The Tubercle Bacillus in the Pulmonary Lesion of Man: Histobacteriology and Its Bearing on the Therapy of Pulmonary Tuberculosis

Sweany, Henry C.

doi:10.1378/chest.28.6.699

Cited by 11 publications

(18 citation statements)

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“…In sum, improved permeabilization permits RNAscope probes to detect Mtb bacillary rods. Secondly, a halo surrounding bacilli suggests RNA leakage, indicating cellular disintegration that supports Canetti's findings of bacillary disintegration and loss of acid-fastness in vivo (4). Thirdly, our findings show that Mtb mRNA is stable enough for detection with RNAscope in numerous microenvironments.…”

Section: Rnascope Detects Intact and Disintegrated Mtb Bacilli And Mr...supporting

confidence: 88%

“…Importantly, studies in the 1940s showed that single Mtb colonies are stratified into three layers; nonacid fast, weakly acid-fast, and strongly acid-fast bacilli (3). Also, in the 1950s, Canetti reported that bacillary destruction generates "ghosts" of non-AFB in the caseum, which became scarcer as the age of necrosis increased (4). Unfortunately, the implications of this important biological property, i.e., acid-fastness, have been underappreciated.…”

Section: Introductionmentioning

confidence: 99%

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Detection ofMycobacterium tuberculosisin human tissue via RNAin situhybridization

Nargan,

Naidoo,

Msimang

et al. 2023

Preprint

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RationaleAccurate TB diagnosis is hampered by the variable efficacy of the widely-used Ziehl-Neelsen (ZN) staining method to identifyMycobacterium tuberculosis(Mtb) acid-fast bacilli (AFB). Here, we sought to circumvent this current limitation through direct detection ofMtbmRNA.ObjectivesTo employ RNAscope to determine the spatial distribution ofMtbmRNA within tuberculous human tissue, to appraise ZN-negative tissue from confirmed TB patients, and to provide proof-of-concept of RNAscope as a platform to inform TB diagnosis andMtbbiology.MethodsWe examined ante- and postmortem human TB tissue using RNAscope to detectMtbmRNA and a dual ZN/immunohistochemistry staining approach to identify AFB and bacilli producing antigen 85B (Ag85B).Measurements and main resultsWe adapted RNAscope forMtband identified intact and disintegratedMtbbacilli and intra- and extracellularMtbmRNA.MtbmRNA was distributed zonally within necrotic and non-necrotic granulomas. We also foundMtbmRNA within, and adjacent to, necrotic granulomas in ZN-negative lung tissue and in Ag85B-positive bronchial epithelium. Intriguingly, we observed accumulation ofMtbmRNA and Ag85B in the cytoplasm of host cells. Notably, many AFB were negative for Ag85B staining.MtbmRNA was observed in ZN-negative antemortem lymph node biopsies.ConclusionsRNAscope has diagnostic potential and can guide therapeutic intervention as it detectsMtbmRNA and morphology in ZN-negative tissues from TB patients, andMtbmRNA in ZN-negative antemortem biopsies, respectively. Lastly, our data provide evidence that at least two phenotypically distinct populations ofMtbbacilli existin vivo.

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Section: Rnascope Detects Intact and Disintegrated Mtb Bacilli And Mr...supporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Detection ofMycobacterium tuberculosisin human tissue via RNAin situhybridization

Nargan,

Naidoo,

Msimang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…32 The organisms are often concentrated in the centre of the granuloma, which commonly turns necrotic. 33 Duplication of M. tuberculosis is stopped in most people with normal immune systems as soon as cell-mediated immunity forms, however, if a few numbers of live bacilli remain in the granuloma. Although a main complex could often be seen on a chest radiograph, the majority of pulmonary TB infections are clinically and radiographically undetectable.…”

Section: Pathogenesis Of Tuberculosismentioning

confidence: 99%

Innovative Therapeutic Approaches Based on Nanotechnology for the Treatment and Management of Tuberculosis

Kia¹,

Ruman²,

Pratiwi³

et al. 2023

IJN

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Tuberculosis (TB), derived from bacterium named Mycobacterium tuberculosis, has become one of the worst infectious and contagious illnesses in the world after HIV/AIDS. Long-term therapy, a high pill burden, lack of compliance, and strict management regimens are disadvantages which resulted in the extensively drug-resistant (XDR) along with multidrug-resistant (MDR) in the treatment of TB. One of the main thrust areas for the current scenario is the development of innovative intervention tools for early diagnosis and therapeutics towards Mycobacterium tuberculosis (MTB). This review discusses various nanotherapeutic agents that have been developed for MTB diagnostics, anti-TB drugs and vaccine. Undoubtedly, the concept of employing nanoparticles (NPs) has strong potential in this therapy and offers impressive outcomes to conquer the disease. Nanocarriers with different types were designed for drug delivery applications via various administration methods. Controlling and maintaining the drug release might be an example of the benefits of utilizing a drug-loaded NP in TB therapy over conventional drug therapy. Furthermore, the drug-encapsulated NP is able to lessen dosage regimen and can resolve the problems of insufficient compliance. Over the past decade, NPs were developed in both diagnostic and therapeutic methods, while on the other hand, the therapeutic system has increased. These "theranostic" NPs were designed for nuclear imaging, optical imaging, ultrasound, imaging with magnetic resonance and the computed tomography, which includes both single-photon computed tomography and positron emission tomography. More specifically, the current manuscript focuses on the status of therapeutic and diagnostic approaches in the treatment of TB.

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“…Phagocytes and granulocytes penetrate poorly into these necrotic areas creating an immune-sheltered zone of bacterial growth. High oxygen levels within the cavity also provide a rich environment with high rates of bacterial replication leading to a large bacillary burden at the inner edge of the cavity (107-109 bacilli), estimated to be a hundred thousand times higher than in necrotic TB lesions [26][27][28]. Rapid bacterial proliferation increases the frequency of replicationinduced mutations and the likelihood of developing drug resistance [29][30][31][32].…”

Section: Figurementioning

confidence: 99%

‘Stepladder Lung Cavities’ with ‘Starry Sky Pattern’ in HRCT Thorax with Constitutional Symptoms: A Strong Predictor of Active Pulmonary Tuberculosis

Patil¹,

Dahiphale²,

Raka³

et al. 2023

SAR J Med

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Pulmonary Tuberculosis is most common diseases in India with significant mortality and morbidity. Tuberculosis can cause diverse thoracic presentations ranging from nodules, consolidations & cavitation, mediastinal adenopathy, pleural effusion to diffuse endobronchial disease presenting like bronchial asthma. In this case report, 29- year male, presented with constitutional symptoms for 4 months duration with partial response to medical treatment received according to their knowledge and experience towards bronchial asthma, enteric fever and jaundice. Radiological investigations documented only prominent hilum left side of thorax which was underestimated due to presence of wheeze. Recurrent, progressive and partially responding constitutional symptoms was the reason for referral to our center. We have also noted prominent hilum with inhomogeneous infiltrates left lung field and localized wheeze and crepitations on left side of thoracic cavity in mammary and interscapular region. We have further evaluated with HRCT thorax and observed thick-walled cavities in left upper lobe posterior segment. ‘Stepladder Lung Cavities’ in HRCT is defined as multiple cavities adjacent with each other partially communicating to noncommunicating of variable size and shape unilaterally or bilaterally in stepladder fashion. ‘Starry sky pattern’ in HRCT Thorax is defined as randomly placed nodular opacities presenting as discrete or conglomerated, interstitial and acinonodular opacities unilateral or bilateral adjacent to pulmonary cavities usually reported as satellite nodules. Satellite nodules are defined as nodular opacities adjacent to pulmonary primary caviatary lung disease and indicator lymphatic local spread and active pulmonary tuberculosis. We have done sputum examination and documented acid-fast bacilli in sputum smear and MTB genome with rifampicin sensitivity in cartridge based nucleic acid amplification test. Treatment initiated with anti-tuberculosis (ATT) and recorded near complete radiological resolution, bacteriological cure after six months with good compliance. High index of suspicion is must while managing these cases with constitutional symptoms with typical ‘Stepladder Lung Cavities’ with ‘starry sky pattern’ in HRCT Thorax to have successful treatment outcome.

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The Tubercle Bacillus in the Pulmonary Lesion of Man: Histobacteriology and Its Bearing on the Therapy of Pulmonary Tuberculosis

Cited by 11 publications

References 0 publications

Detection ofMycobacterium tuberculosisin human tissue via RNAin situhybridization

Detection ofMycobacterium tuberculosisin human tissue via RNAin situhybridization

Innovative Therapeutic Approaches Based on Nanotechnology for the Treatment and Management of Tuberculosis

‘Stepladder Lung Cavities’ with ‘Starry Sky Pattern’ in HRCT Thorax with Constitutional Symptoms: A Strong Predictor of Active Pulmonary Tuberculosis

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