What do mycobacteria possess?
A lipid-rich cell wall
What does the lipid-rich cell well of mycobacteria do?
Retains some dyes, even resisting decolourisation with acid (acid-fast)
How is TB spread from person to person?
By the aerosol route
What is the first site of infection for TB?
What is the outcome of primary TB?
Most infections resolve with local scarring
What does TB post-primary infection refer to?
The development of tuberculosis beyond the first few weeks
What may happen in TB post-primary infection?
The infection may progress throughout the body
What is it called when TB spreads throughout the body?
What is the outcome of miliary spread of TB?
- May resolve spontaneously
- May develop into localised infection
Give an example of a localised infection that may result from miliary spread of TB
What happens to Mycobacterium TB once inside the body?
It is ingested by macrophages
What happens to Mycobacterium TB once it has been ingested by macrophages?
It escapes from the phagolysosome to multiply in the cytoplasm
What does the intense immune response to Mycobacterium TB cause?
Local tissue destruction and cytokine-mediated systemic effects
What does local tissue destruction as a result of TB infection cause?
Cavitation in the lung
What cytokine-mediated systemic effects are caused by infection with TB?
Fever and weight loss
What organs may TB affect?
Any organ of the body
What does TB mimic?
Both inflammatory and malignant diseases
How may pulmonary TB present?
- Chronic cough
- Weight loss
- Recurrent bacterial pneumonia
What happens if pulmonary TB is left untreated?
It follows a chronic, deteriorating course
How does tuberculous meningitis present?
- Slowly deteriorating level of consicousness
How may a kidney infection present?
- Local infection
- Weight loss
What are the potential complications of a kidney infection?
- Ureteric fibrosis
What is a common site of bone infection?
The lumbosacral spine
What may progression of a bone infection in the lumbosacral spine cause?
- Vertebral collapse
- Nerve compression
What may inflamamation of large joints lead to?
What does Mycobacterium TB stimulate once it has escaped from macrophages?
An immune response, with the release of IL-12
What is the effect of IL-12?
It drives the release of IFN-γ and TNF-α from NK and CD4 cells
What is the effect of IFN-γ and TNF-α?
They activate and recruit more macrophages to the site of infection, resulting in the formation of granulomas
What are the primary changes in TB?
- Few symptoms
- Lymph nodes may become englarged in young people
What is the classical presentation of post-primary TB?
- Cough (not always productive)
- Fevers towards the end of the day, or at night
- Weight loss and general debility
What does a chest x-ray show in a patient with post-primary TB?
- Pulmonary shadowing, which may be patchy with solid lesions
- Cavitated solid lesions
- Streaky fibrosis
- Flecks of calcification
What are the signs of respiratory TB?
- Weight loss
- Palpable lymph nodes
What are the symptoms of respiratory TB?
Primary usually asymptomatic
- Tiredness and malaise
- Weight loss and anorexia
- Occasionally, haemoptysis
What are the x-ray changes shown in respiratory TB?
- Miliary seeds
Who is pleural TB more common in?
What are the two mechanisms of pleural involvement in TB?
- Hypersensitivity response to primary infection
- Tuberculous empyema with ruptured cavity
What does tuberculous empyema have a tendancy to do?
Burrow through the chest wall
What is almost always present with pleural tuberculosis?
Some pulmonary disease
Who is lymph node TB more common in?
What is often true of lymph node TB?
It is painless
Where does lymph node TB most commonly occur?
In the neck
What happens in oesto-articular TB?
TB burrows into bone
Give two types of osteo-articular TB
- Poncet's disease
- Tuberculous Spondylitis
What is the most common form of oestoarticular TB?
What is the passage of Tuberculous Spondylitis?
- Starts in sub-chondral bone
- Spreads to vertebral bodies and joint space
- Follows longitudinal ligaments, anterior and posterior to spine
Where does Tuberculous Spondylitis mainly occur?
In the lower thoracic and lumbar spine, but can be very high
What is it called when Tuberculous Spondylitis occurs very high?
What may result from Tuberculous Spondylitis?
Parapledia and quadriplegia
In what % of Tuberculous Spondylitis cases does parapledia and quadripledia result?
What is Poncet's Disease?
Where does Poncet's disease affect?
Knees, ankles, and elbows
What happens in miliary TB?
Bacilli spread through the blood stream
When does miliary TB occur?
Either during primary infection or as reactivation
When are the lungs involved in miliary TB?
How is mililary TB spread throughout the lungs?
Why is miliary TB spread throughout both lungs?
It is in the blood
How can miliary TB in the lungs be visualised?
Many visibile on an x-ray
What do headaches suggest in miliary TB?
What are the clinical features of miliary TB?
- Ascites may be present
- Retinal involvement in children
- Few respiratory symptoms
How is TB diagnosed?
- Clinical features
- Radiological features
What clinical features aid in the diagnosis of TB?
- Night fever
- Weight loss
What radiological features aid in the diagnosis of TB?
- Miliary seeds
What microbiological features aid in the diagnosis of TB?
- Indentification of bacillus
- Direct smear and subsequent culture of the appropriate body fluid
What is important when considering the microbiology of TB?
To isolate organism and determine its susceptibility to drugs
How is TB treated?
Initially, patients are treated with four drugs for two months, after which two of them are dropped and the others continued for another four months
What drugs are used in the initial phase of treatment of TB?
What drugs are used in the continuation phase of treatment of TB?
Why are multiple drugs used in the treatment of TB?
In an attempt to combat resistance
What % of TB patients are resistant to isoniazid?
Why does TB treatment have problems with compliance?
It is quite a long regime, with several different pills to take
How is compliance with TB treatment improved in the US?
15% of patients receive Directly Observed Therapy (DOT)
What are the benefits of Directly Observed Therapy?
Improved cure rate, reduction in rate, drug resistance, and relapses
What are the potential reactions to rifampicin?
- Flu-like symptoms
- Thrombocytopenic purpura
What are the potenital reactions to isoniazid?
- Peripheral neuropathy
What are the potential reactions to pyrazinamide?
What are the potential reactions to ethambutol?
What is happening to the incidence of multidrug-resistant TB?
There is a rising trend
How many TB bacilli are spontaneously resistant?
About 1 in a million
What is a case of multidrug-resistant TB (MDRTB) suggested by?
- A history of previous incomplete treatment
- Residence in a country with high incidence of MDRTB
- Failure to response clinically to an adequate regimen
What is used to attempt to combat TB resistance?
A regimen of several drugs at once
What is the BCG vaccine?
A vaccination against TB that is prepared from a strain of the Attenuated Liver Bovine Tuberculosis Bacillus
What must be true for the TB bacteria to act as a vaccine for human TB?
They must retain a strong enough antigenicity
What are the problems with the BCG vaccine?
- The vaccine has variable efficacy
- Efficacy only lasts 15 years at most
What does the efficacy of the BCG vaccine depend on?
Genetic variation of populations and BCG strains
What are the UK regulations regarding the BCG vaccine?
Up until 2005, all children ages 13 were immunised along with all neonates born into high-risk groups.
Post 2005, the vaccination was only given to high-risk groups
Why was the BCG vaccine only given to high-risk groups post 2005?
Falling incidence of TB had reduced the vaccine's cost effectiveness
What groups are at high risk of TB?
- IV drug abusers
- Chronic lung disease
- Corticosteroid users
- Anti α-TNF antibody (infliximab) users
Where may overcrowding be a problem?
- Homeless shelters
Who is at risk of developing chronic lung disease?
By how much does the risk of developing TB increase in HIV infected people compared to uninfected people?
Estimated to be 20-37 times greater
What is the problem with TB in HIV patients?
Its a leading cause of morbity and mortality
What happens if a patient has suspected TB?
Contact is immediately made with TB radiology. The patient goes straight into a TB clinic, with no waiting times, and is given a questionnaire and sputum samples taken
How long after TB is suspected does treatment begin?
Within 7 days