Predictors of time to sputum culture conversion in multi-drug-resistant tuberculosis and extensively drug-resistant tuberculosis in patients at Tshepong-Klerksdorp Hospital

Setting: Klerksdorp-Tshepong Hospital Complex MDR-TB Unit, North-West Province, South Africa.Background: To determine the time to sputum culture conversion (TTSCC) and factors predictive of TTSCC in patients with multi-drug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in the North-West Province.Methods: A retrospective cohort study, abstracting patient demographic and clinical data, laboratory results, dates of sputum testing and sputum culture conversion results, from medical records of 526 MDR-TB and 47 XDR-TB patients started on TB treatment between 01 January 2012 and 31 December 2014. Predictors of TTSCC were determined by Cox proportional hazards regression.Results: The median age was 38 years (interquartile range 31­47) with 64% being male. Overall, 79% (449) were Human Immunodeficiency Virus (HIV)-infected. The median TTSCC was 56.5 days and 162.5 days for MDR-TB and XDR-TB patients, respectively. In the multivariate analysis, age [hazard ratio (HR): 0.89, 95% confidence interval (CI): 0.96­0.99], being underweight (HR: 0.631.61, 95% CI: 0.451.03­0.882.51), Acid Fast Bacilli (AFB) positivity (HR: 0.72, 95% CI: 0.51­1.01) and having XDR-TB (HR: 0.36. 95% CI: 0.19­0.69) were predictive of longer TTSCC.Conclusion: Predictors of TTSC allow for MDR-TB- and XDR-TB-diagnosed patients to be identified early for effective management. Those with risk factors for delayed sputum culture conversion which are being underweight and having XDR-TB should be monitored carefully during treatment so that they can achieve sputum culture conversion early

Tuberculosis congénita pre-extensivamente resistente a drogas: reporte de caso / Pre-extensively drug-resistant congenital tuberculosis: case report

RESUMEN La tuberculosis en el lactante es un cuadro de difícil diagnóstico por las pruebas diagnósticas que muchas veces resultan negativas y por la dificultad de identificar la fuente de transmisión. Se presenta el caso de un lactante varón de un mes de vida que presenta irritabilidad, taquipnea, fiebre, pobre ganancia de peso desde el nacimiento y hepatomegalia, además, tiene el antecedente materno de tuberculosis pre-extensivamente resistente a drogas y reacción granulomatosa tuberculoide con tinción auramina positiva para bacilos ácido-alcohol resistentes en la histopatología de placenta. Ante la sospecha de tuberculosis congénita, es referido al Instituto Nacional de Salud del Niño para estudio diagnóstico y tratamiento; el paciente presenta una evolución clínica favorable y sin reacciones adversas al tratamiento. El diagnóstico de tuberculosis congénita debe considerarse en lactantes con signos clínicos sugestivos de la enfermedad y mantener la sospecha ante la presencia del antecedente materno de infección por Mycobacterium tuberculosis.

ABSTRACT Tuberculosis in infants is a clinical case difficult to diagnose by regular testing which often yield negative results; additionally, the source of transmission is difficult to identify. This work presents the case of a one-month old nursing boy presenting irritability, tachypnea, fever, poor gain weight from birth, and hepatomegaly. Additionally, he had the maternal history of pre-extensively drug- resistant tuberculosis and tuberculoid granulomatosis reaction with positive auramine tincture for acid-alcohol resistant bacilli at histopathology of the placenta. With a suspected congenital tuberculosis, he was referred to the National Children's Health Institute for diagnosis and treatment. The patient showed a favorable clinical evolution and no adverse reactions to treatment. The diagnosis of congenital tuberculosis must be considered in infants with suggestive clinical signs of the disease and such suspicion must be maintained with the presence of a maternal history of Mycobacterium tuberculosis infection.

Frequência e perfil epidemiológico de pacientes com tuberculose multirresistente e extensivamente resistente em um hospital de referência na cidade do Rio de Janeiro / Frequency and epidemiological profile of patients with multidrug-resistant and extensively drug-resistant tuberculosis in a reference hospital in the city of Rio de Janeiro

A Tuberculose Multirresistente (TBMR) é um dos grandes problemas de saúde enfrentados em países em desenvolvimento, apresentando-se como um grande desafio global para o controle da Tuberculose (TB). Destacamos ainda o surgimento de formas mais graves de resistência, como a Tuberculose Extensivamente Resistente (TB-XDR). No Brasil foram implantadas diversas estratégias e ações com o objetivo de garantir o controle da doença, sua erradicação e redução nos indices de abandono terapêutico. Porém, na cidade do Rio de Janeiro, o índice de incidência da doença permanece elevado e se destaca como um dos mais altos do Brasil. O presente estudo tem por objetivos, avaliar a frequência e o perfil epidemiológico de pacientes com TBMR e TB-XDR diagnosticados em um Hospital de referência no município do Rio de Janeiro, no período de 2016 a 2018, com a determinação de contribuir para a geração de dados epidemiológicos sobre a situação da doença na cidade do Rio de Janeiro, identificar o grupo de pessoas mais vulneráveis, ajudar a completar o quadro clínico da doença além de estimular outros estudos, sobre o conhecimento da TBMR e TB-XDR. Estudo foi descritivo transversal. Os dados foram secundários coletados através de informações disponíveis em prontuários de pacientes diagnosticados com TB que tiveram como desfecho de interesse a resistência às medicações. Para a obtenção dos dados foi utilizado um instrumento estruturado, que possibilitou a captura de informações referentes à frequencia, o perfil sociodemográfico, características clínico-epidemiológicas, dentre outros. Foi realizada análise das variáveis sociodemógraficas, epidemiológicas e história de tratamento anterior com os resultados coletados armazenados em um banco de dados específico, sendo as análises de frequências e de associações realizadas por meio do software estatístico SPSS. Foram coletados dados de 100 pacientes com TBMR, 44% deles abandonaram o tratamento anteriormente. Dos pacientes investigados 61.6% eram do sexo masculino e 38.4% do sexo feminino. A média de idade encontrada neste estudo foi de 37.9 anos, com a variação entre 18 e 77 anos, 45.3% se declararam pardos e 39.3% possuíam de 4-7 anos de estudo, 19% dos pacientes apresentaram coinfecção HIV/TBMR, foi verificada associação entre abandono de tratamento anterior e caso de TBMR. Podemos concluir que os pacientes que foram encaminhados para tratamento no hospital de estudo apresentaram uma taxa elevada de casos de abandono de tratamento de tuberculose, o que se faz necessário o incremento de ações de planejamento para a adesão ao tratamento da tuberculose.

Multidrug-resistant tuberculosis (MDR-TB) is one of the major health problems faced in developed and developing countries, presenting itself as a major global challenge for Tuberculosis (TB) control. We also highlight the emergence of more severe forms of resistance, such as Extensively Resistant Tuberculosis (TB-XDR). In Brazil several strategies and actions were implemented with the objective of guaranteeing the control of the disease, its eradication and reduction in the rates of therapeutic abandonment. However, in the city of Rio de Janeiro, the incidence rate of the disease remains high and stands out as the highest in Brazil. The present study aims to evaluate the prevalence and epidemiological profile of patients with MDR-TB and MDR-TB diagnosed in a reference hospital in the city of Rio de Janeiro, from 2016 to 2018, with the determination to contribute to the generation epidemiological data on the disease situation in the city of Rio de Janeiro, identifying the group of most vulnerable individuals, helping to complete the clinical picture of the disease, and stimulating other studies on the knowledge of MDR-TB and XDR-TB. The thesis is that patients with MDR-TB and XDR-TB reported in a referral hospital in the city of Rio de Janeiro had abandoned previous treatment. Descriptive cross-sectional study. The data were collected through information available in medical records of patients diagnosed with TB who had as an outcome of interest the resistance to medications. To obtain the data, a structured instrument was used, which enabled the capture of information regarding prevalence, sociodemographic profile, clinical and epidemiological characteristics, among others. An analysis of sociodemographic, epidemiological and previous treatment history was performed with the collected data stored in a specific database, and the frequency and association analyzes were performed using the SPSS statistical software. Data were collected from 100 patients with MDR-TB, 44% of whom had previously discontinued treatment. Of the patients investigated, 61.6% were male and 38.4% female. The mean age found in this study was 37.9 years, ranging from 18 to 77 years, 45.3% were declared pardos and 39.3% had 4-7 years of schooling, 19% of the patients had HIV / MDR coinfection, was verified association between early cessation of treatment and case of MDR-TB. We can conclude that the study hospital had a high rate of cases of abandonment of tuberculosis treatment, which necessitates an increase in planning actions for adherence to tuberculosis treatment.

La Tuberculosis Multirresistente (TBMR) es uno de los grandes problemas de salud enfrentados en los países desarrollados y en desarrollo, presentándose como un gran desafío global para el control de la Tuberculosis (TB). Estamos de acuerdo con el surgimiento de formas más graves de resistencia, la Tuberculosis Extensivamente Resistente (TB-XDR). En Brasil se implantaron diversas estrategias y acciones con el objetivo de garantizar el control de la enfermedad, su erradicación y reducción en las tasas de abandono terapéutico. Sin embargo, en la ciudad de Río de Janeiro, el índice de incidencia de la enfermedad permanece elevado y se destaca como el más alto de Brasil. El presente estudio tiene por objetivos, evaluar la prevalencia y el perfil epidemiológico de pacientes con TBMR y TB-XDR diagnosticados en un Hospital de referencia en el municipio de Río de Janeiro, en el período de 2016 a 2018, con la determinación de contribuir a la generación de datos epidemiológicos sobre la situación de la enfermedad en la ciudad de Río de Janeiro, identificar el grupo de personas más vulnerables, ayudar a completar el cuadro clínico de la enfermedad además de estimular otros estudios, sobre el conocimiento de la TBMR y TB-XDR. la tesis es que los pacientes de TBMR y TB-XDR notificados en un hospital de referencia en la ciudad de Río de Janeiro tuvieron abandono de tratamiento anterior. Estudio descriptivo transversal. Los datos fueron recolectados a través de informaciones disponibles en prontuarios de pacientes diagnosticados con TB que tuvieron como resultado de interés la resistencia a las medicaciones. Para la obtención de los datos se utilizó un instrumento estructurado, que posibilitó la captura de informaciones referentes a la prevalencia, el perfil sociodemográfico, características clínico-epidemiológicas, entre otros. Se realizaron análisis de las variables sociodemóficas, epidemiológicas e historia de tratamiento anterior con los resultados recogidos almacenados en un banco de datos específico, siendo los análisis de frecuencias y de asociaciones realizadas por medio del software estadístico SPSS. Se recogieron datos de 100 pacientes con TBMR, el 44% de ellos abandonaron el tratamiento anteriormente. De los pacientes investigados 61.6% eran del sexo masculino y 38.4% del sexo femenino. La media de edad encontrada en este estudio fue de 37.9 años, con la variación entre 18 y 77 años, el 45.3% se declaró pardos y el 39.3% poseía de 4-7 años de estudio, el 19% de los pacientes presentaron coinfección VIH / TBMR, fue verificada asociación entre el abandono del tratamiento anterior y el caso de TBMR. Podemos concluir que el hospital de estudio presentó una tasa elevada de casos de abandono de tratamiento de tuberculosis, lo que se hace necesario el incremento de acciones de planificación para la adhesión al tratamiento de la tuberculosis.

Precisión diagnóstica de tres pruebas moleculares para detectar la tuberculosis multirresistente / Diagnostic accuracy of three technologies for the diagnosis of multi-drug resistant tuberculosis

Resumen Introducción. La tuberculosis multirresistente (TB-MDR) y la extremadamente resistente (TB-XDR) constituyen un problema de salud pública a nivel mundial. Su detección oportuna permitiría reducir la carga de la enfermedad y su impacto económico en los sistemas de salud. Objetivo. Revisar sistemáticamente la información relacionada con la precisión diagnóstica de tres pruebas moleculares para detectar la tuberculosis multirresistente y la extremadamente resistente. Materiales y métodos. Se hizo una revisión sistemática de la literatura, según los lineamientos de Cochrane, de los estudios en población inmunocompetente relacionados con la precisión diagnóstica de tres pruebas moleculares para detectar la tuberculosis multirresistente y la extremadamente resistente. La búsqueda de los estudios publicados a partir del 2007 se hizo en Medline y Embase. La precisión diagnóstica de las pruebas se estableció con base en los valores máximos y mínimos de sensibilidad y especificidad, y en los valores predictivos positivos y negativos. Resultados. Se detectaron ocho estudios sobre la precisión diagnóstica de la prueba GeneXpert MTB/RIF(r), 12 sobre la de GenoType MTBDRplus(r) y 13 sobre la de GenoType MTBDRsl(r). La especificidad de GeneXpert MTB/RIF(r) osciló entre 91 y 100 % y su sensibilidad, entre 33,3 y 100 %. La sensibilidad de GenoType MTBDRplus(r) varió entre 82 y 100 %, en tanto que la sensibilidad y la especificidad de GenoType(r) MTBDRsl fluctuaron entre 56 y 100 % y 21 y 100 %, respectivamente. Conclusión. Según los estudios consultados, los tres métodos de diagnóstico evaluados presentabanuna adecuada eficacia diagnóstica para detectar la tuberculosis multirresistente y la extremadamente resistente.

Abstract Introduction: Multi-drug resistant (MDR-TB) and extensively drug-resistant (XDR-TB) tuberculoses are a global public health problem. Their timely detection might reduce the burden of the disease and the economic impact on health systems worldwide. Objective: To conduct a literature review of the diagnostic accuracy of three molecular tests to detect multi-drug resistant and extensively drug-resistant tuberculoses. Materials and methods: A systematic literature review following Cochrane methodology was carried out to study the diagnostic accuracy of three molecular tests to detect MDR-TB and XDR-TB in previous studies among immunocompetent population. Articles indexed in Medline and Embase were reviewed starting in 2007. Diagnostic accuracy was reported by sensitivity, specificity, and positive and negative predictive values of each test. Results: In total, 8, 12 and 13 studies were included to assess the diagnostic accuracy of GeneXpert MTB/RIF(r), GenoType MTBDRplus (r) and GenoType MTBDRsl (r), respectively. The specificity of GeneXpert MTB/RIF(r) ranged between 91 and 100%, and its sensitivity between 33.3 and 100%. The sensitivity of GenoType(r) MTBDRplus (r) ranged between 88 and 100%. The sensitivity and specificity of GenoType MTBDRsl (r) to evaluate drug resistance ranged between 56 and 100% and 21 and 100%, respectively. Conclusion: The three diagnostic tests evaluated have shown an adequate diagnostic accuracy to detect MDR and XDR tuberculoses.

A molecular platform for the diagnosis of multidrug-resistant and pre-extensively drug-resistant tuberculosis based on single nucleotide polymorphism mutations present in Colombian isolates of Mycobacterium tuberculosis

Developing a fast, inexpensive, and specific test that reflects the mutations present in Mycobacterium tuberculosis isolates according to geographic region is the main challenge for drug-resistant tuberculosis (TB) control. The objective of this study was to develop a molecular platform to make a rapid diagnosis of multidrug-resistant (MDR) and extensively drug-resistant TB based on single nucleotide polymorphism (SNP) mutations present in therpoB, katG, inhA,ahpC, and gyrA genes from Colombian M. tuberculosis isolates. The amplification and sequencing of each target gene was performed. Capture oligonucleotides, which were tested before being used with isolates to assess the performance, were designed for wild type and mutated codons, and the platform was standardised based on the reverse hybridisation principle. This method was tested on DNA samples extracted from clinical isolates from 160 Colombian patients who were previously phenotypically and genotypically characterised as having susceptible or MDR M. tuberculosis. For our method, the kappa index of the sequencing results was 0,966, 0,825, 0,766, 0,740, and 0,625 forrpoB, katG, inhA,ahpC, and gyrA, respectively. Sensitivity and specificity were ranked between 90-100% compared with those of phenotypic drug susceptibility testing. Our assay helps to pave the way for implementation locally and for specifically adapted methods that can simultaneously detect drug resistance mutations to first and second-line drugs within a few hours.

XDR-TB: An outcome of programmatic management of TB in India.

A significantly strengthened Revised National Tuberculosis Control Programme (RNTCP) is currently operational in India. In this case-based commentary, we describe the plight of a patient who developed extensive drug-resistant tuberculosis (XDR-TB) despite having received treatment under the RNTCP for a long period. Our aim is to analyse the programmatic management of tuberculosis in India by highlighting and discussing various issues related to the treatment received by the patient. Further, the article explores whether there is a need to incorporate an ethical element into the RNTCP as it stands today.

New approaches in the diagnosis and treatment of susceptible, multidrug-resistant and extensively drug resistant tuberculosis

Tuberculosis [TB] is killing nearly two million people worldwide every year. The current global burden of TB is mainly due to the expanding human immunodeficiency virus infection and its association with active TB disease and increasing resistance of Mycobacterium tuberculosis strains to most-effective [first-line] anti-TB drugs. Incomplete/ improper treatment of TB patients leads to evolution of drug-resistant M. tuberculosis strains as a result of chromosomal mutations in genes encoding drug targets. Sequential accumulation of mutations in target genes generate multidrug-resistant [resistant atleast to rifampin and isoniazid] M. tuberculosis [MDR-TB] and extensively drug-resistant [additionally resistant to fluoroquinolones and an injectable anti-TB agent] M. tuberculosis [XDR-TB] strains. While proper treatment of susceptible TB has > 95% cure rate, effective treatment of MDR-TB is difficult in developing countries as it is heavily dependent on rapid diagnosis, supervised aggressive therapy with several [5 - 6] expensive, toxic and less efficacious drugs for 18 - 24 months and regular monitoring for bacteriological and clinical improvement. Treatment of XDR-TB is far more difficult even in developed countries. Several anti-TB drugs with novel mechanism of action are under clinical development, which may shorten treatment duration of susceptible TB to around three months and also help in effective treatment of MDR-TB / XDR-TB

Extensively drug-resistant tuberculosis: a case report and literature review

Extensively drug-resistant tuberculosis (XDR-TB) is an emerging health problem that threatens tuberculosis (TB) control worldwide, since suitable treatment for this disease has not yet been found. We report a case of secondary pulmonary XDR-TB in a 54-year-old, HIV-negative male from Goiânia, Brazil. The patient had long-standing pulmonary tuberculosis (nine years) with extensive bilateral lung damage and had been treated with multiple antituberculosis drugs (self-administered) before XDR-TB diagnosis. The strain of Mycobacterium tuberculosis was resistant to R- rifampicin, H-isoniazid, E-ethambutol, Eto-ethionamide, Ofx-ofloxacin, and Am-amikacin. This patient died with multiple organ failure due to sepsis secondary to bacterial pneumonia.