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

RR (95% CI)

INH

Controls

INH

Controls

INH

Controls

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.