Transmission characteristics in Tuberculosis by WGS: nationwide cross-sectional surveillance in China

Figures & data

Figure 1. Minimum spanning tree of all Mycobacterium tuberculosis isolates. We defined genetic distances within 12 SNPs isolates were clusters, only clustered isolates were retained. Each circle represents a cluster. The size of the circle represents the number of isolates in the cluster. The colour of each circle represents the surveillance site of the isolates. Isolates isolated from the same county within a cluster were coloured by white but not mean all white colour isolates isolated from same site.

Table 1. The risk/protective factors associated with the likelihood of clustering.

Characteristics	Cluster rate	Crude OR	P-value	Adjusted OR*	P-value
Demographic factors
Gender
Male	782 (22.29)	ref		ref
Female	312 (23.94)	1.10 (0.95–1.28)	0.224	1.00 (0.84–1.18)	0.958
Age
<20	86 (29.76)	ref		ref
20–39	334 (23.08)	0.71 (0.54–0.94)	0.016	0.74 (0.51–1.07)	0.106
40–59	401 (23.49)	0.73 (0.55–0.96)	0.022	0.80 (0.55–1.17)	0.254
60–79	249 (20.46)	0.61 (0.46–0.81)	0.001	0.65 (0.43–0.97)	0.037
80+	24 (16.00)	0.45 (0.27–0.75)	0.002	0.52 (0.28–0.96)	0.037
P-trend		<0.001		0.01
Current residence
County	231 (19.85)	ref		ref
Town	767 (22.77)	1.19 (1.01–1.41)	0.038	1.06 (0.85–1.33)	0.597
Family population size		1.12 (1.08–1.16)	<0.001	1.11 (1.07–1.15)	<0.001
Nationality
Han	1022 (22.87)	ref		ref
Other	72 (20.87)	0.89 (0.68–1.16)	0.392	0.79 (0.57–1.09)	0.156
Occupations
Farmer	753(23.48)	ref		ref
Student	56 (25.23)	1.10 (0.80–1.51)	0.554	1.05 (0.66–1.65)	0.85
^#Non-physical workers	122 (16.8)	0.66 (0.53–0.81)	<0.001	0.72 (0.54–0.95)	0.022
Other (housekeeper or unemployed)	163 (24.96)	1.08 (0.89–1.32)	0.417	1.05 (0.82–1.36)	0.691
Education
Primary and below	435 (21.79)	ref		ref
Middle school	515 (22.99)	1.07 (0.93–1.24)	0.351	0.99 (0.82–1.19)	0.909
University and above	46 (15.38)	0.65 (0.47–0.91)	0.012	0.57 (0.37–0.88)	0.011
Clinical factors
Diabetes
Yes	68 (17.53)	ref		ref
No	1017 (23.16)	1.42 (1.08,1.86)	0.012	1.31 (0.97–1.76)	0.076
Hepatitis B
Yes	27 (18.00)	ref		ref
No	936 (22.19)	1.30 (0.85,1.98)	0.225	1.37 (0.87–2.14)	0.17
Previous TB
Yes	206 (18.44)	ref		ref
No	888 (24.03)	1.40 (1.18–1.66)	<0.001	1.48 (1.22–1.79)	<0.001
Smear microscopy
Negative	187 (16.45)	ref		ref
Positive	877 (25.58)	1.75 (1.47–2.08)	<0.001	1.52 (1.26–1.83)	<0.001
Bacteriological factors
MDR
Yes	99 (28.95)	1.40 (1.10–1.79)	0.007	1.60 (1.21–2.10)	0.001
No	1061(22.53)	ref		ref
Lineage
1	4 (13.79)	ref		ref
2	898 (23.79)	1.95 (0.68–5.62)	0.216	2.65 (0.91–7.75)	0.075
3	2 (28.57)	2.50 (0.36–17.57)	0.357	0.01 (0.01–99.9)	0.969
4	256 (20.61)	1.62 (0.56–4.70)	0.373	2.16 (0.73–6.35)	0.163

Abbreviations: OR, odds ratio; TB, tuberculosis; MDR, multidrug-resistant.

* The logistic model was adjusted for age, gender, current residence, family size, nationality, occupations, education, diabetes history, hepatitis B, previous TB, smear microscopy, MDR/RR, and lineage, except for the stratified factors.

^# Non-physical workers: commercial service personnel, enterprise staff, medical personnel, educational staff, civil servant and public institutional person.

Figure 2. WGS-clusters of multidrug resistant or rifampin-resistant isolates with rifampin-sensitive isolates. 98 multidrug resistant (MDR) isolates, 23 rifampin-resistant (RR) isolates and 28 rifampin-sensitive (RS) isolates clustered in 50 WGS – clusters.

Figure 3. Classification of MDR/RR-TB based on treatment history and genomic analysis. MDR/RR-TB: multidrug resistant or rifampin-resistant tuberculosis.

Table 2. Univariable analysis of risk factors associated with multidrug-resistance in genomic clusters.

Characteristics	Cluster rate	Crude OR	P-value
Age
<20	7 (35)	ref
20–39	32 (24.24)	0.59 (0.22–1.62)	0.3084
40–59	44 (26.99)	0.69 (0.26–1.83)	0.453
60–79	32 (38.1)	1.14 (0.41–3.17)	0.7972
80+	2 (33.33)	0.93 (0.14–6.40)	0.94
Gender
Male	92 (30.77)	ref
Female	25 (23.58)	0.69 (0.42–1.16)	0.1622
Current residence
Town	77 (29.96)	ref
County	33 (26.83)	1.17 (0.72–1.89)	0.529
Diabetes
Yes	8 (23.53)	ref
No	108 (29.27)	1.35 (0.59–3.06)	0.4809
Hepatitis B
Yes	1 (6.25)	ref
No	104 (29.89)	6.39 (0.83–49.03)	0.0743
Previous treatment
Yes	32 (17.88)	ref
No	85 (37.61)	2.77 (1.74–4.42)	<.0001
Smear microscopy
Negative	12 (18.46)	ref
Positive	105 (31.91)	2.07 (1.06–4.04)	0.0328
Nationality
Han	111 (29.21)	ref
Other	6 (23.08)	0.73 (0.28–1.86)	0.5058
Education
Primary and below	49 (30.43)	ref
Middle school	57 (30.32)	1.00 (0.63–1.57)	0.9813
University and above	3 (10)	0.25 (0.07–0.88)	0.0302
Occupations
Farmer	82 (33.33)	ref
Student	6 (35.29)	1.09 (0.39–3.05)	0.8684
Non-physical workers	13 (18.06)	0.44 (0.23–0.85)	0.0144
Other (housekeeper or unemployed)	16 (22.54)	0.58 (0.31–1.08)	0.0852
Family populations size		1.13 (1.01–1.26)	0.0323