Figure 1.
Flow chart of patients recruited to the multi-centric study stratified by active tuberculosis and non-active tuberculosis patient subgroups.
Footnotes: HIV: Human Immunodeficiency Virus; LTBI: latent tuberculosis infection.
Figure 2.
Individual IgG antibody levels against PGL-Tb1 and ESAT-6/CFP10 in subjects with or without active tuberculosis disease stratified by HIV status.
Dot plot indicates the single antibody level per subject analyzed; median is indicated by the red line. ***: p<0.0001. Footnotes: HIV: Human Immunodeficiency Virus; LTBI: latent tuberculosis infection; OD: optical density.
Figure 3.
Individual IgG antibody levels against PGL-Tb1 and ESAT-6/CFP10 in subjects with active tuberculosis disease stratified by HIV status and disease localization (pulmonary and extrapulmonary).
Dot plot indicates the single antibody level per subject analyzed; median is indicated by the red line. ***: p<0.0001. Footnotes: HIV: Human Immunodeficiency Virus; P-TB: pulmonary tuberculosis; Extra P-TB: extrapulmonary tuberculosis; OD: optical density.
Table 1.
Quantitative levels of anti-PGL-Tb1 and anti-ESAT-6/CFP10 antibodies (median) as measured by optical density in different groups of active TB patients according to their HIV status, disease localization and in individuals without active TB according to their risk of TB infection.
Figure 4.
Individual IgG antibody levels against PGL-Tb1 and ESAT-6/CFP10 in subjects without active tuberculosis disease stratified by the risk of tuberculosis infection.
Dot plot indicates the single antibody level per subject analyzed; median is indicated by the red line. ***: p<0.0001. Footnotes: LTBI: latent tuberculosis infection; Ab: antibody; ATB: active tuberculosis; HCW: health care workers; HFC: healthy family contacts; HCA: healthy community adults; OD: optical density.
Table 2.
Evaluation of the quantitative level of anti-PGL-Tb1 and anti-ESAT-6/CFP10 antibodies in patients with active TB stratified by HIV status and center of enrolment.
Table 3.
Evaluation of the statistical difference of PGL-Tb1 and anti-ESAT-6/CFP10 antibodies in HIV-infected active TB patients stratified by the center of enrolment (as reported in Table 2).
Table 4.
Evaluation of the statistical difference of PGL-Tb1 and anti-ESAT-6/CFP10 antibodies in HIV-uninfected and unknown active TB patients stratified by the center of enrolment (as reported in Table 2).
Table 5.
Evaluation of quantitative levels of anti-PGL-Tb1 and anti-ESAT-6/CFP10 antibodies (medians) in individuals with varying risk of latent tuberculosis infection stratified by the center of enrolment.
Figure 5.
Receiving operative curves of a serology test for active tuberculosis in patients stratified by HIV status.
Receiving operative curves calculated in HIV-uninfected (blue spot), HIV-unknown (red spot) or HIV-infected (black spot) patients with active TB and in healthy individuals with low risk of latent TB infection for antibodies: A. against PGL-Tb1 (left graph); B. ESAT-6/CFP10 (right graph) antigens. Footnotes: HIV: Human Immunodeficiency Virus.
Table 6.
Evaluation of areas under the curve of the Receiver Operating Characteristic (ROC) of anti-PGL-Tb1 and anti-ESAT6/CFP10 antibodies of 102 HIV-infected, 316 HIV-uninfected, 360 HIV-unknown active TB patients and additional subjects without active TB (459 healthy subjects as in the blood donors).
Table 7.
Sensitivity of the serology test using ELISA based on the PGL-Tb1 or the ESAT-6/CFP10 antigen and their cumulative results in the different groups of active TB enrolled patients stratified by HIV status and TB localization.
Table 8.
Specificity of the serology test based on the ELISA using the PGL-Tb1 or the ESAT-6/CFP10 antigens and their cumulative results in the different groups of individuals classified as low risk of TB infection.
Table 9.
Accuracy of active tuberculosis diagnosis by the serology test based on the ELISA using the PGL-Tb1, ESAT-6/CFP10 or both antigens in ATB patients (pulmonary and extrapulmonary TB) stratified by HIV status.
Table 10.
Sensitivity of the serology test based on the ELISA using the PGL-Tb1 and ESAT-6/CFP10 antigens and their cumulative results in active TB patients stratified by Smear Microscopy (SM), TB localization and HIV status.
Table 11.
Sensitivity of the SM test and combined sensitivity of the SM with the serology results based on the cumulative anti-PGL-Tb1 and anti-ESAT-6/CFP10 ELISA positive data among the SM-negative (serology positive) active TB patients stratified by disease localization and HIV status.
Figure 6.
Impact of mycobacterial load and antibody responses stratified by HIV status.
Relationship between individual time to positivity (TTP in days) of a liquid culture and individual serological tests based on optical density values against PGL-Tb1 antigen (blue spot) or ESAT-6/CFP10 (red spot) antigen in (A) the whole group of 270 HIV-uninfected and 293 HIV-unknown patients and in (B) the group of 68 HIV-infected patients with active pulmonary TB. The continuous lines represent the linear regression curve for anti-PGL-Tb1 antibody or for anti-ESAT-6/CFP10 antibody tested individuals; the hatched lines represent the 95% confidence intervals. Footnotes: HIV: Human Immunodeficiency Virus; OD: optical density; TTP: time to positivity.
Table 12.
Sensitivity of the serology test based on the ELISA using the PGL-Tb1 and ESAT-6/CFP10 antigens and their cumulative results in active pulmonary TB patients stratified by SM grade and HIV status.
Figure 7.
Impact of CD4 counts on antibody responses in HIV-infected active tuberculosis patients
A. Correlation between individual CD4 cell counts and individual serological tests based on optical density values of ELISA against PGL-Tb1 antigen (blue spot) (R2 = 0.00103; p = 0.8141) or ESAT-6/CFP10 antigen (red spot) (R2 = 0.01574; p = 0.3569) in 53 HIV-infected ATB patients. The continuous lines represent the linear regression curve for anti-PGL-Tb1 antibody or for anti-ESAT-6/CFP10 antibody tested individuals; the hatched lines represent the 95% confidence intervals. B. Anti-PGL-Tb1 and anti-ESAT-6/CFP10 antibody levels stratified by CD4 cell counts among the 56 HIV-infected ATB patients. Horizontal red lines indicate the median value. Footnotes: OD: optical density.
Table 13.
Comparison of the sensitivity of the TST and the serology test based on ELISA using each antigen and their cumulative results in HIV-infected active TB patients stratified by CD4 cell counts/µL (lower or above 200/µL).
Figure 8.
Correlation between the tuberculin skin test and antibody responses in active tuberculosis patients stratified by HIV status.
Correlation between the individual tuberculin skin test diameter (in mm) and the individual serological tests based on optical density values of the ELISA against PGL-Tb1 antigen (blue spot) and ESAT-6/CFP10 (red spot) antigen in (A) the whole group of 127 HIV-uninfected and 119 HIV-unknown patients and in (B) the group of 30 HIV-infected patients with active pulmonary TB. The continuous lines represent the linear regression curve for anti-PGL-Tb1 antibody or for anti-ESAT-6/CFP10 antibody tested individuals; the hatched lines represent the 95% confidence intervals. Footnotes: HIV: Human Immunodeficiency Virus; TB: tuberculosis; TST: tuberculin skin test; OD: optical density.