Tuberculosis: Role of Nuclear Medicine and Molecular Imaging With Potential Impact of Neutrophil-Specific Tracers

With Tuberculosis (TB) affecting millions of people worldwide, novel imaging modalities and tools, particularly nuclear medicine and molecular imaging, have grown with greater interest to assess the biology of the tuberculous granuloma and evolution thereof. Much early work has been performed at the pre-clinical level using gamma single photon emission computed tomography (SPECT) agents exploiting certain characteristics of Mycobacterium tuberculosis (MTb). Both antituberculous SPECT and positron emission tomography (PET) agents have been utilised to characterise MTb. Other PET tracers have been utilised to help to characterise the biology of MTb (including Gallium-68-labelled radiopharmaceuticals). Of all the tracers, 2-[18F]FDG has been studied extensively over the last two decades in many aspects of the treatment paradigm of TB: at diagnosis, staging, response assessment, restaging, and in potentially predicting the outcome of patients with latent TB infection. Its lower specificity in being able to distinguish different inflammatory cell types in the granuloma has garnered interest in reviewing more specific agents that can portend prognostic implications in the management of MTb. With the neutrophil being a cell type that portends this poorer prognosis, imaging this cell type may be able to answer more accurately questions relating to the tuberculous granuloma transmissivity and may help in characterising patients who may be at risk of developing active TB. The formyl peptide receptor 1(FPR1) expressed by neutrophils is a key marker in this process and is a potential target to characterise these areas. The pre-clinical work regarding the role of radiolabelled N-cinnamoyl –F-(D) L – F – (D) –L F (cFLFLF) (which is an antagonist for FPR1) using Technetium 99m-labelled conjugates and more recently radiolabelled with Gallium-68 and Copper 64 is discussed. It is the hope that further work with this tracer may accelerate its potential to be utilised in responding to many of the current diagnostic dilemmas and challenges in TB management, thereby making the tracer a translatable option in routine clinical care.

Sterile tuberculous granuloma in a patient with XDR-TB treated with bedaquiline, pretomanid and linezolid

Drug-resistant tuberculosis (DR-TB) continues to pose a threat to the global eradication of TB. Regimens for extensively drug-resistant (XDR) TB are lengthy and poorly tolerated, often with unsuccessful outcomes. The TB Alliance Nix-TB trial investigated the safety and efficacy of a 26-week regimen of bedaquiline, pretomanid and linezolid (BPaL) in participants with XDR-TB, multidrug-resistant (MDR) TB treatment failure or intolerance. In this trial 9 out of 10 participants were cured. We describe a trial participant with XDR-TB who presented with new-onset seizures soon after BPaL treatment completion. Imaging showed a right temporal ring-enhancing lesion, and a sterile tuberculous granuloma was confirmed after a diagnostic, excisional biopsy. Learning points include management of a participant with a tuberculoma after BPaL completion, efficacy of new medications for central nervous system (CNS) TB and a review of their CNS penetration. This is the first case of pretomanid use in CNS TB.

Tuberculous granuloma of maxillary antrum and ethmoid sinus mimicking malignancy and trigeminal neuralgia: A case report and review of the literature

Tuberculosis is a multi-system disease, but paranasal sinuses involvement is uncommon, and most cases occur secondary to pulmonary tuberculosis. Tuberculous granuloma of the paranasal sinuses is rare and only a few cases are reported. Due to non-specific ways of clinical presentations, diagnosis of paranasal tuberculosis can be missed, delayed or confused with other entities like malignancy. We present an uncommon case of tuberculous granuloma of the left maxillary antrum and ethmoid sinus in a 56-year-old man which mimicked trigeminal neuralgia and malignancy. Medial maxillectomy and anterior ethmoidectomy with clearance of the lesion followed by antituberculous treatment prevented permanent loss of his vision. Depending on the chief complaints, patients may present to various specialties. Early cross-referral is important for early diagnosis, appropriate management and prevention of complications.

Is there a dependence between expression of integrin receptors by peripheral blood immune cells and duration of tuberculous granuloma existence in the patients?

Over recent years, the number of patients with tuberculosis has not decreased in the country and in worldwide. This is due to high resistance of the pathogen and changing mechanisms of bacterial perception by the human immune system thus requiring closer examination of the issue. Cell fusion during the formation of pulmonary tuberculous granuloma involves a large number of adhesive events. Importance of α1β1 integrin has been shown for the granuloma integrity during the chronic phase of infection. It has been proven that pulmonary tuberculous granuloma should be monitored, including with the detection of cells expressing CD11c, since they support the continuous priming of T cells at different stages of infection. The aim of this study was to answer the question, if there is a different expression of integrin receptors by immune cells from the patient’s peripheral blood at different stages of the existence of pulmonary tuberculous granuloma? The study involved 38 people: the first group (control) consisted of 15 practically healthy people; a second group included 11 subjects with pulmonary tuberculous granuloma; the condition was first diagnosed 2 to 10 months before the present study. A third group consisted of 12 patients with pulmonary tuberculous granuloma, with primary diagnosis established 12 to 219 months before this study. All the participants underwent a general clinical blood tests using a 5 Diff Mythic 22 AL analyzer (Cormay, Poland). The adhesion markers CD11b, CD11c were detected with a Coulter Epicx XL instrument (Beckman Coulter, USA). The following peripheral blood cell populations were determined: CD14- CD13lowCD11b+, CD14- CD13lowCD11c+, CD14+CD11b+, CD14+CD11c+, CD45+CD3- CD16+CD56+, CD45+CD3- CD16+CD56+CD11b+. Statistical processing of the results was performed in the Windows 10 operating environment (Microsoft Corp., USA), using Statistica v. 12.5 software (StatSoft, USA). Kruskal–Wallis one-way analysis of variance (pk-w), with differences significant at p < 0.017, as well as the Wald–Wolfowitz test (pw-w) at a significance level of p < 0.05 were used as criteria for assessing differences between the compared groups. In addition, cluster and factor analysis were implemented. When studying the role of β2-integrins, we have found that they play an important role in maintaining the existence of pulmonary tuberculous granuloma. An increase in total number of granulocytes, and CD11b-expressing granulocytes, a decrease in the population of lymphocytes, NK cells and NK cells expressing CD11c proved to be distinctive in cases of pulmonary tuberculous granuloma detected 0.5 years before the study. Characteristic changes observed in the study of peripheral blood in the patients with pulmonary tuberculous granuloma detected 9.5 years before the study were as follows: an increase in the leukocyte population, total monocyte number, as well as CD11band CD11c-expressing monocytes.