The application value of GeneXpert MTB/RIF Ultra in the detection of special specimens of tuberculosis / 中国热带医学

@#Abstract: Objective To compare the diagnostic efficacy of the upgraded version of the GeneXpert automated fluorescent quantitative PCR system (GeneXpert MTB/RIF Ultra, GeneXpert Ultra) and the original version of the GeneXpert system (GeneXpert MTB/RIF, Xpert), real-time fluorescent quantitative nucleic acid detection (FQ-PCR), real-time fluorescent thermostatic amplification of Mycobacterium tuberculosis RNA (SAT-RNA), real-time fluorescent thermostatic amplification detection of DNA (thermostatic amplification method) and traditional BACTEC MGIT 960 liquid culture (culture method) for special specimens of tuberculosis, in order to analyze its application value in clinical detection. Methods Using prospective research methods, a total of 170 special specimens (including 47 pleural and ascites effusion samples, and 34 24-hour urinary sediment specimens, 49 tissue specimens and 40 fester specimens) were collected i'an Chest Hospital from January to September 2021. GeneXpert Ultra, Xpert, FQ-PCR, SAT-RNA, isothermal amplification, and traditional culture were used for detection. Clinical diagnosis was used as the standard, and sensitivity, specificity, positive predictive value, negative predictive value, coincidence rate, and Kappa value were compared among the methods. Results The sensitivities of GeneXpert Ultra, Xpert, FQ-PCR, SAT-RNA, isothermal amplification, and traditional culture were 65.18% (73/112), 49.11% (55/112), 37.50% (42/112), 19.64% (22/112), 8.04% (9/112), and 22.32% (25/112), respectively. The sensitivity of GeneXpert Ultra was higher than that of the other five methods, and the differences were statistically significant (χ2=66.25, 42.10, 28.89, 13.09, 4.92, 15.18, all P<0.05). GeneXpert Ultra result analysis showed that: 5.48%(4/73) cases had trace, that is, trace Mycobacterium tuberculosis load, 79.45% (58/73) cases were extremely low, 10.96% (8/73) cases were low, 2.74% (2/73) were medium, , and 1.36% (1/73) were high load. In 4 trace samples, the Xpert detection was negative for all. Of the 73 GeneXpert Ultra positive reports, 63 were rifampicin-sensitive, 6 were rifampicin-resistant, and 4 were rifampicin-resistant but of unclear resistance. Of the 55 Xpert positive reports, 45 were rifampicin-sensitive, 2 were rifampicin-resistant, and 8 were rifampicinresistant but of unclear resistance.. Conclusions The new generation of GeneXpert MTB/RIF Ultra has high sensitivity, specificity and drug resistance detection rate, and its advantage is even more apparent in the pathogenic diagnosis of special specimens of tuberculosis. It can be used as one of the preferred methods in samples with low bacterial load.

Application of GeneXpert MTB/RIF technology in rifampicin resistance gene mutation of Mycobacterium tuberculosis / 中国热带医学

@#Abstract: Objective To analyze the accuracy and feasibility of GeneXpert MTB/RIF (GeneXpert) detection in the detection of Mycobacterium tuberculosis and the characteristics of rifampicin-resistant rpoB gene mutations. Methods A total of 4 234 sputum samples from suspected tuberculosis patients diagnosed in Sanya tuberculosis designated hospitals from 2015 to 2021 were selected and subjected to sputum smear, solid culture, drug sensitivity test by solid proportion method and GeneXpert detection. Results The positive detection rates of sputum smear, solid culture and GeneXpert of 4 234 sputum samples were 29.24% (1 238/4 234), 32.17% (1 362/4 234) and 35.40% (1 499/4 234), respectively. The positive detection rate of GeneXpert was higher than that of sputum smear, and the difference was statistically significant (χ2=36.775, P<0.01). It was slightly higher than solid culture, and the difference was not statistically significant (χ2=9.908, P=0.02). Taking solid culture results as the gold standard, the sensitivity and specificity of GeneXpert for detecting MTB were 91.04% (1 240/1 362) and 90.98% (2 613/2 872), respectively. According to the proportional drug susceptibility test results as the gold standard, the sensitivity and specificity of GeneXpert in detecting rifampicin resistance were 96.96% (96/99) and 98.86% (1 128/1 141), respectively, with the consensus rate of 98.71%. The accuracy of rifampicin resistance in GeneXpert group without probe mutation was significantly lower than that in group with probe mutation. There was a statistical difference in probe mutation frequency between newly treated and retreated cases. The analysis of rpoB gene mutation frequency characteristics showed: Probe E (50.00%) > Probe A (22.12%) > Probe D (14.42%) > Probe B (6.73%) > combined probe (5.77%) > Probe C (0.96%). Conclusions GeneXpert detection can quickly and effectively diagnose rifampicin-resistant tuberculosis, which is helpful for early clinical diagnosis and treatment. In this region, the rpoB gene mutation probes of rifampicin-resistant tuberculosis mainly occurr in Probe E and Probe A, with the least mutations in Probe C.

Recurrent Appendicular Abscess-An Interesting Case Report

Background: Anorectal abscess, a common surgical condition, can rarely spread upwards to involve complex anatomical compartments leading to sepsis. A 45-year-old diabetic male presented in the ER with complaints of recurrent Right Iliac Fossa (RIF) pain with local swelling and dysuria, along with high-grade fever with chills and rigour for the last few days. He had been diagnosed with a case of recurrent appendicular abscess and treated with repeated Incision & Drainage during three previous hospitalizations. He also complained of simultaneous painful swelling in the left gluteal region during every episode of RIF pain. Methods: On examination, there was a parietal fluctuant swelling and tenderness in RIF over the previous appendicectomy scar. On Digital Rectal Examination (DRE), there was left-sided fullness and a tender induration at the 6 o'clock position on the dentate line, indicating some crypto-glandular disease. At the bedside, incision and drainage at RIF were performed, and pus was sent for C/S which came positive for an ESBL-producing strain of Escherichia coli. He was provisionally diagnosed with a case of the parietal abscess. Results: CECT W/A showed features of necrotizing fasciitis involving the anterior abdominal wall, forming an abscess, which crossed the midline along the pre-vesical space, extending to the pelvis and left ischio-anal fossa. Thus, the primary source of sepsis was a complex Ano-Rectal Abscess. Appropriate surgical management was done for source control. Conclusion: Unusual sources of infection should be suspected in patients with persistent sepsis or recurrent abscess and appropriate imaging modalities should be utilized before surgical intervention.

Prueba Xpert® MTB/RIF para el diagnóstico de Tuberculosis en el Instituto Médico La Floresta

La necesidad de un diagnóstico rápido, sensible y específico para tuberculosis es apremiante; se estiman 4 000 muertes cada día y aproximadamente 28 000 personas se contagian de esta enfermedad. La prueba Xpert®MTB/RIF consiste en un ensayo de diagnóstico in vitro de reacción en cadena de la polimerasa (PCR) en tiempo real automatizada, semicuantitativa, que en tan solo dos horas, permite detectar el ácido desoxirribonucleico (ADN) del complejo Mycobacterium tuberculosis (MTB) y mutaciones asociadas a la resistencia a rifampicina. Objetivo: Describir la experiencia del ensayo Xpert®MTB/ RIF y su valor diagnóstico en Dpto. de Microbiología del Instituto Médico La Floresta, desde abril 2012 hasta abril 2021. Métodos: Estudio descriptivo de muestras respiratorias y de otras procedencias, de pacientes con sospecha de tuberculosis, ensayadas por PCR a través del Xpert®MTB/RIF. Adicionalmente se realizó Ziehl-Neelsen y cultivo por el método de Ogawa Kudoh modificado, dependiendo del volumen de muestra recibida. Resultados: De 618 PCR realizadas, 58 muestras fueron positivas (9,4 %), 56 correspondieron a adultos y 2 a niños, 81 % se clasificaron como tuberculosis pulmonar y 19 % como extrapulmonar. A 37 se les realizó cultivo, de las cuales 10 no desarrollaron crecimiento, y a 33 adicionalmente Ziehl-Neelsen, de las cuales 12 presentaron baciloscopias negativas. En cinco de las muestras se detectó resistencia a rifampicina. Conclusiones: A través de la prueba Xpert®MTB/RIF fue posible detectar MTB en aquellas con baciloscopias negativas, en las que no desarrollaron crecimiento en el cultivo y permitió la rápida instauración de tratamiento en la tuberculosis multirresistente.

The rapid, sensitive, and specific diagnosis for tuberculosis is urgent; 4 000 deaths are estimated every day and approximately 28 000 people are infected with this disease. The Xpert®MTB/RIF test consists of an automated, semi-quantitative real-time polymerase chain reaction (PCR) in vitro diagnostic assay that, in just two hours, allows the detection of Mycobacterium tuberculosis complex (MTB) DNA and mutations associated with resistance to rifampicin. Objective: To describe the experience of the Xpert®MTB/RIF assay and its diagnostic value in the Department of Microbiology of the La Floresta Medical Institute, from April 2012 to April 2021. Methods: Descriptive study of respiratory samples and other sources, from patients with suspected of tuberculosis, assayed by PCR through Xpert®MTB/RIF. Additionally, Ziehl-Neelsen and culture were performed by the modified Ogawa Kudoh method, depending on the volume of sample received. Results: Of 618 PCR performed, 58 samples were positive (9.4 %), 56 corresponded to adults and 2 to children, 81 % were classified as pulmonary tuberculosis and 19 % as extrapulmonary. Culture was performed on 37, of which 10 did not develop growth, and on 33 additionally Ziehl-Neelsen, of which 12 presented negative bacilloscopy. Rifampicin resistance was detected in five of the samples. Conclusions: Through the Xpert®MTB/RIF test, it was possible to detect MTB in those with negative bacilloscopy, in which they did not develop growth in the culture and allowed the rapid establishment of treatment in multidrug-resistant tuberculosis.

Contribución del uso de XPERT MTB/RIF y su costo-efectividad en el diagnóstico de tuberculosis pulmonar y la resistencia a rifampicina: una comparación con métodos diagnósticos no moleculares / Contribution of the use of xpert MTB/RIF and its cost-effectiveness in the diagnosis of pulmonary tuberculosis and resistance to rifampicin: a comparison with non molecular diagnostic methods

Resumen Introducción: La tuberculosis es un problema de salud pública; su control requiere diagnóstico temprano y tratamiento oportuno. Xpert MTB/RIF® es una tecno logía diagnóstica basada en PCR en tiempo real, detecta el Complejo Mycobacterium tuberculosis y la susceptibilidad a rifampicina. Objetivo: Determinar la contribución del Xpert MTB/RIF y su costo-efectividad en la detección de tuberculosis y la resistencia a rifampicina en muestras respirato rias al compararlo con métodos de diagnóstico no moleculares Materiales y Métodos: Se analizaron 1.574 muestras de pacientes con sospecha de tuberculosis pulmonar que fueron procesadas para microscopía con coloración fluorescente de auramina-rodamina, Xpert MTB/RIF y cultivo en BACTEC MGIT 960. Los resultados obtenidos se compararon entre los métodos no moleculares y los moleculares para la detección de M. tuberculosis y susceptibilidad a rifampicina y se realizó un análisis comparativo de costos y costo efectividad. Resultados: 19,2% de las muestras fueron positivas por alguna de las técnicas usadas. Xpert MTB/RIF detectó M. tuberculosis en 90,4% del total de muestras positivas con un índice Kappa de 0,77 (IC95%: 0,74-0,82) comparado con el cultivo. La resistencia a rifampicina por Xpert fue 8,1%, sensibilidad 94,1% (IC95%: 73,0-99,0%), especificidad 98,4% (IC95%: 95,5-99,5%) y Kappa de 0,88 (IC95%: 0,76-1,00). La razón incremental de costo efectividad (RICE) fue menor en Xpert MTB/RIF comparada con el cultivo. Conclusión: Xpert MTB/RIF es una prueba eficiente y costo efectiva en la detección de casos de M. tuberculosis en muestras pulmonares comparado con los mé todos de diagnóstico basados en cultivo, sin embargo y a diferencia del Xpert MTB/RIF, estos pueden aportar en el diagnóstico con el aislamiento de especies de micobacterias no tuberculosas y la susceptibilidad a isoniazida y otros medicamentos.

Abstract Introduction: Tuberculosis is a public health problem its control requires early diagnosis and timely treatment. Xpert MTB/RIF is a real-time PCR based diagnostic technology, detects the Mycobacterium tuberculosis complex and rifampicin resistance. Objective: To determine the contribution of Xpert MTB/RIF and its cost-effectiveness in the detection of potential positive cases for tuberculosis and resistance to rifampicin in respiratory samples comparatively with diagnostic non molecular methods Materials and Methods: From 2013 to 2015, 1.574 clinical samples of patients with suspected pulmonary tuberculosis were evaluated by smear microscopy using auramina-rodamina stain, Xpert and culture in liquid medium BACTEC MGIT 960®. Results: 19,2% of the samples were positive for any of the methods used, Xpert detected M. tuberculosis in 90,4% of the positive samples and the concordance between Xpert and cultures had a Kappa index of 0,71 (IC95%: 0,62-0,72). Xpert identified resistance to rifampicin in 8,1% of the clinical samples studied with a sensitivity 94.1% (IC95%: 73,0-99,0%), specificity 98,4% (IC95%: 95,5-99,5%) and Kappa index 0,88 (IC95%: 0,76-1,00). Xpert had an incremental cost effectiveness ratio lower than culture (RICE). Conclusion: Xpert MTB/Rif is efficient diagnostic technique and comparable with culture in cost effectiveness for pulmonary tuberculosis diagnosis. However, culture based methods, in contrast to Xpert, may allow the isolation and identification of non tuberculosis mycobacterial species and the possibility to perform susceptibility for other antituberculous drugs.

Caracterización clínica y microbiológica de pacientes con trazas en Xpert MTB/RIF Ultra / Clinical and microbiological characterization of patients with Xpert MTB/RIF Ultra traces

INTRODUCCIÓN: El Xpert MTB/RIF Ultra (Ultra) ha mejorado dramáticamente el diagnóstico de la tuberculosis (TBC). Con él ha nacido la categoría de trazas, que es la menor carga bacilar detectable por este examen. OBJETIVO: Describir las características clínicas de los pacientes con presencia de trazas en el Ultra y evaluar la confirmación de la TBC como diagnóstico clínico. MATERIALES Y MÉTODOS: Estudio descriptivo de serie de casos. Se extrajo la información de fichas clínicas de pacientes con positividad a trazas. Se confrontaron datos clínicos, microbiológicos e histopatológicos. RESULTADOS: Se analizaron 21 pacientes. La edad promedio fue de 52 años. Todos los casos presentaron baciloscopias negativas. Cuatro cultivos en medio líquido MGIT fueron positivos, dos en pleura parietal, uno en líquido pleural y otro en expectoración. En pleura parietal, tres casos presentaron granulomas con necrosis caseosa y un granuloma esbozos de necrosis. En tejido pulmonar se observaron dos casos con granulomas con esbozos de necrosis y dos con granulomas no necrotizantes. Tres pacientes tenían el antecedente de TBC previa, se interpretó la positividad de trazas en ellos como falsos positivos. Finalmente se diagnosticaron 13 casos como TBC activa, donde cinco de ellos fueron TBC pleurales. La mayor concordancia clínica, microbiológica e histopatológica fue en muestras de líquido y tejido pleural. DISCUSIÓN: Se debe interpretar con cautela los hallazgos de esta prueba en muestras de vía aérea; el análisis multidisciplinario (clínica, imágenes, microbiología, histología) es crucial en las decisiones de nuestras conductas clínicas futuras. El hallazgo de trazas en pleura tiene, a nuestro parecer, un alto valor diagnóstico en el estudio de la tuberculosis en esta localización.

INTRODUCTION: Xpert MTB/RIF Ultra has dramatically changed the diagnosis of tuberculosis. A new category called traces appeared, which is the smallest amount of bacillar load detectable. OBJECTIVE: Describe the clinical characteristics of patients that present traces in Xpert MTB/RIF Ultra test, and to evaluate the confirmation of tuberculosis as clinical diagnosis. METHODS: We perform a descriptive case series study. Information was recovered from clinical records of patients with positive test for traces. Clinical, histopathological and microbiological results were confronted. RESULTS: Twenty one patients were analyzed. The mean age was 52 years-old. All cases had negative smear microscopy and four MGIT cultures were positive, two in pleural fluid and another in sputum. In parietal pleura, three cases presented granulomas with caseous necrosis, and one showed granuloma with very little necrosis. In pleural tissue we observed two cases of granulomas with traces of necrosis and two with non-necrotizing granulomas. Three patients had history of previous tuberculosis and positive traces, the test was interpreted as a false positive result. Finally, active tuberculosis was diagnosed in 13 cases, and five of them were pleural tuberculosis. The highest clinical, microbiological and histopathological agreement was in fluid and pleural tissue samples. DISCUSSION: The findings of Xpert MTB/RIF Ultra in airway samples must be interpreted carefully. Multi-disciplinary analysis is crucial in future clinical decisions. The finding of traces in pleura has, in our opinion, a high diagnostic value in the study of tuberculosis in this location.

Apport du test expert MTBRIF dans le diagnostic de la tuberculose toute forme à Saint-Louis / contribution of the Xpert MTB / Rif test in the diagnosis of tuberculosis of any form in Saint-Louis

Introduction: le test Xpert MTB/RIF présente un double avantage d'une part le diagnostic rapide des cas mêmes difficiles par la technique standard de l'examen direct à la microscopie et d'autre part par la détection de la résistance à la rifampicine. Notre objectif était de déterminer l'apport du test Xpert dans le diagnostic de la tuberculose toutes formes confondues. Matériels et méthode : étude transversale, descriptive à collecte rétrospective menée dans le service de Pneumophtisiologie de CHRU de Saint-Louis. Tous les cas suspects de tuberculose qui avaient bénéficié d'un test Xpert de 2018 à 2020avec un dossier médical accessible et exploitable ont été inclus. Les paramètres étudiés étaient les données sociodémographiques, cliniques et biologiques. Résultats : Nous avions colligés 524dossiers de malades avec un sex-ratio de 1,3. L'âge moyen des patients était de 37 ans+/-15 ans. Il y'avait 285 prélèvements positifs au GeneXpert dont 224 d'origine pulmonaire et 61d'origine extra pulmonaire. Le nombre d'échantillons résistants à la rifampicine était de cinq, tous d'origine respiratoire. Conclusion: le test Xpert est une nouvelle technique moléculaire recommandée par l'OMS dans le diagnostic de la tuberculose pulmonaire. Toutefois il doit être évaluer dans le diagnostic de la tuberculose extra pulmonaire

Introduction: The Xpert MTB / RIF assay has a dual advantage on the one hand, the rapid diagnosis of even difficult cases by the standard technique of direct microscopic examination and on the other hand by the detection of resistance to rifampicin. Our objective was to determine the contribution of the Xpert test in the diagnosis of tuberculosis of all forms. Materials and method: retrospective, descriptive and analytical study carried out in the Pneumophtisiology department of the CHRU of Saint-Louis. All suspected tuberculosis cases who had received an Xpert test from 2018 to 2020 were included. The parameters studied were socio-demographic, clinical and biological data. Results: 524 patient records included in the study with a sex ratio of 1.3. The mean age of the patients was 37 +/-15 years. There were 285 positive GeneXpert samples, of which 224 were of pulmonary origin and 61 of extra-pulmonary origin. The number of rifampicin resistant samples was five, all of respiratory origin. Conclusion: the Xpert test is a new molecular technique recommended by the WHO in the diagnosis of pulmonary tuberculosis

Clinical study of GeneXpert combined with T-SPOT and TB-Ab on bacterial-negative pulmonary tuberculosis / 中国热带医学

@#Abstract: Objective　To investigate the diagnostic efficacy of rifampin-resistant real-time fluorescent quantitative nucleic acid amplification detection technology (GeneXpert MTB/RIF) in bronchoalveolar lavage fluid (BALF) combined with peripheral blood tuberculosis infection T cell spot test (T-SPOT) and tuberculosis antibody (TB-Ab) in smear-negative pulmonary tuberculosis. Methods　The clinical data of 114 cases of clinically diagnosed smear-negative pulmonary tuberculosis, 80 cases of non-tuberculous pulmonary diseases and 22 cases of smear-positive pulmonary tuberculosis in our hospital from January 2019 to January 2021 were retrospectively analyzed. The detection results of peripheral blood T-SPOT, TB-Ab and BALF GeneXpert in the three groups were analyzed. The sensitivity, specificity, negative predictive value, positive predictive value, false negative rate, false positive rate and Youden index of the three detection methods were compared. The differences in the positive detection rate of smear-negative pulmonary tuberculosis between the separate detection and the combined detection of the three methods were compared. The receiver operating characteristic curve (ROC) was performed to calculate the area under the curve (AUC). Results　The sensitivity of BALF GeneXpert and peripheral blood T-SPOT and TB-Ab was 66.91%, 80.88% and 90.44%, respectively. The specificity was 98.75%, 73.75% and 41.25%, respectively; the diagnostic coincidence rates were 78.70%, 78.24% and 72.22%, respectively, which were higher than 70.00%. In the smear-negative pulmonary tuberculosis group, the positive detection rates of these three methods in the smear-negative pulmonary tuberculosis group were 63.15%, 79.82% and 90.35%, respectively, and the differences were statistically significant compared with those in the non-tuberculosis pulmonary disease group (all P<0.01). The positive detection rate of the three combined methods in the smear-negative pulmonary tuberculosis group was 96.49 %, which was significantly higher than that of TB-GeneXpert method and T-SPOT, and the differences were statistically significant (χ2=37.283, P<0.01; χ2=13.612, P<0.01); the Youden index of combined detection was significantly higher than that of single detection, and the AUC of combined detection was 0.977, which was significantly higher than that of single detection. Conclusion　BALF GeneXpert combined with peripheral blood T-SPOT and TB-Ab can significantly improve the diagnostic rate of bacterial-negative pulmonary tuberculosis, providing a strong basis for guiding clinical treatment.

De la Hogra al Hirak: neocolonialismo, memoria y disidencia política juvenil en el Rif / From Hogra to Hirak: Neocolonialism, memory and youth political dissidence in the Rif / De Hogra para Hirak: Neocolonialismo, memória e dissidência política juvenis no Rif

Resumen (analítico) Las teorías sobre movimientos sociales dominantes basadas en experiencias occidentales, pero ¿en qué medida pueden ayudarnos a comprender el proceso de construcción solidaria de prácticas políticas en contextos no occidentales políticamente cerrados? Según Bayat parece imprescindible una aproximación teórica que tenga en cuenta tanto la excepcionalidad árabe como la aplicación crítica de los modelos de las ciencias sociales en otros contextos que, muchas veces, olvidan los rasgos específicos que la protesta política ha adoptado en el mundo árabe. Este artículo, en el marco del proyecto Transgang, analizará un movimiento social marroquí aparecido en el Rif en 2016, protagonizado por poblaciones en edad juvenil, atendiendo a sus especificidades culturales usando las perspectivas decoloniales. Con este análisis, se presentarán algunas conclusiones para la investigación sobre movimientos sociales juveniles en sociedades árabes.

Abstract (analytical) Dominant social movement theories are based on Western experiences, but to what extent can they help us to understand the process of solidarity construction of political practices in closed political non-Western contexts? As Bayat points out, a theoretical approach that takes into account both the Arab exceptionality and the critical application of social science models in other contexts -that often forget the specific features that political protest has adopted in the Arab World- seems essential. This article, within the framework of the Transgang project, will analyse a Moroccan social movement that appeared in the Rif in 2016, led by youth populations, attending to their cultural specificities, and using decolonial perspectives. Through this analysis, some conclusions will be presented for research on youth social movements in Arab societies.

Resumo (analítico) As teorias sobre os movimentos sociais dominantes são baseadas em experiências ocidentais. No entanto, ¿em que medida elas podem nos ajudar a compreender o processo de construção solidária de práticas políticas em contextos politicamente autoritário não-ocidentais? Bayat e a sua excepcionalidade árabe nos advertem que, nas ciências sociais, o uso de modelos epistemológicos ocidentais em contextos não-ocidentais tem frequentemente esquecido as múltiplas particularidades desses territórios, sociedades, dos processos que nelas surgem e se desenvolvem. Este artigo, no âmbito do projeto Transgang, tomará como caso de estudo um movimento social que surgiu na região do Rif em 2016 o qual foi liderado por jovens, visando analisar as suas particularidades culturais a partir de perspectivas decoloniais. Finalmente, apresentar-se-ão algumas conclusões abertas para futuras pesquisas sobre movimentos sociais juvenis nas sociedades árabes.

Tuberculous Laryngitis mimicking as Fungal Laryngitis: A case report

@#Tuberculous laryngitis was considered common during pre-antibiotic area but after the effective antitubercular medication, the incidence of laryngeal tuberculosis had decreased to less than one percent2. Clinical presentation is mostly unclear but usually presents with odynophagia, cough, hoarseness of voice and frequently confused with other diseases, more importantly fungal laryngitis. This is a case of a diagnostic dilemma of an immunocompetent 55-year-old male presenting with odynophagia, dysphagia and hoarseness of voice that was initially managed as a case of fungal laryngitis due to history of prolonged use of dexamethasone and findings of leukoplakia in laryngoscopy. Despite adequate time for treatment, no significant improvement was noted. Acid fast bacilli microscopy tested negative. A previous history of pulmonary tuberculosis treatment and chest radiographs revealing fibrosis on both upper lungs puts tuberculous laryngitis as one of the differentials. Sputum GeneXpert/RIF taken and tested positive, hence lead to the diagnosis of tuberculous laryngitis. Guideline-based quadruple anti-tubercular therapy started and had showed a positive response. Laryngeal tuberculosis (LTB) requires a high index of suspicion since it mimics various laryngeal diseases such as fungal laryngitis or malignancy. Clinicians should always be aware of the atypical clinical features of laryngeal tuberculosis and the possibility of primary laryngeal tuberculosis, for early diagnosis and prompt treatment, thus preventing morbid complications. A positive mycobacterial culture along with a typical histopathological appearance remain the cornerstone of diagnosis, but sputum AFB in microscopy and GeneXpert/RIF must not be ignored as these can be cost-effective diagnostic alternatives.

Cost-effectiveness of Xpert®MTB/RIF in the diagnosis of tuberculosis: pragmatic study

Abstract INTRODUCTION: The intensification of research and innovation with the creation of networks of rapid and effective molecular tests as strategies for the end of tuberculosis are essential to avoid late diagnosis and for the eradication of the disease. We aimed to evaluate the cost-effectiveness of Xpert®MTB/RIF (Xpert) in the diagnosis of drug-resistant tuberculosis in reference units, in scenarios with and without subsidies, and the respective cost adjustment for today. METHODS: The analyses were performed considering as criterion of effectiveness, negative culture or clinical improvement in the sixth month of follow-up. The comparison was performed using two diagnostic strategies for the drug susceptibility test (DST), BactecTMMGITTM960 System, versus Xpert. The cost effectiveness and incremental cost-effectiveness ratio (ICER) were calculated and dollar-corrected for American inflation (US$ 1.00 = R$ 5,29). RESULTS: Subsidized Xpert had the lowest cost of US$ 33.48 (R$67,52) and the highest incremental average efficiency (13.57), thus being a dominated analysis. After the inflation was calculated, the mean cost was DST-MGIT=US$ 74.85 (R$ 396,73) and Xpert = US$ 37.33 (R$197,86) with subsidies. CONCLUSIONS: The Xpert in the diagnosis of TB-DR in these reference units was cost-effective with subsidies. In the absence of a subsidy, Xpert in TB-DR is not characterized as cost effective. This factor reveals the vulnerability of countries dependent on international organizations' subsidy policies.

Rendimiento del GeneXpert en el diagnóstico de tuberculosis pulmonar y extrapulmonar en la edad pediátrica / GeneXpert for the diagnosis of pulmonary and extrapulmonary tuberculosis in pediatric patients / GeneXpert para o diagnóstico da tuberculose pulmonar e extrapulmonar em pacientes pediátricos

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Summary: Introduction: the World Health Organization (WHO) recommends molecular biology techniques, such as Xpert MTB/RIF, for the diagnosis of tuberculosis (TB) and for the detection of Rifampicin resistance. In Uruguay, the Xpert MTB/RIF has been used since 2014, and no research papers have yet assessed its performance. A Cochrane review recommends the assessment of the Xpert diagnostic accuracy in difficult to diagnose groups, such as, children, people living with HIV and with extrapulmonary tuberculosis. Objectives: describe cases of TB in children of under 15 years of age in Uruguay during 2018 and 2019 and describe the influence of the various diagnostic tests on the bacteriological confirmation of the disease. Evaluate the performance of the Xpert MTB/RIF for the diagnosis of TB in respiratory and non- respiratory samples using the culture as a reference standard. Compare the performance of GeneXpert with smear microscopy for TB diagnosis. Material and methods: analytical, retrospective study of children of under 15 years of age in Uruguay between January 2018 and June 2019, based on data obtained from the PNC-TB information system. Clinical-epidemiological characteristics of the TB cases were described. Definitions were taken from CHLA-EP, as per WHO recommendations. All respiratory and non-respiratory samples received by the National Reference Laboratory in Tuberculosis of the CHLA-EP from 1/1/2018 to 6/30/2019, entered in the IT system ("TB soft") were analyzed; they belonged to patients with clinical suspicion of TB, studied as contacts, or to TB risk groups (patients with immunodeficiency or at risk of immunosuppression, mainly). All samples underwent smear microscopy and/or Xpert MTB/RIF (according to the CHLA-EP protocol) and culture. The detection of Rifampicin resistance in the Xpert was compared with first- line drug sensitivity tests using molecular methods made from the cultures. The sensitivity, specificity, PPV and NPV of GeneXpert and ZN microscopy were calculated using Mycobacterium tuberculosis culture as gold standard. We calculated the Xpert positive and negative likelihood ratio (LR). Results: 67 patients under 15 years of age were diagnosed with TB, and 46% cases were bacteriologically confirmed. A total of 1670 samples were analyzed; 82% respiratory and 17% non-respiratory. A total of 32 samples showed a positive culture for M. tuberculosis (14 respiratory and 18 non- respiratory). One rifampicin resistance sample was detected in the Xpert that was not confirmed in the culture. The sensitivity of Xpert for all samples was 80%; the specificity 99,5%; PPV 80%; NPV 99,5%. In the case of smear microscopy for all samples: S 44,4%, specificity 99,4%, PPV 70,6%; NPV 98,2%. Respiratory samples: Xpert S 100%; E 99,4%; PPV 66,7%; NPV 100%. Bacilloscopy: S 72,7%; E 99,6%; PPV 72,7%; NPV 99,6%. Non-respiratory samples: Xpert S: 66,7%; E 100%; PPV 100%; NPV 97,9%. Bacilloscopy: S 25%; E 98,8%; PPV 66,7%; NPV 93,2%. The LR + of the Xpert for all samples was 160 and the LR - 0,2. Conclusions: TB in children under 15 remains difficult to diagnose. Bacteriological confirmation was attempted in 88% of TB cases, and almost 50% showed positive results by some bacteriological technique. The Xpert showed a good sensitivity and specificity profile in both respiratory and non-respiratory samples, similar to those reported in international papers. The main contribution in relation to smear microscopy is the greater sensitivity for the diagnosis of TB in children under 15 years of age. The Xpert is very useful for TB diagnosis when it is positive, although it does not ensure we can rule out the disease in case of negative results.

Resumo: Introdução: a Organização Mundial da Saúde (OMS) recomenda técnicas de biologia molecular, como o Xpert MTB / RIF para o diagnóstico de tuberculose (TB) e para a detecção de resistência à Rifampicina. No Uruguai, o Xpert MTB / RIF é usado desde 2014, e o seu desempenho ainda não tem sido avaliado. Uma revisão recente da Cochrane promove que pesquisas futuras devem avaliar a precisão diagnóstica do Xpert, em grupos difíceis de diagnosticar, como crianças, pessoas vivendo com HIV e pessoas com tuberculose extrapulmonar. Objetivos: descrever os casos de tuberculose em crianças menores de 15 anos no Uruguai nos anos 2018-2019 e a contribuição dos diferentes testes de diagnóstico na confirmação bacteriológica da doença. Avaliar o desempenho do Xpert MTB / RIF para o diagnóstico de TB em amostras respiratórias e não respiratórias de pacientes menores de 15 anos, utilizando a cultura como padrão de referência. Comparar o desempenho do GeneXpert com a baciloscopia para o diagnóstico da TB. Material e métodos: estudo analítico e retrospectivo de crianças menores de 15 anos estudadas para TB no Uruguai entre janeiro de 2018 e junho de 2019, utilizando a base em dados do sistema informático PNC-TB. Descrevemos as características clínico-epidemiológicas dos casos de TB. As definições foram retiradas do CHLA-EP de acordo com as recomendações da OMS. Todas as amostras respiratórias e não respiratórias recebidas pelo Laboratório Nacional de Referência (LNR) em Tuberculose do CHLA-EP de 01/01/2018 a 30/06/2019, inseridas no sistema computacional (TB Soft), corresponderam a pacientes com suspeita clínica de TB, estudados como contatos ou na detecção de TB em grupos de risco (pacientes com imunodeficiências ou com risco de imunossupressão, principalmente). As amostras foram realizadas por esfregaço (baciloscopia) e/ou Xpert MTB/RIF (de acordo com o protocolo CHLA-EP) e por cultura. A detecção da resistência à Rifampicina no Xpert foi comparada com os testes de sensibilidade a drogas de primeira linha (PSD), utilizando os métodos moleculares das culturas. A sensibilidade, especificidade, PPV e NPV do Xpert e esfregaço foram calculados usando a cultura como padrão de referência. Calculamos a razão de verossimilhança positiva e negativa (LR) do Xpert. Resultados: 67 crianças menores de 15 anos foram diagnosticadas com TB, e 46% dos casos foram confirmados bacteriologicamente. 1670 amostras foram analisadas; 82% respiratórias e 17% não respiratórias. 32 amostras tiveram uma cultura positiva para M. tuberculosis (14 respiratórias e 18 não respiratórias). A sensibilidade (S) do Xpert para todas as amostras foi de 80% (IC95% 37,5-96,3), especificidade (E) 99,5% (IC95% 97,3-99,9), PPV 80% (37,5-96,3), NPV 99,5% (97,3-99,9). Baciloscopia: S de 46,1% (28,7-64,5), E 99,5% (98,7-99,8), PPV 75% (50,5-89,8), VPL 98,3% (97,2-99). Amostras respiratórias: Xpert S 100%; E 99,3% VPP 66% e VPN 100%. Baciloscopia: S 66,6%, E 99,8%, PPV 80%, NPV 99,7%. Amostras não respiratórias: Xpert S: 66,6%, E 100%, PPV 100%, NPV 97,9%; Esfregaço S: 25%, E 99,3%, PPV 80%, NPV 93%. O LR + do Xpert para todas as amostras foi de 160 e o LR - 0,2. Conclusões: a TB em crianças menores de 15 anos é ainda difícil de diagnosticar. Tentamos a confirmação bacteriológica em 88% dos casos de TB, e quase 50% deles tiveram resultados positivos utilizando alguma técnica bacteriológica. O Xpert mostrou um bom perfil de sensibilidade e especificidade em amostras respiratórias e não respiratórias, semelhante ao relatado em papers internacionais. A principal contribuição em relação à baciloscopia é a maior sensibilidade para o diagnóstico de TB em menores de 15 anos. O Xpert é muito útil para o diagnóstico de TB em caso de ser positivo, embora não permita descartar a doença em casos negativos.

Combination Of Momordica Charantia And Phyllanthus Amarus For Hepatoprotective Activity In Ethanol And Anti-Tubercular Drugs Induced Hepatotoxicity In Rats

Objective: To evaluate the synergistic protective effect of Momordica charantia and Phyllanthus amarus combination (MC+PA) of doses 200 and 400 mg/kg on the liver in different experimental models of hepatotoxicity. Methods: The hepatoprotective activity was evaluated in ethanol and anti-tubercular drugs (isoniazid-INH, rifampicin-RIF) induced hepatotoxicity models. Hepatotoxicity in both models was induced to all groups except the normal control. Intoxicated rats were treated with silymarin and various doses of MC+PA for 8 d in ethanol-induced and 21 d in INH+RIF induced hepatotoxicity models. At the completion of study, the biochemical markers and the anti-oxidant status (SOD and MDA) were measured and also the histopathological evaluation of the liver tissue was carried out. Results: Combination therapy remarkably reduced the elevated profile of the biochemical markers and thereby improved the anti-oxidant status, thus exhibiting the synergistic hepatoprotective effect when compared with the positive control group (p<0.001). Histopathological evaluation demonstrated that MC+PA decreased the liver damage significantly in comparison with the positive group. Conclusion: The current work suggests that the combined extract showed synergistic effects on ethanol and anti-tubercular drugs induced hepatotoxicity models by significantly decreasing the liver damage.

Jejunal gastrointestinal stromal tumors masquerading as an appendicular mass: an unusual presentation

Gastrointestinal stromal tumors (GISTs) are a rare variety of tumors of mesenchymal origin found in the gastrointestinal (GI) tract forming about 1% of all GI tumors. These originate from the interstitial cells of Cajal. Small bowel GISTs have been shown to present as obscure GI bleeding, obstruction and perforation in literature. We report a 57 years old female patient presenting with pain abdomen, fever and vomiting and palpable right iliac fossa (RIF) mass diagnosed as an appendicular mass and managed conservatively. She was planned interval appendicectomy and was discovered to have a jejunal GIST at laparotomy treated with resection and anastomosis. There are case reports of small bowel GISTs presenting as sources of obscure or overt GI bleeding and luminal or extra luminal mass causing small bowel obstruction. Surgery is mainstay of treatment with imatinib for adjuvant or neoadjuvant therapy. This case highlights an unusual presentation of a jejunal GIST with a sealed off perforation mimicking an appendicular mass in the RIF treated by surgical resection followed by adjuvant Imatinib therapy. GIST being an uncommon tumor with varied presentations can lead to misdiagnosis and delays in treatment. This differential should be kept in mind while evaluating small bowel pathologies to aid a timely diagnosis.

Serious discordance between MTBC trace positivity by Xpert MTB/RIF ultra and follow up culture

Authors wish to report a major discordance between Xpert MTB/RIF Ultra Trace positivity (GeneXpert, Cepheid) and follow up by liquid culture.

GeneXpert MTB/RIF evaluated in diagnosis of pulmonary tuberculosis / 上海预防医学

Objective To evaluate GeneXpert MTB/RIF in diagnosis of pulmonary tuberculosis by comparing the lab results of diagnosed patients. Methods A total of 97 diagnosed pulmonary tuberculosis patients were enrolled from July 2017 to June 2018.Sputum smear microscopy (Ziehl-Neelsen stain), sputum culture (MGIT liquid culture) and Xpert MTB/RIF were conducted in all patients.Drug susceptibility test and strain identification by PNB were done for culture positive sputum samples.Consistency rate was calculated. Results In terms of M.tuberculosis detection, sensitivity and specificity of GeneXpert were 93.44% and 55.55%, respectively, compared with bacteriological examination (consistency rate 79.38%).Consistency rate of GeneXpert and PNB is 94.55%.In terms of RIF resistance test, sensitivity and specificity of GeneXpert were 66.67% and 98.08%, respectively, compared with phenotypic drug-susceptibility testing (consistency rate 96.36%). Conclusion GeneXpert MTB/RIF can be utilized in combination with smear microscopy and liquid culture to diagnose more etiologically positive patients, and can spot RIF resistance patients early.But strain identification and drug susceptibility test are still needed for individualized therapy and optimal treatment outcome.

GeneXpert MTB/RIF evaluated in diagnosis of pulmonary tuberculosis / 上海预防医学

Objective To evaluate GeneXpert MTB/RIF in diagnosis of pulmonary tuberculosis by comparing the lab results of diagnosed patients. Methods A total of 97 diagnosed pulmonary tuberculosis patients were enrolled from July 2017 to June 2018.Sputum smear microscopy (Ziehl-Neelsen stain), sputum culture (MGIT liquid culture) and Xpert MTB/RIF were conducted in all patients.Drug susceptibility test and strain identification by PNB were done for culture positive sputum samples.Consistency rate was calculated. Results In terms of M.tuberculosis detection, sensitivity and specificity of GeneXpert were 93.44% and 55.55%, respectively, compared with bacteriological examination (consistency rate 79.38%).Consistency rate of GeneXpert and PNB is 94.55%.In terms of RIF resistance test, sensitivity and specificity of GeneXpert were 66.67% and 98.08%, respectively, compared with phenotypic drug-susceptibility testing (consistency rate 96.36%). Conclusion GeneXpert MTB/RIF can be utilized in combination with smear microscopy and liquid culture to diagnose more etiologically positive patients, and can spot RIF resistance patients early.But strain identification and drug susceptibility test are still needed for individualized therapy and optimal treatment outcome.

The reliability of a rapid molecular detection method in determining the prevalence of rifampicin-resistant Mycobacterium tuberculosis in an urban district health facility in Malaysia

@#Introduction: Rifampicin is a key first-line antimycobacterial agent employed for the treatment of pulmonary tuberculosis (PTB). This study sought to obtain prevalence data on rifampicin-resistant Mycobacterium tuberculosis among smear-positive PTB patients in the Klang District of Malaysia. Materials and Methods: A total of 103 patients from the Chest Clinic of Hospital Tengku Ampuan Rahimah with sputum smears positive for acid-fast bacilli were included in this cross-sectional study. All sputa were tested using Xpert MTB/RIF to confirm the presence of M. tuberculosis complex and detect rifampicin resistance. Sputa were also sent to a respiratory medicine institute for mycobacterial culture. Positive cultures were then submitted to a reference laboratory, where isolates identified as M. tuberculosis complex underwent drug susceptibility testing (DST). Results: A total of 58 (56.3%) patients were newly diagnosed and 45 (43.7%) patients were previously treated. Xpert MTB/RIF was able to detect rifampicin resistance with a sensitivity and specificity of 87.5% and 98.9%, respectively. Assuming that a single resistant result from Xpert MTB/RIF or any DST method was sufficient to denote resistance, a total of 8/103 patients had rifampicinresistant M. tuberculosis. All eight patients were previously treated for PTB (p<0.05). The overall prevalence of rifampicin resistance among smear-positive PTB patients was 7.8%, although it was 17.8% among the previously treated ones. Conclusion: The local prevalence of rifampicin-resistant M. tuberculosis was particularly high among previously treated patients. Xpert MTB/RIF can be employed in urban district health facilities not only to diagnose PTB in smear-positive patients, but also to detect rifampicin resistance with good sensitivity and specificity.

Value of GeneXpertMTB/RIF and Hain techniques for the diagnosis of sputum smear negative tuberculosis and for the assessment of rifampin resistance / 公共卫生与预防医学

Objective To investigate the application value of Xpert mycobacterium tuberculosis/rifampicin (GeneXpertMTB/RIF) and Hain techniques for the diagnosis of sputum smear negative tuberculosis and for the assessment of rifampin resistance. Methods A total of 254 patients with suspected pulmonary tuberculosis treated in our hospital from March 2018 to June 2019 were enrolled. GeneXpertMTB/RIF, Hain techniques, Roche culture and drug susceptibility testing were performed. Taking Roche culture results as a gold standard, the efficacy of GeneXpertMTB/RIF and Hain techniques in detecting sputum smear-negative pulmonary tuberculosis was analyzed by ROC curve. Based on the results of drug susceptibility testing, the efficacy of GeneXpertMTB/RIF and Hain techniques in detecting rifampicin resistance was analyzed. Results The sensitivity, specificity and accuracy of GeneXpertMTB/RIF in the diagnosis of sputum smear negative pulmonary tuberculosis were 82.18%, 86.93% and 83.52%, respectively. The sensitivity, specificity and accuracy of Hain technique in the diagnosis of sputum smear negative pulmonary tuberculosis were 67.33%, 77.12% and 73.23%, respectively. The sensitivity, specificity and accuracy of GeneXpertMTB/RIF in evaluating rifampicin resistance were 73.33%, 98.84% and 95.05%, respectively. The sensitivity, specificity and accuracy of Hain technique in evaluating rifampicin resistance were 86.67%, 82.56% and 83.17%, respectively. Conclusion Compared with Hain technology, GeneXpertMTB/RIF had better clinical value for diagnosis of sputum smear negative tuberculosis and for the assessment of rifampin resistance. This study demonstrates that GeneXpertMTB/RIF technique has a good application value in the rapid diagnosis and treatment of sputum smear negative pulmonary tuberculosis.

Accuracy of Xpert® MTB/RIF for the detection of tuberculosis and rifampicin-resistance tuberculosis in China: A systematic review and meta-analysis / 北京大学学报(医学版)

OBJECTIVE@#To systematically review the diagnostic accuracy of Xpert® Mycobacterium tuberculosis/rifampicin (Xpert® MTB/RIF) for the detection of active tuberculosis (TB) and rifampicin-resistance TB in Chinese patients.@*METHODS@#Four Chinese databases (SinoMed, CNKI, WanFang database, and VIP) and three English databases (PubMed, Embase, and The Cochrane Library) were searched from January 1, 2000 to September 15, 2017, to identify diagnostic tests about the accuracy of Xpert® MTB/RIF in Chinese patients. Two investigators screened the articles and extracted the information independently, and then the quality of each included study was evaluated by Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2. Bivariate random-effects meta-analysis was conducted to pool the sensitivity and specificity. In addition, subgroup analyses were performed based on patient type (TB patient and TB suspected patient), sample type (sputum, bronchoalveolar lavage fluid and others). All statistical analyses were conducted with Stata version 13.0.@*RESULTS@#A total of 47 articles were included in this systematic review. Most of them (38 articles) were in Chinese and only 9 articles were in English. All the articles were published during 2014 to 2017, and the sample size ranged from 31 to 3 151. Forty articles including 42 comparisons about TB were finally included with the pooled sensitivity of 0.94 (95%CI: 0.92, 0.95) and the pooled specificity of 0.87 (95%CI: 0.84, 0.91). Subgroup analysis showed that different patient and specimen types had no significant differences on sensitivity, but the specificity of sputum group was higher than that of bronchoalveolar lavage fluid. As for the detection of rifampicin-resistant TB, 33 articles (38 comparisons) were analyzed, the pooled sensitivity and specificity were 0.92 (95%CI: 0.89, 0.94) and 0.98 (95%CI: 0.97, 0.99) respectively. There were no significant differences between the patient and specimen in the subgroup analyses. The Deeks funnel plot showed a possible publication bias for detecting active tuberculosis (P=0.08) and no publication bias for rifampicin-resistant TB (P=0.24). The likelihood ratio scatter gram showed that in clinical applications, Xpert® MTB/RIF had a good diagnostic ability for detecting active tuberculosis, and it had good clinical diagnostic value in detecting rifampicin-resistant TB.@*CONCLUSION@#Xpert® MTB/RIF has good sensitivity and specificity in detecting TB and rifampicin-resistant TB in Chinese people. In particular, it has good clinical value in diagnosing rifampicin-resistance TB.