TB chemoprophylaxis

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TB chemoprophylaxis

• Graham Bothamley
• Clinical Director, NE London TB Network

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Questions

1. Do we know who will develop TB?
2. Who should take treatment?
3. How many will receive unnecessary treatment?
4. How many actually take treatment?
5. Is it cost-effective?
6. 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
Criterion TB cases/ positives (95 CI) Sensitivity ()
PPD ? 10 mm 9/288 3.1 (1.3-5.0) 100
PPD ? 15 mm 7/184 3.8 (1.7-5.9) 88
QFT-GIT 5/178 2.8 (1.0-4.6) 63
T-SPOT.TB 6/181 3.3 (1.3-5.3) 75
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
Subjects (n) Tests (n) False results Mean Range
NPV 2242 3257 40 98.8 82.1 - 100
PPV 1034 1467 17/400 4.25 6 - 32
PPV-HIV 1031 1031 5/56 8.93 1.2 - 32
TBNET review Diel et al (ECDC)
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PPD NNT to prevent 1 case TB
Condition NNT Condition NNT
Transplant 5 Diabetes 53.5
HIV 13.5 Silicosis 61
Gastrectomy 23.5 Unexplained WL 66.5
Child contact 24.5 CRF on dialysis 67
PPD conversion 24.5 Leukaemia 91
IVDU 30.5 Immigrants 93
Steroids 98.5
No risk 123.5
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)