TB Flashcards
Tuberculosis
Re-emergence of an old disease.
Epidemic in 18th century and still major cause of death until early 20th century.
Caused by
Disease caused by more opportunistic environmental strains have become more common with the rise in
M.marinum causes
Re-emergence of an old disease.
Epidemic in 18th century and still major cause of death until early 20th century.
Caused by M.tuberculosis or M.bovis.
Disease caused by more opportunistic environmental strains have become more common with the rise in HIV infection and concurrent TB (eg. M.avians intracellulare,M.kansasii, M.africanum, M.abscessus)
M.marinum causes skin lesions, fishtank granuloma
Re-emergence of tb
Vaccine has become
Attenuated strain differs in … from present infective strains.
Not all ethnic groups respond as well to BCG.
Range from 0-80% effectiveness.
- Need …. response
- Need new
Difficult to detect new disease in
Concurrent rise in …. figures have significantly raised reactivation and new infections.
Lack of compliance of drug regimes, …… have led to ….. in many countries.
Vaccine has become less effective.
Attenuated strain differs in genetic material from present infective strains.
Not all ethnic groups respond as well to BCG.
Range from 0-80% effectiveness.
Need Th1 response
Need new DNA vaccines.
Difficult to detect new disease in vaccinated individuals.
Concurrent rise in HIV figures have significantly raised reactivation and new infections.
Lack of compliance of drug regimes, black market drugs have led to MDRTB in many countries.
Pathogenesis of TB
….. shaped bacterium
- Gram positive cell wall
- A high lipid content
- Lipids called mycolic acids.
- Gives rise to acid fast properties
- Need for special stains, eg auramine or Ziehl Neilson.
Passed by sharing air- enters the …. on small ……. …..that help bypass the ……..
Rod shaped bacterium Gram positive cell wall A high lipid content Lipids called mycolic acids. Gives rise to acid fast properties Need for special stains, eg auramine or Ziehl Neilson.
Passed by sharing air- enters the lungs on small liquid droplets that help bypass the ciliated cells.
Pathogenesis of TB
Enters the ……….. where it multiplies and kills the cell.
Cells of immune system attracted to the area.
……… continue to control the infection and cause ….. damage by
- Release of …… substances
- ….enzymes
- ….. alpha.
Area of dead tissue develops surrounded by …. – tubercle.
Often walled off and …. to form …… when ….. respond early and control infection.
Mostly asym…..
Enters the alveolar macrophages where it multiplies and kills the cell.
Cells of immune system attracted to the area.
Macrophages continue to control the infection and cause tissue damage by
Release of toxic substances
Lysosomal enzymes
TNF alpha.
Area of dead tissue develops surrounded by immune cells – tubercle.
Often walled off and calcified to form granuloma when macrophages respond early and control infection.
Mostly asymptomatic.
Pathogenesis of TB
If immune response i….., the interior …. and the bacteria break out, enter the ….. and spread to other organs.
Bacteria are coughed out in the ….. and the patient with active …. is highly infectious.
If untreated, active TB is fatal in ….. of cases.
Higher in ….. and the immunocompromised.
Can cause disease in ….
If immune response inadequate, the interior liquefies and the bacteria break out, enter the bloodstream and spread to other organs.
Bacteria are coughed out in the sputum and the patient with active TB is highly infectious.
If untreated, active TB is fatal in 50% of cases.
Higher in infants and the immunocompromised.
Can cause disease in bones and joints.
Pathogenesis of TB
Most infected people do not develop the disease but form …… of individuals who are able to reactivate the disease.
….. of world population
Reactivation rates are normally ,,,,, per lifetime,
5% in first five years.
Rise to 5-10% annually if co-infection with ……
Reactivation influenced by ……., concurrent lung disease, eg. Miners etc.
Can reactivate in lungs, ….. and …….
Most infected people do not develop the disease but form a large pool of individuals who are able to reactivate the disease.
1/3 world population
Reactivation rates are normally 2-23% per lifetime,
5% in first five years.
Rise to 5-10% annually if co-infection with HIV.
Reactivation influenced by lowered immune system, concurrent lung disease, eg. Miners etc.
Can reactivate in lungs, bones, bladder etc.
symptoms of TB Fe...... We...... N..... Cou..... Haem..... Symptoms develop over several ..... 9000 cases diagnosed in UK in 2009
Fever Weight loss Night sweats Cough (if pulmonary) Haemoptysis (if pulmonary) Symptoms develop over several months 9000 cases diagnosed in UK in 2009
Diagnosis of TB
Immune suppression of the TB by …..cells is the normal response to the disease
When injected with … derivative (PPD) of TB an infected person (current or past) will have a …. of a red raised lesion 24-48 hours later.
- ….. test.
Limitations are, vaccinated people also respond but not as strongly as infected patients.
No response until 3-4 weeks after infection.
Compromised cellular responses in …. lead to anergy
Also b… tests to diagnose active …. by measuring …… response
Immune suppression of the TB by T cells is the normal response to the disease
When injected with purified protein derivative (PPD) of TB an infected person (current or past) will have a cellular response of a red raised lesion 24-48 hours later.
Mantoux test.
Limitations are, vaccinated people also respond but not as strongly as infected patients.
No response until 3-4 weeks after infection.
Compromised cellular responses in HIV lead to anergy
Also blood tests to diagnose active TB by measuring cytokine response
Diagnosis of TB
….. testing for bacteria.
- ….. stain of sputum + culture.
- Conventional culture can take up to ….. weeks as slow growing.
- ….. in automated systems faster.
Requires ….. of specimen before culture.
Molecular methods developed directly from ….. samples
….. tests also take time but are vital to identify drug ……….
….. and …… drug treatment regimes needed
Sputum testing for bacteria.
Acid fast stain of sputum + culture.
Conventional culture can take up to 10 weeks as slow growing.
Liquid culture in automated systems faster.
Requires decontamination of specimen before culture.
Molecular methods developed directly from sputum samples
Susceptibility tests also take time but are vital to identify drug resistant species.
Complex and lengthy drug treatment regimes needed
Treatment of TB
Very …. growing therefore …… mutants appear if treat with single drug.
Combination therapy over a long period is needed.
Cells are naturally …… and also …….
Frontline drugs used are Isoni Eth Rifamp Pyrazinamide for first 2 months.
Isoniazid and rifampicin for further 4 months.
Isoniazid activated by ….. and ….. mycolic …. production.
Resistant bacteria cease ….. production and drug not activated.
Very slow growing therefore resistant mutants appear if treat with single drug.
Combination therapy over a long period is needed.
Cells are naturally impermeable and also intracellular.
Frontline drugs used are Isoniazid Ethambutol Rifampicin Pyrazinamide for first 2 months.
Isoniazid and rifampicin for further 4 months.
soniazid activated by catalase and inhibits mycolic acid production.
Resistant bacteria cease catalase production and drug not activated.
Treatment of TB.
Rifampicin binds to …. ……. and blocks m…. with greater ….. for bacterial …. than human.
….. synthetic molecule which inhibits but does not kill ….., may interfere with……..
Problems with compliance has led to ….. in many parts of the world with effective results.
Treatment of TB.
Rifampicin binds to RNA polymerase and blocks mRNA with greater affinity for bacterial polymerases than human.
Ethambutol synthetic molecule which inhibits but does not kill bacteria, may interfere with RNA synthesis.
Problems with compliance has led to DOTS in many parts of the world with effective results.
