Active pulmonary tuberculosis: something old, something new, something borrowed, something blue

Tuberculosis remains a major global health issue affecting all countries and age groups. Radiology plays a crucial role in the diagnosis and management of pulmonary tuberculosis (PTB). This review aims to improve understanding and diagnostic value of imaging in PTB. We present the old, well-established findings ranging from primary TB to the common appearances of post-primary TB, including dissemination with tree-in-bud nodularity, haematogenous dissemination with miliary nodules and lymphatic dissemination. We discuss new concepts in active PTB with special focus on imaging findings in immunocompromised individuals. We illustrate PTB appearances borrowed from other diseases in which the signs were initially described: the reversed halo sign, the galaxy sign and the cluster sign. There are several radiological signs that have been shown to correlate with positive or negative sputum smears, and radiologists should be aware of these signs as they play an important role in guiding the need for isolation and empirical anti-tuberculous therapy.

Randomized clinical trial: does using zinc and zinc ionophore EGCG as supplements improve outcome of active pulmonary tuberculosis

Tuberculosis is a big health challenge especially during the Covid-19 pandemic because of the similarity of symptoms between the two diseases, active pulmonary T.B is associated with malnutrition. Tuberculosis is still a global disease burden worldwide especially at low-income countries affecting families and health authorities because of the cost of medicine and health costs. There are growing numbers of multidrug resistants’ T.B patients. Epigallocatechin-3-gallate (EGCG) as antioxidant and inhibition of mycobacterium life in macrophages increase the potency of rifampicin oral anti-tuberculous drug. EGCG is an iron chelator which can be useful in T.B patients (1). Zinc is the most abundant trace element in the human body, Dabbagh-Bazarbachi et al. (2014) have demonstrated that EGCG can act as an ionophore that helps transport zinc to across cell membrane and exert cytotoxicity effect. EGCG can enhance the cytotoxicity of zinc ions to cancer. It is possible that the zinc(ii)-EGCG complex reduces the pH inside organelles, and might bind effectively to DNA in the nucleus. At our study use of EGCG and zinc as adjuvant therapy to national protocol may help at malnutrition and accelerate of sputum conversion to negative and faster improvement and less risk for infection transmission and lower the inflammatory cytokines like il-6 and increase weight of patients. Methodology: The objective of our study is to evaluate oral zinc administration as zinc sulfate 50 mg and zinc ionophore EGCG 200 mg in new smear positive active pulmonary tuberculosis patients above 18 year old for one month in an open labeled randomized controlled clinical trial (RCT) in line with directly observed treatment short course (DOTS) strategy recommended by WHO. We will do sputum tests at 0 and 2 weeks and 1 month for evaluation of conversion of positive to negative samples and also measure the serum zinc levels before the start of treatment, and serum interleukin 6 as cytokine marker. We are conducting this study at cat I patients as WHO classification of tuberculosis having active lung tuberculosis to see efficacy and change in immunological parameters. Place of study: Saudia Arabia – Ministry of health, public health department, First health cluster, Riyadh, Tuberculosis clinics of Mobile team tuberculosis program.Informed Consent will be taken from patients before the start the study.The clinical trial registration number for this trial is NCT05116098.

Down-regulation of hsa_circ_0045474 induces macrophage autophagy in tuberculosis via miR-582-5p/TNKS2 axis

Macrophage autophagy plays a major role in the control and elimination of invading Mycobacterium tuberculosis. However, the function and mechanism of circRNA on macrophage autophagy in tuberculosis remain unclear. Therefore, this study aimed to explore the role of circRNA underlying macrophage autophagy in tuberculosis. Quantitative real-time polymerase chain reaction was used to detect the expression of hsa_circ_0045474, miR-582-5p and TNKS2. Autophagy was detected by LC3B immunofluorescence and transmission electron microscopy. Dual-luciferase reporter assays were used to detect the relationship of miR-582-5p and hsa_circ_0045474 or TNKS2. Western blot was used to detect the expression of LC3-І and LC3-ІІ. The results showed that hsa_circ_0045474 was down-regulated in monocytes from patients with tuberculosis and induced autophagy in macrophages. hsa_circ_0045474 sponged miR-582-5p and negatively regulated miR-582-5p expression. Overexpression of miR-582-5p affected by hsa_circ_0045474 induced autophagy in macrophages. TNKS2 served as a target of miR-582-5p and down-regulation of TNKS2 induced autophagy in macrophages regulated by miR-582-5p. In conclusion, our results demonstrated that hsa_circ_0045474 down-regulation induced macrophage autophagy in tuberculosis via miR-582-5p/ TNKS2 axis, implying a novel strategy to treat the occurrence of active pulmonary tuberculosis caused by immune escape of M. tuberculosis.

Quantitative Rapid Test for Detection and Monitoring of Active Pulmonary Tuberculosis in Nonhuman Primates

Nonhuman primates (NHPs) are relevant models to study the pathogenesis of tuberculosis (TB) and evaluate the potential of TB therapies, but rapid tools allowing diagnosis of active pulmonary TB in NHPs are lacking. This study investigates whether low complexity lateral flow assays utilizing upconverting reporter particles (UCP-LFAs) developed for rapid detection of human serum proteins can be applied to detect and monitor active pulmonary TB in NHPs. UCP-LFAs were used to assess serum proteins levels and changes in relation to the MTB challenge dosage, lung pathology, treatment, and disease outcome in experimentally MTB-infected macaques. Serum levels of SAA1, IP-10, and IL-6 showed a significant increase after MTB infection in rhesus macaques and correlated with disease severity as determined by pathology scoring. Moreover, these biomarkers could sensitively detect the reduction of bacterial levels in the lungs of macaques due to BCG vaccination or drug treatment. Quantitative measurements by rapid UCP-LFAs specific for SAA1, IP-10, and IL-6 in serum can be utilized to detect active progressive pulmonary TB in macaques. The UCP-LFAs thus offer a low-cost, convenient, and minimally invasive diagnostic tool that can be applied in studies on TB vaccine and drug development involving macaques.

A History of Sarcoidosis and a New Brain Lesion

A 59-year-old man with long-standing hypertension sought a second opinion for a left-sided posterior headache and aphasia of approximately 1 week’s duration. Eight months before neurologic symptom presentation, he was febrile with night sweats, weight loss, arthralgias, dyspnea, and wheezing. Bronchoscopy and hilar lymph node biopsy showed noncaseating granulomatous inflammation consistent with pulmonary sarcoidosis. Remotely, as a teenager, given exposure to a family member with active pulmonary tuberculosis infection, he had a purified protein derivative skin test, which was positive; he received 6 months of isoniazid treatment. On examination, he was aphasic but had an otherwise normal neurologic examination. Brain magnetic resonance image performed at hospital admission (1 week after symptom onset) showed extensive T2 signal abnormality in the left temporal neocortex, with vasogenic edema, and abnormal gyriform gadolinium enhancement. There was no restricted diffusion in the left temporal lobe on diffusion-weighted imaging, but an apparent diffusion coefficient map showed a gyriform hypointense pattern. Prior outside magnetic resonance image obtained 1 day into the patient’s symptoms showed similar findings on T2/fluid-attenuated inversion recovery and T1 postgadolinium images but also gyriform hyperintensity on diffusion-weighted imaging, with hypointensity on apparent diffusion coefficient map in the same region. The patient was diagnosed with subacute cerebral infarction in the context of cardioembolic disease secondary to hereditary hypertrophic cardiomyopathy. As a result of the findings and diagnosis, the patient received an implantable cardioverter-defibrillator and was treated with warfarin, aiming for an international normalized ratio of 2.0 to 3.0 to reduce the risk of recurrent cardioembolic disease. The patient had a subacute ischemic stroke mimicking a brain mass radiologically. The acuity of symptom onset could have been a key clinical clue in this case but was absent from the patient history. Patients with stroke typically have hyperacute symptom onset (over seconds to minutes). Autoimmune and inflammatory central nervous system disease symptoms tend to have subacute evolution (over days to weeks) or might be chronic (over months).