Antituberculosis Therapy and Gut Microbiota: Review of Potential Host Microbiota Directed-Therapies

Tuberculosis (TB) remains a major public health concern with millions of deaths every year. The overlap with HIV infections, long treatment duration, and the emergence of drug resistance are significant obstacles to the control of the disease. Indeed, the standard first-line regimen TB treatment takes at least six months and even longer for the second-line therapy, resulting in relapses, drug resistance and re-infections. Many recent reports have also shown prolonged and significant damage of the gut microbial community (dysbiosis) from anti-TB drugs that can detrimentally persist several months after the cessation of treatment and could lead to the impairment of the immune response, and thus re-infections and drug resistance. A proposed strategy for shortening the treatment duration is thus to apply corrective measures to the dysbiosis for a faster bacterial clearance and a better treatment outcome. In this review, we will study the role of the gut microbiota in both TB infection and treatment, and its potential link with treatment duration. We will also discuss, the new concept of “Host Microbiota Directed-Therapies (HMDT)” as a potential adjunctive strategy to improve the treatment effectiveness, reduce its duration and or prevent relapses. These strategies include the use of probiotics, prebiotics, gut microbiota transfer, and other strategies. Application of this innovative solution could lead to HMDT as an adjunctive tool to shorten TB treatment, which will have enormous public health impacts for the End TB Strategy worldwide.

Sternal swelling presenting as tuberculosis: a case report

Background Tuberculosis continues to be a worldwide public health problem. Despite the noted gradual decline in tuberculosis case rates in the UK, clinicians should still be aware of these unusual presentations. Sternal tuberculosis is an uncommon form of extrapulmonary tuberculosis and it can initially be a diagnostic challenge for paediatricians. These lesions can present with nonspecific signs and symptoms that may mimic malignancy. Case presentation We present a case of a 3-year-old African descent girl with a sternal swelling that was confirmed to be Mycobacterium tuberculosis complex DNA on gastric aspirate. The child had additional radiological investigations that corresponded accordingly. She was started on quadruple antituberculosis therapy with good outcome. Conclusion Tuberculosis sternal abscess is as rare finding, especially in developed countries where tuberculosis is not endemic. Tuberculosis may not always present with pulmonary symptoms in children. There should be a high suspicion of tuberculosis, especially in immigrant population presenting with unusual presentations. Our aim is to increase awareness around atypical presentations of tuberculosis in children. Although, tuberculosis is endemic to underdeveloped countries, clinicians should still be aware of presentations in view of current global migration.

The Role of QuantiFERON-TB Gold Plus in Mycobacterium Tuberculosis Detection in a Severe HIV Immunocompromised Patient—Case Report

Tuberculosis (TB) is an important opportunistic infection in HIV-positive people. We are reporting a case of a 31-year-old HIV-infected patient who was hospitalized in July 2021 for dyspnea, cough with mucopurulent sputum and asthenia. He was confirmed to have Serratia liquefaciens pneumonia and acute respiratory failure. The evolution was unfavorable despite the antibiotic, pathogenic and symptomatic treatment. Because the patient had severe immunosuppression (CD4 count = 37 cell/mm3), we used QuantiFERON-TB Gold Plus for the detection of the Mycobacterium tuberculosis infection. The antituberculosis therapy was initiated, which resulted in a significant improvement of the general condition and the patient was discharged with the recommendation to continue antiretroviral therapy, antituberculosis treatment and Trimethoprim/Sulfamethoxazole—single tablet daily for the prophylaxis of Pneumocystis pneumonia.

Antiviral Therapy with Entecavir following Antituberculosis Therapy Alleviates Liver Injury and Restores Innate Immunity in Tuberculosis Patients Coinfected with Hepatitis B Virus

Objective. Coinfection of tuberculosis (TB) and viral hepatitis may increase the risk of antituberculosis treatment-induced hepatotoxicity, which is regarded as a common cause of termination of the first-line antituberculosis drugs. The study aimed at investigating the protective effects of antiviral therapy on the liver and innate immunity in patients with TB-HBV coinfection. Methods. A total of 100 patients with TB-HBV coinfection were recruited and split into antituberculosis and antiviral groups, 50 per group, according to odd or even date of hospital admission from December 2019 to October 2020. The patients in the anti-TB group received antituberculosis therapy, and those in the antiviral group received antiviral therapy. The clinical effectiveness; HBV-DNA negative conversion rate; liver function assessment involving alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL); immune function evaluation including CD4+, CD8+, CD4+/CD8+, and CD3+ T cells; inflammatory cytokines containing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interferon-γ (IFN-γ); and intestinal microflora including bifidobacterium, lactobacillus, enterobacterium, enterococcus, and clostridium were main outcome measures after treatment. Results. It was found that the total response rate in the antiviral group was significantly higher than the anti-TB group after treatment (χ2 = 3.157, P = 0.017 ). There was a significant difference in HBV-DNA negative conversion rates between the antiviral group and anti-TB group (82% vs. 58%, χ2 = 6.384, P = 0.001 ). The ALT, AST, and TBIL in the two groups were all increased after treatment ( P < 0.05 ), but the antiviral group indicated a rise of the above indices compared to the anti-TB group ( P < 0.05 ). The two groups showed a rise on the concentration of CD3+, CD4+, and CD4+/CD8+ T cells and a decline on the CD8+ T cells after treatment ( P < 0.05 ), but these changes in the antiviral group were more evident to those in the anti-TB group ( P < 0.05 ). There was an increase on the IFN-γ level and decrease on the TNF-α and IL-6 levels in both groups after treatment ( P < 0.05 ), but the antiviral group revealed a higher level of IFN-γ with lower levels of TNF-α and IL-6 compared to the anti-TB group ( P < 0.05 ). After treatment, the number of bifidobacteria and lactobacilli was increased, and the number of enterobacteria, enterococci, and clostridium were decreased in the two groups ( P < 0.05 ), while these changes in the antiviral group were more remarkable compared to the anti-TB group ( P < 0.05 ). There was no significant difference in the incidence of adverse reactions between the two groups (χ2 = 0.267, P = 0.731 ). Conclusion. Antiviral therapy for tuberculosis-HBV coinfected patients could inhibit HBV replication, providing protection against liver damage, improving innate immunity, and balancing intestinal microflora.

MUSCULAR TUBERCULOSIS: RARE PRESENTATION OF A COMMON ENTITY

Tuberculosis is a global health problem mainly affecting people in developing countries although muscular involvement is rarely seen. Authors hereby, describe a case of tuberculosis of triceps muscle in a 35-year-old immunocompetent female who presented with swelling in right upper arm. Radiological examination ruled out involvement of underlying bones. Excision biopsy was performed and on histopathological examination cyst wall showed presence of foamy macrophages in sheets, inammatory cells and few scattered epithelioid cells but no well-formed granulomas or giant cells were seen. ZN stain for acid fast bacilli was positive. Based on the above ndings a diagnosis of tuberculosis of triceps muscle was made. The patient responded well to antituberculosis therapy and is currently on follow up.

Computational Drug Repurposing for Antituberculosis Therapy: Discovery of Multi-Strain Inhibitors

Tuberculosis remains the most afflicting infectious disease known by humankind, with one quarter of the population estimated to have it in the latent state. Discovering antituberculosis drugs is a challenging, complex, expensive, and time-consuming task. To overcome the substantial costs and accelerate drug discovery and development, drug repurposing has emerged as an attractive alternative to find new applications for “old” drugs and where computational approaches play an essential role by filtering the chemical space. This work reports the first multi-condition model based on quantitative structure–activity relationships and an ensemble of neural networks (mtc-QSAR-EL) for the virtual screening of potential antituberculosis agents able to act as multi-strain inhibitors. The mtc-QSAR-EL model exhibited an accuracy higher than 85%. A physicochemical and fragment-based structural interpretation of this model was provided, and a large dataset of agency-regulated chemicals was virtually screened, with the mtc-QSAR-EL model identifying already proven antituberculosis drugs while proposing chemicals with great potential to be experimentally repurposed as antituberculosis (multi-strain inhibitors) agents. Some of the most promising molecules identified by the mtc-QSAR-EL model as antituberculosis agents were also confirmed by another computational approach, supporting the capabilities of the mtc-QSAR-EL model as an efficient tool for computational drug repurposing.

Eales’ Disease: When the Rare Sounds Frequent

Eales’ disease is a peripheral occlusive retinal phlebitis, with an unclear pathogenesis. The classic association with hypersensitivity to Mycobacterium tuberculosis protein infers that immunologic disturbance may be involved. Here, we described three cases of Eales’ disease. All patients are Caucasian men aged 27-58 years and presented with vitreous hemorrhage and/or peripheral venous vasculitis. Tuberculin skin sensitive test (Mantoux screening test) and interferon-gamma release assay (IGRA) were positive in all patients. Therapeutic approach included antituberculosis therapy and systemic steroids, associated or not to immunosuppressive therapy, and retinal scatter photocoagulation in all cases. Antivascular endothelial grow factor (VEGF) intravitreal injections were also required in two cases. Since various retinal diseases can resemble this presentation, Eales’ disease is considered a diagnosis of exclusion. Early diagnosis and appropriate therapeutic approach are both essential to accomplish disease control and reduce ophthalmologic complications.

Long-term echocardiographic follow-up of a patient with constrictive pericarditis treated with antituberculosis drugs and pericardiectomy

A middle-aged man presented to the Department of Medicine of our hospital due to exertional dyspnoea, ascites and peripheral oedema. He was later transferred to the Department of Heart Disease as his echocardiography indicated constrictive pericarditis, confirmed by cardiac MRI and cardiac catheterisation. After a thorough investigation, his constrictive pericarditis was assumed to be caused by tuberculosis. He was treated with antituberculosis therapy followed by successful surgical subtotal pericardiectomy, leading to immediate improvement of haemodynamics, regression of symptoms and recovery of cardiac function. The patient remained stable at 5-year echocardiographic follow-up with no evidence of diastolic dysfunction.

Pengaruh Terapi Antituberkulosis Fase Intensif Terhadap Status Gizi Penderita Tuberkulosis Anak di RSUP Haji Adam Malik Medan Tahun 2018

Background: Tuberculosis (TB) is one of the 10 main causes of death from infectious diseases. Indonesia is among the 3 countries with the highest TB incidence in the world. The proportion of pediatric TB patients in North Sumatra Province is 2%. Antituberculosis therapy is a treatment used in TB patients. Successful diagnosis and treatment can prevent millions of deaths each year. Low endurance and malnutrition are factors that influence the possibility of someone becoming a TB patient. This situation can disrupt growth in children. Child growth can be monitored through nutritional status assessments. Objectives: This study aims to determine the effect of intensive phase antituberculosis therapy on the nutritional status of children with tuberculosis in Haji Adam Malik General Hospital Medan in 2018. Methods: This study uses an observational analytic method using a retrospective cohort design, using secondary data derived from medical records at Haji Adam Malik General Hospital Medan in 2018. Data obtained will then be processed and analyzed by the Wilcoxon test using a data processing program. The Wilcoxon test had a significant result (p = 0.001). Results: The mean increase in nutritional status after being given antituberculosis therapy in the age group of children 0-1 years and >1-5 years is a good nutritional status. The mean weight gain after being given antituberculosis therapy in the age group of children 0-1 years was 7.81 kg and >1-5 years was 15.32 kg. The pattern of a child's weight gain after reaching antituberculosis during the intensive phase has increased. Conclusion: In this study, it was found that antituberculosis therapy affected the nutritional status of children with tuberculosis during the intensive phase. Keywords: antituberculosis therapy, child growth, childhood TB, infectious disease Latar Belakang: Tuberkulosis (TB) merupakan salah satu dari 10 penyebab utama kematian dari golongan penyakit infeksi. Indonesia termasuk 3 negara dengan angka kejadian TB tertinggi di dunia. Proporsi pasien TB anak di Provinsi Sumatera Utara sebesar 2%. Terapi OAT merupakan tatalaksana yang digunakan pada pasien TB. Diagnosis dan pengobatan yang berhasil dapat mencegah jutaan kematian setiap tahunnya. Daya tahan tubuh yang rendah dan malnutrisi merupakan faktor yang mempengaruhi kemungkinan seseorang menjadi pasien TB. Keadaan ini dapat menyebabkan terganggunya pertumbuhan pada anak. Pertumbuhan anak dapat dipantau melalui penilaian status gizi. Tujuan: Penelitian ini bertujuan untuk mengetahui pengaruh terapi antituberkulosis fase intensif terhadap status gizi penderita tuberkulosis anak di RSUP Haji Adam Malik Medan tahun 2018. Metode: Penelitian ini menggunakan metode analitik observasional dengan menggunakan desain kohort retrospektif, menggunakan data sekunder yang berasal dari rekam medik di RSUP Haji Adam Malik Medan tahun 2018. Data yang diperoleh selanjutnya akan diolah dan dianalisis dengan uji Wilcoxon menggunakan program pengolahan data. Uji Wilcoxon memiliki hasil yang signifikan (p = 0,001). Hasil: Rerata peningkatan status gizi setelah diberikan terapi antituberkulosis pada kelompok usia anak 0-1 tahun dan > 1-5 tahun adalah berstatus gizi baik. Rerata peningkatan berat badan setelah diberikan terapi antituberkulosis pada kelompok usia anak 0-1 tahun adalah 7,81 kg dan > 1-5 tahun adalah 15,32 kg. Pola kenaikan berat badan anak setelah terapi antituberkulosis selama fase intensif mengalami peningkatan. Kesimpulan: Pada penelitian ini didapatkan bahwa terapi antituberkulosis berpengaruh terhadap status gizi anak penderita tuberkulosis selama fase intensif. Kata Kunci: penyakit infeksi, pertumbuhan anak, TB anak, terapi OAT

Tuberculous Meningitis: Literature Review

Background: Tuberculous meningitis is the most severe form of M.tuberculosis infection, and occurs when there is an invasion of the membranes and cerebrospinal fluid by the bacteria. It develops as a complication of primary infection and reactivation in immunosuppressed. Objectives: This study aims to characterize tuberculous meningitis and bring updates. Design and setting: This is a literature review from the Escola de Medicina Souza Marques‘s students, Brazil. Methods: The used articles were published between 2012 and 2021, from the UpToDate, Scielo, PubMed, and Google Scholar databases. Results: Relevant epidemiological factors, such as HIV, and the absence of the Tuberculosis vaccine could raise the diagnosis hypothesis for the disease. Furthermore, clinical features as headaches, myalgia, fever, emesis, and sudden mood swings are also red flags. Patients should always be tested for HIV infection since mortality in these cases is about 60%. Tuberculous meningitis has a high lethality due to the delay in diagnosis and, in the absence of therapeutics, it worsens the prognosis. The complications are hydrocephalus, cranial nerve paralysis, strabismus, and coma. The diagnostic methods include CSF examination, computed tomography, magnetic resonance imaging, and GeneXpert. The treatment consists of antituberculosis therapy with glucocorticoids. Conclusions: It is essential to identify the disease and start immediate treatment, in addition to emphasizing the BCG vaccine and HIV prevention to reduce cases.