Demographic and clinical characteristics of persons screened with chest X-ray
We analysed the final dataset of 8,386 CXRs and medical data after excluding 133 CXRs because of 59 duplications and 74 without any matching medical data. Table 1 shows the demographic and clinical characteristics of persons screened with CXR; 5,584 (67% of the participants) were female, and 2,839 (34%) were 65 years or older. A total of 5,202 (62%) had a cough for more than two weeks. The percentages of the participants with diabetes mellitus, positive HIV status, and smoking as TB risk were 5.3%, 0.5%, and 14%, respectively. A total of 1,145 (14%) had contacts of TB, and 993 (12%) had a past history of TB. Overall, 1,371 (16%) were examined by Xpert on the ground. Of them, 130 (1.6% of the participants and 9.5% of the persons examined by Xpert) were positive for Xpert.
Table 1
Demographic and clinical characteristics of persons screed with chest X-ray
| Xpert test | | Total |
| Positive (%) | | Negative (%) | | Not examined | |
N | 130 (1.6) | | 1,241 (14.8) | | 7,015 (83.7) | | 8,386 (100) |
Sex | | | | | | | |
Male | 65 (2.3) | | 517 (18.5) | | 2,220 (79.2) | | 2,802 (100) |
Female | 65 (1.2) | | 724 (13.0) | | 4,795 (85.9) | | 5,584 (100) |
Age | | | | | | | |
15–24 | 4 (2.0) | | 6 (3.0) | | 189 (95.0) | | 199 (100) |
25–34 | 6 (1.4) | | 20 (4.5) | | 415 (94.1) | | 441 (100) |
35–44 | 18 (2.2) | | 52 (6.4) | | 742 (91.4) | | 812 (100) |
45–54 | 22 (1.4) | | 165 (10.8) | | 1,339 (87.7) | | 1,526 (100) |
55–64 | 27 (1.1) | | 361 (14.3) | | 2,133 (84.6) | | 2,521 (100) |
65- | 53 (1.9) | | 634 (22.3) | | 2,152 (75.8) | | 2,839 (100) |
unknown | 0 (0.0) | | 3 (6.3) | | 45 (93.8) | | 48 (100) |
TB symptoms | | | | | | | |
Cough (yes) | 108 (2.1) | | 908 (17.5) | | 4,186 (80.5) | | 5,202 (100) |
(no) | 22 (0.7) | | 333 (10.5) | | 2,829 (88.9) | | 3,184 (100) |
Fever (yes) | 86 (1.9) | | 758 (16.3) | | 3,800 (81.8) | | 4,644 (100) |
(no) | 44 (1.2) | | 483 (12.9) | | 3,215 (85.9) | | 3,742 (100) |
Night sweat (yes) | 54 (1.3) | | 621 (15.2) | | 3,402 (83.4) | | 4,077 (100) |
(no) | 76 (1.8) | | 620 (14.4) | | 3,613 (83.8) | | 4,309 (100) |
Weight loss (yes) | 79 (2.2) | | 636 (17.5) | | 2,919 (80.3) | | 3,634 (100) |
(no) | 51 (1.1) | | 605 (12.7) | | 4,096 (86.2) | | 4,752 (100) |
Lymph node swelling (yes) | 4 (1.5) | | 26 (9.7) | | 239 (88.8) | | 269 (100) |
(no) | 126 (1.6) | | 1,215 (15.0) | | 6,776 (83.5) | | 8,117 (100) |
Other risk factors | | | | | | | |
Diabetes mellitus (yes) | 9 (2.0) | | 64 (14.4) | | 372 (83.6) | | 445 (100) |
(no) | 121 (1.5) | | 1,177 (14.8) | | 6,643 (83.7) | | 7,941 (100) |
HIV (yes) | 0 (0.0) | | 12 (30.8) | | 27 (69.2) | | 39 (100) |
(no or unknown) | 130 (1.6) | | 1,229 (14.7) | | 6,988 (83.7) | | 8,347 (100) |
Smoking (yes) | 22 (1.9) | | 200 (16.8) | | 965 (81.3) | | 1,187 (100) |
(no) | 108 (1.5) | | 1,041 (14.5) | | 6,050 (84.0) | | 7,199 (100) |
Family TB history (yes) | 13 (1.4) | | 127 (14.0) | | 764 (84.5) | | 904 (100) |
(no) | 117 (1.6) | | 1,114 (14.9) | | 6,251 (83.5) | | 7,482 (100) |
TB contact (yes) | 17 (1.5) | | 141 (12.3) | | 987 (86.2) | | 1,145 (100) |
(no) | 113 (1.6) | | 1,100 (15.2) | | 6,028 (83.2) | | 7,241 (100) |
Past TB history (yes) | 15 (1.5) | | 299 (30.1) | | 679 (68.4) | | 993 (100) |
(no) | 115 (1.6) | | 942 (12.7) | | 6,336 (85.7) | | 7,393 (100) |
Table 2 CXR reading by human reader and Xpert results | | |
Results of CXR reading | Xpert | | Total |
Positive | | Negative | | Not examined | |
Normal lung field | 1 (0.0) | | 568 (8.3) | | 6,266 (91.7) | | 6,835 (100) |
Active TB | 99 (23.9) | | 179 (43.2) | | 136 (32.9) | | 414 (100) |
Suspect TB | 10 (5.0) | | 99 (49.3) | | 92 (45.8) | | 201 (100) |
Healed TB | 17 (2.0) | | 346 (41.1) | | 478 (56.8) | | 841 (100) |
Other lung disease | 3 (3.2) | | 49 (51.6) | | 43 (45.3) | | 95 (100) |
Total | 130 (1.6) | | 1,241 (14.8) | | 7,015 (83.7) | | 8,386 (100) |
Table 3 Performance of F-CAD against WHO's Target Product Profile by reference | |
Reference | Xpert results | "abnormality suggestive of TB" | "any abnormality in the lung fields" |
Sensitivity ≧ 95 | Actual sensitivity | 0.954(0.902–0.983) | 0.951(0.931–0.967) | 0.950(0.938–0.961) |
| TB score | 0.72 | 0.36 | 0.15 |
| Specificity (95%CI) | 0.517(0.488–0.545) | 0.747(0.737–0.757) | 0.525(0.513–0.537) |
Sensitivity ≧ 90 | Actual sensitivity | 0.900(0.835–0.946) | 0.901(0.874–0.923) | 0.900(0.884–0.915) |
| TB score | 0.88 | 0.53 | 0.28 |
| Specificity (95%CI) | 0.621(0.594–0.648) | 0.844(0.835–0.852)* | 0.750(0.739–0.760)* |
Specificity ≧ 80 | Actual specificity | 0.800(0.777–0.822) | 0.800(0.791–0.809) | 0.800(0.790–0.809) |
| TB score | 0.97 | 0.44 | 0.34 |
| Sensitivity (95%CI) | 0.715(0.630–0.791) | 0.930(0.907–0.949) | 0.879(0.862–0.895) |
Specificity ≧ 70 | Actual specificity | 0.700(0.674–0.726) | 0.700(0.690–0.710) | 0.700(0.689–0.711) |
| TB score | 0.93 | 0.31 | 0.25 |
| Sensitivity (95%CI) | 0.854(0.854–0.910) | 0.964(0.946–0.977)* | 0.914(0.899–0.928) |
*) significantly over Target Product Profile | | |
Table 4 Performance in triage purposes and screening purposes at sensitivity of 90% | |
Purpose | TB score as threshold | N of CXR selected (% of 8,386) | N of sputum exams* (% of 8,386) | N of Xpert-positive (% of 130) | N of CXR with "abnormality suggestive of TB" (% of 615) | N of CXR with "any abnormality in the lung fields" (% of 1,551) |
Triage | 0.5340 | 1,770 (21.1) | 1,246 (14.9) | 125 (96.2) | 554 (90.1) | 1,246 (80.3) |
Screening | 0.2835 | 3,107 (37.0) | 1,396 (16.6) | 127 (97.7) | 594 (96.6) | 1,396 (90.0) |
* N of sputum exams = N of CXR selected - N of normal CXR by human reading | | |
Chest X-ray reading and Xpert results
The results of human reading by the chest physician indicated many abnormal findings on CXR, as shown in Table 2, probably reflecting a past epidemic of TB in Cambodia and the participation of elderly individuals: 6,835 (82%) with normal CXR, 414 (5%) with active TB, 201 (2%) with suspected TB, 841 (10%) with healed TB, and 95 (1%) with other lung diseases. Of the “active TB” individuals, positive Xpert, negative Xpert, and not performed Xpert were 24%, 43%, and 33%, respectively. Of the “suspect TB”, positive Xpert, negative Xpert, and not performed Xpert were 5%, 49%, and 46%, respectively. There were 17 Xpert-positive cases in “healed TB” and 3 in “other lung diseases”. No rifampicin-resistant TB was detected among the Xpert-positive TB cases.
Results of human reader and TB scores
The IQR of TB scores by human readings for CXR are shown in Fig. 1. The TB scores of F-CAD were significantly associated with the results of the human reader for CXR as indicated by the severity of TB disease: the median of “active TB with cavity”, “active TB without cavity”, “suspect TB”, “healed TB”, “other lung disease”, and “normal” was 0.99, 0.95, 0.91, 0.86, 0.66, and 0.14, respectively.
Performance with the bacteriological reference by Xpert results
The ROC curve of TB scores with the bacteriological reference is shown in Fig. 2, as well as the sensitivities and specificities based on the classification by the human reader. The AUROC of F-CAD was 0.86 (95% confidence interval (CI): 0.83–0.89). By age group, the AUROC for those aged 65 or older was significantly lower (0.80 (95% CI: 0.73–0.80)) than that for those aged under 65 years old (0.91 (95% CI: 0.88–0.91)). We plotted the sensitivities and specificities by the human reader based on “abnormality strongly suggestive of TB”, “abnormality suggestive of TB”, “abnormality suggestive of any TB”, and “any abnormality in lung fields” with 76%/85༅, 84༅/78༅, 97༅/50༅, and 99༅/46༅, respectively.
Figure 3 shows the PRC curves of TB scores with the bacteriological reference. It declined in a linear manner as the sensitivity increased, and reached a positive predictive value (PPV) of 0.1, which was obtained from 130 divided by 1,371 as the lowest PPV. The area under the PRC (AUPRC) was 0.47. Sensitivities and PPVs by the human reader were 76%/36% for “abnormality strongly suggestive of TB”, 84%/28% for “abnormality suggestive of TB”, 97%/17% for “abnormality suggestive of any TB”, and 99%/16% for “any abnormality in lung fields”.
Performance with the radiological reference by human readings
The AUROCs with the reference of “abnormality suggestive of TB” as a triage purpose, and with the reference of “any abnormality in the lung fields” as a screening purpose were 0.93 (95% CI: 0.92–0.94), and 0.92 (95% CI: 0.91–0.93), respectively, as shown in Fig. 2. The AUPRCs with the reference of “abnormality suggestive of TB” and with the reference of “any abnormality in the lung fields” shown in Fig. 3 were 0.52 and 0.83, respectively. The PPVs at 90% sensitivity were nearly 30% for triage purposes, and more than 40% for screening purposes.
Performance against WHO’s Target Product Profile by reference
The performance against the WHO’s TPP by reference is shown in Table 3. With the bacteriological reference, no sensitivity or specificity met the WHO’s TPP: 62% (95% CI: 0.59–0.65) specificity at 90% sensitivity, and 85% (95% CI: 0.85–0.91) sensitivity at 70% specificity. With the radiological reference of “abnormality suggestive of TB”, however, the corresponding sensitivities or specificities reached the targets: 84% (95% CI: 0.84–0.85) specificity at 90% sensitivity and 96% (95% CI: 0.95–0.98) sensitivity at 70% specificity. With the radiological reference of “any abnormality in the lung fields”, 75% (95% CI: 0.74–0.76) specificity at 90% sensitivity reached the target; however, the lower margin of 91% (95% CI: 0.90–0.93) sensitivity at 70% specificity did not exceed 90%.
Performance set at 90% sensitivity for community-based ACF
Given that we used a TB score by F-CAD as the threshold for triage purposes or screening purposes set at 90% sensitivity, we examined how many CXRs by human reader and bacteriological examinations could be decreased in number, and how many cases with positive Xpert, with “abnormality suggestive of TB”, and with “any abnormality in the lung fields” could be missed by using F-CAD. As shown in Table 4, if we used a threshold of 0.5340 for triage purposes, the bacteriological examinations fell to 15% of the original number by the reduction to 21% of CXR to be interpreted, followed by the exclusion of 524 normal CXRs by human reading. On the other hand, TB cases detected as “abnormality suggestive of TB” and positive Xpert could be maintained at 90% and 96%, respectively. Similarly, if we used a threshold of 0.2835 for screening purposes, we could maintain TB cases detected as “abnormality suggestive of TB” and positive Xpert at 97% and 98%, respectively, while the bacteriological examinations fell to 17% in number by the reduction of CXRs by human reading to 37%, followed by the exclusion of the cases with normal CXRs.