TB chemoprophylaxis

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TB chemoprophylaxis

• Graham Bothamley
• Clinical Director, NE London TB Network

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Questions

• Do we know who will develop TB?
• Who should take treatment?
• How many will receive unnecessary treatment?
• How many actually take treatment?
• Is it cost-effective?
• Is isoniazid the right treatment?

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Latent TB infection or long-lasting TB immunity?

• Cochrane review 1.68 over 5 years
• HIV PPD cohort 4 over 22 months (7.9 cases
  per 100 person years)
• Human macrophages cannot kill Mtb
• 1-3 tubercle bacilli required for disease
• Selwyn et al. 1989. NEJM 320 545

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Children tuberculin responses, risk of TB over
first 9 years and timing of exposure
Horsburgh. NEJM 2004 3502060 US data 1962-1974
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Adults tuberculin responses, risk of TB over
first 9 years and timing of exposure
Horsburgh. NEJM 2004 3502060 US data 1962-1974
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Progression to TBImmigrant contacts of Sve
cases gt16 yrs in Holland
All IGRA patients had PPDgt10 mm 1/8 patients
missed if 15 mm Kaplan Meier for progression, pos
vs. neg even PPD gt15 mm P0.081 812 contacts
from 380 index cases Kik et al. Eur Respir J
2010 (in press)
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Predictive values of IGRA
TBNET review Diel et al (ECDC)
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PPD NNT to prevent 1 case TB
Rose. Arch Intern Med 2000 1601513
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Treatment and harm

• Treat 72 to prevent one case of TB
• Treat 333 to cause isoniazid induced hepatitis
  (varies with age)

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Hepatotoxicity of isoniazid
Comstock Edwards. Am Rev Respir Dis 1795 111
573
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Adherence

• Horsburgh et al. Chest 2010 137 401-9
• 32 clinics
• 123/720 declined (17.1 14.5 - 20)
• 1045/1994 (52.4) failed to complete
• IJTLD 2008 12 1235 1352
• 3582 seen
• 8 had TB (0.2)
• PPD 996
• 227 refused and only 40 eligible (gt35 yrs)
• 320 (8.9 total 67 who started) completed

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Isoniazid

• Active against rapidly dividing population
• Course longer than TB treatment
• Most hepatotoxic of TB drugs
• Cheap

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Chemoprophylaxis?

• 3 year old
• Mother has smear-positive pulmonary tuberculosis
• BCG vaccinated
• PPD 5 mm response

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Chemoprophylaxis?

• 16 year old
• Somali
• Mother had LN TB
• BCG vaccinated
• PPD 12 mm response

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Chemoprophylaxis?

• 34 year old Russian
• Screened as a new entrant to EU
• Chest x-ray normal
• PPD 35 mm response

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Chemoprophylaxis?

• 45 year old health care worker
• Occupational health screening
• To work with HIV
• Born in UK
• Visited relatives in India for 3m last year
• Chest x-ray normal
• PPD 16 mm response

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Chemoprophylaxis?

• 37 year old from Guinea-Bissau
• HIV
• BCG vaccinated
• PPD 15 mm response

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Chemoprophylaxis?

• 45 year old from Turkey
• Screened as new entrant
• BCG vaccinated
• Chest x-ray one calcified granuloma
• PPD 12 mm response
• Quantiferon 0.52 IU/ml (gt0.35 IU/ml)