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    7 views12 pages

    Cavitary Tuberculosis The Gateway of Disease Transmission

    Uploaded by

    Kenny BT

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    © All Rights Reserved
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    of 12
    Review Cavitary tuberculosis: the gateway of disease transmission Michal Uibanousk, Alvaro A Ordonez" Cail A Ruiz-Bedoya, Sanjay Kin Wiliam Rishi ‘Tuberculosis continues to be a major threat to global health. Cavitation is a dangerous consequence of pulmonary tuberculosis associated with poor outcomes, treatment relapse, higher transmission rates, and development of drug, resistance. However, in the antibiotic era, cavities are often identified as the most extreme outcome of treatment filure and are one of the least-studied aspects of tuberculosis. We review the epidemiology, clinical features, and concurrent standards of care for individuals with cavitary tuberculosis. We also discuss developments in the understanding of tuberculosis cavities as dynamic physical and biochemical structures that interface the host response with a unique mycobacterial niche to drive tuberculosisassociated morbidity and transmission. Advances in preclinical models and non-invasive imaging can provide valuable insights into the drivers of cavitation, These insights will guide the development of specific pharmacological interventions to prevent cavitation and improve lung function for individuals with tuberculosis Introduction ‘Tuberculosis was responsible for an estimated 1. 4million deaths in 2018, and is among the leading causes of morbidity and mortality worldwide! Cavitation is a seminal event and a key pathological feature of human tuberculosis, Ithas negative implications not only forthe patient, being associated with poor teatment outcomes, including delayed sputum culture conversion, relapse afer treatment, and development of drug resistance, bt also at public level, since cavitation greatly inereases the risk of person-to-person transmission.” Several factors combine within the cavity to deve in creased transmission, morbidity, and mortality (figure 1), In the widely accepted model for tuberculosis cavity formation, the necrotic centre of a granulomatous lung, abscess erodes into an airway while some necrotic debris remains inside the newly formed cavity” Phagocytes and granulocytes penetrate poorly into these necrotic areas ‘creating an immune-sheltered zone of bacterial growth, High oxygen concentration within the cavity also provides a rich environment with high rates of bacterial replication, leading to a large bacillary burden at the inner edge of the cavity (10'10' bacilli, estimated to be a 100000 times higher than in necrotic tuberculosis lesions." Rapid bacterial proliferation increases the frequency of replcation-induced mutations and the likelihood of developing drag resistance." These concentrated bacili aze poised to be expelled from the Ings by the bronchial ree dusing transmission events, Finally, the inner contents of cavities ate also poorly vvascularised, which limits the penetration of anti mycobacterial drags and could further promote selection, for drug-resistant mutants.*""™* Apart from providing a growth niche, the cavity air spice is not useful for respiration. During cavity formation, both the basement membrane and alveolar architecture are permanently destroyed. Even after successful tuberculosis treatment, tuberculosis cavities ‘an persist, leading to lifelong pulmonary deficits and recurrent opportunistic infections." In this Review we discuss developments in the understanding of tuber. culosis cavities as dynamic physical and biochemical smartlnecomfntcon Wl20 Joe2020 Descanpnds ps snonymous User (n/a) en Pontifical Xavierian University de ClinicaliCey es por Elsevier em structures that interface the host response with a unique mycobacterial niche to drive tuberculosis-associated ‘morbidity and transmission Clinical importance and epidemiology of tuberculosis cavities Fstimated rates of cavitary tuberculosis at the time of diagnosis range from 29% to 87%," However, these rates could be overestimated because patients with cavitary tuberculosis are more likely to have positive sputum samples, and thus easier to diagnose, Similarly, chest radiography—a clinical standard in tuberculosis dhiagnostics—might underestimate the presence of cai tation compared with CT scans." Rates of cavitation are higher in patents with diabetes," but lower in patients with poorly managed THIV co-infection although increased cavitation is seen after 6 months of ant retroviral therapy)" transplant recipients, and older tients (> 60 years of ge)" Finally, the differences in risk of cavitation altributed to infection by different Key messages + Cavitation isa dangerous consequence of pulmonary tuberculosis associated with poor outcomes, treatment relapse ighertransmision rats, and development of drug resistance + Modeling cavities or precinical studies is challenging since cavities are the consequence of complexand. heterogeneous hest-pathogen interactions + Advances in medeling tuberculosis aie enable studies te probe the complexpathelogcanche occupied by Mycabacteriom toberulesis acl tin the cavity all + Cavitation is complex phenotype riven by biochemical biophysical immunological. and micobilogial proceses that needto be beter understaod io be taigeted with potential therapies + Drugpenetration inte cavitary lesions should be considered when electing anti-tuberculbsis drugs for «linia tial, and treatment resimens shouldbe ‘optimised for patients with cavitary disease @k® ee fet 2026 pita it) he, Deputies Pot St} the oeipine net Shale atne, arto ah oot Review a € > z Irate F pens Fone The coy of eating ena aber (Wtigh concentrate fetal bce gr inthe lot neat seis thine sore theca B) cea prletion leds ‘epetonnaceaineatone drut determi ath Data mtartewth squeedeng eane (Beta Colagen mtn aeltedwthncealeonardinthe cant wal Dolan fxr claen mata aah oman sg onth tess see the anager ies rove the Devine ng ater ()Treine pra the atl comporect [Nycobactrum berlssrpleaton hich artbertothe higher Steen) seo recs th ety nthe tong runing oper o seo rk por anorabuterl dugpereatenhch {te contitvas tothe igh bce brden” eben dng penton ‘rahabocivescktn ordneresstant mata” F)cartesokenpest Cenatertheywesterbed of jahocee me reaedthser sve [Khredhnaba Thro aviation an dos of ingore aed ‘drnicplmenary dete the cots pri aerate roy {ener aing) tethay bcre ate cera cloatonby ‘rpetrsiitciare Te cobation wat epee high ‘mai neering ade sane of mate eee provi eppeity secondary calrsatan en spp sees year tbe sins Bling eee) are sill unclear" Cavitary tuberculosis carries & poor prognosis, with a higher risk of treatment failure and relapse if cavities are radiographically present during the first 2 months of therapy: If cavities persist after 6 months of treatment, the risk of relapse doubles compared with patients whose cavities close by treatment completion.” The association between cavitation and relapse could be attributable to poor drug penetration into the poorly vascularised cavity. Alternatively, cavitation could be a ‘marker for high baillary burden from extensive disease.* ‘Descangado pers Amamyenous User (ia) em Pontifical Xavierian University de CtiniealSey-ex Cavitary tuberculosis can also result in liethreatening, sequelae (eg, Rasroussen aneurysm." Individuals with cavitary disease pose a risk to their community and contacts. Higher bacterial burdens were detected in sputuen samples from patients with cavitary tuberculosis” and the presence of cavities and their proximity to an airway correlated with increased coughing. during tuberculosis treatment" Therefore, patients with cavitary tuberculosis and a higher bacterial burden, are more likely 0 release M tuberculosis leading to increased transmission.” Outbreaks and case studies suggest that cavities are the likely pathophysiologial driver behind tuberculosis superspreaders ** However, there is no consensus on the exact contuibution of individuals with cavitary tuberculosis tothe total number of transmission events, and the need for selective isolation ae 4 precaution based on radiographic findings is still, debated. To determine the value of selective isolation for patients with cavitary disease, computational models of tuberculosis transmission need to include prevalence estimates for cavitary tuberculosis combined with adjusted transmission rates for the sub-population with cavities" Cavity structure Avtuberculosis cavity is a pathological, gas-filled space in the lung parenchyma with a border resulting from (M tuberculosis infection * Tuberculosis cavities are hetero geneous in size, morphology, and wall composition, Which can be evaluated non-invasively by radiological Images and post-mortem analysis of gross appearance, oF bstological characteristics. Imaging Noninvasive anatomical imaging (eg. xray and CT) allows cavities to be evaluated by size (correlated with the extent of disease), shape, and wall thickness (Figure 24) Despite common belief, radiographical imaging is tunable to reliably determine the age of 2 cavity ‘The radiological manifestations of tuberculosis cavities are heterogeneous, with some patients having single or ‘multiple cavities ‘surrounded by consolidated, fibro: nodular, or mixed pattems. Upper lobe cavities are commonly seen in irumunocompetent adults, whereas cavities in the lower Tobes associated with adenopathy and pleural effusions can also be found in children and immunocompromised adults. Multiple adjoining small cavities can also fuse together to produce a large cavity* Thicker cavity walls are associated with higher con- centrations of bacili m the sputum, whereas thinner ‘walls are usually observed afer successful treatment" Airfluid levels are seen in 10-20% of tuberculosis cavities, and endobronchial spread {small nodules distant to the cavity) is also evident in 10-20% of cases {appendix pp 2-3)" Most tuberculosis cavities occur in the apical oF posterior segments ofthe superior lobes and, in seller owner com/ntton Vl20 Jone 2020 Review numbers, the upper segments of the inferior lobes, We analysed the location and size of 287 cavities in CT scans. ‘from 143 patients with cavitary tuberculosis taken from the National Institute of Allergy and Infectious Diseases ‘TB Portals database.” We found that 58% of all the cavities ‘were localised in the apical segments, whereas. 21% vwere located in the inferior lobes, with a distribution pattern similar to those reported previously (figure 2B, appendix p 4)" Although most lage cavities occur in the hing apices, some can also be found in the upper segments of the inferior lobes, and smaller nodular cavities occur throughout the hinge (figure 2). Historically this distribution towards vulnerable regions at the apices of the Iungs was attributed to reduced vascular supply, higher oxygen tension, and impaired lymphatic drainage in these regions compared with the inferior lobes." However, the actual mechanism behind, apically-oriented tuberculosis cavitation is still poorly understood ** ‘Gross appearance ‘The superlcil surface of the lungs fom individuals with pulmonary tuberculosis appears covered with areas of pneumonia (igure 2D, appendix p 5). Some areas appear az discrete and well

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