Tuberculosis Flashcards
TB global scale
burden from TB globally is falling
- worldwide incidence rate is falling roughly at about 2% a year
what is the number 1 killer of communicable/ infectious diseases in the world?
TB
what is meant by a communicable disease?
one that can spread from one person to another through a variety of ways
TB kills more than ____ and ____ together
HIV and Malaria
examples of countries with high TB burden
India
China
Indonesia
Philippines
how many people on estimate are infected worldwide?
2 billion
TB in the UK
major problem in London- immigration from high incidence areas
2/3 of cases born abroad
vulnerable groups in the UK
those from high prevelence countries
HIV+ or immunosuppressed
elderly, neonates, diabetics
Homeless, alcoholics, injecting drug user, prisoners
Why are diabetics at risk of TB?
tuberculosis might induce glucose intolerance and worsen glycaemic control
-disease presentation and treatment can also be affected
mycobacteria
non-motile bacillus, very slow growing- long treatment
aerobic
unique thick fatty cell wall
what are a few diseases caused by mycobacteria infection
TB
non- tuberculous mycobacteria infections
leprosy
what is so important about the unique thick fatty cell wall in mycobacteria?
means it is resistant to acids, alkalis and detergents
resistant to neutrophil and macrophage destruction
acid- and alcohol- fast bacilli (but not all AAFBs are TB)
how is TB spread
airborne if pulmonary or laryngeal TB but others aren’t
TB bacteria in the air
attached to aerosol droplets which can remain suspended in air for many hours, especially if there is poor air circulation
what is outdoors mycobacteria eliminated by?
UV radiation
dilution
what is one exception to how TB is spread?
mycobacterium bovis - can be spread by consumption of unpasteurized infected cow’s milk (v uncommon in the UK)
What is the result of activated macrophages?
Damaged epithelioid cells
Langhan’s giant cells
Accumulation of macrophages, epithelioid & Langhan’s cells GRANULOMA
Central caseating necrosis (may later calcify)
what happens in the granuloma in TB
central caseating necrosis- tissues turn into a cheesy substance- this may calcify later
two edged sword of Th1 cell mediated immunological response
Eliminates / Reduces number of invading mycobacteria
Tissue destruction is a consequence of activation of macrophages
primary infection in TB
No preceding exposure or immunity
Mycobacteria spread via lymphatics to draining hilar lymph nodes
Usually no symptoms, can be fever, malaise. rarely chest signs
can be cleared/cured
what happens when primary infection progresses to tuberculous bronchopneumonia- 1% of people (3)
Primary focus continues to enlarge - cavitation
Enlarged hilar lymph compress bronchi, lobar collapse
Enlarged lymph node discharges into bronchus
Miliary TB (1-3% of people)
develops, with hematogenous (blood) spread of bacteria to multiple organs
CNS TB (affects 10-30%)
3 clinical categories:- foci of granuloma bursting causes tuberculous meningitis, intracranial tuberculoma, and spinal tuberculous arachnoiditis
what is latent TB disease? (reactivated/ secondary TB)
usually occurs during the two years following the initial infection
- TB enters a dormant stage with low or no replication over prolonged periods of time
balanced state of replication and destruction by immune mechanisms
only develops further in humans not animals
disease timeline TB
primary complex
progressive primary disease
Miliary, meningeal, pleural TB
latent disease
Pulmonary, skeletal
Genitourinary, Cutaneous TB
clinical presentation of TB (9)
cough- haemoptysis SOB fever malaise sweats - mainly at night weight loss CRP normal in 15% ESR normal in 21% Erythema nodosum - fat swelling under skin
what is CRP?
c-reactive protein - produced by the liver in response to inflammation
what is ESR
erythrocyte sedimentation
- indirect measure of the degree of inflammation present in the body
fall in RBC means increased ESR
when to consider a CT scan in TB diagnosis
after carrying out CXR that appears normal
Miliary TB
cavitation and other differental
lymphadenopathy, alternative diagnosis
what is lymphadenopathy?
disease of the lymph nodes, in which they are abnormal in size, number, or consistency
diagnosing active pulmonary TB in CXR
mediastinal lymphadenopathy
pleural effusion
miliary - discrete foci of granulomatous tissue through the lung
pneumonic lesion with enlarged hilar nodes
investigations for TB (8) N.B think different investigations for different types of TB
sputum sample
lumbar puncture in CNS TB
urine in urogenital TB
bronchoscopy with BAL (bronchoalveolar lavage - fluid is squirted into a small part of the lung and then collected for examination)
induced sputum (for those that have trouble producing sputum- inhaled gas)
Endobronchial ultrasound (EBUS) with biopsy
aspirate/biopsy from tissue (lymph-node, bone, joint, brain, abscess)
Endobronchial ultrasound (EBUS) with biopsy
what is NOT routinely used in diagnosing active TB
Mantoux or IGRA
what is IGRA
Interferon Gamma Release Assay- blood test used to detect TB
rules in treatment of TB (6)
multiple drug therapy is essential!!! as single agent treatment leads to drug resistant organisms within 14 days
Therapy must continue for at least 6 months
- Rifampacin, isoniazid, ethambutol and pyrazinamide for 2 months (given as one drug)
- then Rifampicin and isoniazid for a further 4 months
Legal requirement to notify all cases of TB
Test for HIV, Hepatitis B and C
how many tablets does a standard 70kg patient take daily?
12 a day
which drug can be paired with isoniazid to reduce risk of neuropathy
pyridoxine
what is used to treat CNS, MIliar or pericardial TB
steroids
side effects of rifampicin (5)
orange urine/tears/lenses induces liver enzymes hormonal contraception becomes ineffective hepatitis rash
side effects of isoniazid (3)
hepatitis
peripheral neuropathy
rash
side effects of pyrazinamide (3)
hepatitis
gout
rash
side effects of ethambutol (2)
optic neuropathy
rash
BCG vaccination
given selectively since 2005
given to neonates or unvaccinated children under 5, whose parents/grandparents were born in a high risk country
treatment of latent TB
different combos of Rifampicin, Isoniazide, Rifapentine
What stimulates the macrophages to become activated?
Th1 helper cells from the lymph node, these Th1 cells are activated by antigen presenting cells.
These Th1 cells after receiving the signal from the antigen presenting cell then clonially proliferate in the lymph node
Which specific chemical activates Macrophages?
Interferon gamma CD40 - which is produced by Th1 cells in the lymph node
What is the pathology for a susceptible host?
tissue destruction
Organism contained
Disease
Who is normally affected by the primary infection?
Usually children, 80% Infected focus in alveolus, (lymph nodes, gut)
How do we analyse sputum samples for TB?
ZN stain - immediate answer if AAFB
Culture
Sputum PCR
what is the number 1 killer of infectious diseases?
TB
key points of the WHO report on TB 2018
- 6 million TB deaths a year
0. 3 million of these also had HIV
signs of TB
patches of crepitations (crackles)
shadowing on CXR
positive Mantoux test
Diagnosis/investigation of TB
high index of suspicion - mantoux test 3 sputum specimens on successive days CXR PCR histology - caseating granuloma (granuloma round necrotic tissue/cells)
how long should treatment last for monoresistant TB ie resistance to one first-line anti-TB drug only
7-9 months
how long should treatment last for CNS TB, H monoresistance extensive disease?
12 months
