Tuberculosis in Children in a Pediatric Hospital in Mexico.

Tuberculosis (TB) remains a global problem and a diagnostic challenge, especially in pediatrics. The aim of this study was to describe the clinical, microbiological, radiological, and histopathological data of TB in children. A 7-year retrospective and descriptive cohort study that included 127 patients under 18 years of age with diagnosis of active TB was conducted from 2011 to 2018 in a pediatric hospital. Tuberculosis was microbiologically confirmed using Ziehl-Neelsen (ZN) staining, culture or polymerase chain reaction (PCR) in a total of 94 (74%) cases. Thirty-three cases were defined as probable TB based on tuberculin skin test result and epidemiological evaluation. The TB forms found were lymph node (39.3%), bone (15.7%), lung (13.6%), and meningeal TB (8.6%). The most common symptoms were fever (48.8%) and adenopathy (45.6%). History of contact was established in 34.6%. Positive ZN staining (sensitivity 30%) and culture (sensitivity 37%) were found in 29% and 37.7% of subjects, respectively. About 64.5% depicted abnormal chest X-ray. Xpert MTB/RIF® (PCR) was positive in 9.4% and biopsy was compatible in 52.7% of these samples. It is fundamental to have laboratory and epidemiological evaluation that support the diagnosis of the disease in children and thus, define its management; since, in most cases, early microbiologic confirmation is lacking.

Real-time Polymerase Chain Reaction for Mycobacterium tuberculosis Meningitis is More Sensitive in Patients with HIV Co-Infection.

BACKGROUND: Tuberculous meningitis (TbM) is the most severe complication of extra pulmonary tuberculosis (Tb). There is a higher frequency of positive cerebrospinal fluid (CSF) cultures for Mycobacterium tuberculosis (MTb) in samples from human immunodeficiency virus (HIV) co-infected patients than in those from HIV-negative patients. We hypothesized that real time PCR assays for MTb (MTb qPCR) using CSF would be more sensitive in HIV co-infected patients owing to a greater MTb burden. The present study aimed to verify the diagnostic performance of MTb qPCR in CSF of TbM patients who either were co-infected with HIV or were HIVnegative. METHODS: A total of 334 consecutive participants with suspected TbM were divided into two groups: HIV co-infected and HIV-negative; each group was categorized into definite TbM, probable TbM, possible TbM, and TbM-negative subgroups based on clinical, laboratory and imaging data. We evaluated the diagnostic characteristics of MTb qPCR analysis to detect TbM in CSF by comparing the results to those obtained for definite TbM (i.e., positive MTb culture) and/or probable TbM in CSF, as gold standard. RESULTS: The sensitivity of MTb qPCR in the definite and probable subgroups of the HIV coinfected participants (n = 14) was 35.7%, with a specificity of 93.8%, negative predictive value (NPV) of 94.4%, and negative clinical utility index (CUI-) of 0.89. Results of the HIV-negative group (n = 7) showed lower sensitivity (14.3%) and similar specificity, NPV, and CUI-. CONCLUSION: The findings confirmed our hypothesis, despite the low sensitivity. MTb qPCR may significantly contribute to diagnosis when associated with clinical criteria and complementary examinations.

[Cerebral tuberculosis without meningitis in a immunocompetent child]. / Tuberculosis cerebral sin meningitis en un niño inmunocompetente.

Cerebral tuberculosis TB (tuberculomas) without meningitis is an uncommon disease with a high morbidity and mortality. We report on a case that illustrates the complexity of this clinical presentation. An 11 month old, previously healthy male infant was brought to the clinic due to fever present during the last 1.5 months, associated with loss of neurodevelopmental goals and signs of endocranial hypertension. CT scan of the skull revealed dilatation of the ventricular system with transependimary edema; MRI showed multiple intra- and extra-axial micronodular images and hydrocephalus. Studies of CSF (cyto-chemical analysis, staining, culture for aerobes, fungi, mycobacteria, and molecular tests for TB were negative). Empirical management for subacute meningoencephalitis was prescribed complemented with tetraconjugated treatment for TB and steroids. As there was no microbiological isolation, biopsy of a cerebellar lesion was performed, which revealed chronic necrotizing granulomatous inflammation and acid-alcohol resistant bacilli. The diagnosis of cerebral TB without meningeal involvement was confirmed. The objective of the present report is to emphasize the importance of considering this presentation of TB in children, to remark the need of exhaustive search for the etiologic agent by obtaining samples of the different fluids and tissues even if it implies recurring to invasive methods.

[Optochiasmatic tuberculomas as a paradoxical reaction to treatment for meningeal tuberculosis]. / Tuberculomas optoquiasmaticos como reaccion paradojica al tratamiento de tuberculosis meningea.

TITLE: Tuberculomas optoquiasmaticos como reaccion paradojica al tratamiento de tuberculosis meningea.

Tuberculosis cerebral sin meningitis en un niño inmunocompetente / Cerebral tuberculosis without meningitis in a immunocompetent child

Resumen La tuberculosis (TBC) cerebral o tuberculoma(s) sin meningitis es una enfermedad poco frecuente y de alta morbimortalidad. Presentamos el caso clínico de un lactante de 11 meses, previamente sano, que consultó por fiebre prolongada y síntomas neurológicos. La RM de encéfalo mostró múltiples imágenes micronodulares e hidrocefalia. El estudio de LCR para bacterias, hongos y micobacterias fue negativo. Se prescribió terapia empírica como una meningoencefalitis subaguda y tratamiento antituberculoso tetraconjugado y corticoesteroides. La confirmación del diagnóstico de TBC cerebral se realizó por biopsia de la lesión, con presencia de inflamación granulomatosa crónica necrosante y bacilos ácido-alcohol resistentes. Se enfatiza la importancia de considerar esta presentación de TBC en niños, y la necesidad de la búsqueda exhaustiva del agente etiológico en diferentes líquidos y tejidos, aun por métodos invasores.

Cerebral tuberculosis TB (tuberculomas) without meningitis is an uncommon disease with a high morbidity and mortality. We report on a case that illustrates the complexity of this clinical presentation. An 11 month old, previously healthy male infant was brought to the clinic due to fever present during the last 1.5 months, associated with loss of neurodevelopmental goals and signs of endocranial hypertension. CT scan of the skull revealed dilatation of the ventricular system with transependimary edema; MRI showed multiple intra- and extra-axial micronodular images and hydrocephalus. Studies of CSF (cyto-chemical analysis, staining, culture for aerobes, fungi, mycobacteria, and molecular tests for TB were negative). Empirical management for subacute meningoencephalitis was prescribed complemented with tetraconjugated treatment for TB and steroids. As there was no microbiological isolation, biopsy of a cerebellar lesion was performed, which revealed chronic necrotizing granulomatous inflammation and acid-alcohol resistant bacilli. The diagnosis of cerebral TB without meningeal involvement was confirmed. The objective of the present report is to emphasize the importance of considering this presentation of TB in children, to remark the need of exhaustive search for the etiologic agent by obtaining samples of the different fluids and tissues even if it implies recurring to invasive methods.

Neurotuberculosis in cattle in southern Brazil.

Tuberculosis in cattle is a chronic infectious-contagious disease characterized by the development of nodular lesions (granulomas) in mainly the lungs and regional lymph nodes. It is caused by Mycobacterium tuberculosis complex, an acid-fast bacillus (AFB). Tuberculosis in the central nervous system is a rare condition in cattle. Herein, we describe the clinical and pathological findings of six neurotuberculosis cases in cattle diagnosed in Southern Brazil. The average age of the cattle affected was 12 months, and they varied in breed and sex. The clinical history ranged from 5 to 30 days and was characterized by motor incoordination, opisthotonus, blindness, and progression to recumbency. The cattle were euthanized, and grossly, the leptomeninges at the basilar brain showed marked and diffuse expansion, with nodular yellowish lesions ranging in size. On microscopic examination, there were multifocal granulomas located mainly in the meninges, though sometimes extending to adjacent neuropil or existing as isolated granulomas in neuropil. AFBs were observed in the cytoplasm of epithelioid macrophages and multinucleated giant cells through Ziehl-Neelsen histochemical staining and identified as Mycobacterium sp. through immunohistochemistry.

Fatal Case of Polymicrobial Meningitis Caused by Cryptococcus liquefaciens and Mycobacterium tuberculosis Complex in a Human Immunodeficiency Virus-Infected Patient.

We describe a fatal case of polymicrobial meningitis in a human immunodeficiency virus-infected patient from Guatemala caused by Cryptococcus liquefaciens and Mycobacterium tuberculosis complex. Central nervous system infections caused concurrently by these species are extremely rare. This is also the first report of disseminated disease caused by C. liquefaciens.

Tuberculoma masked by glioma: a case report.

Tuberculous meningitis (TM), a common infectious disease of the central nervous system that is also seen in other types of tuberculosis infections, has higher mortality rates in young and middle-aged patients. TM is difficult to diagnose and treat owing to its non-specific clinical features and often atypical cerebrospinal fluid changes. Patients who present with focal neurologic signs, cough, low-grade fever and illness duration of more than 5 days, have intracalvarial abnormalities, and do not meet Thwaites' criterion findings should be diagnosed using computed tomography or magnetic resonance imaging. Mycobacterium infections can also be diagnosed by acid-fast staining of smears, cerebrospinal fluid culture, diagnostic polymerase chain reaction for Mycobacterium tuberculosis, and purified protein derivative test. To prevent TM misdiagnosis, clinicians must have sufficient knowledge of the clinical manifestations of tuberculosis. Appropriate application of tuberculosis chemotherapy drug principles, including early diagnosis and treatment, combination therapies, and consistent administration of treatment at appropriate dosages, can greatly reduce TM mortality rates and improve satisfactory treatment outcomes.

TB meningitis in HIV-positive patients in Europe and Argentina: clinical outcome and factors associated with mortality.

OBJECTIVES: The study aimed at describing characteristics and outcome of tuberculous meningitis (TBM) in HIV-positive patients and comparing these parameters with those of extrapulmonary TB (TBEP) and pulmonary TB (TBP). METHODS: Kaplan-Meier estimation and Poisson regression models were used to assess the mortality following TB diagnosis and to evaluate potential prognostic factors for the 3 groups of TB patients separately. RESULTS: A total of 100 patients with TBM, 601 with TBEP, and 371 TBP were included. Patients with TBM had lower CD4 cell counts and only 17.0% received antiretroviral therapy (ART) at TB diagnosis. The cumulative probability of death at 12 months following TB was 51.2% for TBM (95% CI 41.4-61.6%), 12.3% for TBP (8.9-15.7%), and 19.4% for TBEP (16.1-22.6) (P<0.0001; log-rank test). For TBM, factors associated with a poorer prognosis were not being on ART (adjusted incidence rate ratio (aIRR) 4.00 (1.72-9.09), a prior AIDS diagnosis (aIRR=4.82 (2.61-8.92)), and receiving care in Eastern Europe (aIRR=5.41 (2.58-11.34))). CONCLUSIONS: TBM among HIV-positive patients was associated with a high mortality rate, especially for patients from Eastern Europe and patients with advanced HIV-infection, which urgently calls for public health interventions to improve both TB and HIV aspects of patient management.

Neurotuberculosis. Hallazgos intracraneanos en RM / Neurotuberculosis. Intracranial MRI findings

Objetivos. Mostrar nuestra casuística de pacientes con diagnóstico de tuberculosis intracraneana y describir los diferentes tipos de lesiones documentadas en Resonancia Magnética (RM) que caracterizan a esta entidad. Materiales y Métodos. Para el presente trabajo fueron seleccionados, de forma retrospectiva, 20 pacientes con hallazgos positivos de tuberculosis intracraneana. Doce eran de sexo masculino y 8 de sexo femenino, conun rango etario de 8 meses a 49 años de edad (edad media: 21 años). El diagnóstico clínico fue realizado con punción lumbar y cultivo de LCR. Once pacientes presentaron serología positiva para VIH. Las RM fueron realizadas en resonadores de 0.5T y 1.5T, complementadas en dos casos con Tomografía Computada (TC) de cerebro. A dos pacientes se les realizó difusión (DWI) y a un paciente espectroscopía. Resultados. Del total de pacientes (n=20), 14 presentaron compromiso subaracnoideo en la convexidad y 13 compromiso subaracnoideo cisternal basal (afectación leptomeníngea). En 13 se observaron tuberculomas y 11 presentaron angeítis de grandes vasos; mientras que 7 tuvieron angeítis de pequeños vasos, 7 hidrocefalia, 6 infartos parenquimatosos y 1 afectación paquimeníngea. Quince pacientes tenían lesiones combinadas.Conclusión. La localización más frecuente de neurotuberculosis en esta serie fue meníngea con compromiso leptomeníngeo (14 pacientes con afectación subaracnoidea, seguido de afectación cisternal en 13 pacientes) y sólo en un caso fue paquimeníngea. La manifestación parenquimatosa más frecuente fue el tuberculoma (granulomas tuberculosos) con 13 casos. De estos, 5 presentaron un patrón miliar y sólo uno comportamiento pseudotumoral...

Specific bacterial genotypes of Mycobacterium tuberculosis cause extensive dissemination and brain infection in an experimental model.

Meningeal tuberculosis is a severe type of extrapulmonary disease, which is thought to begin with respiratory infection, followed by hematogenous dissemination and brain infection. Host genetic susceptibility factors and specific mycobacterial substrains could be involved in its development. From an epidemiological study in Colombia, we selected three Mycobacterium tuberculosis clinical strains isolated from the cerebrospinal fluid (CSF) of patients with meningeal tuberculosis, and used them to infect BALB/c mice through the intratracheal route. These strains showed a distinctive spoligotype pattern. The course of infection in terms of strain virulence (mice survival, bacillary loads in lungs), bacilli dissemination and extrapulmonary infection (bacilli loads in blood, brain, liver, kidney and spleen), and immune responses (cytokine expression determined by real time PCR in brain and lung) was studied and compared with that induced by the laboratory strain H37Rv and other five clinical strains isolated from patients with pulmonary TB. All the clinical isolates from meningeal TB patients disseminated extensively through the hematogenous route infecting the brain, producing inflammation in the cerebral parenchyma and meninges, whereas H37Rv and clinical isolates from pulmonary TB patients showed very limited efficiency to infect the brain. Thus, it seems that mycobacterial strains with a distinctive genotype are able to disseminate extensively after the respiratory infection and infect the brain.

[Cerebrovascular disease as an initial finding in childhood tuberculosis meningoencephalitis]. / Enfermedad cerebrovascular como síntoma inicial de meningoencefalitis tuberculosa en la infancia.

INTRODUCTION: The prevalence of tuberculosis in developing countries, such as Brazil, remains high with important morbidity and mortality rates among children. Neurological complications are frequent and tuberculous meningo-encephalitis (TBM) is the most dreaded of them in infancy. CASE REPORT: Our case involves a 7-year-old white female patient who was previously in good health. Over a period of two weeks she suffered from high temperatures and vomiting and was given amoxicillin. She later suffered an attack of focal seizures. Electroencephalogram studies showed a temporary double focus and lesions in the left hemisphere. A cranial computerised tomography (CT) scan revealed a periventricular haemorrhage on the left side. The control CT (carried out 20 days later) showed a reduction in the haemorrhage and localised hypodensity. Owing to the suspected existence of an abscess, the patient was administered vancomycin. A new cranial CT scan (40 days after the first) showed gliosis alongside the basal nuclei with impregnation in the carotid trifurcation, which led us to suspect that we were dealing with a case of vasculitis or a granuloma. All the microbacterial cultures were negative and there was no history of contact with tuberculosis. The adenosine deaminase (ADA) value in the sample of cerebrospinal fluid (taken seven weeks after the first) was found to be 21.2 UI. Treatment was started with tuberculostatic compounds. Two weeks later the fever disappeared. The control CT scan showed decreased hypodensity and impregnation. The patient was discharged from hospital, with a slight monoparesis in the upper right limb. DISCUSSION: The presentation of a cerebrovascular disease within a context of TBM, like the case reported here, is relatively rare in the literature. We concluded that the uncommon initial symptoms of TBM, associated with the negative cultures, contributed to the delay in reaching a diagnosis. A cerebrovascular accident must be included in the clinical picture of TBM and this disease has to be taken into account when dealing with a case of cerebrovascular accident.

Meningitis tuberculosa en menores de 14 años vacunados con BCG. Hospital del niño Ovidio Alaiga Uria / Tuberculous meningitis in children under 14 years vaccinated with BCG

Pregunta de ivestigación. Encontrar casos de meningitis tuberculosa en niños vacunados con BCG: Tipo de estudio. Trabajo no experimental, reotrospectivo, descriptivo y de corte transversal. Lugar. Pacientes con meningitis tuberculosa internados en el Hospital del niño "Ovidio Aliaga Uria" de la ciudad de La Paz. Sujetos. Se considero un universi de 38 pacientes menores de 14 años con el diagnostico de meningitis tuberculosa, internados en el Hospital del Niño de la ciudad de La Paz, durante el periodo comprendido entre enero de 1999 hasta marzo de 2003. De los cuales se analizo una muestra de 17 pacientes los cuales tenían la vacuna BCG. Materiales.- Formulario de recolección de datos, historias clínicas y expediente clinico. Procediiento.- Sse realizó la revisión de hsitorias clínicas y expedientes clínicos de pacientes con el diagnóstico de meningitis tuberculosa desde enero de 1999 hasta marzo de 2003 y se procedió al llenado del formulario diseñado para el estudio. Resultados.- De untotal de 38 pacientes diagnosticados con meningitis tuberculosa, se encontró 17 pacientes 44.7 por cento que habian sido inmunizados con BCG y 23 pacientes 55.3 por ciento que no habían recibido la inmunización. El 52.6 por ciento de pcientes correspondían al sexo femenino y 47.4 por ciento al sexo masculino. Del total de pacientes inmuinizados con la vacuna BCG y que presentaron meningiis tuberculosa, 64.7 por ciento se encontraban con bajo peso para su edad; 64.7 por ciento provenian de áreas urbano marginales; 88.2 por ciento tuvieron parto doiciliario; 76.5 por ciento presentaron alzas térmicas como signo sintomatología fue: bueno en 35.3 por ciento, malo en 35.3 por ciento y fallecieron 29.4 por ciento. Conclusiones.- El estudio demostró que en nuestro medio existe un alto porcentaje de pacientes con meningitis tuberculosa a pesar de haber recibido inmunización con la vacuna BCG (44.7 por ceinto), lo que lleva a pensar en la coexistencia de otros factores, como estado nutritivo deficiente (64.7 por ciento venían de áreas urbano marginales, 88.2 por ciento tuvieron parto domiciliario) y quizas que la vacuna BCG fue inefectiva.

Neurotuberculose em crianças: aspectos clínicos, laboratoriais e epidemiológicos / Neurotuberculosis in children: clinical, laboratory and epidemiological

A tuberculose hoje em dia é a doença por agente único que mais mata em todo o mundo, principalmente em países em desenvolvimento, como o Brasil. A neurotuberculose, infecção do sistema nervoso central pelo Mycobacterium tuberculosis, é uma das formas mais temidas, por ser acompanhada de morbi-mortalidade alta. O prognóstico depende do diagnóstico oportuno, que muitas vezes é de difícil definição. Com o objetivo de analisar a casuística de neurotuberculose do Instituto da Criança, HC, FMUSP, foi realizado um estudo retrospectivo baseado em dados obtidos da revisão de prontuários das crianças admitidas com este diagnóstico entre 1981 e 1997. Do total de 52 crianças incluídas, a maioria era do sexo feminino, com menos de dois anos de idade e desnutridas. As queixas mais comuns à admissão foram febre, vômitos, convulsões e alteração do nível de consciência. Todos os casos, exceto dois, apresentavam anormalidades ao exame neurológico inicial. As mais comuns foram a diminuição do nível de consciência, os sinais piramidais, os sinais de irritação meníngea e o comprometimento de nervos cranianos. A metade dos pacientes estivera em contato prévio com bacilífero. A maioria dos pacientes havia sido previamente vacinada com BCG, muito embora tardiamente. Os exames de imagens foram úteis no auxílio ao diagnóstico, por mostrar alterações sugestivas de tuberculose

Actividad de adenosina deaminasa en líquido cefalorraquídeo para el diagnóstico de meningitis tuberculosa

La actividad de la enzima Adenosina Deaminasa en líquido cefaloraquídeo (LCR) fue evaluada como ayuda diagnóstica para pacientes con Meningitis Tuberculosa. Este trabajo se realizó en los Servicios de Medicina, Neurología, Pediatría de los Hospitales Honorio Delgado, IPSS y Goyeneche, contó con la participación de 69 sujetos divididos en cuatro grupos: 22 pacientes diagnosticados con Meningitis Tuberculosa, 10 pacientes con Meningitis Bacteriana, 16 pacientes con Meningitis Viral y 21 pacientes con otras enfermedades neurológicas como ACV, Leucemia, Enfermedad de Alzeheimer, Epilepsia, Hipertensión Endocraneana, Neurocisticercosis, Tec, Glioma, Astrocitoma, Cáncer Metastásico y Absceso Cerebral. Se dosó la enzima Adenosina Deaminasa en LCR de todos los pacientes de acuerdo al método de Bertholot, se utilizó la tabla de cuatro casillas para hallar sensibilidad y especificidad; Andeva para comparar la media entre los cuatro grupos; T Student, para determinar diferencias entre los diversos grupos en forma individual; estas comparaciones fueron realizadas de ods en dos siendo p=0,05. Por ajuste de Bonferroni, p=0,008. Se usó como criterio de positividad 6 u/l (valor normal de referencia). En este estudio se obtuvo unsa sensibilidad del 95,45 por ciento del test de ADA en LCR de pacientes con Meningitis Tuberculosa, su especifidad es de 87,27 por ciento;el nivel alto de ADA en LCR es útil para el diagnóstico diferencial de pacientes con Meningitis Tuberculosa, en relación a pacientes con Meningitis Aséptica y otras patologías neurológicas, como ACV, Leucemia, Enfermedad de Alzeheimer, Epilepsia, Hipertensión Endocraneana, Neurocisticercosis, TEC, Glioma, Astrocitoma. En el presente estudio se obtiene que no existe diferencia significativa del test de ADA en LCR de pacientes con Meningitis Tuberculosa y Bacteriana.

Presumed ocular and central nervous system tuberculosis in a patient with the acquired immunodeficiency syndrome.

PURPOSE: To elucidate a case of tuberculous choroiditis in a patient with the acquired immunodeficiency syndrome (AIDS). METHODS: We treated a 35-year-old woman who had AIDS with neurologic involvement caused by Mycobacterium tuberculosis. She developed a yellow-white chorioretinal infiltrate with indistinct borders and mild vitreitis in the right eye, probably caused by this pathogen. RESULTS: The patient's visual acuity improved in the right eye with healing of the ocular lesion and her neurologic condition improved after specific therapy with isoniazid, rifampin, and ethambutol. CONCLUSION: Tuberculosis must be considered in the differential diagnosis of posterior uveitis and choroiditis in AIDS patients.

Algunos datos de la neurotuberculosis obtenidos de la revisión de 13,689 autopsias / Neurotuberculosis. Findings in 13,689 autopsies

En una serie de 13,689 autopsias del Hospital General más grande de México, se hizo el diagnóstico de tuberculosis en 1.129 casos, de los cuales 321 tuvieron afección del sistema nervioso central. Se presentan las gráficas de las distintas formas de lesiones en el encéfalo y de los territorios afectados por la isquemia en los casos de leptomeningitis. Se presentan datos de edad, sexo, y extensión de las lesiones extracraneanas y su coexistencia con lesiones en el sistema nervioso central. Debido a que el número de niños atendidos en el Hospital General de México es bajo, no es posible concluir, como en otras series, si la coexistencia entre lesiones extracraneanas e intracraneanas es semejante en ambos grupos de población.

[The involvement of the choroid plexus and ependyma in tuberculosis: its importance in dissemination of the disease in the central nervous system]. / O envolvimento do plexo coróide e epêndima na tuberculose: sua importância na disseminação da doença no sistema nervoso central.

It is reported in this paper, the study of the choroid plexus and ependyma in 42 cases of tuberculous meningitis. Granulomatous lesions were found as a very frequent lesion in the choroid plexus (75%). In some cases detached granulomas were found free among the villi. The ependymal lesions seen in 97% of the cases are characteristic of the tuberculous granular ependymitis. The report points out the role of these lesions, played in the pathogenesis of the tuberculous meningitis.