occasionally bone marrow cultures

Respiratory samples – esp. induced sputa, bronchoalveolar lavage and lung biopsy. Microscopy - Gram, ZN, fungal and silver stains. Viral immunofluorescence. Bacterial culture including Legionella, TB. Fungal culture, viral culture +/- PCR. Histology.

Other samples as systems suggest e.g. urine

Serology samples (e.g. Toxoplasma spp.) +/- PCR. Aspergillus antigen +/- PCR
(surveillance cultures)
Imaging studies e.g. X ray/CT chest, MRI

Question 22

What can be done to prevent infections in immunocompromised patients?

Answer 22

Hand washing /aseptic technique / protective isolation / HEPA air filtration (allografts)

Vaccines (avoid live vaccines in T-cell deficient)

Prophylactic antimicrobials (e.g. penicillin, septrin, aciclovir) and passive immunoglobulin

Special diet