An atlas overview of characteristic features of tuberculosis that may be encountered at autopsy.

Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis. Although primarily a disease of the respiratory system it may be found in any organ or tissue. Global population movements and the emergence of resistant strains are contributing to increasing numbers of cases in certain populations. Subtlety of symptoms and signs, chronicity of disease and failure to seek medical assistance may result in the diagnosis only being made at the time of autopsy. For this reason forensic pathologists need to understand the protean manifestations of the disease and the variable mechanisms by which TB may cause death. This atlas overview provides descriptions of the pathological manifestations of TB in a variety of organs with accompanying illustrations. It serves as a summary of conditions that should be checked for at autopsy in suspected or confirmed cases.

Standardized radiographic interpretation of thoracic tuberculosis in children.

There is a lack of standardized approach and terminology to classify the diverse spectrum of manifestations in tuberculosis. It is important to recognize the different clinical and radiographic patterns to guide treatment. As a result of changing epidemiology, there is considerable overlap in the radiologic presentations of primary tuberculosis and post-primary tuberculosis. In this article we promote a standardized approach in clinical and radiographic classification for children suspected of having or diagnosed with childhood tuberculosis. We propose standardized terms to diminish confusion and miscommunication, which can affect management. In addition, we present pitfalls and limitations of imaging.

Establishment of a neonatal rhesus macaque model to study Mycobacterium tuberculosis infection.

Mycobacterium tuberculosis (Mtb) is the causative agent of human tuberculosis (TB) with an estimated 8.8 million new TB cases and 1.4 million deaths annually. Tuberculosis is the leading cause of death in AIDS patients worldwide but very little is known about early TB infection or TB/HIV co-infection in infants. A clinically relevant newborn animal model to study TB infection is urgently needed. We have successfully established an aerosol newborn/infant model in neonatal nonhuman primates (NHPs) that mimics clinical and bacteriological characteristics of Mtb infection as seen in human newborns/infants. Further, this model will allow the establishment of a TB coinfection model of pediatric AIDS. Aerosol versus intra broncho-alveolar Mtb infection was studied. Interestingly, 42 days post infection specific lesions were detected suggestive of the classic Ghon focus in human children. Concurrently, specific cellular immune responses developed 4-6 weeks after Mtb infection. Using the enzyme-linked immunospot (ELISPOT) assays, we found that IL-12 production correlated with early Mtb infection lesions seen by routine thoracic radiographs. Overall, this work represents the first example of early Mtb infection of newborn macaques. This study gives us a unique opportunity to further characterize immunopathogenesis and establish a TB/SIV co-infection model for pediatric AIDS.

Tuberculosis de tipo adulto en los niños / Adult-type tuberculosis in children

One of the fascinating aspects of childhood tuberculosis (TB) is the diverse spectrum of pathology, which necessitates accurate disease classification. This manuscript provides a brief overview of the disease diversity observed in children with TB, with particular emphasis on adult-type TB. Cavitary disease in children may result from three distinct pathologic processes; 1) poor containment within the Ghon focus (mainly very young and/or immune compromised children), 2) aspiration of virulent bacilli following eruption of a diseased lymph node into an airway with resultant caseating pneumonia and parenchymal destruction (mainly children < 5 yrs of age), and 3) from adulttype disease (mainly children > 10 yrs of age). The exact pathological mechanism underlying adult-type disease remains uncertain. The combination of a destructive cell mediated immune response together with increased organism survival and proliferation in the lung apices, may initiate a vicious circle of parenchymal destruction. This hypothesis may explain the sudden emergence of adult-type disease around puberty, as well as the typical anatomical location of the lung cavities. Most children with adult-type disease are sputum smear-positive and can be diagnosed with routine sputum smear microscopy at primary health care level. Due to the high organism load the same treatment rationale used in adults with sputum smear-positive TB would apply, which justifies the use of four drugs during the initial intensive phase. These children pose a considerable transmission risk, particularly in congregate settings such as schools, and screening of close contacts should also be considered

Uno de los aspectos fascinantes de la tuberculosis (TB) infantil es el amplio espectro de las alteraciones histopatológicas, lo que requiere una clasificación precisa de los hallazgos. Este manuscrito proporciona un breve panorama general de la diversidad de presentaciones clínicas observadas en los niños con TB y hace hincapié particularmente en la TB que imita las formas del adulto. La enfermedad cavitaria en los niños puede ser el resultado de tres procesos anatomopatológicos distintos: 1) la escasa limitación dentro del foco de Ghon (principalmente en los niños muy pequeños o inmunocomprometidos), 2) la aspiración de bacilos virulentos luego de la erupción de una adenopatía en una vía aérea con neumonía caseosa consiguiente y destrucción del parénquima (principalmente en los menores de 5 años) y 3) la enfermedad de tipo adulto (principalmente en los niños mayores de 10 años). Es incierto aún el mecanismo fisiopatológico exacto subyacente a la enfermedad de tipo adulto. La combinación de una intensa respuesta inmune mediada por células junto con la mayor supervivencia y proliferación del microorganismo en los vértices pulmonares puede iniciar un círculo vicioso de destrucción parenquimatosa. Esta hipótesis puede explicar la aparición súbita de la enfermedad de tipo adulto alrededor de la pubertad, así como la localización anatómica típica de las cavidades pulmonares. La mayoría de los niños con enfermedad de tipo adulto tienen frotis de esputo positivos y el diagnóstico se puede realizar con la microscopia de rutina del frotis de esputo en la atención primaria. Debido a la gran carga de microorganismos se debe aplicar el mismo fundamento terapéutico utilizado en los adultos con TB con frotis de esputo positivo, lo cual justifica el uso de cuatro drogas durante la fase intensiva inicial. Estos niños plantean un riesgo considerable de transmisión, sobre todo en comunidades cerradas como las escuelas y también se debe considerar la pesquisa de los contactos cercanos