Journal Article > ResearchFull Text
AIDS. 2019 October 1; Volume 33 (Issue 12); 1881-1889.; DOI:10.1097/QAD.0000000000002303
Sacks JA, Fong Y, Gonzalez MP, Andreotti M, Baliga S, et al.
AIDS. 2019 October 1; Volume 33 (Issue 12); 1881-1889.; DOI:10.1097/QAD.0000000000002303
BACKGROUND
Coverage of viral load testing remains low with only half of the patients in need having adequate access. Alternative technologies to high throughput centralized machines can be used to support viral load scale-up; however, clinical performance data are lacking. We conducted a meta-analysis comparing the Cepheid Xpert HIV-1 viral load plasma assay to traditional laboratory-based technologies.
METHODS
Cepheid Xpert HIV-1 and comparator laboratory technology plasma viral load results were provided from 13 of the 19 eligible studies, which accounted for a total of 3790 paired data points. We used random effects models to determine the accuracy and misclassification at various treatment failure thresholds (detectable, 200, 400, 500, 600, 800 and 1000 copies/ml).
RESULTS
Thirty percent of viral load test results were undetectable, while 45% were between detectable and 10 000 copies/ml and the remaining 25% were above 10 000 copies/ml. The median Xpert viral load was 119 copies/ml and the median comparator viral load was 157 copies/ml, while the log10 bias was 0.04 (0.02–0.07). The sensitivity and specificity to detect treatment failure were above 95% at all treatment failure thresholds, except for detectable, at which the sensitivity was 93.33% (95% confidence interval: 88.2–96.3) and specificity was 80.56% (95% CI: 64.6–90.4).
CONCLUSION
The Cepheid Xpert HIV-1 viral load plasma assay results were highly comparable to laboratory-based technologies with limited bias and high sensitivity and specificity to detect treatment failure. Alternative specimen types and technologies that enable decentralized testing services can be considered to expand access to viral load.
Coverage of viral load testing remains low with only half of the patients in need having adequate access. Alternative technologies to high throughput centralized machines can be used to support viral load scale-up; however, clinical performance data are lacking. We conducted a meta-analysis comparing the Cepheid Xpert HIV-1 viral load plasma assay to traditional laboratory-based technologies.
METHODS
Cepheid Xpert HIV-1 and comparator laboratory technology plasma viral load results were provided from 13 of the 19 eligible studies, which accounted for a total of 3790 paired data points. We used random effects models to determine the accuracy and misclassification at various treatment failure thresholds (detectable, 200, 400, 500, 600, 800 and 1000 copies/ml).
RESULTS
Thirty percent of viral load test results were undetectable, while 45% were between detectable and 10 000 copies/ml and the remaining 25% were above 10 000 copies/ml. The median Xpert viral load was 119 copies/ml and the median comparator viral load was 157 copies/ml, while the log10 bias was 0.04 (0.02–0.07). The sensitivity and specificity to detect treatment failure were above 95% at all treatment failure thresholds, except for detectable, at which the sensitivity was 93.33% (95% confidence interval: 88.2–96.3) and specificity was 80.56% (95% CI: 64.6–90.4).
CONCLUSION
The Cepheid Xpert HIV-1 viral load plasma assay results were highly comparable to laboratory-based technologies with limited bias and high sensitivity and specificity to detect treatment failure. Alternative specimen types and technologies that enable decentralized testing services can be considered to expand access to viral load.
Journal Article > ResearchFull Text
Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 2022 May 1; Volume 27; 100316.; DOI: 10.1016/j.jctube.2022.100316
Rucker SCM, Lissouba P, Akinyi M, Lubega AV, Stewart RC, et al.
Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 2022 May 1; Volume 27; 100316.; DOI: 10.1016/j.jctube.2022.100316
BACKGROUND
The novel urine-based FujiLAM test identifies tuberculosis in HIV-positive patients but may be challenging to use at point-of-care (POC).
OBJECTIVES
We assessed the feasibility and acceptability of using the FujiLAM test at the point of care in outpatient settings.
METHODS
We conducted a mixed-methods study in four outpatient settings in Kenya, Mozambique, South Africa, and Uganda between November 2020 and September 2021. The test was performed at POC in existing clinic laboratories and consultation spaces. We performed direct observations in the four health facilities, individual questionnaires, proficiency testing evaluations, and individual interviews among healthcare workers performing the FujiLAM test (healthcare workers), and group discussions with programme managers.
RESULTS
Overall, 18/19 (95%) healthcare workers and 14/14 (100%) managers agreed to participate in the study. Most assessed healthcare workers, including lay health workers (10/11; 91%), met the minimum required theoretical knowledge and practical skill in performing the FujiLAM test. Most healthcare workers (17/18; 94%) found the FujiLAM test overall “Easy/Very easy” to perform. Some challenges were mentioned: many timed steps (5/18; 28%); ensuring correct incubation period (5/18; 28%); test result readability (4/18; 22%); and difficulties with cartridge buttons (3/18; 17%). Half of the healthcare workers regularly performing the test (4/7; 57%) found it “Easy” to integrate into routine activities. Most healthcare workers and managers believed that any healthcare worker could perform the test after adequate training.
CONCLUSIONS
Implementing the FujiLAM test in outpatient POC settings is feasible and acceptable to healthcare workers and managers. This test can be performed in various clinic locations by any healthcare worker. The timed, multi-step test procedure is challenging and may affect the workload in resource-constrained health facilities.
The novel urine-based FujiLAM test identifies tuberculosis in HIV-positive patients but may be challenging to use at point-of-care (POC).
OBJECTIVES
We assessed the feasibility and acceptability of using the FujiLAM test at the point of care in outpatient settings.
METHODS
We conducted a mixed-methods study in four outpatient settings in Kenya, Mozambique, South Africa, and Uganda between November 2020 and September 2021. The test was performed at POC in existing clinic laboratories and consultation spaces. We performed direct observations in the four health facilities, individual questionnaires, proficiency testing evaluations, and individual interviews among healthcare workers performing the FujiLAM test (healthcare workers), and group discussions with programme managers.
RESULTS
Overall, 18/19 (95%) healthcare workers and 14/14 (100%) managers agreed to participate in the study. Most assessed healthcare workers, including lay health workers (10/11; 91%), met the minimum required theoretical knowledge and practical skill in performing the FujiLAM test. Most healthcare workers (17/18; 94%) found the FujiLAM test overall “Easy/Very easy” to perform. Some challenges were mentioned: many timed steps (5/18; 28%); ensuring correct incubation period (5/18; 28%); test result readability (4/18; 22%); and difficulties with cartridge buttons (3/18; 17%). Half of the healthcare workers regularly performing the test (4/7; 57%) found it “Easy” to integrate into routine activities. Most healthcare workers and managers believed that any healthcare worker could perform the test after adequate training.
CONCLUSIONS
Implementing the FujiLAM test in outpatient POC settings is feasible and acceptable to healthcare workers and managers. This test can be performed in various clinic locations by any healthcare worker. The timed, multi-step test procedure is challenging and may affect the workload in resource-constrained health facilities.
Journal Article > ResearchFull Text
Public Health Action. 2019 December 21
Nyagadza B, Kudya N, Mbofana E, Masaka S, Garone DB, et al.
Public Health Action. 2019 December 21
Background: Demand for viral load (VL) monitoring is expected to increase; however, implementation of the multifaceted VL testing poses numerous challenges. We report experiences from Médecins Sans Frontiéres (MSF) and partners in the scale-up of HIV VL in collaboration with the Ministry of Health and Child Care (MoHCC) of Zimbabwe.
Methods: A retrospective data review of routine reports from MSF-supported health facilities in Manicaland Province (Zimbabwe) was conducted. These secondary aggregate data were triangulated, and emerging themes of lessons learnt from VL monitoring were shared.
Results: A VL testing coverage of 63% (5966/9456) was achieved among the 40 health facilities, together with a switch rate to second-line antiretroviral therapy (ART) of 46.4% (108/233). The key enablers to scaling-up the VL monitoring were well-equipped and supported VL laboratories, the operationalisation of the on-the-job clinical mentoring and systematic weaning off of better performing health facilities. Concerted efforts from different implementing partners and funders in the HIV programme, and close collaboration with MoHCC were pivotal.
Conclusion: Our experience indicates that clinical mentoring is effective, and resulted in high VL testing coverage and up-skilling primary health care workers in VL monitoring. Attention must be focused on innovations for improving VL result utilisation, especially the identification and management of patients who fail ART.
Methods: A retrospective data review of routine reports from MSF-supported health facilities in Manicaland Province (Zimbabwe) was conducted. These secondary aggregate data were triangulated, and emerging themes of lessons learnt from VL monitoring were shared.
Results: A VL testing coverage of 63% (5966/9456) was achieved among the 40 health facilities, together with a switch rate to second-line antiretroviral therapy (ART) of 46.4% (108/233). The key enablers to scaling-up the VL monitoring were well-equipped and supported VL laboratories, the operationalisation of the on-the-job clinical mentoring and systematic weaning off of better performing health facilities. Concerted efforts from different implementing partners and funders in the HIV programme, and close collaboration with MoHCC were pivotal.
Conclusion: Our experience indicates that clinical mentoring is effective, and resulted in high VL testing coverage and up-skilling primary health care workers in VL monitoring. Attention must be focused on innovations for improving VL result utilisation, especially the identification and management of patients who fail ART.
Journal Article > ResearchFull Text
PLOS One. 2020 April 3; Volume 15 (Issue 4); e0230453.; DOI:10.1371/journal.pone.0230453.
Ndlovu Z, Massaquoi L, Bangwen NE, Batumba JN, Bora RU, et al.
PLOS One. 2020 April 3; Volume 15 (Issue 4); e0230453.; DOI:10.1371/journal.pone.0230453.
BACKGROUND
In sub-Saharan Africa, a third of people starting antiretroviral therapy and majority of patients returning to HIV-care after disengagement, present with advanced HIV disease (ADH), and are at high risk of mortality. Simplified and more affordable point-of-care (POC) diagnostics are required to increase access to prompt CD4 cell count screening for ambulatory and asymptomatic patients. The Visitect CD4 Lateral Flow Assay (LFA) is a disposable POC test, providing a visually interpreted result of above or below 200 CD4cells/mm3. This study evaluated the diagnostic performance of this index test.
METHODS
Consenting patients above 18years of age and eligible for CD4 testing were enrolled in Nsanje district hospital (Malawi), Gutu mission hospital (Zimbabwe) and Centre hopitalier de Kabinda (DRC). A total of 708 venous blood samples were tested in the index test and in the BD FACSCount assay (reference test method) in the laboratories (Phase 1) to determine diagnostic accuracy. A total of 433 finger-prick (FP) samples were tested on the index test at POC by clinicians (Phase 2) and a self-completed questionnaire was administered to all testers to explore usability of the index test.
RESULTS
Among 708 patients, 67.2% were female and median CD4 was 297cells/mm3. The sensitivity of the Visitect CD4 LFA using venous blood in the laboratory was 95.0% [95% CI: 91.3-97.5] and specificity was 81.9% [95% CI: 78.2-85.2%]. Using FP samples, the sensitivity of the Visitect CD4 LFA was 98.3% [95% CI: 95.0-99.6] and specificity was 77.2% [95% CI: 71.6-82.2%]. Usability of the Visitect CD4 LFA was high across the study sites with 97% successfully completed tests. Due to the required specific multiple incubation and procedural steps during the Visitect CD4 LFA testing, few health workers (7/26) were not confident to manage testing whilst multi-tasking in their clinical work.
CONCLUSIONS
Visitect CD4 LFA is a promising test for decentralized CD4 screening in resource-limited settings, without access to CD4 testing and and it can trigger prompt management of patients with AHD. Lay health cadres should be considered to conduct Visitect CD4 LFA testing in PHCs as well as coordinating all other POC quality assurance.
In sub-Saharan Africa, a third of people starting antiretroviral therapy and majority of patients returning to HIV-care after disengagement, present with advanced HIV disease (ADH), and are at high risk of mortality. Simplified and more affordable point-of-care (POC) diagnostics are required to increase access to prompt CD4 cell count screening for ambulatory and asymptomatic patients. The Visitect CD4 Lateral Flow Assay (LFA) is a disposable POC test, providing a visually interpreted result of above or below 200 CD4cells/mm3. This study evaluated the diagnostic performance of this index test.
METHODS
Consenting patients above 18years of age and eligible for CD4 testing were enrolled in Nsanje district hospital (Malawi), Gutu mission hospital (Zimbabwe) and Centre hopitalier de Kabinda (DRC). A total of 708 venous blood samples were tested in the index test and in the BD FACSCount assay (reference test method) in the laboratories (Phase 1) to determine diagnostic accuracy. A total of 433 finger-prick (FP) samples were tested on the index test at POC by clinicians (Phase 2) and a self-completed questionnaire was administered to all testers to explore usability of the index test.
RESULTS
Among 708 patients, 67.2% were female and median CD4 was 297cells/mm3. The sensitivity of the Visitect CD4 LFA using venous blood in the laboratory was 95.0% [95% CI: 91.3-97.5] and specificity was 81.9% [95% CI: 78.2-85.2%]. Using FP samples, the sensitivity of the Visitect CD4 LFA was 98.3% [95% CI: 95.0-99.6] and specificity was 77.2% [95% CI: 71.6-82.2%]. Usability of the Visitect CD4 LFA was high across the study sites with 97% successfully completed tests. Due to the required specific multiple incubation and procedural steps during the Visitect CD4 LFA testing, few health workers (7/26) were not confident to manage testing whilst multi-tasking in their clinical work.
CONCLUSIONS
Visitect CD4 LFA is a promising test for decentralized CD4 screening in resource-limited settings, without access to CD4 testing and and it can trigger prompt management of patients with AHD. Lay health cadres should be considered to conduct Visitect CD4 LFA testing in PHCs as well as coordinating all other POC quality assurance.
Conference Material > Slide Presentation
Khan S, Silsarma A, Iyer AS, Galindo MA, Chavan VV, et al.
MSF Scientific Day International 2023. 2023 June 7; DOI:10.57740/0dpv-wz08
Conference Material > Abstract
Ronoh Y, Some D, Ortuno R, Kuwenyi K, Mupepe T, et al.
MSF Scientific Days International 2020: Research. 2020 May 20
INTRODUCTION
Cervical cancer is now largely a preventable disease; however, implementation of highly sensitive molecular screening technologies in low-resource settings is partly hindered by the need for intensive investment in equipment and highly trained, skilled laboratory personnel. Resource limitations often preclude the possibility of same-day screening and treatment, as recommend by WHO. We sought to assess the diagnostic accuracy of self-collected versus nurse-collected high vaginal samples (HVS) for human papillomavirus (HPV) screening using GeneXpert, for within-country validation and to further inform its scale-up within routine point-of-care testing in primary healthcare systems.
METHODS
Consenting women presenting for routine cervical screening in selected health facilities in Gutu District, Zimbabwe, were asked to provide three HVS obtained at the same time on a single visit; the first, self-collected, and the following two, nurse-collected. Nurse-collected HVS were tested with GeneXpert (Cepheid, Sunnyvale, USA) and Cobas HPV (Roche, Pleasanton, USA; used as the reference test), whilst self-collected HVS were tested only using GeneXpert. Those testing positive on the reference test were offered visual inspection with acetic acid and cervicography (VIAC). Women with a positive VIAC examination were offered cryotherapy or loop electrosurgical excision procedure.
ETHICS
This study was approved by the MSF Ethics Review Board.
RESULTS
279 participants consented to provide HVS; none reported discomfort or side effects during or after swabbing. Among nurse-collected HVS, 11/279 participants were found positive on genotyping for HPV-16 using Cobas HPV, and nine of 279 were positive using GeneXpert. Eight out of 279 were identified on genotyping for HPV-18/45 using both platforms. The sensitivities of testing for HPV-16 and 18/45 using GeneXpert as compared to the reference test, Cobas, were 89% (95%CI 53-100) and 63% (95%CI 25-92) respectively. The sensitivity of self- and nurse-collected HVS for HPV-16 tested using GeneXpert, as compared to the reference test, was 89% (eight of nine; 95%CI 52-100). Specificity was 100% (95%CI 97-100), with a positive predictive value of 89% (95%CI 52-100), and negative predictive value of 100% (95%CI 97-100). However, sensitivity for detection of HPV-18/45 was 68.3% (95%CI 34-100).
CONCLUSION
Performance of cervical cancer screening using self-collected HVS tested with GeneXpert is comparable to that with nurse-collected HVS. Integrated GeneXpert platforms are already in wide use, enabling rapid diagnosis of tuberculosis, detection of HIV viral load, and early infant diagnosis of HIV, using a single piece of equipment. Deploying GeneXpert for HPV screening using self-collected HVS could help to provide timely results, especially in settings where VIAC is unavailable.
Cervical cancer is now largely a preventable disease; however, implementation of highly sensitive molecular screening technologies in low-resource settings is partly hindered by the need for intensive investment in equipment and highly trained, skilled laboratory personnel. Resource limitations often preclude the possibility of same-day screening and treatment, as recommend by WHO. We sought to assess the diagnostic accuracy of self-collected versus nurse-collected high vaginal samples (HVS) for human papillomavirus (HPV) screening using GeneXpert, for within-country validation and to further inform its scale-up within routine point-of-care testing in primary healthcare systems.
METHODS
Consenting women presenting for routine cervical screening in selected health facilities in Gutu District, Zimbabwe, were asked to provide three HVS obtained at the same time on a single visit; the first, self-collected, and the following two, nurse-collected. Nurse-collected HVS were tested with GeneXpert (Cepheid, Sunnyvale, USA) and Cobas HPV (Roche, Pleasanton, USA; used as the reference test), whilst self-collected HVS were tested only using GeneXpert. Those testing positive on the reference test were offered visual inspection with acetic acid and cervicography (VIAC). Women with a positive VIAC examination were offered cryotherapy or loop electrosurgical excision procedure.
ETHICS
This study was approved by the MSF Ethics Review Board.
RESULTS
279 participants consented to provide HVS; none reported discomfort or side effects during or after swabbing. Among nurse-collected HVS, 11/279 participants were found positive on genotyping for HPV-16 using Cobas HPV, and nine of 279 were positive using GeneXpert. Eight out of 279 were identified on genotyping for HPV-18/45 using both platforms. The sensitivities of testing for HPV-16 and 18/45 using GeneXpert as compared to the reference test, Cobas, were 89% (95%CI 53-100) and 63% (95%CI 25-92) respectively. The sensitivity of self- and nurse-collected HVS for HPV-16 tested using GeneXpert, as compared to the reference test, was 89% (eight of nine; 95%CI 52-100). Specificity was 100% (95%CI 97-100), with a positive predictive value of 89% (95%CI 52-100), and negative predictive value of 100% (95%CI 97-100). However, sensitivity for detection of HPV-18/45 was 68.3% (95%CI 34-100).
CONCLUSION
Performance of cervical cancer screening using self-collected HVS tested with GeneXpert is comparable to that with nurse-collected HVS. Integrated GeneXpert platforms are already in wide use, enabling rapid diagnosis of tuberculosis, detection of HIV viral load, and early infant diagnosis of HIV, using a single piece of equipment. Deploying GeneXpert for HPV screening using self-collected HVS could help to provide timely results, especially in settings where VIAC is unavailable.
Journal Article > CommentaryFull Text
PLOS Med. 2021 November 24; Volume 18 (Issue 11); e1003867.; DOI:10.1371/journal.pmed.1003867
Ndlovu Z, Ellman T
PLOS Med. 2021 November 24; Volume 18 (Issue 11); e1003867.; DOI:10.1371/journal.pmed.1003867
SUMMARY POINTS
-- Lack of access to testing plays a major role in the underdiagnosis of infectious and noncommunicable diseases, leading to higher morbidity and mortality.
-- Point-of-care (POC) tests can offer rapid results, allowing for timely initiation of therapy. However, mere availability of POC tests in health facilities does not ensure utilization. Conducting POC tests has been shown to be a burden on highly trained frontline healthcare workers (HCWs; clinicians and nurses), who often have a broader scope of responsibilities and are critically scarce in many settings.
-- The continual emergence of easy-to-use POC tests has not been accompanied by investment in a cadre of health workers to support their delivery, especially at decentralized health facilities where patients initially seek healthcare support.
-- Historically, implementation of task shifting for POC tests has proven difficult due to lack of integration into national human resource structures and fiscal plans and lack of explicit national policies promoting task shifting, together with resistance from laboratory professionals.
-- We propose that the scope of work for existing lay health worker (LHW) cadres could be broadened/remodeled to include POC tests for HIV services including for advanced HIV disease and other priority diseases, especially in primary healthcare or lower level facilities without laboratories. Policy makers and national program managers could ensure that this is part of broader national health workforce policies.
-- Concerns of professional and/or regulatory bodies must be addressed, and these bodies (medical and laboratory councils) can guide national policy on which POC tests can be task shifted to less laboratory-trained cadres, and they could also lead in the development of a framework of education and supervision to ensure sustainability and maintenance of professional standards.
-- Lay testing initiatives can scale up access to the multitude of available essential POC tests, for maximal impact of disease testing, closer to where people live. This can improve global health and accelerate progress toward universal health coverage.
-- Lack of access to testing plays a major role in the underdiagnosis of infectious and noncommunicable diseases, leading to higher morbidity and mortality.
-- Point-of-care (POC) tests can offer rapid results, allowing for timely initiation of therapy. However, mere availability of POC tests in health facilities does not ensure utilization. Conducting POC tests has been shown to be a burden on highly trained frontline healthcare workers (HCWs; clinicians and nurses), who often have a broader scope of responsibilities and are critically scarce in many settings.
-- The continual emergence of easy-to-use POC tests has not been accompanied by investment in a cadre of health workers to support their delivery, especially at decentralized health facilities where patients initially seek healthcare support.
-- Historically, implementation of task shifting for POC tests has proven difficult due to lack of integration into national human resource structures and fiscal plans and lack of explicit national policies promoting task shifting, together with resistance from laboratory professionals.
-- We propose that the scope of work for existing lay health worker (LHW) cadres could be broadened/remodeled to include POC tests for HIV services including for advanced HIV disease and other priority diseases, especially in primary healthcare or lower level facilities without laboratories. Policy makers and national program managers could ensure that this is part of broader national health workforce policies.
-- Concerns of professional and/or regulatory bodies must be addressed, and these bodies (medical and laboratory councils) can guide national policy on which POC tests can be task shifted to less laboratory-trained cadres, and they could also lead in the development of a framework of education and supervision to ensure sustainability and maintenance of professional standards.
-- Lay testing initiatives can scale up access to the multitude of available essential POC tests, for maximal impact of disease testing, closer to where people live. This can improve global health and accelerate progress toward universal health coverage.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2023 January 1; Volume 27 (Issue 1); 41-48.; DOI:10.5588/ijtld.22.0138
Mansoor H, Hirani N, Chavan VV, Das M, Sharma J, et al.
Int J Tuberc Lung Dis. 2023 January 1; Volume 27 (Issue 1); 41-48.; DOI:10.5588/ijtld.22.0138
BACKGROUND
In high TB burden countries, access to drug susceptibility testing is a major bottleneck. Targeted next-generation sequencing (tNGS) is a promising technology for rapid resistance detection. This study assessed the role of tNGS for the diagnosis of drug-resistant TB (DR-TB).
METHODS
A total of 161 samples from bacteriologically confirmed TB cases were subjected to tNGS using the Deeplex® Myc-TB kit and sequenced using the MiSeq platform. These samples were also processed for conventional phenotypic DST (pDST) using 13 drugs on Mycobacteria Growth Indicator Tube and line-probe assays (MTBDR plus and MTBDRsl).
RESULTS
There were 146 DR-TB and 15 drug-susceptible TB (DS-TB) samples. About 70% of patients with DR-TB had no previous TB treatment history. Overall, 88.2% had rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB), 58.5% pre-extensively drug-resistant TB (pre-XDR-TB) and 9.2% had XDR-TB as defined by the WHO (2020). Around 8% (n=13) of samples were non-culturable; however, identified 8 were resistant to first and second-line drugs using tNGS. Resistance frequency was similar across methods, with discordance in drugs less reliable using pDST or with limited mutational representation within databases. Sensitivities were aligned with literature reports for most drugs. We observed 10% heteroresistance, while 75% of strains were of Lineages 2 and 3.
CONCLUSIONS
Programme data supported tNGS in the diagnosis of DR-TB for early treatment using individualised regimens.
In high TB burden countries, access to drug susceptibility testing is a major bottleneck. Targeted next-generation sequencing (tNGS) is a promising technology for rapid resistance detection. This study assessed the role of tNGS for the diagnosis of drug-resistant TB (DR-TB).
METHODS
A total of 161 samples from bacteriologically confirmed TB cases were subjected to tNGS using the Deeplex® Myc-TB kit and sequenced using the MiSeq platform. These samples were also processed for conventional phenotypic DST (pDST) using 13 drugs on Mycobacteria Growth Indicator Tube and line-probe assays (MTBDR plus and MTBDRsl).
RESULTS
There were 146 DR-TB and 15 drug-susceptible TB (DS-TB) samples. About 70% of patients with DR-TB had no previous TB treatment history. Overall, 88.2% had rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB), 58.5% pre-extensively drug-resistant TB (pre-XDR-TB) and 9.2% had XDR-TB as defined by the WHO (2020). Around 8% (n=13) of samples were non-culturable; however, identified 8 were resistant to first and second-line drugs using tNGS. Resistance frequency was similar across methods, with discordance in drugs less reliable using pDST or with limited mutational representation within databases. Sensitivities were aligned with literature reports for most drugs. We observed 10% heteroresistance, while 75% of strains were of Lineages 2 and 3.
CONCLUSIONS
Programme data supported tNGS in the diagnosis of DR-TB for early treatment using individualised regimens.
Journal Article > Meta-AnalysisAbstract
AIDS. 2019 October 1; DOI:10.1097/QAD.0000000000002303.
Sacks JA, Fong Y, Gonzalez MP, Andreotti M, Baliga S, et al.
AIDS. 2019 October 1; DOI:10.1097/QAD.0000000000002303.
Journal Article > Review
Lab Chip. 2021 December 31; Volume 22 (Issue 17); 3122-3137.; DOI:10.1039/d2lc00380e
Ongaro AE, Ndlovu Z, Sollier E, Otieno C, Ondoa P, et al.
Lab Chip. 2021 December 31; Volume 22 (Issue 17); 3122-3137.; DOI:10.1039/d2lc00380e
Single-use, disposable, point-of-care diagnostic devices carry great promise for global health, including meeting urgent needs for testing and diagnosis in places with limited laboratory facilities. Unfortunately, the production and disposal of single-use devices, whether in lateral flow assay, cartridges, cassettes, or lab-on-chip microfluidic format, also poses significant challenges for environmental and human health. Point-of-care devices are commonly manufactured from unsustainable polymeric materials derived from fossil sources. Their disposal often necessitates incineration to reduce infection risk, thereby creating additional release of CO2. Many devices also contain toxic chemicals, such as cyanide derivatives, that are damaging to environmental and human health if not disposed of safely. Yet, in the absence of government regulatory frameworks, safe and sustainable waste management for these novel medical devices is often left unaddressed. There is an urgent need to find novel solutions to avert environmental and human harm from these devices, especially in low- and middle-income countries where waste management infrastructure is often weak and where the use of point-of-care tests is projected to rise in coming years. We review here common materials used in the manufacture of single-use point-of-care diagnostic tests, examine the risks they pose to environmental and human health, and investigate replacement materials that can potentially reduce the impact of microfluidic devices on the production of harmful waste. We propose solutions available to point-of-care test developers to start embedding sustainability at an early stage in their design, and to reduce their non-renewable plastic consumption in research and product development.