Week Two - Case Three Flashcards
what is TB and what is it caused by
chronic infection disease, caused by mycobacterium tuberculosis. (MTB)
what are the three types that infect humans
- M.tuberculosis (commonest)
- M.bovis (bovine TB)
- M.africanum
in how much of the global population is tuberculosis present in
about 30% of the global population, but in developed countries it is rate since the advent of TB inoculation
what happens to MTB when it is encountered by the immune system
it is engulfed by macrophages
what does the MTB and macrophages complex form
granulomas
where do these granulomas typically occur
the lungs, but the bacteria can also be carried to distant sites throughout the lymphatics, and granulomas can form at other sites
what is the test for latent TB
interferon gamma release assay (IGRA) or tuberculin skin testing (TST)
what is the test for active TB
XCR and microbiology (usually sputum) for acid fast bacilli
how is TB transmitted
via droplet spread - only the pulmonary form is infectious
usually needs sustained close contact with the infectious case
roughly how much of the worlds population has been infected with TB
roughly one third
in what patients do a signifiant amount of cases occur
those co-infected with HIV
how many cases are reported each year in the UK
9000 cases each year
what are the risk factors for TB
HIV (13% cases also have HIV)
Overcrowding/close contact with active case (1/3 chance of contracting from household member)
Ethnic minority groups
Malnutrition
IV drug use
Homelessness
Chronic lung disease
Immunosuppression
how many people will patients with active TB infect per year
on average 10-15
next few questions are on the pathogenesis
where does the mycobacteria go
the pulmonary alveoli
what happens to these mycobacteria
these are engulfed by alveolar macrophages and replicated within them
where is the primary site of infection
Primary site of infection (in the lungs) = “Ghon focus” (generally in upper lobe)
what surrounds the infected macrophages
lymphocytes and fibroblasts
what does this surrounding causes
granuloma formation
what does this granuloma formation prevent
dissemination of bacteria - prevents extra-pulmonary TB
what happens inside these lesions/granulomas
the bacteria may develop abnormal cell death in the centre (caseous necrosis) and can eliminate the bacteria
what is this sometimes called
LTBI - latent tuberculosis infection
what is the risk that LTBI will develop into active TB
there is a 10% chance that LTBI can develop into active TB during a patient’s lifetime.
the risk is greatest during the first two years of infection
how does active TB usually present
with fever, night sweats, weight loss and cough, usually lasting more than 2-3 weeks
what happens if there is a failure of the above mechanism
the bacteria may gain entry into the blood stream and spread throughout the body and set up many foci of infection (tubercles)
what is this called
extra-pulmonary TB
what happens to those tin less effective immune systems
progress to primary progressive TB
what happens to less immunocompetent people,
granulomas are formed but then the necrotic tissue undergoes liquefaction and the fibrous walls break down
what then happens to the necrotic material
it then drains into the bronchi and is coughed up and can infect others
drains into nearby blood vessels and seeds to other areas leading to extrapulmonary TB
what do 90% of the cases exhibit
90% of cases exhibit pulmonary features only
what do 10% of cases exhibit
extrapulmonary features
what are the differentials for TB
carcinomas
pneumonia
PUO
lymphoma
fibrosis lung disease
what is the big complication of TB
multi-drug resistant TB (MDR-TB) can develop if TB is not properly treated
what are the signs on a CXR seen with active TB
patchy nodal shadows in the upper zones
cavitating lesions
fibrous contractions
air space consolidation
typically apical lesions
what would be seen on a CXR for milliary TB
multiple 1-10mm nodules throughout the lungs
what sputum samples are carried out for TB
3 separate sputum samples in pulmonary TB including one early morning sample
what is the stain used to test for TB
Ziehl-Neelsen (ZN) stain - rapid direct microscopy for acid-fast bacilli
what percentage of cases does ZN detect on a single sample
detects about 50% of cases of TB on a single sample
why does TB bacteria stain in a characteristic way
due to the waxy nature of their walls
what is used to confirm TB diagnosis
culture
what is the culture taken
Lowenstein-Jensen
how long does the culture take
takes 4-8 weeks due to slow bacterial growth and sensitivities take 3-4 weeks more
what do the molecular assays detect
detect MTB DNA
also detect if rifampicin resistant
when should treatment be started
treatment should be started before culture results are back, and continued even if cultures are negative
what is the skin test used to screen people at a high risk for TB
Mantoux tuberculin skin test (TST)
what does the TST involve
tuberculin protein is injected into the dermis
what happens after it is injected
patient re-presents after 48-72 hours and the level of inflammation at the inject site is assessed - by measuring the size of the induration
what gives an indication of the likelihood of TB infections
The diameter of the induration (inflammation) gives an indication of the likelihood of TB infection
what does positive TB results require
“Positive” (i.e. TB present) results require correlation with a patient’s risk factors
> 5mm induration – positive result for patients with HIV or other immunosuppression, recent contact with known TB
> 10mm induration – positive result for patients in high risk areas, or moved from high risk area
<5 years ago, IV drug users, residential care / hospital patients
> 15mm induration – positive result for patients with no underlying risk factors
who are there false positives in
those previously immunised
what conditions can potentially give false negatives
sarcoidosis, Hodgkin’s Lymphoma
what does a positive test indicate
Positive test indicates that the patient’s immune system has prior recognition of TB antigens (not due to vaccination) and thus indicates previous, latent or active TB. Further testing is required (as above) to assess if test indicates latent or active disease
what is the drug regimen for prolonged period in active disease
(isoniazid and rifampicin, pyrazinamide and ethambutol)
All 4 for 2 months, then,
what is the treatment for latent TB
single antibiotic treatment for latent TB for 3-6 months
how should MDR-TB be treated
with at least four effective antibiotics for 18-24 months is recommended
what is the prevention for TB
vaccination (BCG)
public health measurements
what is the mode of action of rifamycins
inhibits DNA transcription
what kind of drug is rifamycins
bactericidal
what are the side effects of rifamycins
Nausea, anorexia, pseudomembranous colitis, hepatotoxicity, orange colouration of excreted bodily fluids, toxicity syndromes, drug interactions
what is rifamycins also used in
mycobacterial infections - these most commonly occur in those with HIV
resistance prevents widespread use
what is the mode of action of isoniazid
inhibits synthesis of the cell wall
what kind of drug is isoniazid
bactericidal
what are the side effects of isoniazid
Nausea, vomiting, constipation, peripheral neuropathy, hepatitis, SLE-like-symptoms
what are the features of isoniazid
bactericidal on dividing organisms, static onrushing
what is isoniazid only effective against
mycobacteria
what is the mode of action of pyrazinamide
lowers intracellular pH, disrupting synthesis of fatty acids
what kind of drug is pyrazinamide
bactericidal
what are the side effects of pyrazinamide
Hepatotoxicity, nausea, vomiting, arthralgia, sideroblastic anaemia
what is the only bacteria pyrazinamide is effective against
mycobacteria
what is the mode of action of ethambutol
interferes with cell wall synthesis
what type of drug is ethambutol
bacteriostatic
what is the side effect of ethambutol
Optic neuritis – resulting in red/green colourblindness. neuritis
what are the features of mycobacteria
This is its own genus of bacteria (like G+ or G-). The group include TB and leprosy. They are acid fast. They are also aerobic.
what does acid fast mean
this means that the organisms are difficult to stain using normal staining techniques. the name refers to the fact that they can’t be stained by normal acid (ethanol) staining techniques. these bacteria are often particularly difficult to culture and identify
e.g TB takes around 6-8 weeks
what samples do you take before prescribing IV co-amoxiclav
- U&Es
- sputum culture
- respiratory viral swab
- LFTs
- blood cultures
- HIV
- lactate
- FBC
what are the common organisms that should be considered when dealing with a HAP
Staphylococci (including MRSA)
Enterococci
Gram negative bacilli (such as E-Coli or pseudomonas) or a mixed flora if aspiration pneumonia is suspected
what is HAP defined as
defined as new onset of symptoms along with a compatible x- ray developing more than 48 hours after the patient’s admission to hospital. It occurs in around 1% of in-patients and its consequences can range from extending the patient’s hospital stay to increased mortality.
what is a VAP
HAP occurring in patients on mechanical ventilation. The mortality rate from VAP can reach 50% or higher.
how do you differentiate between an effusion and consolidation radiologically
- In consolidation, the margins of opacification are not clear as compared to effusions.
- In effusions the opacification is dense and there are no markings visible in the lung field. In consolidation you can see air bronchograms, so the opacification is not dense.
- The diaphragm / costo-phrenic and cardio-phrenic angles are not visible in effusions. While these may still be visible in consolidation depending on areas of lung affected.
what is the most common cause of fungal pneumonia
In the UK, Pneumocystis jirovecii is the most common cause of fungal pneumonia. It is mainly seen in patients with altered cell-mediated immunity (immunodeficiency incl. HIV, immunosuppression e.g. after transplantation) but can also occur in patients with a severe underlying respiratory condition (COPD, Cystic Fibrosis). Pneumonia is also a key symptom for so-called endemic mycoses (e.g. histoplasmosis, blastomycosis, coccidioidomycosis) that are limited to specific geographic areas (Americas primarily) and seen in fully immunocompetent patients.
what is an environment mould that can also cause lung disease
Aspergillus is an environmental mold that can also cause lung disease. The type of disease is dependent on the host immune response.
what type of TB has a high mortality rate
Disseminated TB (milliary TB) has high mortality despite treatment.
what is the standard treatment for TB
While TB is a serious condition that can be fatal if left untreated, deaths are rare if treatment is completed. Active pulmonary TB requires a 6-month course of a combination of antibiotics. The standard treatment is 2 antibiotics (isoniazid and rifampicin) for 6 months and 2 additional antibiotics (pyrazinamide and ethambutol) for the first 2 months. It may take several weeks before the patient starts to feel better. Most patients become staining negative and non-infectious in 2 weeks.
what kind of fungus is more likely in someone with an impaired immune system
Pneumocystis jiroveci (PJP) is a fungus that can cause pneumonia in anyone whose immune system is impaired by, for example, HIV virus or immunosuppressant drugs such as those used for rheumatoid arthritis and inflammatory bowel disease.
what is the choice of treatment for PJP
Co-trimoxazole is the treatment of choice for PJP
