Correction: Ambulatory management of pre- and extensively drug resistant tuberculosis patients with imipenem delivered through port-a-cath: A mixed methods study on treatment outcomes and challenges.

[This corrects the article DOI: 10.1371/journal.pone.0234651.].

Correction: Challenging drug-resistant TB treatment journey for children, adolescents and their care-givers: A qualitative study.

[This corrects the article DOI: 10.1371/journal.pone.0248408.].

Management of rifampicin-resistant tuberculosis in conflict-affected areas: The case of Iraq.

Since December 2019, the World Health Organization (WHO) has encouraged National Tuberculosis Programs to deprioritize the use of injectable-containing regimens and roll-out all-oral bedaquiline-containing regimens for rifampicin-resistant tuberculosis (RR-TB) treatment. Consequently, Iraq gradually replaced the injectable-containing regimen with an all-oral regimen, including bedaquiline. To assess treatment enrolment and outcomes of both regimens during a transitioning phase in Iraq, where health system services are recovering from decades of war, we conducted a nationwide retrospective cohort study using routinely collected programmatic data for patients enrolled between 2019-2021. We describe treatment enrolment and use logistic regression to identify predictors of unfavorable treatment outcomes (failure, death, or lost to follow-up), including regimen type. Nationwide, a total of 301 RR-TB patients started treatment, of whom 167 concluded treatment. The proportion of patients enrolled on the all-oral regimen increased from 53.2% (50/94) in 2020, to 75.5% (80/106) in 2021. Successful treatment was achieved in 82.1% (32/39) and 63.3% (81/128), for all-oral and injectable-containing regimens respectively. Moreover, the proportion of lost to follow-up was lower among those treated with the all-oral versus the long injectable-containing regimen; respectively 2.6% (1/39) versus 17.9% (23/128: p = 0.02). Unfavorable treatment outcome was associated with male gender (aOR 2.12, 95%CI:1.02-4.43) and age <15 years (vs 30-49 years, aOR 5.80, 95%CI:1.30-25.86). Regimen type (aOR 2.37, 95%CI: 0.91-6.13) was not significantly associated with having an unfavorable treatment outcome. In Iraq, the use of bedaquiline-containing all-oral regimen resulted in a high treatment success and reduced lost to follow-up.

Correction: Psychiatric comorbidities among patients with complex drug-resistant tuberculosis in Mumbai, India.

[This corrects the article DOI: 10.1371/journal.pone.0263759.].

Diagnostic yield of urine lipoarabinomannan and sputum tuberculosis tests in people living with HIV: a systematic review and meta-analysis of individual participant data.

BACKGROUND: Sputum is the most widely used sample to diagnose active tuberculosis, but many people living with HIV are unable to produce sputum. Urine, in contrast, is readily available. We hypothesised that sample availability influences the diagnostic yield of various tuberculosis tests. METHODS: In this systematic review and meta-analysis of individual participant data, we compared the diagnostic yield of point-of-care urine-based lipoarabinomannan tests with that of sputum-based nucleic acid amplification tests (NAATs) and sputum smear microscopy (SSM). We used microbiologically confirmed tuberculosis based on positive culture or NAAT from any body site as the denominator and accounted for sample provision. We searched PubMed, Web of Science, Embase, African Journals Online, and clinicaltrials.gov from database inception to Feb 24, 2022 for randomised controlled trials, cross-sectional studies, and cohort studies that assessed urine lipoarabinomannan point-of-care tests and sputum NAATs for active tuberculosis detection in participants irrespective of tuberculosis symptoms, HIV status, CD4 cell count, or study setting. We excluded studies in which recruitment was not consecutive, systematic, or random; provision of sputum or urine was an inclusion criterion; less than 30 participants were diagnosed with tuberculosis; early research assays without clearly defined cutoffs were tested; and humans were not studied. We extracted study-level data, and authors of eligible studies were invited to contribute deidentified individual participant data. The main outcomes were the tuberculosis diagnostic yields of urine lipoarabinomannan tests, sputum NAATs, and SSM. Diagnostic yields were predicted using Bayesian random-effects and mixed-effects meta-analyses. This study is registered with PROSPERO, CRD42021230337. FINDINGS: We identified 844 records, from which 20 datasets and 10 202 participants (4561 [45%] male participants and 5641 [55%] female participants) were included in the meta-analysis. All studies assessed sputum Xpert (MTB/RIF or Ultra, Cepheid, Sunnyvale, CA, USA) and urine Alere Determine TB LAM (AlereLAM, Abbott, Chicago, IL, USA) in people living with HIV aged 15 years or older. Nearly all (9957 [98%] of 10 202) participants provided urine, and 82% (8360 of 10 202) provided sputum within 2 days. In studies that enrolled unselected inpatients irrespective of tuberculosis symptoms, only 54% (1084 of 1993) of participants provided sputum, whereas 99% (1966 of 1993) provided urine. Diagnostic yield was 41% (95% credible interval [CrI] 15-66) for AlereLAM, 61% (95% Crl 25-88) for Xpert, and 32% (95% Crl 10-55) for SSM. Heterogeneity existed across studies in the diagnostic yield, influenced by CD4 cell count, tuberculosis symptoms, and clinical setting. In predefined subgroup analyses, all tests had higher yields in symptomatic participants, and AlereLAM yield was higher in those with low CD4 counts and inpatients. AlereLAM and Xpert yields were similar among inpatients in studies enrolling unselected participants who were not assessed for tuberculosis symptoms (51% vs 47%). AlereLAM and Xpert together had a yield of 71% in unselected inpatients, supporting the implementation of combined testing strategies. INTERPRETATION: AlereLAM, with its rapid turnaround time and simplicity, should be prioritised to inform tuberculosis therapy among inpatients who are HIV-positive, regardless of symptoms or CD4 cell count. The yield of sputum-based tuberculosis tests is undermined by people living with HIV who cannot produce sputum, whereas nearly all participants are able to provide urine. The strengths of this meta-analysis are its large size, the carefully harmonised denominator, and the use of Bayesian random-effects and mixed-effects models to predict yields; however, data were geographically restricted, clinically diagnosed tuberculosis was not considered in the denominator, and little information exists on strategies for obtaining sputum samples. FUNDING: FIND, the Global Alliance for Diagnostics.

Novel FujiLAM assay to detect tuberculosis in HIV-positive ambulatory patients in four African countries: a diagnostic accuracy study.

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. FUNDING: ANRS and Médecins Sans Frontières.

Psychiatric comorbidities among patients with complex drug-resistant tuberculosis in Mumbai, India.

BACKGROUND: People with drug-resistant tuberculosis (DR-TB) are known to suffer from many mental-health disorders. This study aims to describe the proportion of patients diagnosed with psychiatric comorbidities, the different psychiatric diagnoses made, and treatment outcomes among DR-TB patients with or without psychiatric comorbidity and initiated on DR-TB treatment between January 2012 and March 2019 at Médecins Sans Frontières independent clinic in Mumbai, India. METHODS: This is a retrospective study using routinely collected clinical data. DR-TB care included individualised treatment, psychosocial support, and integrated psychiatric care. RESULTS: During the study period, 341 DR-TB patients were enrolled, with a median age of 25 years (IQR:20.0-36.5 years), 185 (54.2%) females, 143 (41.9%) with PreXDR-TB, and 140 (41.0%) with XDR-TB. All 341 patients were screened by a counsellor, 119 (34.9%) were referred for psychiatric evaluation, and 102 (29.9% of 341) were diagnosed with a psychiatric comorbidity. Among 102 diagnosed with a psychiatric comorbidity, 48 (47.0%) were diagnosed at baseline, and 86 (84.3%), or 25.2% of all 341 patients enrolled, were treated with psychotropic drugs. Depressive disorders were diagnosed in 49 (48.0%), mixed anxiety and depression in 24 (23.5%), neurocognitive disorders and anxiety in five (4.9%), and medication induced psychosis in two (2.0%). No anti-TB drugs were significantly associated with psychiatric comorbidities developed during treatment. Of 102 DR-TB patients with a psychiatric comorbidity, 75.5% (77) had successful DR-TB treatment outcomes, compared to 61.1% (146/239) not diagnosed with a psychiatric comorbidity (p = 0.014). CONCLUSION: In our setting, among people started on DR-TB treatment, and with a complex TB resistance profile, about one in three patients experienced a psychiatric comorbidity, of which half developed this comorbidity during treatment. With comprehensive psychiatric care integrated into DR-TB care delivery, treatment outcomes were at least as good among those with psychiatric comorbidities compared to those without such comorbidities.

Challenging drug-resistant TB treatment journey for children, adolescents and their care-givers: A qualitative study.

BACKGROUND: Childhood multidrug-resistant TB (MDR-TB) still affects around 25000 children every year across the globe. Though the treatment success rates for drug-resistant TB (DR-TB) in children are better than adults, children and adolescents face unique hurdles during DR-TB (MDR-TB, Pre-XDR TB and XDR-TB) treatment. This study aimed to understand the patients, guardians and healthcare providers' perspectives about DR-TB treatment journey of patients and caregivers. METHODS: This is a qualitative study involving in depth-interviews of purposively selected adolescents (n = 6), patients guardians (for children and adolescents, n = 5) and health care providers (n = 8) of Médecins Sans Frontières (MSF) clinic, Mumbai, India. In-depth face to face interviews were conducted in English or Hindi language using interview guides during September-November 2019. The interviews were audio-recorded after consent. Thematic network analysis was used to summarize textual data. ATLAS.ti (version 7) was used for analysis. RESULT: The age of adolescent patients ranged from 15-19 years and four were female. Five guardians (of three child and two adolescent patients) and eight healthcare providers (including clinicians- 2, DOT providers-2, counselors-2 and programme managers-2) were interviewed. The overarching theme of the analysis was: Challenging DR-TB treatment journey which consisted of four sub-themes: 1) physical-trauma, 2) emotional-trauma, 3) unavailable social-support and 4) non-adapted healthcare services. Difficulties in compounding of drugs were noted for children while adolescents shared experiences around disruption in social life due to disease and treatment. Most of the patients and caregivers experienced treatment fatigue and burnout during the DR-TB treatment. Participants during interviews gave recommendations to improve care. DISCUSSION: The TB programmes must consider the patient and family as one unit when designing the package of care for paediatric DR-TB. Child and adolescent friendly services (paediatric-formulations, age-specific counselling tools and regular interaction with patients and caregivers) will help minimizing burnout in patients and caregivers.

Treatment outcomes of children and adolescents receiving drug-resistant TB treatment in a routine TB programme, Mumbai, India.

BACKGROUND: Childhood and adolescent drug-resistant TB (DR-TB) is one of the neglected infectious diseases. Limited evidence exists around programmatic outcomes of children and adolescents receiving DR-TB treatment. The study aimed to determine the final treatment outcomes, culture conversion rates and factors associated with unsuccessful treatment outcome in children and adolescents with DR-TB. METHODS: This is a descriptive study including children (0-9 years) and adolescents (10-19 years) with DR-TB were who were initiated on ambulatory based treatment between January 2017-June 2018 in Shatabdi hospital, Mumbai, India where National TB elimination programme(NTEP) Mumbai collaborates with chest physicians and Médecins Sans Frontières(MSF) in providing comprehensive care to DR-TB patients. The patients with available end-of-treatment outcomes were included. The data was censored on February 2020. RESULT: A total of 268 patients were included; 16 (6%) of them were children (0-9 years). The median(min-max) age was 17(4-19) years and 192 (72%) were females. Majority (199, 74%) had pulmonary TB. Most (58%) had MDR-TB while 42% had fluoroquinolone-resistant TB. The median(IQR) duration of treatment (n = 239) was 24(10-25) months. Median(IQR) time for culture-conversion (n = 128) was 3(3-4) months. Of 268 patients, 166(62%) had successful end-of-treatment outcomes (cured-112; completed treatment-54). Children below 10 years had higher proportion of successful treatment outcomes (94% versus 60%) compared to adolescents. Patients with undernutrition [adjusted odds-ratio, aOR (95% Confidence Interval, 95%CI): 2.5 (1.3-4.8) or those with XDR-TB [aOR (95% CI): 4.3 (1.3-13.8)] had higher likelihood of having unsuccessful DR-TB treatment outcome. CONCLUSION: High proportion of successful treatment outcome was reported, better than global reports. Further, the nutritional support and routine treatment follow up should be strengthened. All oral short and long regimens including systematic use of new TB drugs (Bedaquiline and Delamanid) should be rapidly scaled up in routine TB programme, especially for the paediatric and adolescent population.

One Step Forward: Successful End-of-Treatment Outcomes of Patients With Drug-Resistant Tuberculosis Who Received Concomitant Bedaquiline and Delamanid in Mumbai, India.

BACKGROUND: The Médecins Sans Frontières Clinic in Mumbai, India, has been providing concomitant bedaquiline (BDQ) and delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment. METHODS: This was a retrospective cohort study based on routinely collected program data. In clinic, treatment regimens are designed based on culture drug sensitivity test patterns and previous drug exposures, and are provided for 20-22 months. BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February 2016-February 2018 were included. RESULTS: Of the 70 patients included, the median age was 25 (interquartile range [IQR], 22-32) years and 56% were females. All except 1 were fluoroquinolone resistant. The median duration of exposure to BDQ and DLM was 77 (IQR, 43-96) weeks. Thirty-nine episodes of SAEs were reported among 30 (43%) patients, including 5 instances of QTc prolongation, assessed as possibly related to BDQ and/or DLM. The majority (69%) had culture conversion before 24 weeks of treatment. In 61 (87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49 (70%) patients. CONCLUSIONS: The successful treatment outcomes of this cohort show that regimens including concomitant BDQ and DLM for longer than 24 weeks are effective and can be safely administered on an ambulatory basis. National TB programs globally should scale up access to life-saving DR-TB regimens with new drugs.

Ambulatory management of pre- and extensively drug resistant tuberculosis patients with imipenem delivered through port-a-cath: A mixed methods study on treatment outcomes and challenges.

BACKGROUND: Imipenem, an intravenous antibiotic is recommended for use in drug resistant tuberculosis (DR-TB) when an effective regimen with combination of other second line drugs is not possible. Though the treatment success rates with carbapenems are promising, the twice daily injection of Imipenem usually requires patients to be hospitalized. The Médecins Sans Frontières independent clinic in Mumbai, India implemented ambulatory and home based management of patients receiving Imipenem through the use of port-a-cath. OBJECTIVE: We aimed to describe the adverse events and treatment outcomes of ambulatory pre- and XDR-TB patients initiated on imipenem through port-a-cath between January 2015 and June 2018 and to explore the challenges with this regimen as perceived by healthcare providers and patients. METHODS: A convergent mixed methods study with quantitative (longitudinal descriptive study using the routine data) and qualitative (descriptive study) part conducted concurrently. For the quantitative component, all XDR-TB and pre-XDR-TB initiated on imipenem containing regimen during January 2015-June 2018 were included. For qualitative component, interviews were carried out including patients who initiated on imipenem (n = 5) and healthcare providers (n = 7) involved in providing treatment. Treatment outcomes, culture conversion and adverse events during treatment were described. Thematic analysis was carried out for qualitative component. RESULTS: Of the 70 patients included, the mean age was 28.1 (standard deviation: 11.2) years and 36 (51.4%) were females. Fifty one (72.9%) had XDR-TB. All patients were resistant to fluoroquinilone, levofloxacin. Vomiting was reported by 55 (78.6%) patients and at least one episode of QTC prolongation (more than 500 msec by Fredrecia method) was detected in 25 (35.7%). Port-a-cath block and infection was seen in 11 (15.7%) and 20 (28.6%) patients respectively. Favourable outcomes were seen in 43 (61.4%) patients. Mortality was seen in 22 (31.4%) patients, 2 (2.9%) were lost-to-follow-up and 3 (4.3%) were declared as treatment failure. The overarching theme of the qualitative analysis was: Challenges in delivering Imipenem via port-a-cath device in ambulatory care. Major challenges identified were difficulties in adhering to drug dose timelines, vomiting, restricted mobility due to port-a-cath, paucity of infection control and space constraints at patients' home for optimal care. CONCLUSION: Administration of imipenem was feasible through port-a-cath. Though outcomes with ambulatory based imipenem containing regimens were promising, there were several challenges in providing care. The feasibility of infusion at day care facilities needs to explored to overcome challenges in infusion at patients home.

Yield of Systematic Longitudinal Screening of Household Contacts of Pre-Extensively Drug Resistant (PreXDR) and Extensively Drug Resistant (XDR) Tuberculosis Patients in Mumbai, India.

While risk of tuberculosis (TB) is high among household contacts (HHCs) of pre-extensively drug resistant (pre-XDR) TB and XDR-TB, data on yield of systematic longitudinal screening are lacking. We aim to describe the yield of systematic longitudinal TB contact tracing among HHCs of patients with pre-XDR-TB and XDR-TB. At the Médecins Sans Frontières (MSF) clinic, Mumbai, India a cohort comprising 518 HHCs of 109 pre-XDR and XDR index cases was enrolled between January 2016 and June 2018. Regular HHC follow-ups were done till one year post treatment of index cases. Of 518 HHCs, 23 had TB (21 on TB treatment and two newly diagnosed) at the time of first visit. Of the rest, 19% HHCs had no follow-ups. Fourteen (3.5%) TB cases were identified among 400 HHCs; incidence rate: 2072/100,000 person-years (95% CI: 1227-3499). The overall yield of household contact tracing was 3% (16/518). Of 14 who were diagnosed with TB during follow-up, six had drug susceptible TB (DSTB); six had pre-XDR-TB and one had XDR-TB. Five of fourteen cases had resistance patterns concordant with their index case. In view of the high incidence of TB among HHCs of pre-XDR and XDR-TB cases, follow-up of HHCs for at least the duration of index cases' treatment should be considered.

Improving pediatric TB diagnosis in North Kivu (DR Congo), focusing on a clinical algorithm including targeted Xpert MTB/RIF on gastric aspirates.

BACKGROUND: The incidence of tuberculosis (TB) in the Democratic Republic of the Congo (DRC) is 323/100,000. A context of civil conflict, internally displaced people and mining activities suggests a higher regional TB incidence in North Kivu. Médecins Sans Frontières (MSF) supports the General Reference Hospital of Masisi, North Kivu, covering a population of 520,000, with an elevated rate of pediatric malnutrition. In July 2017, an adapted MSF pediatric TB diagnostic algorithm, including Xpert MTB/RIF on gastric aspirates (GAs), was implemented. The aim of this study was to evaluate whether the introduction of this clinical pediatric TB diagnostic algorithm influenced the number of children started on TB treatment. METHODS: We performed a retrospective analysis of pediatric TB cases started on treatment in the inpatient therapeutic feeding centre (ITFC) and the pediatric ward. We compared data collected in the second half (July to December) of 2016 (before introduction of the new diagnostic algorithm) and the second half of 2017. For the outcome variables the difference between the two years was calculated by a Pearson Chi-square test. RESULTS: In 2017, 94 GAs were performed, compared to none in 2016. Twelve percent (11/94) of samples were Xpert MTB/RIF positive. Sixty-eight children (2.9% of total exits) aged between 3 months and 15 years started TB treatment in 2017, compared to 19 (1.4% of total exits) in 2016 (p 0.002). The largest increase in pediatric TB diagnoses in 2017 occurred in patients with a negative Xpert MTB/RIF result, but clinically highly suggestive of TB according to the newly introduced diagnostic algorithm. Fifty-two (3.1%) children under five years old started treatment in 2017, as compared to 14 (1.3%) in 2016 (p 0.004). The increase was less pronounced and not statistically significant in older patients: sixteen children (2.6%) above 5 years old started TB treatment in 2017 as compared to five (1.3%) in 2016 (p 0.17). CONCLUSION: After the introduction of an adapted clinical pediatric TB diagnostic algorithm, including Xpert MTB/RIF on gastric aspirates, we observed a significant increase in the number of children - especially under 5 years old - started on TB treatment, mostly on clinical grounds. Increased 'clinician awareness' of pediatric TB likely played an important role.

Routine viral load monitoring and enhanced adherence counselling at a public ART centre in Mumbai, India.

BACKGROUND: Routine viral-load (VL) measurements along with enhanced adherence counselling (EAC) are recommended to achieve virological suppression among people living with HIV/AIDS (PLHA) on anti-retroviral therapy (ART). The Mumbai Districts AIDS Control Society along with Médecins Sans Frontières has provided routine VL measurements and EAC to PLHA on ART at King Edward Memorial (KEM) hospital, Mumbai since October-2016. This study aims to describe the initial VL results and impact of EAC on viral suppression and factors associated with initial viral non-suppression among patients with an initial detectable VL, in a cohort of patients tested between October-2016 and September-2018. METHODS: This is a descriptive study of PLHA on ART who received VL testing and EAC during October-2016 to September-2018. Log-binomial regression was used to identify factors associated with a high VL. RESULTS: Among 3849 PLHA who underwent VL testing, 1603(42%) were female and median age was 42 years (IQR:35-48). Majority were referred for routine testing (3432(89%)) and clinical/immunological failure (233(6%)). Overall, 3402(88%) PLHA had suppressed VL at initial testing. Among 3432 tested for routine monitoring, 3141(92%) had VL suppressed. Of 291 with VL>1000c/ml, 253(87%) received EAC and after repeat VL, 70(28%) had VL<1000c/ml. Among 233 referred for clinical/immunological failure, 122(52%) had VL>1000c/ml and 109 have been switched to second-line ART. CD4 count<500 (aOR-5.0[95%CI 3.8-6.5]), on ART for<5 years (aOR-1.5[1.1-2.0]) and age<15 years (aOR-5.2[3.0-8.9]) were associated with an initial VL>1000c/ml. Factors associated with follow-up VL suppression included EAC (p<0.05) and being on second-line ART (p<0.05). CONCLUSION: Results from a routine VL program in public sector in India were encouraging and in line with UNAIDS 90-90-90 targets. Routine VL monitoring along with EAC resulted in early switch to alternative optimised regimens while also preventing unnecessary switches. Along with the vital scale up of routine VL monitoring, implementation of enhanced adherence strategies for patients with detectable viral load should be ensured.

MDR/XDR-TB management of patients and contacts: Challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network.

The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts. The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines. After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities.

Cost-effectiveness of diagnostic algorithms including lateral-flow urine lipoarabinomannan for HIV-positive patients with symptoms of tuberculosis.

BACKGROUND: Tuberculosis (TB) is the leading cause of death among HIV-positive patients. We assessed the cost-effectiveness of including lateral-flow urine lipoarabinomannan (LF-LAM) in TB diagnostic algorithms for severely ill or immunosuppressed HIV-positive patients with symptoms of TB in Kenya. METHODS: From a decision-analysis tree, ten diagnostic algorithms were elaborated and compared. All algorithms included clinical exam. The costs of each algorithm were calculated using a 'micro-costing' method. The efficacy was estimated through a prospective study that included severely ill or immunosuppressed (CD4<200cells/µL) HIV-positive adults with symptoms of TB. The cost-effectiveness analysis was performed using the disability-adjusted life year (DALY) averted as effectiveness outcome. A 4% discount rate was applied. RESULTS: The algorithm that added LF-LAM alone to the clinical exam lead to the least average cost per TB case detected (€47) and was the most cost-effective with a cost/DALY averted of €4.6. The algorithms including LF-LAM, microscopy and X-ray, and LF-LAM and Xpert in sputum, detected a high number of TB cases with a cost/DALY averted of €6.1 for each of them. In the comparisons of the algorithms two by two, using LF-LAM instead of microscopy (clinic&LAM vs clinicµscopy) and using LF-LAM along with GeneXpert in sputum instead of GeneXpert in urine along with GeneXpert in sputum, (clinic&LAM&Xpert_sputum vs clinic&Xpert_sputum&Xpert_urine) led to the highest increase in the cost-effectiveness ratios (ICERs): €-7.2 and €-12.6 respectively. In these two comparisons, using LF-LAM increased the number of TB patients detected while reducing costs. Adding LF-LAM to smear microscopy alone or to smear microscopy and Xray led to the highest increase in the additional number of TB cases detected (31 and 25 respectively) with an incremental efficiency estimated at 134 and 344 DALYs respectively. The ICERs were €22.0 and €8.6 respectively. CONCLUSION: Including LF-LAM in TB diagnostic algorithms is cost-effective for severely ill or immunosuppressed HIV-positive patients.

GeneXpert and Community Health Workers Supported Patient Tracing for Tuberculosis Diagnosis in Conflict-Affected Border Areas in India.

Médecins Sans Frontières (MSF) has been providing diagnosis and treatment for patients with tuberculosis (TB) via mobile clinics in conflict-affected border areas of Chhattisgarh, India since 2009. The study objectives were to determine the proportion of patients diagnosed with TB and those who were lost-to-follow-up (LTFU) prior to treatment initiation among patients with presumptive TB between April 2015 and August 2018. The study also compared bacteriological confirmation and pretreatment LTFU during two time periods: a) April 2015-August 2016 and b) April 2017-August 2018 (before and after the introduction of GeneXpert as a first diagnostic test). Community health workers (CHW) supported patient tracing. This study was a retrospective analysis of routine program data. Among 1042 patients with presumptive TB, 376 (36%) were diagnosed with TB. Of presumptive TB patients, the pretreatment LTFU was 7%. Upon comparing the two time-periods, bacteriological confirmation increased from 20% to 33%, while pretreatment LTFU decreased from 11% to 4%. TB diagnosis with GeneXpert as the first diagnostic test and CHW-supported patient tracing in a mobile-clinic model of care shows feasibility for replication in similar conflict-affected, hard to reach areas.