28. Tuberculosis Flashcards
How many people infected by TB worldwide?
2 billion infected
How many new cases of TB every year world-wide?
8.6 million annually
What do 75% of Africans with TB also suffer from?
HIV (1.1 million)
Is TB the second leading cause of death form an infectious disease worldwide?
Yes (1.3 million deaths annually)
Where is the highest prevalence of TB worldwide? (3)
- south Africa
- sub-saharan Africa
- south-East Asia (including India and China)
What is the symmetry aspect for both HIV and TB?
They both make each other worse
TB was in decline and under control in the UK until which time period?
untilmid- 1980s
Where are majority of TB cases in the whole of UK?
In London (39% of all cases in UK) 45/100,000 compraed to 11% in W. Midlands due to immigration from high incidence areas
What type of pathogen is responsible for TB? Where is it found?
Mycobacteria; found in soil and water
Only a specific 2 types of mycobacterium species causes TB, what are they?
- Mycobacterium tuberculosis
- M. bovis (bovine TB)
What are 5 mycobacteria other than tuberculosis which contribute to the 30% of UK isolations?
- mycobacterium avium-intracellulare (HIV patients more likely to suffer)
- M. kansasii
- M. malmonse
- M. xenopii
- mycobacterium leprae (leprosy)
What type of bacillus is mycobacteria tuberculosis?
Non-motile bacillus (can’t move)
AAFB: acid and alcohol fast bacilli
What are mycobacteria TB growing properties? Is it aerobic or anaerobic?
- very slow growing
- disease is slow and treatment is long
- AEROBIC
What makes up mycobacteria TB cell wall which makes it very thick? (3)
- lipids
- peptidoglycans
- arabinomannans
What 2 features does the cell wall thickness of mycobacteria TB give to the organism?
- resistant to acids, alkali and detergents
2. resistant to neutrophil and macrophage destruction
What diagnostic stain needs to be used on mycobacteria TB?
ZN (Ziehl Neilson) stain
What dye cannot be removed from the thick cell wall when it reacts together?
Aniline based dyes such as carbol fuschin
Where is mycobacteria more likely to reside in the lungs since it’s aerobic?
preference for apices of the lungs
What is the source of mycobacterium TB? How is it spread?
- case of “open” pulmonary TB though coughing and sneezing
- respiratory droplets evaporate and droplet nuclei produced contain mycobacteria which remains airborne for long periods of time
TB is especially easy to catch in what conditions?
In overcrowding (because it remains air-borne for a long time)
What happens to outdoor mycobacteria TB?
They are eliminated by UV radiation and infinite dilution of the orgnism
What is the effect of inhaled large and small droplets of mycobacterium?
- large droplet nuclei impact on large airways and cleared
- small droplet nuclei (<5 micrometers) have 1-3 organisms impact in alveoli and slowly proliferate
How is mycobacterium bovis spread?
spread through infected cow’s milk
Where is mycobacterium bovis deposited? (2)
- cervical lymph nodes
2. interstitial lymph nodes
Describe what happens in an immunological response when TB enters the body.
- Macrophage engulfs mycobacterium TB in alveoli and presents its antigens for TH1 recognition
- T helper cells (TH1) will undergo clonal proliferation in lymph node which are all specific to antigen and migrate to alveoli and bind to antigen presenting cell (APC)
- Macrophages then become activated and become epithelioid cell
- Epithelioid cell produced free radicals leading to tissue damage
What is the dilemma that our immune system faces when exposed to TB?
Finding the balance between fighting TB off and not harming the body
What do activated macrophages become once TB is detected in body? (2)
they become epithelioid cells and then Langhan’s giant cells
What does accumulation of macrophages, epithelioid cells and Langhan’s cells lead to?
lead to formation of a granuloma
What does formation of granulomas in TB cause?
central caseating necrosis which may later calcify
What word ALWAYS implies TB?
Caseating (caseating granuloma is cheese- like and characteristic of TB)
Why is TH1 cell mediated immune response seen as a “2 edged sword”?
- eliminates/ reduces number of invading mycobacteria
2. tissue destruction is a consequence of activation of macrophages
What affects the infection progress in TB? (2)
- virulence
2. number
What affects the susceptibility progress in TB? (5)
- genetics
- race
- nutrition
- age
- immunosuppression
What are the main 2 susceptible TB hosts?
- malnutritioned people
2. elderly
What are TB effects on susceptible hosts?
- tissue destruction is big
- organism proliferates quickly
- progressive disease
What are the main 2 resistant TB hosts?
- healthy diet people
2. people >20 years
What are TB effects on resistant hosts?
- tissue destruction can vary
- organism relatively contained disease
What is a primary infection of TB?
People who have never been exposed to TB (no preceding exposure or immunity to TB)
Who is most susceptible to primary TB infection?
Usually children; 80% infected focus is in alveolus (lymph nodes and gut too)
How does mycobacteria spread and where to?
Spreads via lymphatics to the draining HILAR lymph nodes
To which 3 places especially does haematogenous seeding of mycobacteria in body organs occur?
- lungs
-bone
-genitourinary system
(but also to all other body organs)
What are the primary infection of TB symptoms?
Usually no specific symptoms, but can have:
- fever
- malaise
- erythema nodosum (round lumps form under the skin)
- rarely chest signs
What occurs in the majority (85%) of TB patients?
- initial lesion and local lymph node (primary complex)
- heals with or without scar but may calcify to Ghon focus +complex (calcification of scar)
During primary infection, what is immunity created against?
immunity against tuberculoprotein (found on mycobacterium TB)
What is the basis of Heaf/ Tuberculin tests?
- Intra-dermal administration of tuberculoprotein (PPD; purified protein derivative) results in lymphocytic and macrophage based area of inflammation/ induration after 48 hours
- TB is isolated, ground up and body’s reaction is tested if it’s been exposed to it before
What are 3 forms of primary infection in TB?
- progressive disease
- contained latent (a few organisms still alive in body and reactive when patient is immunosuppressed)
- cleared/cured
In a small number (1%) of primary infection patients, TB can have a very poor prognosis. Describe the sequence of events which lead to tuberculous bronchopneumonia. (5)
- primary infection progresses
- primary focus continues to enlarge leading to cavitation
- enlarged hilar lymph nodes compress bronchi leading to lobar collapse
- enlarged lymph node discharges into bronchus
- TUBERCULOUS BRONCHOPNEUMONIA develops
In a small number (1%) of primary infection patients, TB can have a very poor prognosis. Describe the sequence of events which lead to tuberculous pleural effusion. (5)
- occurs 6-12 months after primary infection
- miliary (small seeds) TB fine mottling (spots) on x ray and widespread of small granulomatas
- meningeal TB, very severe leading to high protein in CSF and high lymphocyte numbers
- TUBERCULOUS PLEURAL EFFUSION DEVELOPS
Only a small number survive primary exposure to TB. What are 2 possible outcomes for a TB patient after primary exposure?
- tuberculous bronchopneumonia
2. tuberculous pleural effusion
What are 2 forms of post primary disease?
- Reactivation of mycobacterium (from latent primary infection disseminated by blood stream around the body)
- Reinfected individual from outside source, susceptible and previously infected host
Why is there a different host response if a person is re-infected with TB? (post-primary disease)
- Because of previous sensitisation
- If insufficient immunity is present, then progressive tissue damage occurs
TB affects nearly every organ in the body. What are some examples?
- pulmonary disease
- lymph nodes;usually cervical
- bones and joints (spine, hip etc)
- genito-urinary (kidney, ureter, bladder)
- males (infertility; vas deferens)
- females ( infertility; uterus, fallopian tubes)
- pericardium (constrictive pericarditis)
- abdomen ( ascites, ileal TB and obstruction)
- adrenal ( Addison’s disease)
- lupus vulgaris
Explain the order of events from primary complex to genitourinary, cutaneous TB (chronic)
- primary complex
- progressive primary disease
- miliary (dissemination/seeds of TB), meningeal or pleural TB
- Post primary disease (pulmonary or skeletal)
- genitourinary, cutaneous TB
At roughly what age does miliary or meningeal or pleural TB occur?
6-12 months
At roughly what age does post primary disease (pulmonary and skeletal) TB occur?
typically 1-5 years (maybe 30-40 as well)
At roughly what age does genitourinary and cutaneous TB occur?
Typically 10-15 years (maybe 30-40 as well)
At what age does post-primary TB occur?
can occur at any age (usually reactivation of latent disease)
What is the symptom development in post-primary TB?
very slow, progressive and can take several months rather than days
What are the respiratory symptoms of post-primary pulmonary TB? (5)
- cough
- sputum
- haemoptysis
- pleuritic chest pain
- breathlessness/dyspnoea
What are the general symptoms of post-primary pulmonary TB? (4)
- malaise
- fever
- night sweats
- sudden weight loss
What information needs to be asked in patient’s past medical history when managingTB? (3)
- diabetes
- immunosuprpessive diseases
- previous tB
What information needs to be asked in patient’s drug history when managing TB? (1)
Immunosuppressive drugs
What information needs to be asked in patient’s past social history when managing TB?
- alcohol
- IVDA; intravenous drug abuser
- poor social circumstances
- immigrants from high incidence areas
Why is TB difficult to diagnose?
extensive TB can be present without any physical signs
What can be found in chronic or advanced TB? (3)
- finger clubbing
- crackles
- bronchial breathing
What are the groups of people which fit into the high index of TB suspicion?
- Immunocompromised (HIV, corticosteroid therapy patients, in Africa 70% of TB patients have HIV)
- Malnourished, alcoholics, vegants (without home)
- Previous gastric surgery
- Malignancy
- Diabetes mellitus
- Adolescence or elderly
- Recent immigrants
What are 2 essential investigations in diagnosis of TB?
- 3 sputum specimens on successive days
2. chest radiograph
What are the 3 sputum specimens that need to be collected for TB diagnosis?
- sputum smear (ZN stain, immediate answer if many AAFB)
- sputum culture (can take 8 weeks( now there are quicker methods)
- sputum PCR (as good as a well done smear)
Do sputum samples need to be induced if none produced spontaneously?
Yes; if cant’ cough then stain injected through larynx and patient coughs sputum up
What 3 features can be seen on a chest radiograph suggesting TB?
- Patchy: shadowing, often apices/ upper zones or apex of lower zones, often bilateral (related to high ventilation and poor perfusion at apex= lots O2)
- Cavitation (if advanced)
- May calcify ( if chronic or healed TB)
What are 3 further diagnostic investigations done if sputum sample comes back negative?
- CT scan of thorax
- bronchoscopy with bronchoalveolar lavage and transbronchial biopsy (ZN stain, culture, PCR and biopsy histology)
- pleural aspiration and biopsy if pleural effusion
What is carried out after pleural aspiration and biopsy is obtained in a pleural aspiration during further diagnosis of TB? (4)
- fluid cytology (lymphocytes)
- fluid for AAFB and culture
- biopsy histology
- 1 biopsy sent in saline for culture
What did TB treatment in 1950s include?
- fresh air, sunshine, bed rest, good food, improving immunity and vitamin D and cathelecidin
- surgery; cavity was collapsed, anaerobic conditions caused phrenic crush, artificial pneumothorax, pneumoperinoeum, thoracoplasty, lung resection and not many survived (5 year survival rate only)
Why must multiple drug therapies be used to treat TB nowadays?
as single agent lead to drug resistant organisms within 14 days
How long must TB therapy last for?
at least 6 months (job for committed specialists only)
What is the treshold for HIV testing in TB patients?
low treshold
What is the link between AIDS and TB?
TB is an AIDS defining condition
What 4 medications need to be given over 2 months to treat TB? (RIPE)
- rifampicin
- isoniazid
- ethambutol
- pyrazinamide
What 2 medications need to be given over 4 months to treat TB?
- rifampicin
2. isoniazid
What does WHO recommend for most TB situations?
Directly Observed Therapy (DOT)
What is the greatest global threat to TB treatment worldwide?
multi-drug resistant organisms
What is the treatment for TB in terms of drug numbers and amount of time?
- 4 drugs over 2 months
- 2 drugs over 4 months
When is a person rendered non-infectious?
no symptoms for 2 weeks
What are the side effects for Rifampicin? (5)
- orange “Irn Bru” urine
- tears
- induces liver enzymes, prednisolone and anticonvulsants (against seizures)
- oral contraceptive pill ineffective
- hepatitis
What are the side effects for Isoniazid? (2)
- hepatitis
2. peripheral neuropathy (pyridoxine B6)
What is the side effect for ethambutol?
optic neuropathy (check visual acuity)
What is the side effect for pyraziamide?
gout
What are 2 rules for TB contact tracing?
- identify source (notify)
2. identify transmission
What does likelihood of infection with TB depend on?
- duration of contact
2. intensity of infection
Who needs to be screened if an individual is diagnosed with TB?
screen close household contacts (5-14% become infected and 1 in 6 develop serious disease)
Who needs to be screened if close household contacts have been infected and suggests virulent organism and high transmission?
-screen casual contacts
Would a person who is younger than 16 and has no BCG have immunity to tuberculoprotein?
No, no immunity to tuberculoprotein
For a healthy individual, what should the Heaf/ Mantoux test be? (tuberculin test)
should be NEGATIVE (absence of disease)
What is the grading scale for the Heaf test?
Grade 1: 4-6 papules
Grade 2: indurated ring
Grade 3: disc of induration
Grade 4: induration outside ring, blistering
What 2 tests can be done to screeen for tuberculoprotein?
- Mantoux test
2. Heaf test
What is the management plan if Heaf test is positive ( grade 2-4) which suggest past TB exposure?
CHEST X RAY
- if normal; at risk of disease (miliary, meningeal):
1. chemoprophylaxis to kill mycobacteria
2. rif +inh 3 months (rifampicin)
3. inh (isoniazid) for 6 months - if abnormal: primary TN and treat as per TB
What is the management plan if HEaf test is negative?
- no exposure but repeat test after 6 weeks
- if 2nd Heaf negative, give patient BCG
- if 2nd Heaf positive, it suggests recent infection (treat for TB)
What is the management plan for a patient who is older than 16 and had their BCG?
- chest x ray
If normal; reassure the patient and discharge
If abnormal; investigate for TB and treat it necessary
What are the 3 essential investigations for TB?
- sputum examination
- chest x ray
- bronchoscopy and biopsy
Should patients always be notified?
Yes, always notify patients and people close to them
