Characteristics of original studies
Initially, 2026 articles were identified. After deduplicating, 1201 unduplicated articles were obtained. 1121 articles unrelated to this analysis were removed, the remaining 80 articles were examined by full text reading. Among these 80 publications, 47 were excluded for various reasons (Figure 1). Finally, 33 articles assessing TM infection in HIV-infected individuals, with a total of 159,064 PLWHA, were included. As shown in Table 1, the identified studies were conducted in five countries in Asia. There were 47,644 participants (19 studies) from China; 108,285 participants (7 studies) from Thailand, 2,370 participants (3 studies) from Vietnam; 620 participants (3 studies) from India and 145 participants (1 study) from Malaysia (Figure 1, Table 1). 25 publications were reported in English, and 8 in Chinese.
Prevalence of TM infection in Asian countries
The prevalence of TM infection in PLWHA reported in the included articles ranged from 0.13 to 19.63% in different areas (Table 1). Overall, the estimated pooled prevalence of TM infection in Asia was 4.0% (95% CI:2.0-5.0, N=33 studies, 159,064 participants, I2=98%, p<0.001). The prevalence by country was as follows: 6.4%(95%CI: 4.4-9.5) in Vietnam, 3.9% (95%CI:1.8-8.3) in Thailand, 3.3%(95%CI:1.8-5.8) in China, 3.2%(95%CI:0.3-32.6) in India, and 2.1%(95%CI:0.7-6.6) in Malaysia, respectively (Figure 2).
We also assessed the geographical distribution of TM infection in China. The prevalence of TM infection in PLWHA in China ranged from 0.2% (95%CI: 0.1-0.5) to 26.5% (95%CI: 16.2-43.5%; Figure 2). South China had the highest prevalence, estimated at 15.0% (95%CI: 11.0-20.4), while Southwest China had the lowest prevalence, estimated at 0.3% (95%CI: 0.1-0.9; Figure 5).
Analysis of data heterogeneity
We found a substantial heterogeneity (I2=99.2%, P<0.001; Table 2) in the included studies. We further analyzed the source of the heterogeneity. Our univariate meta-regression analyses indicated that latitude (P=0.002) was a source of heterogeneity and that there was no influence of publication year (P=0.057) and income levels (P=0.393) on heterogeneity. Subsequently, multivariate meta-regression analysis results showed that latitude was a possible cause of heterogeneity (P=0.013). We further made a comparison between lower latitude (crossing tropic of cancer or south of tropic of cancer) and higher latitude area (north of the tropic of cancer), and found that TM infection in PLWHA in lower latitude area was significantly more prevalent than that in higher latitude area (OR 2.838, 95%CI: 2.376-3.390, P<0.001).
Prevalence of TM infection in different ART eras
In this meta-analysis, we divided treatment into two eras: limited ART era (before 2008) and widespread ART era (2008 and thereafter) and compared the prevalence of TM infection in the two different eras. The prevalence of TM infection was 5.2% (95%CI: 3.1-8.8; n=112520) in limited ART era and 2.5% (95%CI: 1.4-4.5; n=19086) in widespread ART era (Figure 6). However, we did not detect significant statistical difference in the prevalence of TM infection between different eras (Table 3).
We have noticed the large difference in sample size between the two groups. In order to determine whether the large difference in sample size would have an impact on results, we further did a sensitivity analysis for comparability, which excluded the study of Chariyalertsak et al. [42] with the large sample size. The sensitivity analysis showed that our results are stable. The prevalence of TM infection after excluding the study with the large sample size was 5.3% (95%CI: 2.9-9.8; n=10575) in limited ART era and 2.5% (95%CI: 1.4-4.5; n=19086) in widespread ART era (Supplementary Figure 3, Supplementary Table 2).
The impact of CD4 counts and on-ART treatment on TM infection
Four studies (N=7809) described the number of PLWHA with CD4 counts below 200 cells/mm3 and the number of PLWHA on-ART (Table 4). Our results showed that PLWHA with CD4 counts below 200 cells/mm3 had a higher TM infection prevalence than those with CD4 counts≥200 cells/mm3 (OR 12.68, 95%CI: 9.58-16.77, Figure 7). However, there was no significant statistical difference in TM infection prevalence between PLWHA with ART and PLWHA without ART (OR 0.53, 95%CI: 0.14-2.01, Figure 8).
[12]Table 1: The detailed characteristics of included studies
Study
|
Latitude
|
Country
|
No. of TM infection patients
|
No. of PLWHA
|
Prevalence
|
Jiang et al. (2018) [8]
|
Lower
|
China
|
1093
|
6791
|
16.09%
|
Pang et al. (2018) [20]
|
Higher
|
China
|
5
|
2298
|
0.22%
|
Li et al. (2018) [21]
|
Lower
|
China
|
2
|
200
|
1.00%
|
Ni et al. (2018) [22]
|
Higher
|
China
|
8
|
852
|
0.94%
|
Yen et al. (2017) [23]
|
Lower
|
China
|
126
|
21375
|
0.59%
|
Kaur et al. (2016) [24]
|
Higher
|
India
|
4
|
280
|
1.43%
|
Qi et al. (2016) [25]
|
Higher
|
China
|
43
|
2442
|
1.76%
|
Zhai et al. (2016) [26]
|
Higher
|
China
|
2
|
827
|
0.24%
|
Zheng et al. (2015) [27]
|
Higher
|
China
|
47
|
981
|
4.79%
|
Kolalapudi et al. (2014) [28]
|
Lower
|
India
|
1
|
142
|
0.70%
|
Son et al. (2014) [9]
|
Lower
|
Vietnam
|
103
|
2100
|
4.90%
|
Nguyen et al. (2013) [29]
|
Lower
|
Vietnam
|
14
|
170
|
8.24%
|
Xiao et al. (2013) [10]
|
Higher
|
China
|
12
|
1104
|
1.09%
|
Han et al. (2013) [30]
|
Lower
|
China
|
40
|
348
|
11.49%
|
Su et al. (2012) [31]
|
Lower
|
China
|
17
|
177
|
9.60%
|
Xie et al. (2012) [32]
|
Lower
|
China
|
389
|
3905
|
9.96%
|
Huang et al. (2011) [33]
|
Higher
|
China
|
5
|
796
|
0.63%
|
Huang et al. (2010) [34]
|
Lower
|
China
|
136
|
762
|
17.85%
|
Lin et al. (2009) [35]
|
Lower
|
China
|
18
|
1790
|
1.01%
|
Zeng et al. (2009) [36]
|
Lower
|
China
|
19
|
71
|
26.76%
|
Tang et al. (2009) [37]
|
Lower
|
China
|
99
|
1559
|
6.35%
|
Manosuthi et al. (2007) [38]
|
Lower
|
Thailand
|
1
|
793
|
0.13%
|
Tang et al. (2007) [39]
|
Lower
|
China
|
50
|
319
|
15.67%
|
Sun et al. (2006) [11]
|
Lower
|
China
|
25
|
1047
|
2.39%
|
Chierakul et al. (2004) [40]
|
Lower
|
Thailand
|
57
|
2602
|
2.19%
|
Louie et al. (2004) [12]
|
Lower
|
Vietnam
|
7
|
100
|
7.00%
|
Subsai et al. (2004) [41]
|
Lower
|
Thailand
|
19
|
155
|
12.26%
|
Ranjana et al. (2002) [13]
|
Lower
|
India
|
36
|
198
|
18.18%
|
Chariyalertsak et al. (2001) [42]
|
Lower
|
Thailand
|
3054
|
101945
|
3.00%
|
Wananukul et al. (1999) [43]
|
Lower
|
Thailand
|
3
|
91
|
3.30%
|
Jing et al. (1999) [44]
|
Lower
|
Malaysia
|
3
|
145
|
2.07%
|
Tansuphasawadikul et al. (1999) [45]
|
Lower
|
Thailand
|
50
|
2261
|
2.21%
|
Supparatpinyo et al. (1994) [1]
|
Lower
|
Thailand
|
86
|
438
|
19.63%
|
Supparatpinyo et al. (1994) [1] Lower Thailand 86 438 19.63%
Articles ranked by year of publication. The lower latitude is defined as crossing the tropic of cancer or south of the tropic of cancer and the higher latitude is defined as north of the tropic of cancer.
Table 2: The influence of variables on the heterogeneity of prevalence (N=159064)
|
No. of study
|
No. of TM infection patients
|
No. of PLWHA
|
Prevalence of TM infection
|
Heterogeneity
|
Univariate meta-regression
|
|
|
|
|
|
c2
|
p value
|
I2
|
Coefficient(95%CI)
|
p value
|
Latitude
|
|
|
|
|
|
|
|
1.726 (0.663 to 2.788)
|
0.002
|
Higher
|
8
|
126
|
9580
|
1.0% (0.5-2.0)
|
87.65
|
0.000
|
92.0%
|
|
|
Lower
|
25
|
5448
|
149484
|
5.5% (3.4-8.7)
|
3960.18
|
0.000
|
99.4%
|
|
|
Income level
|
|
|
|
|
|
|
|
-0.764 (-2.562 to 1.034)
|
0.393
|
Low
|
3
|
124
|
2370
|
6.4% (4.4-9.5)
|
4.09
|
0.129
|
51.1%
|
|
|
Middle
|
30
|
5450
|
156694
|
3.4% (2.2-5.2)
|
4148.53
|
0.000
|
99.3%
|
|
|
Publication year
|
33
|
5574
|
159064
|
-
|
-
|
-
|
-
|
-0.076 (-0.153 to 0.002)
|
0.057
|
Total
|
33
|
5574
|
159064
|
|
|
|
|
|
|
Table 3: The influence of variables on the heterogeneity of prevalence (N=131606)
|
No. of study
|
No. of TM infection patients
|
No. of PLWHA
|
Prevalence of TM infection
|
Heterogeneity
|
Univariate meta-regression
|
|
|
|
|
|
c2
|
p value
|
I2
|
Coefficient(95%CI)
|
p value
|
ART era
|
|
|
|
|
|
|
|
-0.791 (-2.038 to 0.456)
|
0.203
|
Limited
|
11
|
3514
|
112520
|
5.2% (3.1-8.8)
|
727.31
|
0.000
|
98.1%
|
|
|
Widespread
|
15
|
1612
|
19086
|
2.5% (1.4-4.5)
|
565.88
|
0.000
|
98.2%
|
|
|
Table 4: Influence of CD4 counts and ART treatment on TM infection
|
CD4<200 group
|
CD4≥200 group
|
OR
|
ART group
|
Without ART group
|
OR
|
|
TM infection
|
Total
|
TM infection
|
Total
|
|
TM infection
|
Total
|
TM infection
|
Total
|
|
Jiang [8]
|
873
|
2760
|
52
|
2026
|
12.32
|
393
|
2021
|
700
|
3677
|
1.02
|
Pang [20]
|
5
|
587
|
0
|
362
|
6.79
|
5
|
824
|
0
|
125
|
1.67
|
Han [30]
|
39
|
162
|
1
|
146
|
35.64
|
16
|
243
|
24
|
65
|
0.18
|
Huang [33]
|
5
|
353
|
0
|
438
|
13.64
|
0
|
145
|
5
|
646
|
0.40
|