Infection In The Immunocompromised Host

Question 1

Define an immunocompromised host

Answer 1

An individual who has one or more defects in the normal host defences leaving them susceptible to infection

Question 2

Who is immunocompromised?

Answer 2

Congenital or primary defects, which are relatively uncommon
Acquired or secondary - broad category which is more common
Immunosuppressive therapy related to cytotoxics, radiation, long term steroids, monoclonal therapies
Physiological immunosuppression (Diabetes, elderly, pregnancy, neonates)
Autoimmune disease (SLE, RA)
Splenectomy (trauma, or functional asplenia)
Toxicity due to alcohol
Acquired immunodeficiency secondary to infection (HIV)

Question 3

Immunosuppression: number or function may be affected

Answer 3

Phagocytic capacity e.g. neutropaenia or a defect in neutrophil function
Cellular - T cells
Humoral - B cells/immunoglobulins
Complement deficiency
Locally reduced immune function e.g. lymphoedema

Question 4

How to spot an immunodeficient patient

Answer 4

History of recurrent infections or failure to thrive
End organ damage eg bronchiectasis
Family history
Ask about alcohol, IVDU history
History of immunosuppressive therapy for CTD, transplant, tumours, leukemia’s, myeloma
Often present with unusual or opportunistic pathogens
Increased risk of severe infections

Question 5

Neutropenia is common after chemotherapy, what is the definition and management?

Answer 5

Common after chemotherapy
Patients ring up with history of rigors, and if neutropaenic will be admitted to haem or onc wards.
Definition of neutropaenia <0.5-1.0 x 109/l
Greatest risk of infection with Neut count of <0.1 and prolonged duration

Question 6

Common bacterial pathogens in neutropaenics

Answer 6

May be Gram negative or Gram positive
Line related e.g. Staph aureus, coagulase negative staphs, or environmental organisms like pseudomonas
Organisms which may translocate across inflamed mucosa e.g. E.coli, Enterococci spp.

Question 7

Fungal infections associated with increased morbidity and mortality

Answer 7

Candida or yeasts
- often line related
- may be cultured from blood
Aspergillus or molds
- after prolonged neutropaenia may present with fungal balls in lungs
- Difficult to diagnose, may require bronchoscopy

Treatment for both are antifungals (eg Fluconazole or Amphotericin) and removal of lines.
Can consider using Granulocyte Colony Stimulating Factor (G-CSF) to improve neutrophil numbers

Question 8

Splenectomy

Answer 8

May occur in traumatic situation or as a result of elective surgery
Some conditions are said to result in functional asplenia eg UC, coeliac, sickle cell, SLE, RA
Patients are at higher risk of developing infections due to encapsulated bacteria eg Streptococcus pneumoniae, N. meningitidis and Haemophilus influenzae

Question 9

Prevention of post-splenectomy infection

Answer 9

Immunization (prior to surgery if possible)
Pneumovax
Haemophilus influenzae B (Hib)/meningitis C (Menitorix)
Meningitis B
Meningitis ACWY (one month later)
Influenza vaccine annually
Life-long Penicillin prophylaxis if high risk
Low risk – may discontinue after 2 years
Early therapy (eg home supply of Amoxycillin)

Question 10

Pneumocystis jiroveci causes Pneumocystis pneumonia or PCP

Answer 10

Silver stain from BAL

Question 11

Normal alveoli and PCP

Answer 11

Question 12

Pneumocystis pneumonia PCP

Answer 12

The most common life-threatening infection in AIDS patients in developed countries prior to HAART
AIDS defining illness in 60%
Occurs in 80% of AIDS patients in absence of antibiotic prophylaxis

Question 13

Overview of PCP

Answer 13

Unicellular eukaryote-Fungus
Ubiquitous geographic distribution
Caused infection in patients with underlying T-lymphocyte disorders
AIDS
Lymphoproliferative disorders
CLL
Post stem cell transplantation
Prolonged corticosteroid therapy

Question 14

Treating PCP

Answer 14

Trimethoprim/ sulfamethoxazole
Dapsone/clindamycin
Pentamidine iv
Steroids
If HIV + and CD4 count <200 should be given PCP prophylaxis + HAART

Question 15

Cell mediated immunity defect

Answer 15

Aetiology
AIDS
Lymphoma
Organ transplantation and immunosuppression
Microbes
Intracellular bacteria e.g. Listeria
Mycobacteria
Fungal e.g. cryptococcus, Pneumocystis jirovecii
Viral e.g. EBV, CMV
Protozoal eg Toxoplasma

Question 16

Bronchiectasis -chronic dilation of bronchioles

Answer 16

Question 17

Hypogammaglobulinaemia

Answer 17

Common variable immunodeficiency (CVID)
X linked agammaglobulinaemia (XLA) due to a mutation on the X chromosome affecting the btk gene coding for tyrosine kinase involved in B cell maturation
Lymphomas and myeloma may also present with altered levels of immunoglobulins
Commonly present with recurrent bacterial infections affecting sinuses and lungs - capsulated bugs eg. H.influenzae and pneumococci
Can consider treatment with intravenous immunoglobulins

Question 18

Complement deficiency

Answer 18

Rare genetic disorders which results in certain components being missing
Unable to form the Membrane Attack Complex (MAC) which is responsible for killing capsulated organisms such as Neisseria meningitidis

Question 19

Summary of infections in immunocompromised patients

Answer 19

Neutropaenia is the most commonly observed form of immunocompromise seen in hospitals
Other immunodeficiencies present with unusual opportunistic infections which do not affect a normal host
You can sometimes predict the sort of infection to which a patient is most susceptible, by studying the immune defect.