TB-related catastrophic costs in Ethiopia.

OBJECTIVES: To measure the progress towards reducing TB-related catastrophic costs in 19 zones of Amhara, Oromia, SNNP (Southern Nations and Nationalities, and Peoples) and Sidama Regions of Ethiopia. METHODS: A baseline survey was conducted in randomly selected health facilities from all districts within the 19 zones from November 2020 to February 2021. Interventions targeting the major drivers of catastrophic costs identified in the baseline survey, such as installation of 126 GeneXpert and 13 Truenat machines, securing connectivity of 372 GeneXpert, establishing alternative specimen referral systems, and capacity-building of health workers, were implemented. A follow-up survey was conducted from October to December 2022. The WHO generic tool was used to collect data based on probability proportional to size. Data were entered into STATA software, and the proportion of catastrophic costs was calculated and compared between the two surveys. RESULTS: A total of 433 and 397 patients participated in the baseline and follow-up surveys, respectively. The proportion of catastrophic costs reduced from 64.7% to 43.8% (P < 0.0001). The share of direct non-medical costs decreased from 76.2% to 19.2%, while medical and indirect costs increased from 11.6% and 12.3% to 30.4% and 52.4 %. CONCLUSION: The proportion of households facing TB-related catastrophic costs has significantly reduced over the 2-year period. However, it remains unacceptably high and varies among regions. Further reducing the catastrophic costs requires multisectoral response, reviewing the TB service exemption policy, further decentralisation and improving the quality of TB services.

OBJECTIFS: Mesurer les progrès accomplis dans la réduction des coûts catastrophiques liés à la TB dans 19 zones des régions d'Amhara, d'Oromia, de SNNP (Région des nations, nationalités et peuples du Sud) et de Sidama en Éthiopie. MÉTHODES: Une enquête de base a été menée dans des établissements de santé sélectionnés au hasard dans tous les districts des 19 zones de novembre 2020 à février 2021. Des interventions ciblant les principaux facteurs de coûts catastrophiques identifiés dans l'enquête de référence, telles que l'installation de 126 machines GeneXpert et 13 Truenat, la sécurisation de la connectivité de 372 GeneXpert, la mise en place de systèmes alternatifs d'orientation des échantillons et le renforcement des capacités des agents de santé, ont été mises en œuvre. Une enquête de suivi a été menée d'octobre à décembre 2022. L'outil générique de l'OMS a été utilisé pour recueillir des données fondées sur une probabilité proportionnelle à la taille. Les données ont été saisies dans le logiciel STATA, et la proportion des coûts catastrophiques a été calculée et comparée entre les deux enquêtes. RÉSULTATS: Au total, 433 et 397 patients ont participé respectivement à l'enquête de base et à l'enquête de suivi. La proportion des coûts catastrophiques est passée de 64,7% à 43,8% (P < 0,0001). La part des coûts non médicaux directs a diminué, passant de 76,2% à 19,2%, tandis que les coûts médicaux et indirects sont passés de 11,6% et 12,3% à 30,4% et 52,4%. CONCLUSION: La proportion de ménages confrontés à des coûts catastrophiques liés à la tuberculose a considérablement diminué au cours de la période de 2 ans. Cependant, il reste inacceptable et varie selon les régions. Pour réduire davantage les coûts catastrophiques, il faut une réponse multisectorielle, une révision de la politique d'exemption des services de lutte contre la TB, une décentralisation plus poussée et une amélioration de la qualité des services de lutte contre la TB.

Drug-resistant tuberculosis care and treatment outcomes over the last 15 years in Ethiopia: Results from a mixed-method review of trends.

BACKGROUND AND OBJECTIVES: Drug resistant tuberculosis (DR-TB) remains a global challenge with about a third of the cases are not detected. With the recent advances in the diagnosis and treatment follow-up of DR-TB, there have been improvements with treatment success rates. However, there is limited evidence on the successful models of care that have consistently registered good outcomes. Our aim was to assess Ethiopia's experience in scaling up an ambulatory, decentralized model of care while managing multiple regimen transition processes and external shocks. METHODS: This was a cross-sectional, mixed-method study. For the quantitative data, we reviewed routine surveillance data for the period 2009-2022 and collected additional data from publicly available reports. We then analyzed the data descriptively. Qualitative data were collected from program reports, quarterly presentations, minutes of technical working group meetings, and clinical review committee reports and analyzed thematically. RESULTS: The number of DR-TB treatment initiating centers increased from 1 to 67, and enrollment increased from 88 in 2010 to 741 in 2019, but declined to 518 in 2022. A treatment success rate (TSR) of over 70% was sustained. The decentralized and ambulatory service delivery remained the core service delivery model. The country successfully navigated multiple regimen transitions, including the recently introduced six-month short oral regimen. Several challenges remain, including the lack of strong and sustainable specimen transportation system, lack of established systems for timely tracing and linking of missed DR-TB cases, and data quality issues. CONCLUSIONS: Ethiopia scaled up a decentralized ambulatory model of care, kept up to date with recent developments in treatment regimens, and maintained a high TSR, despite the influence of multiple external challenges. The recent decline in case notification requires a deeper look into the underlying reasons. The feasibility of fully integrating DR-TB treatment and follow up at community level should be explored further.

Descriptors of multidrug-resistant TB deaths in Ethiopia.

Deaths related to multidrug-resistant TB among patients who had received a second-line anti-TB drugs in Ethiopia were analysed. Respectively 38/704 (5.4%) and 44/995 (4.4%) deaths were identified in two cohorts (2015 and 2022). In the 2015 cohort, severe malnutrition was less prevalent, previous treatment rates were three times higher, hypokalaemia was more frequent, and the use of the Xpert® MTB/RIF assay, respiratory failure and severe anaemia/pancytopenia were less common than in the 2022 cohort. We observed that there were variations in adverse events when different treatment regimens were used over different time periods. To ensure proper patient care, correct guidance must be consistently implemented.

Les décès liés à la TB multirésistante chez les patients ayant reçu des médicaments antituberculeux de seconde ligne en Éthiopie ont été analysés. Respectivement 38/704 (5,4%) et 44/995 (4,4%) décès ont été identifiés dans deux cohortes (2015 et 2022). Dans la cohorte 2015, la malnutrition sévère était moins fréquente, les taux de traitement antérieur étaient trois fois plus élevés, l'hypokaliémie était plus fréquente, et l'utilisation du test Xpert® MTB/RIF, l'insuffisance respiratoire et l'anémie/pancytopénie sévère étaient moins fréquentes que dans la cohorte 2022. Nous avons observé des variations dans les effets indésirables lorsque différents schémas thérapeutiques étaient utilisés sur différentes périodes. Pour garantir des soins adéquats aux patients, des consignes appropriées doivent être appliquées de manière régulière.

Experiences of introducing new drugs for drug-resistant TB at the ALERT Hospital, Addis Ababa, Ethiopia, 2017-2019.

BACKGROUND: Drug-resistant TB (DR-TB) remains a major public health concern. DR-TB patient data from ALERT (All Africa Leprosy, Tuberculosis and Rehabilitation Training Centre) Hospital, Addis Ababa, Ethiopia, who received bedaquiline (BDQ) and/or delamanid (DLM) containing regimens were analysed. RESULTS: From 2017 to 2019, 51 DR-TB patients were enrolled. Of 33 patients, 31 (93.9%) had culture converted at 6 months. Of those with final outcomes, 77% (n = 10) were cured. Thirty (58.8%) developed adverse events, the most frequent of which were gastrointestinal disorders (70%), haematological disorders (16.7%) and QTc prolongation (16.7%). Twenty patients discontinued the offending drug permanently. CONCLUSION: With close monitoring, introduction of new DR-TB regimens brought good early results, which encouraged wider programmatic implementation in Ethiopia.

CONTEXTE: La TB pharmacorésistante (DR-TB) reste une préoccupation de santé publique majeure. Les données des patients DR-TB de l'hôpital ALERT (All Africa Leprosy, Tuberculosis and Rehabilitation Training Centre, Addis Ababa, Ethiopie) qui ont reçu des protocoles contenant de la bédaquiline et/ou du délamanide ont été analysées. RÉSULTATS: Des 51 patients DR-TB ont été enrôlés de 2017 à 2019, 90 ont eu une conversion de culture à 6 mois, 77% ont été guéris, 30 ont eu des effets secondaires, les plus fréquents étant des troubles gastro-intestinaux (70%), des troubles hématologique (16,7%) et un allongement de QTc (16,7%). Vingt patients ont définitivement arrêté le médicament incriminé. CONCLUSION: Moyennant une surveillance étroite, l'introduction de nouveaux protocoles DR-TB a eu de bons résultats précoces qui encouragent une mise en œuvre programmatique plus large en Ethiopie.

Epistasis between Toll-like receptor-9 polymorphisms and variants in NOD2 and IL23R modulates susceptibility to Crohn's disease.

OBJECTIVES: Recent data suggest functional interactions between NOD2 and other receptors of the innate immune system modulating inflammatory responses. Here we analyzed the role of Toll-like receptor 9 (TLR-9) gene variants with respect to susceptibility to inflammatory bowel disease (IBD) and tested for genetic interactions with NOD2 and other susceptibility genes for Crohn's disease (CD). METHODS: The single-nucleotide polymorphisms (SNPs) -1237T/C (rs5743836) and 2848A/G (rs352140=p.Pro545Pro) in TLR9, the main CD-associated variants within the genes for NOD2, IL23R, ATG16L1, and variants in the IBD5 locus and in the DLG5 gene were assessed in 956 patients with IBD (606 CD and 350 ulcerative colitis) and in 792 healthy controls. The associations with disease susceptibility and phenotype, and epistatic gene-gene interactions, were analyzed. RESULTS: The TLR9 -1237T/C polymorphism showed significant interactions with NOD2 mutations. The frequency of -1237C was significantly higher in CD patients with at least one NOD2 mutation (P=0.004 vs. controls, odds ratio (OR) 1.60, 95% confidence interval (CI) (1.15-2.21)) and further increased in CD patients with two mutated NOD2 alleles (P=0.002 vs. controls, OR 2.37, 95% CI (1.35-4.15)). Significant gene-gene interactions were also observed for the TLR9 polymorphism -1237T/C with IL23R variants (most significantly with rs1004819, P=0.0007), with a particular high frequency of -1237C in CD patients carrying CD-protective IL23R variants. Epistatic interactions of the TLR9 -1237T/C SNP were also noted with the DLG5 113G/A variant (P=0.0007). CONCLUSIONS: Our results provide evidence for genetic interactions between polymorphisms in TLR9 and CD-associated variants in NOD2, IL23R, and DLG5, differentially modulating CD susceptibility.

The 14-bp deletion polymorphism in the HLA-G gene displays significant differences between ulcerative colitis and Crohn's disease and is associated with ileocecal resection in Crohn's disease.

HLA-G is a non-classical MHC class Ib molecule predominantly expressed in cytotrophoblasts and under pathological conditions also in chronically inflamed and in malignant tissues. Recently an increased expression of HLA-G was found in ulcerative colitis (UC), but not in Crohn's disease (CD). The HLA-G gene is located in IBD3, a linkage region for inflammatory bowel disease (IBD). A 14-bp deletion polymorphism (Del+/Del-) within exon 8 of the HLA-G gene might influence transcription activity and is therefore of potential functional relevance. To investigate whether the 14-bp deletion polymorphism is associated with IBD, 371 patients with CD, 257 patients with UC and 739 controls were genotyped. The heterozygous genotype (P = 0.031) and the Del+ phenotype (P = 0.038) were significantly increased, whereas the homozygous Del- phenotype (P = 0.038) was significantly decreased in UC when compared with CD. Thus, the 14-bp deletion polymorphism within the HLA-G gene displayed significant differences between UC and CD. Moreover, a significant increase of the Del+ allele (P = 0.002) and the Del+/Del+ genotype (P = 0.013) and a consecutive decrease of the Del-/- genotype (P = 0.024) were observed in those CD cases positive for ileocecal resection. Thus, a potential effect of the HLA-G gene in IBD may affect both UC and CD. Other polymorphisms linked to the 14-bp deletion polymorphism might also contribute to immunopathogenesis. As there are several partly functional polymorphisms within the promoter region potentially influencing HLA-G expression, further studies in IBD are necessary in the context of differential expression of HLA-G between UC and CD.