T2-L7: Infections in the Immunocompromised Host Flashcards
Give examples of innate defences against pathogens.
- Skin (barrier, serum, normal flora) e.g. burns
- Mucous membranes (tears, urine flow, phagocytes)
- Lungs (goblet cells, muco-ciliary escalator. Cystic fibrosis)
- Interferons, complement, lysozyme, acute phase proteins
- Normal commensal flora in gut – antibiotic treatment alters flora leading to infection such as C. difficile, Candida spp.
What is the second line of defence against pathogens?
Neutrophils
What are the two types of neutrophil defects?
Neutropenia puts you ate risk of infection. Very low numbers lead to a high susceptibility.
- There are quantitative defects (less neutrophils present). This is common. The main causes include cancer treatment, bone marrow malignancy, aplastic anaemia drugs. They are known as Neutropenic. - Qualitative defects - The neutrophils do not work properly. These are very are. There could be problems with chemotaxis - congenital issues could include` inadequate signalling. It could also be problems with killing power e.g. Chronic Granulomatous Disease - problems with NADPQ complex in phagocytises.
What types of infections do neutropenic patients usually get? How do we treat this?
Infections:
- Patients commonly get Staph aureus due to lines, e. Coli because the chemotherapy can cause them to have ulcers and mucositis in the gut. Gut bacteria can cross the bowl and into the bloodstream to cause a bacteraemia - Low pathogenicity organising can cause infections such as coag neg staph - stick to plastic in long lines - Fungal. Infections - candida spp., aspergillus spp. (spores can be breathed in the air like healthy people do but this will lead to an infection in the alveoli) - Viruses
Treatment:
- Empirical therapy - Treatment is given broad therapy including that for pseudomonas e.g. Antipseudomonal penicillin (Tacizcil) and gentamicin (aminoglycoside) - Patients may not get batter with first line therapy. Second line treatment could be carbapenem e.g. Meropenem
What are causes of T cell deficiencies?
- Congenital deficiencies are rare. T helper dysfunction may include hypogammaglobulinemia
- Acquired deficiencies are more common e.g. from ciclosporin treatment after transplantation (decreases graft virus host disease and rejection), steroids
- Viral causes such as HIV
What type of pathogens infect patients with T cell deficiencies?
If T cell different you are more likely more unusual bacteria.
- May be intracellular - Bacteria – Listeria monocytogenes (gram positive bacillus e.g. found in soft cheese, can grow in the fridge and so whey pregnant women need to be careful with sell by dates), Mycobacteria - Viral – such as those seen after transplants - HSV, CMV, VZV (Herpes Viruses) - treatment with e.g. acyclovir and ganciclovir - Fungal – e.g. Candida spp., Cryptococcus spp. - Protozoan and parasitic infections also are common in T cell deficiencies such as Cryptosporidium parvum - oocysts shed by cattle/humans. Faecal oral route and Toxoplasma gondii.
Give causes of hypogammaglobinaemias.
Low antibody account. This can be congenital (rare) such as X-lined agammaglobinaemia or acquired. Acquired can be due to multiple myeloma and burns patients (due to loss of serum and proteins).
What pathogens typically infect hypogammaglobinaemic patients?
Usually encapsulated bacteria e.g. Step. Pneumonia. Can also get Giardia parasitic infection which can be picked up from water. The way to treat this is to replace the antibodies by immunoglobulin therapy.
What are causes of complement deficiencies?
It is hereditary but rare - this can cause frequent, serious Step. Pneumoniae infections as poor quality opsonisation.
Which deficiency can lead to Neisseria meningitidis?
C5-C8
Why are patients with a splenectomy susceptible to infection?
- Reasonable common
- Can happen due to trauma, surgical or functional e.g. sickle cell anaemia - the spleens gets matted and destroyed by the disease and so does not work
- Spleen is the source of complement and antibody producing B-cells and removes opsonised bacteria from the blood
- It is again the encapsulated organism that causes the disease - S. pneumoniae, Haemophilus influenzae type B (has a vaccination now), N. meningitidis, malaria
- High mortality associated with this as they can get an overwhelming infection quickly. Often they would have antibiotics at home to take if they have a chest infection for example to manage it. They are educated to know to go seek treatment if unwell.
- Prophylactic penicillin is also given
How can we use bioloigics in the treatment of immunocompromised patients?
- Antibodies or other peptides that can be given to immunocompromised patients as a part of immunomodulation or cancer treatment
- Inhibit inflammatory cytokine signals e.g. tumour necrosis factor or TNF, inhibiting T-cell activation, or depleting B-cells. This can have unintended consequences. Certain biologics can lead to certain infections
- E.g. used in severe rheumatoid arthritis
Risk of tuberculosis, herpes zoster, Legionella pneumophila, and Listeria monocytogenes (looks like T cell organism problems)
Why are patients with an organ transplant susceptible to infection?
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 and organ involved.
Susceptibility can occur at the following stages:
1. The initial disease acquired at birth e.g. HBV, now have end stage liver disease due to cirrhosis 2. Surgery and hospital admission and so at risk of infection such as S. aureus wound infection 3. Organ receipt - donor may have infection such as Toxoplasmosis, CMV. This is tested for, we minimise this with treatment. 4. Opportunistic infection during initial immunosuppression (initial 3 months, e.g. CMV, Aspergillus) 5. Later opportunistic infection (after 3 months, e.g. Zoster, Listeria, pneumocystis, pneumonia). If at risk if this we give them cotrimoxazole to prevent them getting a PCP infection.
How is infection in immunocompromised patients managed?
- Treat the known infection – empirical, need specimens from likely site of infection to guide therapy
- Remove the foreign body which is infected e.g. the line or catheter
- Reverse defect if possible/stop immunosuppression
- Prevention most important
How do we investigate infections?
Investigation of infections
- History and exam - Urgent diagnosis and treatment - Blood culture - Respiratory samples - Other samples as system suggest e.g. urine, serology samples (antibody and antigen) - Radiology e.g. Aspergillus and histology
