Infections in the Immunocompromised

Question 1

What leads to someone becoming immunosuppressed?

What tends to cause infections and how can you predict them?

Answer 1

Disruption of specific defence of an organ/system

you can often predict the infection if you know the underlying disease

infections can be caused by organisms of low pathogenicity / opportunistic infections

Question 2

What are the 2 host defences against infection?

What are the 2 types of infection

Answer 2

1. Non-specific innate immune system
2. Specific adaptive immune system - humoral or cellular

Infections can be congenital or acquired

Question 3

What are the innate defences against infection?

Answer 3

Skin:

• barriers
• sebum
• normal flora

Mucous membranes:

• tears
• urine flow
• phagocytes

Lungs:

• ​goblet cells
• muco-ciliary escalator

Other:

• interferons
• complement
• lysozyme
• acute phase proteins

Question 4

What general things can make someone more susceptible to infection?

Answer 4

• Extremes of age
• pregnancy
• malnutrition

Question 5

What happens if the normal commensal flora in the gut are altered?

Answer 5

Antibiotic treatment can kill/alter the normal commensal flora in the gut

this increases susceptibility to C. Diff and Candida spp. Infections

Question 6

Which infections are burns patients susceptible to?

Answer 6

Infections by pseudomonas and streptococcus

Question 7

At which stage of infection are neutrophils important?

What happens if someone was to have less neutrophils?

Answer 7

Neutrophils are important after the initial breach of innate defences

if someone has less neutrophils, they have an increased risk of contracting an infection

Question 8

What are the 2 categories of neutrophil defects and the differences between them?

Answer 8

Qualitative defects:

• this is when the neutrophils are present, but they don’t work properly

Quantitative defects:

• this is when there are not enough neutrophils present to be effective

Question 9

What are examples of qualitative neutrophil defects?

Answer 9

Neutrophils lose the ability to kill or chemotaxis

• e.g. Inadequate signalling
• chronic granulomatous disease

Question 10

What infection is someone with chronic granulomatous disease more susceptible to?

Answer 10

Staphylococcus aureus infection

Question 11

What may quantative neutrophil defects lead to?

In which patients is this seen?

Answer 11

Neutropenia

this is a lack of neutrophils

• cancer treatment
• bone marrow malignancy
• aplastic anaemia from drug use

Question 12

What is aplastic anaemia?

Answer 12

A rare disorder in which the bone marrow fails to produce enough blood cells

Question 13

When is neutropenia particularly clinically important?

Answer 13

If neutrophil count is < 0.5 x 10⁹

or

if neutropenia is prolonged over long periods of time

e.g. In AML patients who have neutropenia for weeks are at more risk of bacterial or fungal infections

Question 14

What infection is particularly prominent in neutropenia patients?

Answer 14

>50% of neutropenia patients are prone to infection with high mortality

>50% of those with pseudomonas infections will die in 24 hours if they are not treated

Question 15

What is the treatment for infection in neutropenic patients?

Answer 15

They are treated with a broad spectrum antibiotic which includes defence against pseudomonas

antipseudomonal penicillin +/- gentamicin

if first line treatment is not effective, the second line treatment is carbapenem

Question 16

What opportunistic infection are neutropenia patients more susceptible to?

Answer 16

Infections with normal flora - coagulase negative staphylococcus

this is a low pathogenicity organism which can enter the blood

Question 17

Which bacterial infections are more prominent in neutropenic patients?

Answer 17

E. Coli, Staphylococcus aureus

look for skin infections as chemotherapy can lead to ulcers and bacteraemia

Question 18

Which fungal infections are neutropenic patients more susceptible to?

Answer 18

Candida spp. , aspergillus spp.

the spores will enter the alveoli and cause fungal pneumonitis

Question 19

Why is it important to try and prevent infections in neutropenic patients?

What treatment can be used?

Answer 19

Cancer patients may need to have chemotherapy delayed due to infection

this can worsen the cancer outcome

granulocyte stimulating factors (GCSF) are used to try and prevent immunosuppression

Question 20

What are the different types of T cell deficiencies?

Answer 20

Congenital:

• these are rare
• T helper dysfunction +/- hypogammaglobulinaemia

Acquired:

• drugs e.g. ciclosporin after transplantation and steroids
• viruses e.g. HIV

Question 21

What opportunistic bacterial infections are T cell deficient patients susceptible to?

Answer 21

Listeria monocytogenes

this grows in fridge temperatures and comes from food such as Brie cheese

mycobacteria

Question 22

Which viral infections are T cell deficient patients susceptible to?

What is the treatment?

Answer 22

Herpes viruses - herpes simplex, cytomegalovirus and varicella zoster

serological testing followed by prophylaxis and treatment with aciclovir and gangciclovir

Question 23

What fungal infections are T cell deficient patients susceptible to?

Answer 23

Candida spp. , cryptococcus spp.

new patients with HIV usually present with cryptococcus meningitis

this has a thick capsule to help prevent it from phagocytosis

Question 24

What is the difference with varicella zoster virus in a T cell deficient patient?

Answer 24

Shingles will be much more severe

this means that the skin is much more prone to secondary infection by staphylococcus aureus

Question 25

Which protozoan/parasitic infections are T cell deficient patients more susceptible to?

Answer 25

**Cryptosporidium parvum** and **Toxoplasma gondii**

Question 26

What are the characteristics of cryptosporidium parvum? How is it treated and how long does it take to recover?

Answer 26

Oocysts are shed by cattle/humans into the water so it is spread via faecal-oral route most patients recover after prolonged illness of up to 3 weeks recovery takes much longer in T cell deficiencies in most cases, only **symptomatic treatment** is used and antibiotics are not given

Question 27

What is meant by hypogammaglobulinaemia? What are the 2 different types?

Answer 27

This is having an antibody level below normal **Congenital:** * x-linked agammaglobulinaemia (rare) **Acquired:** * multiple myeloma * burns

Question 28

What is the treatment for hypogammaglobulinaemia? Which bacteria and parasites tend to cause infection?

Answer 28

It is treated with immunoglobulin to replace the antibodies it is **encapsulated bacteria** that cause problems e.g. **streptococcus pneumoniae** the parasite that usually causes infection is **giardia lamblia**

Question 29

What are the 2 forms of giardia lamblia? What symptoms can it cause?

Answer 29

**Trophozyte form:** * this is the form of the disease which is present in the water **cystic form:** * this is the form of the disease that is ingested * it has a hard shell to stop it from drying out It causes diarrhoea, fatty stools and can cause weight loss

Question 30

What type of infections tend to be present in complement deficiency?

Answer 30

**Encapsulated bacteria** - complement is needed to help kill organisms If the C5-8 section is deficient - **Neisseria meningitidis** is important this is a gram negative coccus that causes meningitis there are **frequent serious S. Pneumoniae** infections due to poor quality opsonisation

Question 31

What can cause splenectomy?

Answer 31

The spleen is a source of complement and antibody producing B-cells it removes opsonised bacteria from the blood splenectomy can be caused by: 1. Traumatic 2. Surgical 3. Functional asplenia e.g. sickle cell disease

Question 32

What are the treatments for infections in splenectomy? Which infections are common?

Answer 32

1. S. Pneumoniae 2. Haemophilus influenzae type B 3. N. Meningitidis 4. Malaria these are mostly encapsulated organisms these infections have high mortality and can be prevented through vaccination and **prophylactic penicillin**

Question 33

What are biologics and how do they work?

Answer 33

They are antibodies or other peptides they inhibit inflammatory cytokine signals e.g. tumour necrosis factor this inhibits T cell activation and depletes B cells they are used in severe rheumatoid arthritis

Question 34

What are the risks associated with biologics

Answer 34

1. Risk of tuberculosis 2. Risk of herpes zoster 3. Risk of legionella pneumonophilia 4. Risk of listeria monocytogenes

Question 35

What are the 2 types of organ transplantation? What treatment is required afterwards and why?

Answer 35

Solid organ transplants - e.g. liver in paracetamol overdose stem cells in haematological malignancy anti-rejection treatment is needed to suppress cell mediated immunity this stops the effects of cytotoxic and natural killer cells

Question 36

What affects the degree of immunosuppression in organ transplants?

Answer 36

The degree of immunosuppression varies on how closely the donor and recipient are matched and the organ involved

Question 37

What are the general principles for management of infection?

Answer 37

* Treat the known infection - need specimens from the likely site of infection to guide therapy * remove catheters and lines * reverse the defect if possible - stop immunosuppression - GCSF * prevention is most important i.e. hand washing

Question 39

What techniques can help in prevention of infection?

Answer 39

* Hand washing, aseptic technique, protective isolation, HEPA air filtration * vaccines (avoid live in T cell deficient patients as this can cause infection) * prophylactic antimicrobials and passive immunoglobulin * special diets

Question 40

In a febrile neutropenic, what treatment should be given?

Answer 40

Broad spectrum anitbiotics **piperacillin / tazobactam**

Question 41

What are the stages involved in treating candida infections?

Answer 41

Start antifungal therapy and remove any lines give **liposomal amphotericin B** (broad spectrum antifungal) followed by **fluconazole treatment** this is an oral agent given for 2 weeks after treatment

Question 42

What is the treatment for lobar pneumonia?

Answer 42

Lobar pneumonia caused by streptococcus pneumoniae is treated with **IV benzylpenicillin**