31 Infections in the compromised host Flashcards
What are primary and secondary defects of innate immune system?
Primary is more common in paediatric population
Secondary more common in adults
Primary -
- complement deficiency
- phagocyte cell deficiencies - e.g chronic granulomatous disease
Secondary -
- burns
- trauma
- surgery
- catheter
- foreign body e.g joint/ shunt
What are defects of adaptive immune system?
Primary
Primary (T/ B cell defects) -
- B cells - Burton-type agammaglobulinaemia due to lymphocyte production error in bone marrow
- T cells - DiGeorge. Thymus problem means lymphocytes cannot mature
- SCID (severe combined immunodeficiency) which is genetic defect in which antibodies cannot be fully formed by B cells, and T cells cannot produce antigen recognition receptors
What are defects of adaptive immune system?
Secondary
Secondary -
- malnutrition
- infectious disease
- neoplasia
- radiation
- chemotherapy
- splenectomy
Which infections cause immunosuppression?
Measles Mumps Rubella EBV CMV HIV HTLV
Mycobacterium tuberculosis/ leprae
Brucella
Burn wound become colonised within few hours of injury. What are most common pathogens?
Pseudomonas Staph aureus Staph pyogenes enterococci Candida
Once skin invaded, can easily invade lymphatics/ blood
Staph epidermidis in blood culture is often contaminant.
In which clinical situations should we be concerned?
IE
Prosthetic joint septic arthritis
Haematological malignancy - why are they risk of infection?
Significant neutrophil deficiency
What are examples of opportunistic pathogens?
Any opportunistic pathogen infection should mean we consider testing patient for HIV
Viruses
HBV HCV HIV Polyomaviruses - BK, JC Adenovirus Herpes - HSV, VZV, EBV, CMV, HHV6, HHV7, HHV8
What are examples of opportunistic pathogens?
Any opportunistic pathogen infection should mean we consider testing patient for HIV
Fungi
Candida Aspergillus Cryptococcus Histoplasma PCP
What are examples of opportunistic pathogens?
Any opportunistic pathogen infection should mean we consider testing patient for HIV
Parasites
Toxoplasma
Strongyloides
What are examples of opportunistic pathogens?
Gram-positive
Staph aureus Coagulase-negative staph Streptococci Listeria Nocardia Mycobacterium TB/ MAC
What are examples of opportunistic pathogens?
Gram negative
Enterobacteraceae
Pseudomonas
Legionella
Bacteroides
How do glucocorticoids cause immunosuppression?
- induce the apoptosis of lymphocytes
- alter leukocyte migration and redistribution
- inhibition of cytokine gene expression, resulting in a decreased release of interleukins (IL), interferons (IFN) and tumor necrosis factor (TNF), such as IL-2, IL-6, IFN-γ and TNF-α,
Histoplasmosis lives in soil, transmitted airborne. Causes mild infection in immunocompetent. Can cause infection in immunocompromised years after exposure
Which countries have histoplasmosis?
Have low threshold for investigation if have ever visited these areas -
USA
SA
Sub-Saharan Africa (African histoplasmosis)
Asia
Histoplasma can spread from alveoli, via lymphatics, and cause disseminated disease many years later.
How to diagnose histoplasma infection?
Culture of blood, sputum, BAL may yield organism
May need bone marrow/ lymph node biopsy
What is treatment of histoplasma infection?
Amphotericin
Itraconazole can be given after for long term prophylaxis
Aspergillus has worldwide distribution. Lives in soil, transmitted airborne. Causes mild infection in immunocompetent.
Invasive aspergillosis has high mortality rate
What are treatment options for invasive aspergillus?
What is prophylaxis?
Treatment -
- Amphotericin B IV
- reduction in steroids/ immunosuppression may be required
Prophylaxis - capsofungin, posaconazole, voriconazole
How to diagnose PCP infection?
BAL sample required
PCR - NNUH
What is treatment of PCP?
Moderate-severe PCP (PaO2 <9.3kPa) -
- co-trimoxazole high dose, 21 days
- plus corticosteroids 40mg BD 5 days, 40mg OD 5 days, 20mg OD 11 days
Mild PCP
- co-trimoxazole oral 21 days
Pentamidine/ dapsone/ primaquine alternatives
Actinomycetes are gram positive rods, closely related to mycobacterium. Different in that they form branching filaments.
Primarily infect lungs or skin, but can spread to kidney/ CNS. Ubiquitous in soil
What are main species of Actinomycetes?
Actinomyces
Nocardia asteroides
Actinomycetes (actinomyces/ nocardia) are slow growing, and easily overgrown by commensals. Therefore need special culture media
What is treatment?
Co-trimoxazole
Sulphonamides
Aminoglycosides
Antibiotics for 6-12 months
MAC affects those who are immunocompromised. Ubiquitous in water
How does it present?
Usually pulmonary involvement
Can affect any system - CNS, liver, bone marrow/ GI
How does MAC treatment differ to M. TB?
MAC is resistant to conventional antituberculosis drugs
High dose azithromycin/ clarithromycin with rifampicin and ethambutol
Continue for 1 year after culture negative
Diagnosis of MAC is important.
How to diagnose?
Culture/ stain on sputum/ blood/ stool depending on symptoms
Often cases of MAC mis-diagnosed as TB
HIV/ HTLV are associated with strongyloides activation and can cause life threatening disseminated infections. Lungs/ brain/ liver most commonly infected
Which countries have strongyloides?
NA
SA
Africa
Asia
What is epidemiology spread of HTLV?
SA
Africa
Asia
NA/ UK/ Australia to lesser extent
Complement deficiency/ asplenia increases risk of infection.
Which organisms?
Encapsulated organisms
Neisseria meningitidis
Neisseria gonorrhoea
Streptococcus pneumoniae
Hameophilus influenzae
Patient presents with candidaemia. What other investigations are required?
Investigate source e.g cannula
Investigate immunodeficiency - HIV test
ECHO
Ophthalmology
27 year old Carribbean woman with SLE, treated with rituximab. Presents with diarrhoea.
What is most likely cause of symptoms?
Cryptosporidium Cyclospora Giardia Isospora Strongyloides
Giardia
Rituximab is monoclonal antibody to CD20, expressed on all mature B cells (except plasma cells) and can cause hypogammaglobulinaemia
No travel history definitely given, so giardia is most likely. Although others (except strongyloides) can be acquired in UK
Renal patient about to receive transplant. She is CMV IgG negative. Potential living donor is CMV IgG positive
What is next step?
Do not go ahead with transplant
Give IVIG post-operatively
Give valganciclovir prophylaxis for 90 days
Transplant and monitor CMV DNA monthly
Transplant with no prophylaxis/ monitoring
Give valganciclovir prophylaxis for 90 days as high risk of primary infection
57 year old with RA about to commence rituximab. HBV serology
HBsAg neg
HBcAb pos
HBsAb 10 MIU/ml
HB DNA <20 IU/ ml
What is next step?
- Do nothing - is now immune to HBV after past exposure
- Monitor HBV DNA/ LFTs weekly
- Offer booster HBV vaccine prior to rituximab
- Start entecavir prophylaxis until end of rituximab
- Start prophylaxis lamivudine before rituximab
Start prophylaxis lamivudine before rituximab and continue for 18 months after cessation of rituximab.
Tenofovir/ entecavir are newer drugs, which may be offered
All B-cell depleting therapies with anti-HBc positive should be on prophylaxis
If HBsAg and anti-HBc positive - should be on full HBV treatment
