Tuberculosis

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  • Created by: LBCW0502
  • Created on: 22-03-19 09:02
Outline key facts about TB (1)
Greatest global killers due to single infectious agent (alongside HIV/AIDS). >95% of TB deaths occur on low/middle income countries. Among top 5 causes of death in women aged 15-44
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Outline key facts about TB (2)
In 2014, 1 million children fell ill with TB (killed 140,000 children). Leading killer of HIV-positive people causing 1/4 of all HIV-related deaths. Estimated number of people falling ill with TB each year is declining
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What is the global impact of TB? (1)
TB occurs in every part of the world. Largest number of new TB causes in 2014 was in South-East Asia/Western Pacific (58% of new cases globally). India (23%), Indonesia (10%), China (10%)
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What is the global impact of TB? (2)
Africa had 28% of the world's cases in 2014 (281 cases per 100,000 people population, global average 133/100,000). About 80% of reported TB in 2014 occurred in 22 high burden countries. Some show significant decline in numbers (China/Brazil/Cambodia)
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State the estimates of global TB incidence
Majority in Africa, Indonesia, India etc. (map)
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Who is most at risk of TB? (1)
Mostly young adults (but all age groups can be at risk). >95% of cases and deaths are in developing countries. People with HIV (26-31 times more likely to become sick with TB)
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Who is most at risk of TB? (2)
Big burden in children (1 million new cases of TB in children in 2014, 140,000 deaths in children)
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Outline facts about TB and HIV (1)
In 2014, an estimated 1.2 million (12%) of the 9.6 million people who developed TB worldwide were HIV-positive. Many more HIV-positive patients may have latent TB. In 2014 about 390,000 people died of HIV-associated TB
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Outline facts about TB and HIV (2)
TB accounted for 1/3 of deaths from HIV/AIDS in 2014. HIV-associated TB deaths accounted for 25% of all TB deaths in 2014 (HIV and TB form a lethal combination, speed up other's progress). 51% of TB patients have documented HIV test in 2014
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State the estimates of global HIV prevalence
Majority in South Africa (map)
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Outline key facts about TB in the UK (1)
In 2017, 5102 people notified with TB in England (lowest number since 1990, 5010). Incidence rate in 2017 was 9.2 per 100,000 population (UK's lowest record rate). First time we've fallen under 10 per 10,000 (WHO definition of low incidence country)
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Outline key facts about TB in the UK (2)
Between 2011 and 2017, there was a large decline in both number of TB notifications (-38%) and rate (-41%). People born outside UK (71% of TB notifications in 2017, rate of TB among population is 13 x higher than those born in UK)
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Outline key facts about TB in the UK (1)
(between 2016 and 2017 there was a decrease of 13% and 17% in numbers/rate of TB, no change among people born in the UK)
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Outline facts about TB resistance and deprivation in the UK (1)
31% of people with pTB continue to experience delay of 4+ months between symptom onset and treatment start (in 2017, delays highest in those born in the UK, 37% and age >65y, 38%)
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Outline facts about TB resistance and deprivation in the UK (2)
Number of people with confirmed MDR/RR-TB at diagnosis decreased 2016-2017 (60 vs 55). Proportion was similar (1.7% vs 1.8%). Only 3 of these people had confirmed initial XDR-TB, fewer than last 2y
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Outline facts about TB resistance and deprivation in the UK (3)
In 2017, 12.6% of people notified with TB had a social risk factor (SRF). Higher in those born in the Uk (21%) than those born outside (9.4%). MDR/RR-TB almost 2x higher in people with SRF (2.7%) than those without (1.5%)
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Outline facts about TB resistance and deprivation in the UK (4)
Rate of TB is the most deprived 10% of population (18.4 per 100,000) more than 7 times higher than the least deprived (2.5 per 100,000)
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Outline the TB outcome facts for the UK (1)
In 2016, small increase in proportion of people notified with drug sensitive TB (with an expected treatment duration of <12 months) who completed treatment by 12 months from 83.7% in 2015 to 84.4% in 2016
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Outline the TB outcome facts for the UK (2)
The proportion who died at the last record outcome was 5.5%, lower than in 2015 (6.1%). 58% of drug resistant cohort with drug sensitive TB who had SRF were worse (6.3% died and 6.5% were lost to follow up) compared to those without SRF (4.6%, 3.3%)
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What are the 10 key areas for action in the collaborative TB strategy for England 2015-2020? (1)
Improve access and earlier diagnosis. Provide universal high quality diagnostics. Improvement treatment and care services. Ensure comprehensive contact tracing. Improve BCG vaccination uptake. Reduce drug resistant TB
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What are the 10 key areas for action in the collaborative TB strategy for England 2015-2020? (2)
Tackle TB in under served populations. Implement new entrant latent TB (LTBI) testing and treatment. Strengthen surveillance and monitoring. Ensure an appropriate workforce to deliver TB control
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Outline the trend for TB notifications and rates in England 1971-2017
Number of TB notifications before enhanced surveillance introduced (general decrease, rate decrease). Number since enhanced surveillance introduced (slight increase, rate slightly increased)
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Outline the observed and projected rate of TB notifications in England 2010-2035
2012-2017 (annual decline of 8.2%). Aim to achieve a 90% reduction in rate from 2015-2035. Aim to achieve elimination by 2015 (annual decline of 22.2% required)
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Which area in England has the highest number of TB notifications and rates?
London and South of England
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Who gets TB in the UK? (1)
Young people (55% of cases were 15-44 year olds in 2017, rate highest in 30-34y, 16.1 per 100,000 and 35-39y, 16.0 per 100,000, rate lowest in children 5-9y, 1.3 per 100,000)
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Who gets TB in the UK? (2)
Born outside of UK (71% born outside UK, large decrease in population 2016-17, but still 13x higher than rate of those born in UK, if born outside UK - highest rate seen in 75y+, 55.2 per 100,000, highest numbers since those aged 25-39y)
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Who gets TB in the UK? (3)
(if born in UK, rate is 3.1 per 100,000, even distribution of numbers and rates across all adults age groups, highest in 80y and older in 15-24y, both about 4.2 per 100,000)
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What are the other risk factors for TB?
Homeless people, prisoners, EtOH/substance abusers, people in large urban areas, immunosuppressed (HIV, iatrogenic)
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What causes TB? (1)
Mycobacterium tuberculosis, slow-growing organism, most often affect lungs, TB is curable and preventable. TB is spread from person to person through the air. Coughing, sneezing, spitting propels TB bacteria into air
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What causes TB? (2)
Contacts need to inhale only a few of these germs to become infected
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Describe features of latency (1)
1/3 of the world's population has latent TB (infected by TB bacteria but are not yet ill with disease, cannot transmit disease). People infected with TB have a lifetime risk of falling ill with TB of 10%
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Describe features of latency (2)
(but if there is a compromised immune system then the risk is much higher e.g. HIV, malnutrition, diabetes, smokers, immunosuppression for cancer or other conditions e.g. anti-TNF alpha therapy). Symptoms of active TB may be mild for months
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Describe features of latency (3)
Can lead to delays in healthcare and diagnosis. Can increase risk of onward transmission (someone ill with TB can infect up to 10-15 others in close contact in 1 year)
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What are the symptoms and diagnosis for TB?
-
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Describe features of latency (3)
Can lead to delays in healthcare and diagnosis. Can increase risk of onward transmission (someone ill with TB can infect up to 10-15 others in close contact in 1 year)
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What are the symptoms and diagnosis for TB? (1)
Common symptoms of active lung TB (cough with sputum and blood at times, chest pains, weakness, weight loss, fever, night sweats). Much diagnosis is carried out using microscopy (sputum smear)
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What are the symptoms and diagnosis for TB? (2)
But doesn't detect many cases of less infectious forms of TB. Diagnosing TB in HIV and in children is more difficult and diagnosing resistant TB can be harder still
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State features of mycobacterium tuberculosis
90% of cases asymptomatic, Ghon focus, activated macrophages, T cells, granuloma
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What is the mantoux response?
A person who is exposed to bacteria is expected to mount an immune response in the skin containing bacterial proteins. Reaction is read by measuring diameter of induration across forearm. Tuberculin purified protein derivative (PPD)
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What is primary tuberculosis?
Lung infection as a result of breathing in air droplets from a cough/sneeze of an infection person (mycobacterium TB)
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What are the signs of a post-primary infection?
Regional lymph nodes, fevers, sweats, weight loss, scrofula (glandular swelling)
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Can a healed primary TB reactivate?
Yes
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What is cavitary TB? (1)
Involves upper lobes of the lung. Bacteria cause progressive lung destruction by forming cavities/enlarged air spaces (upper lobes affected because they are highly oxygenated/environment where bacteria thrives
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What is cavitary TB? (2)
Bacterial replication, immune activation, tissue destruction
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What is miliary TB?
Widespread dissemination of mycobacterium TB via hematogenous spread (can affect bowel, spine, pericardium etc.)
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Which type of TB is the most prevalent in England?
Pulmonary TB (2017)
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What is the most common co-morbidity for people with TB in England?
Diabetes (2017)
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When should TB be considered?
If symptoms are for a long duration, failure to identify conventional pathogens or 'at risk' patients
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Outline features of TB treatment (1)
TB is treatable and curable. Active, drug-sensitive TB disease is treated with a standard 6 month course. Use 4 anti-microbial drugs. Patients need information, supervision and support
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Outline features of TB treatment (2)
(adherence can be poor leading to poor outcomes and spread of infection). Vast majority of cases can be cured when compliance is good. Between 2000 and 2014, an estimated 43 million lives were saved through TB diagnosis and treatment (graph)
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Which drugs are used to treat TB? (1)
1st line - isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin. 2nd lin - amikacin, capreomycin, clarithromycin, cycloserine, etionamide, moxifloxacin, para-amino salicylic acid, protionamide, thioacetazone
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Which drugs are used to treat TB? (2)
3rd line - clofazimine, co-amoxiclav, linezolid
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Outline the development of modern TB therapy
Streptomycin (1946), isoniazid (1952 - allowed cure in most patients), rifampicin (1970 - most effect regimens). Duration fo therapy decreased (~ 2y prior to RMP then to 9m with INH and RMP, finally to 6m with addition of PZA)
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Why are combination therapies used? (1)
To cure patients (must destroy all TB bacilli in tissues, if any survive then high change of relapse, bactericidal drugs needed that work in vivo). TB in vivo is a number of different states (freely dividing extracellular bacilli - in cavity walls)
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Why are combination therapies used? (2)
(slowly dividing bacilli - found within macrophages and in acidic, inflammatory lesions, dormant and near dormant bacilli, within cells and inform caseous material)
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Why are combination therapies used? (3)
Anti-TB drugs vary in their ability to destroy bacilli in these states and so prevent resistance
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Describe the targets for drug therapy (1)
Isoniazid (mycolic acid synthesis, inhA, katG, KasA, oxyR-ahpC). Rifampin (DNA dependent RNA polymerase, rpoB). Pyrazinamide (fatty acid synthetase-1, pncA)
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Describe the targets for drug therapy (2)
Ethambutol (arabinosyl transferase, involved in cell wall arabinogalactan synthesis, embA, embB, embC). Streptomycin (30S ribosomal subunit, rspL - encodes for ribosomal protein S12)
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What is the mode of action for TB drug therapy? (1)
Differing MOA and delivery to TB lesions determines regimens. INH/RMP/ETB (active against large populations in cavities). PZA (only active in acidic conditions/inactive in neutral or alkaline pH EC)
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What is the mode of action for TB drug therapy? (2)
TM (2nd line), other aminoglycosides and CAP (penetrate cells poorly, inactive at acidic pH). Slowly replicating organisms in necrotic foci are killed by RMP and less readily by INH. All 1st line agents (except ETB) are bactericidal
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What is the mode of action for TB drug therapy? (3)
(INH/RMP - active in cavitary, intracellular or necrotic foci, basis for short course of INH-RMP regimens)
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Outline the PK the for drugs used in TB treatment (1)
Isoniazid (very low protein binding, very rapid absorption from GI tract, 30-60 mins, good entry into CSF). Rifampin (up to 95% protein binding, rapid absorption from GI tract, 2 hours, poor entry into CSF)
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Outline the PK the for drugs used in TB treatment (2)
Pyrazinamide (very low protein binding, rapid absorption from GI tract, 1-2 hours, good entry into CSF). Ethambutol (binds to erythrocytes, rapid absorption from GI tract, 2 hours, 80% of dose absorbed, poor entry into CSF)
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Outline the PK the for drugs used in TB treatment (3)
Streptomycin (30-35% protein binding, not absorbed from GI tract, poor entry into CSF)
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Outline the metabolism and excretion for drugs used in TB treatment (1)
Isoniazid (metabolised to acetyl derivatives, rate of acetylation is genetically controlled, excreted unchanged and as acetyl derivatives in urine, ratio depends on rate of acetylation)
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Outline the metabolism and excretion for drugs used in TB treatment (2)
Rifampin (metabolised to desacetyl derivative, excreted as desacetylrifampin in bile). Pyrazinamide (metabolised to pyrazinoic acid, excreted mosting ac pyrazinoic acid in urine)
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Outline the metabolism and excretion for drugs used in TB treatment (3)
Ethambutol (metabolised to oxidation products and aldehydes, excreted mostly unchanged in urine, about 15% as metabolites). Streptomycin (no metabolites, excreted unchanged in urine)
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What are the adverse reactions of isoniazid? (1)
Uncommon - hepatitis, cutaneous hypersensitivity reactions (erythema multiforme, peripheral neuropathy). Rate - vertigo, convulsions, optic neuritis and atrophy, psychiatric disturbance, haemolytic anaemia, aplastic anaemia, dermal reactions
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What are the adverse reactions of isoniazid? (2)
(pellagra, purpura and lupoid syndrome, gynecomastia, hyperglycema, arthralgia)
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What are the adverse reactions of rifampin? (1)
Uncommon - hepatitis, flushing, itching with/without rash, GI upsets, flu-like syndrome, headache. Rare (associated with intermittent therapy) - dyspnea, hypotension with/without shock
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What are the adverse reactions of rifampin? (2)
Addisonian crisis, haemolytic anaemia, acute renal failure, thrombocytopenia with or without purpura, transient leukopenia or eosinophilia, menstrual disturbances, muscular weakness, pseudomembranous colitis
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What are the adverse reactions of pyrazinamide?
Common - anorexia. Uncommon - hepatitis, nausea, vomiting, urticaria, nausea, arthralgia. Rare - sideroblastic anaemia, photosensitisation, gout, dysuria, aggravation or peptic ulcer
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What are the adverse reactions of ethambutol?
Uncommon - optic neuritis, arthralgia. Rare - hepatitis, cutaneous hypersensitivity including pruritus and urticaria, photosensitive lichenoid eruptions, paresthesia of the extremities, interstitial nephritis
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What are the drug regimens for TB treatment?
INH, RIF, PZA, EMB 7 days/week for 56 doses (8 weeks) or 5 days/weel for 40 doses (8 weeks). Use four drugs for first 8 weeks then reduce number of drugs over time
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State features of spontaneous drug resistance
Sputum sample. Smear +ve TB > 1 x 10^5 MTB/mL. Smear +ve case > 1 x 10^7-8 MTB/mL. Spontaneous mutation resistance 1 x 10^8-10. Very high risk of resistance generation with single drug therapy
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Describe features of multi drug resistant (MDR) TB (1)
Standard anti-Tb drugs used to decades (resistance is widespread/seen in every country surveyed). MDR-TB caused by bacteria not responding to at least isoniazid/rifampicin
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Describe features of multi drug resistant (MDR) TB (2)
Primary cause of MDR-TB is inappropriate treatment (or incorrect use of anti-TB drugs, use of poor quality medicines). MDR-TB is treatable/curable using second line drugs (limited/not always available, longer duration of therapy required)
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Describe features of multi drug resistant (MDR) TB (3)
(increased costs of treatment and care, increased risk and range of ADRs). Highest number of cases in India and China (map)
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What are the issues with MDR-TB treatment? (1)
RMP resistance (compromises outcome). Treatment failure/relapse (higher when initial drug resistance). INH/RMP resistant strains (testing for second line drugs needed, individualised treatment based on results)
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What are the issues with MDR-TB treatment? (2)
INH/RMP resistance but fluoroquinolone susceptible (always include fluoroquinolone). Risk of treatment failure increased if fluoroquinolone resistant. Important to use an injectable agent as well. (graph, table)
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Describe features of extensively-drug resistance (XDR) TB (1)
Form of MDR-TB that responds to even fewer available medicines (including most effective 2nd line anti-TB drugs). About 480,000 people developed MDR-TB in world in 2013, over 50% were in India, China and Russian Federation
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Describe features of extensively-drug resistance (XDR) TB (2)
About 9.0% of MDR-TB cases had XDR-TB. (map)
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What is XDR-TB defined as?
Resistance to INH, RMP, any fluoroquinolone. And at least one of three injectable 2nd line drugs (amikacin, kanamycin, capreomycin). Difficult to treat, poor outcomes, need to use at least 5 drugs to which organism if susceptible. (table, graph)
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What are the specific roles of a pharmacist in TB treatment?
Compliance/progress, urine spot tests, weight gain, inflammatory markers, defecting side effects, urine colour, lethargy/nausea, pins and needles, LFTs
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What are the drug interactions for RMP? (1)
RMP induces hepatic CYP450. Reduces levels of warfarin, hormonal contraceptives, azole anti fungal agents, methadone, corticosteroids, ciclosporin, tacrolimus, NNRTIs, Pis and many others
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What are the drug interactions for RMP? (2)
Can lead to increased need for monitoring and therapeutic failure in some cases (significant dose increases may be necessary). Counselling on oral contraceptive pill is mandatory for all women
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Which drugs need to be modified in hepatic failure?
Pyrazinamide, rifampin, rifabutin and ethionamide
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Which drugs need to be modified in renal failure?
Pyrazinamide, ethambutol, amikacin, capreomycin, kanamycin, streptomycin, quinolones, para-aminosalicylic acid and cycloserine
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Outline features of TB in pregnancy
Standard regimen is safe (cannot use STM). RMP stops OCP working. Avoid etionamide/protionamide, aminoglycosides
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Outline features of TB in HIV patients
Treatment very effective, regimens unchanged, risk of drug resistance higher, importance of rifampicin and compliance greater, consider interactions with ART
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What is the role of steroids?
Reduce fibrosis (indicated in pericardial TB, TB meningitis). Counteract 'upgrading'. Consider in endobronchial TB, ureteric TB, pleural TB, extensive pulmonary disease. Dose adjustment if on rifampicin
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State features for fixed dose combination (1)
Useful preparations. Rifater - INH 50 mg, RMP 120 mg, PZA 300 mg per tablet. Rifinah 150 (RMP) / 100 (INH) mg. Rifinah 300 (RMP) / 150 (INH) mg. Voractiv - INH 75 mg, RMP 150 mg, PZA 400 mg, ETB 275 mg per tablet
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State features for fixed dose combination (2)
Only useful for drug sensitive TB not MDR-TB or XDR-TB
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Describe features of directly observed therapy (DOT) (1)
Used for expected poor adherence (associated with development of MDR-TB and low cure rates). Cost effective (compliance improved, resistance reduced). Sectioning for completion of therapy (option is available)
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Describe features of directly observed therapy (DOT) (2)
5 elements of DOTS - political commitment to sustained TB control, access to quality assured TB sputum microscopy, standardised short-course drug treatment including observation of therapy, an uninterrupted supply of quality assured drugs.
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Describe features of directly observed therapy (DOT) (3)
Standardised recording and reporting system, enabling assessment of outcome in all patients
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Describe features of re-treatment (1)
Recurrent disease may be due to either relapse or reinfection. Need determine susceptibility to 1st/2nd line drugs is required
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Describe features of re-treatment (2)
1. If drug-susceptible TB and patient had RMP-based DOT - relapse likely due to drug susceptible organism. 2. If compliance has been irregular and if no DOT (probably resistance present). 3. When resistance is suspected, use INH/RMP/PZA/EMB, FQ
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Describe features of re-treatment (3)
And injectable agent (STM) pending susceptibility results. 4. Capreomycin or amikacin can replace STM
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Card 2

Front

Outline key facts about TB (2)

Back

In 2014, 1 million children fell ill with TB (killed 140,000 children). Leading killer of HIV-positive people causing 1/4 of all HIV-related deaths. Estimated number of people falling ill with TB each year is declining

Card 3

Front

What is the global impact of TB? (1)

Back

Preview of the front of card 3

Card 4

Front

What is the global impact of TB? (2)

Back

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Card 5

Front

State the estimates of global TB incidence

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