About: Ghon focus is a(n) research topic. Over the lifetime, 11 publication(s) have been published within this topic receiving 110 citation(s).
TL;DR: A lymphocentric model proposes that spread of organisms outside the lung parenchyma is essential to induce adaptive immunity, which is crucial for the generation of transmissible pathology.
Abstract: Tuberculosis most commonly presents as a pulmonary disease, in which infection, persistence, and induction of transmissible pathology all occur in the lungs. If viewed as a pulmonary disease, enlarged lymph nodes represent reactive adenitis, and extrapulmonary forms of tuberculosis (including lymphatic tuberculosis) are not transmissible, hence representing an evolutionary dead-end for the pathogen. In an alternative theory, Mycobacterium tuberculosis passes asymptomatically through the lungs and rapidly establishes a chronic lymphatic infection. After a period of weeks to decades secondary lung pathology develops, ultimately allowing transmission to occur. Evidence that supports this lymphatic model includes historical descriptions of human tuberculosis from the preantibiotic era, analogy with other mycobacterial infections, observations of tuberculosis in non-human hosts, and experimental models of tuberculosis disease. At a fundamental level, a lymphocentric model proposes that spread of organisms outside the lung parenchyma is essential to induce adaptive immunity, which is crucial for the generation of transmissible pathology. Furthermore, a lymphatic model could explain why the lesion associated with primary infection (Ghon focus) is anatomically separated from the most common site of reactivation disease (the apex). More practically, an alternative perspective that classes tuberculosis as a lymphatic disease might affect strategies for preclinical and clinical assessment of novel diagnostics, drugs, and vaccines.
TL;DR: This study analyzes drug delivery to granulomas by means of a nanoparticle delivery system and reveals significant differences in drug concentrations between the plasma and macrophages.
Abstract: Tuberculosis, which typically presents as a pulmonary disease, has a complex pathology. The primary site of infection, the Ghon focus, recruits immune cells and a granuloma forms. At earlier stages the granuloma is still vascularized, offering the best opportunity for drug treatment. In the more progressive state blood flow is reduced and a distinct caseous structure develops. Effective delivery of drugs to bacilli in the core of the granuloma becomes very difficult. It is perceivable that granuloma cores could create conditions where bacilli persist and develop resistance. In this study we analyze drug delivery to granulomas by means of a nanoparticle delivery system. The model consists of two parts; the overall distribution of the nanoparticles is described by a simple circulatory model and this result is used in the second part, focusing on transport in a capillary lined with macrophages. Nanoparticles enter the macrophages where they are metabolized and the drugs are released. The model reveals significant differences in drug concentrations between the plasma and macrophages. Based on the results of the model, strategies for improved drug delivery are proposed.
TL;DR: An aerosol newborn/infant model in neonatal nonhuman primates (NHPs) is established that mimics clinical and bacteriological characteristics of Mtb infection as seen in human newborns/infants and allows the establishment of a TB coinfection model of pediatric AIDS.
Abstract: 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.
TL;DR: The spectrum of radiological signs as reported in the recent literature is analysed, in light of the series over a 15-year period, to pinpoint the most common radiological patterns in a developed country and to determine the role played by the different chest imaging techniques in diagnosis improvement.
Abstract: The incidence of tuberculosis is increasing in the developed world and children in particular represent a high-risk group for developing the disease. The aim of this review is to analyse the spectrum of radiological signs as reported in the recent literature, in light of our series over a 15-year period, to pinpoint the most common radiological patterns in a developed country and to determine the role played by the different chest imaging techniques in diagnosis improvement. Lung TB was present in 217 out of 255 patients (85 %): 146 patients were under 5 years of age (76 under 2 years) and 71 over 5 years (41 over 10 years). We describe different patterns differentiating adolescents and young adults from infants and children. Adolescents and young adult tuberculosis are apical and cavitary. Thoracic TB in infants and children is characterized by lymph node and parenchymal disease. In 21 cases with lymphadenopathies without lymph-bronchial diffusion (age range 2 months–7 years), CT identified the Ghon focus in 16/21 cases; chest X-ray never identified the Ghon focus. In our series, pleural TB was present in 8 cases out of 146 under 5 years of age, 5 cases out of 76 under 2 years, and 18 cases out of 71 over 5 years. Radiologists should be aware of typical patterns of tuberculosis, to provide an early diagnosis.
TL;DR: This review highlights aspects of Ghon’s anatomical pathology studies in children and adults not necessarily dying of tuberculosis but with signs of tuberculosis infection, as suggested by Ghon, lympho-haematogenous spread of tuberculosis may be more common than is usually appreciated.
Abstract: Anton Ghon is well known in the field of childhood tuberculosis, and the tuberculosis primary focus and complex are frequently called the Ghon focus and complex; this is largely the result of the wide publication of the English translation of his monograph "Der primare Lungenherd bei der Tuberkulose der Kinder." Ghon's studies are frequently quoted, but precise details of his monograph are neglected, his results often misquoted, and his later publications virtually unknown. This review highlights aspects of Ghon's anatomical pathology studies in children and adults not necessarily dying of tuberculosis but with signs of tuberculosis infection. Ghon found a single primary tuberculosis focus in approximately 80% of tuberculosis-infected children situated close to the pleura in two-thirds of cases. Cavitation of the focus was common, and lymphatic spread involved lymph nodes in the abdomen and neck in many children. Studies amongst adults and children frequently found the healed primary tuberculosis focus to be completely calcified without histological signs of tuberculosis activity; however, particularly in the presence of pulmonary tuberculosis, histological signs of tuberculosis activity were often found in the lymph nodes of the angulus venosus, despite apparent healing with extensive calcification. Both earlier studies and more recent investigations, with molecular biological tools, unavailable to Ghon and earlier researchers, have confirmed the presence of viable mycobacteria in apparently normal or healed thoracic nodes and also found molecular biological indications of viable mycobacteria in these nodes. As suggested by Ghon, lympho-haematogenous spread of tuberculosis may be more common than is usually appreciated.