Unsuccessful Xpert® MTB/RIF results: the Nigerian experience.

Setting: Nigeria, a high tuberculosis (TB) burden country. Objective: To study the rate, distribution and causes of unsuccessful Xpert® MTB/RIF test outcomes, with the aim of identifying key areas that need to be strengthened for optimal performance of the assay. Design: This was a retrospective analysis of data uploaded between January and December 2015 from Xpert facilities to the central server using GXAlert. Result: Of 52 219 test results uploaded from 176 Xpert machines, 22.5% were positive for Mycobacterium tuberculosis, 10.8% of which were rifampicin-resistant; 4.7% of the total number of results were invalid, 4.2% had error results and 2.1% no result outcomes. Technical errors were most frequent (69%); these were non-seasonal and occurred in all geopolitical regions and at all health facility levels. Temperature-related errors were more prevalent in the North-West Region, with peaks in April to June. Peak periods for temperature and machine malfunction errors coincided with the periods of low utilisation of the assay. Conclusion: The key challenge affecting performance was poor adherence to standard operating procedures. Periodic refresher training courses, regular supervision, preventive maintenance of Xpert machines and proper storage of cartridges are strategies that could improve Xpert performance.

Contexte : Le Nigeria, pays lourdement frappé par la tuberculose.Objectif : Etudier le taux, la distribution et les causes de mauvais résultats du test Xpert dans le but d'identifier les domaines clés qui doivent être renforcés pour une performance optimale du test.Schéma : Analyse rétrospective des données téléchargées entre janvier et décembre 2015 depuis les structures équipées de Xpert vers le serveur central à travers le GXAlert.Résultats : Sur 52 219 tests téléchargés à partir de 176 machines, 22,5% ont été positifs pour Mycobacterium tuberculosis, dont 10,8% ont été résistants à la rifampicine ; globalement, 4,7% ont été invalides, 4,2% ont eu des résultats erronés et 2,1% n'ont eu aucun résultat. Les erreurs d'origine technique ont été les plus fréquentes, à 69%, n'ont pas eu de variation saisonnière et sont survenues dans toutes les zones géopolitiques et à tous les niveaux des structures de santé. Les erreurs liées à la température ont été prévalentes dans la région nord-ouest, avec des pics d'avril à juin. Les périodes de pic en termes de température et de dysfonction des machines ont coïncidé avec les périodes de faible utilisation du test.Conclusion : Le problème principal qui a affecté la performance du test a été l'adhérence médiocre aux procédures opératoires standardisées. Des révisions périodiques de la formation, une supervision régulière, une maintenance préventive de la machine à Xpert et un stockage approprié des cartouches constituent des stratégies susceptibles d'améliorer la performance du Xpert.

Marco de referencia: Nigeria, un país con alta carga de morbilidad por tuberculosis.Objetivo: Estudiar la tasa de resultados fallidos de la prueba Xpert, su distribución y sus causas con el objeto de reconocer las esferas prioritarias que precisan fortalecimiento, a fin de obtener un funcionamiento óptimo de la prueba.Método: Fue este un análisis retrospectivo de los datos enviados al servidor central por los establecimientos que practican la prueba Xpert, mediante el sistema GXAlert, de enero a diciembre del 2015.Resultados: De 52 219 pruebas realizadas en 176 dispositivos y subidas al sistema, 22,5% fueron positivas para Mycobacterium tuberculosis y de ellas el 10,8% presentó resistencia a rifampicina; de todos los resultados, 4,7% fueron inválidos, 4,2% exhibieron error y 2,1% de las pruebas no comportaban un resultado. El error más frecuente fue el de tipo técnico (69%), el cual no siguió un carácter estacional y ocurrió en todas las regiones geopolíticas y en establecimientos de salud de todos los niveles. Los errores debidos a la temperatura predominaron en la región noroeste, con períodos de mayor frecuencia de abril a junio. Los períodos de mayor frecuencia de errores causados por la temperatura o el disfuncionamiento de los dispositivos coincidieron con épocas de baja utilización de la prueba.Conclusión: El principal problema que interfirió con el buen funcionamiento de la prueba fue el incumplimiento de los procedimientos normalizados de trabajo. Se podría mejorar la eficacia de la prueba Xpert mediante estrategias como los cursos periódicos de actualización, la supervisión constante y el mantenimiento preventivo de los dispositivos, además del almacenamiento adecuado de los cartuchos de la prueba.

p53-mediated upregulation of BAX gene transcription is not involved in Bax-alpha protein overexpression in the left ventricle of spontaneously hypertensive rats.

An association of increased apoptosis with overexpression of the proapoptotic protein Bax-alpha has been reported in the left ventricle of adult spontaneously hypertensive rats (SHR). Both alterations were corrected in SHR that received long-term treatment with the AT1 antagonist losartan. To gain insight into the regulation of cardiac Bax-alpha protein in genetic hypertension, we investigated the expression of the protein p53 (a BAX gene transcription factor) and BAX mRNA in the left ventricle of 30-week-old Wistar-Kyoto rats (WKY), SHR, and SHR treated with losartan (20 mg. kg-1. d-1) during 14 weeks before death. The expression of p53 and Bax proteins was assessed by Western blot analysis. The expression of BAX mRNA was assessed by Northern blot analysis. The density of apoptotic cells was assessed by direct immunoperoxidase detection of biotin-labeled deoxyuridine nucleotides. Compared with WKY, untreated SHR exhibited increased apoptosis (P<0.05), increased Bax-alpha protein (P<0.05), and similar levels of p53 protein and BAX mRNA. Losartan given long term was associated with the normalization of apoptosis and Bax-alpha protein expression. The expression of BAX mRNA was decreased (P<0. 05) in treated SHR compared with untreated SHR. No changes in the expression of p53 protein were observed in losartan-treated SHR. These results suggest that overexpression of the Bax-alpha protein seen in the left ventricle of adult SHR with increased apoptosis is not related to a p53-mediated upregulation of BAX gene transcription. Our data also suggest that normalization of Bax-alpha protein observed in SHR after long-term blockade of angiotensin II type 1 receptors may be due to the inhibition of BAX gene transcription.

Fibrinolytic activity in women on oral contraceptive pills: variation due to haemoglobin genotype.

Plasma fibrinogen levels and euglobulin lysis time (ELT) were determined in 84 women with haemoglobin genotype AA (HbAA) and in 38 with haemoglobin genotype AS (HbAS), aged 17-35 years, who were on oral contraceptive pills (OCP). The control group included 23 HbAA and 27 HbAS age-matched, apparently healthy women, who had regular menstruation and no history of OCP usage. The controls showed statistically significant elevations in fibrinogen levels in women with genotype HbAS (+13%; P < 0.05) compared with women with genotype HbAA. Among OCP users, the difference in fibrinogen levels (+5%) between HbAS and HbAA women was not statistically significant. The elevation in fibrinogen levels which was restricted to the HbAA women, was probably caused by OCP use, and may be dependent on the Hb genotype. In contrast, the observed elevations in euglobulin lysis time among OCP users (P < 0.005) were independent of Hb genotype. Thus, while OCP may constitute a risk factor for the development of thromboembolism in women, the S-gene may confer partial protection against this development in women who have the HbAS genotype.