Diagnosis, Treatment and Outcomes of Latent Tuberculosis in the Household Contact Investigation Programme

Park Yong-joon; Kim Youngman; Shin Ji-ae; Han Sunmi; Park Shin Young; Kim Jieun; Park Young Joon; Jung Sun-young; Choi Jae Chol

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Epidemiology and Surveillance

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Public Health Weekly Report 2020; 13(18): 1231-1246

Published online April 29, 2020

Diagnosis, Treatment and Outcomes of Latent Tuberculosis in the Household Contact Investigation Programme

Park Yong-joon, Kim Youngman, Shin Ji-ae, Han Sunmi, Park Shin Young, Kim Jieun, Park Young Joon, Jung Sun-young, Choi Jae Chol

Division of Tuberculosis Epidemic Investigation, Center for Disease Prevention, KCDC; Chung-Ang University hospital

^*교신저자 : pahmun@korea.kr, 043-719-7280

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) which permits unrestricted distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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This study was conducted to check the risk of tuberculosis caused by family contact check-ups and treatment for latent tuberculosis infection, and to provide a basis for management and policy utilization of the linked and analyzed database. This study aimed to confirm the feasibility and effectiveness of an analysis that links latent tuberculosis infection survey data for tuberculosis patients' family contacts with tuberculosis reported data from the National Health Insurance Corporation (NHI), and aimed to determine tuberculosis according to epidemiological characteristics and treatment of family contacts. Preventive effects were analyzed.
This study used a linked database between 1) household contact investigation database in KCDC between 2015 and 2018, 2) TB registry database in the Korea Centers for Disease Prevention and Control (KCDC) for household contacts and index TB cases between 2015 and 2018, and 3) NHI database for household contacts between 2014 and 2018.
In the multivariable Cox proportional hazard model, non-participation in the household contact investigation (Hazard ratio [HR], 1.93), no treatment in LTBI (HR, 2.11), and non-completion of LTBI treatment (HR, 1.48) showed increased risk of active TB infection, whereas completion of LTBI treatment (HR, 0.32), diagnosed as no LTBI with 1-step test (HR, 0.38) or 2-step test (HR, 0.12) showed significantly decreased risk of active TB infection, compared with no test for LTBI. In addition, we found that the incidence of TB was 6.11 times higher than those who treated LTBI when contact investigation was not performed.

Key words Latent tuberculosis infection (LTBI), Household contacts investigation, Treatment of LTBI

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Table 1.

The incidence of active tuberculosis by category of close contacts

	Not performed contact investigation (n=633) n (%)	Subjects for TB screening
		Performed LTBI screening					Not performed LTBI screening (n=53,565) n (%)
		Positive for LTBI screening			Negative for LTBI screening
		Performed treatment		Not treated (n=16,837) n (%)	1 step screening (n=49,643) n (%)	2 step screening (n=10,110) n (%)
		Complete (n=5,357) n (%)	Stop treatment (n=1,010) n (%)	Not treated (n=16,837) n (%)	1 step screening (n=49,643) n (%)	2 step screening (n=10,110) n (%)
Total	18 (2.8)	13 (0.2)	12 (1.2)	165 (1.0)	144 (0.3)	8 (0.1)		544 (1.0)
≤ 1 year	15 (2.4)	5 (0.1)	9 (0.9)	117 (0.7)	85 (0.2)	7 (0.1)	261 (0.5)
1-2 years	3 (0.5)	3 (0.1)	3 (0.3)	36 (0.2)	39 (0.1)	1 (0.0)	137 (0.3)
2-3 years	0 (0.0)	2 (0.0)	0 (0.0)	8 (0.0)	14 (0.0)	0 (0.0)	127 (0.2)
> 3years	0 (0.0)	3 (0.1)	0 (0.0)	4 (0.0)	6 (0.0)	0 (0.0)	19 (0.0)

Table 2.

Baseline characteristics of close contacts and index patients

Characteristics		Close contacts	Index patients
Characteristics		N (%)	N (%)
Total		138,335 (100)	67,638 (100)
Sex	Male	57,424 (41.5)	41,130 (60.8)
Sex	Female	80,911 (58.5)	26,508 (39.2)
Age	Mean±SD	42.28±22.56 57.79±20.25
	≤ 5 years old	8,702 (6.3)	84 (0.1)
	6–18 years old	18,657 (13.5)	1,816 (2.7)
	19–40 years old	32,467 (23.5)	13,463 (19.9)
	41–60 years old	47,169 (34.1)	19,135 (28.3)
	61–75 years old	22,051 (15.9)	16,812 (24.9)
	76 ≤ years old	9,289 (6.7)	16,328 (24.1)

Table 3.

Baseline characteristics of close contacts

Characteristics		N (%)
Relation	Parents	16,768 (12.1)
	Spouse	41,333 (29.9)
	Children	59,689 (43.1)
	Others (sibling, relatives)	20,545 (14.9)
Years of contact investigation	Not done	633 (0.5)
	2015	38,200 (27.6)
	2016	38,769 (28.0)
	2017	32,045 (23.2)
	2018	28,688 (20.7)
Comorbidity*	Hypertension	25,435 (18.4)
	Chronic lung disease	35,786 (25.9)
	Diabetes	15,077 (10.9)
	Renal failure	25,563 (18.5)
	Liver disease	6,859 (5.0)
	Malignancy	4,902 (3.5)
	Rheumatic disease	3,796 (2.7)
	Alcohol intoxication	1,233 (0.9)
	Use of steroid	56,919 (41.2)

* Comorbidity : variables form National Health Insurance Service

Table 4.

Baseline characteristics of index patients

		N (%)
Number of contact	Mean	3
	Standard deviation	4
	Minimum	1
	Median	3
	Maximum	101
	First quartile	2
	Third quartile	4
Present of symptoms	Yes	48,452 (71.6)
Present of symptoms	No	19,186 (28.4)
Symptoms	Sough	33,431 (49.4)
	Sputum	22,702 (33.6)
	Hemoptysis	2,969 (4.4)
	Weight loss	5,931 (8.8)
Cavity on chest PA	Absent	50,138 (74.1)
	Present	14,891 (22)
	Missing	2,609 (3.9)
Acid fast bacilli smear result	Positive	25,875 (38.3)
	Negative	39,722 (58.7)
	Undetermined	82 (0.1)
	Not-done	1,671 (2.5)
	Missing	284 (0.4)

Table 5.

Risk factors for development of tuberculosis

			Incidence of TB cases (n)	Incidence per 1000 person -year	Incidence for 1 year	Hazard Ratio I			Hazard Ratio II (adjusted)
			Incidence of TB cases (n)	Incidence per 1000 person -year	Incidence for 1 year	HR	95% CI		aHR	95% CI
Contacts	Status of LTBI	Not performed LTBI screening	544	3.36	0.49	1.00			1.00
		Not performed contact investigation	18	8.01	2.37	1.46	0.78	2.73	1.93	1.03	3.61
		No LTBI by 1-step	144	1.34	0.17	0.36	0.30	0.43	0.38	0.30	0.47
		No LTBI by 2-step	8	0.34	0.07	0.09	0.05	0.19	0.12	0.06	0.26
		LTBI with treatment discontinuation	12	6.11	0.89	1.57	0.88	2.78	1.48	0.83	2.65
		LTBI with treatment complete	13	1.14	0.09	0.30	0.17	0.52	0.32	0.18	0.55
		LTBI without treatment	165	4.64	0.69	1.23	1.03	1.47	1.22	1.00	1.48
	Sex	Male	390	2.73	0.39	1.00			1.00
	Sex	Female	514	2.54	0.35	0.93	0.82	1.06	0.89	0.78	1.03
	Age(yr)	Under	5	7	0.31	0.07	1.00			1.00
		6–18	76	1.57	0.24	5.07	2.34	10.99	4.54	2.08	9.90
		19–40	222	2.71	0.44	8.69	4.10	18.43	6.71	3.14	14.33
		41–60	267	2.28	0.32	7.25	3.43	15.36	3.98	1.86	8.56
		61–75	173	3.22	0.36	10.23	4.81	21.78	5.52	2.54	12.01
		Over 76	159	7.54	0.91	23.54	11.05	50.17	11.74	5.35	25.74
	Comorbidities	No				1.00			1.00
		Hypertension	222	3.67	0.45	1.50	1.29	1.75	0.88	0.73	1.07
		Chronic lung disease	248	2.81	0.40	1.10	0.95	1.27	1.09	0.93	1.28
		Diabetes	137	3.81	0.42	1.51	1.26	1.81	1.06	0.86	1.31
		Renal failure	15	6.76	0.70	2.53	1.52	4.21	1.71	1.00	2.94
		Liver disease	53	3.28	0.38	1.24	0.94	1.64	1.06	0.80	1.42
		Malignancy	40	3.61	0.47	1.35	0.98	1.85	1.08	0.78	1.51
		Rheumatic disease	29	3.12	0.35	1.18	0.82	1.71	0.98	0.67	1.44
		Use of steroid	390	2.67	0.36	1.03	0.91	1.18	0.98	0.85	1.13
Index	Cavity	Presence	539	2.13	2.93	2.07	1.80	2.36	1.59	1.38	1.84
	Cavity	Absence	346	4.37	0.61	1.00			1.00
	Sputum culture	Positive	724	3.41	0.48	2.60	2.17	3.11	1.52	1.24	1.88
	Sputum culture	Negative	139	1.30	0.16	1.00			1.00
	TB-PCR	Positive	498	3.51	0.50	2.86	2.38	3.44	1.43	1.16	1.76
	TB-PCR	Negative	145	1.23	0.16	1.00			1.00
	AFB smear	Positive	604	4.34	0.63	3.12	2.70	3.59	2.07	1.75	2.45
	AFB smear	Negative	276	1.42	0.18	1.00			1.00
	Symptoms	Yes	741	2.95	0.43	0.49	0.41	0.59	0.66	0.54	0.80
	Symptoms	No	140	1.49	0.20	1.00			1.00

Table 6.

The risk of tuberculosis according to screening and treatment of latent tuberculosis infection in household contacts

		N	PY	Incidence per 1000 PY	crude HR (95% CI)	adjusted HR^* (95% CI)
Screening	Performed	886	342,584.8	2.59	0.50 (0.27-0.93)	0.40 (0.22-0.75)
Screening	Not performed	18	2,248.0	8.01	(Ref)	(Ref)
Result of LTBI screening	Negative	152	131,632.7	1.15	0.30 (0.25-0.38)	0.33 (0.26-0.41)
Result of LTBI screening	Positive	190	48,856.3	3.89	(Ref)	(Ref)
Treatment of LTBI	Not treated	165	35,533.7	4.64	(Ref)	(Ref)
	Stopped treatment	12	1,963.5	6.11	1.26 (0.70-2.26)	1.23 (0.68-2.22)
	Treatment complete	13	11,359.0	1.14	0.25 (0.14-0.43)	0.26 (0.15-0.45)

*PY : person-year, HR : hazard ratio, LTBI : latent tuberculosis infection, Ref : reference

*variables : sex, age, comorbidities (hypertension, chronic lung disease, diabetes, renal failure, liver disease, malignancy, rheumatic disease, using of steroid), presence of cavity, culture result, smear result, presence of symptoms and Tuberculosis-polymerase chain reaction result.

Figure 1. Flow diagram of study population

Figure 2. Status of LTBI screening and treatment in the household contact investigation

References

Sections

Abstract
Reference

World Health Organization. Global tuberculosis report 2019.
Korea Centers for Diseases Control and Prevention. 2019 Annual report on the notified tuberculosis in Korea 2019. KCDC; 2020.
Shim TS, Koh WJ, Yim JJ, Lew WJ. Treatment of latent tuberculosis infection in Korea. Tuberc Respir Dis 2008;65:79-90.
Fox Greg J., Nhung Nguyen V., et al. Household- Contact Investigation for Detection of Tuberculosis in Vietnam. N Engl J Med 2018;378:221-229.
Lobue P, Menzies D. Treatment of latent tuberculosis infection: an update. Respirology 2010;15:603-622.
Getahun Haileyesus, Matteelli Alberto, et al. Latent Mycobacterium tuberculosis Infection. N Engl J Med 2015;372(22):2127-2135.
Joint Committee for the Development of Korean Guideline for TuberculosisKorean Centers for Disease Control and Prevention. Korean guidelines for tuberculosis, 3rd ed. Seoul: Medrang Inforang Ltd.; 2017.

Epidemiology and Surveillance

Public Health Weekly Report 2020; 13(18): 1231-1246

Published online April 29, 2020

Diagnosis, Treatment and Outcomes of Latent Tuberculosis in the Household Contact Investigation Programme

Park Yong-joon, Kim Youngman, Shin Ji-ae, Han Sunmi, Park Shin Young, Kim Jieun, Park Young Joon, Jung Sun-young, Choi Jae Chol

Division of Tuberculosis Epidemic Investigation, Center for Disease Prevention, KCDC; Chung-Ang University hospital

Correspondence to:^*교신저자 : pahmun@korea.kr, 043-719-7280

Abstract

Keywords: Latent tuberculosis infection (LTBI), Household contacts investigation, Treatment of LTBI

Body

Table 1 . The incidence of active tuberculosis by category of close contacts.

	Not performed contact investigation (n=633) n (%)	Subjects for TB screening
		Performed LTBI screening					Not performed LTBI screening (n=53,565) n (%)
		Positive for LTBI screening			Negative for LTBI screening
		Performed treatment		Not treated (n=16,837) n (%)	1 step screening (n=49,643) n (%)	2 step screening (n=10,110) n (%)
		Complete (n=5,357) n (%)	Stop treatment (n=1,010) n (%)	Not treated (n=16,837) n (%)	1 step screening (n=49,643) n (%)	2 step screening (n=10,110) n (%)
Total	18 (2.8)	13 (0.2)	12 (1.2)	165 (1.0)	144 (0.3)	8 (0.1)		544 (1.0)
≤ 1 year	15 (2.4)	5 (0.1)	9 (0.9)	117 (0.7)	85 (0.2)	7 (0.1)	261 (0.5)
1-2 years	3 (0.5)	3 (0.1)	3 (0.3)	36 (0.2)	39 (0.1)	1 (0.0)	137 (0.3)
2-3 years	0 (0.0)	2 (0.0)	0 (0.0)	8 (0.0)	14 (0.0)	0 (0.0)	127 (0.2)
> 3years	0 (0.0)	3 (0.1)	0 (0.0)	4 (0.0)	6 (0.0)	0 (0.0)	19 (0.0)

Table 2 . Baseline characteristics of close contacts and index patients.

Characteristics		Close contacts	Index patients
Characteristics		N (%)	N (%)
Total		138,335 (100)	67,638 (100)
Sex	Male	57,424 (41.5)	41,130 (60.8)
Sex	Female	80,911 (58.5)	26,508 (39.2)
Age	Mean±SD	42.28±22.56 57.79±20.25
	≤ 5 years old	8,702 (6.3)	84 (0.1)
	6–18 years old	18,657 (13.5)	1,816 (2.7)
	19–40 years old	32,467 (23.5)	13,463 (19.9)
	41–60 years old	47,169 (34.1)	19,135 (28.3)
	61–75 years old	22,051 (15.9)	16,812 (24.9)
	76 ≤ years old	9,289 (6.7)	16,328 (24.1)

Table 3 . Baseline characteristics of close contacts.

Characteristics		N (%)
Relation	Parents	16,768 (12.1)
	Spouse	41,333 (29.9)
	Children	59,689 (43.1)
	Others (sibling, relatives)	20,545 (14.9)
Years of contact investigation	Not done	633 (0.5)
	2015	38,200 (27.6)
	2016	38,769 (28.0)
	2017	32,045 (23.2)
	2018	28,688 (20.7)
Comorbidity*	Hypertension	25,435 (18.4)
	Chronic lung disease	35,786 (25.9)
	Diabetes	15,077 (10.9)
	Renal failure	25,563 (18.5)
	Liver disease	6,859 (5.0)
	Malignancy	4,902 (3.5)
	Rheumatic disease	3,796 (2.7)
	Alcohol intoxication	1,233 (0.9)
	Use of steroid	56,919 (41.2)

* Comorbidity : variables form National Health Insurance Service.

Table 4 . Baseline characteristics of index patients.

		N (%)
Number of contact	Mean	3
	Standard deviation	4
	Minimum	1
	Median	3
	Maximum	101
	First quartile	2
	Third quartile	4
Present of symptoms	Yes	48,452 (71.6)
Present of symptoms	No	19,186 (28.4)
Symptoms	Sough	33,431 (49.4)
	Sputum	22,702 (33.6)
	Hemoptysis	2,969 (4.4)
	Weight loss	5,931 (8.8)
Cavity on chest PA	Absent	50,138 (74.1)
	Present	14,891 (22)
	Missing	2,609 (3.9)
Acid fast bacilli smear result	Positive	25,875 (38.3)
	Negative	39,722 (58.7)
	Undetermined	82 (0.1)
	Not-done	1,671 (2.5)
	Missing	284 (0.4)

Table 5 . Risk factors for development of tuberculosis.

			Incidence of TB cases (n)	Incidence per 1000 person -year	Incidence for 1 year	Hazard Ratio I			Hazard Ratio II (adjusted)
			Incidence of TB cases (n)	Incidence per 1000 person -year	Incidence for 1 year	HR	95% CI		aHR	95% CI
Contacts	Status of LTBI	Not performed LTBI screening	544	3.36	0.49	1.00			1.00
		Not performed contact investigation	18	8.01	2.37	1.46	0.78	2.73	1.93	1.03	3.61
		No LTBI by 1-step	144	1.34	0.17	0.36	0.30	0.43	0.38	0.30	0.47
		No LTBI by 2-step	8	0.34	0.07	0.09	0.05	0.19	0.12	0.06	0.26
		LTBI with treatment discontinuation	12	6.11	0.89	1.57	0.88	2.78	1.48	0.83	2.65
		LTBI with treatment complete	13	1.14	0.09	0.30	0.17	0.52	0.32	0.18	0.55
		LTBI without treatment	165	4.64	0.69	1.23	1.03	1.47	1.22	1.00	1.48
	Sex	Male	390	2.73	0.39	1.00			1.00
	Sex	Female	514	2.54	0.35	0.93	0.82	1.06	0.89	0.78	1.03
	Age(yr)	Under	5	7	0.31	0.07	1.00			1.00
		6–18	76	1.57	0.24	5.07	2.34	10.99	4.54	2.08	9.90
		19–40	222	2.71	0.44	8.69	4.10	18.43	6.71	3.14	14.33
		41–60	267	2.28	0.32	7.25	3.43	15.36	3.98	1.86	8.56
		61–75	173	3.22	0.36	10.23	4.81	21.78	5.52	2.54	12.01
		Over 76	159	7.54	0.91	23.54	11.05	50.17	11.74	5.35	25.74
	Comorbidities	No				1.00			1.00
		Hypertension	222	3.67	0.45	1.50	1.29	1.75	0.88	0.73	1.07
		Chronic lung disease	248	2.81	0.40	1.10	0.95	1.27	1.09	0.93	1.28
		Diabetes	137	3.81	0.42	1.51	1.26	1.81	1.06	0.86	1.31
		Renal failure	15	6.76	0.70	2.53	1.52	4.21	1.71	1.00	2.94
		Liver disease	53	3.28	0.38	1.24	0.94	1.64	1.06	0.80	1.42
		Malignancy	40	3.61	0.47	1.35	0.98	1.85	1.08	0.78	1.51
		Rheumatic disease	29	3.12	0.35	1.18	0.82	1.71	0.98	0.67	1.44
		Use of steroid	390	2.67	0.36	1.03	0.91	1.18	0.98	0.85	1.13
Index	Cavity	Presence	539	2.13	2.93	2.07	1.80	2.36	1.59	1.38	1.84
	Cavity	Absence	346	4.37	0.61	1.00			1.00
	Sputum culture	Positive	724	3.41	0.48	2.60	2.17	3.11	1.52	1.24	1.88
	Sputum culture	Negative	139	1.30	0.16	1.00			1.00
	TB-PCR	Positive	498	3.51	0.50	2.86	2.38	3.44	1.43	1.16	1.76
	TB-PCR	Negative	145	1.23	0.16	1.00			1.00
	AFB smear	Positive	604	4.34	0.63	3.12	2.70	3.59	2.07	1.75	2.45
	AFB smear	Negative	276	1.42	0.18	1.00			1.00
	Symptoms	Yes	741	2.95	0.43	0.49	0.41	0.59	0.66	0.54	0.80
	Symptoms	No	140	1.49	0.20	1.00			1.00

Table 6 . The risk of tuberculosis according to screening and treatment of latent tuberculosis infection in household contacts.

		N	PY	Incidence per 1000 PY	crude HR (95% CI)	adjusted HR^* (95% CI)
Screening	Performed	886	342,584.8	2.59	0.50 (0.27-0.93)	0.40 (0.22-0.75)
Screening	Not performed	18	2,248.0	8.01	(Ref)	(Ref)
Result of LTBI screening	Negative	152	131,632.7	1.15	0.30 (0.25-0.38)	0.33 (0.26-0.41)
Result of LTBI screening	Positive	190	48,856.3	3.89	(Ref)	(Ref)
Treatment of LTBI	Not treated	165	35,533.7	4.64	(Ref)	(Ref)
	Stopped treatment	12	1,963.5	6.11	1.26 (0.70-2.26)	1.23 (0.68-2.22)
	Treatment complete	13	11,359.0	1.14	0.25 (0.14-0.43)	0.26 (0.15-0.45)

*PY : person-year, HR : hazard ratio, LTBI : latent tuberculosis infection, Ref : reference.

Figure 1. Flow diagram of study population

Figure 2. Status of LTBI screening and treatment in the household contact investigation

Abstract
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Figure 1.Flow diagram of study population

Public Health Weekly Report 2020; 13: 1231-1246

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Figure 2.Status of LTBI screening and treatment in the household contact investigation

Public Health Weekly Report 2020; 13: 1231-1246

Table 1 . The incidence of active tuberculosis by category of close contacts.

	Not performed contact investigation (n=633) n (%)	Subjects for TB screening
		Performed LTBI screening					Not performed LTBI screening (n=53,565) n (%)
		Positive for LTBI screening			Negative for LTBI screening
		Performed treatment		Not treated (n=16,837) n (%)	1 step screening (n=49,643) n (%)	2 step screening (n=10,110) n (%)
		Complete (n=5,357) n (%)	Stop treatment (n=1,010) n (%)	Not treated (n=16,837) n (%)	1 step screening (n=49,643) n (%)	2 step screening (n=10,110) n (%)
Total	18 (2.8)	13 (0.2)	12 (1.2)	165 (1.0)	144 (0.3)	8 (0.1)		544 (1.0)
≤ 1 year	15 (2.4)	5 (0.1)	9 (0.9)	117 (0.7)	85 (0.2)	7 (0.1)	261 (0.5)
1-2 years	3 (0.5)	3 (0.1)	3 (0.3)	36 (0.2)	39 (0.1)	1 (0.0)	137 (0.3)
2-3 years	0 (0.0)	2 (0.0)	0 (0.0)	8 (0.0)	14 (0.0)	0 (0.0)	127 (0.2)
> 3years	0 (0.0)	3 (0.1)	0 (0.0)	4 (0.0)	6 (0.0)	0 (0.0)	19 (0.0)

Table 2 . Baseline characteristics of close contacts and index patients.

Characteristics		Close contacts	Index patients
Characteristics		N (%)	N (%)
Total		138,335 (100)	67,638 (100)
Sex	Male	57,424 (41.5)	41,130 (60.8)
Sex	Female	80,911 (58.5)	26,508 (39.2)
Age	Mean±SD	42.28±22.56 57.79±20.25
	≤ 5 years old	8,702 (6.3)	84 (0.1)
	6–18 years old	18,657 (13.5)	1,816 (2.7)
	19–40 years old	32,467 (23.5)	13,463 (19.9)
	41–60 years old	47,169 (34.1)	19,135 (28.3)
	61–75 years old	22,051 (15.9)	16,812 (24.9)
	76 ≤ years old	9,289 (6.7)	16,328 (24.1)

Table 3 . Baseline characteristics of close contacts.

Characteristics		N (%)
Relation	Parents	16,768 (12.1)
	Spouse	41,333 (29.9)
	Children	59,689 (43.1)
	Others (sibling, relatives)	20,545 (14.9)
Years of contact investigation	Not done	633 (0.5)
	2015	38,200 (27.6)
	2016	38,769 (28.0)
	2017	32,045 (23.2)
	2018	28,688 (20.7)
Comorbidity*	Hypertension	25,435 (18.4)
	Chronic lung disease	35,786 (25.9)
	Diabetes	15,077 (10.9)
	Renal failure	25,563 (18.5)
	Liver disease	6,859 (5.0)
	Malignancy	4,902 (3.5)
	Rheumatic disease	3,796 (2.7)
	Alcohol intoxication	1,233 (0.9)
	Use of steroid	56,919 (41.2)

* Comorbidity : variables form National Health Insurance Service.

Table 4 . Baseline characteristics of index patients.

		N (%)
Number of contact	Mean	3
	Standard deviation	4
	Minimum	1
	Median	3
	Maximum	101
	First quartile	2
	Third quartile	4
Present of symptoms	Yes	48,452 (71.6)
Present of symptoms	No	19,186 (28.4)
Symptoms	Sough	33,431 (49.4)
	Sputum	22,702 (33.6)
	Hemoptysis	2,969 (4.4)
	Weight loss	5,931 (8.8)
Cavity on chest PA	Absent	50,138 (74.1)
	Present	14,891 (22)
	Missing	2,609 (3.9)
Acid fast bacilli smear result	Positive	25,875 (38.3)
	Negative	39,722 (58.7)
	Undetermined	82 (0.1)
	Not-done	1,671 (2.5)
	Missing	284 (0.4)

Table 5 . Risk factors for development of tuberculosis.

			Incidence of TB cases (n)	Incidence per 1000 person -year	Incidence for 1 year	Hazard Ratio I			Hazard Ratio II (adjusted)
			Incidence of TB cases (n)	Incidence per 1000 person -year	Incidence for 1 year	HR	95% CI		aHR	95% CI
Contacts	Status of LTBI	Not performed LTBI screening	544	3.36	0.49	1.00			1.00
		Not performed contact investigation	18	8.01	2.37	1.46	0.78	2.73	1.93	1.03	3.61
		No LTBI by 1-step	144	1.34	0.17	0.36	0.30	0.43	0.38	0.30	0.47
		No LTBI by 2-step	8	0.34	0.07	0.09	0.05	0.19	0.12	0.06	0.26
		LTBI with treatment discontinuation	12	6.11	0.89	1.57	0.88	2.78	1.48	0.83	2.65
		LTBI with treatment complete	13	1.14	0.09	0.30	0.17	0.52	0.32	0.18	0.55
		LTBI without treatment	165	4.64	0.69	1.23	1.03	1.47	1.22	1.00	1.48
	Sex	Male	390	2.73	0.39	1.00			1.00
	Sex	Female	514	2.54	0.35	0.93	0.82	1.06	0.89	0.78	1.03
	Age(yr)	Under	5	7	0.31	0.07	1.00			1.00
		6–18	76	1.57	0.24	5.07	2.34	10.99	4.54	2.08	9.90
		19–40	222	2.71	0.44	8.69	4.10	18.43	6.71	3.14	14.33
		41–60	267	2.28	0.32	7.25	3.43	15.36	3.98	1.86	8.56
		61–75	173	3.22	0.36	10.23	4.81	21.78	5.52	2.54	12.01
		Over 76	159	7.54	0.91	23.54	11.05	50.17	11.74	5.35	25.74
	Comorbidities	No				1.00			1.00
		Hypertension	222	3.67	0.45	1.50	1.29	1.75	0.88	0.73	1.07
		Chronic lung disease	248	2.81	0.40	1.10	0.95	1.27	1.09	0.93	1.28
		Diabetes	137	3.81	0.42	1.51	1.26	1.81	1.06	0.86	1.31
		Renal failure	15	6.76	0.70	2.53	1.52	4.21	1.71	1.00	2.94
		Liver disease	53	3.28	0.38	1.24	0.94	1.64	1.06	0.80	1.42
		Malignancy	40	3.61	0.47	1.35	0.98	1.85	1.08	0.78	1.51
		Rheumatic disease	29	3.12	0.35	1.18	0.82	1.71	0.98	0.67	1.44
		Use of steroid	390	2.67	0.36	1.03	0.91	1.18	0.98	0.85	1.13
Index	Cavity	Presence	539	2.13	2.93	2.07	1.80	2.36	1.59	1.38	1.84
	Cavity	Absence	346	4.37	0.61	1.00			1.00
	Sputum culture	Positive	724	3.41	0.48	2.60	2.17	3.11	1.52	1.24	1.88
	Sputum culture	Negative	139	1.30	0.16	1.00			1.00
	TB-PCR	Positive	498	3.51	0.50	2.86	2.38	3.44	1.43	1.16	1.76
	TB-PCR	Negative	145	1.23	0.16	1.00			1.00
	AFB smear	Positive	604	4.34	0.63	3.12	2.70	3.59	2.07	1.75	2.45
	AFB smear	Negative	276	1.42	0.18	1.00			1.00
	Symptoms	Yes	741	2.95	0.43	0.49	0.41	0.59	0.66	0.54	0.80
	Symptoms	No	140	1.49	0.20	1.00			1.00

Table 6 . The risk of tuberculosis according to screening and treatment of latent tuberculosis infection in household contacts.

		N	PY	Incidence per 1000 PY	crude HR (95% CI)	adjusted HR^* (95% CI)
Screening	Performed	886	342,584.8	2.59	0.50 (0.27-0.93)	0.40 (0.22-0.75)
Screening	Not performed	18	2,248.0	8.01	(Ref)	(Ref)
Result of LTBI screening	Negative	152	131,632.7	1.15	0.30 (0.25-0.38)	0.33 (0.26-0.41)
Result of LTBI screening	Positive	190	48,856.3	3.89	(Ref)	(Ref)
Treatment of LTBI	Not treated	165	35,533.7	4.64	(Ref)	(Ref)
	Stopped treatment	12	1,963.5	6.11	1.26 (0.70-2.26)	1.23 (0.68-2.22)
	Treatment complete	13	11,359.0	1.14	0.25 (0.14-0.43)	0.26 (0.15-0.45)

*PY : person-year, HR : hazard ratio, LTBI : latent tuberculosis infection, Ref : reference.

References

World Health Organization. Global tuberculosis report 2019.
Korea Centers for Diseases Control and Prevention. 2019 Annual report on the notified tuberculosis in Korea 2019. KCDC; 2020.
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