Tuberculous meningitis is a devastating brain infection that is caused by Mycobacterium tuberculosis and is notoriously difficult to diagnose and treat. New technologies characterising the transcriptome, proteome, and metabolome have identified new molecules and pathways associated with tuberculous meningitis severity and poor outcomes that could offer novel diagnostic and therapeutic targets. The next-generation GeneXpert MTB/RIF Ultra assay, when used on CSF, offers diagnostic sensitivity for tuberculous meningitis of approximately 70%, although it is not widely available and a negative result cannot rule out tuberculous meningitis. Small trials indicate that clinical outcomes might be improved with increased doses of rifampicin, the addition of linezolid or fluoroquinolones to standard antituberculosis therapy, or treatment with adjunctive aspirin combined with corticosteroids. Large phase 3 clinical trials are underway worldwide to address these and other questions concerning the optimal management of tuberculous meningitis; these studies also form a platform for studying pathogenesis and identifying novel diagnostic and treatment strategies, by allowing the implementation of new genomic, transcriptomic, proteomic, and metabolomic technologies in nested substudies. 

Tuberculous meningitis: progress and remaining questions

Aim To investigate the treatment effectiveness and outcome in patients with pulmonary tuberculosis relapse and newly diagnosed multidrug resistant pulmonary tuberculosis (MDR-TB). Methods A total of 240 pulmonary MDR-TB patients, including 114 ones with tuberculosis relapse and 126 cases of newly diagnosed pulmonary tuberculosis, were examined. Effectiveness of the basic antimycobacterial therapy course was evaluated based on the time to normalization of tuberculosis clinical manifestation, sputum culture and acid-fast bacilli stain conversion, cavity closure, disappearance of infiltrative and focal changes in the pulmonary tissue. Treatment outcomes were evaluated as cured, treatment completed, treatment failed, died and lost to follow-up according to the World Health Organization guidelines. Results When assessing the treatment effectiveness in patients with MDR-TB, a worse clinical and chest radiograph dynamics was observed in tuberculosis relapse against the background of high parameters of treatment failure (18.4 %) and low cured (34.2 %) compared with newly diagnosed pulmonary tuberculosis (7.1% and 58.7 %, respectively) (p=0.008 and p<0.001, respectively). Conclusion Standard treatment effectiveness in patients with newly diagnosed MDR-TB manifested by faster improvement and stabilization of health, earlier sputum culture and smear conversion, higher frequency of cavity closure and achievement of certain clinical and radiographic improvement against the background of fewer cases of treatment failure and a higher number of cured patients compared with MDR-TB relapse.

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Treatment effectiveness and outcome in patients with a relapse and newly diagnosed multidrug-resistant pulmonary tuberculosis.

The bacilloscopy and culture, the skin test, the BCG vaccine and the discovery of five powerful anti-TB chemicals were assumed sufficient to win the war on TB after World War II but the enigmas and paradoxes uncovered during treatment were given no heed and the humoral immune capacities of the patient were totally ignored. TB resurged at the turn of the century, with a vengeance. The patient suffering from a TB infection mounts a humoral immune response that is as important as a cellular immune reactivity and is useful as a prognostic of treatment outcome and as a diagnostic of latent infections. The anti-TB chemicals are expensive, highly toxic and some destroy the immunocytes of the patient. Their use may provoke a drastic plunge of antibodies' production, which leaves the patient deprived of immunological resources and exposes the successfully treated patient to relapse. The monitoring of the IgG class of anti-TB antibodies synthetized by a subject suffering from a latent infection prone to convert allows the detection of these cases. At the onset of diagnosed cases, the level of these antibodies is sometimes very low, indicating an immunodepression generated by the pathogen. The monitoring of the rise of their production during treatment permits a control of the efficacy of the treatment. A food supplement consisting of RNA oligonucleotides is available, whose property is to stimulate the multiplication of leucocytes and platelets.

Evaluation of the therapeutic, diagnostic, and prognostic means currently applied to counter the surge of tuberculosis

Coronavirus or COVID-19 is a widespread pandemic that has affected almost all countries around the globe. The quantity of infected cases and deceased patients has been increasing at a fast pace globally. This virus not only is in charge of infecting billions of people but also affecting the economy of almost the whole world drastically. Thus, detailed studies are required to illustrating the following trend of the COVID-19 to develop proper short-term prediction models for forecasting the number of future cases. Generally, forecasting techniques are be inculcated in order to assist in designing better strategies and as well as making productive decisions. The forecasting techniques assess the situations of the past thereby enabling predictions about the situation in the future would be possible. Moreover, these predictions hopefully lead to preparation against potentially possible consequences and threats. It's crucial to point out that Forecasting techniques play a vital role in drawing accurate predictions. In this research, we categorize forecasting techniques into different types, including stochastic theory mathematical models and data science/machine learning techniques. In this perspective, it is feasible to generate and develop strategic planning in the public health system to prohibit more deceased cases and managing infected cases. Here, some forecast models based on machine learning are introduced and comprising the Linear Regression model which is assessed for time series prediction of confirmed, deaths, and recovered cases in Ukraine and the globe. It turned out that the Linear Regression model is feasible to implement and reliable in illustrating the trend of COVID-19.

Machine Learning Model of COVID-19 Forecasting in Ukraine Based on the Linear Regression

Background The aim of this study was to investigate the effectiveness of intravenous isoniazid (H) and ethambutol (E) administered in patients with new sputum positive drug-susceptible pulmonary tuberculosis (TB) with tuberculous meningoencephalitis (TM) and human immunodeficiency virus (HIV) co-infection in the intensive phase of treatment. Methods Fifty-four patients with TB/TM and HIV co-infection were enrolled for this study. Group 1 comprised of 23 patients treated with E and H intravenously, while rifampicin and pyrazinamide were prescribed orally. Group 2 consisted of 31 patients treated with the first-line anti-TB drugs orally. The concentrations of H and E in blood serum were detected using a chromatographic method. Results A significant improvement in the clinical symptoms and X-ray signs in patients treated intravenously with H and E was observed and compared to group 2. The sputum Mycobacterium tuberculosis positivity was observed during the second month of the treatment in 25.0% of patients from group 1 and 76.1% of the patients from the control group (p=0.003). In addition, nine patients (39.1%) died up to 6 months when H and E were prescribed intravenously compared with 22 (70.9%) in group 2 (p=0.023). Conclusion In TB/TM with HIV, the intravenous H and E treatment was more effective than oral H and E treatment at 2 months of intensive treatment in sputum conversion as well as in clinical improvement, accompanied by significantly higher mean serum concentrations. In addition, the mortality rate was lower in intravenous H and E treatment compared to oral treatment.

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Effectiveness of Intravenous Isoniazid and Ethambutol Administration in Patients with Tuberculosis Meningoencephalitis and HIV Infection.

Background: To study the effectiveness of antituberculosis chemotherapy in patients with relapse pulmonary tuberculosis (RTB) compared with patients with the newly diagnosed process. Methods: We examined 285 TB patients, including 126 individuals with RTB (Group 1) and 159 patients with newly diagnosed pulmonary tuberculosis (NDPTB) (Group 2). All patients were diagnosed with infiltrative PTB. Effectiveness of the basic course of antimycobacterial treatment was assessed in accordance with the following data: time required for the normalization of clinical manifestations, smear conversion, cavity healing, disappearance of infiltrative and focal changes in the pulmonary tissue, as well as the final clinical effectiveness of therapy. Results: Disappearance of clinical symptoms was statistically significantly faster in Group 2 compared with RTB patients in 2.25 ± 0.11 and 3.40 ± 0.15 months, respectively (P

Alexandr Peshenko

Papers

Effectiveness of Intravenous Isoniazid and Ethambutol Administration in Patients with Tuberculosis Meningoencephalitis and HIV Infection.

Effectiveness of anti-tuberculosis chemotherapy in patients with tuberculosis relapse compared with newly diagnosed patients