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 subject population of 159,064 PLWHA, were included in our study. 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). Twenty-five articles were reported in English, and 8 studies were published in Chinese.
[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%
|
Articles ranked by year of publication. The lower latitude is defined as intersecting the tropic of cancer or south of the tropic of cancer and the higher latitude is defined as north of the tropic of cancer.
Prevalence of TM infection in Asian countries
The prevalence of TM infection in PLWHA reported in the included articles ranged from between 0.13% to 19.63% in different regions (Table 1). Overall, the estimated pooled prevalence of TM infection in Asia was 3.6% (95% CI:2.4-5.4, n=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). The sensitivity analysis showed that our results are stable. After excluding the study of Chariyalertsak et al. [42] with the much larger sample size, the pooled prevalence of TM infection in Asia was 3.6% (95%CI: 2.4-5.5, n=57 119). And in Thailand, the pooled prevalence was 3.6% (95%CI: 1.2-11.4, n=6 340).
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 3). 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 4).
Prevalence of TM infection in different latitudes
The sub-group analysis based on different latitudes was performed in 33 studies. As depicted in Figure 5, The prevalence of TM infection was 5.5% (95%CI: 3.4-8.7; n=149 484) in lower latitude regions and 1.0% (95%CI: 0.5-2.0; n=9 580) in higher latitude regions. The prevalence of TM infection after excluding the study with the much larger sample size [42] was 5.6% (95%CI: 3.5-9.0; n=47 539) in lower latitude regions and 1.0% (95%CI: 0.5-2.0; n=9 580) in higher latitude regions.
Analysis of data heterogeneity
We observed 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 (OR 5.616, 95%CI: 1.941-16.246, p=0.002) was a source of heterogeneity, and that there was no influence on heterogeneity associated with publication year (OR 0.930, 95%CI: 0.862-1.004, p=0.057) and income levels (OR 0.466, 95%CI: 0.077-2.813, p=0.393). Subsequently, multivariate meta-regression analysis results showed that latitude was a possible cause of heterogeneity (OR 4.442, 95%CI: 1.213-16.268, p=0.026).
Table 2: The influence of variables on the heterogeneity of prevalence (n=159 064)
|
No. of study
|
No. of TM infection patients
|
No. of PLWHA
|
Prevalence of TM infection
|
Heterogeneity
|
Univariate meta-regression
|
|
|
|
|
|
c2
|
p value
|
I2
|
OR (95%CI)
|
p value
|
Latitude
|
|
|
|
|
|
|
|
5.616 (1.941 to 16.246)
|
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
|
|
|
|
|
|
|
|
0.466 (0.771 to 2.813)
|
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
|
-
|
-
|
-
|
-
|
0.930 (0.862 to 1.004)
|
0.057
|
Total
|
33
|
5574
|
159064
|
|
|
|
|
|
|
Prevalence of TM infection in different ART eras
In this meta-analysis, we divided HIV 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. Seven studies were excluded from the sub-group analysis of the different ART eras, because the study period spanned the widespread ART era and the limited ART era. The prevalence of TM infection was 5.2% (95%CI: 3.1-8.8; n=112 520) in limited ART era and 2.5% (95%CI: 1.4-4.5; n=19 086) in widespread ART era (Figure 6); however, we did not observe significant statistical difference in the prevalence of TM infection between the different ART eras (Table 3).
Table 3: The influence of ART eras on the heterogeneity of prevalence (n=131 606)
|
No. of study
|
No. of TM infection patients
|
No. of PLWHA
|
Prevalence of TM infection
|
Heterogeneity
|
Univariate meta-regression
|
|
|
|
|
|
c2
|
p value
|
I2
|
OR (95%CI)
|
p value
|
ART era
|
|
|
|
|
|
|
|
0.453(0.130 to 1.578)
|
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%
|
|
|
We did perceive the large difference in sample size between the limited-ART era and the widespread-ART era groups, and in order to determine whether the large difference in sample size would have an impact on our results, we further did a sensitivity analysis for comparability, which excluded the study of Chariyalertsak et al. [42] with the large sample size. Subsequent sensitivity analysis showed that our results were stable. The prevalence of TM infection after excluding the study with the much larger sample size was 5.3% (95%CI: 2.9-9.8; n=10 575) in limited ART era and 2.5% (95%CI: 1.4-4.5; n=19 086) in widespread ART era.
The impact of CD4+ T-cell counts and on-ART treatment on TM infection
Four studies (n=7 809) described the number of PLWHA with CD4+ T-cell counts below 200 cells/mm3 and the number of PLWHA on ART (Table 4). Our results showed that PLWHA with CD4+ T-cell counts below 200 cells/mm3 had a higher TM infection prevalence than those with CD4+ T-cell counts≥200 cells/mm3 (OR 12.68, 95%CI: 9.58-16.77, Figure 7). However, there was no statistically significant difference in TM infection prevalence rates between PLWHA on ART and PLWHA not on ART (OR 0.53, 95%CI: 0.14-2.01, Figure 8).
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
|
Without TM infection
|
TM infection
|
Without TM infection
|
|
TM infection
|
Without TM infection
|
TM infection
|
Without TM infection
|
|
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
|
35.15
|
16
|
243
|
24
|
65
|
0.18
|
Huang [33]
|
5
|
353
|
0
|
438
|
13.64
|
0
|
145
|
5
|
646
|
0.40
|