Journal Article > ResearchFull Text
PLOS Glob Public Health. 23 April 2025; Volume 5 (Issue 4); e0004471.; DOI:10.1371/journal.pgph.0004471
Huerga H, Gouillou M, Ohler L, Taremwa IM, Akinyi M, et al.
PLOS Glob Public Health. 23 April 2025; Volume 5 (Issue 4); e0004471.; DOI:10.1371/journal.pgph.0004471
People living with HIV (PLHIV) have an increased risk of tuberculosis (TB) and severe COVID-19. TB and COVID-19 present with overlapping symptoms and co-infection can lead to poor outcomes. We assessed the frequency of SARS-CoV-2 positive serology and SARS-CoV-2 infection and the risk of mortality at 6 months in PLHIV with TB disease and SARS-CoV-2 infection. This multi-country, prospective, observational study, conducted between 7th September 2020 and 7th April 2022, included ambulatory adult PLHIV investigated for TB (with symptoms of TB or advanced HIV disease) in Kenya, Uganda, and South Africa. Testing included CD4 cell count, Xpert MTB/RIF Ultra assay (sputum), Determine TB LAM Ag assay (urine), chest X-ray, blood SARS-CoV-2 serology test and SARS-CoV-2 PCR (only if TB or COVID-19 symptoms). Individuals were followed for 6 months. Among 1254 participants, 1204 participants had SARS-CoV-2 serology (54% women, median CD4 344 cells/µL [IQR 132–673]), and 487 had SARS-CoV-2 PCR. SARS-CoV-2 serology positivity was 27.0% (325/1204), lower in PLHIV with CD4 counts <200 cells/µL (19.9%, 99/497) than in those with CD4 counts ≥200 cells/µL (31.6%, 222/703), p<0.001. SARS-CoV-2 PCR positivity was 8.6% (42/487) and 27.7% (135/487) had probable or confirmed SARS-CoV-2 infection. Among PLHIV with symptoms of TB or of COVID-19, 6.6% (32/487) had SARS-CoV-2 infection and TB disease. In multivariable analyses, the risk of death was higher in PLHIV with both SARS-CoV-2 infection and TB compared to those with only SARS-CoV-2 infection (adjusted hazard ratio [aHR] 8.90, 95%CI 1.47-53.96, p=0.017), with only TB (aHR 3.70, 95%CI 1.00-13.72, p=0.050) or with none of them (aHR 6.83, 95%CI 1.75-26.72, p=0.006). These findings support SARS-CoV-2 testing in PLHIV with symptoms of TB, and SARS-CoV-2 vaccination, especially for those with severe immunosuppression. PLHIV with COVID-19 and TB have an increased risk of mortality and would benefit from comprehensive management and close monitoring.
Journal Article > ResearchFull Text
Lancet Global Health. 1 January 2023; Volume 11 (Issue 1); e126-e135.; DOI:10.1016/S2214-109X(22)00463-6
Huerga H, Bastard M, Lubega AV, Akinyi M, Antabak NT, et al.
Lancet Global Health. 1 January 2023; Volume 11 (Issue 1); e126-e135.; DOI:10.1016/S2214-109X(22)00463-6
BACKGROUND
Development of rapid biomarker-based tests that can diagnose tuberculosis using non-sputum samples is a priority for tuberculosis control. We aimed to compare the diagnostic accuracy of the novel Fujifilm SILVAMP TB LAM (FujiLAM) assay with the WHO-recommended Alere Determine TB-LAM Ag test (AlereLAM) using urine samples from HIV-positive patients.
METHODS
We did a diagnostic accuracy study at five outpatient public health facilities in Uganda, Kenya, Mozambique, and South Africa. Eligible patients were ambulatory HIV-positive individuals (aged ≥15 years) with symptoms of tuberculosis irrespective of their CD4 T-cell count (group 1), and asymptomatic patients with advanced HIV disease (CD4 count <200 cells per μL, or HIV clinical stage 3 or 4; group 2). All participants underwent clinical examination, chest x-ray, and blood sampling, and were requested to provide a fresh urine sample, and two sputum samples. FujiLAM and AlereLAM urine assays, Xpert MTB/RIF Ultra assay on sputum or urine, sputum culture for Mycobacterium tuberculosis, and CD4 count were systematically carried out for all patients. Sensitivity and specificity of FujiLAM and AlereLAM were evaluated against microbiological and composite reference standards.
FINDINGS
Between Aug 24, 2020 and Sept 21, 2021, 1575 patients (823 [52·3%] women) were included in the study: 1031 patients in group 1 and 544 patients in group 2. Tuberculosis was microbiologically confirmed in 96 (9·4%) of 1022 patients in group 1 and 18 (3·3%) of 542 patients in group 2. Using the microbiological reference standard, FujiLAM sensitivity was 60% (95% CI 51–69) and AlereLAM sensitivity was 40% (31–49; p<0·001). Among patients with CD4 counts of less than 200 cells per μL, FujiLAM sensitivity was 69% (57–79) and AlereLAM sensitivity was 52% (40–64; p=0·0218). Among patients with CD4 counts of 200 cells per μL or higher, FujiLAM sensitivity was 47% (34–61) and AlereLAM sensitivity was 24% (14–38; p=0·0116). Using the microbiological reference standard, FujiLAM specificity was 87% (95% CI 85–89) and AlereLAM specificity was 86% (95 CI 84–88; p=0·941). FujiLAM sensitivity varied by lot number from 48% (34–62) to 76% (57–89) and specificity from 77% (72–81) to 98% (93–99).
INTERPRETATION
Next-generation, higher sensitivity urine-lipoarabinomannan assays are potentially promising tests that allow rapid tuberculosis diagnosis at the point of care for HIV-positive patients. However, the variability in accuracy between FujiLAM lot numbers needs to be addressed before clinical use.
Development of rapid biomarker-based tests that can diagnose tuberculosis using non-sputum samples is a priority for tuberculosis control. We aimed to compare the diagnostic accuracy of the novel Fujifilm SILVAMP TB LAM (FujiLAM) assay with the WHO-recommended Alere Determine TB-LAM Ag test (AlereLAM) using urine samples from HIV-positive patients.
METHODS
We did a diagnostic accuracy study at five outpatient public health facilities in Uganda, Kenya, Mozambique, and South Africa. Eligible patients were ambulatory HIV-positive individuals (aged ≥15 years) with symptoms of tuberculosis irrespective of their CD4 T-cell count (group 1), and asymptomatic patients with advanced HIV disease (CD4 count <200 cells per μL, or HIV clinical stage 3 or 4; group 2). All participants underwent clinical examination, chest x-ray, and blood sampling, and were requested to provide a fresh urine sample, and two sputum samples. FujiLAM and AlereLAM urine assays, Xpert MTB/RIF Ultra assay on sputum or urine, sputum culture for Mycobacterium tuberculosis, and CD4 count were systematically carried out for all patients. Sensitivity and specificity of FujiLAM and AlereLAM were evaluated against microbiological and composite reference standards.
FINDINGS
Between Aug 24, 2020 and Sept 21, 2021, 1575 patients (823 [52·3%] women) were included in the study: 1031 patients in group 1 and 544 patients in group 2. Tuberculosis was microbiologically confirmed in 96 (9·4%) of 1022 patients in group 1 and 18 (3·3%) of 542 patients in group 2. Using the microbiological reference standard, FujiLAM sensitivity was 60% (95% CI 51–69) and AlereLAM sensitivity was 40% (31–49; p<0·001). Among patients with CD4 counts of less than 200 cells per μL, FujiLAM sensitivity was 69% (57–79) and AlereLAM sensitivity was 52% (40–64; p=0·0218). Among patients with CD4 counts of 200 cells per μL or higher, FujiLAM sensitivity was 47% (34–61) and AlereLAM sensitivity was 24% (14–38; p=0·0116). Using the microbiological reference standard, FujiLAM specificity was 87% (95% CI 85–89) and AlereLAM specificity was 86% (95 CI 84–88; p=0·941). FujiLAM sensitivity varied by lot number from 48% (34–62) to 76% (57–89) and specificity from 77% (72–81) to 98% (93–99).
INTERPRETATION
Next-generation, higher sensitivity urine-lipoarabinomannan assays are potentially promising tests that allow rapid tuberculosis diagnosis at the point of care for HIV-positive patients. However, the variability in accuracy between FujiLAM lot numbers needs to be addressed before clinical use.
Conference Material > Abstract
Taremwa IM
TB Research Dissemination Workshop, Epicentre Uganda. 29 June 2022
BACKGROUND
People with immunosuppression may be particularly vulnerable to SARS-CoV-2 and some symptoms of infection by SARS-CoV-2 and TB are similar. Dual infection with both TB and COVID-19 may also lead to poorer treatment outcomes. This study was nested into the FujiLAM study and assessed the prevalence of exposure and infection by SARS-CoV-2 among HIV patients investigated for TB.
METHODS
A prospective observational study including HIV-positive patients with symptoms of TB (group 1) and patients with advanced HIV disease and no symptoms of TB (group 2) in Uganda, Kenya, and South Africa. All patients were investigated for TB and were proposed SARS-CoV-2 antibody testing at the first and the 6-month consultation. SARS-CoV-2 PCR was proposed to patients with symptoms of TB at the first consultation and patients with symptoms of Covid-19 at any time during follow-up. Exposure to SARS-CoV-2 was defined by the detection of antibodies, while the infection was determined by PCR.
FINDINGS
In total, 1466 HIV-positive patients included in the FujiLAM study were investigated for SARS-CoV-2 (985 patients in group 1 and, 481 patients in group 2). Of these, 1254 (85.5%) patients consented to SARS-CoV-2 antibody testing (829 in group 1 and 425 in group 2), and 1188 (94.7%) of them had results. Overall, 27.9% (331/1188) of patients had a positive serology result. According to the CD4 count, a positive serology result was found in 22.3% (110/443) of patients with CD4<200, and 31.7% (213/671) of those with CD4>200, p<0.001. Among patients with symptoms of TB who accepted PCR testing, 8.3% (40/483) had PCR positive results, of whom, 12.5% (5/40) had confirmed TB. Finally, among the 40 patients that were PCR positive, 15 (35.7%) were started on TB treatment.
INTERPRETATIONS
This study reports moderate to high exposure to Covid-19 among patients investigated for TB. Also, it reveals that HIV-positive with CD4<200 have lower Covid-19 serology positivity than those with CD4≥200. This finding may have implications regarding the level of protection for immunosuppressed HIV-positive patients who have passed the disease or for vaccination strategy. Indeed, people living with HIV and with a low levels of CD4 should be prioritized for COVID-19 vaccination. Moreover, a considerable proportion of Covid-19 infected patients were also diagnosed with TB.
These abstracts are not to be quoted for publication
People with immunosuppression may be particularly vulnerable to SARS-CoV-2 and some symptoms of infection by SARS-CoV-2 and TB are similar. Dual infection with both TB and COVID-19 may also lead to poorer treatment outcomes. This study was nested into the FujiLAM study and assessed the prevalence of exposure and infection by SARS-CoV-2 among HIV patients investigated for TB.
METHODS
A prospective observational study including HIV-positive patients with symptoms of TB (group 1) and patients with advanced HIV disease and no symptoms of TB (group 2) in Uganda, Kenya, and South Africa. All patients were investigated for TB and were proposed SARS-CoV-2 antibody testing at the first and the 6-month consultation. SARS-CoV-2 PCR was proposed to patients with symptoms of TB at the first consultation and patients with symptoms of Covid-19 at any time during follow-up. Exposure to SARS-CoV-2 was defined by the detection of antibodies, while the infection was determined by PCR.
FINDINGS
In total, 1466 HIV-positive patients included in the FujiLAM study were investigated for SARS-CoV-2 (985 patients in group 1 and, 481 patients in group 2). Of these, 1254 (85.5%) patients consented to SARS-CoV-2 antibody testing (829 in group 1 and 425 in group 2), and 1188 (94.7%) of them had results. Overall, 27.9% (331/1188) of patients had a positive serology result. According to the CD4 count, a positive serology result was found in 22.3% (110/443) of patients with CD4<200, and 31.7% (213/671) of those with CD4>200, p<0.001. Among patients with symptoms of TB who accepted PCR testing, 8.3% (40/483) had PCR positive results, of whom, 12.5% (5/40) had confirmed TB. Finally, among the 40 patients that were PCR positive, 15 (35.7%) were started on TB treatment.
INTERPRETATIONS
This study reports moderate to high exposure to Covid-19 among patients investigated for TB. Also, it reveals that HIV-positive with CD4<200 have lower Covid-19 serology positivity than those with CD4≥200. This finding may have implications regarding the level of protection for immunosuppressed HIV-positive patients who have passed the disease or for vaccination strategy. Indeed, people living with HIV and with a low levels of CD4 should be prioritized for COVID-19 vaccination. Moreover, a considerable proportion of Covid-19 infected patients were also diagnosed with TB.
These abstracts are not to be quoted for publication
Journal Article > ResearchAbstract
J Clin Microbiol. 16 October 2019
Ardizzoni E, Orikiriza P, Ssuuna C, Nyehangane D, Gumsboga M, et al.
J Clin Microbiol. 16 October 2019
Background: Xpert MTB/RIF (Xpert) and culture are the most reliable methods for tuberculosis diagnosis but are still poorly accessible in many low resource countries. We aimed to assess the effect of OMNIgene® SPUTUM (OM-S) and ethanol in preserving sputum for Xpert and OM-S for mycobacteria growth indicator tube (MGIT) testing over a period of 15 and 8 days respectively.
Methods: Sputum were collected from newly diagnosed smear-positive patients. For Xpert, pooled samples were split into 5 aliquots: 3 for Xpert on day 0, 7 and 15 days without additive and 2 with either OM-S or ethanol at day 15. For MGIT, 2 aliquots were tested without preservative and 2 with OM-S at 0 and 8 days.
Results: A total of 48 and 47 samples were included in the analysis for Xpert and culture. With Xpert, using Day 0 as reference, untreated samples stored for 7 and 15 days showed concordance of 45/46 (97.8%) and 46/48 (95.8%). For samples preserved with OM-S or ethanol for 15 days compared with untreated samples processed at day 0 or after 15 days, OM-S concordance was 46/48(95.8%) and 47/48(97.9%), while ethanol was 44/48 (91.7%) and 45/48 (93.8%). With MGIT, concordance between untreated and OM-S treated samples was 21/41(51.2%) at Day 0 and 21/44(47.7%) at day8.
Conclusions: Xpert equally detected TB in OM-S treated and untreated samples up to 15 days but showed slightly lower detection in ethanol treated samples. Among OM-S treated samples, MGIT positivity was significantly lower compared to untreated samples at both time-points.
Methods: Sputum were collected from newly diagnosed smear-positive patients. For Xpert, pooled samples were split into 5 aliquots: 3 for Xpert on day 0, 7 and 15 days without additive and 2 with either OM-S or ethanol at day 15. For MGIT, 2 aliquots were tested without preservative and 2 with OM-S at 0 and 8 days.
Results: A total of 48 and 47 samples were included in the analysis for Xpert and culture. With Xpert, using Day 0 as reference, untreated samples stored for 7 and 15 days showed concordance of 45/46 (97.8%) and 46/48 (95.8%). For samples preserved with OM-S or ethanol for 15 days compared with untreated samples processed at day 0 or after 15 days, OM-S concordance was 46/48(95.8%) and 47/48(97.9%), while ethanol was 44/48 (91.7%) and 45/48 (93.8%). With MGIT, concordance between untreated and OM-S treated samples was 21/41(51.2%) at Day 0 and 21/44(47.7%) at day8.
Conclusions: Xpert equally detected TB in OM-S treated and untreated samples up to 15 days but showed slightly lower detection in ethanol treated samples. Among OM-S treated samples, MGIT positivity was significantly lower compared to untreated samples at both time-points.
Journal Article > ResearchFull Text
BMC Infect Dis. 24 April 2017; Volume 17 (Issue 1); 299.; DOI:10.1186/s12879-017-2335-7
Atwine D, Orikiriza P, Taremwa IM, Ayebare A, Logoose S, et al.
BMC Infect Dis. 24 April 2017; Volume 17 (Issue 1); 299.; DOI:10.1186/s12879-017-2335-7
BACKGROUND
Estimates of month-2 culture conversion, a proxy indicator of tuberculosis (TB) treatment efficacy in phase-2 trials can vary by culture-type and geographically with lower rates reported among African sites. The sub-study aimed at comparing TB detection rates of different culture media, within and across rifampicin-based regimens (R10, 15 and 20 mg/Kg) over a 6-month treatment follow-up period, and to establish predictors of month-2 culture non-conversion among HIV-negative TB patients enrolled at RIFATOX trial site in Uganda.
METHODS
Unlike in other Rifatox Trial sites, it is only in Uganda were Lowenstein-Jensen (LJ) and Mycobacteria growth indicator tube (MGIT) were used throughout 6-months for treatment monitoring. Conversion rates were compared at month-2, 4 and 6 across cultures and treatment-type. Binomial regression analysis performed for predictors of month-2 non-conversion.
RESULTS
Of the 100 enrolled patients, 45% had converted based on combined LJ and MGIT by month-2, with no significant differences across treatment arms, p = 0.721. LJ exhibited higher conversion rates than MGIT at month-2 (58.4% vs 56.0%, p = 0.0707) and month-4 (98.9% vs 88.4%, p = 0.0391) respectively, more so within the high-dose rifampicin arms. All patients had converted by month-6. Time-to-TB detection (TTD) on MGIT and social service jobs independently predict month-2 non-conversion.
CONCLUSION
The month-2 culture conversion used in phase 2 clinical trials as surrogate marker of treatment efficacy is influenced by the culture method used for monitoring mycobacterial response to TB treatment. Therefore, multi-centric TB therapeutic trials using early efficacy endpoint should use the same culture method across sites. The Time-to-detection of MTB on MGIT prior to treatment and working in Social service jobs bear an increased risk of culture non-conversion at month-2.
Estimates of month-2 culture conversion, a proxy indicator of tuberculosis (TB) treatment efficacy in phase-2 trials can vary by culture-type and geographically with lower rates reported among African sites. The sub-study aimed at comparing TB detection rates of different culture media, within and across rifampicin-based regimens (R10, 15 and 20 mg/Kg) over a 6-month treatment follow-up period, and to establish predictors of month-2 culture non-conversion among HIV-negative TB patients enrolled at RIFATOX trial site in Uganda.
METHODS
Unlike in other Rifatox Trial sites, it is only in Uganda were Lowenstein-Jensen (LJ) and Mycobacteria growth indicator tube (MGIT) were used throughout 6-months for treatment monitoring. Conversion rates were compared at month-2, 4 and 6 across cultures and treatment-type. Binomial regression analysis performed for predictors of month-2 non-conversion.
RESULTS
Of the 100 enrolled patients, 45% had converted based on combined LJ and MGIT by month-2, with no significant differences across treatment arms, p = 0.721. LJ exhibited higher conversion rates than MGIT at month-2 (58.4% vs 56.0%, p = 0.0707) and month-4 (98.9% vs 88.4%, p = 0.0391) respectively, more so within the high-dose rifampicin arms. All patients had converted by month-6. Time-to-TB detection (TTD) on MGIT and social service jobs independently predict month-2 non-conversion.
CONCLUSION
The month-2 culture conversion used in phase 2 clinical trials as surrogate marker of treatment efficacy is influenced by the culture method used for monitoring mycobacterial response to TB treatment. Therefore, multi-centric TB therapeutic trials using early efficacy endpoint should use the same culture method across sites. The Time-to-detection of MTB on MGIT prior to treatment and working in Social service jobs bear an increased risk of culture non-conversion at month-2.