Tuberculosis abdominal en pediatría: presentación de un caso / Abdominal tuberculosis in pediatrics: A case report

La tuberculosis es una enfermedad infectocontagiosa cuya forma de presentación más frecuente es la pulmonar; la afectación abdominal es poco frecuente, por lo que su diagnóstico continúa siendo un desafío. Las manifestaciones clínicas de la tuberculosis abdominal así como sus hallazgos en el examen físico suelen ser inespecíficos y, en muchas ocasiones, similares a los de otras patologías, por lo que es fundamental considerarla entre los diagnósticos diferenciales. Se presenta el caso clínico de un paciente de sexo masculino, de 15 años de edad, hospitalizado por un síndrome febril prolongado asociado a dolor abdominal, diarrea, sudoración nocturna y pérdida de peso

Tuberculosis is an infectious disease which most commonly compromises the respiratory system, whereas abdominal involvement is rare, thus its diagnosis is a challenge. The clinical manifestations of abdominal tuberculosis as well as its physical examination findings are usually non-specific and, frequently, similar to those of other diseases, so it is critical to consider abdominal tuberculosis among the differential diagnoses. Here we report the clinical case of a 15-year-old male patient hospitalized for a prolonged febrile syndrome associated with abdominal pain, diarrhea, night sweats, and weight loss.

Masa nasal como único compromiso extrapulmonar de infección por M. Tuberculosis / Nasal mass as the only extrapulmonary compromise of M. Tuberculosis infection / Massa nasal como único compromisso extrapulmonar da infecção por M. Tuberculose

La tuberculosis aún es un problema de salud pública mundial. La infección causada por Mycobacterium tuberculosis se manifiesta de forma principal a nivel pulmonar. Sin embargo, alrededor del 20 % de los casos se presentan en otras localizaciones anatómicas y solo el 2 % tiene afectación del tracto respiratorio superior. Se presenta el caso de una mujer de 75 años, reconsultante al servicio de otorrinolaringología por epistaxis, lesiones postillosas en cavidad nasal y hallazgo de masa nasal. Posterior a la resección quirúrgica de la lesión, se logró la comprobación microbiológica de infección por M. tuberculosis. Se realizan estudios para descartar compromiso pulmonar y de otras localizaciones. Posterior al inicio de tratamiento antituberculoso se logró resolución completa de la lesión y no recurrencia de los síntomas. Las formas extrapulmonares de la infección por M. tuberculosis y, en especial las que afectan la región de la cabeza y el cuello, requieren un alto índice de sospecha para su diagnóstico. Los métodos de diagnóstico como la prueba de PCR y los cultivos de tejidos permiten un óptimo inicio del manejo médico de acuerdo con la epidemiología local y las condiciones del paciente.

Tuberculosis is still a global public health burden. Infection caused by the bacillus Mycobacterium tuberculosis (M. Tuberculosis) manifests mainly in the lungs. However, around 20 % of cases occur in other anatomical locations and only 2 % have upper respiratory tract involvement. We present the case of a 75-year-old female patient, who returned to the otorhinolaryngology service due to epistaxis and postillomous lesions in the nasal cavity with a finding of a nasal mass. After surgical resection of the lesion, microbiological confirmation of M. tuberculosis infection is achieved. Studies are performed to rule-out lung involvement, as well as other locations. After the initiation of tuberculosis treatment, complete resolution of the lesion and no recurrence of symptoms is documented. Extrapulmonary forms of M. tuberculosis infection, and especially those involving the head and neck region, require a high index of suspicion for their diagnosis. Diagnostic methods such as PCR testing and tissue cultures allow optimal initiation of medical management according to local epidemiology and patient conditions.

A tuberculose ainda é um problema de saúde pública global. A infecção causada pelo Mycobacterium tuberculoses manifesta-se principalmente nos pulmões. Entretanto, cerca de 20% dos casos ocorrem em outras localizações anatômicas e apenas 2% apresentam comprometimento do trato respiratório superior. É apresentado o caso de uma mulher de 75 anos que retornou ao serviço de otorrinolaringologia por quadro de epistaxe, lesões com crostas em cavidade nasal e descoberta de massa nasal. Após ressecção cirúrgica da lesão, foi realizada verificação microbiológica de infecção por M. tuberculoses. Estudos são realizados para descartar envolvimento pulmonar e otras localizações. Após início do tratamento antituberculoso, houve resolução completa dalesão e não houve recidiva dos sintomas. As formas extrapulmonares da infecção por M. tuberculoses, especialmente aquelas que acometem a região de cabeça e pescoço, requerem alto índice de suspeita para diagnóstico. Métodos de diagnóstico, como testes de PCR e culturas de tecidos, permitem o início ideal do tratamento médico de acordó com a epidemiologia local e as condições do paciente.

Mycobacterium tuberculosis latent infection in healthcare students: systematic review of prevalence / Infecção latente por Mycobacterium tuberculosis em estudantes da área da saúde: revisão sistemática de prevalência / Infección latente por Mycobacterium tuberculosis en estudiantes de la salud: revisión sistemática de la prevalencia

ABSTRACT Objective: The aim of this study was to synthesize the evidence on the prevalence of latent Mycobacterium tuberculosis infection (LTBI) among undergraduate health care students. Methods: A systematic review of prevalence with meta-analysis was conducted. Prospective and retrospective cohorts and cross-sectional studies involving probable exposure to M. tuberculosis during undergraduate education, along with the tuberculin skin test (TST) or interferon-γ release assay (IGRA) for investigation of latent tuberculosis were searched. Searches were conducted in MEDLINE, CINAHL, EMBASE, LILACS, Scopus, and Web of Science databases. Independent reviewers were responsible for the selection and inclusion of studies. Data were extracted, critically appraised, and synthesized using the JBI approach. PRISMA was used to report the study. Results: Twenty-two studies were analyzed. The overall prevalence in healthcare undergraduate students was 12.53%. Conclusion: The prevalence of LTBI in undergraduate health students was high for such a highly educated population. Screening with TST and/or IGRA and chemoprophylaxis, when necessary, should be provided to undergraduate health students when in contact with respiratory symptomatic patients.

RESUMO Objetivo: O objetivo deste estudo foi sintetizar as evidências sobre a prevalência de infecção de Mycobacterium tuberculosis (ILTB) entre estudantes de graduação da área da saúde. Método: Foi realizada uma revisão sistemática de prevalência com metanálise. Coortes prospectivas e retrospectivas e estudos transversais envolvendo provável exposição a M. tuberculosis durante a graduação, juntamente com o teste tuberculínico (TT) ou ensaio de liberação de interferon-γ (IGRA) para investigação de tuberculose latente foram pesquisados. As buscas foram realizadas nas bases de dados MEDLINE, CINAHL, EMBASE, LILACS, Scopus e Web of Science. Revisores independentes foram responsáveis pela seleção e inclusão dos estudos. Os dados foram extraídos, avaliados criticamente e sintetizados utilizando a abordagem JBI. PRISMA foi usado para relatar o estudo. Resultados: Vinte e dois estudos foram analisados. A prevalência geral em estudantes de graduação da área da saúde foi de 12,53%. Conclusão: A prevalência de ILTB em estudantes de graduação em saúde foi alta para uma população com alto nível de escolaridade. Triagem com TT e/ou IGRA e quimioprofilaxia, quando necessária, deve ser fornecida aos estudantes de graduação da área da saúde quando em contato com pacientes sintomáticos respiratórios.

RESUMEN Objetivo: El objetivo de este estudio fue sintetizar la evidencia sobre la prevalencia de infección latente por Mycobacterium tuberculosis (ILTB) entre estudiantes universitarios de la salud. Métodos: Se realizó una revisión sistemática de la prevalencia con metanálisis. Cohortes prospectivas y retrospectivas y estudios transversales que involucran exposición probable a M tuberculosis durante la educación universitaria, junto con la prueba cutánea de tuberculina (TST) o el ensayo de liberación de interferón-γ (IGRA) para la investigación de tuberculosis latente. Las búsquedas se realizaron en las bases de datos MEDLINE, CINAHL, EMBASE, LILACS, Scopus y Web of Science. Revisores independientes fueron responsables de la selección e inclusión de los estudios. Los datos se extrajeron, se evaluaron críticamente y se sintetizaron utilizando el enfoque JBI. Se utilizó PRISMA para informar el estudio. Resultados: Se analizaron veintidós estudios. La prevalencia global en estudiantes universitarios en salud fue del 12,53%. Conclusión: La prevalencia de LTBI en estudiantes universitarios de salud fue alta para una población con un nivel educativo tan alto. Se debe proporcionar tamizaje con TST y/o IGRA y quimioprofilaxis, cuando sea necesario, a los estudiantes universitarios en salud cuando estén en contacto con pacientes sintomáticos respiratorios.

Evaluation of the GeneXpert MTB/RIF to diagnose tuberculosis in a public health laboratory

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.

Development and verification of a reversed phase high-performance liquid chromatography method for purity determination of recombinant Mycobacterium tuberculosis Ag85b protein stock solution / 中国生物制品学杂志

@#Objective To develop and verify a reversed phase high-performance liquid chromatography method for the determination of the purity of recombinant Mycobacterium tuberculosis(Mtb)Ag85b protein stock solution.Methods Fourfactor,three-level orthogonal test was designed,with the area,trailing factor,peak area and peak area RSD as the evaluation indexes to explore the optimal detection conditions. The methodology verification of specificity,linear range,precision and durability was conducted in accordance with the general principles of Chinese Pharmacopoeia(Volume Ⅳ,2020 edition)9101.Results The results of all the evaluation indexes were good when the elution ratio of organic phase was30% ～ 95%,the detection temperature was 35 ℃,the sample volume was 3 μg,and the elution time of 95% organic phase was 15 min. The method had the linear correlation coefficient(R2)of 0. 998 5,the linear range of 1. 8 ～ 4. 2 μg,the reproducibility RSD of 0. 01%,and the intermediate precision RSD of 0. 16%,with good durability under slight changes of column temperature and flow rate.Conclusion The reversed phase high-performance liquid chromatography method for the purity determination of recombinant Mtb Ag85b protein stock solution was developed,which has good specificity,precision and durability,and can be used for the quality control of recombinant Mtb Ag85b protein stock solution.

Prokaryotic expression and functional analysis of molecular chaperone Acr2 protein of Mycobacterium tuberculosis / 中国生物制品学杂志

@#Objective To express the molecular chaperone Acr2 protein of Mycobacterium tuberculosis(Mtb)in E.coli and analyze the function. Methods The recombinant plasmid pET-28a-Acr2 was transformed into competent E. coli BL21(DE3),and induced by IPTG. The expressed His-Acr2 protein was purified by Ni-NTA chromatography and SuperdexTM200 10/300 GL gel filtration chromatography to obtain Acr2 protein. The Acr2 protein was refolded by spontaneous refolding and reassembly after thermal denaturation(100 ℃ for 15 min)and chemical denaturation(8 mol/L urea,37 ℃ for 4 h).The secondary structure of Acr2 protein before and after denaturation-renaturation was detected by circular dichroism spectroscopy and non-denaturing SDS-PAGE,and the molecular chaperone function of Acr2 protein in vitro was detected by substrate binding assay. Results The purified Acr2 protein had the relative molecular mass of about 232 000,the purity of over 90%,and the concentration of about 2 mg/mL,which recovered its natural secondary structure after denaturationrenaturation,and formed stable complexes with the denatured malate dehydrogenase(MDH)at 48 ℃. Conclusion The Acr2protein can restore its natural molecular conformation with molecular chaperone activity in vitro after denaturation-renaturation treatment,providing a new strategy for the preparation of Mtb protein antigen with natural activity.

Un desafío terapéutico: la heterorresistencia en Mycobacterium tuberculosis / An emerging problem: heteroresistance in Mycobacterium tuberculosis

Resumen Se considera infección mixta por Mycobacterium tuberculosis (Mtb) a la coexistencia en forma simul tánea y en un mismo paciente de 2 cepas diferentes de Mtb o 2 variantes distintas de la misma cepa. Cuando una de las variantes selecciona mutaciones de resistencia, se denomina heterorresistencia (HTR) monoclonal; en caso de que sean 2 cepas diferentes, una sensible y una resistente (o cepas con diferentes patrones de resistencia), se denomina HTR policlo nal. Se presentan 3 pacientes, HIV/sida, todos con reiterados problemas de adherencia al tratamiento, en los cuales a través de la secuenciación genómica completa de Mtb se diagnosticó HTR monoclonal con coexistencia de 2 variantes de la misma cepa aisladas de muestras de pulmón y ganglios linfáticos, con diferentes perfiles de resistencia en cada uno de los casos. Es importante pensar en la posibilidad de HTR, principalmente en pacientes con múltiples intentos terapéuticos previos y altas poblaciones bacilares, como en el sida avanzado, dado que esta situación compromete potencialmente los resultados del tratamiento al coexistir cepas o variantes de ce pas sensibles y resistentes.

Abstract Mixed infection by Mycobacterium tuberculosis (Mtb) consists in the simultaneous coexistence in the same patient of two different strains of Mtb or 2 different variants of the same strain. When one of the variants selects for resistance mutations, it is called monoclonal heteroresistance (HTR); if there are 2 different strains, one sensitive and one resistant (or with different resis tance patterns), it is called polyclonal HTR. Three cases of HIV/AIDS patients are presented, all with repeated treatment adherence problems, in whom monoclonal HTR was diagnosed through Mtb complete genomic sequentiation with the coexistence of two variants of the same strain isolated from samples from lung and lymph nodes, with different resistance profiles in each case. It is important to consider the possibility of HTR, especially in patients with multiple previous therapeu tic attempts and high bacillary populations, such as in advanced AIDS, since this situation potentially com promises treatment results by coexisting sensitive and resistant variants of a strain (or strains).

Tuberculosis congénita: a propósito de un caso

La tuberculosis (TB) es una de las principales enfermedades infecciosas a nivel mundial y sigue siendo un grave problema de salud pública en muchos países. La Organización Mundial de la Salud (OMS) estima que un tercio de la población está infectada con TB y la tasa de infección aumenta casi un 1% por año. Esta revisión tiene como objetivo exponer la identidad de la tuberculosis congénita rara y fatal si no se trata y resaltar las características clínicas y la dificultad de diagnóstico y la conciencia entre los pediatras para realizar un manejo terapéutico inmediato desde el inicio de la sospecha. Este estudio se propone detectar que el pronóstico es malo para los recién nacidos, seguido de una evolución fatal cuando el diagnóstico se retrasa. Se presenta a continuación el caso de un recién nacido de sexo masculino de 24 días de vida por parto cesárea, por RPM nacido de una madre que presentó infección por SARS-COV-2 14 días previos al parto. A los 5 días de post parto adormecimiento y debilidad de miembros inferiores, sin síntomas respiratorios, posteriormente fiebre de 5 días de evolución, con diagnóstico de TB cerebral sin síntomas respiratorios, RN con fiebre y tos de 3 días, hepatomegalia de 4.5 cm, sin adenopatías. Ecografía abdominal dentro de parámetros normales, ecocardiograma con despegamiento pericárdico laminar, ecografía cerebral, ecografía abdominal fondo de ojo dentro de parámetros normales. Radiografía de tórax mostró infiltrado nodulillar difuso bilateral compatible con diseminación miliar tuberculosa. Al ingreso se inició cobertura antibiótica con Cefotaxima más Ampicilina a dosis meníngea. Analítica laboratorial al ingreso perfil hepático alterado, glóbulos blancos en rango, presentó granulaciones toxicas 3% y reactantes de fase aguda aumentados. Se realizó punción lumbar con cultivo de LCR negativo para gérmenes comunes y micobacterias por lo cual se descendió antibioticoterapia a completando 9 días totales. En muestras seriadas durante 3 días de líquido gástrico tinción de Ziehl-Neelsen BAAR +++ en las 3 muestras, GENEXPERT M. tuberculosis detectado y secreción traqueal tinción de BAAR +++. Inició terapia antibacilar H10/R20/Z20/E20. Durante su internación presenta alteración de perfil hepático por lo cual se ajusta dosis H5/R10/Z15/E15 en conjunto con Piridoxina. Durante tratamiento antibacilar a los 10 meses presentó en ecografía abdominal múltiples calcificaciones en hígado y ecografía cerebral de control con dilatación leve de los ventrículos laterales en ambos lados. Al finalizar tratamiento al examen físico se constató hígado a 2 cm RCD al año de vida, crecimiento y desarrollo normal para la edad, controles oftalmológicos y auditivos sin hallazgos patológicos. El recién nacido recibió 2 meses de HRZE y 10 meses de HR completando 12 meses totales de tratamiento en conjunto con Piridoxina hasta 10 días posterior a la suspensión de antibacilares y la madre recibió 4 meses de HRZE y 8 meses de HR completando 12 meses de tratamiento antibacilar.

Tuberculosis (TB) is one of the major infectious diseases worldwide and continues to be a serious public health problem in many countries. The World Health Organization (WHO) estimates that one third of the population is infected with TB and the infection rate is increasing by almost 1% per year. This review aims to expose the identity of rare and fatal congenital tuberculosis if left untreated and to highlight the clinical features and the difficulty of diagnosis and awareness among pediatricians to perform immediate therapeutic management from the onset of suspicion. This study aims to detect that the prognosis is poor for newborns, followed by a fatal course when diagnosis is delayed. The case of a 24-day-old male newborn by cesarean section, due to PROM born to a mother who presented SARS-COV-2 infection 14 days prior to delivery, is presented below. At 5 days postpartum, numbness and weakness of the lower limbs, without respiratory symptoms, later fever of 5 days of evolution, with a diagnosis of cerebral TB without respiratory symptoms, newborn with fever and cough of 3 days, hepatomegaly of 4.5 cm, without adenopathies. Abdominal ultrasound within normal parameters, echocardiogram with laminar pericardial detachment, brain ultrasound, fundus abdominal ultrasound within normal parameters. Chest X-ray showed bilateral diffuse nodular infiltrate compatible with tuberculous miliary dissemination. On admission, antibiotic coverage was started with Cefotaxime plus Ampicillin at a meningeal dose. Laboratory analysis on admission altered liver profile, white blood cells in range, presented 3% toxic granulations and increased acute phase reactants. A lumbar puncture was performed with a negative CSF culture for common germs and mycobacteria, for which antibiotic therapy was decreased to a total of 9 days. In serial samples for 3 days of gastric fluid Ziehl-Neelsen AFB staining +++ in the 3 samples, GENEXPERT M. tuberculosis detected and tracheal secretion AFB staining +++. He started H10/R20/Z20/E20 antibacillary therapy. During his hospitalization, he presented an alteration in the liver profile, for which the H5/R10/Z15/E15 dose was adjusted in conjunction with Pyridoxine. During antibacillary treatment at 10 months, abdominal ultrasound revealed multiple calcifications in the liver and control brain ultrasound with mild dilatation of the lateral ventricles on both sides. At the end of treatment, the physical examination confirmed the liver at 2 cm RCD at one year of life, normal growth and development for age, ophthalmological and hearing controls without pathological findings. The newborn received 2 months of HRZE and 10 months of HR, completing a total of 12 months of treatment in conjunction with Pyridoxine up to 10 days after the suspension of antibacillary drugs, and the mother received 4 months of HRZE and 8 months of HR, completing 12 months of treatment. antibacillary.

Hemoptisis secundaria a tuberculosis pulmonar complicada con pseudoaneurisma de Rasmussen. Reporte de un caso en pediatría. / Hemoptysis in Pulmonary Tuberculosis Complicated by Rasmussen's Pseudoaneurysm. A Pediatric Case Report.

Presentamos el caso de un niño de 12 años que consultó por hemoptisis, sin otros sín- tomas asociados. Se realizó radiografía de tórax (patológica), laboratorio con aumen- to moderado de reactantes de fase aguda, PPD (negativa), esputos x 3 con bacilosco- pias negativas y tomografía de tórax con contraste i.v. que mostró imágenes de árbol en brote en todos los lóbulos y una imagen de dilatación vascular de una rama de la ar- teria pulmonar en lóbulo superior izquierdo. Se plantearon diagnósticos diferenciales: malformación vascular primaria o lesión secundaria a infección. La angiografía digital permitió confirmar el pseudoaneurisma y embolizarlo. Luego de 17 días, 2/3 cultivos de esputo fueron positivos para Mycobacterium tuberculosis. El niño realizó tratamiento antituberculoso con drogas de primera línea con evolución clínica favorable. Este caso resalta la importancia de considerar el pseudoaneurisma de Rasmussen en- tre las posibles complicaciones de un paciente con tuberculosis y hemoptisis recurren- te o masiva.

We present the case of a 12-year-old boy admitted to the hospital due to hemoptysis without other symptoms. We performed a Thorax X-Ray (pathological), laboratory with elevated acute phase reactants, TST (negative), sputum x 3 with negative smear and computed tomography angiography showing a tree-in-bud pattern in all lobes, and di-latation of a brunch of the pulmonary artery in the upper left lobe. We considered pri-mary vascular anomaly or lesion due to infection as a differential diagnosis. The patient underwent digital angiography and therapeutic embolization of this pseudoaneurysm. After seventeen days, 2/3 of the sputum cultures were positive for Mycobacterium tu-berculosis. The patient received standard anti-TB therapy with favorable evolution. This case highlights the importance of considering complications such as Rasmussen's pseudoaneurysm in patients with pulmonary tuberculosis and recurrent or massive hemoptysis.

Evaluación de los patrones de farmacorresistencia de mycobacterium tuberculosis en un hospital público de Lima, Perú durante 2022

Antecedentes: La tuberculosis es un problema de salud pública considerado la principal causa mundial de muerte por una enfermedad infecciosa entre los adultos. El diagnóstico suele ser difícil y se basa en hallazgos clínicos, epidemiológicos, radiológicos, bacteriológicos, histológicos y bioquímicos. El diagnóstico oportuno, la identificación del perfil de susceptibilidad y el cumplimiento del seguimiento son importantes para permitir un tratamiento más eficaz y evitar formas graves de la enfermedad. Objetivo: Describir los patrones de resistencia de Mycobacterium tuberculosis identificados en el periodo del año 2022 en el Hospital María Auxiliadora. Material y métodos: Se trata de un estudio observacional, transversal, de pacientes diagnosticados de tuberculosis durante todo el año 2022 en el Centro de Excelencia en Tuberculosis (COE-TB), división del servicio de medicina respiratoria del Hospital María Auxiliadora, Lima, Perú. Los datos fueron recolectados de las historias clínicas que luego fueron incluidas para el análisis estadístico. Las características clínicas y demográficas se describieron mediante frecuencias absolutas y porcentajes. Para evaluar la asociación entre el perfil de sensibilidad de la tuberculosis y las variables independientes se utilizó la prueba de Chi cuadrado y la prueba exacta de Fisher. Un valor p < 0,05 se consideró estadísticamente significativo. Resultados: Se incluyeron en el presente estudio 261 historias clínicas. El grupo de edad más frecuente fue el de 17-59 años, la mayoría eran varones (62,1%) y el 15,7% eran recidivantes, según lo establecido en la norma técnica nacional. Del total, el 89,7% eran sensibles a fármacos de primera línea; el 6,1% de los pacientes eran multirresistentes (MDR), y el 0,8% presentaban resistencia extensiva a fármacos (XDR); asimismo, el 0,8% y el 2,7% presentaban resistencia sólo para rifampicina y resistencia sólo para isoniazida respectivamente. La infección por VIH se detectó en el 14,2%. La forma más frecuente de tuberculosis fue la pulmonar (49%), seguida de la tuberculosis pleural (21,8%). Conclusiones: La tuberculosis es una afección mundial cuyos patrones de farmacorresistencia continúan evolucionando. Sin embargo, en nuestro hospital, un centro de referencia del sur del Perú, la mayoría de los pacientes con TB siguen siendo sensibles a los fármacos de primera línea. Sólo se encontró una pequeña cantidad de pacientes MDR y XDR. Además, la presentación clínica más frecuente fue la tuberculosis pulmonar seguida de la pleural.

Background: Tuberculosis is a public health problem considered to be the world's leading cause of death from an infectious disease among adults. Diagnosis is often challenging and is based on clinical, epidemiological, radiological, bacteriological, histological and biochemical findings. Timely diagnosis, identification of the susceptibility profile and follow-up compliance is important to enable more effective treatment and avoid severe forms of the disease. Objective: Describe the resistance patterns of Mycobacterium tuberculosis identified in the period of the year 2022 at Hospital María Auxiliadora. Material and Methods: This is an observational, cross-sectional study of patients diagnosed with tuberculosis throughout the year 2022 in the Tuberculosis Center of Excellence (TB COE), division of the respiratory medicine department at the Hospital Maria Auxiliadora, Lima, Peru. Data was collected from the medical records which was then included for the statistical analysis. The clinical and demographic characteristics were described by absolute frequencies and percentages. Chi-square test and Fisher's exact test were used to evaluate the association between the sensitivity profile of tuberculosis and the independent variables. A p-value < 0.05 was considered as statistically significant. Results: A total of 261 medical records were included in the present study. The most frequent age group was 17-59 years old, the majority were male (62.1%) and 15.7% were relapses, as established on national technical standard. Of the total, 89.7% were sensitive to first line drugs; 6.1% of the patients were multidrug-resistant (MDR), and 0.8% presented extensively drug-resistance (XDR); likewise, 0.8% and 2.7% presented resistance for rifampicin only and resistance for isoniazid only respectively. HIV infection was found at 14.2%. The most common form of tuberculosis was pulmonary (49%) followed by pleural tuberculosis (21.8%). Conclusion: Tuberculosis is a worldwide condition whose drug-resistance patterns continue evolving. However, in our hospital, a southern Peru reference Center, most TB patients are still sensitive to first line drugs. Only a small amount of MDR and XDR patients were found. Moreover, the most common clinical presentation was pulmonary followed by pleural tuberculosis.

A Case Report of Primary Hepatic Tuberculosis

This case report presents an incidental finding of primary tuberculosis in the liver of a 54-year-old female patient who had a history of multiple hospital admissions due to abdominal pain, jaundice, persistent fever, nausea with vomiting, weight loss, and asthenia. The evaluation involved considering differential diagnoses of cholangiocarcinoma, Caroli's disease, hepatocellular carcinoma, and hepatic tuberculosis based on the patient's history, imaging studies, and laboratory tests. The aim of this report is to provide healthcare professionals with a new diagnostic perspective when encountering patients with this ambiguous presentation, even in regions with low epidemiological incidence. Hepatic tuberculosis should be included in the differential diagnosis of patients with focal intrahepatic lesions or liver abscesses who have a history of recurrent hospitalizations and evidence on imaging studies.

Se trata de un hallazgo incidental de tuberculosis primaria en el hígado en una paciente femenina de 54 años con historia de múltiples ingresos por síntomas de dolor abdominal, ictericia, fiebre persistente, náuseas acompañadas de vómitos de contenido gástrico, pérdida de peso y astenia. A la evaluación se consideraron los diagnósticos diferenciales de colangiocarcinoma, enfermedad de Caroli, carcinoma hepatocelular y tuberculosis hepática, basados en anamnesis, estudios de imágenes y pruebas de gabinete. Este reporte de caso brinda una nueva perspectiva diagnóstica para el personal de salud que reciba pacientes con esta presentación ambigua, aun en el contexto de baja incidencia epidemiológica. La tuberculosis hepática debe ser considerada en el diagnóstico diferencial de pacientes con lesiones focales a nivel intrahepático o abscesos hepáticos con hospitalizaciones recurrentes y evidencia de imágenes.

Aplicación de PCR a partir de cultivo en la identificación de subespecies del complejo Mycobacterium Tuberculosis / The use of culture-based PCR for the identification of subspecies of the mycobacterium tuberculosis complex

Los métodos diagnósticos clásicos de tuberculosis (TB) se basan en la utilización de baciloscopía y cultivo. La identificación del agente etiológico desde la positivización del cultivo requiere entre 10 y 15 días, mientras que el empleo de la reacción en cadena de la polimerasa (PCR) disminuye el tiempo a 24 h, lo que permite no solo identificar las subespecies del complejo Mycobacterium tuberculosis (CMTB) sino también diferenciarlas de otras especies ambientales clínicamente importantes (MOTT) facilitando el diagnóstico y tratamiento. El objetivo del presente trabajo fue determinar la utilidad de la PCR en la identificación temprana de las micobacterias pertenecientes al CMTB, a partir de cultivos positivos, de pacientes con sospecha de TB, atendidos en un hospital pediátrico de alta complejidad, durante un período de cuatro años. A cada muestra, se le realizó baciloscopía y cultivo en medio líquido. A los cultivos positivos, una inmunocromatografía lateral (TBIDR) y luego PCR. El 4,6% del total de muestras (510/11.162) pertenecientes a 198 pacientes presentó cultivos positivos. Cuatrocientos veintiseis (84%) correspondieron a muestras respiratorias. El rendimiento de la baciloscopía directa fue del 41% (194/470). Cuatrocientos treinta y ocho (86%) resultaron M. tuberculosis, 21 (4%) Mycobacterium bovis, 7 (1%), M. bovis-BCG y 44 (9%) MOTT. La utilización de medios de cultivos líquidos junto con el empleo de PCR favorecen una rápida orientación microbiológica y constituye una estrategia útil para optimizar el manejo clínico de estas infecciones, desde el punto de vista terapéutico y epidemiológico, especialmente en pediatría (AU)

Classical diagnostic methods for tuberculosis (TB) are based on the use of smear microscopy and culture. The identification of the etiological agent from positive culture requires 10 to 15 days, while the use of the polymerase chain reaction (PCR) reduces the time to 24 h, which allows not only to identify the subspecies of the Mycobacterium tuberculosis complex (MTC) but also to differentiate them from clinically important environmental mycobacteria other than tuberculosis (MOTT), facilitating diagnosis and treatment. The aim of this study was to determine the usefulness of PCR in the early identification of mycobacteria belonging to the MTC, from positive cultures of patients with suspected TB seen in a pediatric tertiary hospital over a 4-year period. For each sample, smear microscopy and culture in liquid medium was performed. Positive cultures were subjected to lateral immunochromatography (TBIDR) and then PCR. Of the total number of samples (510/11,162) belonging to 198 patients, 4.6% showed positive cultures; 426 (84%) were respiratory samples. The direct smear microscopy yield was 41% (194/470). Overall, 438 (86%) were found to be M. tuberculosis, 21 (4%) Mycobacterium bovis, 7 (1%), M. bovis-BCG, and 44 (9%) MOTT. The use of liquid culture media together with the use of PCR favors a rapid microbiological orientation and is a useful strategy to optimize the clinical management of these infections, from a therapeutic and epidemiological point of view, especially in children (AU)

Changes of lymphocyte subsets in smear-negative pulmonary tuberculosis

Background and Aims: The host immune system plays an important role in the pathogenesis and defense mechanism of Mycobacterium tuberculosis (Mtb). This study aimed to explore the different changes in the immune system between smear-negative pulmonary tuberculosis (PTB) and smear-positive PTB patients. Materials and Methods: A total of 85 active PTB patients and 50 healthy adults were enrolled. The participants were divided into smear-negative PTB, smear-positive PTB, and control groups. Chest computed tomography (CT) and lymphocyte subgroup counts in peripheral blood were measured in all participants. Results: There were higher numbers of CD4 + T-cells, NK cells, and pulmonary cavities in the smear-positive PTB group, whereas the numbers of B-ells were significantly increased in the smear-negative PTB group. Conclusions: Smear-negative PTB showed fewer pulmonary cavities, mild inflammatory response, lower numbers of immune cells, and higher numbers of B- cells.

Infección del miocardio por Mycobacterium tuberculosis: una localización infrecuente de una infección antigua

La tuberculosis miocárdica es una localización infrecuente que, en general, se caracteriza por cuadros clínicos silentes. Su diagnóstico se basa en la alta sospecha clínica y hallazgos inespecíficos en las imágenes cardíacas, pero la histopatología continúa siendo el estándar de oro para establecer el diagnóstico. La terapia antituberculosa ha sido exitosa, presentando mejoría radiológica y clínica en la mayoría de los casos. Presentamos el caso de una infección miocárdica por Mycobacterium tuberculosis en un hombre de 34 años que consultó por un cuadro de disnea de varias semanas de evolución. Se pesquisó un derrame pleural derecho y pericárdico grave, sin signos de taponamiento cardíaco. La RPC para M. tuberculosis en líquido pleural resultó positiva. El estudio histológico de pericardio y miocardio evidenció una pericarditis crónica y una inflamación granulomatosa, no necrosante, con células gigantes multinucleadas en el tejido miocárdico. Se estableció el diagnóstico de tuberculosis pleural, pericárdica y miocárdica y se inició tratamiento antituberculoso, presentando una mejoría clínica significativa.

Myocardial tuberculosis is a rare location that is generally characterized by silent clinical pictures. Diagnosis is based on high clinical suspicion and some nonspecific findings on cardiac imaging, but histological findings remain the gold standard. Treatment with standard antitubercular drugs llave been successful, presenting radiological and clinical improvement in most cases. We report a case of myocardial infection by Mycobacterium tuberculosis in a 34-year-old man, who presented with several weeks of dyspnea and evidence of right pleural effusion and severe pericardial effusion, without signs of cardiac tamponade. PCR for M. tuberculosis was positive in pleural fluid. The histologic study of pericardium and myocardium showed myocardial fibers with non-necrotizing granulomatous inflammation with multinucleated giant cells. Due to all the above, a diagnosis of pleural and myocardial tuberculosis was made, and tuberculosis treatment was started with significant clinical improvement.

EVALUATION OF THE ANTI-MYCOBACTERIAL ACTIVITY OF ALLIUM ASCALONICUM AND ALLIUM SATIVUM

Mycobacterium tuberculosis (MTB), the organism causing tuberculosis (TB) remains a major cause of morbidity and mortality. Plant-based drugs have been used worldwide in traditional medicines for the treatment of various diseases including tuberculosis. Medicinal plants are an important source of new antimicrobial agents and remain an attractive alternative strategy. The present study was performed to evaluate anti-MTB activity of two medicinal plants viz., Allium ascalonicum, and Allium sativum. Different concentrations of extracts of these plants were tested for their anti MTB activity against MTBH37Rv strain and the inhibitory activity was expressed as CFU inhibition, % inhibition and IC50. In our study Allium sativum showed higher anti TB activity however this bactericidal property was not signi?cantly different between each groups. The overall anti mycobacterial activity of these extracts might be attributed due to the presence of ?avonoids, saponins, steroids, terpenoids, tannins and other phytoconstituents. The extract of the plant also exhibited promising antitubercular activity.

Incidence, Diagnosis and Treatment of Otorhinolaryngologicl, Head and Neck Tuberculosis: A Prospective Clinical Study

Abstract Introduction Tuberculosis is a disease of diversified presentation. It affects almost all organs in the body, and otorhinolaryngological, head and neck involvement is not an exception. Objective To increase awareness about the different clinical presentations of otorhinolaryngological, head and neck tuberculosis, the techniques employed to diagnose it, and to assess the response to the treatment. Methods We conducted a prospective study of 114 patients who presented primarily with otorhinolaryngological, head and neck tuberculosis. Routine blood investigations, chest radiographs, the tuberculin test, and sputum examination for the presence of acid-fast bacilli were performed in all cases. Site-specific investigations were performed in relevant cases only. The patients were treated according to the antitubercular treatment (ATT) regimen recommended by the Indian Ministry of Health and Family Welfare's National Tuberculosis Elimination Program (NTEP), and they were followed up clinically two and six months after starting the ATT. Results Tubercular cervical lymphadenopathy was the most common clinical presentation (85.96%), followed by deep neck abscess (5.27%). Fine-needle aspiration cytology proved to be a reliable tool for the diagnosis of tubercular lymphadenopathy. Improvement at the end of 2 and 6 months of the ATT was observed in 90.35% and 96.50% of the cases respectively. Conclusion The diagnosis of otorhinolaryngological, head and neck tuberculosis requires a high index of clinical suspicion, and the ATT proved to be very effective in reducing the severity of the disease.

Histone deacetylase (HDAC) inhibitors- based drugs are effective to control Mycobacterium tuberculosis infection and promote the sensibility for rifampicin in MDR strain

BACKGROUND Tuberculosis (TB) is a major public health problem, which has been aggravated by the alarming growth of drug-resistant tuberculosis. Therefore, the development of a safer and more effective treatment is needed. OBJECTIVES The aim of this work was repositioning and evaluate histone deacetylases (HDAC) inhibitors- based drugs with potential antimycobacterial activity. METHODS Using an in silico pharmacological repositioning strategy, three molecules that bind to the catalytic site of histone deacetylase were selected. Pneumocytes type II and macrophages were infected with Mycobacterium tuberculosis and treated with pre-selected HDAC inhibitors (HDACi). Subsequently, the ability of each of these molecules to directly promote the elimination of M. tuberculosis was evaluated by colony-forming unit (CFU)/mL. We assessed the expression of antimicrobial peptides and respiratory burst using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) FINDINGS Aminoacetanilide (ACE), N-Boc-1,2-phenylenediamine (N-BOC), 1,3-Diphenylurea (DFU), reduce bacillary loads in macrophages and increase the production of β-defensin-2, LL-37, superoxide dismutase (SOD) 3 and inducible nitric oxide synthase (iNOS). While only the use of ACE in type II pneumocytes decreases the bacterial load through increasing LL-37 expression. Furthermore, the use of ACE and rifampicin inhibited the survival of intracellular multi-drug resistance M. tuberculosis. MAIN CONCLUSIONS Our data support the usefulness of in silico approaches for drug repositioning to provide a potential adjunctive therapy for TB.

Primary extensive perianal cutaneous tuberculosis: A challenging diagnosis. Case report and a review of the literature

Abstract Rationale Perianal tuberculosis is extremely rare without previous or active pulmonary infection. Ulcerative skin lesion is a rare presentation of extrapulmonary tuberculosis in the oral, perianal, or genital mucosa and the adjacent skin. Case report A 71-year-old woman complained of pain during evacuation and fecal incontinence for two years. There was an ulcerated lesion in the perianal and intergluteal region and perianal fistulous tracts. A polymerase chain reaction test on blood and biopsies of perianal ulcers, perianal fistula, and the intergluteal area was positive for Mycobacterium tuberculosis. The pathological examination revealed a chronic epithelioid granulomatous inflammatory process with the presence of multinucleated giant cells. After the end of the tuberculosis drug regimen, there was marked improvement in the patient's clinical condition. Conclusion Even in the absence of an identifiable primary focus, tuberculosis should be considered in the differential diagnosis of ulcerative and fistulous lesions of the perianal area.

Tuberculose chez les enfants de 0-14 ans: résistance primaire de Mycobacterium tuberculosis aux antituberculeux et variants génétiques à Kinshasa / Tuberculosis in children aged 0-14: primary resistance of Mycobacterium tuberculosis to antituberculosis drugs and genetic variants in Kinshasa

Dans les régions endémiques y compris la République Démocratique du Congo, les enfants sont susceptibles d'être exposés à la tuberculose (TB) par un contact dans l'entourage. L'absence de diagnostic peut avoir des conséquences dévastatrices. L'objectif de la présente étude était de déterminer la fréquence de TB, la résistance primaire des souches de Mycobacterium tuberculosis aux antituberculeux ainsi que des variants génétiques. Méthodes. Cette étude transversale et descriptive a été réalisée, entre juin 2011 et décembre 2017, à Kinshasa chez les enfants présumés TB. Les enfants ayant les signes évocateurs de TB figurant dans la tranche d'âge de 0-14 ans étaient inclus. Les échantillons ont été examinés par le Ziehl et mis en culture sur le milieu de Löwenstein-Jensens. Les souches étaient testées aux antituberculeux par la technique des proportions et typées par Spoligotyping. La comparaison des proportions a été faite à l'aide du test de chi-carré de Pearson. Résultats. Quarante-huit souches de Mycobacterium tuberculosis (15,4 %) ont été isolées. Dix souches (20,8%) étaient résistantes à au moins un antituberculeux plus fréquemment à l'INH. Le génotype LAM (66,7 %) et Haarlem (33,3%) était observé. Conclusion. La recherche active de TB infantile confirme qu'elle est relativement fréquente et est résistante à au moins un antituberculeux (surtout à l'INH).

Characterization of the cellular immune response induced by Mycobacterium tuberculosis Rv2626c / 生物工程学报

Nearly a quarter of the world's population is infected with Mycobacterium tuberculosis and remains long-term asymptomatic infection. Rv2626c is a latent infection-related protein regulated by DosR of M. tuberculosis. In this study, the Rv2626c protein was prokaryotically expressed and purified, and its immunobiological characteristics were analyzed using RAW264.7 cells and mice as infection models. SDS-PAGE and Western blotting analysis showed that the Rv2626c-His fusion protein was mainly expressed in soluble form and specifically reacted with the rabbit anti-H37RV polyclonal serum. In addition, we found that the Rv2626c protein bound to the surface of RAW264.7 macrophages and up-regulated the production of NO. Moreover, the Rv2626c protein significantly induced the production of pro-inflammatory cytokines IFN-γ, TNF-α, IL-6 and MCP-1, and induced strong Th1-tendency immune response. These results may help to reveal the pathogenic mechanism of M. tuberculosis and facilitate the development of new tuberculosis vaccine.