ABSTRACT OBJECTIVES To evaluate the performance of geneXpert MTB/Rif versus conventional methods (bacilloscopy and culture) in the diagnosis of tuberculosis in a Central Public Health Laboratory (LACEN, Tocantins), Northern Brazil. METHODS Retrospective study, with information from 1,973 suspected cases of tuberculosis from patients treated from January 2015 to December 2020. RESULTS From the culture (reference standard), the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the geneXpert MTB/Rif were 100%, 97%, 74%, 100%, and 97%, respectively, against 85%, 98%, 80%, 98%, and 97% of bacilloscopy. CONCLUSIONS The geneXpert MTB/Rif performed similarly to culture and better than bacilloscopy. Although positive cases with negative culture should be evaluated with caution, its routine use is important for the early detection of tuberculosis.

RESUMO Introdução: A infecção tuberculosa afeta o mundo apesar de anos de estudo e avanços tecnológicos no seu diagnóstico.O ensaio Xpert® MTB/RIF permite, em grande medida, a identificação do bacilo de Koch em qualquer amostra patológica, e fá-lo com elevada sensibilidade, especificidade e rapidez em comparação com outros métodos. Objetivo: Diagnosticar tuberculose com o ensaio Xpert® MTB/RIF. Método: Foi realizado um estudo transversal em 46 amostras analisadas (n 46) das províncias orientais de Cuba com o ensaio Xpert® MTB/RIF, entre abril e setembro de 2023, pelo Centro Provincial de Higiene, Epidemiologia e Microbiologia de Holguín.As variáveis estudadas foram: província de origem, idade, sexo, tipo de amostra, fatores de risco, resultado de exame e resistência à rifampicina. Resultados: Santiago de Cuba e Guantánamo foram as províncias que notificaram o maior número de casos, com 14 casos cada (30,4%).O sexo masculino teve a maior incidência, 33 casos (71,7%), independentemente da província.A faixa etária de 25 a 34 anos foi a que apresentou maior prevalência, com 26,1%.Os grupos de risco mais acometidos foram: fumantes (37,0%), presidiários (32,6%), adultos acima de 60 anos (26,6%) e alcoolistas (23,9%). Conclusões: A introdução do GeneXpert no seu diagnóstico é muito eficaz, devido à sua alta sensibilidade e especificidade em relação aos estudos tradicionais, como baciloscopia e cultura, além da rapidez na obtenção do resultado.Também relata a resistência à rifampicina, atribuível ao gene rpoβ, que é muito oportuna numa altura em que a resistência a múltiplos medicamentos está a aumentar rapidamente.

RESUMEN Introducción: La infección por tuberculosis repercute en el mundo a pesar de los años de estudio y avances tecnológicos en su diagnóstico. El ensayo Xpert® MTB/RIF permite, en gran medida, la identificación del bacilo de Koch en cualquier muestra patológica, y lo hace con una alta sensibilidad, especificidad y rapidez con respecto a otros métodos. Objetivo: Realizar el diagnóstico de tuberculosis con ensayo Xpert® MTB/RIF. Método: Se realizó un estudio transversal en 46 muestras analizadas (n=46) de las provincias orientales de Cuba con ensayo Xpert® MTB/RIF, entre abril y septiembre de 2023, por el Centro Provincial de Higiene, Epidemiología y Microbiología de Holguín. Las variables estudiadas fueron: provincia de procedencia, edad, sexo, tipo de muestra, factores de riesgo, resultado al ensayo y resistencia a la rifampicina. Resultados: Santiago de Cuba y Guantánamo fueron las provincias que mayor cantidad de casos reportaron, con 14 casos cada una (30,4 %). El sexo masculino fue el de mayor incidencia, 33 casos (71,7 %), independientemente de la provincia. El grupo de edad de 25 a 34 años fue el de mayor prevalencia, con el 26,1 %. Los grupos de riesgos más afectados fueron: los fumadores (37,0 %), los reclusos (32,6 %), los adultos mayores de 60 años (26,6 %) y los alcohólicos (23,9 %). Conclusiones: La introducción del GeneXpert en su diagnóstico es muy efectivo, por su alta sensibilidad y especificidad con relación a los estudios tradicionales, como son la baciloscopia y el cultivo, además de la rapidez en la obtención del resultado.Informa también sobre la resistencia a la rifampicina, atribuible al gen rpoβ, lo que resulta muy oportuno en momentos en que la multidrogorresistencia aumenta aceleradamente.

ABSTRACT Introduction: Tuberculosis infection affects the world despite years of study and technological advances in its diagnosis.The Xpert® MTB/RIF test allows, to a largeextent, the identification of Koch bacillus in any pathological sample, and does so with high sensitivity, specificity and speed compared too ther methods. Objective: To diagnose tuberculosis with the Xpert® MTB/RIF test. Method: A cross-sectional study was carried out on 46 analyzed samples (n 46) from the eastern provinces of Cuba with the Xpert® MTB/RIF test, between April and September 2023, by the Centro Provincial de Higiene, Epidemiología y Microbiología de Holguín (Provincial Center of Hygiene, Epidemiology and Microbiology of Holguín).The variables studied were: province of origin, age, sex, type of sample, risk factors, test resultand resistance to rifampicin. Results: Santiago de Cuba and Guantánamo were the provinces that reported the highest number of cases, with 14 cases each(30.4%).The maleshad the highest incidence, 33 cases (71.7%), regardless of the province.The age group of 25 to 34 years was the one with the highest prevalence, with 26.1%.The most affected risk groups were: smokers (37.0%), prisoners (32.6%), adults over 60 years of age (26.6%) and alcoholics (23.9%). Conclusions: The introduction of GeneXpert in tuberculosis diagnosis is very effective, due to its high sensitivity and specificity in relation to traditional studies, such as smear microscopy and culture, in addition to the speed in obtaining the result. It also reports on resistance to rifampicin, attributable to the rpoβ gene, which is timely at a moment when multidrug resistance is increasing rapidly.

Resumo A tuberculose é uma doença transmissível com altas taxas de morbimortalidade nos países em desenvolvimento. O objetivo principal do estudo é comparar métodos convencionais, como cultura de bacilo álcool-ácido resistente (BAAR) e microscopia, com métodos de diagnóstico rápido. O objetivo secundário é comparar os achados histopatológicos e microbiológicos em pacientes com suspeita de linfadenite tubercular. Um total de 111 amostras (agosto de 2018 a setembro de 2019) de gânglios linfáticos foi processado para microscopia de AFB, culturas de AFB, teste de susceptibilidade a drogas (DST), histopatologia e Xpert Mycobacterium tuberculosis (MTB)/ensaios de resistência à rifampicina (RIF). Das 111 amostras de linfonodos, 6 (5,4%) foram positivas para baciloscopia de AFB, 84 (75,6%) foram positivas para cultura de AFB, 80 (70,7%) foram positivas para o GeneXpert e 102 (91,8%) foram indicativas de tuberculose para estudos histopatológicos. A positividade da cultura do tubo indicador de crescimento de micobactérias (MGIT) foi 84 (75,6%), maior que a cultura sólida de Lowenstein-Jensen (LJ), 74 (66,6%). As culturas positivas foram submetidas a DST fenotípico. Dois casos eram multirresistentes (MDR) ao DST, enquanto três casos eram resistentes à rifampicina no GeneXpert. A sensibilidade do GeneXpert foi 62% contra o método convencional de cultura AFB. O fraco desempenho dos métodos convencionais de diagnóstico de linfadenite requer metodologia de diagnóstico precoce e precisa. O teste Xpert MTB/RIF pode ajudar no tratamento de casos de tuberculose multirresistente. No entanto, métodos rápidos e convencionais devem ser usados para o isolamento completo do Mycobacterium tuberculosis.

Abstract Tuberculosis is a communicable disease with high morbidity and mortality rates in developing countries. The study's primary objective is to compare conventional methods such as acid-fast bacillus (AFB) culture and microscopy with rapid diagnostic methods. The secondary objective is to compare histopathological and microbiological findings in suspected patients with tubercular lymphadenitis. A total of 111 samples (August 2018 to September 2019) of lymph nodes were processed for AFB microscopy, AFB cultures, drug-susceptibility testing (DST), histopathology, and Xpert Mycobacterium Tuberculosis (MTB)/resistance to Rifampin (RIF) assays. Out of 111 lymph node samples, 6 (5.4%) were positive for AFB smear microscopy, 84 (75.6%) were positive for AFB culture, 80 (70.7%) were positive on Gene Xpert, and 102 (91.8%) were indicative of tuberculosis for histopathology studies. Mycobacteria growth indicator tube (MGIT) culture positivity was 84 (75.6%) higher than solid Lowenstein-Jensen (LJ) culture 74 (66.6%). Positive cultures underwent phenotypic DST. Two cases were Multidrug-resistant (MDR) on DST, while three cases were Rifampicin resistant on Gene Xpert. The sensitivity of Genexpert was (62%) against the conventional AFB culture method. The poor performance of conventional lymphadenitis diagnostic methods requires early and accurate diagnostic methodology. Xpert MTB/RIF test can help in the treatment of multidrug-resistant TB cases. Nonetheless, rapid and conventional methods should be used for complete isolation of Mycobacterium tuberculosis.

BACKGROUND: The rollout of GeneXpert aimed at increasing early diagnosis of tuberculosis to improve treatment outcomes and global tuberculosis targets. OBJECTIVE: This study evaluated trends in tuberculosis diagnosis and outcomes pre- and post-introduction of GeneXpert in three African countries - the Democratic Republic of the Congo (DRC), Nigeria and South Africa. METHODS: Data from 2001 to 2019 were extracted from the World Health Organization's data repository. Descriptive analysis, paired t-tests and interrupted time series models were used. RESULTS: Estimated tuberculosis incidence decreased from 327/100 000 to 324/100 000 in the DRC, and from 1220/100 000 to 988/100 000 in South Africa. Incidence remained at 219/100 000 in Nigeria. The tuberculosis case notification rate did not change significantly. Increases in the new case treatment success rates were statistically significant (DRC: p = 0.0201; Nigeria: p = 0.0001; South Africa: p = 0.0017); decreases in mortality were also statistically significant (DRC: p = 0.0264; Nigeria: p = 0.0001; South Africa: p < 0.0001). Time series models showed insignificant increases in new tuberculosis cases in DRC (n = 1856, p = 0.085) and Nigeria (n = 785, p = 0.555) from 2011 to 2019; and a statistically significant decrease in South Africa (n = 15 269, p = 0.006). CONCLUSION: Improvements in tuberculosis treatment outcomes were achieved, but little progress has been made in new case notification due to varied implementation and scale-up of GeneXpert across the three countries. Implementation barriers need to be addressed to achieve the required tuberculosis targets.

RESUMEN La meningitis por Mycobacterium tuberculosis es la forma extrapulmonar más letal de la tuberculosis activa, con alta prevalencia en los países en desarrollo, lo que constituye un problema de salud pública. Las formas de presentación extrapulmonar que comprometen el sistema nervioso incluyen la tuberculosis meníngea, el granuloma tuberculoso, el absceso tuberculoso y la radiculomielitis, con una presentación clínica inespecífica que dificulta su oportuno diagnóstico, sumado a la falta de pruebas rápidas con alta sensibilidad y especificidad, el alto costo y la pobre asequibilidad a las pruebas en muchos países. El diagnóstico se basa en pruebas microbiológicas, moleculares y en aquellas basadas en la respuesta del huésped. El diagnóstico microbiológico se basa en la tinción de Ziehl-Neelsen y en el cultivo, este último considerado durante mucho tiempo la prueba diagnóstica de oro. El diagnóstico molecular es más preciso utilizando las pruebas de amplificación de ácidos nucleicos, la reacción en cadena de la polimerasa, la prueba de GeneXpert MTB/RIF y la prueba Xpert MTB/ RIF Ultra. Debido a la ausencia de una prueba rápida, existen escalas que ayudan a orientar el diagnóstico del paciente, dentro de las cuales merecen citarse la de Thwaites y la de Marais. El tratamiento de la tuberculosis de cepas sensibles incluye un esquema estructurado con isoniazida, rifampicina, pirazinamida y etambutol, sin embargo, en la actualidad la resistencia a los antimicrobianos constituye un problema, por lo cual el tratamiento en la tuberculosis multirresistente debe ser individualizado, con un régimen de tratamiento prolongado.

SUMMARY Mycobacterium tuberculosis meningitis is the most lethal extrapulmonary form of active tuberculosis with high prevalence in developing countries, which constitutes a public health problem. The extrapulmonary presentation that compromise the nervous system include meningeal tuberculosis, tuberculous granuloma, tuberculosis abscess and radiculomyelitis. A nonspecific clinical presentation, the lack of rapid tests with high sensitivity and specificity, the high cost and poor affordability of testing in many countries make the diagnosis more complicated. The diagnosis is based on microbiological, molecular, and host response based testing. Microbiological diagnosis is based on Ziehl - Neelsen staining and culture, the latter long considered the gold standard diagnostic test. Molecular diagnosis is more accurate using nucleic acid amplification tests, the chain reaction of polymerase, the GeneXpert MTB / RIF test, and the Xpert MTB / RIF Ultra test. Given the absence of a rapid test, there are scales that help guide the patient's diagnosis, within which the Thwaites Scale and the Marais Scale deserve to be mentioned. The treatment of tuberculosis of susceptible strains includes a structured regimen with isoniazid, rifampicin, pyrazinamide and ethambutol, however, antimicrobial resistance is currently a problem for which the treatment of multidrug-resistant tuberculosis must be individualized, with a long-term treatment regimen.

ABSTRACT In infections caused by Mycobacterium tuberculosis (Mtb), the clinical evolution is dissimilar, so it is important to achieve a quick and correct diagnosis, it is necessary to implement new diagnostic tools. In the present study, a comparison was made between the molecular technique GeneXpert MTB / RIF, an important diagnostic tool that also allows the detection of sensitivity and / or resistance to Rifampicin, and the established conventional diagnostic techniques; smear microscopy (BK) and culture in Löwenstein-Jensen (L-J), to demonstrate its diagnostic applicability from clinical samples. 287 samples from symptomatic patients were analyzed, 146 (50.9%) were HIV / AIDS patients. The highest percentage of Mtb detection was obtained by the GeneXpert MTB / RIF molecular technique, however, if we observe the difference between the percentage obtained by Xpert MTB / RIF and the bacteriological culture, it was not statistically significant, obtaining a value of p = 0.2324. It is important to note that Xpert MTB / RIF allowed us to detect resistance to Rifampicin in 3 patients. The BK was the technique that obtained the lowest percentage of positivity. This study reaffirmed the applicability of this molecular tool for the diagnosis of TB in both pulmonary and extrapulmonary samples; the shortening of the diagnostic time allows the clinician to start specific treatment, avoiding the spread of the infection in the patient.

RESUMEN En las infecciones producidas por Mycobacterium tuberculosis (Mtb) la evolución clínica es disímil, por lo que es importante lograr un rápido y correcto diagnóstico, se hace necesario implementar nuevas herramientas diagnósticas. En el presente estudio se realizó la comparación entre la técnica molecular GeneXpert MTB/RIF importante herramienta diagnóstica que permite también detectar la sensibilidad y/o resistencia a la Rifampicina, y las técnicas convencionales diagnósticas establecidas; baciloscopía (BK) y cultivo en Löwenstein-Jensen (L-J), para demostrar su aplicabilidad diagnóstica a partir de muestras clínicas. Se analizaron 287 muestras procedentes de pacientes sintomáticos, 146(50.9%) eran pacientes VIH/Sida. El mayor por ciento de detección de Mtb se obtuvo por la técnica molecular GeneXpert MTB/RIF, sin embargo, si observamos la diferencia entre el porciento obtenido por Xpert MTB/RIF y el cultivo bacteriológico no fue estadísticamente significativo obteniendo un valor de p=0.2324. Es importante señalar que Xpert MTB/RIF nos permitió detectar en 3 pacientes resistencia a la Rifampicina. La BK fue la técnica que obtuvo menor porciento de positividad. Este estudio reafirmó la aplicabilidad de dicha herramienta molecular para el diagnóstico de TB tanto en muestras pulmonares como extrapulmonares, el acortamiento de tiempo diagnóstico permite al clínico el inicio del tratamiento específico, evitando en el paciente la diseminación de la infección.

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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.

Abstract Objective To assess the impact of introducing Xpert as a follow-on test after smear microscopy on the total number pulmonary TB notifications. Method Genexpert systems were installed in six departments across Guatemala, and Xpert was indicated as a follow-on test for people with smear-negative results. We analyzed notifications to national tuberculosis (TB) programmes (NTP) and the project's laboratory data to assess coverage of the intervention and case detection yield. Changes in quarterly TB notifications were analyzed using a simple pre/post comparison and a regression model controlling for secular notification trends. Using a mix of project and NTP data we estimated the theoretical yield of the intervention if testing coverage achieved 100%. Results Over 18,000 smear-negative individuals were eligible for Xpert testing during the intervention period. Seven thousand, one hundred and ninety-three people (39.6% of those eligible) were tested on Xpert resulting in the detection of 199 people with smear-negative, Xpert positive results (2.8% positivity rate). In the year before testing began 1098 people with smear positive and 195 people with smear negative results were notified in the six intervention departments. During the intervention, smear-positive notification remained roughly stable (1090 individuals, 0.7%), but smear-negative notifications increased by 167 individuals (85.6%) to an all-time high of 362. After controlling for secular notifications trends over an eight-quarter pre-intervention period, combined pulmonary TB notifications (both smear positive and negative) were 19% higher than trend predictions. If Xpert testing coverage approached 100% of those eligible, we estimate there would have been a + 41% increase in TB notifications. Conclusions We measured a large gain in pulmonary notifications through the introduction of Xpert testing alone. This indicates a large number of people with TB in Guatemala are seeking health care and being tested, yet are not diagnosed or treated because they lack bacteriological confirmation. Wider use of more sensitive TB diagnostics and/or improvements in the number of people clinically diagnosed with TB have the potential to significantly increase TB notifications in this setting, and potentially in other settings where a low proportion of pulmonary notifications are clinically diagnosed.

Resumen Objetivo Evaluar el impacto en la notificación de casos de tuberculosis pulmonar de la introducción de Xpert como prueba de continuación después del análisis microscópico. Método Se instalaron sistemas Genexpert es seis departamentos de Guatemala y se indicó como prueba consecutiva en todos los resultados negativos en la baciloscopia microscópica. Se analizaron los datos del Programa Nacional y los del laboratorio del proyecto para medir la cobertura y la productividad en detección de casos. Las notificaciones trimestrales se compararon con los valores anteriores a la intervención y se adoptó un modelo de regresión para controlar por las tendencias temporales. Se estimó la contribución teórica de la intervención en términos de notificación si se obtuviera una cobertura del 100%. Resultados Durante el período de intervención, más de 18.000 personas con baciloscopia negativa fueron elegibles en los seis departamentos. El esputo de 7193 (36,9%) de ellos fue analizado también por Xpert y se detectaron 199 personas con baciloscopia negativa y Xpert positivo (positividad: 2,8%). En el año anterior a la intervención se notificaron 1098 casos de tuberculosis pulmonar y baciloscopia positiva, y 195 con baciloscopia negativa. Durante la intervención, la notificación de casos con baciloscopia positiva se mantuvo estable (1090 personas, 0,7%), pero las notificaciones con baciloscopia negativa, que incluía los casos con baciloscopia negativa y Xpert positivo, aumentó en 167 casos (85,6%), llegando a los 362 casos. Después de controlar por la tendencia temporal de notificación en los ocho trimestres anteriores, la notificación de tuberculosis pulmonar (con baciloscopia positiva o no) fue un 19% mayor que las predicciones de la tendencia. Si la cobertura de Xpert se acercase al 100%, se estima que se habría producido un incremento del 41% en las notificaciones. Conclusiones Se identifica un importante aumento de las notificaciones de tuberculosis pulmonar solo con la introducción de Xpert. Ello indica que un número importante de personas con tuberculosis en Guatemala son atendidos por los servicios de salud y son sometidos a bacteriología microscópica, pero no son diagnosticados ni tratados porque no disponen de confirmación bacteriológica. La utilización de técnicas diagnósticas más sensibles o la mejora en el diagnóstico clínico tienen potencial para aumentar significativamente las notificaciones de tuberculosis pulmonar en esta zona y en cualquier otro lugar donde exista una proporción baja de diagnósticos clínicos no confirmados por microscopía.

Abstract Objective To assess the impact of introducing Xpert as a follow-on test after smear microscopy on the total number pulmonary TB notifications. Method Genexpert systems were installed in six departments across Guatemala, and Xpert was indicated as a follow-on test for people with smear-negative results. We analyzed notifications to national tuberculosis (TB) programmes (NTP) and the project's laboratory data to assess coverage of the intervention and case detection yield. Changes in quarterly TB notifications were analyzed using a simple pre/post comparison and a regression model controlling for secular notification trends. Using a mix of project and NTP data we estimated the theoretical yield of the intervention if testing coverage achieved 100%. Results Over 18,000 smear-negative individuals were eligible for Xpert testing during the intervention period. Seven thousand, one hundred and ninety-three people (39.6% of those eligible) were tested on Xpert resulting in the detection of 199 people with smear-negative, Xpert positive results (2.8% positivity rate). In the year before testing began 1098 people with smear positive and 195 people with smear negative results were notified in the six intervention departments. During the intervention, smear-positive notification remained roughly stable (1090 individuals, 0.7%), but smear-negative notifications increased by 167 individuals (85.6%) to an all-time high of 362. After controlling for secular notifications trends over an eight-quarter pre-intervention period, combined pulmonary TB notifications (both smear positive and negative) were 19% higher than trend predictions. If Xpert testing coverage approached 100% of those eligible, we estimate there would have been a + 41% increase in TB notifications. Conclusions We measured a large gain in pulmonary notifications through the introduction of Xpert testing alone. This indicates a large number of people with TB in Guatemala are seeking health care and being tested, yet are not diagnosed or treated because they lack bacteriological confirmation. Wider use of more sensitive TB diagnostics and/or improvements in the number of people clinically diagnosed with TB have the potential to significantly increase TB notifications in this setting, and potentially in other settings where a low proportion of pulmonary notifications are clinically diagnosed.

Resumen Objetivo Evaluar el impacto en la notificación de casos de tuberculosis pulmonar de la introducción de Xpert como prueba de continuación después del análisis microscópico. Método Se instalaron sistemas Genexpert es seis departamentos de Guatemala y se indicó como prueba consecutiva en todos los resultados negativos en la baciloscopia microscópica. Se analizaron los datos del Programa Nacional y los del laboratorio del proyecto para medir la cobertura y la productividad en detección de casos. Las notificaciones trimestrales se compararon con los valores anteriores a la intervención y se adoptó un modelo de regresión para controlar por las tendencias temporales. Se estimó la contribución teórica de la intervención en términos de notificación si se obtuviera una cobertura del 100%. Resultados Durante el período de intervención, más de 18.000 personas con baciloscopia negativa fueron elegibles en los seis departamentos. El esputo de 7193 (36,9%) de ellos fue analizado también por Xpert y se detectaron 199 personas con baciloscopia negativa y Xpert positivo (positividad: 2,8%). En el año anterior a la intervención se notificaron 1098 casos de tuberculosis pulmonar y baciloscopia positiva, y 195 con baciloscopia negativa. Durante la intervención, la notificación de casos con baciloscopia positiva se mantuvo estable (1090 personas, 0,7%), pero las notificaciones con baciloscopia negativa, que incluía los casos con baciloscopia negativa y Xpert positivo, aumentó en 167 casos (85,6%), llegando a los 362 casos. Después de controlar por la tendencia temporal de notificación en los ocho trimestres anteriores, la notificación de tuberculosis pulmonar (con baciloscopia positiva o no) fue un 19% mayor que las predicciones de la tendencia. Si la cobertura de Xpert se acercase al 100%, se estima que se habría producido un incremento del 41% en las notificaciones. Conclusiones Se identifica un importante aumento de las notificaciones de tuberculosis pulmonar solo con la introducción de Xpert. Ello indica que un número importante de personas con tuberculosis en Guatemala son atendidos por los servicios de salud y son sometidos a bacteriología microscópica, pero no son diagnosticados ni tratados porque no disponen de confirmación bacteriológica. La utilización de técnicas diagnósticas más sensibles o la mejora en el diagnóstico clínico tienen potencial para aumentar significativamente las notificaciones de tuberculosis pulmonar en esta zona y en cualquier otro lugar donde exista una proporción baja de diagnósticos clínicos no confirmados por microscopía.

ABSTRACT GeneXpert is one of the recent technological instruments used to diagnose tuberculosis in a short span of time. In this study, the performance of GeneXpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis (EPTB) was compared with light-emitting diode Fluorescent Microscopy (LED-FM) in Khyber Pakhtunkhwa, Pakistan. A total of 737 EPTB samples were collected from tuberculosis (TB) suspected patients. Out of these samples, male to female ratio was 53% (n = 390) to 47% (n = 347) respectively. The sensitivity and specificity was 73% and 100% for GeneXpert, while 40% and 100% for LED-FM microscopy. This shows that the sensitivity of GeneXpert is 40–50%, higher than LED-FM microscopy. GeneXpert also detected low number of bacilli as compared to LED-FM microscopy.

BACKGROUND. GeneXpert MTB/RIF is useful for the diagnosis of pulmonary TB in adults, but there is limited evidence on its usefulness in extrapulmonary TB. OBJECTIVES. To investigate the diagnostic accuracy of GeneXpert MTB/RIF in HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. METHODS. A prospective study of patients with suspected musculoskeletal (bone and joint) TB was undertaken. The diagnostic accuracy of GeneXpert MTB/RIF was compared with the reference standards of culture and histopathology. RESULTS. A total of 206 biopsies from 201 patients (23% HIV-infected) were evaluated. The sensitivity and specificity of GeneXpert MTB/ RIF was 92.3% (84/91) and 99.1% (114/115), respectively. GeneXpert MTB/RIF detected 8.8% more cases than culture (84/91 (92.3%) v. 76/91 (83.5%), respectively; p=0.069). GeneXpert MTB/RIF also detected all 4 multidrug-resistant TB cases and an additional 2 rifampicin-resistant cases in culture-negative samples. The sensitivity of GeneXpert MTB/RIF in HIV-infected patients was 96.9% (31/32) v. 89.6% (43/48) in HIV-uninfected patients (p=0.225). CONCLUSION. GeneXpert MTB/RIF is an accurate test for the detection of TB in tissue samples of HIV-infected and HIV-uninfected patients with suspected musculoskeletal TB. A positive GeneXpert MTB/RIF result should be regarded as microbiological confirmation of TB.

Resumen Introducción: La tuberculosis (TB) en niños posee limitaciones en la confirmación microbiológica. Por su naturaleza paucibacilar y la dificultad para obtener muestras microbiológicas adecuadas, la positividad de cultivos es baja. En adultos, la prueba Gene Xpert MTB/RIF(r) ha mostrado utilidad por su buen rendimiento, rapidez de resultados y facilidad en su realización. La Organización Mundial de la Salud (OMS) recomienda el empleo de esta prueba en niños, sin embargo, los datos de esta prueba en nuestro medio son limitados. Objetivo: Estudio de cohorte retrospectivo para describir nuestra experiencia con la prueba Gene Xpert MTB/RIF en menores de 15 años hospitalizados en un centro de alta complejidad con sospecha de TB pulmonar. Método: Se revisaron 116 historias clínicas con resultados disponibles de Xpert MTB/RIF en muestras respiratorias tomadas entre junio de 2012 y diciembre de 2013. Se excluyeron 33 casos. Los 83 pacientes incluidos se clasificaron como: TB confirmada 8 (10%), probable 16 (19%) y descartada 59 (71%) según criterios de la OMS. El análisis estadístico se realizó en SPSS 20 y EpiDat 3.1. Resultados: Xpert MTB/RIF mostró para TB confirmada una sensibilidad del 50%, especificidad 96% y valores predictivos positivos y negativos del 57,14 y 94,7%, respectivamente. Al evaluarla en el total de niños que ameritaron inicio de tratamiento (TB confirmada y probable), la sensibilidad fue del 29% con especificidad del 100%. Xpert MTB/RIF detectó una cepa resistente a rifampicina. Conclusión: Xpert MTB/RIF mostró ser útil para el diagnóstico de TB, con una sensibilidad superior a la baciloscopia. Un resultado positivo puede definir el inicio temprano de tratamiento en casos dudosos, confirma el diagnóstico y permite conocer rápidamente si existe resistencia a rifampicina. Un resultado negativo no descarta el diagnóstico ni debe impedir el inicio del tratamiento si cumple con la sumatoria de los otros criterios recomendados por la OMS.

Abstract Introduction: Microbiological confirmation of tuberculosis (TB) in children is difficult. Due to its paucibacillary course, the positivity of cultures is low and samples are not easy to obtain. In adults, Genexpert MTB/RIF is useful for diagnosing TB. It shows good test performance, offers fast results and is a simple technique for laboratory personnel. The World Health Organization (WHO) recommends its use for children, but clinical studies on this age group are scarce. Objective: This was a retrospective, descriptive cohort study. The purpose of this study was to describe our experience with Gene Xpert MTB/RIF in children younger than 15 years of age with clinical suspicion of pulmonary TB, who were admitted to a high complexity hospital. Methods: A total of 116 clinical charts with available results of Xpert MTB/RIF in respiratory samples taken between June 2012 and December 2013 were reviewed and of these, 33 were excluded. The 83 included patients were classified according to the WHO criteria into confirmed TB (n = 8; 10%), probable (n = 16; 19%) and no TB (n = 59; 71%). An analysis was performed using SPSS 20 and EpiDat 3.1. Results: The Xpert MTB/RIF was 50% sensitive and 96% specific, with a positive predictive value of 57.14% and an negative predictive value of 94.7% for children with confirmed TB. When evaluating Xpert MTB/RIF in all children who received TB treatment (confirmed plus probable TB disease) the sensitivity was 29% with 100% specificity. Among our cohort, the Xpert MTB/RIF detected one child with rifampicin resistance. Conclusions: Xpert MTB/RIF was useful for the diagnosis of TB. A positive result can lead to the early initiation of treatment in doubtful cases. It confirms the diagnosis and quickly reveals rifampicin resistance. A negative result, however, just as with cultures, does not exclude the diagnosis and should not prevent the initiation of treatment, if it is considered needed based on other criteria.

Resumo: O objetivo do estudo foi estimar o impacto orçamentário do GeneXpert MTB/RIF para o diagnóstico da tuberculose sob a perspectiva do Programa Nacional de Controle da Tuberculose, valendo-se de um modelo estático apoiado no método epidemiológico entre 2013 e 2017. Comparou-se um teste Xpert MTB/RIF com duas baciloscopias diagnósticas. Utilizaram-se dados epidemiológicos, populacionais, de custos, a taxa de câmbio e bases de dados do Sistema Único de Saúde. Foi realizada análise de sensibilidade por cenários. A incorporação do GeneXpert MTB/RIF demandaria um montante de R$ 147 milhões em cinco anos e representaria um impacto de 23% a 26% nos dois primeiros anos, e de cerca de 11% entre 2015 e 2017. Os resultados podem apoiar os gestores brasileiros e dos países latino-americanos no planejamento e gestão na sua decisão de incorporação da tecnologia.

Abstract: The study aimed to estimate the budget impact of GeneXpert MTB/RIF for diagnosis of tuberculosis from the perspective of the Brazilian National Program for Tuberculosis Control, drawing on a static model using the epidemiological method, from 2013 to 2017. GeneXpert MTB/RIF was compared with two diagnostic sputum smear tests. The study used epidemiological, population, and cost data, exchange rates, and databases from the Brazilian Unified National Health System. Sensitivity analysis of scenarios was performed. Incorporation of GeneXpert MTB/RIF would cost BRL 147 million (roughly USD 45 million) in five years and would have an impact of 23 to 26% in the first two years and some 11% between 2015 and 2017. The results can support Brazilian and other Latin American health administrators in planning and managing the decision on incorporating the technology.

Resumen: El objetivo del estudio fue estimar el impacto presupuestario del GeneXpert MTB/RIF para el diagnóstico de la tuberculosis, desde la perspectiva del Programa Nacional de Control de la Tuberculosis de Brasil, valiéndose de un modelo estático, apoyado en el método epidemiológico entre 2013 y 2017. Se comparó un test Xpert MTB/RIF con dos baciloscopias diagnósticas. Se utilizaron datos epidemiológicos, poblacionales, de costes, la tasa de cambio y bases de datos del Sistema Único de Salud. Se realizó un análisis de sensibilidad por escenarios. La incorporación del GeneXpert MTB/RIF demandaría un montante de R$ 147 millones en cinco años y representaría un impacto de 23 a 26% durante los dos primeros años, y de cerca de un 11% entre 2015 y 2017. Los resultados pueden apoyar a los gestores brasileiros y de los países latinoamericanos en la planificación y gestión a la hora de decidir incorporar este tipo de tecnología.

Resumo: O objetivo do estudo foi estimar o impacto orçamentário do GeneXpert MTB/RIF para o diagnóstico da tuberculose sob a perspectiva do Programa Nacional de Controle da Tuberculose, valendo-se de um modelo estático apoiado no método epidemiológico entre 2013 e 2017. Comparou-se um teste Xpert MTB/RIF com duas baciloscopias diagnósticas. Utilizaram-se dados epidemiológicos, populacionais, de custos, a taxa de câmbio e bases de dados do Sistema Único de Saúde. Foi realizada análise de sensibilidade por cenários. A incorporação do GeneXpert MTB/RIF demandaria um montante de R$ 147 milhões em cinco anos e representaria um impacto de 23% a 26% nos dois primeiros anos, e de cerca de 11% entre 2015 e 2017. Os resultados podem apoiar os gestores brasileiros e dos países latino-americanos no planejamento e gestão na sua decisão de incorporação da tecnologia.

Abstract: The study aimed to estimate the budget impact of GeneXpert MTB/RIF for diagnosis of tuberculosis from the perspective of the Brazilian National Program for Tuberculosis Control, drawing on a static model using the epidemiological method, from 2013 to 2017. GeneXpert MTB/RIF was compared with two diagnostic sputum smear tests. The study used epidemiological, population, and cost data, exchange rates, and databases from the Brazilian Unified National Health System. Sensitivity analysis of scenarios was performed. Incorporation of GeneXpert MTB/RIF would cost BRL 147 million (roughly USD 45 million) in five years and would have an impact of 23 to 26% in the first two years and some 11% between 2015 and 2017. The results can support Brazilian and other Latin American health administrators in planning and managing the decision on incorporating the technology.

Resumen: El objetivo del estudio fue estimar el impacto presupuestario del GeneXpert MTB/RIF para el diagnóstico de la tuberculosis, desde la perspectiva del Programa Nacional de Control de la Tuberculosis de Brasil, valiéndose de un modelo estático, apoyado en el método epidemiológico entre 2013 y 2017. Se comparó un test Xpert MTB/RIF con dos baciloscopias diagnósticas. Se utilizaron datos epidemiológicos, poblacionales, de costes, la tasa de cambio y bases de datos del Sistema Único de Salud. Se realizó un análisis de sensibilidad por escenarios. La incorporación del GeneXpert MTB/RIF demandaría un montante de R$ 147 millones en cinco años y representaría un impacto de 23 a 26% durante los dos primeros años, y de cerca de un 11% entre 2015 y 2017. Los resultados pueden apoyar a los gestores brasileiros y de los países latinoamericanos en la planificación y gestión a la hora de decidir incorporar este tipo de tecnología.

BACKGROUND. The GeneXpert MTB/RIF (Cepheid, USA) (Xpert) has proved successful for pulmonary tuberculosis (TB) diagnosis on decontaminated/concentrated induced sputum specimens from children. Capacity to perform induction in many settings is limited. OBJECTIVE: To Assess: (i) volumes of 'routinely obtained' sputum in a district-level academic hospital; (ii) whether sputum specimens not meeting Xpert-required testing volumes could still be tested; and (iii) performance of Xpert on a single paediatric sputum specimen at point of care (POC METHODS. Two sputa were collected from paediatric TB suspects (<14 years) at Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa. One specimen was weighed at POC; if the volume was >0.1 mL but <0.5 mL, it was increased to 0.5 mL using saline. On-site Xpert testing (G3 cartridge) was performed by a dedicated laboratory technician. The second specimen was referred for TB smear microscopy and culture as per standard of care (SOC). RESULTS. A total of 484 patients presumed to have TB (median age 24 months) were eligible for this study, performed between June 2011 and May 2012. Xpert could not be used on 4.1% of specimens because of volumes <0.1 mL, and 62.8% required addition of saline prior to Xpert testing. Xpert generated a 2.2% error and 3.7% invalid rate, compared with the SOC that rejected 2.3% because of insufficient volume and 2.3% that were contaminated. The diagnostic performance compared with culture was 62.5% (95% confidence interval (CI) 24.7 - 91) and 99.1% (95% CI 97.4 - 99.8) sensitivity and specificity, respectively, for Xpert (n=345) and 33.3% (7.9 - 69.9) and 99.5% (98.1 - 99.9) sensitivity and specificity, respectively, for smear microscopy (n=374). CONCLUSIONS. Up to 67% of 'routinely obtained' sputum specimens from children (<14 years) are below the required volume for Xpert testing but can be 'topped up' with saline. Xpert MTB/RIF performed better than microscopy and generated clinically relevant, timeous results, but sensitivity did not reach the same levels as culture in children.