Flashcards in Infection in the immunocompromised host Deck (22):
What are examples of innate defences?
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
What are the classifications of immunodeficiencies?
Congenital or primary
Acquired or secondary
What is the '2nd line of defence'?
Neutrophils (NE) very important after initial breach of innate defences
What defects can occur in the second line of defence (NE)
Qualitative defects (e.g. lose ability to kill or chemotaxis) or
Quantitative defects (less present)
What are examples of qualitative defects in neutrophils to do with chemotaxis?
Chemotaxis – rare, congenital, inadequate signalling, abnormality in receptors or NE movement
What are examples of qualitative defects in neutrophils to do with killing power?
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
What are causes of quantitative defects in neutrophils?
- cancer treatment, bone marrow malignancy, aplastic anaemia caused by drugs
>50% those with ________ infections will die in 24hrs if not treated
What infections are neutropenic patients most susceptible to?
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.
How are infections in neutropenic patients treated?
Treatment – broad spectrum. An aminoglycoside and an antipseudomonal penicillin, 2nd line treatment e.g. a carbapenem, then antifungals, remember viruses
What are the causes of T cell deficiencies?
Congenital – rare
Acquired – drugs e.g. ciclosporin after transplantation (decreases graft versus host disease and rejection), steroids
Acquired – viruses e.g. HIV
What are the common opportunistic pathogens in T cell deficiencies?
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.
What protozoan/parasitic infection are most common in T cell deficient patients?
Cryptosporidium parvum – Sporozoa
What are Hypogammaglobulinaemias?
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
What are the features of complement deficiency?
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
What are the features of a splenectomy?
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
What are biologics?
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
What does anti-rejection treatment do?
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.
What are the opportunities for infection in organ transplantation?
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)
What are the general principles of management of infection in transplant patients?
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
What investigations are done when infection suspected in immunocompromised patients?
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
Imaging studies e.g. X ray/CT chest, MRI