What causes Complex and Chronic Lung Infections ?
Mycobacterial (NTM) and Fungal Lung infections
What is NTM ?
Non-Tuberculous Mycobacteria
-mycobacterial species other than those belonging to Mycobacterium tuberculosis complex or those causing leprosy
-found in infected soil and water, contracted through environment to susceptible host
-Usually not transferred from person-person
-Most common are the slow growing Mycobacterium avium complex (MAC) e.g. M.avium, M.intracellulare, M.chimaera
When can a human contract an NTM ?
NTM is found in infected soil and water, contracted through environment to susceptible host
-Susceptible host = immunocompromised, other pre-existing lung conditon (COPD, CF)
Usually not transferred from person-person except in CF patients there is some evidence of cross infectivity
Also bronchiecstasis makes susceptible but does so another way
What are NTM good and bad at fighting ?
Found in environment so contact fungi often
-Resistant to fungi produced antimicrobials
-Good at fighting other bugs
Suck at fighting immune system
-chill if youre normal, immunocompromisation dangerous and is also hard to treat
Compare the specificity of NTM and TM
NTM more lung specific
How is a potential NTM infection investigated ?
1) Clinical features
-Respiratory symptoms (cough, sputum, breathlessness)
-B-symptoms (fever, weight loss, night sweats)
-Haemoptysis
2) Microscopy & Culture, one of the following:
-Two positive sputum cultures
-One positive BAL (bronchoalveolar lavage) sample
-Positive PCR
3) Radiology (usually CT)
-Bronchiectasis with nodules
-Cavitary disease
-Tree-in-bud pattern
Hard to determine if NTM is causative, since environmntal can just be found
How are NTM stained ?
Are acid-fast bacill
Mycobacteria are acid fast
How is an NTM infection treated ?
18 months of relevant Abx as per severity
-Rifampicin, ethambutol, azithromicin 3x/week if non-severe or daily if severe
-Isoniazid or moxifloxacin instead of clarithromicin/azithromicin if resistant
-drugs are really mean so possibly better to not treat if not worth it
What is this ?
Cavitating NTM disease
Give examples of fungi
Aspergillus most relevant to human health
-We breath in loads of aspergillus spores everyday but its fine for most people
-Pneumocystis is also a fungi
-Histoplasmosis most common worldwife; found in bird droppings e.g. in caves n stuff
Describe the graph modelling disease severity
What does galactomannan presence mean ?
Detects hyphal growth of Aspergillus
What does Aspergillus IgG mean ?
detects memory antibodies to Aspergillus
What does Aspergillus IgE mean ?
detects ‘allergic’ antibodies to Aspergillus
What is an aspergiloma ?
Ball of aspergillus which grows inside a cavity
Give an example of a class of oral drugs which can be used to treat aspergillus
Itraconazole
-Only oral anti-fungals end in ‘azole’
How damaging is an aspergiloma and how does this come about ?
Only need to treat if problematic
How damaging is invasive aspergillosis and how does this come about ?
A patient is tried on voriconazole but is not tolerating it. What can be used instead ?
Posaconazole (branded: noxafil)
voriconazole causes photosensitivity and sight problems
Which immune cells are important against mycobacteria ?
T cells, especially CD4+ T cells, are crucial for controlling Mycobacteria (like Mycobacterium tuberculosis).
-They coordinate cell-mediated immunity, activating macrophages to kill the bacteria inside them.
-People with HIV/AIDS or other T-cell deficiencies are much more susceptible to TB
Steroids suppress T cells and other immune functions → higher risk of fungal infections.
What is the first line of defence against many fungi, including aspergillus ?
Neutrophils are the first line of defense against many fungi, like Aspergillus.
-They engulf fungal spores (phagocytosis). They release enzymes and reactive oxygen species that kill fungi.
-People with neutropenia (low neutrophils) are at high risk for invasive fungal infections.
-Chemotherapy, bone marrow transplants, and some medications can reduce neutrophil counts.
What can predispose to fungal lung infections ?
People with structural lung damage are more prone to fungal colonization, even if neutrophils are normal:
-Fibrosis
-COPD
-Bronchiectasis
-Old cavities from TB or pneumonia
These abnormal spaces allow fungi to settle and grow (like aspergillomas).