Tuberculosis Flashcards
What is tuberculosis (TB)?
It is defined as a granulomatous infectious disease caused by the mycobacterium tuberculosis bacteria
TB is a multi-system disease, which organ does it primarily affect?
Lungs
What are the three bacteria in the mycobacterium tuberculosis complex?
M. tuberculosis
M. bovis
M. africanum
What is the most common bacteria to cause TB?
M. tuberculosis
What are the three characteristic features of mycobacterium tuberculosis?
Bacillus shaped
Gram-positive
Aerobic in nature
What are the three classifications of TB?
Primary Tuberculosis
Secondary Tuberculosis
Miliary Tuberculosis
What is primary TB?
It is defined as the initial exposure to mycobacterium tuberculosis in a non-immune host
How is TB transmitted?
Droplet inhalation
Therefore commonly spread through coughing and sneezing
Describe the pathophysiology of TB following exposure
There is activation of the immune system, which results in the migration of macrophages to the lungs
These macrophages engulf the mycobacterium and then migrate to regional hilar lymph nodes
There is then granuloma formation, with central caseating necrosis, within the lung and regional lymph nodes
What hypersensitivity reaction mediates the inflammatory response associated with TB?
Type 4
What is the Ghon focus?
It is the term used to refer to the tubercle-laden macrophage lesions within the lung
What is the Ghon complex?
It is the term used to refer to the collective tubercle-laden macrophage lesions within the lung and regional lymph nodes
What are the three subclassifications of primary TB?
Cleared Primary Tuberculosis
Latent Primary Tuberculosis
Progressive Primary Tuberculosis
What is cleared primary TB?
It is defined as tuberculosis infection in which the mycobacterium are completely destroyed through the activation of macrophages
What is latent primary TB?
It is defined as tuberculosis infection in which the mycobacterium remain dormant within the lungs
What is another term for progressive primary TB?
Active TB
What is progressive primary TB?
It is defined as uncontrolled tuberculosis infection, in which the multiplication of bacteria occurs
What is another term for secondary TB?
Post-primary TB
What is secondary TB?
It is defined as reactivation of initial latent infection
What is miliary TB?
It is defined as a disseminated form of tuberculosis, in which infection is spread from one area of the body to other organ systems via haematogenous mechanisms
What are the six most common extrapulmonary sites of TB?
Central nervous system
Cervical lymph nodes
Vertebral bodies of the spine
Gastrointestinal system
Genitourinary system
Pleural structures
How does TB affect the CNS?
Meningitis
How does TB affect the cervical lymph nodes?
Scrofula
How does TB affect the pleural structures?
Pleurisy
How does TB affect the pleural vertebral bodies of the spine?
Pott’s disease
What are the six risk factors of TB?
Tuberculosis Infection Close Contact
Immigration From High Prevalence Areas
Immunosuppression
Homelessness
Intravenous Drug Users
Alcoholism
What are the two main countries with high TB prevalence?
India
Sub-Saharan Africa
What are three immunosuppression conditions associated with TB?
HIV
Malignancy
Steroids
What are the nine clinical features associated with TB?
Fever > 38°C
Weight Loss
Lymphadenopathy
Chronic Productive Cough
Haemoptysis
Dyspnoea
Pleuritic Chest Pain
Bronchial Breathing
Percussion Dullness
What rash is asssociated with tuberculosis?
Erythema Nodosum
What additional clinical features may be associated with TB?
In cases of extra-pulmonary disease, individuals will present with additional clinical features relevant to the organ system affected
What are the clinical features seen in primary TB?
These patients are usually asymptomatic, or present with a fever only
What six investigations are used to diagnose TB?
Mantoux Test
Interferon-Gamma Release Assays (IGRAs)
Microscopy
Chest X-Ray (CXR)
Sputum Culture
Nucleic Acid Amplification Test (NAAT)
When is the Mantoux test used?
It is used to identify a previous immune response to tuberculosis – which can be related to previous vaccination, latent tuberculosis or active tuberculosis infection
What is the Mantoux test?
It involves the injection of PPD tuberculin into the intradermal space on the forearm
This results in the formation of a bleb under the skin following a 72 hour period
What is PDD tuberculin?
It is a collection of tuberculosis proteins that have been isolated from the bacteria
What induration diameter defines a negative Mantoux test?
< 6mm
What are two causes for a false negative Mantoux test?
Long Term Steroid Administration
Sarcoidosis
What induration diameter defines a positive Mantoux test?
6mm - 15mm
What induration diameter defines a strongly positive Mantoux test?
> 15mm
What should be conducted following a positive Mantoux test result?
There should be further investigations to assess for active disease
When is IGRA used?
It is used to identify a previous immune response to tuberculosis – which can be related to previous vaccination and latent tuberculosis infection
An IGRA test cannot be used to confirm the presence of active tuberculosis infection, unlike the Mantoux test
What is an IGRA?
It involves collecting a blood sample and mixing it with antigens from the tuberculosis bacteria
What is defined as a positive IGRA result? Explain the pathophysiology of this result
The release of interferon-gamma
This is due to the sensitisation of WBCs to those antigens during a previous immune response
How does TB appear on gram stained microscopy?
Gram stained microscopy is deemed ineffective due to the bacteria’s resistance to acids used in the staining procedure
This is termed as acid-fastness, and therefore tuberculosis bacteria are described as acid-fast bacilli (AFB)
What is important to note about the gram staining of TB?
All mycobacteria will stain positive for an AFB smear
This result is therefore not specific for tuberculosis
How does TB appear on Ziehl-Neelsen stained microscopy?
The bacilli appear bright red against a blue background
What are the three features of primary TB on CXR?
Patchy consolidation
Pleural effusions
Hilar lymphadenopathy
What is the feature of secondary TB on CXR?
Patchy/nodular consolidation with cavitation in the upper lung zones
What is cavitation?
It is defined as gas filled spaces in the lungs
What is the feature of miliary TB on CXR?
‘Millet seeds’ uniformly distributed throughout the lung fields
What is the gold standard investigation used to diagnose TB?
Sputum culture
How is sputum culture used to diagnose TB?
It is used to enable bacterial culture to be performed and therefore assess drug sensitivities
How many sputum culture samples are required to test for TB?
Three
One has to be in the morning
What two techniques can be used to produce sputum if individuals are struggling?
Hypertonic saline
Bronchoscopy with lavage
How long does it take to receive sputum culture results?
1 - 3 weeks
Do we wait for sputum culture results before starting treatment?
No
In which patients is sputum culture first line for diagnosing TB?
HIV
What is NAAT?
It checks directly for the DNA or RNA of a bacterial organism
What bacteria sample is used to conduct NAAT in TB?
Sputum sample
How quickly do we receive NAAT results?
24 - 48 hours
Therefore, faster than a traditional sputum culture
When is NAAT used?
It is only used when this information would alter treatment or there is a high risk of complication development
What are the four pharmacological options used in active TB?
RIPE
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
What is the mechanism of action of rifampicin?
It inhibits bacterial DNA dependent RNA polymerase, preventing transcription of DNA into mRNA
How long do we administer rifampicin for to treat active TB?
6 months
What are the three side effects of rifampicin?
Orange Secretions (Urine/Tears)
P450 Liver Enzyme Inducer
Hepatitis
What does P450 liver enzyme inducement mean?
There is a reduced effect of drugs that are metabolised by the liver (contraception pills*)
How do we remember the key side effect of rifampicin?
Rifampicin = Red an orange pissin
What is the mechanism of action of isoniazid?
It inhibits mycolic acid synthesis
How long do we administer isoniazid for to treat active TB?
6 months
What are the five side effects associated with isoniazid?
Peripheral Neuropathy
Hepatitis
Agranulocytosis
Liver Enzyme Inhibitor
Drug-Induced Lupus
How do we prevent the isoniazid side effect of peripheral neuropathy?
We administer pyridoxine (vitamin B6)
How do we remember the key side effect of isoniazid?
Isoniazide = im so numb acid
Due to isoniazid inhibiting the P450 system, which drug should be monitored? Why?
Warfarin
This inhibition reduces the metabolism of warfarin, causing prolongation of its effects which increases INR
What is the mechanism of action of pyrazinamide?
It is converted by pyrazinamidase into pyrazinoic acid, which inhibits fatty acid synthase I
How long do we administer pyrazinamide for to treat active TB?
2 months
What are the four side effects of pyrazinamide?
Gout
Hepatitis
Arthralgia
Myalgia
What is the mechanism of action of ethambutol?
It inhibits the enzyme arabinosyl transferase, which polymerizes arabinose into arabinan
How long do we administer ethambutol for to treat active TB?
2 months
What are the three side effects of ethambutol?
Optic Neuritis
Reduced Visual Acuity
Colour Blindness
How do we remember the key side effect of ethambutol?
Ethambutol = eye thambutol
In active TB with CNS involvement, how do we adjust pharmacological management?
We administer isoniazid and rifampicin for twelve months instead of six months
What are the four conservative management options for active TB?
Infectious disease testing
Public health notification
Contact tracing
Isolation
What three infectious diseases do we screen for in TB patients?
HIV
Hepatitis B
Hepatitis C
How long should TB patients isolate for?
Until they have been administered at least two weeks of pharmacological treatment
In hospitals how do we prevent airborne spread of TB?
Negative pressure rooms
How do we treat latent TB?
It doesn’t require treatment in individuals who are asymptomatic
We only treat individuals who are at high risk of re-activation
How do we treat latent TB patients who are at high risk of re-activation?
Isoniazid and rifampicin for three months
OR
Isoniazid for six months
What is the BCG vaccine?
It involves an intradermal injection of live attenuated tuberculosis
What does attenuated mean?
Weakened
Which individuals receive the BCG vaccine?
Those at high risk of TB
What are the six high risk groups of TB?
Neonates Born In UK Areas With High TB Prevalence
Neonates With Relatives From Countries With High TB Prevalence
Neonates With TB Family History
Unvaccinated Individuals With TB Close Contact
Unvaccinated Individuals From Countries With High TB Prevalence
Healthcare Workers
What investigation is conducted prior to BCG vaccine administration? Why?
Mantoux test
It should be negative, otherwise vaccination should result in secondary TB development
