Immunodeficiencies and Fungal Infections Flashcards
What are primary immunodeficiencies?
- Group of > 300 rare, chronic disorders in which part of the body’s immune system is missing or functions improperly
- Can affect a single part of the immune system or multiple components
What are primary immunodeficiencies caused by?
Single gene defects
What are secondary immunodeficiencies?
- Acquired diseases affecting the immune system and/or treatments negatively influencing the immune system.
- Components of the immune system itself are all present and functional
Give examples of secondary immunodeficiency.
- HIV infection
- Patients receiving treatment for malignancy
What types of primary immunodeficiencies are there?
- Antibody deficiency
- Cellular immunodeficiency
- Innate immune disorders
What are antibody deficiencies characterised by?
- Characterised by a deficiency of 1 or more subclasses of antibodies due to defective B cell function
- Absence of mature B-cells
What are cellular immunodeficiencies characterised by?
Characterised by impaired T-cell function or the absence of normal T-cells
What are innate immune disorders characterised by?
- Defects in phagocyte function
- Complement deficiencies
- Absence or polymorphisms in pathogen recognition receptors
What infections are associated with antibody deficiencies?
- Recurrent bacterial infections of the upper and/or lower respiratory tract
- S pneumonia, H influenzae
What infections are associated with cellular immunodeficiencies?
- Unusual or opportunistic infections often combined with failure to thrive
- Pneumocystic jirvecii, CMV(pneumonia)
What infections are associated with defects in phagocyte function?
- Staph aureus (sepsis, skin lesions, abscesses in internal organs)
- Aspergillus infections (lung, bone and brain )
What infection is associated with complement deficiency?
N. meningitidis
How can primary immunodeficiencies be recognised?
Be suspicious of infection that is:
- Severe: requires hospitalisation or IV antibiotics
- Persistent: won’t completely clear up or clears very slowly
- Unusual: caused by an uncommon organism
- Recurrent: keeps coming back
- Runs in the family
How can HIV/AIDS present in paediatrics?
- Recurrent common childhood RTIs
- Persistent oral thrush
- Erythematous papilar rash
- Generalised lymphadenopathy
- recurrent/disseminated VZV/HSV infections
- Failure to thrive
- Developmental delay
- Opportunistic infections: CMV, pnumoniae/retinitis, PCP( pneumocystic jirovecii pneumonia)
What is the inheritance of chronic granulomatous disease?
- 65% X-linked
- 35% autosomal recessive
How does chronic granulomatous disease present?
-Life-threatening recurrent severe bacterial and fungal infections
What is a curative treatment option in chronic granulomatous disease?
Haematopoietic Stem Cell Transplant
What is the main cause of death in chronic granulomatous disease?
Invasive aspergillosis
-Life-time incidence 25-40%
Mortality 35%
How is chronic granulomatous disease diagnosed?
DHR test
-Non-fluorescent rhodamine derivative oxidised by NADPH oxidase to green fluorescent compound
In what circumstances can invasive fungal infections present?
- Symptom of primary immunodeficiency
- Children with neutropenia due to leukaemia and/or chemotherapy
- Invasive candidiasis in premature neonates due to immature immune system
- Children admitted to PICU, treated with broad-spectrum antibiotics and abdominal surgery
What are the features of candida infection?
- Endogenous species
- Transmitted by birth canal, hands of health care workers
- Positive blood cultures
- Presents with candidemia
- Budding of yeast cells
- Pseudohyphae in tissue
- Metastatic foci
What are the features of aspergillus infection?
- Exogenous species
- Transmitted by air, water and environment
- Negative blood cultures
- Presents with pulmonary disease
- No sporulation in vivo
- Hyphal growth in tissue
- Angio-invasive
What is the incidence of neonatal candidaemia?
- > 1500g <1%
- 750-1500g 3%
- <750g 12%
What is the mortality of neonatal candidaemia?
20-40%
How does neonatal candidaemia present?
- Presents in the 2nd/3rd week of life
- Sepsis syndrome
- Thrombocytopenia
- Hyperglycaemia
Give examples of risk factors for neonatal candidaemia.
- Extreme prematurity
- Extremely low birth weight
- Indwelling catheters
- Hyperglycaemia
- Immunosuppression
- Broad-spectrum antibiotics
