supplementary webappendix - thelancet.com supplementary file 1. baseline survey questionnaire the...

Supplementary webappendixThis webappendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors.

Supplement to: Gao L, Li X, Liu J, et al, for the LATENTTB-NSTM study team. Incidence of active tuberculosis in individuals with latent tuberculosis infection in rural China: follow-up results of a population-based, multicentre, prospective cohort study. Lancet Infect Dis 2017; published online July 14. http://dx.doi.org/10.1016/S1473-3099(17)30402-4.

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Supplementary file 1. Baseline survey questionnaire

The relationship between you and respondents: □1）Myself; □2）Families/Guardian;

□3）Other

Part One. Physical examination

Height：[ ]cm； Weight：[ ]kg；Waistline：[ ]cm.

Blood pressure：[ / ]mmHg； Pulse：[ ]time/min.

BCG scar number：□1）None；□2）There is .

Part Two. Personal information

A01 Gender：□1）Male；□2）Female

A02 Date of birth（Gregorian calendar）：└─┴─┘month└─┴─┘day└─┴─┴─┴─┘year

A03 How long have you lived here：□1）6-12 month；□2）12-18 month；□3）18-24 month；

□4）≥24 month

A04 At present, your main profession is (please select one from the following three

categories)：

Agricultural labor：

□1）Farming；

□2）Forestry；

□3 ） Livestock

breeding；

□4）Fisheries；

Migrant workers：

□5）Construction

workers；

□6）Weaving and

dyeing and other

handicraft industry；

□7）Agricultural and

sideline products

processing；

□8）Mining；

□9）The papermaking

industry/chemical

industry；

□10）Building materials

manufacturing or

processing；

Others：

□11）Teacher；

□12）Student (In residence)；

□13）Student (off campus)

□14）Doctors/nurses；

□15）Business/service staff；

□16）Driver；

□17）Self-employed businessman；

□18 ） Administrative

management；

□19）Retirees；

□20） House worker；

□21）Agricultural technology

personnel；

□22）Others， .

2

A05 Your highest education level：□1）Illiterate；□2）Primary school；□3）Junior high

school；□4）High school (technical or training school)；□5）Junior college or

College；□6）Graduate and above.

A06 Your marital status：□1）Married；□2）Never married；□3）Divorced；□4）Widowed.

A07 The medical system you are attending（please choose one or more）：□1）New rural

cooperative medical system (NCMS)；□2）Urban residents' basic medical

insurance(URBMI)；□3）Urban employee basic medical insurance(UEBMI)；

□4） Free medical service；□5）Other social medical insurance；□6）Commercial

health insurance；□7）Did not participate any medical insurance.

A08 Your annual net income in 2012 was Yuan.

A09 The number of people that share you income is .Your annual net family income

in 2012 was Yuan.

Part Three. Living habits

B01 Do you often open the windows at your house? □1）Yes；□2）No

B02 Do you smoke？□1）Yes, currently（on average more than 5 cigarettes per

month）； □2）Yes，but I have quitted for years；□3）Never（less than 5

cigarettes per month, Jump to QB06）；

B03 The kind of the cigarettes you often smoke（please choose one or more）: □1）The

cigarette without a cigarette filter tip；□2）Filter-tip cigarette；□3）Tobacco leaves；

□4）None of the above:

B04 The age when you started smoking: years old.

B05 At present or before quit smoking, how many cigarettes on average do/did you

smoke daily?：□1）More than 20 cigarettes；□2）10-20 cigarettes；□3）5-10cigarettes；

□4）1-5 cigarettes；□5） Less than 1 cigarettes a day

B06 Did you drink alcohol in the past year? □1）No（Jump to QB08）；□2）Yes.

B07 The type and frequency :

Types Average frequency Average alcohol consumption at a

time

Liquor [ ] Times/month [ ]ml

Beer [ ] Times/month [ ] bottle （If less than a bottle

3

of, calculated at 0.5 bottle.）

Others， [ ] Times/month [ ]ml

B08 In the past three months, how often did you eat vegetables/fruit per week?

□1）Everyday；□2）4 to 6 days a week；□3）1-3 days a week；□4）Less than 1 day

per week

B09 In the past three months, how often did you eat meat/eggs per week?


per week

B10 In the past three months, how often did you eat bean products per week?


per week

B11 How many hours do you sleep every day on average? □1）Less than 5 hours；□2）

5-7 hours；□3）7-9 hours；□4）More than 9 hours.

Part Four. Health status

C01 Have you ever been diagnosed with the following diseases: （please choose one or

more）□1）Asthma；□2）Pneumonia；□3）Chronic pharyngitis；□4）Chronic

bronchitis；□5）Chronic rhinitis；□6）Essential hypertension；□7）Cancer（Please

fill in the parts ）；□8）Hepatitis；□9）DiabetesⅡ ；□10）Heart disease；

□11）Cerebral apoplexy；□12）No diagnosed the above diseases.

C02 Have you ever been diagnosed with TB? □1）Yes；□2）No（Jump to QC04）

C03 The type of the TB is（please choose one or more）：

□1）Pulmonary tuberculosis：

Date of diagnosis： (M) (Y) Current status of therapies：[ ]；

□2）Tuberculous pleuritis:

Date of diagnosis： (M) (Y)；Current status of therapies：[ ]；

□3）Extrapulmonary tubereulosis:

Date of diagnosis： (M) (Y)；Current status of therapies：[ ]；

And the type of extrapulmonary tuberculosis：□1）Scrofula；□2）Enterophthisis；

□3）Bone tuberculosis；□4）Nephrotuberculosis；□5）Nervous system tuberculosis；

□6）Tubercular meningitis；□7）Others

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C04 Have your immediate family members ever been diagnosed with TB?

□1）Yes；□2）No（Jump to QC07）；□3）Sorry, I don't know（Jump to QC07）

C05 The date when your immediate family member was diagnosed with TB was:

□1） (M) (Y)，□2）Sorry, I don't know

C06 Current status of therapies：

□1）Has been cured.；□2） Therapy discontinued；□3）Undergoing treatment.；

□4）No treatment.；□5）Sorry, I don't know

C07 Have you ever had close contact with tuberculosis patients?

□1）Yes；□2）No (Jump to QC10)；□3）Sorry, I don't know (Jump to QC10)

C08 If yes, the relationship between your and the patient is： □1）Family；□2） Neighbor；

□3）Colleagues/classmates/friends；□4）Contact in the hospital；□5）Others

C09 When you had contact with TB patients, did you wear face masks or other protective

measures such as strengthen ventilated to avoid infection?

□1）Yes；□2）No

C10 Have you ever been diagnosed with the following immune system diseases?（please

choose one or more）：

□1）Hyperthyroidism；□2）Diabete I；□3）Myasthenia gravis；□4）Systemic lupus

erythematosus；□5）Rheumatoid arthritis；□6）Ankylosing spondylitis (AS)；□7）

AIDS；□8）None of the above.

C11 Have you ever had any transplants?：□1）Yes；□2）No

C12 Have you ever received any immunosuppressive therapy?：□1）Yes；□2）No

C13 Have you ever had any tuberculosis preventive treatment?：□1）Yes；□2）No (Jump

to QD01)；□Sorry, I don't know (Jump to QD01)

C14 TB preventive treatment drugs you are taking ：

□1）Isoniazide；□2）Rifampicin；□3）Isoniazide + Rifapentine；□4）Others ；

□5）Sorry, I don't know.

C15 The beginning and ending points of tuberculosis preventive treatment are：

□1）Undergo treatment， (M) (Y)；

□2）Had to stop treatment，from (M) (Y)to (M) (Y)

Part Five. TB symptoms investigation

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D01 At present, do you have the following symptoms?（please choose one or more） □1）

Cough, sputum；□2）Hemoptysis/ blood-stained sputum；□3）Chest pain；□4）

Chest congestion, shortness of breath；□5）Fever；□6）Night sweat；□7）Limb

weakness；□8）Inappetence；□9）Emaciation；□10）Without the above symptoms.

（Jump to QD03）

D02 How long have you coughed with sputum?

□1）Less than 1 week； □2）1-2 weeks；□3）2 to 3 weeks；□4）More than 3 weeks

D03 Your diagnosis from your doctor：

□1）Have suspected tuberculosis symptoms； □2）No suspicious tuberculosis

symptoms.

Signature of counselor： Date： (D) (M) (Y)

Signature of supervisor： Date： (D) (M) (Y)

6

Supplementary file 2. The implement of quality control (QC) in the study

Key Points of QCa QC Measures

Eligible participant

identification

To repeat door-to-door survey randomly in 10 household in

each site

Inform consent and

questionnaire

To check the completeness of inform consent and the

authenticity and integrity of the questionnaires (randomly

sampling 10% daily)

Blood Collection

To guarantees the volume of the collected blood and the

environment temperature for blood samples transport and

storage (randomly sampling 10% daily)

TST

To check the performance of TST (dose of PPD, location of

injection, environment temperature for PPD storage, etc.)

(randomly sampling 10% daily)

To repeat the measurement of tuberculin reaction size


Digital chest radiography Re-read 10% of the digital chest radiography images

independently by the experts group

QFT

To monitor the operation of the test independently by

experienced laboratory technicians

Repeat all the samples with indeterminate results

Repeat 3% of the detected samples randomly

Data Input To check the authenticity and integrity of the inputted data


Data Cleaning To check the integrity of the data for each participant

To check the authenticity of the data for each participant

Abbreviation: NA, not available; TST, tuberculin skin test; QFT, QuantiFERON-TB Gold In-Tube.

a, Besides the key points listed above, the QC work has also been done on the following procedures:

samples processing and storage, data entry, and the performance of taking digital chest radiography; b,

concordance rate; c, the total of Individuals had the QFT-GIT results; d, the inputted QC of QFT-GIT; e,

the inputted QC of PPD Injecting and measuring of the tuberculin reaction size; f the inputted QC of

digital chest radiography; g, the number of individuals lack any results; h, the number of individuals

had any inaccurate results.

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Supplementary file 3. Flow chart of set-up and follow-up of the study cohort.

After excluding 334 patients with current active TB, 4455 of 21832 (20.41%) healthy

residents without active TB were baseline QFT positive and 6404 (29.33%) were

baseline TST positive (induration ≥ 10mm). A total of 7505 eligible participants were

included in TB infection test positive cohorts. During two years follow-up based on

quarterly suspected symptoms investigation and a two-year chest radiography

screening, a total of 84 patients were diagnosed as incident cases.

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Supplementary file 4. Characteristics of individuals included in TB infected cohort (baseline

QFT+ or TST induration ≥10mm, Part 1/2)

QFT+ TST+ p for

χ2 test n* (%) n* (%)

Total* 4455 6404

Gender 0·379

Female 2012 (45·2) 2947 (46·0)

Male 2443 (54·8) 3457 (54·0)

Study site <0·001

A 1109 (25·9) 2063 (32·2)

B 889 (20·0) 845 (13·2)

C 1500 (33·7) 2460 (38·4)

D 957 (21·5) 1036 (16·2)

Age (years) <0·001

5-9 43 (1·0) 129 (2·0)

10-19 65 (1·5) 294 (4·6)

20-29 187 (4·2) 590 (9·2)

30-39 340 (7·6) 721 (11·3)

40-49 952 (21·4) 1559 (24·3)

50-59 1028 (23·1) 1231 (19·2)

60-69 1095 (24·6) 1157 (18·1)

≥ 70 745 (16·7) 723 (11·3)

Highest education level <0·001

< Primary school 937 (21·0) 841 (13·1)

Primary school 1638 (36·8) 2238 (35·0)

Middle school 1384 (31·1) 2345 (36·6)

High school 422 (9·5) 771 (12·0)

≥College 74(1·7) 209 (3·3)

Household per capita income (USD) #

<0·001

< 860 2784 (62·5) 3541 (55·3)

≥ 860 1671 (37·5) 2863 (44·7)

Smoking status 0·006

Never smoker 2775 (62·3) 4129 (64·5)

Former smoker 133 (3·0) 140 (2·2)

Current smoker 1547 (34·7) 2135 (33·3)

Current alcohol drinking (within past 12 months) 0·002

No 1117 (25·1) 1443 (22·5)

Yes 3338 (75·0) 4961 (77·5)

BCG scars <0·001

Absent 2265 (50·8) 2713 (42·4)

Present 2190 (49·2) 3691 (57·6)

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Supplementary file 4. Characteristics of individuals included in TB infected cohort (baseline

QFT+ or TST induration ≥ 10mm, Part 2/2)

QFT+ TST+ p for

χ2 test n* (%) n* (%)

BMI (kg/m2)

<18·5 299 (6·7) 557 (8·7) 0·001

≥18·5-<24 2307 (51·8) 3328 (52·0)

≥24-<28 1361 (30·6) 1881 (29·4)

≥28 488 (11·0) 637 (10·0)

Self-reported history of T2D 0·745

No 4160 (93·4) 5990 (93·5)

Yes 295 (6·6) 414 (6·5)

Self-reported history of immunological diseases 0·875

No 4383 (98·4) 6298 (98·3)

Yes 72 (1·6) 106 (1·7)

Self-reported history of household close contacts* 0·259

No 4223 (95·5) 6091 (95·7)

Yes (2 years ago) 152 (3·4) 188 (3·0)

Yes (in 2 years) 59 (1·3) 98 (1·5)

History of prior TB& <0·001

No 3964 (88·98) 5863 (91·55)

Yes 491 (11·02) 541 (8·45)

Abbreviation: BCG, bacille Calmette–Guérin; BMI, body mass index; QFT, QuantiFERON-TB Gold In-Tube; TB,

tuberculosis; TST, tuberculin skin test; T2D, type 2 diabetes.

*Data may not sum to total due to missing data.

#Grouped by the national mean level (6000 RMB) in 2010 (China Statistical Yearbook-2010. China Statistics

Press, 2010).

&Self-reported or baseline identified with fibrotic chest radiography abnormalities.

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455 with suspected symptoms

Quarterly follow-up during 2013-2015:

By screening suspected symptoms

The two-year close-out survey in 2015:

By screening suspected symptoms and digital

chest radiography

232 with suspected symptoms and

abnormal chest radiography

Digital chest radiography

3 sputum samples for

each person

Selected 2 sputum

samples for culture

Select 1 sample for

GeneXpert test

Microbiological tests

15 being positive for any

test

488 negative for all three

tests

271 with suspected symptoms and

abnormal chest radiography

Undergo anti-inflammation therapy for 2 weeks

and if showed no response then undergo

subsequent anti-tuberculosis treatment

15 Microbiological

confirmed cases

419 with good response to

anti-inflammation therapy

69 clinically confirmed cases

69 with radiographic improvement after

1-2 months anti-tuberculosis treatment

Supplementary file 5. The process and

evidence for incident cases diagnosis.

Individuals with positive results for any of

the three-kinds of pathogological

bacteriological evidence were defined as

microbiologically confirmed cases. For

both of microbiologically confirmed and

clinically diagnosed cases, the diagnosis

of active TB would be confirmed by their

responses to the following

anti-tuberculosis treatment as well.

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Supplementary file 6. The detailed information on diagnosis for each incident case (Part 1/4)

Site ID Gender Age (years) Year of diagnosis Evidence for diagnosis

Sputum tests Gene-Xpert Response to treatment

Microbiologically confirmed

D 21217301 Female 29 2015 Smear positive N/A Yes

C 11038706 Male 66 2014 Smear positive N/A Yes



C 13027302 Male 78 2014 Smear-positive N/A Yes

A 32008403 Female 43 2015 Smear negative, culture positive Positive Yes

A 32056403 Male 22 2015 Smear negative, culture positive Positive Yes

B 51000201 Male 46 2014 Smear negative, culture positive Positive Yes


B 51083202 Female 73 2014 Smear negative, culture positive Positive Yes


C 12000301 Male 69 2015 Smear negative, culture positive Positive Yes

C 11034801 Male 57 2014 Smear negative, culture positive Positive Yes

A 32024401 Male 78 2015 Smear and culture negative Positive Yes

D 23604201 Female 66 2015 Smear and culture negative Positive Yes

Clinically diagnosed

C 11023301 Female 57 2015 Smear and culture negative Negative Yes

C 12004002 Male 56 2014 Smear and culture negative Negative Yes





12







D 21107401 Male 70 2015 Smear and culture negative Negative Yes








D 23317002 Female 72 2015 Smear and culture negative Negative Yes

D 23502302 Female 75 2015 Smear and culture negative Negative Yes



A 31022101 Male 49 2015 Smear and culture negative Negative Yes






13






A 32011501 Female 62 2015 Smear and culture negative Negative Yes

A 32069705 Female 68 2015 Smear and culture negative Negative Yes


B 51063202 Female 63 2014 Smear and culture negative Negative Yes


B 51081801 Male 60 2015 Smear and culture negative Negative Yes
















14























Abbreviation: N/A, not available; TB, tuberculosis.

15

Supplementary file 7. Characteristics of individuals with success close-out follow-up in 2015

in TB infected cohort (baseline QFT+ or TST induration ≥ 10mm, Part 1/2)

TST+/QFT- TST-/QFT+ QFT+/TST+ p for

χ2 test

n* (% of success

follow-up)

n* (% of success

follow-up)

n* (% of success

follow-up)

Total* 2152 (70·6) 920 (83·6) 2721 (81·1)

Gender 0·004

Female 1051 (71·6) 455 (85·4) 1216 (82·2)

Male 1101 (69·6) 465 (81·9) 1505 (80·3)

Study site <0·001

A 811 (72·0) 135 (80·8) 1079 (80·9)

B 225 (64·3) 224 (82·7) 570 (83·1)

C 895 (71·8) 240 (82·2) 652 (79·8)

D 221 (67·6) 321 (86·5) 420 (81·1)

Age (years) <0·001

5-9 101 (85·6) 28 (87·5) 11 (100)

10-19 145 (57·1) 17 (68) 28 (70)

20-29 243 (55·1) 24 (63·2) 90 (60·4)

30-39 313 (71·0) 48 (80) 202 (72·1)

40-49 610 (74·6) 178 (84·4) 587 (79·2)

50-59 327 (74·1) 205 (86·1) 667 (84·4)

60-69 274 (78·1) 253 (87·5) 714 (88·6)

≥ 70 139 (74·7) 167 (80·3) 422 (78·6)

Highest education level <0·001

< Primary school 163 (74·4) 266 (84·4) 521 (83·8)

Primary school 745 (76·6) 324 (87·1) 1052 (83·1)

Middle school 902 (71·4) 249 (82·2) 850 (78·6)

High school 264 (59·7) 68 (73·1) 255 (77·5)

≥College 78 (51·0) 13 (72·2) 43 (76·8)

Household per capita income (USD)# <0·001

< 860 1057 (70·0) 648 (86·2) 1697 (83·5)

≥ 860 1095 (71·1) 272 (77·9) 1024 (77·5)

Smoking status <0·001

Never smoker 1508(70·9) 656(84·8) 1640 (82·0)

Former smoker 36 (80·0) 33 (86·8) 72 (75·8)

Current smoker 644 (69·8) 264 (80·7) 1081 (79·9)

Current alcohol drinking (within past 12 months) <0·001

No 421 (70·6) 223 (82·6) 675 (79·7)

Yes 1731 (70·5) 697 (83·9) 2046 (81·6)

BCG scars <0·001

Absent 758 (71·7) 507 (83·3) 1348 (81·4)

Present 1394 (69·9) 413 (83·9) 1373 (80·9)

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Supplementary file 7. Characteristics of individuals with success close-out follow-up in 2015

in TB infected cohort (baseline QFT+ or TST induration ≥ 10mm, Part 2/2)

TST+/QFT- TST-/QFT+ QFT+/TST+ p for

χ2 test

n* (% of success

follow-up)

n* (% of success

follow-up)

n* (% of success

follow-up)

BMI (kg/m2)

<18.5 251 (70·3) 82 (82·8) 161 (80·5) <0·001

≥18.5-<24 1078 (68·3) 464 (83·3) 1416 (70·8)

≥24-<28 608 (73·2) 255 (82·0) 862 (82·1)

≥28 214 (75·6) 119 (88·8) 282 (79·7)

Self-reported history of T2D <0·001

No 2058(70·2) 877(83·7) 2548(81·3)

Yes 94(78·3) 43(81·1) 173(79·0)

Self-reported history of immunological diseases 0·511

No 2112 (70·4) 908 (83·6) 2678 (81·2)

Yes 40 (90·9) 12 (80·0) 43 (75·4)

Self-reported history of household close contacts <0·001

No 2077 (70·9) 888 (83·6) 2556 (80·9)

Yes (2 years ago) 38 (57·6) 26 (86·7) 104 (85·2)

Yes (in 2 years) 31 (70·5) 4 (80·0) 45 (83·3)

History of prior TB & <0·001

No 2060 (70·5) 860 (84·1) 2406 (81·8)

Yes 92 (71·3) 60 (75·9) 315 (76·5)

Abbreviation: BMI, body mass index; BCG, bacille Calmette–Guérin; QFT, QuantiFERON-TB Gold In-Tube; TB,

tuberculosis; TST, tuberculin skin test; T2D, type 2 diabetes.

*Data may not sum to total due to missing data. No significant difference on frequency of missing data was

observed between sites.

#Grouped by the national mean level (6000 RMB) in 2010 (China Statistical Yearbook-2010. China Statistics Press,

2010).


17

Supplementary file 8. Risk of active TB among baseline QFT positives when using different

cut-off values

Cut-off values

of baseline QFT

(IU/ml)

Number of

positives

Number of

incidence cases

Person Time

(person-years)

Incidence

density

Cumulative

incidence HR (95% CI)

0.35 4302 72 8300 0·87 1·67 4·01 (2·17, 7·38)

0.40 4091 68 7890·3 0·86 1·66 3·20 (1·88, 5·52)

0.45 3911 64 7542·3 0·85 1·64 2·67 (1·62, 4·41)

0.50 3748 61 7230·3 0·84 1·63 2·41 (1·49, 3·90)

0.55 3602 56 6950 0·81 1·55 1·97 (1·25, 3·10)

0.60 3480 53 6715 0·79 1·52 1·80 (1·16, 2·81)

0.65 3349 52 6460·5 0·80 1·55 1·85 (1·19, 2·88)

0.70 3240 52 6247·8 0·83 1·60 1·97 (1·27, 3·06)

0.75 3136 51 6044·8 0·84 1·63 1·99 (1·28, 3·08)

0.80 3041 50 5863·5 0·85 1·64 2·00 (1·29, 3·08)

0.85 2963 49 5710·3 0·86 1·65 1·99 (1·29, 3·07)

0.90 2886 49 5560 0·88 1·70 2·09 (1·35, 3·22)

0.95 2813 48 5418 0·89 1·71 2·07 (1·35, 3·19)

1.00 2757 48 5308·5 0·90 1·74 2·14 (1·39, 3·30)

1.05 2682 46 5160·5 0·89 1·72 2·04 (1·33, 3·14)

1.10 2612 46 5025 0·92 1·76 2·13 (1·39, 3·28)

1.15 2548 46 4903·3 0·94 1·81 2·21 (1·44, 3·40)

1.20 2489 46 4786·3 0·96 1·85 2·31 (1·50, 3·54)

1.25 2433 46 4678·5 0·98 1·89 2·39 (1·55, 3·67)

1.30 2381 46 4577·5 1·00 1·93 2·47 (1·61, 3·80)

1.35 2320 45 4459 1·01 1·94 2·45 (1·60, 3·77)

1.40 2260 44 4345·5 1·01 1·95 2·42 (1·58, 3·71)

1.45 2212 41 4251·5 0·96 1·85 2·17 (1·41, 3·33)

1.50 2156 41 4141 0·99 1·90 2·26 (1·47, 3·46)

2.00 1782 38 3424·3 1·11 2·13 2·55 (1·66, 3·91)

5.00 708 17 1362·3 1·25 2·40 2·32 (1·36, 3·94)

Abbreviation: CI, confidence interval; HR, hazard ratio; QFT, QuantiFERON-TB Gold In-Tube; TB, tuberculosis.

18

Supplementary file 9. Risk of active TB among baseline TST positives when using different

cut-off values

Cut-off values

of baseline TST

(mm)

Number of

positives

Number of

incidence cases

Person Time

(person-years)

Incidence

density

Cumulative

incidence HR (95% CI)

10 6404 62 12281·5 0·50 0·97 0·52 (0·32, 0·85)

11 6010 60 11527·8 0·52 1·00 0·66 (0·41, 1·06)

12 5640 57 10818·5 0·53 1·01 0·73 (0·46, 1·16)

13 5255 55 10081·5 0·55 1·05 0·84 (0·53, 1·31)

14 4862 51 9319·5 0·55 1·05 0·87 (0·56, 1·35)

15 4454 48 8538 0·56 1·08 0·94 (0·61, 1·45)

16 4012 47 7698 0·61 1·17 1·13 (0·73, 1·73)

17 3686 44 7071·5 0·62 1·19 1·16 (0·76, 1·78)

18 3403 40 6530 0·61 1·18 1·11 (0·73, 1·71)

19 3134 36 6014·8 0·60 1·15 1·05 (0·68, 1·62)

20 2914 34 5601·8 0·61 1·17 1·07 (0·70, 0·66)

21 2632 31 5062·8 0·61 1·18 1·08 (0·69, 1·68)

22 2421 26 4650·8 0·56 1·07 0·95 (0·60, 1·50)

23 2242 22 4307 0·51 0·98 0·84 (0·52, 1·36)

24 2082 19 3998·3 0·48 0·91 0·77 (0·46, 1·28)

25 1930 17 3703 0·46 0·88 0·74 (0·44, 1·26)

26 1790 17 3439·8 0·49 0·95 0·81 (0·48, 1·38)

27 1665 16 3198·8 0·50 0·96 0·83 (0·48, 1·43)

28 1541 14 2960·3 0·47 0·91 0·78 (0·44, 1·38)

29 1435 14 2754·5 0·51 0·98 0·85 (0·48, 1·52)

30 1350 9 2593·5 0·35 0·67 0·55 (0·27, 1·09)

40 602 6 1157·3 0·52 1·00 0·86 (0·38, 1·98)

50 191 1 365·5 0·27 0·52 0·44 (0·06, 3·18)

Abbreviation: CI, confidence interval; HR, hazard ratio; TST, tuberculin skin test; TB, tuberculosis.

19

Supplementary Table 10. Risk of active TB development among those with a history of prior

TB in baseline QFT positives

n/N* (%) Adjusted HR

(95% CI) #

p value

Analyses conducted in all baseline QFT positives

Classified by treatment of prior TB

Without prior TB 42/3964 (1·1) Ref.

With untreated prior TB 22/332 (6·6) 6·47 (3·83, 10·92) <0·001

With treated prior TB 11/159 (6·9) 5·80 (2·98, 11·30) <0·001

Classified by diagnosis time of prior TB


With prior TB 2 years ago 10/111 (9·0) 7·42 (3·71, 14·87) <0·001

With prior TB in 2 years 23/380 (6·1) 5·82 (3·48, 9·73) <0·001

Classified by result of CXR


With prior TB and current CXR normality 5/94& (5·3) 4·34 (1·72, 11·00) <0·001

With prior TB and current CXR abnormality 28/397§(7·1) 6·79 (4·16, 11·08) <0·001

Analyses conducted in individuals with a prior TB history and baseline QFT positive

Classified by treatment of prior TB

With untreated prior TB 21/322 (6·5) Ref.

With treated prior TB 12/169 (7·1) 0·91 (0·44, 1·85) 0·789

Classified by diagnosis time of prior TB

With prior TB 2 years ago 10/111 (9·0) Ref.

With prior TB in 2 years 23/380 (6·1) 0·78 (0·37, 1·64) 0·505

Classified by result of CXR

With prior TB and current CXR normality 5/94& (5·3) Ref.

With prior TB and current CXR abnormality 28/397§(7·1) 1·78 (0·67, 4·73) 0·245

Abbreviation: CI, confidence interval; CXR, digital chest radiography; QFT, QuantiFERON-TB Gold In-Tube; TB,

tuberculosis; HR, hazard ratio.


#Adjusted for age and gender.

&94 participants self-reported prior tuberculosis history.

§100 participants self-reported prior tuberculosis history.

20

Supplementary file 11. Factors associated with the development of active TB among participant

with baseline TST+/QFT- (Part 1/2)

n/N % Univariable Cox regression Multivariable Cox regression

HR (95% CI) p value aHR (95% CI) p value

Total* 9/3050

Gender

Female 2/1468 0·1 Ref. Ref.

Male 7/1582 0·4 3·32 (0·69, 15·96) 0·135 1·37 (0·17, 10·76) 0·767

Age (years)

<40 0/1254 0 NA NA

40-59 3/1259 0·2 NA NA

≥60 6/537 1·1 NA NA

Highest education level

Primary school 5/1191 0·4 Ref.

Middle or High school 4/1706 0·2 0·60 (0·16, 2·23) 0·446

≥College 0/153 0 NA 0·994

Household per capita income (USD)#

< 860 5/1509 0·3 Ref.

≥ 860 4/1541 0·3 0·77 (0·21, 2·88) 0·702

Smoking status

Never smoker 4/2128 0·2 Ref. Ref.

Former smoker 3/45 6·7 32·85 (7·35, 146·84) <0·001 7·38 (1·15, 47·26) 0·035

Current smoker 2/877 0·2 1·23 (0·23, 6·71) 0·812 0·33 (0·04, 2·46) 0·277

Current alcohol drinking (within past 12 months)

No 5/2454 0·2 Ref. Ref.

Yes 4/596 0·7 3·29 (0·88, 12·26) 0·076 3·65 (0·73, 18·15) 0·114

BCG scar

No 2/1057 0·2 Ref.

Yes 7/1993 0·4 1·89 (0·39, 9·09) 0·428

BMI (Kg/m2)

<18.5 2/357 0·6 1·24 (0·26, 5·95) 0·792

≥18.5-<24 7/1578 0·4 Ref.

≥24 0/1114 0 NA 0·993

T2D

No 9/2878 0·3 Ref.

Yes 0/172 0 NA 0·993

History of immune diseases

No 9/3001 0·3 Ref.

Yes 0/49 0 NA 0·994

Close contact with TB patients

No 8/2930 0·3 Ref. Ref.

Yes (2 years ago) 0/66 0 NA 0

Yes (in 2 years) 1/44 2·3 8·37 (1·05, 66·08) 0·045 1·95 (0·20, 18·86) 0·565

21


with baseline TST+/QFT- (Part 2/2)

n/N %

Univariable Cox regression Multivariable Cox regression


History of prior TB &

No 3/2921 0·1 Ref. Ref.

Yes 6/129 4·7 46·25 (11·56, 184·94) <0·001 37·24 (8·63, 160·73) <0·001

Abbreviation: aHR, adjusted hazard ratio; BCG, bacille Calmette–Guérin; BMI, body mass index; CI, confidence interval;

HR, hazard ratio; NA, not available; QFT, QuantiFERON-TB Gold In-Tube; TB, tuberculosis; TST, tuberculin skin test;

T2D, type 2 diabetes.


#Grouped by the national mean level (6000 RMB) in 2010 (China Statistical Yearbook-2010. China Statistics Press, 2010).


22

Supplementary file 12. Factors associated with the development of active TB among participants

with baseline TST-/QFT+ (Part 1/2)


HR (95% CI) p value aHR (95% CI) &

p value

Total* 22/1101

Gender


Male 16/568 2·8 2·61 (1·02, 6·67) 0·045 2·83 (1·10, 7·29) 0·317

Age (years)

< 40 3/155 1·9 Ref. Ref.

40-59 5/449 1·1 0·52 (0·12, 2·16) 0·366 0·35 (0·08, 1·50) 0·158

≥ 60 14/497 2·8 1.31 (0·38, 4·57) 0·668 0·94 (0·26, 3·33) 0·918




≥College 0/18 0 NA 0·991


< 860 17/752 2·3 Ref.

≥ 860 5/349 1·4 0·69 (0·26, 1·88) 0·474

Smoking status

Never smoker 12/774 1·6 Ref.

Former smoker 1/38 2·6 1·66 (0·22, 12·77) 0·626

Current smoker 9/289 3·1 2·13 (0·90, 5·05) 0·087


No 16/831 1·9 Ref.

Yes 6/270 2·2 1·18 (0·46, 3·01) 0·735

BCG scar

No 14/609 2·3 Ref.

Yes 8/492 1·6 0·70 (0·29, 1·67) 0·425

BMI (Kg/m2)

<18.5 3/99 3·0 1·42 (0·40, 5·03) 0·589

≥18.5-<24 12/557 2·2 Ref.

≥24 7/445 1·6 0·73 (0·29, 1·85) 0·502

Self-reported history of T2D

No 19/1048 1·8 Ref. Ref.

Yes 3/53 5·7 3·02 (0·89, 10·19) 0·076 2·84 (0·83, 9·71) 0·097

Self-reported history of immunological diseases

No 21/1086 1·9 Ref.

Yes 1/15 6·7 3·60 (0·48, 26·76) 0·211

Self-reported history of household close contacts

No 20/1062 1·9 Ref. Ref.

Yes (2 years ago) 2/30 6·7 3·43 (0·80, 14·69) 0·096 4·02 (0·93, 17·47) 0·063

Yes (in 2 years) 0/5 0 NA 0 0

23


with baseline TST-/QFT+ (Part 2/2)

n/N %




No 13/1022 1·3 Ref. Ref.

Yes 9/79 11·4 9·86 (4·22, 23·07) <0·001 10·30 (4·33, 24·52) <0·001







24

Supplementary file 13. Factors associated with the development of active TB among participants

with baseline TST+/QFT+ (Part 1/2)


HR (95% CI) p value aHR (95% CI) &

p value

Total* 53/3354

Gender


Male 39/1875 2·1 2·24 (1·22, 4·13) 0·010 1·89 (1·02, 3·50) 0·043

Age (years)

<40 6/480 1·3 Ref. Ref.

40-59 20/1531 1·3 0·91 (0·37, 2·26) 0·838 0·90 (0·36, 2·24) 0·813

≥60 27/1343 2·0 1·37 (0·57, 3·31) 0·488 1·03 (0·42, 2·53) 0·942




≥College 1/56 1·8 1·12 (0·15, 8·17) 0·914


< 6000 38/2032 1·9 Ref.

≥ 6000 15/1322 1·1 0·64 (0·35, 1·17) 0·148

Smoking status


Former smoker 4/95 4·2 3·00 (1·06, 8·51) 0·039

Current smoker 19/1258 7·6 1·02 (0·58, 1·81) 0·943


No 38/2507 1·5 Ref.

Yes 15/847 1·8 1·19(0·65, 2·16) 0·576

BCG scar

No 16/1656 1·0 Ref. Ref.

Yes 37/1698 2·2 2·26 (1·26, 4·06) 0·006 1·99 (1·10, 3·60) 0·023

BMI (Kg/m2)

<18.5 6/200 3·0 1·56 (0·66, 3·72) 0·313 1·21 (0·50, 2·91) 0·672

≥18.5-<24 34/1750 1·9 Ref. Ref.

≥24 13/1404 0·9 0·47 (0·25, 0·90) 0·022 0·62 (0·32, 1·20) 0·155


No 48/3112 1·5 Ref.

Yes 5/242 2·1 1·41 (0·56, 3·55) 0·462


No 51/3297 1·6 Ref.

Yes 2/57 3·5 2·40 (0·59, 9·86) 0·224


No 48/3161 1·5 Ref. Ref.

Yes (2 years ago) 1/122 0·8 0·51 (0·07, 3·69) 0·504 0·42 (0·06, 3·08) 0·396

Yes (in 2 years) 3/54 5·6 3·54 (1·10, 11·35) 0·034 2·24 (0·69, 7·32) 0·181

25


with baseline TST+/QFT+ (Part 2/2)

n/N %




No 29/2942 1·0 Ref. Ref.

Yes 24/412 5·8 6·28 (3·66, 10·79) <0·001 4·87 (2·76, 8·61) <0·001


HR, hazard ratio; QFT, QuantiFERON-TB Gold In-Tube; TB, tuberculosis; TST, tuberculin skin test; T2D, type 2

diabetes.




26

Supplementary file 14. Stratified analysis on the association of TB risk with age, gender, and

history of prior TB among QFT positives

Incidence of TB

n/N* (%)

Adjusted HR

(95% CI)

p for likelihood

ratio test

<60 years Females 7/1207 (0·6) Ref. <0·001

Males 27/1408 (1·9) 1·62 (0·84, 3·13) †

≥60 years Females 13/805 (1·6) Ref.

Males 28/1035 (2·7) 2·66 (1·15, 6·15) †

Males Without a history of prior TB 32/2126 (1·5) Ref. <0·001

With a history of prior TB 23/317 (7·3) 5·17 (3·02, 8·87) ‡

Females Without a history of prior TB 10/1838 (0·5) Ref.

With a history of prior TB 10/174 (5·8) 9·43 (3·83, 23·25) ‡

<60 years Without a history of prior TB 17/2404 (0·7) Ref. <0·001

With a history of prior TB 17/211 (8·1) 10·51 (5·33, 20·72) #

≥60 years Without a history of prior TB 25/1560 (1·6) Ref.

With a history of prior TB 16/280 (5·7) 3·86 (2·06, 7·23) #

Abbreviations: CI, confidence interval; HR, hazard ratio; QFT, QuantiFERON-TB Gold In-Tube; TB, tuberculosis.

†Adjusted for history of prior TB.

‡ Adjusted for age.

# Adjusted for gender.

27

Supplementary file 15. Factors associated with the development of active TB in baseline QFT

positive who completed two-year survey (Part 1/2)



Total* 75/3653 2·1

Gender

Female 20/1675 1.2 Ref. Ref.

Male 55/1978 2·8 2·34 (1·40, 3·90) 0·001 2·26 (1·33-3·84) 0·003

Age (years)

< 40 9/450 2·0 Ref. Ref.

40-59 25/1640 1·5 0·76 (0·35, 1·62) 0·476 0·70 (0·32-1·52) 0·365

≥ 60 41/1563 2·6 1·31 (0·64, 2·69) 0·467 0·88 (0·42-1·85) 0·730

Education level



≥ College 1/56 1·8 0·82 (0·11, 5·95) 0·845


< 860 55/2353 2·3 Ref.

≥ 860 20/1300 1·5 0·66 (0·39, 1·10) 0·108 0·66 (0·38, 1·15) 0·143

Smoking status


Former smoker 5/107 4·7 2·59 (1·03, 6·55) 0·044

Current smoker 28/1245 2·3 1·23 (0·77, 1·99) 0·389


No 54/2752 2·0 Ref.

Yes 21/901 2·3 1·19 (0·72, 1·97) 0·505

BCG scars

Absent 30/1857 1·6 Ref. Ref.

Present 45/1796 2·5 1·55 (0·98, 2·47) 0·062 1·33(0·83-2·13) 0·239

BMI (Kg/m2)

<18.5 9/243 3·7 1·52 (0·74, 3·10) 0·251 1·12 (0·54-2·32) 0·769

≥18.5-<24 46/1889 2·4 Ref. Ref.

≥24 20/1521 1·3 0·54 (0·32, 0·91) 0·021 0·70 (0·41-1·19) 0·184


No 67/3421 2·0 Ref. Ref.

Yes 8/232 3·5 1·77 (0·85, 3·68) 0·128 1·95 (0·93-4·08) 0·077


No 72/3597 2·0 Ref. Ref.

Yes 3/56 5·4 2·71 (0·85, 8·59) 0·091 2·75 (0·86-8·81) 0·090


No 68/3455 2·0 Ref. Ref.

Yes (2 years ago) 3/120 2·3 1·16 (0·36, 3·67) 0·805 0·95 (0·30-3·06) 0·934

Yes (in 2 years) 3/50 6·0 3·06 (0·96, 9·71) 0·058 1·76 (0·54-5·69) 0·347

28

Supplementary file 15. Factors associated with the development of active TB in baseline QFT

positives who completed two-year survey (Part 2/2)

n/N %




No 42/3274 1·3 Ref. Ref.

Yes (2 years ago) 33/379 8·7 6·86 (4·35, 10·83) <0·001 5·50 (3·41-8·86) <0·001







29

Supplementary file 16.The LATENTTB-NSTP study team member list

Site A team: Wen Kong, Cheng Chen, Yuejin Wang, Fengqiu Gong, Lili Guo, Zhonghui

Huang,Wenjuan Shao, Ping Sun, Chunhua Xue, Yiqing Zhu, Weiping Jiang, Yaxiang Gui, Hao Wang,

Ping Yang, Ruiyong Yao, Wenhua Yin, Nong Chao, Tao Jiang, Baima village:Qinxiao Qian, Hongqin

Shi, Yungen Tao, Meiqin Wu, Yuping Yang, Dongmei Zhang, Guoxian Zhang, Jianguo Wang, Xiaojun

Chen, Zhaosheng Ding, Huajie Fu, Li Hang, Yu Huang, Huiping Jiang, Huaxin Jiang, Junlian Li,

Baoxia Liu, Lijun Pan, Caiyun Shao, Huixia Tan, Qiuwei Tan, Weizhong Wang, Jianping Yang, Meiqin

Yi, Qianlu Yin, Hua Yuan, Weixing Zhang, Hong Zhu, Haojun Fei, Liwei Jiang, Wenhong Li, Zhaoer

Shen, Xiaomei Sun, Wenjuan Tang, Mingming Wang, Jinlong Wu, Songqing Zhang, Xiaozhong

Zhang.

Site B team: Ling Guan, Xueling Guan, Wantong Liu, Wei Cui, Zhaokuan Lei, Yongming Wang,

Yongmin Yu, Liucun Song, Tao Wang, Xiaolong Li, Jianrong Luo, Hebin Wang, Weiguo Liu, Fude

Zhang, Fang Zhang, Yongfu Wang, Qingna Zhao, Yinbiao Liu, Jianli Li, Liujie Dan, Dakuan Wang,

Jiaoxia Yan, Guofu Zhu, Zisen Liu, Zhoulun He, Yongfen Yan, Ping Li, Huailiang Shang, Baichao

Heng, Shuli Liu, Zhe Ran, Kun Jiang, Xin Zhu, Haibin Wu, Liling Liang, Jianhui Yuan, Zhigang Wang,

Aijing Meng, Jing Wang, Xia Guan, Jiannan Yang, Yan Li, Haixia Liu, Wuying Wang, Xinhao Liu, Fuke

Qiao, Xianmin Li, Herong Zhao, Chunyuan Zhu, Yanan Lu, Ning Liu, Yanan Peng, Li Wan, Hairui

Chen, Xiaoming Song, Qingtao Lou, Wei Wang, Changshui Liu, Lijuan Zhang, Zhanjiang Zhang,

Shijie Yuan, Yongxin Yang, Suqin Chen, Changjie Dong, Jianguo Ran, Weiling Wu, Zhen Li, Hui

Zhang, Liujia Duan, Fan Yang, Ying Liu, Kun Wang, Lina Yan, Jiangli Ma, Liuyan Wan, Yanfen Li, Han

Wang, Bing Yuan, Ruiling Du, Jie Zhang, Jingge Zhang, Lin Li, Aihua Zhao, Junhong Wei, Ning Zhao,

Yonghui Zhu, Wuyi Mao, Qi Luo, ZhongpuHuang, Hongbin Guo, Na Zheng, Weiwei Pan, Meng Qin,

Ying Li, Shanshan Xiao, Yun Zhang, Weiying Wu, Jing Li, Liusen Song.

Site C team: Yi Tang, Qineng Yao, Kunyun Yang, Meixiong Kuang, Changlin Bao, Tao Xiao, Yanping

Wan, Xiaojie Wan, Binbin Liu, Tieliu Jiang, Xiaoping Zhang, Zhen Tan, Xiaobing Zhang, Zhaoguo Liu,

Zhenhua Chen, Yu Wang, Yanyan Yu, Saibo Dai, PeiLei Hu, Chuanfang Zhang, Yanhong Li, Dehua

Gong, Liqin Liu, Xiaohong Li, Jie Ling, Xinhua Shan, Z huo Zhang, Haibing Deng, Zhengbiao Zeng,

Honghua Li, Shuiping Zhou, Ying Xu, Can Zhang, Haifeng Chen, Xiaoling Wang, Yao Chen, Sheng

30

Yang, Weiping Peng, Huan Sun, Hui Liao, Xiping Xie, Fang Liang, Cheng Hu, Siwei Hu, Xinyu Liu, Jun

Peng, Wenxin Liu, Decheng Liu, Wenbin Liu, Xiangmei Li, Hui Guo.

Site D team: Wen Wang, Yujue He, Bo Wang, Yaping Zhang, Qiaofen Gao, Jianxi Zhao, Weitao

Chen, Qing Li, Taojun Mu, Qijun Liang, Jixiu Gu, Ling Ma, Ning An, Junwen Li, Qinhua Yao,

Chengzhi Liang, Xiuqun Ge, Yalin Chen, Shumao Luan, Yanhong Sun, Ruifang Yang, Bin Ma,

Suiqiang Zhang, Fusheng Liang, Yuan Tian, Hongxia Zhang, Fanqin Yang, Qifeng Lu, Jun Chen, Yan

Dong, Hui Zhang, Shunsheng Zhang, Ziming Jin, Jintao Wang, Jianwei Lan, Zhanjun Zhang, Yumin

Wu, Jianlin Shi, Zhaoping Shi, Yan Chen, Jianxin Ding, Xiaofeng An, Jun Yang, Dongdong Ling.,

Zhenzhou Nie, Chunli Liu, Guangyin Mi, Hongxia Zhang, Jun Ma, Jiyun Guo.

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