Clinical value of the MeltPro MTB assays in detection of drug-resistant tuberculosis in paraffin-embedded tissues / 中华病理学杂志

Objective: To evaluate the clinical value of the MeltPro MTB assays in the diagnosis of drug-resistant tuberculosis. Methods: A cross-sectional study design was used to retrospectively collect all 4 551 patients with confirmed tuberculosis between January 2018 and December 2019 at Beijing Chest Hospital, Capital Medical University. Phenotypic drug sensitivity test and GeneXpert MTB/RIF (hereafter referred to as "Xpert") assay were used as gold standards to analyze the accuracy of the probe melting curve method. The clinical value of this technique was also evaluated as a complementary method to conventional assays of drug resistance to increase the detective rate of drug-resistant tuberculosis. Results: By taking the phenotypic drug susceptibility test as the gold standard, the sensitivity of the MeltPro MTB assays to detect resistance to rifampicin, isoniazid, ethambutol and fluoroquinolone was 14/15, 95.7%(22/23), 2/4 and 8/9,respectively; and the specificity was 92.0%(115/125), 93.2%(109/117), 90.4%(123/136) and 93.9%(123/131),respectively; the overall concordance rate was 92.1%(95%CI:89.6%-94.1%),and the Kappa value of the consistency test was 0.63(95%CI:0.55-0.72).By taking the Xpert test results as the reference, the sensitivity of this technology to the detection of rifampicin resistance was 93.6%(44/47), the specificity was100%(310/310), the concordance rate was 99.2%(95%CI:97.6%-99.7%), and the Kappa value of the consistency test was 0.96(95%CI:0.93-0.99). The MeltPro MTB assays had been used in 4 551 confirmed patients; the proportion of patients who obtained effective drug resistance results increased from 83.3% to 87.8%(P<0.01); and detection rate of rifampicin, isoniazid, ethambutol, fluoroquinolone resistance, multidrug and pre-extensive drug resistance cases were increased by 3.2%, 14.7%, 22.2%, 13.7%, 11.2% and 12.5%, respectively. Conclusion: The MeltPro MTB assays show satisfactory accuracy in the diagnosis of drug-resistant tuberculosis. This molecular pathological test is an effective complementary method in improving test positivity of drug-resistant tuberculosis.

Diagnosis of cutaneous tuberculosis (lymph node scrofuloderma) using the Xpert MTB/RIF® method

Abstract Cutaneous tuberculosis is a rare infection that is difficult to diagnose, because it shows less sensitivity and specificity in classic complementary exams when compared with the pulmonary form. The Xpert MTB/RIF® method offers an early diagnosis that identifies the DNA of Mycobacterium tuberculosis and the main mutations that give the bacterium resistance to rifampicin. The authors present a case of scrofuloderma whose diagnosis was quickly obtained through the secretion of a cervical lesion, allowing an early diagnosis and the initiation of appropriate treatment.

Cranial osteomyelitis as a complication of furuncular myiasis / Osteomielite craniana como complicação de miíase furuncular

ABSTRACT Objective: To report the case of an infant with infrequent cranial osteomyelitis as a complication of furuncular myiasis. Case description: The patient was a 4-month-old male who presented to the emergency department with a nodular skull lesion with edema, tenderness, pain, and purulent drainage, as well as progress of the ulcerated lesion and evidence of larvae inside. Antibiotic treatment was initiated, and the patient was taken to the operating room to remove the larvae, but he had no symptomatic improvement. A skull radiograph was taken to visualize the osteolytic lesion, and a 3D computed tomography scan showed osteomyelitis of the external parietal surface. Antibiotic management readjustment continued for a total of six weeks, and a skin flap was used with clinical improvement. Comments: Myiasis is defined as the infestation of vertebrates with fly larvae. In mammals, larvae can feed on host tissue and cause a wide range of infestations depending on their location in the body. The cranial osteomyelitis as a complication of myiasis described in this report seems to be an exceptional case.

RESUMO Objetivo: Relatar um caso de criança com osteomielite craniana infrequente como complicação da miíase furuncular. Descrição do caso: Paciente do sexo masculino, com quatro meses de idade, que se apresentou no pronto-socorro com lesão nodular no crânio com edema, sensibilidade, dor e drenagem purulenta, com evolução da lesão ulcerada e evidência de larva no interior. O tratamento com antibióticos foi iniciado e o paciente foi levado à sala de cirurgia para remover as larvas, mas não houve melhora. Uma radiografia do crânio foi realizada para visualizar a lesão osteolítica e uma tomografia computadorizada em 3D mostrou osteomielite da superfície parietal externa. O reajuste do tratamento com antibióticos foi mantido por um total de seis semanas e um retalho cutâneo foi realizado com melhora clínica. Comentários: Miíase é definida como a infestação de vertebrados com larvas de moscas. Nos mamíferos, as larvas podem se alimentar do tecido hospedeiro e causar uma ampla variedade de infestações, dependendo da sua localização no corpo. A osteomielite como complicação da miíase, apresentada nesse caso, parece ser uma forma não usual de complicação dessa doença.

Can diabetes mellitus modify the plasma concentrations of rifampicin in patients under treatment for tuberculosis?

Abstract Rifampicin is a key component of treatment for tuberculosis and its efficacy is determined by the blood levels attained after therapeutic doses. However, there is a high variability of rifampicin blood levels that is related to both the patient and the formulation used. To date, the effect of diabetes mellitus on the plasma levels of rifampicin was low exploited, which could be relevant either by the significant increase of the comorbidity worldwide as by the probable influence of diabetes on the rifampicin exposure. The study aims to evaluate whether diabetes mellitus contribute to the variation of the maximum concentration of rifampicin in patients with tuberculosis treated with a daily dose of 10 mg/kg. Rifampicin and glycated hemoglobin were measured by high-performance liquid chromatography, and blood glucose by spectrophotometry. A total of 62 male patients were included in the study, and 26 presented diabetes mellitus. Rifampicin plasma levels in 2-h plasma samples collected at day 61 ranged from 3 µg/mL to 14.2 µg/mL. Drugs levels were similar between diabetic and non-diabetic patients and were not correlated with blood glucose and glycated hemoglobin. Moreover, a high percentage of patients in both groups presented low levels of rifampicin.

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.

Enfermedad por bacilo de Calmette-Guérin a distancia en un lactante: Presentación de un caso / Distant bacillus Calmette-Guérin disease in an infant: Case report

La vacuna con el bacilo de Calmette-Guérin es una vacuna atenuada utilizada para prevenir formas graves de tuberculosis. Se aplica a los recién nacidos en países con alta prevalencia de tuberculosis. Pueden presentarse, después de su aplicación, complicaciones a nivel local, como supuración o adenopatías regionales. La enfermedad por diseminación del bacilo es infrecuente y ocurre, por lo general, en pacientes con alteraciones inmunitarias subyacentes. Se presenta el caso de un niño de 5 meses que ingresó por un cuadro de 2 meses de evolución con detención del aumento de peso y nódulos subcutáneos. Se sospechó enfermedad por diseminación del bacilo y se diagnosticó por la biopsia de las lesiones. Se realizó el tratamiento con tres drogas antituberculosas, y se recuperó clínicamente. Si bien se realizaron estudios inmunológicos, no logró demostrarse ninguna inmunodeficiencia como afección predisponente.

The bacillus Calmette-Guérin vaccine is an attenuated vaccine historically used to prevent severe forms of tuberculosis. It is applied to all newborns in countries with high prevalence of tuberculosis. Local complications, such as suppuration or regional adenopathies, may occur after application. Disease due to the spread of the bacillus is infrequent, usually occurring in a patient with an underlying immune alteration. We present the case of a 5-month-old child who was admitted due to a 2-month evolution with weight loss and subcutaneous nodules. Disease was suspected to be due to bacillus Calmette-Guérin dissemination, being diagnosed by biopsy of the lesions. Treatment was carried out with three antituberculous drugs, evolving towards clinical recovery. Although immunological studies were carried out, no immunodeficiency could be demonstrated as a predisposing condition.

Unilateral acute posterior multifocal placoid pigment epitheliopathy in a patient with a strongly positive purified protein derivative test / Epiteliopatia pigmentar placóide multifocal posterior aguda unilateral na presença de reação forte positiva para o teste tuberculínico

ABSTRACT A 27-year-old man presented with a complaint of decreased visual acuity in the right eye. Best-corrected visual acuity was 20/60 in the right eye and 20/20 in the left eye. Right eye fundoscopy revealed mild vitritis, multifocal yellowish lesions, and macular serous retinal detachment. Left eye evaluation was normal. Acute posterior multifocal placoid pigment epitheliopathy was diagnosed in the right eye. Complementary exams revealed a strong reaction to the Mycobacterium tuberculosis purified protein derivative test, thus treatment for tuberculosis was initiated. Baseline fluorescein angiography of the right eye revealed early hypofluorescence and late staining of the lesions. Optical coherence tomography of the right eye demonstrated the accumulation of subretinal and intraretinal fluid associated with cystoid macular edema. During follow-up, the retinal fluid and cysts disappeared, which was followed by disorganization of foveal interdigitation and ellipsoid zones. This is the second described case of unilateral acute posterior multifocal placoid pigment epitheliopathy in a patient with a strong positive result to the M. tuberculosis purified protein derivative test.

RESUMO Um homem de 27 anos apresentou uma queixa de diminuição da acuidade visual no olho direito. A acuidade visual melhor corrigida foi 20/60 no olho direito e 20/20 no olho esquerdo. A fundoscopia do olho direito revelou vitreíte leve, lesões amareladas multifocais e descolamento seroso da retina em região macular. A avaliação do olho esquerdo foi normal. Epiteliopatia pigmentar placóide multifocal posterior aguda foi diagnosticada no olho direito. Os exames complementares revelaram forte reação ao teste do derivado proteico purificado Mycobacterium tuberculosis, iniciando terapia antibiótica contra tuberculose. A angiografia fluoresceínica basal do olho direito revelou hipofluorescência precoce e tardia das lesões. A tomografia de coerência óptica do olho direito demonstrou fluído sub- e intrarretiniano associado a edema macular cistóide. Durante o seguimento, os fluídos e cistos retinianos desapareceram, seguido da desorganização das zonas de interdigitação e elipsóide em região foveal. Este é o segundo caso descrito de epiteliopatia pigmentar placóide multifocal posterior aguda unilateral em um paciente com um forte resultado positivo para o teste tuberculínico.

Tratamento clínico de zumbido primário em adultos e idosos: revisão sistemática / Clinical treatment of primary tinnitus in adults and in the elderly: systematic review

O zumbido no ouvido é definido como uma ilusão auditiva ou sensação sonora endógena, não relacionada a nenhuma fonte externa de estimulação. É um sintoma frequente na população idosa. Até hoje, vários autores argumentam que o desconhecimento da etiologia do zumbido, aliado à subjetividade desta manifestação, mais a sobreposição das enfermidades e dos sintomas que, geralmente, acometem os pacientes idosos, dificultam a obtenção de um bom resultado terapêutico. O objetivo desta revisão foi levantar quais os tratamentos clínicos mais utilizados na prática clínica no tratamento do zumbido primário em adultos e idosos. Procedeu-se à verificação do status dos últimos 5 anos de estudos em textos de acesso livre, no banco de dados eletrônicos da PubMed. Apresentaram tratamentos clínicos para o zumbido primário 25 artigos; aqueles com resultados satisfatórios foram quatro artigos sobre acupuntura, dois sobre neuromodulação de resenha coordenada acústica, um sobre uso combinado de amplificação e gerador de som, e um sobre psicoterapia corporal, que incluíam tanto adultos e idosos, tendo a idade média entre 51 a 54 anos. Não se pode afirmar que os tratamentos propostos são eficazes na cura dos sintomas de zumbido em adultos e idosos, mas sim que existem algumas terapêuticas de baixo custo que apresentam respostas relativamente satisfatórias. (AU)

Tinnitus is defined as a hearing illusion or endogenous auditory sensation that is not related to any external stimulation source. It is a frequent symptom among elderly people. To date, many authors have argued that the lack of knowledge about the tinnitus etiology, added to the subjectivity of this manifestation, and the overlap of other diseases and symptoms that often occur with aged patients make the obtainment of a good therapeutic result difficult. The objective of this review was to find the most used clinical treatment in clinical practice for primary tinnitus on adults and elderly. The status of the last five years of studies in free full texts on PubMed database was checked. Twenty-five articles showed clinical treatment for primary tinnitus, with four articles about acupuncture, two about acoustic coordinate reset neuromodulation, one about sound generator associated with conventional amplification, and one about body-psychotherapy which included adults and elderly with an average age between 51 to 54 years old showing satisfactory results. It is difficult to state that the proposed treatment is efficient on healing the tinnitus symptoms on adults and elderly but there are some low-cost therapies showing relatively satisfactory responses. (AU)

Rapid molecular test for tuberculosis: impact of its routine use at a referral hospital / Teste rápido molecular para tuberculose: avaliação do impacto de seu uso na rotina em um hospital de referência

ABSTRACT Objective: To evaluate the impact of the use of the molecular test for Mycobacterium tuberculosis and its resistance to rifampin (Xpert MTB/RIF), under routine conditions, at a referral hospital in the Brazilian state of Bahia. Methods: This was a descriptive study using the database of the Mycobacteriology Laboratory of the Octávio Mangabeira Specialized Hospital, in the city of Salvador, and georeferencing software. We evaluated 3,877 sputum samples collected from symptomatic respiratory patients, under routine conditions, between June of 2014 and March of 2015. All of the samples were submitted to sputum smear microscopy and the Xpert MTB/RIF test. Patients were stratified by gender, age, and geolocation. Results: Among the 3,877 sputum samples evaluated, the Xpert MTB/RIF test detected M. tuberculosis in 678 (17.5%), of which 60 (8.8%) showed resistance to rifampin. The Xpert MTB/RIF test detected M. tuberculosis in 254 patients who tested negative for sputum smear microscopy, thus increasing the diagnostic power by 59.9%. Conclusions: The use of the Xpert MTB/RIF test, under routine conditions, significantly increased the detection of cases of tuberculosis among sputum smear-negative patients.

RESUMO Objetivo: Avaliar o impacto do teste rápido molecular automatizado Xpert MTB/RIF, utilizado para a detecção de Mycobacterium tuberculosis e sua resistência à rifampicina, em condições de rotina, em um hospital de referência no estado da Bahia. Métodos: Estudo descritivo retrospectivo utilizando o banco de dados do Laboratório de Micobacteriologia do Hospital Especializado Octávio Mangabeira, localizado na cidade de Salvador, e um programa de georreferenciamento. Entre junho de 2014 e março de 2015, foram incluídas no estudo 3.877 amostras de escarro coletadas de pacientes sintomáticos respiratórios em condições de rotina. Todas as amostras coletadas foram submetidas tanto à baciloscopia quanto a Xpert MTB/RIF. Os pacientes foram estratificados por sexo, idade e georreferenciamento. Resultados: Das 3.877 amostras de escarro analisadas, Xpert MTB/RIF detectou a presença de M. tuberculosis em 678 pacientes (17,5%). Desses, 60 (8,8%) apresentaram resistência à rifampicina. O Xpert MTB/RIF detectou 254 pacientes com baciloscopia negativa, representando um acréscimo diagnóstico de 59,9%. Conclusões: A implantação do Xpert MTB/RIF, sob condições de rotina, teve um impacto significativo no aumento da detecção de casos de tuberculose em pacientes com baciloscopia negativa.

An evaluation of false-positive rifampicin resistance on the Xpert MTB/RIF

BACKGROUND Mycobacterium tuberculosis (MTB) is one of the most significant causes of mortality and morbidity. Early diagnose is important especially in multiple drug resistant tuberculosis to avoid transmission. Traditional techniques requires at least one to three weeks for diagnosis of tuberculosis. Diagnostic delays with multiple drug resistant tuberculosis are associated with worse clinical outcomes and increased transmission The Xpert MTB/RIF assay is one of the new diagnostic device for the diagnosis of tuberculosis and rapid detection of rifampicin resistance. OBJECTIVE We assessed the performance of Xpert MTB/RIF assay for detecting rifampicin resistance using phenotypic drug susceptibility tests as automated BD MGIT 960. METHODS Total of 2136 specimens were included in the study. Xpert MTB/RIF testing was performed on samples, using version 4 cartridges, according to the manufacturer's recommendations. The MTBC culture and first-line phenotypic DST were performed in automated BD MGIT 960 (Becton & Dickinson, USA) according to the recommendations of the manufacturer. Agar proportion was used in the case of inconsistency for rifampicin resistance. FINDINGS Thirty-four samples (19 respiratory and 15 nonrespiratory samples) were determined as positive for M. tuberculosis complex by Xpert MTB/RIF (Cepheid GeneXpert® System, USA). Xpert MTB/RIF assay detected 4/34 (11.7%) specimens as rifampicin resistant. One of the rifampicin resistant isolates was determined susceptible in MGIT 960 automated system. This isolate was also tested with agar proportion method and found susceptible to rifampicin. MAIN CONCLUSION The Xpert MTB/RIF assay can be used as first-line assay for the detection of M. tuberculosis. However, microbiologists must be aware of the limitations of the assay.

Estimated rates of recurrence, cure, and treatment abandonment in patients with pulmonary tuberculosis treated with a ­four-drug fixed-dose combination regimen at a tertiary health care facility in the city of Rio de Janeiro, Brazil / Estimativas das taxas de recidiva, cura e abandono de tratamento em pacientes com tuberculose pulmonar tratados com esquema de dose fixa combinada de quatro drogas em uma unidade de saúde terciária na cidade do Rio de Janeiro

ABSTRACT Objective: To estimate the rates of recurrence, cure, and treatment abandonment in patients with pulmonary tuberculosis treated with a four-drug fixed-dose combination (FDC) regimen, as well as to evaluate possible associated factors. Methods: This was a retrospective observational study involving 208 patients with a confirmed diagnosis of pulmonary tuberculosis enrolled in the Hospital Tuberculosis Control Program at the Institute for Thoracic Diseases, located in the city of Rio de Janeiro, Brazil. Between January of 2007 and October of 2010, the patients were treated with the rifampin-isoniazid-pyrazinamide (RHZ) regimen, whereas, between November of 2010 and June of 2013, the patients were treated with the rifampin-isoniazid-pyrazinamide-ethambutol FDC (RHZE/FDC) regimen. Data regarding tuberculosis recurrence and mortality in the patients studied were retrieved from the Brazilian Case Registry Database and the Brazilian Mortality Database, respectively. The follow-up period comprised two years after treatment completion. Results: The rates of cure, treatment abandonment, and death were 90.4%, 4.8%, and 4.8%, respectively. There were 7 cases of recurrence during the follow-up period. No significant differences in the recurrence rate were found between the RHZ and RHZE/FDC regimen groups (p = 0.13). We identified no factors associated with the occurrence of recurrence; nor were there any statistically significant differences between the treatment groups regarding adverse effects or rates of cure, treatment abandonment, or death. Conclusions: The adoption of the RHZE/FDC regimen produced no statistically significant differences in the rates of recurrence, cure, or treatment abandonment; nor did it have any effect on the occurrence of adverse effects, in comparison with the use of the RHZ regimen.

RESUMO Objetivo: Estimar as taxas de recidiva, cura e abandono de tratamento em pacientes com tuberculose pulmonar tratados com o esquema de dose fixa combinada (DFC) de quatro drogas e avaliar possíveis fatores associados. Métodos: Estudo observacional retrospectivo com 208 pacientes com diagnóstico confirmado de tuberculose pulmonar registrados no Programa de Controle da Tuberculose Hospitalar do Instituto de Doenças do Tórax, localizado na cidade do Rio de Janeiro. Os pacientes tratados entre janeiro de 2007 e outubro de 2010 receberam o esquema rifampicina-isoniazida-pirazinamida (RHZ), e aqueles tratados entre novembro de 2010 e junho de 2013 receberam o esquema rifampicina-isoniazida-pirazinamida-etambutol em DFC (RHZE/DFC). Os dados dos pacientes sobre recidiva e óbito foram obtidos no Sistema de Informação de Agravos de Notificação e no Sistema de Informação de Mortalidade, respectivamente. O período de acompanhamento foi de dois anos após o encerramento do tratamento. Resultados: As taxas de cura, abandono e óbito foram de 90,4%, 4,8% e 4,8%, respectivamente. Houve 7 casos de recidivas durante o período de acompanhamento. Não houve diferenças significativas na taxa de recidiva entre os grupos de tratamento RHZ e RHZE/DFC (p = 0,13). Não foram identificados fatores associados com a ocorrência de recidiva, nem houve diferenças estatisticamente significativas na ocorrência dos efeitos adversos ou nas taxas de cura, abandono e óbito entre os grupos de tratamento. Conclusões: A adoção do esquema de tratamento RHZE/DFC não produziu diferenças estatisticamente significativas nas taxas de recidiva, cura e abandono nem na ocorrência de efeitos adversos em comparação com o esquema RHZ.

Xpert MTB/RIF test performance assay in respiratory samples at real work settings in a developing country / Rendimiento de la prueba Xpert MTB/RIF en muestras respiratorias en el escenario real de trabajo en un país en desarrollo

Introduction: The Xpert MTB/RIF test detects DNA from Mycobacterium tuberculosis complex and susceptibility to rifampin. It has been evaluated repeatedly under "ideal" conditions including centrifugation of sputum and bronchoalveolar lavage, Ziehl Neelsen (ZN) and auramine/rhodamine staining, as well as with solid and liquid automated culture methods. Results from such evaluations cannot be extrapolated to low-income countries that do not routinely use all these processes. Objective: To assess the performance of the Xpert MTB/RIF test in respiratory samples under "real" conditions of work in a low-income country and its correlation with phenotypic susceptibility testing. Materials and methods: We conducted a cross-sectional study to assess the performance of the Xpert MTB/RIF test in =12 year-old patients with suspected pulmonary tuberculosis. In routine sample processing at the Hospital we do not use sputum centrifugation, staining with auramine/rhodamine or automated liquid culture. Results: We screened 152 patients of whom 108 were eligible for the study and 103 were included in the analysis; 34% of the samples were positive. The overall test sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 91%, 92%, 83% and 96%, respectively. In ZN-negative samples the sensitivity, specificity, PPV and NPV were 87%, 91%, 68% and 97%, respectively. The results of sensitivity and resistance to rifampin were concordant with susceptibility testing using the multiple proportions method (kappa=1, p<0.0001). Conclusions: The Xpert MTB/RIF test overall performance was similar to the one achieved under ideal conditions. Its performance in ZN-negative samples was better under "real" conditions of work in a low-income country.

Introducción. La prueba Xpert MTB/RIF detecta el ADN del complejo Mycobacterium tuberculosis y la sensibilidad a rifampicina. La prueba ha sido evaluada en condiciones "ideales" que incluyen la centrifugación de esputo y el lavado broncoalveolar, la tinción de Ziehl Neelsen (ZN) y de auramina-rodamina y los métodos de cultivo sólido y de cultivo líquido automatizado. Los resultados de tales evaluaciones no pueden extrapolarse a países de bajos ingresos que no utilizan habitualmente todos estos procesos. Objetivo. Evaluar el rendimiento de la prueba Xpert MTB/RIF en muestras respiratorias bajo condiciones "reales" de trabajo y su correlación con las pruebas fenotípicas de sensibilidad. Materiales y métodos. Se llevó a cabo un estudio transversal para evaluar el rendimiento de la prueba Xpert MTB/RIF en pacientes =12 años con sospecha de tuberculosis pulmonar. En el procesamiento rutinario de muestras en el Hospital del estudio no se usa la centrifugación del esputo, la tinción con auramina-rodamina ni el cultivo líquido automatizado. Resultados. Se incluyeron 152 pacientes, de los cuales 108 eran elegibles y 103 se incluyeron en el análisis. El 34 % de las muestras fueron positivas; la sensibilidad de la prueba fue de 91 %, la especificidad de 92 %, el valor diagnóstico positivo de 83 % y el valor diagnóstico negativo global de 96 %. En las muestras negativas con Ziehl Neelsen, la sensibilidad fue de 87 %, la especificidad de 91 % y los valores diagnósticos positivo y negativo alcanzaron 68 y 97 %, respectivamente. Los resultados de sensibilidad o resistencia a la rifampicina concordaron con los de la prueba fenotípica de sensibilidad (valor de kappa=1, p<0,0001). Conclusiones. El rendimiento global de la prueba fue similar al obtenido bajo condiciones "ideales". En las muestras negativas con Ziehl Neelsen se obtuvo un mejor rendimiento en las condiciones "reales" de trabajo de un país de bajos ingresos.

Cutaneous tuberculosis: diagnosis, histopathology and treatment - Part II

The evolution in the knowledge of tuberculosis' physiopathology allowed not only a better understanding of the immunological factors involved in the disease process, but also the development of new laboratory tests, as well as the establishment of a histological classification that reflects the host's ability to contain the infectious agent. At the same time, the increasing bacilli resistance led to alterations in the basic tuberculosis treatment scheme in 2009. This article critically examines laboratory and histological investigations, treatment regimens for tuberculosis and possible adverse reactions to the most frequently used drugs.

Tuberculosis intestinal / Intestinal tuberculosis

La tuberculosis (TBC) es una enfermedad infecciosa crónica, de tipo granulomatosa, producida por el Mycobacterium tuberculosis. En Chile es endémica, con tasas de 18 casos por 100.000 habitantes. La forma extrapulmonar constituye el 24 por ciento de los casos totales, siendo el compromiso intestinal uno de los más frecuentes, destacando la región ileo-cecal como la más afectada (90 por ciento de los casos). El diagnóstico es complejo ya que las manifestaciones clínicas son inespecíficas y el bacilo difícil de aislar, lo que muchas veces retrasa el inicio del tratamiento aumentando la morbimortalidad. Las manifestaciones clínicas habituales son: dolor abdominal, fiebre, baja de peso y compromiso ileal, siendo frecuente la duda diagnóstica con otras enfermedades que afectan el íleon distal, principalmente la enfermedad de Crohn. El diagnóstico definitivo sólo puede ser realizado a través de la histología o la detección directa del bacilo. La notificación de los casos de TBC es obligatoria en nuestro país; el tratamiento estándar con drogas antituberculosas es altamente efectivo y está garantizado para toda la población chilena.

Tuberculosis (TBC) is a chronic infectious disease of granulomatous type, caused by Mycobacterium tuberculosis. In Chile, the disease is endemic with rates of 18 cases per 100,000 inhabitants. The extrapulmonary form accounts for 24 percent of the total cases. Of these, intestinal tuberculosis is the most frequent, being the ileo-colonic region the most affected (90 percent of cases). Diagnosis is complex because the clinical manifestations are non specific and the bacteria is difficult to isolate, which often delays the onset of treatment thus increasing morbidity and mortality. The most common clinical manifestations are abdominal pain, fever, weight loss and ileal disease, increasing the diagnostic uncertainty in relation to other diseases affecting the distal ileum, mainly Crohn’s disease. A definitive diagnosis can only be made through histology or direct detection of the bacillus. Notification of TBC cases is mandatory in our country; standard treatment with antituberculosis drugs is highly effective and is guaranteed for the entire Chilean population.

Tuberculosis miliar en paciente inmunocompetente: caso clínico y revisión de la literatura / Miliary tuberculosis in immunocompetent patient: case report and literature review

La tuberculosis en Chile ha tenido un considerable descenso en incidencia y mortalidad, encontrándonos en la etapa de eliminación como problema de salud pública. Sin embargo, a medida que la tuberculosis pulmonar disminuye en frecuencia, la proporción de tuberculosis extrapulmonar se incrementa. Como es conocido, el pulmón es el órgano diana por excelencia, pero cualquier órgano puede ser afectado. Dentro de las tuberculosis extrapulmonares, la forma miliar corresponde sólo a un 5 por ciento de los casos. La diseminación miliar es rara en pacientes inmunocompetentes, estando prácticamente restringida a grupos de riesgo. El diagnóstico de la tuberculosis miliar requiere de un alto índice de sospecha, ya que su clínica es inespecífica, y el aislamiento del bacilo de Koch difícil.

Anti-mycobacterial treatment reduces high plasma levels of CXC-chemokines detected in active tuberculosis by cytometric bead array

Chemokines recruit and activate leukocytes, assisting granuloma formation. Herein, we evaluated plasma chemokines in patients with active tuberculosis (ATB) and after completing treatment (TTB) and compared them to BCG-vaccinated healthy controls (HC). Levels of chemokines were measured by cytometric bead array. Levels of CXCL8, CXCL9 and CXCL10 were higher in ATB patients compared to HC, but they decreased in TTB. Levels of CCL2 and CCL5 in ATB patients were similar to those observed in HC. Thus, the high levels of CXC-chemokines detected during ATB, which can modulate the trafficking of immune cells from the periphery to the site of infection, were reversed by anti-mycobacterial treatment.

Tuberculosis experimental y nanopartículas de las drogas específicas / Experimental tuberculosis and nanoparticles of specific drugs

La tuberculosis (TB) sigue siendo un problema epidemiológico dificil de controlar, especialmente en los países en vías de desarrollo. Por ello, será bienvenido todo lo que implique una mejoría en su manejo. La incorporación de las nanopartículas a la medicina, producida en los últimos años, puede traer aparejada ventajas en su diagnóstico y tratamiento, así como un control en el número creciente de pacientes enfermos con gérmenes multirresistentes a las drogas específicas. Se actualiza en esta publicación que, en diversos países del mundo, animales de laboratorio, cobayos y ratones, inoculados por el Mycobacterium tuberculosis, tuvieron mejorías llamativas de su enfermedad o su esterilización después de ser tratados con las drogas específicas (Isoniacida, Rifampicina, Pirazinamida y Estreptomicina) suministradas como nanopartículas. No se han efectuado hasta ahora experimentos en tuberculosis humana, pero las posibilidades son promisorias. Las nanopartículas tienen varias ventajas terapéuticas: gran estabilidad, gran capacidad para conducir múltiples drogas, varias vías de administración (inhalatoria, oral, intravenosa y subcutánea). Esperamos que en un futuro próximo podamos asistir a mejoras en el manejo de la tuberculosis humana.

Tuberculosis (TB) continues to be a difficult to control epidemiologic problem, particularly in the developing countries. For such reason, anything that may imply an improvement in its management will be welcome. The adoption of nanoparticles by the medical science, over the last few years, may entail advantages regarding its diagnosis and treatment as well as a control of the increasing number of patients infected with specific drug multi-resistant germs. The present publication introduces the information that in several countries laboratory animals, guinea-pigs and mice, inoculated with Mycobacterium tuberculosis, either showed striking recoveries or the sterilization of their disease after being treated with the specific drugs (Isoniazid, Rifampycin, Pyrazinamide and Streptomycin) administered as nanoparticles. No experiments have been made to date in human tuberculosis but there exist promising possibilities. Nanoparticles have several therapeutic advantages: great stability, a large capacity to carry multiple drugs, different routes of administration (inhalatory,oral, intravenous and subcutaneous). We expect that in the near future we will be able to see an improvement in the management of human tuberculosis.