Contacts of 123 index cases were enrolled in the study. Complete data for this analysis were available for 955 of 1006 contacts (95%), including 119 index cases (Figure S1). The median age of index cases was 28 years (IQR, 23–36) while 82% were men. Almost one in five index cases were living with HIV (17%). Contacts were similarly distributed in terms of sex (52% female). The median age was 23 years (IQR, 13–31) (Table 1). Almost two-thirds of contacts were from outside the household (61%).
Table 1
Characteristics of the enrolled contacts of 119 tuberculosis cases from Kampala, Uganda that answered the social network survey.
Characteristic
|
N
|
%
|
Contacts enrolled
|
1006
|
100
|
Contacts enrolled with complete data
|
955
|
95
|
Gender
|
|
|
Male
|
462
|
48
|
Female
|
493
|
52
|
Type of contact
|
|
|
Household
|
369
|
39
|
Extra-household
|
586
|
61
|
Age, years, median [IQR]
|
23 [13–31]
|
Age group, years
|
|
|
0–4
|
110
|
12
|
5–14
|
141
|
15
|
≥ 15
|
704
|
74
|
Residence
|
|
|
Lives in Rugaba
|
920
|
96
|
Do not live in Rugaba
|
34
|
4
|
No information available
|
1
|
0
|
HIV Result
|
|
|
Positive
|
71
|
7
|
Negative
|
874
|
92
|
Not done/refusals
|
10
|
1
|
BCG vaccine
|
|
|
Yes¶
|
816
|
85
|
No
|
80
|
8
|
Don’t’ know/Missing
|
59
|
6
|
Tuberculous infection
|
|
|
Yes
|
493
|
52
|
TST Result > = 10 mm
|
431
|
45
|
Previous history of TB/current TB disease
|
62
|
6
|
No (TST Result < 10 mm)
|
462
|
48
|
Abbreviations: HIV, human immunodeficiency virus. BCG, Bacillus Calmette–Guérin. TST, tuberculin skin test. IQR,interquartile range |
¶ Reported by verbal communication or by proof of immunization card.
|
Sex assortment with cases differed by sex; one-third of female contacts were exposed to a female index case whereas 73% of male contacts were exposed to a male index case.
The overall prevalence of tuberculous infection in social networks was 52% (95% CI, 48–55). Both setting and relationship scores were positively associated with tuberculous infection in contacts (Figure S2). Contacts who had setting scores ≥ 14 units and relationship scores ≥ 11 units had a higher prevalence of tuberculous infection than other contacts (77% versus 49%, respectively; P < 0.0001) (Fig. 1; also Figure S3).
When we categorized contact scores into quartiles, we found a rise in the risk of infection with each increasing quartile. In very low, low, medium, and high setting-contact quartiles, the prevalence of tuberculous infection was 44%, 40%, 53% and 70%, respectively (Table 2, Ptrend<.0001). This corresponded to a crude prevalence ratio of 1.0 (95% CI 0.81–1.24), 1.30 (95% CI 1.04–1.63) and 1.64 (95% CI 1.33–2.01) for each quartile compared to the very low quartile. As for the relationship score, in very low, low, medium, and high-contact groups, the prevalence of tuberculous infection was 41%, 47%, 53%, and 66%, respectively (Ptrend<.0001). This corresponded to a crude prevalence ratio of 1.13 (95% CI 0.93–1.37), 1.24 (95% CI 1.01–1.52) and 1.62 (95% CI 1.35–1.96) for each quartile compared to the very low quartile.
Table 2
Prevalence and crude prevalence ratio (95% CI) for tuberculous infection among social contacts of tuberculosis cases by the setting and relationship scores.
|
Score range
|
N
|
Prevalence tuberculous infection
|
Crude prevalence ratio
(95% CI)
|
Category
|
|
|
N
|
% (95% CI)
|
|
Overall
|
|
955
|
493
|
52 (48–55)
|
|
Setting score (continuous)
|
5.3–18.6
|
955
|
|
|
1.05 (1.03–1.07)
|
Setting score (categorical)
|
|
|
|
|
|
Very low
|
5.3-7.0
|
239
|
105
|
44 (38–50)
|
1
|
Low
|
7.0-10.3
|
238
|
95
|
40 (34–46)
|
1.00 (0.81–1.24)
|
Medium
|
10.3–13.7
|
239
|
126
|
53 (46–59)
|
1.30 (1.04–1.63)
|
High
|
13.7–18.6
|
239
|
167
|
70 (64–76)
|
1.64 (1.33–2.01)
|
Relationship score (continuous)
|
4.0-14.8
|
955
|
|
|
1.08 (1.05–1.10)
|
Relationship score (categorical)
|
|
|
|
|
|
Very low
|
4.0-6.4
|
242
|
99
|
41 (35–47)
|
1
|
Low
|
6.4–7.7
|
236
|
111
|
47 (41–53)
|
1.13 (0.93–1.37)
|
Medium
|
7.7–10.1
|
238
|
126
|
53 (46–59)
|
1.24 (1.01–1.52)
|
High
|
10.2–14.8
|
239
|
157
|
66 (60–72)
|
1.62 (1.35–1.96)
|
The relationship between the 12 component variables of the two factors and tuberculous infection prevalence followed a similar pattern as the overall factor scores (Table 3). In the setting score, indoor meetings with reduced ventilation resulted in higher prevalence of infection for contacts of index cases as compared with outdoor meetings or rooms with ventilation. Similarly, the prevalence of infection was higher among contacts spending more than 66.5 hours/week with the case (74%) and individuals who shared meals daily with the index case (64%). Contacts who slept in the same room and/or same bed as the index case had a higher prevalence of tuberculous infection (62–75%) than contacts who did not sleep in the same room as the index case (48%) (Table 3).
Table 3
Association between individual variables that comprised the setting and relationship domains and prevalence of tuberculous infection among contacts of tuberculosis cases.
Variable
|
|
Prevalence TBI *
|
N ¥
|
n
|
Prop %
(95% CI) †
|
SETTING DOMAIN
|
|
|
|
Nature of ventilation at usual meeting place
|
|
|
|
Full ventilation
|
459
|
209
|
46 (41–50)
|
Fair ventilation
|
188
|
100
|
53 (46–60)
|
Minimal ventilation
|
154
|
100
|
65 (57–72)
|
Poor ventilation
|
154
|
84
|
55 (47–62)
|
Frequency of sleeping in the same room and bed
|
|
|
|
No slept in same room, nor bed
|
748
|
358
|
48 (44–51)
|
Slept same room, but not same bed
|
139
|
91
|
65 (57–73)
|
Slept same room and same bed, not daily
|
16
|
12
|
75 (54–96)
|
Slept same room and same bed, daily
|
52
|
32
|
62 (48–79)
|
Most recent meeting was indoor or outdoor
|
|
|
|
Mostly meeting outdoors
|
452
|
201
|
44 (40–49)
|
Equally indoors/outdoors
|
251
|
132
|
53 (46–59)
|
Mostly meeting indoors
|
252
|
160
|
63 (58–69)
|
Frequency of sharing meals with contact
|
|
|
|
Not shared meals
|
365
|
168
|
46 (41–51)
|
Shared meals, less than a day per week
|
83
|
32
|
39 (28–49)
|
Shared meals 1–3 days/week
|
134
|
62
|
46 (38–55)
|
Shared meals 4–6 days/week
|
59
|
31
|
52 (40–65)
|
Shared meals daily
|
314
|
200
|
64 (58–69)
|
Location of usual meeting with contact
|
|
|
|
Outside home of tuberculosis case
|
415
|
49
|
49 (44–53)
|
Home of tuberculosis case
|
540
|
54
|
54 (50–58)
|
Frequency and duration of contact over the past month
|
|
|
|
Less than 3.5 hours/week
|
276
|
107
|
39 (33–44)
|
Between 3.5–28 hours/week
|
378
|
187
|
49 (44–54)
|
Between 28-66.5 hours/week
|
216
|
136
|
63 (56–69)
|
Greater 66.5 hours/week
|
85
|
63
|
74 (65–83)
|
RELATIONSHIP DOMAIN
|
|
|
|
Case discuss and confide important life issues with contact
|
|
|
|
No discuss nor confide
|
410
|
186
|
45 (40–50)
|
Discuss but not confide
|
293
|
150
|
51 (45–57)
|
Discuss and confide
|
252
|
157
|
62 (56–68)
|
Case shared tuberculosis diagnosis with contact
|
|
|
|
No
|
537
|
245
|
46 (41–50)
|
Yes
|
418
|
248
|
59 (55–64)
|
Frequency of care provided by contact in the past three months
|
|
|
|
No care by contact
|
800
|
394
|
49 (46–53)
|
Care provided, less than a day per week
|
35
|
18
|
51 (35–68)
|
Provided care 1–3 days/week
|
41
|
25
|
61 (46–76)
|
Provided care 4–6 days/week
|
15
|
7
|
47 (21–72)
|
Provided care daily
|
64
|
49
|
76 (66–87)
|
Length knowing the contact
|
|
|
|
Less than 2 years
|
375
|
164
|
44 (39–49)
|
2–4 years
|
165
|
83
|
50 (43–58)
|
5–6 years
|
190
|
109
|
57 (50–64)
|
More than 6 years
|
225
|
137
|
61 (54–67)
|
How well does the case knows contact
|
|
|
|
Not well/almost do not know
|
15
|
1
|
7 (0–19)
|
Somewhat well
|
131
|
53
|
40 (32–49)
|
Moderately well
|
229
|
100
|
44 (37–50)
|
Very well
|
580
|
339
|
58 (54–62)
|
Means of transportation used most often with contact.
|
|
|
|
None/walking
|
782
|
398
|
51 (47–54)
|
Another type of transportation
|
173
|
95
|
55 (47–62)
|
¥ N represents the number of contacts in that category, n indicates the number of contacts with tuberculous infection. |
*TBI = tuberculous infection |
†Prop = Proportion of contacts (%) with tuberculous infection. 95% CI = 95% Confident interval of the proportion. |
For each variable in the relationship score, there was a monotonic increase in proportion of infection as the extent of exposure increased within each category, except in care of contact (Table 3). The highest prevalence of tuberculous infection occurred in contacts who discuss and confide with the case (62%), knew the tuberculosis diagnosis of the case (59%), provided daily care to the case (76%), known each other for more than 6 years (61%) and were known very well by their index case (58%).
Since the nature of exposure may differ according to household or extra-household exposure (Figure S4), we stratified the analysis by each category. Among household contacts, the majority had setting scores in the medium and high quartiles and the prevalence of tuberculous infection was highest in the highest quartile (70%, Ptrend <0.0001). Similarly, for the relationship score, the prevalence of tuberculous infection increased with increasing quartile in the contact score, from 41% in the very low quartile to 68% in the high quartile (Ptrend=0.0052). Among extra-household contacts, the prevalence of tuberculous infection tended to increase across quartiles from very low (44%), low (42%) medium (54%), to high (70%) (Ptrend =0.0713). For the relationship score, the prevalence of tuberculous infection in extra-household contacts was 41%, 42%, 50 and 60% in the very low, low, middle, and high relationship-contact quartiles, respectively (Ptrend=0.0048).
Among contacts exposed to index cases with a high-smear grade, the prevalence of tuberculous infection increased from 42% in the lowest quartile of the setting score to 69% in the highest quartile (Ptrend <0.0001) (Figure S5). Among contacts of index cases with a low smear grade, this pattern was not found. Instead, the prevalence of tuberculous infection did not differ markedly among contacts in the lowest three quartiles (40%, 46%, 32%, respectively), and was highest among contacts in the highest quartile of the setting score (75%) (Ptrend=0.0716). For the relationship score, both contacts of index cases with low or high smear grade results showed an increase in the prevalence of tuberculous infection according to the relationship quartiles (Figure S5).
After adjustment for covariates, the setting and relationship scores continued to be associated with the prevalence of tuberculous infection in contacts (Fig. 2). This association was most pronounced in children. In the contacts 0–4 years old, the prevalence ratio for infection was 1.11 (95% CI, 1.04–1.19) for the setting score, meaning that with each increment of one unit in the score, the risk of infection was 11% higher. Similarly, for the relationship score where the prevalence ratio for infection was 1.42 (95% CI, 1.10–1.82). For contacts 5–14 years old, the adjusted prevalence ratio was 1.26 (95% CI, 1.15–1.39) for setting score and 1.14 (95% CI, 1.06–1.23) for the relationship score. Among adults, both scores were associated with infection, but magnitude of effect of the score was less. When analysed by quartiles, the results were like the ones of the crude prevalence ratio. For the setting score, the adjusted prevalence ratios were 1.00 (95% CI 0.82–1.22), 1.33 (95% CI 1.07–1.65) and 1.81 (95% CI 1.47–2.23) for each quartile compared to the very low quartile. For the relationship score, these values were 1.10 (95% CI 0.91–1.34), 1.22 (95% CI 1.0—1.49) and 1.47 (95% CI 1.21–1.79).