(14) Infection in the immunocompromised Flashcards
What are the categories of host defences?
- non-specific (innate)
- specific (adaptive - humoral and cellular)
- congenital or acquired
Give examples of innate defences
- skin
- interferons, complement, lysozyme, acute phase proteins
- mucous membranes (tears, urine flow, phagocytes)
- lungs
- normal commensal flora in gut
What about the skin makes it an innate defence system?
- physical barrier
- sebum
- normal flora
What can disrupt the sion as an innate defence system?
- IV or urinary catheters
- surgery
- burns
What about the lungs make them an innate defence barrier?
- goblet cells
- muco-ciliary escalator
Which condition can affect the lungs being an innate defence?
Cystic fibrosis
What can alter the normal commensal flora in the gut?
Antibiotic treatment alters flora e.g. C. difficile, candida spp.
Which states/conditions can cause innate immunity to be less effective?
- extremes of age
- pregnancy
- malnutrition
What are the classifications of immunodeficiencies?
- congenital or acquired
- acquired or secondary
What is the ‘2nd line of defence’?
The neutrophil
When are neutrophils important?
After initial breach of innate defences
Less NE = increasing infection
What two types of defects can you have in neutrophils?
- qualitative defects (eg. lose ability to kill or chemotaxis)
- quantitive defects (less present)
What two things may be affected in qualitative neutrophil defects?
- chemotaxis
- killing power
How does chemotaxis of neutrophils become defective?
- rare
- congenital
- inadequate signalling
- abnormality in receptors
- or abnormality in NE movement
How does killing power of neutrophils become defective?
- inherited
- chronic granulomatous disease
- NE fail to mount a respiratory burst in phagocytosis
- deficient in NADPH oxidase
- hydrogen peroxide not formed (would normally help kill bacteria)
Which infection are you at risk of when the killing power of neutrophils is defective?
Staph. aureus
What causes quantitive defects in neutrophils (neutrophil lack)?
- cancer treatment
- bone marrow malignancy
- aplastic anaemia caused by drugs
What does “neutropenic” mean?
Low level of neutrophils
Neutropenia is especially important when…?
When levels are
How many patients with neutropenia will develop an infection?
> 50%
How serious is pseudomonal infection in neutropenia?
> 50% of those with pseudomonal infections will die in 24 hours if not treated
What treatment would you give to neutropenic patients?
Broad spectrum antibiotics first eg. an aminoglycoside and an antipseudomonal penicillin
2nd line treatment eg. a carbapenem, then antifungals, remember viruses
When giving neutropenic patients a broad spectrum antibiotic, it is important than the spectrum includes what?
Pseudomonas
What does GCSF stand for?
Granulocyte stimulating factors
- used to boost immune system in neutropenic patients
Which bacterial infections are seen in neutropenic patients?
- gram negative bacilli (eg. E. coli)
- gram positive cocci (eg. S. aureus) - often normal flora eg. coagulase negative staph
Which final infections are seen in neutropenic patients?
- candida spp (normal in gut but can translocate across into blood)
- aspergillus spp. (breathed in, infection in lung)
How do patients get T cell deficiencies?
- congential (rare)
- acquired - drugs eg. ciclosporin after transplantation (decreases graft versus host disease and rejection), steroids
- acquired - viruses eg. HIV
What are the bacterial opportunistic infections seen in T cell deficiencies?
- listeria monocytogenes (food)
- mycobacteria - MTB, MAI
What are the viral opportunistic infection seen in T cell deficiencies?
- HSV
- CMV (pre-emptive treatment)
- VZV
Viral opportunistic infections are seen in which patients?
Leukaemia and transplanted patients
How would you manage/treat patients with viral opportunistic infections?
- serological testing
- prophylaxis
- treatment with aciclovir and ganciclovir
The pathogens that affect those with T cell deficiencies tend to be what?
Organisms that like to invade into the cell (intracellular)
What are the fungal opportunistic infections seen in T cell deficiencies?
- candida spp.
- cryptococcus spp.
Why are pregnant women advised not to eat pate and soft cheese?
May contain listeria monocytogenes (this is one of the bacterial opportunistic infections)
What type of bacteria is listeria monocytogenes?
Gram-positive bacillus
What are the protozoan/parasitic infections seen in T cell deficiencies?
- cryptosporidium parvum
- toxoplasma gondii
- strongyloides stercoralis
How is cryptosporidium parvum transmitted?
- sporozoa - oocysts shed by cattle/humans
- faecal-oral route
How long is recovery from cryptosporidum parvum?
Most patients recover after prolonged illness of up to 3 weeks
May take longer in T cell deficient patients, if at all
What treatment is given for cyptosporidium parvum?
Symptomatic treatment only (in most cases)
How is toxoplasma gondii transmitted?
Sporozoa
Humans infected by contact with cat faeces
Or from eg. transplanted heart with the bradyzoites present
How may patients with toxoplasma gondii present?
With lesion in brain and neurological signs
but most immunocompetent patients are asymptomatic
How is strongyloides stercoralis transmitted?
Nermatode
Larvae penetrate skin, migrate
What are the symptoms of strongyloides stercoralis?
Normal patients are asymptomatic or rash of Larva Currens
But immunocompromsied get multiplication, huge invasion of tissues, esosinophilia
May get gram negative septicaemia as larvae move
Who should strongyloides stercoralis be suspected in?
Suspect in patients from tropical counties or old POW patients
What are hypogammaglobulinaemias?
Reduction in antibody levels
How are hypogammaglobulinaemias caused?
- congential eg. X-linked agammaglobulinaemia
- acquired - multiple myeloma, chronic lymphocyte leukaemia, burns
How are hypogammaglobulinaemias treated?
Immunoglobin replacement
Which bacteria are normally involved in hypogammaglobulinaemias?
Encapsulated bacteria eg. S. pneumoniae in the resp. tract or eg. giardia lamblia or cytoptosporidum in the GIT
Give examples of encapsulated bacteria (associated with hypogammaglobulinaemias)
- streptococcus penumoniae
- neisseria meningitidis
- E. coli
- group B strep
- salmonella typhi
- hib
How do you get complement deficiency?
- hereditary
- rare
Which bacteria are a common problem in patients with complement deficiency?
- encapsulated bacteria
- need complement to help kill organisms
- the earlier the defect in the pathway, the greater the number of organisms that may infect
What are the two types of complement?
- classical
- alternative
Which bacteria is specifically important in C-5-C8 defects of the complement pathway and why?
Neisseria meningitidis
Lysis not achieved via membrane attack complex as MAC not formed
50-60% of patients will have 1 episode of disease in life
Why do you get frequent and serious S. pneumoniae infections in complement deficiency?
Poor quality opsonisation
Why is the spleen so important in immunity?
- source of complement and antibody producing B cells
- removes opsonised bacteria from blood
What are the causes of splenectomy?
- traumatic
- surgical
- functional eg. sickle cell anaemia
Which infections are important in splenectomy?
- streptococcus penumoniae
- haemophilus influenzae type B
- N. meningitidis
- malaria
What measures should be taken in splenectomy?
- vaccination
- prophylactic penicillin
- education (seek help if unwell)
High mortality
What are biologics?
Antibodies or other peptides
Aprotein-based drug derived from living cells cultured in a laboratory
What do biologics do?
Inhibit inflammatory cytokine signals eg. TNF, inhibiting T cell activation, or depleting B cells
Biologics are often used for which condition?
Rheumatoid arthritis
What is there a risk of when using biologics?
- tuberculosis
- herpes zoster
- legionella pneumophila
- listeria monocytogenes
Give examples of organ transplantation
- HCV/paracetamol OD requiring liver transplantation (solid organ transplants)
- haematological malignancy requiring sen cell transplantation
How is organ transplantation related to immunodeficiency?
Anti-rejection treatment suppresses cell mediated immunity to stop effects of cytotoxic and natural killer cells
In organ transplantation, what does the degree of immunosuppression vary on?
How closely the donor and recipient are matched
Give an example diary of infections in transplantation
- the initial disease (e.g. HBV, liver transplant)
- surgery and hospital admission (e.g ventilator acquired pneumonia, S. aureus wound infection)
- organ receipt (eg. toxoplasmosis, CMV), patient matching
- opportunistic infections during initial immunosuppression (initial 3/12, e.g. CMV, aspergillus)
- later opportunistic infection (after 3/12, e.g., zoster, listeria)
Give 2 examples of initial opportunistic infections in an organ transplant recipient
- CMV
- aspergillus
Give 2 examples of later opportunistic infections (after 3/12) in organ transplant recipient
- zoster
- listeria
What are the general principles of management of infection in immunodeficient patients?
- treat the known infection - empirical, need specimens from likely site of infection to guide therapy
- eg. remove catheters
- reverse defect if possible/stop immunosuppression
How is investigation of infections carried out?
- history and examination
- urgent diagnosis and treatment
- blood cultures (occasionally bone marrow cultures)
- respiratory samples
- other samples as systems suggest eg. urine
- serology samples (eg. toxoplasma spp.) +/- PCR. Aspergillus antigen +/- PCR
- surveillance cultures
- imaging studies eg. X-ray/CT chest/MRI
How are respiratory samples analysed?
- induced sputa
- bronchoalveolar lavage
- lung biopsy
- microscopy (gram, ZN, fungal and silver stains)
- viral immunofluorescence
- bacterial culture including legionella, TB
- fungal culture
- viral culture +/– PCR
- histology
How are infections in the immunocompromised prevented?
- hand washing/aseptic technique/protective isolation/HEPA air filtration (allografts)
- vaccines (avoid live vaccines in T-cell deficient)
- prophylactic antimicrobials (eg. penicillin, septrin, aciclovir) and passive immunoglobin
- special diet
Which vaccines should be avoided in T cell deficient patients?
Live vaccines
Give some examples of prophylactic microbials
- penicillin
- septrin
- aciclovir
