TB Flashcards
What is TB
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
TB Transmission
airborne - aerosol form from one persons lung (cough) to another.
& spitting & sneezing on plates/hands
Natural history of TB
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
Latent TB
no clinical disease
may be tiny granulomata that becomes calcified
Detectable CMI to TB on tuberculin skin test
What happens to the 2-5% of those infected with TB?
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
S&S TB
Cough, Fever, Weight loss, night sweats, dyspnoea, chest pain.
Indicative symptoms: weight loss & night sweats
Difference between TB infection & disease
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
Extrapulmonary TB
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
Is TB a notifiable disease
Yes
Gender epidemiology of TB
Slightly more women than men
Who does TB effect
Economically productive people of a nation
What number killer is TB in LMICs
Top 10
TB and HIV
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
Global epidemiology of TB
Most cases concentrated to 30 countries
Predominantly in Africa, Nepal, India, Afghanistan & Pakistan, Russia,
Time trends of TB in last 100 years (UK)
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
BCG Vaccine
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
PH Strategies to manage TB
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)
TB Testing
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.
TB treatment
RIPE for 2 months then RI for 4 months
Rifampin, Isoniazid, Pyrazinamide, Ethambutol
Observation in TB treatment
Necessary because of long treatment time.
Missing doses –> resistance
Adherence & outcomes are better if observed
Optional IM administration requires nurse
Monitoring of TB treatment
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
Outcomes of TB treatment
Cured (Pos –> Neg)
Completed (Neg –> Neg)
Died
Failed (Pos –> Pos)
Defaulted (after 2 months Rx misses at least 2 months Rx)
Transferred out
Issues with DOTS
- 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
Current TB strategy
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
Pillar 1 of end TB strategy
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
Pillar 2 of end TB strategy
- 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
Pillar 3 of End TB Strategy
- discovery, development & rapid uptake of new tools, interventions and strategies
- research to optimize implementation and impact & promote innovations.
Drug resistant TB
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.
Conditions that increase likelihood of reactivation of TB
HIV
Silicosis
Recent latent infection (very significant)
Injecting drug user
Malnutrition
Rate of latent TB in global population
25-30%
Latent TB testing
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
Latent TB treatment
Isoniazid + rifapentine 3 months
Rifampin 4 months
Isoniazid + Rifampin 3 months
Or alternatively just Isoniazid
Issues with latent TB treatment
Hard to persuade people they need treatment when they’re well
Only 1 option for drug resistance (levofloxacin)
