Infection In Immunocompromised Patients Flashcards
List the innate defence mechanisms of the body
- skin
- resident flora (colonisation resistent)
- complement
- lysozyme
- acute phase reactants
- phagocytes (macrophages, neutrophils)
- spleen
- NK cells
List the adaptive immune mechanisms of the body
- humoural B cells (neutralisation, C1 activation, opsonisation)
- cellular T cells (help macrophages + B cells, kill virus infected cells)
What are the different types of immunodeficiency?
Primary (rare):
- inherited
- exposure in utero to environmental factors
Secondary (common):
- due to underlying disease state
- requires treatment for disease
- common
What developments in healthcare have had a detrimental effect on immunodeficiency?
- improved survival at extremes of life
- improved cancer treatment
- development in transplant techniques
- developments in intensive care
- management of chronic inflammatory conditions
- steroids
Describe the pathogenesis of neutropenia
- caused by things like cytotoxic chemotherapy/therapeutic irradiation (reduction in chemotaxis, phagocytic activity + intracellular killing)
- leads to decrease in proliferation of haemopoietic progenitor cells (responsible for forming neutrophils)
- depletion of marrow reserves (normally high turnover)
- neutropenia = <0.5x10^9/L
(Relative neutropenia = <1x10^9/L + falling)
What pathogens can take advantage of neutropenia?
- gram positive cocci (S. aureus, CoNS, S. viridans, enterococci)
- anaerobes (bacteriodes spp, clostridia spp)
- gram negative bacilli (E.coli, P.aeruginosa, klebsiella pneumoniae, enterobacter spp)
- fungi (candida spp, aspergillus spp.)
Describe features of chronic granulomatous disease
- inherited disorder (X-linked)
- defect in gene which codes for NAPDH oxidase (reduction in production of oxygen radicals leading to defective intracellular killing)
- recurrent bacterial + fungal infections
- abscesses in lung, lymph nodes, skin
- inflammation = widespread granuloma formation
What pathogens can take advantage of chronic granulomatous disease?
Pulmonary infection:
- aspergillus spp
- S. aureus
- nocardia spp (unique to this condition)
List the things that suppress cellular immunity
- DiGeorge syndrome (primary deficiency)
- malignant lymphoma
- cytotoxic chemotherapy
- extensive radiation
- immunosuppressive drugs
- allogenic stem cell transplant (esp if GVHD)
- infections (HIV, mycobacterial, measles, EBV, CMV)
List the immunosuppressive drugs which can affect immunity
- corticosteroids
- cyclosporin (used to prevent organ rejection)
- tacrolimus (more potent form of ^)
- alemtuzumab (anti-CD52 monoclonal)
- rituximab (anti-CD20 monoclonal)
- purine analogues
Describe conditions which affect humoral immunity
- bruton agammaglobinaemia (primary loss of mature B cells)
- lymphoproliferative disorders (decrease antibody production) = CLL, multiple myeloma
- radio + chemotherapy will cause hypogammaglobinaemia
Describe the function of the spleen in defence
- splenic macrophages eliminate non-opsonised microbes (esp encapsulated bacteria)
- site of primary immunoglobulin response (specific opsonising antibody required for phagocytosis of encapsulated bacteria)
What pathogens can take advantage of humoral deficiency/splenectomy/hyposplenism?
- S. pneumoniae
- H. Influenza type B
- N. Meningiditis
Describe the aspects of the skin which helps it as defence
- dry (pathogens like wet environment)
- pH = 5-6
- temperature = 5 or lower
- secretory IgA in sweat (protects)
Describe the pathogenesis of mucosal barrier injury + colonisation resistance
- injury/altered microbiome (antibiotics, diarrhoea etc)
- mucositis
- pain, dysphagia, xerostomia, ulceration
- impaired GI function, alteration in permeability (pathogens from gut to blood)
- altered nutritional status
- possible secondary infection to catheter
What defines severe nutritional deficiency?
- <75% ideal body weight/rapid weight loss
- hypoalbuminaemia
Describe how impaired nutritional status affects immunity
- results in mucositis and metabolic derangements
- compromises host defences
- iron deficiency reduces microbicidal capacity of neutrophils and T cell function
Describe how organ dysfunction + concurrent illness can affect host defences
- eg. Tumours can cause local organ dysfunction (eg. Blockage of bile duct leading to inflammation and infection)
- lung is susceptible
- CNS tumours = spinal cord suppression (loss of cough/swallow reflex, incomplete bladder emptying)
- reduction in removal of pathogens from system
- concurrent illness = diabetes (reduces T cell function), diabetes (reduces opsonisation and chemotaxis)
How is infection risk reduced in solid organ transplants?
- optimal tissue typing
- donor evaluation
- organ procurement
- surgical technique
- tailored immunosuppressive regimen
What is a unique aspect of infection in solid organ transplants?
- they do not present the same as in immunocompetent people
- inflammatory responses are impaired
- symptoms are diminished
- muted clinical and radiological signs
What community acquired pathogens are individuals at risk of following a solid organ transplant?
- pneumococcus, listeria, salmonella, legionella
- viruses: influenza, parainfluenza, RSV
What nosocomial infections are individuals at risk of following a solid organ transplant?
- resistant gram positive and gram negative bacteria
- C. Diff
- fungi
What types of infection are we trying to avoid following solid organ transplants?
- community acquired
- nosocomial
- donor-derived infections (latent/active)
- reactivation of infections (eg. TB/HSV)
- opportunistic pathogens (eg. Aspergillus)
Where can neutropenic fever arise from?
- solid tumours receiving cytotoxic chemotherapy
- non-leukaemic haematological malignancies
- acute leukaemias receiving induction chemotherapy
Describe the pathogenesis of neutropenic fever
- neutropenia
- abnormal antibody production
- T cell defects
- organ dysfunction
- deficient nutritional status
- affect on IV access devices
- concurrent illness
