TUBERCULOSIS Flashcards
Outline the epidemiology of tuberculosis?
An infection with one of the top 10 causes of death worldwide
A large proportion of these deaths were in HIV positive patients
Up to 2 billion people in the world have latent TB (1/3rd) and 5-10% will be expected to develop active disease
Rates are 13x higher for patients not born in the UK and account for 70% of cases
40% of TB cases in the UK occur in London
95% of deaths due to TB occur in low/middle income countries
1/5th of all HIV deaths are die to TB
What is mycobacterium?
A genus of actinobacteria
An aerobic, acid-fast, slow-growing
What causes TB in humans?
Mycobacterium tuberculosis - most common in humans
Mycobacterium bovis (main cause of TB in cattle)
Mycobacterium africanum (mostly in W.Africa)
Mycobacterium microti (mainly affects other mammals)
What are the characteristics of mycobacterium?
Obligate aerobes
Facultative intracellular (can grow outside the cell but find it advantageous to be intracellular)
Acid fast bacilli
What is an acid fast bacilli?
refers to a resistance to decolourisation of staining by acid
Outline the natural history of TB?
Once mycobacterium bacilli have been inhaled patients may follow a number of clinical paths:
Initial inhalation -> infection cleared or primary TB
primary TB -> progressive primary TB or latent TB
Latent TB -> post-primary TB
What is primary TB?
the initial infection, often subclinical, suppressed in the majority of individuals.
What is progressive-primary TB?
primary infection is not suppressed, and prolonged infection occurs.
What is latent TB?
the outcome in the majority of patients with Primary TB. Non-infectious state.
What is post-primary TB?
Aka reactivation TB
It occurs in patients with latent TB, frequently due to immunocompromise (e.g. AIDs). May be pulmonary (55%) or extra-pulmonary (45%).
Outline the pathophysiology of TB
Inhaled bacilli enter alveoli and begin to divide. This may be immediately cleared in some individuals. In others, primary TB occurs
About 3 weeks after infection, cell mediated immunity kicks in and immuebn cells surround the site of TB infection creating a granuloma - the tissue inside dies from caseous necrosis = Ghon focus + associated lymph node = Ghon complex
After 2-10 weeks, a sufficient cell-mediated response halts the proliferation of the bacilli in the majority of individuals and these pt develop latent TB. They may have a Ranke complex. Those with latent TB are at risk of reactivation
A small proportion don’t stop the primary infection and develop primary-progressive TB (particularly those with inadequate T cell immunity e.g. HIV). This infection is often serious and may lead to disseminated TB
What staining technique do myocabacterium need for diagnosis?
Zeihl-Neelsen stain
This turns TB bacteria bright red against a blue background.
Why is TB hard to culture and treat?
Because myocabacterium are very slow dividing and have high oxygen demands
How is TB spread?
From inhaling saliva droplets from infected people
What is secondary TB?
When latent TB reactivates
What is miliary TB?
When the immune system is unable to control the disease this causes a disseminated, severe disease
Whats the most common site for TB infection and why?
The lungs because there is plenty of oxygen
Where can extrapulmonary TB affect?
CNS - tuberculosis mengingitis
Vertebral bodies (Pott’s disease)
Cervical lymph nodes (scrofuloderma)
Renal
GIT
Why are mycobacterium acid fast?
Because they have a waxy cell wall made from mycolic acid
What is a Ghon focus?
A subpleural area of granulomatous inflammartion (immune cells surround mycobacterium)
What is a Ghon complex?
A lesion consisting of a Ghon focus and pulmonary lymphadenopathy - retains viable bacteria which makes them a source of secondary TB
What is a Ranke complex?
A Ghon complex that undergoes progressive fibrosis and calcification - can be seen on CXR
Who’s at risk for reactivation of dormant TB?
Older pt
HIV/AIDS patients
Immunosuppressive drugs e.g. oral steroids
Malnutrition
I.e. immune compromised patients
Why is secondary TB commonly seen in the upper lobes of the lung?
Because oxygenation is greatest and TB is an aerobe
Whats the pathophysiology of secondary TB?
Immune system compromised -> Ghon focus reactivates -> infection spreads to upper lobes of lungs -> memory T cells release cytokines quickly -> caseous necrosis which cavitate -> bacteria can disseminate -> can cause broncho-pneumonia and systemic miliary TB
What is multi drug-resistant TB?
a strain of TB that is resistant to two first-line drugs (isoniazid and rifampicin), with or without any other drug resistance
What is extensively drug-resistant TB?
multidrug-resistant TB with additional resistance to any fluoroquinolone and also any one of the three specialist second-line injectable agents
What are risk factors for TB infection?
Being born in high prevalence areas
<5
Close contacts with active pulmonary/laryngeal TB
History of untreated or inadequately treated active TB infection
Comorbidities e.g. HIV, diabetes, CKD, occupation lung disease, haematological malignancy, malnutrition
Immunosuppressive drugs
Underserved groups
History of excessive alcohol, IV drug use, smokers
What are complications of TB?
Reduced QOL
Transmission to others
Drug resistance
Post-TB bronchiectasis, COPD and aspergillomas\
Post-TB cor pulmonale and respiratory failure
Death
Whats the prognosis of untreated active TB?
It’s a slow progressive disease in most people which may be potentially fatal - takes about 3 years
Increasing age, more extensive disease, and HIV co-infection are associated with a worse prognosis, recurrent infection and/or reinfection, and increased mortality
Multi drug-resistant TB has a poorer prognosis
Where are TB rates the highest?
India
Indonesia
China
The Philippines
Pakistan
Nigeria
Bangladesh
The Democratic Republic of the Congo.
How does TB present?
Weight loss
Fever
Night sweats
Anorexia
Malaise
Productive cough
Dyspnoea
Haemoptysis
Extrapulmonary involvement - lymphadenopathy, bone/joint pain or swelling, abdominal or pelvic pain, constipation, sterile pyuria, headache, vomiting, confusion, skin lesions, chest pain and ankle swelling
What is Potts disease?
Tuberculous spondylitis - vertebral body osteomyelitis and intervertebral discitis from TB
What is the BCG vaccine?
An intruder all infection of live atentuated TB that offer protection against severe and complicated TB
What is the Mantoux tuberculin test?
Injecting PPD tuberculin into skin
A person who has been exposed to the bacteria will mount an immune response and so will have a reaction
This is done before the BCG vaccine is given
Who should you offer the BCG vaccine to?
Neonates born in areas of the UK with high rates of TB
Neonates with relatives from countries with a high rate of TB
Neonates with a family history of TB
Unvaccinated older children and young adults (< 35) who have close contact with TB
Unvaccinated children or young adults that recently arrived from a country with a high rate of TB
Healthcare workers
What is miliary TB?
Disseminated haematogenous spread of the bacilli
(Term miliary comes from the characteristic chest radiograph findings which is the appearance of millet seeds throughout yhe field lungs)
How can TB affect the CNS? How do we test this?
It can cause TB meningitis
The CSF sampling will show high protein, low glucose and lymphocytosis
What are sympotms of Pott’s syndrome?
Fever
Weight loss
Back pain
Paraplegia or paraparesis
Kyphosis or scoliosis
How can TB affect the skin?
It may cause lupus vulgaris, scrofuloderma, erythema nodosum
How do we screen for latent TB?
Mantoux test
Interferon-gamma blood test
How do you carry out the Mantoux test?
Inject 0.1ml of 1:1000 purified protein derivative (PPD) intradermally
Read results 2-3 days later - look for a local skin reaction
How do you interpret the results of the Mantoux test?
If induration is <6mm = negative
6-15mm - positive - previous TB or BCG - dont give BCG
>15mm - strongly positive - suggests Tb infection - dont give BCG
What can cause a false negative Mantoux test?
miliary TB
sarcoidosis
HIV
lymphoma
very young age (e.g. < 6 months)
When do we use the interferon gamma blood test?
When the Mantoux test is positive or equivocal
If the Mantoux test is probably a false negative
What should you do if you screen a pt and you find they are positive for latent TB?
Assess for active TB using symptoms and CXR
If no evidence then treat for latent TB to prevent progression to active disease - 3 months of isoniazid and rifampicin or 6 months of isoniazid
How should you investigate active TB?
CXR
3 sputum samples - stain with Ziehl neelsen stain
Sputum culture - gold standard (but takes 1-3 weeks)
Nucleic acid amplification test (NAAT)
If you suspect active extrapulmonary TB then you may investigate further dependant on likely site of disease e.g. spinal x-ray, urine dipstick, CT CNS etc
What may you see on CXR in active pulmonary TB?
This may show signs of cavitation, pleural effusion, mediastinal or hilar lymphadenopathy, or parenchymal infiltrates, mainly in the upper lobes.
What is the interferon-gamma release assay?
This test involves taking a sample of blood and mixing it with antigens from the TB bacteria. In a person that has had previous contact with TB the white blood cells have become sensitised to those antigens and they will release interferon-gamma as part of an immune response. If interferon-gamma is released from the white blood cells then this is considered a positive result.
The IGRA test is used in patients that do not have features of active TB but do have a positive Mantoux test to confirm a diagnosis of latent TB.
What is Nucleic acid amplification testing?
A way of looking for the DNA of TB bacteria
It’s tested on a sample containing bacteria e.g. sputum and provides information about the bacteria faster than traditional culture
Usually only used where having this information would affect treatment or if they are at higher risk of developing complications
How do you manage latent TB?
If otherwise healthy they wont need treatment
If at risk of reactivation they can be treated with either…
6 months of isoniazid with pyridoxine (6H) or
3 months of isoniazid (with pyridoxine) and rifampicin (3HR)
How is acute pulmonary TB treated?
R – Rifampicin for 6 months
I – Isoniazid for 6 months
P – Pyrazinamide for 2 months
E – Ethambutol for 2 months
How is active TB with CNS involvement treated?
with isoniazid (with pyridoxine) and rifampicin for 12 months whilst pyrazinamide and ethambutol are given for the first 2 months
Adjunctive steroids are offered at the start of treatment and weaned off over 4-8 weeks
What is directly observed therapy?
Involves direct supervision of pt during their TB treatment
It’s thought to improve engagement and adherence to therapy
Which groups of people would benefit from directly observed therapy?
Alcoholics or drug abuse
Major psychiatric, memory or cognitive disorder
Homeless people
Prisonders
Those with a history of poor adherence
Those previously been treated for TB
Those in denial of TB diagnosis
Those with multi-drug resistant TB
Those who request it
Those who are too ill to self-administer treatment
How should you manage multi drug-resistant TB?
18-24 moths of at least 6 drugs that the TB strain does not have resistance against
Whats the moa of rifampicin?
Inhibits DNA-dependant RNA polymerase preventing transcription of DNA into mRNA
What are the important side efefcts of rifampicin?
Nausea + vomiting
Thrombocytopenia
Red/orange discolouration of secretions e.g. urine and tears
Flu-like symptoms
Hepatitis
What drugs does rifampicin reduce the effect of and why?
Contraceptive pill, oral anticoag, glucocorticoids, digoxin, quinidine, methadone, hypoglycaemic, barbiturates
Etc its a potent CYP450 inducer
Whats the moa of isoniazid?
inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall.
What are important SE of isoniazid?
Peripheral neuropathy (this is why it is given alongside pyridoxine)
Hepatitis
Agranulocysis
Also a potent liver enzyme inducer
Whats the moa of Pyrazinamide?
converted by pyrazinamidase into pyrazinoic acid which in turn inhibits fatty acid synthase (FAS) I, preventing its growth
What are the important SE of Pyrazinamide?
hyperuricaemia causing gout
arthralgia, myalgia
hepatitis
Whats the moa of ethambutol?
inhibits the enzyme arabinosyl transferase which polymerizes arabinose into arabinan (Inhibits cell wall synthesis)
What are the impprtant SE of ethambutol?
Optic neuritis (check visual acuity before and during treatment)
Also note that dose needs adjusting in pt with renal impairment
Why do you need pyridoxine supplementation during isoniazid therapy?
As isoniazid is known to interfere with B6 metabolism = this can lead to peripheral neuropathy
What is tuberculosis?
A chronic granulomatous disease caused by mycobacterium
How does TB present when it affects the CNS?
Tb meningitis or tuberculoma
Headache
Meningism
Focal neurological signs
Decreased concsciousness
How does TB present when it affects the genitourinary system?
Sterile pyuria (raised WCC with no bacteria)
Kidney pathology
Asbcess
Salpingitis and infertility
Epididymo-orchitis
How does TB present when it affects the MSK system?
Arthritis, osteomyelitis, psoas abscess, Pott’s disease of the spine
How does TB present when it affects the GI system?
Abdo pain
Obstruction
Appendicitis
Ascites if it spreads to peritoneum
How does TB present when it affects the pericardium?
Pericardial effusions
Constrictive pericarditis
How does TB present when it affects the lymph nodes?
Superficial lymphadenopathy that may later become suppurative (scrofuloderma)
