Tuberculosis Flashcards
Write a note on the frequency of TB according to the WHO Global TB Report 2020
(7)
TB is the leading cause of death from a single infectious agent
In 2020 there were 10 million cases and 1.4 million deaths
8.2% of cases were in people with HIV
500,000 people developed rifampicin-resistant TB (RR-TB)
78% of (RR-TB?) people had multidrug-resistant TB (MDR-TB)
3.3% of new TB cases and 17.7% of previously treated cases had MDR/RR-TB
Covid-19 pandemic threatens to reverse recent progress in reducing the global burden of TB
What is the most recent worldwide study on TB?
WHO Global TB Report 2020
How many cases of TB were there in 2020 and how many deaths?
10 million cases and 1.4 million deaths
How many cases of TB were there in 2020 and how many deaths?
10 million cases and 1.4 million deaths
Of the 10 million cases of TB in 2020, what percentage of these patients had HIV?
8.2% of cases were in HIV patients
Out of the 10 million cases of TB in 2020, how many developed rifampicin-resistant TB
500,000 people developed RR-TB
Out of the 500,000 cases of RR-TB in 2020, what percentage had multidrug-resistant TB
78% had MDR-TB
What is defined as multi-drug resistant TB?
Resistance to at least both isoniazid and rifampicin
What percentage of the 10 million cases of TB in 2020 were MDR TB?
3.3% of newly diagnosed cases were MDR
17.7% of previously treated cases were MDR -> rate of multi-drug resistance increases with failure to complete antiboitic course etc etc
According to the WHO 2020 report, how many estimated patients never get diagnosed or treated with TB?
Why is this significant?
WHO estimates that over 4 million cases of TB are not diagnosed or treated a year
Suggests there could by potentially 4 million infectious patients acting as a reservoire for potential spread
According to the WHO report of 2020, what percentage of resistant TB cases are detected?
Less than 25% of resistant cases are detected
Where in the world is there a significant burden of TB
Mostly Africa
Other third world countries where there is overcrowding etc e.g. India
What are the 6 main reasons why TB has not gone away?
HIV epidemic
Immigration
Increased poverty
Non compliant drug-therapy
Overcrowding
Latent tuberculosis
How has the HIV epidemic affected TB rates?
The HIV epidemic resulted in a large population of immunodeficient patients which were more susceptible to picking up TB
How has immigration affected TB rates?
There has been an increase in immigration from countries such as Africa and India where there is a much higher prevalence of TB
People from other countries entering Ireland with TB, increasing our stats as well as causing spread of disease to Irish population
How has an increase in poverty affected TB stats?
Increased poverty -> increase in homelessness -> increase in intraveous drug use
Think of homeless in Mater getting TB from rats and pigeons due to living conditions etc
How does non-compliant drug therapy affect TB stats?
Course of antibiotics between 6 and 9 months
Very difficult for patients to finish
Not finishing course of antibiotics results in TB returning or multi-drug resistant TB -> patient remains reservoire -> spread to others etc
How does overcrowding affect TB stats?
Overcrowding in prisons -> low socioeconomic inmates -> only need 1 with TB to spread to a lot of other prisoners etc
Overcrowding in hospitals -> spread to nearby patients etc -> immunocompromised patients etc
How does latent TB affect TB stats?
Latent TB stays in the lung as a granuloma
Latent TB can become reactive at any point in life
Potentially infectious individuals
What countries are most affected by TB?
(according to WHO)
India
Indonesia
China
Philippines
Pakistan
Nigeria
Bangladesh
Democratic republic of congo
Out of the 10 million TB cases in 2020, 8.2% were in HIV patients, where was the burden of these cases?
Over 50% of these 8.2% of cases were in Southern Africa
=> Over 4% of worlwide cases of TB were in HIV patients in southern Africa
Write a note on TB in Ireland based on the most recent study in 2019
(9 points of information)
267 TB cases
Incidence rate of 6.7 per 100,000
Incidence rate of 10.2 in those over 65 years old
40% are Irish born
44% are foreign born cases
Only 196 (73%) cases are culture positive
~10%/27 cases were resistant (5 MDR and 5 mono RF)
1 meningitis case caused by M.bovis
6 TB outbreaks
What was the total number of TB cases in ireland in 2019?
267 TB cases
What is the incidence rate of TB in Ireland?
Incidence of 6.7 per 100,000
This increases to 10.2 in those over 65 years old
Out of the 267 TB cases in ireland in 2019, what percentage were irish orn vs foreign born?
40% were irhs and 44% were foreign born
Out of the 267 TB cases in Ireland in 2019 what percentage of these were culture positive?
196/267 were culture positive = 73% were culture positive
Could have potentially missed 71 cases if only traditional culture used
Out of the 276 cases of TB in ireland in 2019, how many of these were resistant
27 of these cases were resistant
5 of these were MDR
5 of these were mono Rf
How many TB outbreaks were there in 2019 in ireland
6 outbreaks
Comment on the rates of TB over the years in Ireland
TB numbers have been steadily decreasing e.g. from nearly 400 in 2013 to justo ver 200 in 2021
There was a slight increas in 2022 but not above pre-pandemic levels
i.e. downward trend in TB cases in Ireland
Talk about the trends in drug resistant TB in Ireland over the years
Numbers always small but resistance is definitely increasing
e.g. only 4 MDR-TB and 1 XDR-TB in 2013 vs 8 MDR-TB, 4 mono Rf-TB and 2 pre-XDR cases in 2022
Doubled
List and explain the different kinds of resistance in TB
(Got these online, american version, who guidelines in layer flashcard)
mono RR-TB: TB resistance against rifampicin only
MDR-TB: Multi-drug resistant TB (rifampicin and isoniazid)
Pre-XDR TB: isoniazid, rifampicin and a fluoroquinolone OR a second line injectable (amikacin, capreomycin and kanamycin)
XDR-TB: extensively drug resistant TB -> isoniazid, rifampicin, a fluoroquinolone AND a second line injectible OR isoniazid, rifampicin, a fluoroquinolone and bedaquiline or linezolid
Explain what is Pre-XDR TB
Resistance against isoniazid, rifampicin and a fluoroquinolone OR a second line injectable (amikacin, capreomycin and kanamycin)
Explain what is Pre-XDR TB
Resistance against isoniazid, rifampicin and a fluoroquinolone OR a second line injectable (amikacin, capreomycin and kanamycin)
What are the second line injectables used to treat TB?
(3)
Amikacin
Capreomycin
Kanamycin
What is meant by XDR TB?
extensively drug resistant TB
Resistance against isoniazid, rifampicin, a fluoroquinolone AND a second line injectible
OR resistance against isoniazid, rifampicin, a fluoroquinolone and bedaquiline or linezolid
Write a short note on the Mycobacterium species
Acid-fast characteristic feature
Over 90 species identified
Characteristic cell wall
What is mean by acid-fast
When Mycobacterium is stained with a basic dye it cannot be decolourised subsequently with dilute acids
Write a note on the mycobacterium cell wall
Acid fast
Major determinant of virulence
Unique stucture
Unique lipid fraction (lipid section of wall)
Role in resistance
Write a note on the mycobacterium cell wall
Acid fast
Major determinant of virulence
Unique stucture
Unique lipid fraction (lipid section of wall)
Role in resistance
What makes the cell wall of mycobacterium unique?
Presence of peptidoglycan and complex lipids
High lipid content - can be up to 60% of wall
Hydrophobic and waxy
This waxy wall takes a lot of nutrients to develop and is one of the reasons why mycobacterium takes so long to grow
What are the three main components of the mycobacterium lipid fraction of the cell wall
Mycolic acids
Cord factor
Wax-D
What is the role of mycolic acids in the lipid fraction of the mycobacterium cell wall?
These allow the bacterium to grow inside macrophages -> immune evasion
Essential for the pathogenisis of tuberculosis and leprae
These are also whats resposible for the acid-fast property of the wall
What is the role of mycobacterium waxy cell wall in resistance?
Makes organism resistant against antibitoics
Resistance against phagocytosis
What is the role of cord factor in the cell wall of mycobacterium?
Cord factor is a major component of the cell wall
It is toxic to mammalian cells
It inhibits phagocytosis
Cord factor induces the formation of granulomas
Major virulence factors -> M. TB without cord factor are avirulent and virulent strains which loose their ability to produce cord factor loses its virulence
How does Cord factor prevent phagocytosis?
Cord factor prevents the fusion between phagosomal vesicles containing the M, tubercuosis cells and the lysosomes that would destroy them
This allows M.TB to survive within immune cells
What is the role of Wax-D in the waxy cell wall of Mycobacterium?
Role in resisting phagocytosis
How does Wax-D prevent phagocytosis?
Regulates internal acidity by preventing hydrogen ion entering the phagosome -> ensures bacterial DNA replication
Prevents oxidation burst inside the phagosome (i have no idea what this means)
What does MTC stand for?
Mycobacterium tuberculosis Complex
What does NTM stand for?
Non Tuberculous mycobacteria
What does NTM stand for?
Non Tuberculous mycobacteria
Give some examples of mycobacterium that are part of the mycobacterium tueberculosis complex
M. tuberculosis
M. bovis subspecies bovis
M. bovis subspecies caprae
M. bovis BCG
Write a note on M tuberculosis
(5)
An acid fast bacillus
Highly contagious
Aerosolised droplets
Mainly affects lungs but can affect any organ
1/3 people carry latent infection worldwide (1 in 4 irish) -> 10 percent may develop an active infection
Write a note on M tuberculosis
(5)
An acid fast bacillus
Highly contagious
Aerosolised droplets
Mainly affects lungs but can affect any organ
1/3 people carry latent infection worldwide (1 in 4 irish) -> 10 percent may develop an active infection
It is estimated that what percentage of people carry latent M. tuberculosis?
1 in 3 carry latent M TB infection worldwide
1 in 4 in Ireland (Cant find stats for this)
It is estimated that what percentage of people carry latent M. tuberculosis?
1 in 3 carry latent M TB infection worldwide
1 in 4 in Ireland (Cant find stats for this)
What percentage of latent MTB will become active at some point in life?
10% will become active
What percentage of latent MTB will become active at some point in life?
10% will become active
what are the five main symptoms of M. TB
Chronic cough
Haemoptysis -> blood in sputa
Drenching night sweats
Weight loss
Pyrexia
What marks the formation of latent TB
Formation of granulomas in the lung
This happens when immune system is unable to clear infection -> TB resides in these granulomas -> can be reactivated at any point
How long will a person have latent TB for?
Latent TB is lifelong
How long will a person have latent TB for?
Latent TB is lifelong
How can you test to see if a person has TB?
TST Skin test
Chest X ray
Interferon gamma
What is the skin test for TB?
Mantoux tuberculin skin test (TST)
Involves injecting purified protein derivative (PPD) solution and measuring the size of the welt/swelling
What is the interferon test for M. TB?
Interferon Gamma Release Assay (IGRA)
A blood test used to see if person infected with M TB
Measures bodys immun response to TB
After exposure to M TB, how would you prove a person TB negative?
Negative TST or IGRA
Patient does not develop latent TB (X ray clear of granulomas)
Patient does not devlop TB disease
Patient not infectious
After exposure to M TB, how would you prove a person TB negative?
Negative TST or IGRA
Patient does not develop latent TB (X ray clear of granulomas)
Patient does not devlop TB disease
Patient not infectious
After exposure to MTB how would you prove a person has latent TB
Positive TST or IGRA
Normal chest radiograph -> no TB Disease
Latent TB -> might develop symptoms later in life but not currently infectious
After exposure to TB, how would you prove a person has a MTB infection?
Positive TST or IGRA
Abnormal chest radiograph - evidence of TB disease
Symptomatic patient
Positive culture -> might have to wait a few weeks
Patient has TB disease and is infectious
What would be a good sign a TB patient will be culture positive?
If interferon gamma positive
In general what is active TB?
Positive skin test/interferon gamma, positive sputum, positive xray
What are the different stages of TB
Primary tuberculosis (infection beginning usually STS and xray negative)
Progressive primary (active) infection (STS, xray and sputum positive)
Latent-dormant tuberculosis (sts positive but xray neg)
Secondary (reactivation) tuberculosis (sts, xay and sputum positive)
What are the different stages of TB
Primary tuberculosis (infection beginning usually STS and xray negative)
Progressive primary (active) infection (STS, xray and sputum positive)
Latent-dormant tuberculosis (sts positive but xray neg)
Secondary (reactivation) tuberculosis (sts, xay and sputum positive)
What are some risk factors for TB?
Exposure to an individual with active TB
Large infecting dose
Age and gender
Health conditions
Malnutrition
Smoking, silicosis
Occupation
Immune condition
Stress
How is infectious dose a risk factor for TB?
A large infectious dose means you are more likely to be infectious
How is infectious dose a risk factor for TB?
A large infectious dose means you are more likely to be infectious
What health conditions are risk factors for TB
Leukaemia
Hodgkins Disease
Diabetes Mellitus
Alcoholism
IV drug abuse
What aspects of malnutrition are risk factors or TB
Low body weight
Vitamin D deficiency
What aspects of malnutrition are risk factors or TB
Low body weight
Vitamin D deficiency
What immune conditions are risk factors for TB?
Immunosuppression
Corticosteroid treatment
What are the requirements for a TB diagnosis?
(5)
Cough for 3+ weeks with at least one additional symptom
Any patient at high risk of TB with unexplained illness including respiratory symptoms of 3+ weeks
Any HIV patient with unexplained cough and fever
Any high risk patient with a diagnosis of CA pneumonia who has not improved after seven days of treatment
Any high risk patient with incidental findings on chest X ray suggestive of TB even if symptoms are minimal or absent
Talk about the microbial investigation of MTB
Microscopy -> cheap and fast but limit of detection not great, negative microscopy doesnt always mean negative patient, positive miroscopy is definitely positive
NAAY -> nucleic acid amplification test -> best method
Culture -> very slow, takes about 8 weeks (clinicians usually start treatment while awaiting culture)
What are three extra pulmonary forms of TB?
Lymphadenitis
Miliary TB
Tuberculosis Meningitis
What are three extra pulmonary forms of TB?
Lymphadenitis
Miliary TB
Tuberculosis Meningitis
What is lymphadenitis in TB?
This is where TB has spread to the cervical lymph nodes
What is miliary TB?
This is where TB has spread to the blood
Will see infected lesions on X ray
Millet seeds (tiny tubercles)
Progressive Disseminated Haematogenous TB
What is miliary TB?
This is where TB has spread to the blood
Will see infected lesions on X ray
Millet seeds (tiny tubercles)
Progressive Disseminated Haematogenous TB
What is tuberculosis meningitis
This is where TB crosses the blood/brain barrier
Not really seen in Ireland -> 1 case in 2019 -> more of a problem in other countries
What are the first line anti tuberculosis drugs?
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol
What are the main side effects of rifampicin?
Many drug interactions, check for any other medication
Discoloration of urine and contact lenses
Hepatotoxic
What are the main side effects of isoniazid?
Pyridoxine (Vit B6) must be given to prevent INH (isoniazid) induced neuropathy
Hepatotoxic
What is the main side effect of pyrazinamide?
Hepatotoxic
What is the main side effect of pyrazinamide?
Hepatotoxic
What are the main side effects of ethambutol
Risk of ocular toxicity
Must check baseline renal function
Regular visual acuity and colour discrimination
What are the main side effects of ethambutol
Risk of ocular toxicity
Must check baseline renal function
Regular visual acuity and colour discrimination
What are the two main concerns with antimicrobial treatment for MTB
Patients have to take medications for 6 to 9 months -> problems with compliance
Long course -> hepatic toxicity
What is the work-around if there is concerns over anti-microbial compliance?
DOTS -> direct obsrved therapy
Done either inpatient or over video call -> clinician has to watch patient take medication
Much shorter course
What is the WHO definition of RR-TB
TB resistant to rifampicin detected using phenotypic or genotypic methods with or without resistance to other anti-TB drugs
What is the WHO definition of XDR TB
TB which are MDR-TB and also resistat to any fluoroquinalone and at least one additional group A drug (loveofloxacin, moxifloxacin, bedaquilline and linezolid)
What does WHO class as group A drugs?
(4)
Levofloxacin
Moxifloxacin
Bedaquiline
Linezolid
