Journal Article > CommentarySubscription Only
Nat Rev Bioeng. 2 April 2024; Volume 2 (Issue 6); 444-446.; DOI:10.1038/s44222-024-00182-5
Street A, Kersaudy Kerhoas M, Ndlovu Z
Nat Rev Bioeng. 2 April 2024; Volume 2 (Issue 6); 444-446.; DOI:10.1038/s44222-024-00182-5
What does global health equity mean? In bioengineering, ‘equity’ is often interpreted as global ‘access’ to technologies, thereby neglecting wider structural inequalities. Here we suggest that the concepts of equity need to be expanded to incorporate principles of equitable representation and recognition within the innovation ecosystem.
Journal Article > ResearchFull Text
Public Health Action. 21 June 2023; Volume 13 (Issue 2); 43-49.; DOI:10.5588/pha.22.0041
Iyer AS, Ndlovu Z, Sharma J, Mansoor H, Bharati M, et al.
Public Health Action. 21 June 2023; Volume 13 (Issue 2); 43-49.; DOI:10.5588/pha.22.0041
English
Français
BACKGROUND
Phenotypic drug susceptibility testing (pDST) for Mycobacterium tuberculosis can take up to 8 weeks, while conventional molecular tests identify a limited set of resistance mutations. Targeted next-generation sequencing (tNGS) offers rapid results for predicting comprehensive drug resistance, and this study sought to explore its operational feasibility within a public health laboratory in Mumbai, India.
METHODS
Pulmonary samples from consenting patients testing Xpert MTB-positive were tested for drug resistance by conventional methods and using tNGS. Laboratory operational and logistical implementation experiences from study team members are shared below.
RESULTS
Of the total number of patients tested, 70% (113/161) had no history of previous TB or treatment; however, 88.2% (n = 142) had rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB). There was a high concordance between resistance predictions of tNGS and pDST for most drugs, with tNGS more accurately identifying resistance overall. tNGS was integrated and adapted into the laboratory workflow; however, batching samples caused significantly longer result turnaround time, fastest at 24 days. Manual DNA extraction caused inefficiencies; thus protocol optimisations were performed. Technical expertise was required for analysis of uncharacterised mutations and interpretation of report templates. tNGS cost per sample was US$230, while for pDST this was US$119.
CONCLUSIONS
Implementation of tNGS is feasible in reference laboratories. It can rapidly identify drug resistance and should be considered as a potential alternative to pDST.
Phenotypic drug susceptibility testing (pDST) for Mycobacterium tuberculosis can take up to 8 weeks, while conventional molecular tests identify a limited set of resistance mutations. Targeted next-generation sequencing (tNGS) offers rapid results for predicting comprehensive drug resistance, and this study sought to explore its operational feasibility within a public health laboratory in Mumbai, India.
METHODS
Pulmonary samples from consenting patients testing Xpert MTB-positive were tested for drug resistance by conventional methods and using tNGS. Laboratory operational and logistical implementation experiences from study team members are shared below.
RESULTS
Of the total number of patients tested, 70% (113/161) had no history of previous TB or treatment; however, 88.2% (n = 142) had rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB). There was a high concordance between resistance predictions of tNGS and pDST for most drugs, with tNGS more accurately identifying resistance overall. tNGS was integrated and adapted into the laboratory workflow; however, batching samples caused significantly longer result turnaround time, fastest at 24 days. Manual DNA extraction caused inefficiencies; thus protocol optimisations were performed. Technical expertise was required for analysis of uncharacterised mutations and interpretation of report templates. tNGS cost per sample was US$230, while for pDST this was US$119.
CONCLUSIONS
Implementation of tNGS is feasible in reference laboratories. It can rapidly identify drug resistance and should be considered as a potential alternative to pDST.
Conference Material > Slide Presentation
Khan S, Silsarma A, Iyer AS, Galindo MA, Chavan VV, et al.
MSF Scientific Day International 2023. 7 June 2023; DOI:10.57740/0dpv-wz08
Conference Material > Abstract
Khan S, Silsarma A, Iyer AS, Galindo MA, Chavan VV, et al.
MSF Scientific Day International 2023. 7 June 2023; DOI:10.57740/k4rh-s938
INTRODUCTION
Bedaquiline (BDQ) and linezolid (LZD) are Group A drugs and form part of shorter and longer BDQ-based regimens under India’s National Tuberculosis (TB) Programme. A systematic review including some data from India on acquired BDQ resistance reports 2.2% phenotypic and 4.4% genotypic resistance in patients treated with BDQ-based regimens. The pooled frequency of LZD resistance among drug-resistant tuberculosis (DR-TB) isolates was 4.2% in a different study. The emergence of resistance to BDQ is concerning as it results in difficulties in constructing regimens, and is associated with unsuccessful treatment outcomes among DR-TB patients. Since 2015, Médecins Sans Frontières (MSF) has provided treatment for TB patients in Mumbai with extensive resistance patterns, who need newer drugs and have limited treatment options under India’s National TB Elimination Programme.
METHODS
We carried out a descriptive retrospective study of routinely collected programmatic data from December 2020 to February 2022. The study population consisted of culture-positive DR-TB patients with BDQ and LZD exposure for over one month, referred to the MSF clinic with 1) suspected or confirmed treatment failure; 2) DR-TB diagnosed household contacts of BDQ-exposed DR-TB patients.
ETHICS
This research fulfilled the exemption criteria set by the MSF Ethics Review Board (ERB) for a posteriori analyses of routinely collected clinical data, and thus did not require MSF ERB review.
RESULTS
88 culture-positive samples were subjected to BDQ and LZD drug susceptibility testing (DST). Of these, 27 showed resistance to BDQ, LZD, or both. 22.7% (20/88) showed BDQ resistance, 17% (15/88) LZD resistance, and eight patients (9%) were simultaneously resistant to BDQ and LZD. Of 88 samples, two were DR-TB diagnosed contacts of BDQ-exposed index cases, and the remaining were BDQ-exposed patients (> one month). In the resistant cohort of 27, equal proportions were male and female, and mean exposure to all Group A drugs was 14 months. 74% (20/27) patients had bilateral disease; 26% (7/27) had unilateral disease, of which 67% (18/27) had lung cavities. Simultaneous resistance to clofazimine and fluoroquinolones was found among 30% (8/27) and 78% (21/27) patients respectively. Within the resistant cohort, two patients refused treatment and 25 started on treatment. Out of 25 patients starting treatment, 8% (2/25) successfully completed treatment, 48% (12/25) died, 20% (5/25) failed, 4% (1/25) were lost to follow-up, and 20% (5/25) were still on treatment at the time of analysis. Of the five patients still on treatment patients, two culture-converted and three are still culture-positive after three months of treatment.
CONCLUSION
We observed a high proportion of BDQ and LZD resistance in patients who previously failed on BDQ and LZD-based regimens. We observe high mortality and unsuccessful outcomes in treating such cases. Designing effective treatment regimens for patients with retreatment episodes and a history of BDQ and LZD exposure is extremely challenging. We urgently recommend increased programmatic access to DST for LZD and BDQ, to ensure early access to effective regimens.
CONFLICTS OF INTEREST
None declared
Bedaquiline (BDQ) and linezolid (LZD) are Group A drugs and form part of shorter and longer BDQ-based regimens under India’s National Tuberculosis (TB) Programme. A systematic review including some data from India on acquired BDQ resistance reports 2.2% phenotypic and 4.4% genotypic resistance in patients treated with BDQ-based regimens. The pooled frequency of LZD resistance among drug-resistant tuberculosis (DR-TB) isolates was 4.2% in a different study. The emergence of resistance to BDQ is concerning as it results in difficulties in constructing regimens, and is associated with unsuccessful treatment outcomes among DR-TB patients. Since 2015, Médecins Sans Frontières (MSF) has provided treatment for TB patients in Mumbai with extensive resistance patterns, who need newer drugs and have limited treatment options under India’s National TB Elimination Programme.
METHODS
We carried out a descriptive retrospective study of routinely collected programmatic data from December 2020 to February 2022. The study population consisted of culture-positive DR-TB patients with BDQ and LZD exposure for over one month, referred to the MSF clinic with 1) suspected or confirmed treatment failure; 2) DR-TB diagnosed household contacts of BDQ-exposed DR-TB patients.
ETHICS
This research fulfilled the exemption criteria set by the MSF Ethics Review Board (ERB) for a posteriori analyses of routinely collected clinical data, and thus did not require MSF ERB review.
RESULTS
88 culture-positive samples were subjected to BDQ and LZD drug susceptibility testing (DST). Of these, 27 showed resistance to BDQ, LZD, or both. 22.7% (20/88) showed BDQ resistance, 17% (15/88) LZD resistance, and eight patients (9%) were simultaneously resistant to BDQ and LZD. Of 88 samples, two were DR-TB diagnosed contacts of BDQ-exposed index cases, and the remaining were BDQ-exposed patients (> one month). In the resistant cohort of 27, equal proportions were male and female, and mean exposure to all Group A drugs was 14 months. 74% (20/27) patients had bilateral disease; 26% (7/27) had unilateral disease, of which 67% (18/27) had lung cavities. Simultaneous resistance to clofazimine and fluoroquinolones was found among 30% (8/27) and 78% (21/27) patients respectively. Within the resistant cohort, two patients refused treatment and 25 started on treatment. Out of 25 patients starting treatment, 8% (2/25) successfully completed treatment, 48% (12/25) died, 20% (5/25) failed, 4% (1/25) were lost to follow-up, and 20% (5/25) were still on treatment at the time of analysis. Of the five patients still on treatment patients, two culture-converted and three are still culture-positive after three months of treatment.
CONCLUSION
We observed a high proportion of BDQ and LZD resistance in patients who previously failed on BDQ and LZD-based regimens. We observe high mortality and unsuccessful outcomes in treating such cases. Designing effective treatment regimens for patients with retreatment episodes and a history of BDQ and LZD exposure is extremely challenging. We urgently recommend increased programmatic access to DST for LZD and BDQ, to ensure early access to effective regimens.
CONFLICTS OF INTEREST
None declared
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 1 January 2023; 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. 1 January 2023; 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 > 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 > Video
Mansoor H, Hirani N, Chavan VV, Joshi A, Oswal V, et al.
MSF Scientific Days International 2022. 7 June 2022; DOI:10.57740/3gdn-kn91
Conference Material > Slide Presentation
Mansoor H, Hirani N, Chavan VV, Joshi A, Oswal V, et al.
MSF Scientific Days International 2022. 11 May 2022; DOI:10.57740/x7k7-xj13
Conference Material > Abstract
Mansoor H, Hirani N, Chavan VV, Joshi A, Oswal V, et al.
MSF Scientific Days International 2022. 11 May 2022; DOI:10.57740/atfq-6s03
INTRODUCTION
In countries with a high tuberculosis (TB) burden, poor access to drug susceptibility testing is a major bottleneck in diagnosing drug-resistant (DR) TB. India is estimated to account for a quarter of multidrug-resistant (MDR)-TB patients globally, with around 124,000 cases in 2020. Mumbai, a densely populated city in Maharashtra State, is a DR-TB hotspot with 24% of treatment- naïve cases, and 41% of previously-treated cases, having MDR-TB, and a high frequency of fluoroquinolone resistance occurring among these MDR-TB cases. Targeted next- generation sequencing (tNGS) is a promising technology for rapid detection of resistance. We assessed the role of tNGS for diagnosis of DR-TB.
METHODS
We performed a laboratory-based study involving Mycobacterium tuberculosis (MTB)-positive samples from patients with presumptive TB or DR-TB identified by GeneXpert in Shatabdi Hospital, Mumbai. A total of 161 sputum samples from bacteriologically-confirmed TB cases were included in the study. The study was conducted at Sir JJ Hospital’s TB lab, with sample collection occurring from patients living in M-East Ward (MEW), Mumbai. Two sputum samples were collected from each presumptive TB patient at MEW. Spot samples with a positive result on Xpert MTB/Rif were sent for tNGS and conventional testing (phenotypic drug sensitivity testing (pDST), line probe assays (LPA), and mycobacteria growth indicator tubes (MGIT)) at Sir JJ Hospital’s TB lab. tNGS samples were processed using Deeplex MycTB-kit (GenoScreen, France) and sequenced on a MiSeq platform (Illumina, USA). These samples were also processed for pDST using 16 drugs on MGIT (Becton Dickinson, USA) and LPA (MTBDRplus and MTBDRsl, Hain Lifesciences, Germany). To ensure sequence quality, Xpert results with cycle threshold values <20 or direct smear results >2+ were prepared for tNGS using direct sputum sediments. Primary cultures were prepared for samples with lower bacterial loads.
ETHICS
This study was approved by the ethics committee of the Grant Medical College & Sir J J Group of Hospitals, Mumbai, India. Permission was granted by the Medical Director of MSF, Operational Centre Brussels.
RESULTS
The median age of patients with samples included was 24 years (interquartile range, 20-40), and 57% were female. Approximately 70% of cases had no previous history of TB. Of 161 samples evaluated, 15 (9.3%) were rifampicin-sensitive and 146 (90.7%) were rifampicin-resistant (RR). 161 samples with completed pDST, tNGS and LPA were analysed. Of these, 88.2% had RR/MDR-TB resistance per WHO definitions, 58.5% had additional fluoroquinolone-resistance (pre-XDR) and 9.2% had fluoroquinolone resistance plus resistance to either linezolid or bedaquiline (extensively drug-resistant (XDR). Thirteen of 161 samples (8%) were culture-negative, yet resistance to one or more drugs was demonstrated in 8/13 samples with tNGS. Resistance frequency was similar across methods, with discordance in drugs less reliable in pDST or limited mutational representation within databases. Sensitivities aligned with the WHO catalogue for most drugs. 10% of the sample showed hetero-resistance and 75% of strains were of lineages 2 and 3.
CONCLUSION
In countries with a high burden of DR-TB, and high transmission rates, tNGS can provide information to rapidly design individualised regimens for early initiation and effective case management. It also gives information regarding lineages, uncharacterized mutations, hetero-resistance and mixed infection status of TB cases. Potentially tNGS could provide a diagnostic tool for rapid initiation of treatment in high DR-TB settings.
CONFLICTS OF INTEREST
None declared.
In countries with a high tuberculosis (TB) burden, poor access to drug susceptibility testing is a major bottleneck in diagnosing drug-resistant (DR) TB. India is estimated to account for a quarter of multidrug-resistant (MDR)-TB patients globally, with around 124,000 cases in 2020. Mumbai, a densely populated city in Maharashtra State, is a DR-TB hotspot with 24% of treatment- naïve cases, and 41% of previously-treated cases, having MDR-TB, and a high frequency of fluoroquinolone resistance occurring among these MDR-TB cases. Targeted next- generation sequencing (tNGS) is a promising technology for rapid detection of resistance. We assessed the role of tNGS for diagnosis of DR-TB.
METHODS
We performed a laboratory-based study involving Mycobacterium tuberculosis (MTB)-positive samples from patients with presumptive TB or DR-TB identified by GeneXpert in Shatabdi Hospital, Mumbai. A total of 161 sputum samples from bacteriologically-confirmed TB cases were included in the study. The study was conducted at Sir JJ Hospital’s TB lab, with sample collection occurring from patients living in M-East Ward (MEW), Mumbai. Two sputum samples were collected from each presumptive TB patient at MEW. Spot samples with a positive result on Xpert MTB/Rif were sent for tNGS and conventional testing (phenotypic drug sensitivity testing (pDST), line probe assays (LPA), and mycobacteria growth indicator tubes (MGIT)) at Sir JJ Hospital’s TB lab. tNGS samples were processed using Deeplex MycTB-kit (GenoScreen, France) and sequenced on a MiSeq platform (Illumina, USA). These samples were also processed for pDST using 16 drugs on MGIT (Becton Dickinson, USA) and LPA (MTBDRplus and MTBDRsl, Hain Lifesciences, Germany). To ensure sequence quality, Xpert results with cycle threshold values <20 or direct smear results >2+ were prepared for tNGS using direct sputum sediments. Primary cultures were prepared for samples with lower bacterial loads.
ETHICS
This study was approved by the ethics committee of the Grant Medical College & Sir J J Group of Hospitals, Mumbai, India. Permission was granted by the Medical Director of MSF, Operational Centre Brussels.
RESULTS
The median age of patients with samples included was 24 years (interquartile range, 20-40), and 57% were female. Approximately 70% of cases had no previous history of TB. Of 161 samples evaluated, 15 (9.3%) were rifampicin-sensitive and 146 (90.7%) were rifampicin-resistant (RR). 161 samples with completed pDST, tNGS and LPA were analysed. Of these, 88.2% had RR/MDR-TB resistance per WHO definitions, 58.5% had additional fluoroquinolone-resistance (pre-XDR) and 9.2% had fluoroquinolone resistance plus resistance to either linezolid or bedaquiline (extensively drug-resistant (XDR). Thirteen of 161 samples (8%) were culture-negative, yet resistance to one or more drugs was demonstrated in 8/13 samples with tNGS. Resistance frequency was similar across methods, with discordance in drugs less reliable in pDST or limited mutational representation within databases. Sensitivities aligned with the WHO catalogue for most drugs. 10% of the sample showed hetero-resistance and 75% of strains were of lineages 2 and 3.
CONCLUSION
In countries with a high burden of DR-TB, and high transmission rates, tNGS can provide information to rapidly design individualised regimens for early initiation and effective case management. It also gives information regarding lineages, uncharacterized mutations, hetero-resistance and mixed infection status of TB cases. Potentially tNGS could provide a diagnostic tool for rapid initiation of treatment in high DR-TB settings.
CONFLICTS OF INTEREST
None declared.
Journal Article > ResearchFull Text
Public Health Action. 21 December 2019
Nyagadza B, Kudya N, Mbofana E, Masaka S, Garone DB, et al.
Public Health Action. 21 December 2019
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.