TB 3 million deaths per annum Impacts on western world - Ease of - - PDF document

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TB and immunosuppression

The disease Clinical + immune defences The cure Public health

Incidence of Tb - UK

1900 1915 1930 1945 1960 1975 1990

N

• t

i f i c a t i

• n

s U K

80k

WW1 WW2 Depression Isoniazid, BCG

TB 33% of the world is infected 3 million deaths per annum Impacts on western world

• Ease of travel
• HIV

(TB resurgence

• 30% infected in Africa)
• Multidrug resistance

TB Clinical aspects

Mr MD - breathless for 2 weeks. Smoker, wt loss, haemoptysis

• Cough - haemoptysis
• Weight loss

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Tb - Ghon focus Tb granuloma

• Multinucleated cells

(fused macrophages)

• T-cells.

Caseation Miliary Tb Tuberculous pleural effusion Tb abscess Thoracoplasty - old treatment making a comeback?

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Tb - Mantoux testing Sputum

• 1. Z-N stain
• 2. Culture
• 3. Sensitivity
• 4. PCR

Mycobacteria

• 1. TB (M.Tb, M Bovis)
• 2. Leprae
• 3. Non-tuberculous

(eg. MAC)

• 4. Non-pathogenic 7

Mr MD

• breathless for 2 weeks.
• Smoker
• wt loss, haemoptysis

Treatment

Rifampicin Isoniazid Pyrazinamide Ethambutol

DOTS Directly Observed Treament, Short course.

• Multinucleated cells

(fused macrophages)

• T-cells.

5μ

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High O2 Low O2 Heart Spleen lung CD4 blood Lung - TB Skin - Mantoux “look what I found” “watch out - I’m coming after you. ” “bang bang” Lymph node APC

IFNγ

CD4 CD4 CD4

Protective immunity Impaired immunity ‘Th1’ response ‘Th2’ response IFNγ IL- 4,5 CD4

• NB. Pregnancy!

CD4 CD4 CD4

Viral RNA load

Primary infection AIDS Asymptomatic 1 4 12 weeks 2 4 6 8 10 12 years

HIV

CD4

CD4 count 600 400 200

400 50

M Tb MAC

5 TB What to do about it.

You are put in charge of the tuberculosis program of a rural subsaharan african region. There are 3 small hospitals, 10 doctors and 100 trained health workers in the whole area. You have one year to do something to help control Tb. Your budget is $1m only and you have to pay for staff, diagnosis and treatment of TB. Population 1 million Incidence of Tb probably 300/100,000 - ? how many are ‘open’

Costs Chest X-ray $20 ZN stain $ 2 Mantoux test $ 2 Anti TB drug course $20 BCG vaccination $ 2 Operation $50 Health worker $2/day Doctor $10/day

What are you going to do?

• 1. Detect open Tb cases

ZN sputum stain ? CXR ? mantoux

• 2. Treat open cases
• 3. check contacts

mantoux +ve = CXR & treat

• ve = watch ?BCG ?isoniazid

(CXR if HIV +ve) Treat HIV?

• 4. HIV – TB joint strategies

(30% of HIV have TB)

Staff Health workers 50 x 365 x $2 $36k (100/day) Doctors 3 x 365 x $10 $10k ZN stains 100,000 x $2 $200k (NB. CXRs for all would be 1m x $20 = $20m) Therapy (assuming 300/100,000) Open cases 3,000 x $20 $60k Screening contacts 10 per case = 30,000ZNs $120k Treat +ves = 6,000 $120k HIV +ve contacts = CXR needed $400k HIV treatment? $ 0 Total $946k

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