Impact of on-site Xpert on TB diagnosis and mortality trends in Uganda.

SETTING: Since 2012, Uganda expanded the Xpert® MTB/RIF network for diagnosis of TB. OBJECTIVES: We compared TB care cascades at health facilities with on-site Xpert vs. facilities that accessed the assay through specimen referral. DESIGN: We analysed secondary aggregate data of the National TB and Leprosy Program (NTLP) from 2016 to 2019. We computed the proportions of notified TB cases and mortality ratios in relation to the estimated TB burden. RESULTS: TB case notifications per annum increased from 24,287 in 2016 to 30,739 in 2019, and the proportion of cases diagnosed at facilities with on-site Xpert testing increased from 62% (15,070/24,287) to 81% (24,829/30,739) (P < 0.001). TB mortality at facilities with on-site Xpert decreased from 8.6% (1,302/15,070) to 7.8% (1,938/24,829) (P = 0.41), while it increased at facilities without on-site Xpert from 6.9% (638/9,217) to 8.8% (521/5,910) (P = 0.23). Furthermore, mortality among TB-HIV co-infected patients at facilities with on-site Xpert dropped from 5.0% (760/15,070) in 2016 to 4.8% (1,187/24,826) in 2019 (P = 0.84) compared to 4.4% (407/9,217) in 2016 to 5.3% (315/5,910) in 2019 (P = 0.57). CONCLUSION: Wider installation and decentralisation of Xpert leads to increased case-finding. However, the impact on reduction in mortality remains limited. Interventions to address TB-related mortality in addition to Xpert roll-out are required.

CONTEXTE: Depuis 2012, l'Ouganda a élargi son réseau de tests Xpert® MTB/RIF destinés au diagnostic de la TB. Nous avons comparé les cascades de soins de la TB dans des centres en mesure de réaliser les tests Xpert « sur place ¼ et dans des centres ayant accès à ces tests par un système d'adresse des prélèvements. MÉTHODES: Nous avons analysé les données agrégées secondaires du programme national de lutte contre la TB (NTLP) de 2016 à 2019. Nous avons calculé les pourcentages de cas de TB ayant fait l'objet d'une notification et les taux de mortalité par rapport au poids sanitaire estimé de la TB. RÉSULTATS: Les notifications annuelles de cas de TB ont augmenté de 24 287 en 2016 à 30 739 en 2019, et la proportion de cas diagnostiqués dans les centres avec tests Xpert sur place a augmenté de 62% (15 070/24 287) à 81% (24 829/30 739) ; P < 0,001. La mortalité liée à la TB dans les centres avec tests Xpert sur place a diminué de 8,6% (1 302/15 070) à 7,8% (1 938/24 829) (P = 0,41), alors qu'elle a augmenté dans les centres sans tests Xpert sur place, de 6,9% (638/9 217) à 8,8% (521/5 910) (P = 0,23). Par ailleurs, la mortalité des patients coinfectés par la TB et le VIH dans les centres avec tests Xpert sur place a diminué de 5,0% (760/15 070) en 2016 à 4,8% (1 187/24 826) en 2019 (P = 0,84), contre une hausse de 4,4% (407/9 217) en 2016 à 5,3% (315/5 910) en 2019 (P = 0,57) dans les centres sans tests Xpert sur place. CONCLUSIONS: La décentralisation et l'élargissement du déploiement des tests Xpert a permis d'accroître le nombre de cas détectés. Toutefois, l'impact sur la réduction de la mortalité reste limité. Des interventions visant à réduire la mortalité liée à la TB, audelà du déploiement des tests Xpert, sont nécessaires.

Hyperglycaemia and pharmacokinetics of rifampicin/isoniazid among TB-HIV co-infected patients in Kampala, Uganda.

OBJECTIVE: 1) To determine the prevalence of diabetes mellitus and impaired fasting glucose (IFG) in patients with TB and HIV co-infection, and 2) to investigate the effect of fasting plasma glucose (FPG) on rifampicin (RIF) and isoniazid (INH) serum concentrations.DESIGN: Retrospective data analysis of a cohort of HIV-infected adults with newly diagnosed pulmonary TB. Plasma glucose and TB drug levels were obtained at Week 0, 2, 8 and 24 of TB treatment.RESULTS: A total of 107 patients were included in this analysis. Random plasma glucose ≥200 mg/dL was found in 1/53 (2%) participant at Week 0. The prevalence of FPG ≥ 126 mg/dL decreased from 8/41 (20%) at Week 2 to 3/89 (3%) at Week 24. IFG (100-125 mg/dL) was observed in 23/41 (56%) participants at Week 2, and 39/89 (44%) at Week 24. FPG was inversely correlated with lower area under the curve (AUC0-24h) for RIF (c = -0.52; 95%CI -0.84 to -0.21; P = 0.001). FPG was not associated with lower INH AUC0-24h.CONCLUSION: We found a high prevalence of FPG ≥ 126 mg/dL, which decreased significantly during treatment, and a high proportion of IFG at the end of TB treatment. Higher FPG was associated with lower AUC for RIF.

Sustained positive impact on tuberculosis treatment outcomes of TB-HIV integrated care in Uganda.

To examine tuberculosis (TB) treatment outcomes from a long-term TB-HIV (human immunodeficiency virus) integrated model of care at the Infectious Diseases Institute Clinic, Kampala, Uganda. We included HIV-positive adults who were new TB cases initiated on anti-tuberculosis treatment between 2009 and 2015 during TB-HIV integration. Trends in TB treatment outcomes and TB-associated deaths were analyzed using respectively the χ² trend test and Kaplan-Meier methods. The analysis involved 1318 cases: most patients were female (>50%); the median age ranged from 34 to 36 years, and >60% were late presenters (CD4 count <200 cells/µl), with a median CD4 cell count of 100-146 cells/µl at TB diagnosis. TB treatment success (cured or treatment completed) was 67-76%. Loss to follow-up (LTFU) declined systematically from 7% in 2010 to 3.4% in 2015 (P < 0.01). Antiretroviral therapy (ART) initiation during the intensive phase improved from 47% in 2009 to 97% in 2015 (P < 0.01). The mortality rate was >15% over time, and the probability of death at month 2 of anti-tuberculosis treatment was 52% higher among late presenters than in early presenters (13% vs. 6%, P < 0.01). Significant LTFU improvement and prompt ART initiation could be due to well-implemented TB-HIV integration care; however, static TB-associated deaths may be due to late presentation. .

Comparison of Löwenstein-Jensen and BACTEC MGIT 960 culture for Mycobacterium tuberculosis in people living with HIV.

OBJECTIVES: The aim of the study was to clarify how HIV infection affects tuberculosis liquid and solid culture results in a resource-limited setting. METHODS: We used baseline data from the Study on Outcomes Related to Tuberculosis and HIV Drug Concentrations in Uganda (SOUTH), which included 268 HIV/tuberculosis (TB)-coinfected individuals. Culture results from Löwenstein-Jensen (LJ) solid culture and mycobacteria growth indicator tube (MGIT) liquid culture systems and culture-based correlates for bacillary density from the sputum of HIV/TB-coinfected individuals at baseline were analysed. RESULTS: Of 268 participants, 243 had a CD4 cell count available and were included in this analysis; 72.2% of cultures showed growth on solid culture and 82.2% in liquid culture systems (P < 0.015). A higher CD4 cell count was predictive of LJ positivity [adjusted odds ratio (OR) 1.14; 95% confidence interval (CI) 1.03-1.25 per 50 cells/µL increase; P = 0.008]. The same, but insignificant trend was observed for MGIT positivity (adjusted OR 1.09; 95% CI 0.99-1.211 per 50 cells/µL increase; P = 0.094). A higher CD4 cell count was associated with a higher LJ colony-forming unit grade (adjusted OR 1.14; 95% CI 1.05-1.25 per 50 cells/µL increase; P = 0.011) and a shorter time to MGIT positivity [adjusted hazard ratio (HR) 1.08; 95% CI 1.04-1.12 per 50 cells/µL increase; P < 0.001]. CONCLUSIONS: In a resource-limited setting, the MGIT liquid culture system outperformed LJ solid culture in terms of culture yield and dependence on CD4 cell counts in HIV/TB-coinfected individuals. We therefore suggest considering an adaptation of diagnostic algorithms: when resources allow only one culture method to be performed, we recommend that MGIT liquid culture should be used exclusively in HIV-positive individuals as a first-line culture method, to reduce costs and make TB culture results accessible to more patients in resource-limited settings.

Tuberculosis treatment success among rural and urban Ugandans living with HIV: a retrospective study.

Setting: Government health centres and hospitals (six urban and 20 rural) providing tuberculosis (TB) treatment for people living with the human immunodeficiency virus (PLHIV) in central and western Uganda. Objective: To identify and quantify modifiable factors that limit TB treatment success among PLHIV in rural Uganda. Design: A retrospective cross-sectional review of routine Uganda National Tuberculosis and Leprosy Programme clinic registers and patient files of HIV-positive patients who received anti-tuberculosis treatment in 2014. Results: Of 191 rural patients, 66.7% achieved treatment success compared to 81.1% of 213 urban patients. Adjusted analysis revealed higher average treatment success in urban patients than in rural patients (OR 3.95, 95%CI 2.70-5.78, P < 0.01, generalised estimating equation model). Loss to follow-up was higher and follow-up sputum smear results were less frequently recorded in TB clinic registers among rural patients. Patients receiving treatment at higher-level facilities in rural settings had greater odds of treatment success, while patients receiving treatment at facilities where drug stock-outs had occurred had lower odds of treatment success. Conclusion: Lower reported treatment success in rural settings is mainly attributed to clinic-centred factors such as treatment monitoring procedures. We recommend strengthening treatment monitoring and delivery.

Contexte: L'étude a été réalisée dans des centres de santé et des hôpitaux publics, six urbains et 20 ruraux, fournissant un traitement de la tuberculose (TB) aux personnes vivant avec le VIH (PVVIH) dans le centre et l'ouest de l'Ouganda.Objectif: Identifier et quantifier les facteurs modifiables qui limitent le succès du traitement de la TB parmi les PVVIH dans l'Ouganda rural.Schéma: Une revue rétrospective transversale des registres cliniques et des dossiers de patients du Programme national tuberculose et lèpre d'Ouganda pour les patients VIH positifs qui ont reçu un traitement de TB en 2014.Résultats: Parmi 191 patients ruraux, 66,7% ont eu un bon résultat de leur traitement, tandis que parmi 213 patients urbains, 81,1% ont eu un bon résultat. Une analyse ajustée a révélé un succès thérapeutique moyen plus élevé chez les patients urbains comparés aux patients ruraux (OR 3,95 ; IC95% 2,70­5,78 ; P < 0,01 ; modèle d'équation d'estimation généralisée). Les pertes de vue ont été plus élevées et les résultats de frottis de crachats de suivi ont été moins souvent enregistrés dans les registres des centres TB pour les patients ruraux. Les patients recevant un traitement dans des structures de plus haut niveau, toujours en zone rurale, avaient plus de chances d'avoir un succès thérapeutique. Les patients recevant leur traitement dans des structures où étaient survenues des ruptures de stock de médicaments avaient moins de chances de succès thérapeutique.Conclusion: Les taux plus faibles de succès du traitement rapportés en zone rurale sont en majorité attribués à des facteurs liés aux centres de santé, comme les procédures de suivi du traitement. Nous recommandons le renforcement de la fourniture et du suivi du traitement.

Marco de referencia: El estudio se llevó a cabo en centros de salud y hospitales del sector público, seis en entornos urbanos y 20 en medio rural y consistió en suministrar el tratamiento antituberculoso a las personas positivas frente al virus de la inmunodeficiencia humana (VIH) en la región central y occidental de Uganda.Objetivo: Determinar y cuantificar los factores modificables que limitan la eficacia del tratamiento antituberculoso en las personas positivas frente al VIH en las zonas rurales de Uganda.Método: Fue este un estudio transversal retrospectivo de análisis de los registros corrientes y las historias clínicas de los pacientes positivos frente al VIH, en los consultorios del Programa Nacional contra la Tuberculosis y la Lepra de Uganda en el 2014.Resultados: De los 191 pacientes de entornos rurales, el 66,7% logró un tratamiento eficaz y en los 213 pacientes en medio urbano esta proporción fue 81,1%. Un análisis ajustado reveló un promedio de éxito terapéutico más alto en los pacientes urbanos en comparación con los pacientes rurales (OR 3,95; IC95% de 2,70 a 5,78; P < 0,01, según un modelo de ecuaciones de estimación generalizadas). En medio rural, se observó una mayor pérdida durante el seguimiento y se consignaban con menor frecuencia los resultados de las baciloscopias de seguimiento en los registros de tuberculosis de los consultorios. Los pacientes que recibían tratamiento en los establecimientos de nivel de atención más alto en medio rural tenían mayores posibilidades de éxito terapéutico. Los pacientes que recibían tratamiento en centros que presentaban desabastecimientos de medicamentos tuvieron menos probabilidades de lograr un tratamiento eficaz.Conclusión: La menor proporción de éxito terapéutico notificada en los entornos rurales se debe en su mayor parte a factores que dependen del consultorio, como los procedimientos de supervisión del tratamiento. Se recomienda reforzar la supervisión y el suministro del tratamiento antituberculoso.

Patients who return to care after tracking remain at high risk of attrition: experience from a large HIV clinic, Uganda.

We determined the retention rate of patients infected with HIV who resumed care after being tracked at the Infectious Diseases Clinic (IDC) in Kampala, Uganda. Between April 2011 and September 2013, patients who missed their clinic appointment for 8-90 days were tracked, and those who returned to the clinic within 120 days were followed up. The proportion of patients retained among tracked patients, and those who resumed care before tracking started was compared. At 18 months of follow up, 33 (39%) of the tracked patients and 72 (61%) of those who had resumed care before tracking started were retained in care. The most important cause of attrition among the traceable was self-transfer to another clinic (38 [73%] patients), whereas among those who resumed care before tracking was loss to follow up (LTFU) (32 [71%] patients). Tracked patients who resume care following a missed appointment are at high risk of attrition. To increase retention, antiretroviral therapy clinics need to adopt a chronic care model which takes into consideration patients' changing needs and their preference for self-management.