TB Flashcards
who identiried the infectious nature of TB?
robert Koch- Kochs postulates
what bacteria causes TB? what are its traits?
- Mycobacterium tuberculosis.
- Aerobic, gram positive, acid-fast bacilli.
- Highly unusual cell surface made up of
lipids and mycolic acid. - Intracellular - Able to survive inside
macrophages.
how is TB transmitted?
- Transmitted by aerosolised droplet from an
infected patient - Inhaled into the alveoli of a new host
what are the outcomes of being infected with TB?
– Primary Tuberculosis (first infection)
– Complete clearance
– Post-primary Tuberculosis (re-infection)
– Active Tuberculosis
– Latent Tuberculosis
how does primary TB occur?
Mostly affects lungs – Pulmonary
Tuberculosis
* Results in an area of granulomatous
inflammation– Seen as a shadow on an x-ray, in TB it is called a Ghon focus
what is the result of 90% of primary TB?
90% of people will never develop active
disease due to a competent immune
response.
what is latent TB?
the bacillus may continue to reside trapped inside the granuloma.
how do you detect latent TB?
- A skin prick test - the tuberculin
test. Is able to detect this hypersensitivity
what can trigger reactivation to latent TB?
abnormalities in cell mediated immunity
what is used to eradiacte latent TB?
- Extended antibiotic regimes used to
eradicate latent TB
what is active or post-primary active TB?
- Small percentage develop at first acquisition.
- More commonly reactivation of latent TB infection.
- May be induced if patient becomes immunocompromised
– E.g. HIV, chemotherapy, high dose corticosteroids. - Results in an aggressive immune reaction which leads to large granulomas with a “cheesy” contents called caseation.
what does active TB look like on x-ray?
- In the lungs this material is coughed up which leads to large cavitating
lesions (observed on x-ray)
what is the 2-year mortality rate of untreated active TB ?
50%
where does extrapulmonary TB cause disease?
at almost ant site in the body
what usually causes extrapulmonary TB?
Usually caused by reactivation of latent infection
what are the most common sites of extrapulmonary tb?
– Lymph nodes; pleura; gastrointestinal tract; bone and CNS
what is disseminated disease?
(Miliary tuberculosis)
– Bacilli transported in blood or lymphatic system
– May develop as a primary infection or post primary reactivation.
– Can affect many organs and may cause diagnostic delay,
particularly if the lungs are not infected.
– More often presents in children and immunocompromised
what is the clinical presentation of active TB?
– cough, weight loss, fever, night sweats, fatigue, dyspnoea, chest pain, haemoptysis.
how do you diagnose active TB?
- Respiratory
– Chest X ray
– Acid fast bacilli test and (multiple) sputum cultures.
– Rapid diagnostic nucleic acid amplification tests (NAAT) often
this is a PCR test (polymerase chain reaction) - Non respiratory
– Biopsy / needle aspiration (culture)
– Culture any surgical / radiological sample
– MRI /CT / Ultrasound as appropriate
– Chest X ray ( to confirm/exclude respiratory disease)
how do you initially manage pulmonary TB in hospital?
- In hospital management – infection control measures required
– Patient must be isolated (single room) if possible
– Personal protective equipment (PPE), staff and visitors.
– Negative pressure room if high risk of multi–drug resistant TB (MDR-TB)
how do you initially manage pulmonary TB in community?
– Advise patient the disease is highly contagious (When active)
– Avoid work / school / crowded places
– Wear face mask in public during first 2 weeks of treatment
what are the two phases of treatment of pulmonary TB?
– Intensive (Initial) phase treatment- normally lasting two months with 4 drugs
– Continuation phase- usually 4-7 months, with 2 drugs
what is the standard treatment for pulmonary TB?
– Initial - rifampicin, isoniazid (with pyridoxine), pyrazinamide and ethambutol for 2 months
– Continuation - rifampicin, isoniazid (with pyridoxine) for a further 4 months.
what is rifampicin? how does it work?
- Bactericidal, blocks RNA polymerase and therefore prevents protein formation.
- Important member of the initial phase treatment
- Kills slowly replicating bacteria throughout the whole course.
- More active than isoniazid in the anaerobic environment of the caseous lesion
when is rifampicin absorption reduced?
- Readily absorbed from the gastrointestinal tract.
- This is reduced if ingested with food.
what are the adverse effects of rifampicin?
– Red orange discolouration of body fluid (stains contact lenses)
– Liver damage
* Common to see elevated liver enzymes, may reflect inflammatory response from disease or a reaction to treatment.
* Enzymes at 4x Upper Limit of Normal (ULN) suggest stopping drug treatment.
* Powerful enzyme inducer major possibility of drug interactions
how does isonaizid work?
- Inhibits the synthesis of the mycolic acids
required for the cell wall. - Bactericidal and very effective at killing rapidly
multiplying mycobacteria. - Acts rapidly to reduce initial bacterial load.
when is isoniazid given?
- Given throughout entire treatment phase to
supplement rifampicin.
where is isonaizid metabolised?
- Metabolised in the liver.
- Acetylation - can be fast or slower.
- This can effect the half life
who is most likely to have more adverse effects from isonaizid? why?
- Slow acetylates and advance HIV more likely to have adverse effects.
what are the adverse effects of isonaizid?
– Hepatotoxicity
– Nausea and vomiting
– Hypersensitivity reaction
– Peripheral neuropathy (PN)
how do we try and avoid peripherap neuropathy with isonaizid?
supplement with B6 (pyridoxine)
what is pyrazinamide? where does it work?
- Bacteriostatic
- Only works in acidic pH - which occurs inside
macrophages in the tubercle
why is pyrazinamide only effective for a short time?
- Only works in acidic pH - which occurs inside
macrophages in the tubercle. - The number of these decrease later in therapy, explaining why this is no longer effective.
what are the side effects of pyrazinamide?
– Hepatotoxicity
– Rashes
– Urticaria
- gout
what kind of drug is ethambutol?
Bacteriostatic
what is the most signifigant side effect with ethambutol?
optic neuritis.
* Manifests as visual alteration, particularly loss of redgreen colour discrimination, progressing to a loss of
visual acuity
what is the standard treatment for continuation phase?
Standard treatment is with rifampicin and
isoniazid for a further four months after
initiation.
what is the risk of non-adherence with TB?
- previous non-adherence, previous treatment failure, history of
homelessness, drug or alcohol misuse, in prison/detention
centre, cognitive or psychological disorders, MDR-TB - Also offer if significantly unwell or the patient requests.
what are ways of promoting adherence?
– Includes Directly Observed Therapy (DOT)
* Medication provided in an appropriate form
* Patient reminders for appointments
* Extensive patient counselling + written information in appropriate language
* Home visits
* Random urine tests and other monitoring
* Access to free TB treatment for everyone
* Social and psychological support (including cultural case management and
broader social support)
* Incentives and enablers to help people follow their treatment regimen
when would there be a treatment interruption?
At least 2 weeks missed or 20% of doses in
initial phase = “treatment interruption”
* Care needed to re-establish treatment
what is multi-drug resistant TB?
– strains which are resistant to both rifampicin AND isoniazid
what is extensive drug resistant TB?
– strains resistant to at least rifampicin and isoniazid, a fluoroquinolone and one
or more of the three available second line injectable drugs:
* kanamycin, amikacin, capreomycin
who are at high risk of being resistant?
- Previous TB drug treatment, particularly with poor adherence
- Contact with a known case of multidrug resistant TB
- Birth or residence in “WHO Hot Spots”
what are examples of novel therapies for multi and extensive drug resistant TB?
Bedaquiline
Delamanid
how does having HIV affect TB?
- The risk of developing TB is estimated to be between 26 and 31 times
greater in people living with HIV
how do you manage HIV-related TB disease?
– Drug Interactions
* Rifampicin with antiretroviral agents (e.g. some of the protease
inhibitors and non-nucleoside reverse transcriptase inhibitors).
how do you diagnose latent TB?
- Mantoux test offered to:
– Household contacts and non household close contacts of patients with active TB
– people who are immunocompromised and at high risk of
– new entrants from high incidence countries presenting for health care
how do you treat latent TB?
3 months of isoniazid and rifampicin OR 6 months of isoniazid
what is the vaccination against TB?
The Bacillus Calmette Guérin (BCG) vaccine
who is BCG given to?
- National programme withdrawn in 2005.
- Now selective neonatal vaccination and those at high risk, under the age of
35.
