Tuberculosis Flashcards
How many people are affected by TB worldwide?
2 mil - it’s a global problem.
What disease is TB often linked with?
HIV
If you have HIV more likely to get TB and if you have TB will make your HIV worse.
Why was there a flare up of TB during the war time?
Because of overcrowding, social destruction and poor nutrition.
Where is TB the biggest problem in the UK?
39% cases in UK are in London.
Due to really dense populations.
What kind of organisms is responsible for TB?
Mycobacteria.
What are mycobacteria?
There are numerous species, ubiquitous in soil and water.
Few species responsible for human disease.
Non-motile, v. slowly growing (disease slow = treatment long)
Aerobic (predilection for apices of lung)
What mycobacterium are responsible for tuberculosis?
Mycobacterium tuberculosis
What are the mycobacterium other than tuberculosis causing (MOTT)?
Mycobacterium avium-intracellulare (HIV)
M. kanasii, M. malmoense, M. xenopii
Mycobacterium leprae = leprosy.
What is unique about the cell walls of mycobacterium?
Very thick
Composed of lipids, peptidoglycan, arabinomannans.
What does the special cell wall allow the mycobacterium to be?
Resistant to acids, alkalis and detergents.
Resistant to neutrophil and macrophage destruction.
What stain is used to identify mycobacterium?
They’re acid and alcohol bacilli which are stained by the Ziehl Nelson stain.
What are the sources of M. tuberculosis?
Case of ‘open’ pulmonary TB, coughing, sneezing…
Respiratory droplets evaporate.
Drop nuclei containing mycobacterium (1 cough 3,500 nuclei = 5 min speech).
Remain airborne for v. long periods.
Can M. tuberculosis spread outside?
Outdoors mycobacteria eliminated by UV radiation and infinite dilution.
How does the size of the infected droplet affect clearance by the immune system?
If larger droplet nuclei - impacts on large airway and cleared.
If small droplet nuclei (<5microm), 1-3 organisms impact in alveoli and slowly proliferate.
Where can you find M. bovis?
In milk from infected cows.
Where is M. bovis deposited in the body?
Deposited in cervical and intestinal lymph nodes.
Describe the body’s immune response to M. tuberculosis.
APC endocytoses the bacteria and migrates to local lymph nodes and presents antigen to T helper cells. Some T cells recognise this and proliferate. These T cells get back to the macrophage and M. tuberculosis and macrophage becomes activated and can now kill the TB causing bacteria by producing cytokines and free radicals but this causes damage also to healthy tissue.
What occurs as a result of the pro-inflammatory cytokines, chemokines, immune cells and lipid produced by the destruction of M. tuberculosis?
Central caseating necrosis (which may later calcify).
The Th1 cell mediated immunological response is a two edged sword - what is meant by this statement?
Eliminates/reduces no. of invading mycobacteria
vs
Tissue destruction as a consequence of activation of macrophages.
What is the outcome of infection dependent on?
Infection - i.e. virulence and number.
Susceptibility - i.e. genetics, race, nutrition, age, immunosupression.
What differs between a resistant and susceptible host?
Susceptible host - malnutrition, elderly = lots of tissue destruction, organism proliferates = progressive disease.
Resistant host - healthy diet, >20 years = some tissue destruction, organism contained, some disease.
What is a primary infection with TB and who normally gets it? Where does the infection normally focus?
No preceding exposure or immunity.
Usually children.
80% infected focus in alveolus (lymph nodes, gut)
How can mycobacterium spread?
Via lymphatics draining into hillier lymph nodes.
Haematogenous seeding of mycobacteria to all organs of the body (lungs, bone, genitourinary system).
What are the symptoms and signs of primary infection with TB?
Usually no symptoms, can be fever and malaise
Erythema nudism, rarely chest signs
In the majority (85%) -
Initial lesion and local lymph node (primary complex)
Heals with or without scar (may calcify - Ghon focus and complex).
Primary infection is associated with development of immunity to what protein?
Tuberculoprotein.
What test will determine whether you have immunity from primary infection?
Heaf/Tuberculin tests.
Describe the Heaf/Tuberculin test.
Intradermal administration of tuberculoprotein (PPD) results in lymphocytic and macrophage based area of inflammation/induration after 48 hours.
What are the three outcomes of primary infection?
Progressive disease
Contained latent (dormant 1 or 2 bacteria in lung waiting until immunosuppressed, poor diet, older…)
Cleared and cured.
In what percent of people does the primary infection progress? And what does this entail?
1%
Primary focus continues to enlarge - cavitation
Enlarged hilar lymph compress bronchi, lobar collapse
Enlarged lymph node discharges into bronchus
= tuberculous bronchopneumonia
POOR PROGNOSIS
6-12 months after infection what happens to 1% of people after primary infection?
Miliary TB fine mottling on X-ray, widespread small granulomata
Meningeal TB, severe, CSF high protein, lymphocytes
Tuberculosis pleural effusion
What is milliary TB?
TB with wide dissemination, millet seed appearance on X-ray. Can present in many organs including the lungs, liver and spleen.
What is meningeal TB?
When the M. tuberculosis gets infects the meninges.
Lifethreatening.
In what two ways may someone end up with post-primary disease?
Reactivation of mycobacterium from latent primary infection disseminated by the bloodstream around the body.
New re-infection from outside source, susceptible previously infected host.
Does the patient react the same in post-primary disease as in primary disease?
Different host response because of previous sensitisation.
If insufficient immunity, tissue damage and progressive disease.
What are some other effects of post primary disease?
Pulmonary disease Lymph nodes, usually cervical Bone and joint, spine, hip etc. Genito-urinary - kidney, urter, bladder Male infertility - vas deferens Female infertility - uterus, Fallopian tubes Pericardium - constrictive pericarditis Abdomen - ascites, ileal TB --> obstruction Adrenal --> Addison's disease Skin - lupus vulgaris Can affect just about any tissue.
When will military, meningeal, pleural TB present?
6-12 months in progressive primary disease since primary complex.
When will post primary disease, e.g. pulmonary and skeletal present?
Typically 1-5 years after primary complex.
Maybe 30-40
When will genitourinary, cutaneous TB present after primary complex?
Typically 10-15 years.
Maybe 30-40
What is unusual about post-primary pulmonary TB?
May be no symptoms for many months.
What symptoms are usually experience in post-primary infection?
Progressive, over several months.
Respiratory - cough, sputum, haemoptysis, pleuritic pain or SoB
Systemically unwell - malaise, fever, weight loss, night sweats.
What kinds of things would you be looking for in PMH to help to diagnose post-primary TB?
Diabetes, immunosupressive diseases, previous TB.
What would you be looking for in drugs and allergies to help diagnose post-primary TB?
Immunosuppressive drugs.
What would you be looking for in PSH to help diagnose post-primary TB?
Alcohol, IVDA, poor social circumstances, immigrants from high incidence areas.
What signs might you seen with post-pulmonary tuberculosis?
May be none at all - extensive TB can be present without any physical signs.
If more advanced may be crackles, bronchial breathing.
Finger clubbing rare unless very chronic infection.
What sort of information received from the patient would raise a high index of suspicion for TB?
Immunosupressed - HIV, corticosteroid therapy etc. In africa 70% TB patients have HIV.
Malnutrition, alcoholism, vagrants, previous gastric surgery, malignancy.
Diabetes mellitus.
Adolescence, elderly
Recent immigrants from high prevalence countries.
What is the most important thing in treating TB?
Finding the organism.
What essential investigations do you want to carry out?
3 sputum specimens on successive days.
CXR.
What are tests do you do with the 3 sputum specimens?
Sputum smear - ZN stain - immediate answer if any AAFB
Sputum culture - can take 8 weeks - now quicker methods if essential (sputum PCR as good as a well done smear)
What do you do if the patient can’t produce sputum samples spontaneously?
Induced sputum samples.
What are you looking for in the CXR?
Patchy shadowing - often apices/upper zones or apex of lower lobes (?related to high ventilation, poor perfusion inc. O2), often bilateral.
Cavitation if advanced
May calcify if chronic or healed TB.
What do you do if the sputum is negative?
Further investigations CT of thorax Bronchoscopy with bronchoalveolar lavage, transbronchial biopsy - ZN stain, culture, PCR, biopsy histology Pleural aspiration and biopsy if pleural effusion Fluid cytology (lymphocytes) Fluid for AAFB and culture Biopsy histology 1 biopsy sent in for saline culture
How did they used to treat TB?
Fresh air, sunshine, red rest, good food, improving immunity, it D, cathelecidin (LL-37).
Sometimes surgery -
Collapse down cavity, anaerobic conditions, phrenic crush, artificial pneumothorax, pneumoperitoneum, thoracoplasty, lung resection.
What is LL-37?
A potent anti-microbial agent, vit D helps make it.
What is the modern treatment of TB?
Multiple drug therapy for at least 6 months.
TB treated by committed specialists.
What does single agent treatment cause?
Drug resistant organism within 14 days.
What are the important things to remember with TB?
LEGAL requirement to notify all cases!
Low threshold for HIV testing, AIDS defining condition.
What are the important things to remember with TB?
LEGAL requirement to notify all cases!
Low threshold for HIV testing, AIDS defining condition.
Must do TB CONTACT tracing.
What drugs are used in the treatment of TB?
Rifampicin, isoniazid, ethambutol, pyrazinamide for 2 months.
Rifampicin, isoniazid for 4 months.
What does WHO recommend for most situations?
Directly observed therapy (DOT).
When is the patient rendered non-infectious?
After 2 weeks of treatment.
What are the possible side effects of rifampicin?
Orange ‘irn bru’ urine, tears
Induces liver enzymes, prednisolone, anticonvulsants, OCP ineffective
Hepatitis
What are the possible side effects of isoniazid?
Hepatitis Peripheral neuropathy (pyridoxine B6)
What are the possible side effects of ethambutol?
Optic neuropathy (check visual activity)
What are the possible side effects of pyrazinamide?
Gout
What is the aim of TB contact tracing?
Have to find out who they got it from and who they’ve given it to.
What does the likelihood of infection with TB depend on?
Duration of contact and intensity of infection.
In general, who do you want to screen?
Close household contacts (5-14% become infected.
If close contacts have been infected what does this mean and who do you screen next?
Virulent organism/high transmission.
Screen casual contacts.
Stone in pond principle.
What group of people should have no immunity to tuberculoprotein?
If younger than 16 and no BCG.
What are the two tuberculin tests?
Mantoux and Heaf test.
Describe the mantoux test.
PPD 1:1,000, 0.1 ml
Intradermal
read at 48-72 hours
Induration > 10mm = positive
Describe the heaf test.
Multiple puncture. Undiluted PPD. Read after 4-7 days. Grade 1 - 4-6 papules Grade 2 - indurated ring Grade 3 - disc of induration Grade 4 - induration outside ring, blistering
If Heaf positive (2-4) exposed to TB what do you do?
CXR - if normal at risk of disease (miliary, meningeal).
Chemoprophylaxis to kill mycobacteria. If + Inh 3 months, Inh 6 months.
CXR abnormal treat as primary TB.
If Heaf test is negative what do you do?
Repeat after 6 weeks.
If 2nd Heaf neg - BCG
If 2nd Heaf pos - recent infection, as above.
If they have a BCG and X-ray is normal, what do you do?
Reassure and discharge.
