infection - immunocompromised host

Question 1

what is an immunocompromised host?

Answer 1

state in which the immune system is UNABLE to respond Appropriate and Effectively to infectious microorganisms

due to defect in 1 or more components of the immune system

Question 2

what is immunodeficiency caused by?

Answer 2

defect in 1 or more components of the immune system

e.g. T, B cells, antibody, phagocytes

Question 3

why is a host ‘immunocompromised’?

Answer 3

1. primary immunodeficiency: congenital - intrinsic gene defect: missing protein, missing cell, non-functional components
2. secondary immunodeficiency: acquired - due to underlying disease / treatment:
   decrease production / function of immune OR increase loss (catabolism)

Question 4

when do you suspect an immunodeficiency?

Answer 4

infections suggesting underlying immune deficiency defined as SPUR
Severe (death if not treated)
Persistent (despite standard treatment)
Unusual (site)
Recurrent (infection)

Question 5

what are the 10 warning signs of PIDs? (slide 10)

Answer 5

1. 4+ ear infections in 1 year
2. 2+ sinus infections in 1 yr
3. 2+ months of antibiotics with little effect
4. 2+ pneumonia within 1 year
5. failure to gain weight / thrive as a child
6. recurrent / deep skin / organ abscesses
7. persistent thrush (mouth) / fungal infection (skin)
8. need for IV antibiotics to clear infections
9. 2+ deep-seated infections - including septicaemia
10. family history of PID

Question 6

what are the limitations of the ‘10 warning signs’?

Answer 6

1. general use: lack of population-based evidence (FH, failure to thrive, diagnosis of sepsis treated with IV meropenem)
2. PID pts with different defects / presentations: T/B cells / phagocytes / complements, infections with subtle presentation
3. PID patients with non-infectious manifestation: autoimmunity, malignancy, inflammatory response

Question 7

what are some examples of primary immunodeficiency diseases of clinical importance?

Answer 7

1. antibody deficiencies: X-linked (Bruton’s disease) - patient unable to produce Ab or correct amount of Ab
2. Combined T & B cell: SCID (severe combined immunodeficiency)
3. phagocytic defects: Chronic Granulomatous disease
4. other cellular immunodeficiencies: hyper-IgE syndrome

Question 8

what are the diagnosis of patients with primary immunodeficiency diseases?

Answer 8

CVID: common variable immunodeficiency (low antibodies - like Bruton’s)
SCID: T & B cell
Chronic Granulomatous disease

Question 9

what are the presentation of primary immunodeficiency diseases in terms of age of symptom onset?

Answer 9

<6 months: T cell / phagocyte (Ig from mother still)
> 6 months - < 5 years: B cell / antibody / phagocyte
> 5 years & later life: B cell / antibody / complement / secondary immunodeficiency

(T cell presents early - wouldn’t live beyond 6 months otherwise)

Question 10

what is the presentation of patients with chronic granulomatous disease? (CGD)

Answer 10

pulmonary Aspergillosis (allergic reaction to the fungus: lung / asthma / CF) - CT scan
skin infections (granulomas on skin - can't clear infection)

Question 11

what is the management of primary immunodeficiency diseases?

Answer 11

1. supportive: prophylactic antimicrobials, passive immunisation, nutrition suport (vit A, D), avoid live-attenuated vaccines
2. specific: regular immunoglobulin therapy (IVIG), haematopoietic stem cell therapy
3. comorbidities: autoimmunity & malignancies, organ damages (LFT), avoid radiation exposure

immunoglobulin replacement therapy: life-long treatment

Question 12

what are causes of secondary immune deficiencies?

Answer 12

decreased production of immune components:
malnutrition, infection (HIV), liver disease, lymphoproliferative diseases, SPLENECTOMY (causes: sickle cell anaemia), congenital, infiltration (trauma))

Question 13

why is the spleen so important?

Answer 13

immune function:

1. against bloodborne encapsulated bacteria
2. antibody production: acute IgM, long-term IgG
3. splenic macrophages: REMOVE opsonised microbes, remove immune complexes

Question 14

risks of asplenic / splenectomised patients?

Answer 14

1. increase susceptibility to encapsulated bac: H. influenza, N. meningitidis, strep pneumoniae
   can lead to sepsis & meningitis (OPSI) - overwhelming post splenectomy infections

Question 15

what are managements for asplenic patients?

Answer 15

life- long PENICILLIN prophylaxis
immunisation (NOT live-attenuated) against encapsulated bac
medic alert band

Question 16

why are patients with haematological malignancy at an increased susceptibility to infections?

Answer 16

1. chemotherapy-induced neutropenia (low neutrophils)
2. vascular catheters
3. chemotherapy-induced mucosal damage (less barrier & IgA)

treat with empirical Abx & assess risk of sepsis

Question 17

what can lead to secondary immune deficiencies?

Answer 17

increased loss / catabolism of immune components:
protein-losing conditions (loose complements) - nephropathy
burns

Question 18

which types of infection leads to which type of deficiency?

Answer 18

virus & fungi - T cell deficiency

Bacteria & fungi - B cell / granulocytes deficiency