TB

Question 1

What is TB

Answer 1

Mycobacterium tuberculosis
Aerobic, non motile, non sporing, slightly curved rod shaped 2-4um long bacteria
Acid fast
Grows slowly: takes 2-6 weeks to appear in lab

Question 2

TB Transmission

Answer 2

airborne - aerosol form from one persons lung (cough) to another.
& spitting & sneezing on plates/hands

Question 3

Natural history of TB

Answer 3

Infection –> majority mount an effective immune response, encapsulate organism forever (>95% don’t have disease).
Infection: initial contact made by alveolar macrophages –> bacilli taken in lymphatics to hilar lymph nodes –> Granulomata forms (macrophages & lymphocytes seal in and contain & kill majority of infecting bacilli) (typically in lung apex) –> this cell mediated immune response from T cells persists even though the primary infection is contained therefore CMI is detected in tuberculin skin test.
= latent TB

Question 4

Latent TB

Answer 4

no clinical disease
may be tiny granulomata that becomes calcified
Detectable CMI to TB on tuberculin skin test

Question 5

What happens to the 2-5% of those infected with TB?

Answer 5

Develop clinically evident primary pulmonary disease.
Granuloma grows & develops a cavity (more in apex as more air and less immune cells) –> cavity full of TB bacilli –> expelled when pt coughs –> Bacilli and macrophages coalesce –> granuloma = Primary (Ghon) focus –> mediastinal lymph nodes enlarge.
Primary focus + mediastinal lymph nodes = Ghon Complex

Question 6

S&S TB

Answer 6

Cough, Fever, Weight loss, night sweats, dyspnoea, chest pain.
Indicative symptoms: weight loss & night sweats

Question 7

Difference between TB infection & disease

Answer 7

Infection = just exposed. May eliminate infection all together or may develop latent TB, 10% lifetime risk of reactivation. Non infected unless activates. In untreated HIV reactivation occurs in 50%

Disease = pulmonary TB patient. Untreated: mortality 60%, can infect other people. With treatment: mortality = 5%; non infectious. Reactivations can be cyclical

Question 8

Extrapulmonary TB

Answer 8

TB can spread beyond the lungs and, usually after a latent period, reactivates as Extrapulmonary TB
E.g. lymph node TB, TB meningitis, miliary TB, pleural TB, bone & joint TB, GU TB, Abdominal TB

Question 9

Is TB a notifiable disease

Answer 9

Yes

Question 10

Gender epidemiology of TB

Answer 10

Slightly more women than men

Question 11

Who does TB effect

Answer 11

Economically productive people of a nation

Question 12

What number killer is TB in LMICs

Answer 12

Top 10

Question 13

TB and HIV

Answer 13

More likely to get TB in areas where HIV is more common
Untreated HIV hampers ability to respond to TB (physiologically) and TB makes HIV progress quicker –> pandemics feeding each other
TB is harder to cure with HIV
HIV makes TB harder to diagnose because might not form a granuloma –> CXR looks different & don’t cough up as much bacillus
RIPE and ART interact –> making it harder to treat both HIV and TB

Question 14

Global epidemiology of TB

Answer 14

Most cases concentrated to 30 countries
Predominantly in Africa, Nepal, India, Afghanistan & Pakistan, Russia,

Question 15

Time trends of TB in last 100 years (UK)

Answer 15

1900-1950 rates fell dramatically due to better housing, nutrition, public health measures.
Plateaued during the war
Post war: vaccine –> continues to fall –> then HIV –> increases –> then decreases as HIV began to be controlled.
Varies with immigration trends
Now TB tends to be imported rather than contracted in UK

Question 16

BCG Vaccine

Answer 16

Attenuated. For vaccine to work has to create infection –> scar.
UK Schools programme: vaccination between 1953 and 2006 for secondary school pupils. Vaccination stopped as incidence fell.
Given to neonates in high risk families.
Reduces chance of getting infection & severity of disease.
Less effective in adults

Question 17

PH Strategies to manage TB

Answer 17

Treatment as prevention (untreated will infect 5-10 people).

Directly Observed Treatment Short course (DOTS) (Direct sputum smear microscopy, Observation of treatment, Treatment monitoring, Short course (6 month treatment)

Question 18

TB Testing

Answer 18

Acid Fast Bacillus
Zeil Nielson stain or Fluorescent (auramine-phenol AP <– more accurate).
Pts with positive smear - much more infective.
Ideally need to smear 3 times for a result - usually only get 1.
If smear is negative –> cultures.
Therefore diagnosis = either smear positive pulmonary TB or smear negative pulmonary TB.
Increased use of PCR tests - portable & just need electricity supply.

Question 19

TB treatment

Answer 19

RIPE for 2 months then RI for 4 months
Rifampin, Isoniazid, Pyrazinamide, Ethambutol

Question 20

Observation in TB treatment

Answer 20

Necessary because of long treatment time.
Missing doses –> resistance
Adherence & outcomes are better if observed
Optional IM administration requires nurse

Question 21

Monitoring of TB treatment

Answer 21

Sputum at 2 months and after finishing RI.
Should go + –> - or remain -
To monitor adherence: check treatment card & dates correspond to number of tablets dispensed

Question 22

Outcomes of TB treatment

Answer 22

Cured (Pos –> Neg)
Completed (Neg –> Neg)
Died
Failed (Pos –> Pos)
Defaulted (after 2 months Rx misses at least 2 months Rx)
Transferred out

Question 23

Issues with DOTS

Answer 23

• Uses passive case finding: hard to find cases & find them early enough
• Diagnosis - 3 samples on separate occasions means several journeys to facility & lab requirements
• Observation: inconvenient travel

Question 24

Current TB strategy

Answer 24

End TB Strategy - 3 pillars: integrated patient centred TB care and prevention; bold policies and supportive systems; intensified research and innovation.

Also needs:
- health system strengthening
- address causes
- empower people
- government stewardship & accountability
- coalition with civil society & communities
- protection & promotion of human rights, ethics, equity
- adoption of strategy & targets at country level with global collaboration

Question 25

Pillar 1 of end TB strategy

Answer 25

Early diagnosis & drug susceptibility testing. Screening of contacts and high risk groups.
Treatment of all people with TB & patient support
Collaborative TB & HIV activities
Preventative treatment of people at high risk & vaccination

Question 26

Pillar 2 of end TB strategy

Answer 26

• Political commitment with adequate resources
• Engagement of communities, civil society, health care providers
• universal health coverage policy & frameworks for monitoring
• social protection, poverty alleviation & action on determinants of TB

Question 27

Pillar 3 of End TB Strategy

Answer 27

• discovery, development & rapid uptake of new tools, interventions and strategies
• research to optimize implementation and impact & promote innovations.

Question 28

Drug resistant TB

Answer 28

Increasing issue. Multi drug resistance not just 1 drug.
There is a higher chance of resistance with just 1 or 2 drugs but if all 4 are taken properly resistance unlikely
Ineffective TB services –> incorrect prescriptions, poor quality drugs, erratic drug supply, non adherence –> drug resistance.
Collapse of health systems (e.g. USSR lead to drug resistance)
Resistance is now mostly spread by transmission
Treatment for resistant TB expensive and complex
‘extensively drug resistant TB’ = resistant to 1st and 2nd line drugs.
Not a priority for big pharma as not a HIC issue.

Question 29

Conditions that increase likelihood of reactivation of TB

Answer 29

HIV
Silicosis
Recent latent infection (very significant)
Injecting drug user
Malnutrition

Question 30

Rate of latent TB in global population

Answer 30

25-30%

Question 31

Latent TB testing

Answer 31

Tuberculin Skin Test (Mantoux)
purified protein derived from TB
Issues:
- sensitivity & specificity (get many false negs and false pos)
- not so effective in HIV???
- needs 2 visits
- if had vaccine –> positive test (but degree of reaction can indicate)

Interferon Gamma Release Assays:
- more accurate as not influenced by BCG vaccine
- Blood test - 1 visit

Question 32

Latent TB treatment

Answer 32

Isoniazid + rifapentine 3 months
Rifampin 4 months
Isoniazid + Rifampin 3 months

Or alternatively just Isoniazid

Question 33

Issues with latent TB treatment

Answer 33

Hard to persuade people they need treatment when they’re well
Only 1 option for drug resistance (levofloxacin)