Other > Pre-Print
Sci Rep. 2024 March 8; DOI:10.21203/rs.3.rs-3967595/v1
Bulti AB, Dumicho AY, Shigayeva A, van Cutsem G, Steele SJ, et al.
Sci Rep. 2024 March 8; DOI:10.21203/rs.3.rs-3967595/v1
BACKGROUND
Tuberculosis (TB) among hospitalized patients is underdiagnosed. This study assessed systematic TB-screening, followed by an enhanced TB-diagnostic package for hospitalized patients implemented by trained lay health workers in KwaZulu-Natal, South Africa.
METHODS
In this before-and-after study we included patients ≥ 18 years. The intervention consisted of systematic clinical screening for TB, HIV and diabetes mellitus by lay health workers and provision of an enhanced TB-diagnostic package including sputum Xpert MTB/Rif Ultra, urine lateral-flow lipoarabinomannan assay (LF-LAM), chest x-ray, and sputum culture. We compared TB case findings with people hospitalized one year preceding the intervention.
RESULTS
In the pre-intervention phase, 5217 people were hospitalized. Among 4913 (94.2%) people not on TB treatment, 367 (7.5%) were diagnosed with TB. In the intervention phase, 4015 eligible people were hospitalized. Among 3734 (93.0%) people not on TB treatment, 560 (15.0%) were diagnosed with TB. The proportion of patients diagnosed with TB was higher in the intervention phase (15.0% vs. 7.5%, p < 0.001). Overall in-hospital mortality was lower in the intervention phase [166/3734(4.5%) vs. 336/4913(6.8%), p < 0.001].
CONCLUSION
Lay health worker-led implementation of systematic TB-screening, coupled with provision of an enhanced TB-diagnostic package significantly improved TB case detection and mortality among hospitalized adults.
Tuberculosis (TB) among hospitalized patients is underdiagnosed. This study assessed systematic TB-screening, followed by an enhanced TB-diagnostic package for hospitalized patients implemented by trained lay health workers in KwaZulu-Natal, South Africa.
METHODS
In this before-and-after study we included patients ≥ 18 years. The intervention consisted of systematic clinical screening for TB, HIV and diabetes mellitus by lay health workers and provision of an enhanced TB-diagnostic package including sputum Xpert MTB/Rif Ultra, urine lateral-flow lipoarabinomannan assay (LF-LAM), chest x-ray, and sputum culture. We compared TB case findings with people hospitalized one year preceding the intervention.
RESULTS
In the pre-intervention phase, 5217 people were hospitalized. Among 4913 (94.2%) people not on TB treatment, 367 (7.5%) were diagnosed with TB. In the intervention phase, 4015 eligible people were hospitalized. Among 3734 (93.0%) people not on TB treatment, 560 (15.0%) were diagnosed with TB. The proportion of patients diagnosed with TB was higher in the intervention phase (15.0% vs. 7.5%, p < 0.001). Overall in-hospital mortality was lower in the intervention phase [166/3734(4.5%) vs. 336/4913(6.8%), p < 0.001].
CONCLUSION
Lay health worker-led implementation of systematic TB-screening, coupled with provision of an enhanced TB-diagnostic package significantly improved TB case detection and mortality among hospitalized adults.
Journal Article > ResearchFull Text
Clin Infect Dis. 2020 December 29; DOI:10.1093/cid/ciaa1894
Tack I, Dumicho A, Ohler L, Shigayeva A, Bulti AB, et al.
Clin Infect Dis. 2020 December 29; DOI:10.1093/cid/ciaa1894
Background
At the end of 2018, South Africa updated its all-oral regimen, to include bedaquiline (BDQ) and two months of linezolid (LZD) for all patients initiating the shorter 9 to 12 months regimen for rifampicin-resistant tuberculosis (RR-TB). We assessed a group of patients in rural KwaZulu-Natal for safety and effectiveness of this treatment regimen under programmatic conditions.
Methods
We conducted a retrospective cohort analysis on RR-TB patients treated with a standardized all-oral short regimen between July 1, 2018 and April 30, 2019 in three facilities in King Cetshwayo District. An electronic register (EDR Web) and facility-based clinical charts were used to collect variables which were entered into an Epi-Info database.
Results
Our cohort included 117 patients; 68.4%(95%CI:59.3-76.3) were HIV positive. The median time to culture conversion was 56 days(95%CI:50-57). Treatment success was achieved in 75.2%(95%CI:66.5-82.3) of patients. Mortality within the cohort was 12.8%(95%CI:7.8-20.3). Anaemia was the most frequent severe adverse event. The median time to develop severe anaemia was 7.1 weeks(IQR 4.0-12.9) after treatment initiation. LZD was interrupted in 25.2%(95%CI:17.8-34.5) of participants.
Conclusions
An all-oral shorter regimen, including BDQ and LZD as core drugs for the treatment of RR-TB, shows good outcomes, in a high HIV burden rural setting. Adverse events (AEs) are common, especially for LZD, but could be managed in the program setting. Support is needed when introducing new regimens to upskill staff in the monitoring, management and reporting of AEs.
At the end of 2018, South Africa updated its all-oral regimen, to include bedaquiline (BDQ) and two months of linezolid (LZD) for all patients initiating the shorter 9 to 12 months regimen for rifampicin-resistant tuberculosis (RR-TB). We assessed a group of patients in rural KwaZulu-Natal for safety and effectiveness of this treatment regimen under programmatic conditions.
Methods
We conducted a retrospective cohort analysis on RR-TB patients treated with a standardized all-oral short regimen between July 1, 2018 and April 30, 2019 in three facilities in King Cetshwayo District. An electronic register (EDR Web) and facility-based clinical charts were used to collect variables which were entered into an Epi-Info database.
Results
Our cohort included 117 patients; 68.4%(95%CI:59.3-76.3) were HIV positive. The median time to culture conversion was 56 days(95%CI:50-57). Treatment success was achieved in 75.2%(95%CI:66.5-82.3) of patients. Mortality within the cohort was 12.8%(95%CI:7.8-20.3). Anaemia was the most frequent severe adverse event. The median time to develop severe anaemia was 7.1 weeks(IQR 4.0-12.9) after treatment initiation. LZD was interrupted in 25.2%(95%CI:17.8-34.5) of participants.
Conclusions
An all-oral shorter regimen, including BDQ and LZD as core drugs for the treatment of RR-TB, shows good outcomes, in a high HIV burden rural setting. Adverse events (AEs) are common, especially for LZD, but could be managed in the program setting. Support is needed when introducing new regimens to upskill staff in the monitoring, management and reporting of AEs.
Journal Article > LetterFull Text
Int J Tuberc Lung Dis. 2022 May 1; Volume 26 (Issue 5); 463-465.; DOI:10.5588/ijtld.22.0001
Conan N, Simons E, Ohler L, Mbatha M, van Custem G, et al.
Int J Tuberc Lung Dis. 2022 May 1; Volume 26 (Issue 5); 463-465.; DOI:10.5588/ijtld.22.0001
Journal Article > ResearchFull Text
Clin Infect Dis. 2021 November 2; Volume 73 (Issue 9); e3563-e3571.; DOI: 10.1093/cid/ciaa1894
Tack I, Dumicho A, Ohler L, Shigayeva A, Bulti AB, et al.
Clin Infect Dis. 2021 November 2; Volume 73 (Issue 9); e3563-e3571.; DOI: 10.1093/cid/ciaa1894
BACKGROUND
At the end of 2018, South Africa updated its all-oral regimen to include bedaquiline (BDQ) and 2 months of linezolid (LZD) for all patients initiating the shorter 9-12 months regimen for rifampicin-resistant tuberculosis (RR-TB). We assessed a group of patients in rural KwaZulu-Natal for safety and effectiveness of this treatment regimen under programmatic conditions.
METHODS
We conducted a retrospective cohort analysis on RR-TB patients treated with a standardized all-oral short regimen between 1 July 2018 and 30 April 2019 in 3 facilities in King Cetshwayo District. An electronic register (EDR web) and facility-based clinical charts were used to collect variables, which were entered into an Epi-Info database.
RESULTS
Our cohort included 117 patients; 68.4% (95% confidence interval [CI]: 59.3-76.3) tested positive for human immunodeficiency virus (HIV). The median time to culture conversion was 56 days (95% CI: 50-57). Treatment success was achieved in 75.2% (95% CI: 66.5-82.3) of patients. Mortality within the cohort was 12.8% (95% CI: 7.8-20.3). Anemia was the most frequent severe adverse event (AE). The median time to develop severe anemia was 7.1 weeks (interquartile range [IQR] 4.0-12.9) after treatment initiation. LZD was interrupted in 25.2% (95% CI: 17.8-34.5) of participants.
CONCLUSIONS
An all-oral shorter regimen, including BDQ and LZD as core drugs for the treatment of RR-TB, shows good outcomes, in a high HIV burden rural setting. AEs are common, especially for LZD, but could be managed in the program setting. Support is needed when introducing new regimens to train staff in the monitoring, management, and reporting of AEs.
At the end of 2018, South Africa updated its all-oral regimen to include bedaquiline (BDQ) and 2 months of linezolid (LZD) for all patients initiating the shorter 9-12 months regimen for rifampicin-resistant tuberculosis (RR-TB). We assessed a group of patients in rural KwaZulu-Natal for safety and effectiveness of this treatment regimen under programmatic conditions.
METHODS
We conducted a retrospective cohort analysis on RR-TB patients treated with a standardized all-oral short regimen between 1 July 2018 and 30 April 2019 in 3 facilities in King Cetshwayo District. An electronic register (EDR web) and facility-based clinical charts were used to collect variables, which were entered into an Epi-Info database.
RESULTS
Our cohort included 117 patients; 68.4% (95% confidence interval [CI]: 59.3-76.3) tested positive for human immunodeficiency virus (HIV). The median time to culture conversion was 56 days (95% CI: 50-57). Treatment success was achieved in 75.2% (95% CI: 66.5-82.3) of patients. Mortality within the cohort was 12.8% (95% CI: 7.8-20.3). Anemia was the most frequent severe adverse event (AE). The median time to develop severe anemia was 7.1 weeks (interquartile range [IQR] 4.0-12.9) after treatment initiation. LZD was interrupted in 25.2% (95% CI: 17.8-34.5) of participants.
CONCLUSIONS
An all-oral shorter regimen, including BDQ and LZD as core drugs for the treatment of RR-TB, shows good outcomes, in a high HIV burden rural setting. AEs are common, especially for LZD, but could be managed in the program setting. Support is needed when introducing new regimens to train staff in the monitoring, management, and reporting of AEs.
Journal Article > ResearchFull Text
Lancet Global Health. 2023 January 1; 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. 2023 January 1; 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.
Journal Article > ResearchFull Text
PLOS One. 2022 March 24; Volume 17 (Issue 3); e0265488.; DOI:10.1371/journal.pone.0265488
Conan N, Simons E, Chihana ML, Ohler L, FordKamara E, et al.
PLOS One. 2022 March 24; Volume 17 (Issue 3); e0265488.; DOI:10.1371/journal.pone.0265488
INTRODUCTION
High coverage of antiretroviral therapy (ART) in people living with HIV (PLHIV) increases viral suppression at population level and may reduce incidence. Médecins sans Frontières, in collaboration with the South African Department of Health, has been working in Eshowe/Mbongolwane (KwaZulu Natal) since 2011 to increase access to quality HIV services. Five years after an initial survey, we conducted a second survey to measure progress in HIV diagnosis and viral suppression and to identify remaining gaps.
METHODS
A cross-sectional, population-based, stratified two-stage cluster survey was implemented in 2018, using the same design as in 2013. Consenting participants aged 15-59 years were interviewed and tested for HIV at home. Those HIV-positive were tested for HIV viral load (viral suppression defined as <1000 copies/mL).
RESULTS
Overall, 3,278 individuals were included. The proportion of HIV-positive participants virally suppressed was 83.8% in 2018 compared to 57.1% in 2013 (p<0.001), with increases in all subpopulations. The largest gap remained in men aged 15-29 years, among whom viral suppression was 51.5%. Nevertheless, of the total unsuppressed participants, 60.3% were women, and 57.4% were individuals aged 30-59 years. Between 2013 and 2018, HIV-positive status awareness progressed from 75.2% to 89.9% and ART coverage among those aware from 70.4% to 93.8%, respectively. Among those on ART, 94.5% were virally suppressed in 2018.
CONCLUSIONS
Viral suppression improved significantly from 2013 to 2018, in all age and gender groups of PLHIV. However, almost half of HIV-positive young men remained unsuppressed, while the majority of virally unsuppressed PLHIV were women and older adults. To continue lowering HIV transmission, specific strategies are needed to increase viral suppression in those groups.
High coverage of antiretroviral therapy (ART) in people living with HIV (PLHIV) increases viral suppression at population level and may reduce incidence. Médecins sans Frontières, in collaboration with the South African Department of Health, has been working in Eshowe/Mbongolwane (KwaZulu Natal) since 2011 to increase access to quality HIV services. Five years after an initial survey, we conducted a second survey to measure progress in HIV diagnosis and viral suppression and to identify remaining gaps.
METHODS
A cross-sectional, population-based, stratified two-stage cluster survey was implemented in 2018, using the same design as in 2013. Consenting participants aged 15-59 years were interviewed and tested for HIV at home. Those HIV-positive were tested for HIV viral load (viral suppression defined as <1000 copies/mL).
RESULTS
Overall, 3,278 individuals were included. The proportion of HIV-positive participants virally suppressed was 83.8% in 2018 compared to 57.1% in 2013 (p<0.001), with increases in all subpopulations. The largest gap remained in men aged 15-29 years, among whom viral suppression was 51.5%. Nevertheless, of the total unsuppressed participants, 60.3% were women, and 57.4% were individuals aged 30-59 years. Between 2013 and 2018, HIV-positive status awareness progressed from 75.2% to 89.9% and ART coverage among those aware from 70.4% to 93.8%, respectively. Among those on ART, 94.5% were virally suppressed in 2018.
CONCLUSIONS
Viral suppression improved significantly from 2013 to 2018, in all age and gender groups of PLHIV. However, almost half of HIV-positive young men remained unsuppressed, while the majority of virally unsuppressed PLHIV were women and older adults. To continue lowering HIV transmission, specific strategies are needed to increase viral suppression in those groups.