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Volume 12, Number 5—May 2006
THEME ISSUE
Tuberculosis Special Section

Research

Isoniazid Preventive Therapy and Risk for Resistant Tuberculosis

Maria Elvira Balcells*1, Sara L. Thomas*, Peter Godfrey-Faussett*, and Alison D. Grant*Comments to Author 
Author affiliations: *London School of Hygiene and Tropical Medicine, London, United Kingdom

Main Article

Table 2

Studies comparing isoniazid treatment with no treatment in HIV-uninfected populations*

Author, country, dates Population Intervention/comparison; blinding Enrolled (n) INH/control Follow-up; loss to follow-up; overall or INH vs. control TB cases: culture positive/total (%)
Definition of INH resistance Resistant cases/total tested (% culture positive tested)
Risk for resistant TB/1,000
INH Controls INH Controls INH Controls RR (95% CI)
Ferebee, USA, 1957–NS (18) Household contacts of TB patients 12 mo INH, 4–7 mg/kg/day/placebo; double blind 7,755/7,996 <10 y; 5.2% vs. 4.9% during Rx NS/86 NS/215 >50 colonies growth in 0.2 μg/mL INH 2/10 NS 2/31 NS 2.22 1.73 1.28 (0.20–8.07)
Katz, USA, 1958–1964 (19) Mental hospital patients with inactive lesions 2 y INH, 300 mg daily/no treatment; not blind 118/107 <4 y post-Rx; 30.6% overall† NS/9 NS/10 Resistance to >0.25 γ INH 1/1 NS 2/5 NS 76.27 37.38 2.04 (0.52–8.08)
Horwitz, Greenland, 1956–1963 (20) 76 villages 2 × 13 wk INH, 400 mg twice weekly/0.1 mg INH; double blind 4,174/3,907 6 y; NS 123/238 (51.7) 186/323 (57.6) (a) > 1 colony at >0.32 μg/mL INH (a) 2/46 (a) 5/66 (a) 2.48 (a) 6.26 (a) 0.40 (0.08–1.97)
(b) Equal to control tube at >0.32 μg/mL INH (b) 2/46 (37) (b) 1/66 (36) (b) 2.48 (b) 1.25 (b) 1.98 (0.18–21.31)
Comstock, USA (Alaska), 1957–1964 (21) Residents of 28 villages and 2 boarding schools 12 mo INH, 300 mg§ daily/placebo; double blind 3,047/3,017 Med.: 69.3 mo (range 43–76 mo); 5.3% observed for <40 mo NS/58 NS/141 NS 4/20 NS 1/50 NS 3.81 0.93 4.07 (0.47–34.98)
Ferebee, USA, 1960–1967 (9) Persons with inactive lesions 12 mo INH, 5 m g/kg/day/placebo; NS 701/714 5 y; 2.2% by 1967 NS/18 NS/49 >50 colonies growth in 0.2 μg/mL INH 2/5 NS 2/25 NS 10.27 5.49 1.87 (0.31–11.19)
Pamra, India, 1958–1968 (22) X-ray screening attendees with inactive TB 12 mo INH, 3–4 mg/kg/day/placebo; NS 139/178 <5 y post-Rx; 8.6% vs. 11.2% 10/18 (55.6) 57/76 (75) Growth on 1 μg/mL INH 3/9 (90) 6/52 (91) 43.17 49.27 0.88 (0.24–3.15)
Hong Kong Chest Service, Hong Kong, 1981–1987 (27) Men with silicosis 24 wk INH, 300 mg daily/placebo;double blind 167/159 2–5 y; 15.8% at 5 y 19/25 (76) 29/36 (80.6) >20 colonies in >1 culture at >0.2 mg/L INH 5/19 (100) 4/28 (97) 39.39 32.35 1.22 (0.34–4.32)

*INH, isoniazid; TB, tuberculosis; RR, relative risk; CI, confidence interval; NS, not stated; med., median; Rx, treatment.
†(a), definition of resistance as >1 colony growth at >0.32 μg/mL INH.
‡(b), definition of resistance as growth equal to control tube at >0.32 μg/mL INH.
§Children were given 5 mg/kg/day INH.

Main Article

1Current affiliation: Department of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

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