BACKGROUND: In South Africa, Xpert® MTB/RIF Ultra (Ultra) is the recommended diagnostic assay for TB with line-probe assays for first- (LPAfl) and second-line drugs (LPAsl) providing additional drug susceptibility testing (DST) for samples that were rifampicin-resistant (RR-TB). To guide implementation of the recently launched Xpert® MTB/XDR (MTB/XDR) assay, a cost-outcomes analysis was conducted comparing total costs for genotypic DST (gDST) for persons diagnosed with RR-TB considering three strategies: replacing LPAfl/LPAsl (centralised level) with MTB/XDR vs. Ultra reflex testing (decentralised level). Further, DST was performed using residual specimen following RR-TB diagnosis.
METHODS: The total cost of gDST was determined for three strategies, considering loss to follow-up (LTFU), unsuccessful test rates, and specimen volume.
RESULTS: For 2019, 9,415 persons were diagnosed with RR-TB. A 35% LTFU rate between RR-TB diagnosis and LPAfl/LPAsl-DST was estimated. Unsuccessful test rates of 37% and 23.3% were reported for LPAfl and LPAsl, respectively. The estimated total costs were $191,472 for the conventional strategy, $122,352 for the centralised strategy, and $126,838 for the decentralised strategy. However, it was found that sufficient residual volume for reflex MTB/XDR testing is a limiting factor at the decentralised level.
CONCLUSIONS: Centralising the implementation of XDR testing, as compared to LPAfl/LPAsl, leads to significant cost savings.
BACKGROUND: En Afrique du Sud, Xpert® MTB/RIF Ultra (Ultra) est le test de diagnostic recommandé pour la TB avec des tests par sonde de ligne pour les médicaments de première (LPAfl) et de deuxième ligne (LPAsl) fournissant des tests de sensibilité aux médicaments (DST) supplémentaires pour les échantillons résistants à la rifampicine (RR-TB). Afin d\'orienter la mise en œuvre du test Xpert® MTB/XDR (MTB/XDR) récemment lancé, une analyse coûts-résultats a été réalisée en comparant les coûts totaux de la DST génotypique (gDST) pour les personnes diagnostiquées avec une RR-TB en tenant compte de trois stratégies : remplacer le LPAfl/LPAsl (niveau centralisé) par le MTB/XDR par rapport au test Ultra reflex (niveau décentralisé). De plus, l\'heure d\'été a été réalisée à l\'aide d\'un échantillon résiduel après le diagnostic de RR-TB.
UNASSIGNED: Le coût total de la gDST a été déterminé pour trois stratégies, en tenant compte de la perte de suivi (LTFU), des taux d\'échec des tests et du volume d\'échantillons.
UNASSIGNED: En 2019, 9 415 personnes ont reçu un diagnostic de RR-TB. Un taux de LTFU de 35% entre le diagnostic de RR-TB et le diagnostic de LPAfl/LPAsl-DST a été estimé. Des taux d\'échec de 37% et de 23,3% ont été signalés pour LPAfl et LPAsl, respectivement. Les coûts totaux estimés étaient de 191 472 dollars pour la stratégie conventionnelle, de 122 352 dollars pour la stratégie centralisée et de 126 838 dollars pour la stratégie décentralisée. Cependant, il a été constaté qu\'un volume résiduel suffisant pour les tests réflexes MTB/XDR est un facteur limitant au niveau décentralisé.
CONCLUSIONS: La centralisation de la mise en œuvre des tests XDR, par rapport à LPAfl/LPAsl, permet de réaliser d\'importantes économies.

METHODS: The Republic of Moldova, one of Europe\'s poorest countries, also bears one of the highest burdens of rifampicin-resistant TB (RR-TB).
OBJECTIVE: To trace the patients\' journey through TB in terms of the relationship with poverty and assess its determinants.
METHODS: This cross-sectional study used secondary data from a survey assessing catastrophic costs in RR-TB-affected households.
RESULTS: Data were obtained from 430 RR-TB patients. The percentage of poor TB-affected households rose from 65% prior to TB to 86% after TB treatment completion (P < 0.001). Social factors leading to poverty were identified for each stage: diagnostic period (history of incarceration: cOR 2.3, 95% CI 1.1-5.2); treatment period (being unemployed or unofficially employed: cOR 6.7, 95% CI 4.3-10.0); and post-treatment (being married or cohabiting: cOR 5.7, 95% CI 2.9-11.0). Participants who had ≥3 members in their households were more likely to be poor at all TB stages: diagnostic period (cOR 5.7, 95% CI 3.7-8.8), treatment period (cOR 3.8, 95% CI 2.5-5.6) and post-treatment (cOR 7.2, 95% CI 3.6-14.3).
CONCLUSIONS: The study identified risk factors associated with poverty at each stage of TB. These findings outline that innovative social protection policies are required to protect TB patients against poverty.
BACKGROUND: La République de Moldavie est l\'un des pays les plus pauvres d\'Europe et l\'un des plus touchés par la TB résistante à la rifampicine (RR-TB).
OBJECTIVE: Nous avons cartographié le parcours des patients atteints de TB en lien avec la pauvreté et évalué les déterminants associés.
UNASSIGNED: Cette étude transversale a analysé des données secondaires issues d\'une enquête évaluant les coûts catastrophiques supportés par les ménages touchés par la RR-TB.
UNASSIGNED: Des données ont été recueillies auprès de 430 patients atteints de RR-TB. Le taux de ménages pauvres touchés par la TB est passé de 65% avant le traitement à 86% après la fin du traitement de la TB (P < 0,001). Pour chaque stade de la TB, les facteurs sociaux conduisant à la pauvreté ont été identifiés : période de diagnostic (antécédents d\'emprisonnement : rapport de cotes brut (cOR) 2,3, IC à 95% 1,1–5,2) ; période de traitement (être au chômage ou employé officieux : cOR 6,7 ; IC 95% 4,3–10,0) ; et post-traitement (être marié ou cohabitant : cOR 5,7, IC 95% 2,9–11,0). Les participants dont le ménage comptait ≥3 membres étaient plus susceptibles d\'être pauvres à tous les stades de la TB : période de diagnostic (cOR 5,7 ; IC à 95% 3,7–8,8), période de traitement (cOR 3,8 ; IC à 95% 2,5–5,6) et post-traitement (cOR 7,2 ; IC à 95% 3,6–14,3).
CONCLUSIONS: L\'étude a permis d\'identifier des facteurs de risque liés à la pauvreté à toutes les étapes de la TB. Ces résultats soulignent l’importance de mettre en place des politiques de protection sociale novatrices pour prévenir l\'appauvrissement des patients atteints de TB.

UNASSIGNED: The implementation of modified, all-oral shorter regimens for treatment of rifampicin-resistant tuberculosis has started in Armenia since August 2020 under the conditions of operational research.
UNASSIGNED: This study aims to evaluate the safety and effectiveness of shorter regimens.
UNASSIGNED: We evaluated cumulative incidence rates of serious adverse events, adverse events of grade 3 and greater and events resulting in treatment modifications or suspension for 52 study participants.
UNASSIGNED: A new, different pattern of adverse events emerged compared with the previous evaluations of drug safety of treatment for rifampicin-resistant tuberculosis. Arthralgia (23.1%) and peripheral neuropathy (21.2%) took leading positions among the adverse events resulting in modifications of treatment. Some adverse events of interest (prolonged QT interval, elevated liver enzymes and anemia) remained relevant for the patients receiving new combinations of anti-TB drugs. The other adverse events (impaired hearing, acute kidney injury and hypokalemia) lost their significance for safety surveillance of rifampicin-resistant tuberculosis treatment. One unexpected serious adverse event (lymphoproliferative skin lesion) brought to a \"failed treatment\" outcome. The other serious adverse event was anemia.
UNASSIGNED: The shorter regimens proved to be safe and effective for treatment of rifampicin-resistant tuberculosis, but proper follow-up of adverse events is necessary.

UNASSIGNED: Treatment for rifampicin-resistant tuberculosis (RR-TB) has been shortened to 12 months or less, with duration depending on the regimen used and treatment response. Treatment shortening has the potential to increase the risk of relapse, with a new episode of RR-TB after cure or completion. The proportion of relapses after standardized all-oral short (12 months or less) RR-TB regimens has not yet been systematically reviewed, which is the main objective of this review.
UNASSIGNED: This is a systematic review and meta-analysis. PubMed, Web of Science and Google scholar databases were systematically investigated to identify studies published between January 2018 and November 2023. Characteristics of studies, demographic data, baseline clinical condition, resistance profile, and definitions used for relapse, failure, and end-of-treatment outcomes are summarized in tables and graphs. Pooled proportions are estimated for relapse.
UNASSIGNED: A total of ten studies were included in this review and meta-analysis, representing 1792 participants. Seven studies were clinical trials and two were cohorts. Five studies investigated all-oral six-month regimens composed of bedaquiline, pretomanid, and linezolid (BPaL). The remaining studies assessed other standardized all-oral short regimens, with treatment duration between 6 and 12 months. Post-treatment follow-up (PTFU) duration ranged from 6 to 30 months. The pooled proportion estimate of relapse was 2·0% (95 % CI, 1·0-3·0%) for all and BPaL-based regimens. Treatment extension due to poor treatment response was poorly documented.
UNASSIGNED: This review showed that the proportion of relapse in RR-TB patients treated with standardized short all-oral regimens was low. The low relapse proportion is similar to what was achieved for drug-susceptible Tuberculosis patients treated with first-line rifampicin-containing regimens. However, most data came from trial settings, and in some studies the post-treatment follow-up was short. Studies of large programmatic cohorts with longer post-treatment follow-up periods are needed to confirm the low relapse rate shown in the clinical trials.

UNASSIGNED: Shorter regimens for drug-resistant tuberculosis (DR-TB) have non-inferior efficacy compared with longer regimens, but QT prolongation is a concern. T-wave morphology abnormalities may be a predictor of QT prolongation.
UNASSIGNED: STREAM Stage 1 was a randomized controlled trial in rifampicin-resistant TB, comparing short and long regimens. All participants had regular ECGs. QT/QTcF prolongation (≥500 ms or increase in ≥60 ms from baseline) was more common on the short regimen which contained high-dose moxifloxacin and clofazimine. Blinded ECGs were selected from the baseline, early (weeks 1-4), and late (weeks 12-36) time points. T-wave morphology was categorized as normal or abnormal (notched, asymmetric, flat-wave, flat peak, or broad). Differences between groups were assessed using Chi-Square tests (paired/unpaired, as appropriate).
UNASSIGNED: Two-hundred participants with available ECGs at relevant times were analyzed (QT prolongation group n = 82; non-prolongation group n = 118). At baseline, 23% (45/200) of participants displayed abnormal T-waves, increasing to 45% (90/200, p < 0.001) at the late time point. Abnormalities were more common in participants allocated the Short regimen (75/117, 64%) than the Long (14/38, 36.8%, p = 0.003); these occurred prior to QT/QTcF ≥500 ms in 53% of the participants (Long 2/5; Short 14/25).
UNASSIGNED: T-wave abnormalities may help identify patients at risk of QT prolongation on DR-TB treatment.
UNASSIGNED: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02409290). Current Controlled Trial number, ISRCTN78372190.

BACKGROUND: Understanding why patients experience loss to follow-up (LTFU) is essential for TB control. This analysis examines the impact of travel distance to RR-TB treatment on LTFU, which has yet to be analyzed within South Africa.
METHODS: We retrospectively analyzed 1436 patients treated for RR-TB at ten South African public hospitals. We linked patients to their residential ward using data reported to NHLS and maps available from the Municipal Demarcation Board. Travel distance was calculated from each patient\'s ward centroid to their RR-TB treatment site using the georoute command in Stata. The relationship between LTFU and travel distance was modeled using multivariable logistic regression.
RESULTS: Among 1436 participants, 75.6% successfully completed treatment and 24.4% were LTFU. The median travel distance was 40.96 km (IQR: 17.12, 63.49). A travel distance > 60 km increased odds of LTFU by 91% (p = 0.001) when adjusting for HIV status, age, sex, education level, employment status, residential locale, treatment regimen, and treatment site.
CONCLUSIONS: People living in KwaZulu-Natal and Eastern Cape travel long distances to receive RR-TB care, placing them at increased risk for LTFU. Policies that bring RR-TB treatment closer to patients, such as further decentralization to PHCs, are necessary to improve RR-TB outcomes.

UNASSIGNED: The fight against tuberculosis in our country has taken a new shape with the inclusion of rapid nucleic acid amplification tests like GeneXpert MTB/RIF assay which rapidly detects Mycobacterium tuberculosis and rifampicin resistance. Rifampicin resistance detected on GeneXpert has been considered as a sine qua non for the presence of isoniazid resistance and hence classified as multidrug-resistant tuberculosis (MDR-TB). However treatment of rifampicin-resistant, isoniazid-monoresistance, and MDR-TB are different. Our study was done with the aim of identification of the prevalence of isoniazid resistance on culture, in cases which had rifampicin resistance on GeneXpert.
UNASSIGNED: Pulmonary samples of patients of presumptive tuberculosis were subjected to GeneXpert testing and liquid MGIT (mycobacterium growth indicator tube) culture. On detection of rifampicin resistance on MTB/RIF assay, the patients were included in our study and cultures were followed-up for sensitivity to isoniazid. A total of 76 patients were included.
UNASSIGNED: 76 patients of rifampicin resistance on GeneXpert MTB/RIF assay were followed-up for the sensitivity of isoniazid on culture media. Out of the 76 cases, 62 (81.57%) were found to have isoniazid resistance. Out of the 14 patients, the cultures showed no growth in 6, and in the rest, isoniazid was found to be sensitive.
UNASSIGNED: GeneXpert MTB/RIF assay is an excellent modality for the detection of M. tuberculosis and rifampicin resistance. The decision to exclude isoniazid from the treatment regimen in patients with rifampicin resistance should be made only after conducting further molecular/phenotypic tests.

Recommendations for treatment of rifampicin-resistant tuberculosis (RR-TB) during pregnancy and post-partum now include Group A and B antituberculosis drugs. While pharmacokinetic data for most of these drugs among adults receiving treatment for RR-TB are limited, the data from pregnant patients and their infants are extremely scarce. Existing data suggest that fluoroquinolones, bedaquiline, clofazimine and terizidone may be used safely in pregnancy. Pharmacokinetic exposures, particularly between trimesters, are potentially sub-optimal; however, there is currently no evidence to support dose adjustment during pregnancy. Linezolid poses a potentially serious toxicity risk, particularly as exposures appear to be high in the later stages of pregnancy and post-partum following extended use, but this should be considered alongside the benefits of this extremely effective drug in the treatment of this life-threatening disease. While plenty of questions remain regarding the exposure to Group A and B antituberculosis drugs through breastmilk, existing literature suggests minimal harm to the breastfed infant. Pregnant patients and their infants should be included in therapeutic trials and pharmacokinetic studies of effective antituberculosis drugs.

UNASSIGNED: This study aimed to determine the prevalence and molecular characterization of bedaquiline (BDQ) resistance among rifampicin-resistant tuberculosis (RR-TB) isolates collected from Zhejiang, China.
UNASSIGNED: A total of 245 RR-TB isolates were collected from 19 municipal TB hospitals in Zhejiang province, China between January and December 2021. Microplate assays were used to determine the minimum inhibitory concentrations (MIC) of BDQ. Whole-genome sequencing (WGS) was performed on isolates with MIC values for BDQ ≥ 0.25 μg/mL.
UNASSIGNED: Five (2.04%) BDQ-resistant strains were isolated from 245 tuberculosis patients. The resistance rate of BDQ was not correlated to the sex, age, treatment history, or occupation of patients. Four BDQ-resistant isolates and three BDQ-sensitive isolates were found to carry Rv0678 mutations, and one BDQ-resistant strain carried both Rv0678 and pepQ mutations. No mutations within the atpE and Rv1979c genes were observed.
UNASSIGNED: BDQ demonstrated strong in vitro antibacterial activity against RR-TB isolates, and the Rv0678 gene was identified as the primary mechanism contributing to BDQ resistance among RR-TB isolates from Zhejiang, China. Furthermore, in addition to the four currently known resistance-associated genes (atpE, Rv0678, Rv1979c, and pepQ), other mechanisms of resistance to BDQ may exist that need further study.

UNASSIGNED: Multidrug-resistant (MDR) and rifampicin-resistant (RR) tuberculosis (TB) is related to high healthcare costs. However, studies on direct healthcare expenditure in different settings remain inconclusive. Hence, we aimed to examine the direct medical expenses (DME) of patients with MDR/RR-TB and assessed which patient characteristics were associated with higher costs.
UNASSIGNED: DME was evaluated using records from the hospital information system in three cities with different economic levels in Zhejiang Province, Eastern China, matching with data (including socio-demographics, disease treatment status, etc.) collected in the Tuberculosis Management Information System. A logistic regression model was used to identify variables associated with higher costs.
UNASSIGNED: Of 193 patients with MDR/RR-TB, the average DME was $10,491 (interquartile range (IQR) $4679-16,710), consisting of $2696 (IQR $1019-5100) out-of-pocket costs, medical reimbursement, and subsidies, accounting for 32%, 50.3% and 14%, respectively. A total of 74.2% and 56% of DME were for drugs and anti-TB drugs, respectively. Only 16.9% of the patients were treated with an all-oral regimen. Higher DME was significantly associated with local residents 7.29 (95% confidence interval (CI) [2.62-20.3]), hospitalization experience 7.63 (95% (CI) [2.54-22.95]), longer duration of treatment 6.63 (95% CI [2.27-19.35]), and lower health insurance reimbursement 5.65 (95% CI [1.90-16.79]).
UNASSIGNED: DME of patients with MDR/RR-TB was still significant, and domestic migrants, hospitalization, long treatment duration, and high health insurance rates increased the financial burden on MDR/RR-TB patients. Reasonable intervention programs should be developed to reduce the medical burden of patients with MDR/RR-TB, according to the DME and its component of MDR-TB patients, besides the economic status of their regions.