Modern Tuberculosis Research Articles

Modern tuberculosis prevention and control programs at the regional level

The article presents an assessment of the effectiveness of measures to prevent the spread of tuberculosis in the Omsk region, where modern approaches and directions of the national strategy of tuberculosis elimination are realized. The qualitative and quantitative changes in the cohorts of first-detected cases of tuberculosis for the analyzed period of 2015 - 2021 are noted. Actual directions of tuberculosis prevention for the Omsk region are revealed.

Acceptability of integrating traditional tuberculosis care with modern healthcare services in the Amhara Regional State of Northwest Ethiopia: A qualitative study

Many people with tuberculosis (TB) rely solely on traditional healthcare services. Integrating traditional healthcare with modern healthcare services can increase access, quality, continuity, consumer satisfaction, and efficiency. However, successful integration of traditional healthcare with modern healthcare services requires stakeholder acceptance. Therefore, this study aimed to explore the acceptability of integrating traditional care with modern TB care in the South Gondar zone, the Amhara Regional State, northwest Ethiopia.Data were collected from patients with TB, traditional healers, religious leaders, healthcare providers, and TB program personnel. Data were collected using in-depth interviews and focus group discussions from January to May 2022.A total of 44 participants were included in the study. The context and perspectives of integration were thematized into the following five major themes: 1) referral linkage, 2) collaboration in awareness creation in the community, 3) collaboration in monitoring and evaluation of integration, 4) maintaining continuity of care and support, and 5) knowledge and skill transfer. Integrating traditional and modern TB care was acceptable to both modern and traditional healthcare providers as well as TB service users. This may be an effective strategy for improving the TB case detection rate by decreasing diagnosis delay, treatment initiation, and catastrophic costs.

Redefining tuberculosis: an interview with Lalita Ramakrishnan.

Professor Lalita Ramakrishnan is at the forefront of modern tuberculosis (TB) research. She has developed vital tools, most notably a robust zebrafish model, to study this disease, leading to seminal discoveries uncovering bacterial and host interactions throughout infection. Her group has harnessed this knowledge to develop new treatments for TB and shape clinical research. By unveiling these complex interactions, they have also improved our understanding of fundamental biology of macrophages and other infectious diseases, such as leprosy.

Rare Presentation of Disseminated Tuberculosis in the Present Era of Modern Tuberculosis Management

Background: Disseminated tuberculosis (TB) is defined as two or more noncontiguous sites resulting from lymphohematogenous dissemination of Mycobacterium tuberculosis. In an immunocompetent host, it is uncommon. The presentation varies, and non-specific early infection symptoms can be noted on chest radiography. Early medication beginning is linked to significantly better outcomes in cases of disseminated tuberculosis. The current case report describes the series of incidents that resulted from a 50-year-old man's excessive usage of the corticosteroid medication tablet Betamethasone, which he was taking for a cough and cold related to his chronic obstructive pulmonary disease (COPD).
 Case Presentation: A 50-year-old Indian male patient with osteoporosis, drug-induced adrenal insufficiency, and bilateral pleural effusion who is receiving anti-tuberculosis therapy which he is on now is presented to the outpatient department of a tertiary hospital with complaints of fever associated with shivering on & off for 4 months, generalized tiredness. He had a history of loose stools for 2-3 days, small joint pain, left knee joint pain and swelling, loss of weight, and loss of appetite.
 Conclusion: The right diagnosis, treatment, patient counseling, diet, and family support helped him recover despite his turbulent recovery phase. As far as steroid therapy is concerned, it is a double-edged sword, meaning that taking (OTC) over-the-counter steroid drugs without first seeking adequate medical advice could have serious negative effects.

Оптимизация работы дифференциально-диагностического отделения в структуре современного противотуберкулезного диспансера

Оптимизация работы дифференциально-диагностического отделения в структуре современного противотуберкулезного диспансера

Designing quinoline-isoniazid hybrids as potent anti-tubercular agents inhibiting mycolic acid biosynthesis

Isoniazid is a cornerstone of modern tuberculosis (TB) therapy and targets the enoyl ACP reductase InhA, a key enzyme in mycolic acid biosynthesis. InhA is still a promising target for the development of new anti-TB drugs. Herein, we report the design, synthesis, and anti-tubercular activity of new isoniazid hybrids. Among these, 1H-1,2,3 triazole-tethered quinoline-isoniazid conjugates 16a to 16g exhibited high activity against Mycobacterium tuberculosis with minimal inhibitory concentrations in the 0.25–0.50 μg/mL range and were bactericidal in vitro. Importantly, these compounds were well tolerated at high doses on mammalian cells, leading to high selectivity indices. The hybrids were dependent on functional KatG production to inhibit mycolic acid biosynthesis. Moreover, overexpression of InhA in M. tuberculosis resulted in high resistance levels to 16a-16g and reduced mycolic acid biosynthesis inhibition, similar to isoniazid. Overall, these findings suggest that the synthesized quinoline-isoniazid hybrids are promising anti-tubercular molecules, which require further pre-clinical evaluation.

The treatment of tuberculosis under current conditions

Study of the current state of problems of treatment of patients with tuberculosis based on literature data and their own experience. In the Russian Federation, the number and proportion of patients with co-infection with HIV/tuberculosis continues to increase against the background of improvement in the main epidemiological indicants for tuberculosis. In 2017, 20.9% of newly diagnosed tuberculosis patients had HIV infection. The combination of the two infections significantly complicates the further improvement of the situation with tuberculosis, and the appearance of drug-resistant strains of Mycobacterium tuberculosis sometimes completely neutralizes the results of chemotherapy. The article describes the schemes of modern tuberculosis chemotherapy taking into account HIV/tuberculosis co-infection, as well as MDR in combination with surgical treatment methods, as well as analyzes the data of epidemiological monitoring of treatment of 1115 tuberculosis patients newly diagnosed in 2017 in Moscow, 360 tuberculosis patients with MDR MBT (cohort 20132014), the results of treatment with the use of new chemotherapy regimens for tuberculosis (bedaquiline, linezolid, moxifloxacin) in 36 patients, the effectiveness and safety of surgical methods in 192 patients. The application of new individualized anti-TB chemotherapy schedules in patients with HIV co-infection/tuberculosis with MDR-MBT has allowed to improve the treatment efficacy. The surgical intervention combined with modern chemotherapy regimens in patients with HIV/tuberculosis co-infection with MDR MBT has been proved to be effective and safe, contributes to the improving the results of treatment for this category of patients. The confluence of two global problems of co-infection HIV/TB and MDR TB, significantly prevents from the end of the tuberculosis epidemic in the world. At the same time, advances in the development and implementation of new anti-TB drugs and surgical treatment methods give hope for significant progress for resolving this situation.

Targeting Unconventional Host Components for Vaccination-Induced Protection Against TB.

The current tuberculosis (TB) vaccine, Bacille Calmette-Guerin (BCG), is effective in preventing TB in young children but was developed without a basic understanding of human immunology. Most modern TB vaccine candidates have targeted CD4+ T cell responses, thought to be important for protection against TB disease, but not known to be sufficient or critical for protection. Advances in knowledge of host responses to TB afford opportunities for developing TB vaccines that target immune components not conventionally considered. Here, we describe the potential of targeting NK cells, innate immune training, B cells and antibodies, and Th17 cells in novel TB vaccine development. We also discuss attempts to target vaccine immunity specifically to the lung, the primary disease site in humans.

Re-evaluating the role of isoniazid in treatment of pulmonary tuberculosis

Re-evaluating the role of isoniazid in treatment of pulmonary tuberculosis

THE ROLE OF SOCIAL AND PSYCHOLOGICAL FACTORS IN IMPROVING THE QUALITY OF CARE FOR PATIENTS WITH TUBERCULOSIS AT THE PRESENT STAGE OF HEALTH CARE

The work is devoted to an overview of the modern tuberculosis epidemic’s characteristic features, expanding care, strengthening prevention and intensifying research, and solving social, medical and psychological factors that require innovative, multi-sectoral and integrated approaches.

Urinary tuberculosis: still a challenge.

Urinary tuberculosis (TB) is a challenging disease to cope with, as there has been no noticeable difference in basic diagnostic and therapeutic options in clinical practice over time. The aim of the current review was the critical assessment and evaluation of TB, which remains a major global health problem. The available literature regarding TB in the PubMed database was extensively searched. New interdisciplinary team approaches such as next-generation sequencing are promising for the diagnosis and treatment of the disease. The epidemiology of the disease is changing with globalization and increasing migration events; however, the knowledge here is limited. Despite ongoing destruction, kidney functions need to be preserved as much as possible, and relatively rapid development of minimally invasive techniques relieved the surgeons in this regard. Experience is increasing in minimally invasive techniques that provide better comfort for patients compared to extensive radical surgeries. Knowing the pathogenesis of urinary TB is essential for understanding the range of clinical manifestations. The onset of the disease is usually insidious. Despite modern TB drugs, reconstructive surgery, and minimally invasive procedures, progression cannot be prevented in some patients, and patient selection is essential, but we still do not have sufficient information and objective parameters to predict progression.

Tuberculosis of the meninges and central nervous system. Experience of clinical diagnostics in St. Petersburg for 50 years

The clinic and diagnostics of tuberculosis meningitis (TM) in 926 patients treated in St. Petersburg hospitals in 1965–1994 (group 1) and in 1995–2018 (group 2) is presented. The TM clinic is demonstrated to be determined by the form of tuberculosis and its characteristic generalization nature in the presence of repeated waves of bacteremia and allergic vasculitis of greater or lesser severity. There is clinical peculiarity of TM in primary pulmonary tuberculosis and its early large-focal and late miliar generalization, as well as in hematogenous tuberculosis. In patients of the 1st and 2nd groups the TM clinic shows in some respects a noticeable similarity, in others — a significant difference. Despite the typical symptoms, early diagnosis of TM took place in less than 20% of patients. Clinical examples illustrating the unusual development of TM, contrasting with its usual course, are given. A number of objective and subjective factors contributing to the adverse evolution of TM and its lethal outcome are discussed. These include the peculiarity of modern tuberculosis, especially when associated with HIV infection, as well as medical errors associated with ignorance of the pathogenesis of tuberculosis and failure to comply with the minimum examination for tuberculosis.

Detection of Novel Gene Mutations Associated with Pyrazinamide Resistance in Multidrug-Resistant Mycobacterium tuberculosis Clinical Isolates in Southern China.

ObjectivePyrazinamide (PZA) is a cornerstone of modern tuberculosis regimens. This study aimed to investigate the performance of genotypic testing of pncA+ upstream region, rpsA, panD, Rv2783c, and clpC1 genes to add insights for more accurate molecular diagnosis of PZA-resistant (R) Mycobacterium tuberculosis.MethodsDrug susceptibility testing, sequencing analysis of PZA-related genes including the entire operon of pncA (Rv2044c-pncA-Rv2042c) and PZase assay were performed for 448 M. tuberculosis clinical isolates.ResultsOur data showed that among 448 M. tuberculosis clinical isolates, 113 were MDR, 195 pre-XDR and 70 XDR TB, while the remaining 70 strains had other combinations of drug-resistance. A total of 60.04% (269/448) M. tuberculosis clinical isolates were resistant to PZA, of which 78/113 were MDR, 119/195 pre-XDR and 29/70 XDR TB strains. PZAR isolates have predominance (83.3%) of Beijing genotype. Genotypic characterization of Rv2044c-pncA-Rv2042c revealed novel nonsynonymous mutations in Rv2044c with negative PZase activity which led to confer PZAR. Compared with phenotypic data, 84.38% (227/269) PZAR strains with mutations in pncA+ upstream region exhibited 83.64% sensitivity but the combined evaluation of the mutations in rpsA 2.60% (7/269), panD 1.48% (4/269), Rv2783c 1.11% (3/269) and Rv2044c 0.74% (2/269) increased the sensitivity to 89.59%. Fifty-seven novel mutations were identified in this study. Interestingly, a frameshift deletion (C−114del) in upstream of pncAwt nullified the effect of A−11G mutation and induced positive PZase activity, divergent from five PZase negative A−11G PZAR mutants. Twenty-six PZAR strains having wild-type-sequenced genes with positive or negative PZase suggest the existence of unknown resistance mechanisms.ConclusionOur study revealed that PZAR rate in MDR and pre-XDR TB was markedly higher in southern China. The concomitant evaluation of pncA+ UFR, rpsA, panD, Rv2783c, and Rv2044c provides more dependable genotypic results of PZA resistance. Fifty-seven novel mutations/indels in this study may play a vital role as diagnostic markers. The upstream region of pncA and PZase regulation are valuable to explore the unknown mechanism of PZA-resistance.

Tuberculosis in South Asia: a tide in the affairs of men

Background: Tuberculosis (TB) remains the most common cause of infectious disease deaths worldwide. What is perhaps less appreciated is that the caseload of tuberculosis patients in South Asia is staggering. South Asia has almost 40% of the global TB burden with 4,028,165 cases in 2015. This region also has a disproportionate share of TB deaths (681,975 deaths, 38% of the global burden). Worldwide just 12.5% of TB cases are in HIV positive individuals, but much research and investment has focused on HIV-associated TB. Only 3.5% of patients with tuberculosis in South Asia have HIV co-infection. Not surprisingly with such a huge burden of disease, this region has an estimated 184,336 multi drug resistant (MDR) cases among notified TB cases which accounts for a third of global MDR burden. Crucially, at least 70% of the estimated MDR cases remain untreated in this region and MDR treatment success ranged from only 46% for India to 88% for Sri Lanka in the 2012 cohort that received treatment. This region represents many of the drivers of the modern TB epidemic: rapid urbanization and high density populations with dramatically rising incidence of diabetes, a burgeoning and largely unregulated private sector with escalating drug resistance and high air pollution both outdoor and household.
 Conclusion: From bacterial biochemistry to policy implementation, we suggest ways in which South Asia can seize the opportunity lead global TB elimination by demonstrating feasibility in some of the world’s most densely populated cities and remotest reaches of the Himalayas. Clearly political will is essential, but we cannot defeat TB without understanding how to eliminate it in South Asia.

Preparing Short Message Service Reminders to Improve Treatment Adherence among Tuberculosis Patients in Sleman District, Indonesia.

Background:Modern tuberculosis (TB) treatment approaches require innovative adherence strategies.Objectives:This study aimed to explore the feasibility of using short message service (SMS) reminders through mobile phones to improve treatment adherence among TB patients.Materials and Methods:An exploratory sequential design was applied; initially, qualitative data collection was conducted among TB patients and TB program officers. A content analysis was done and messages were then developed. The messages were pretested using focus group discussions (FGDs), and a quantitative method using quasi-experiment on 120 TB patients. All the patients received a standard directly observed therapy short reminder, but only intervention group received daily SMS reminders (n = 60), the data were then analyzed using logistic regression.Results:Reminder messages can be sent directly to young TB patients or indirectly to the relatives of elderly patients. There are four phases of emotional states, which TB patients go through during treatment starting with disappointment and desperation after being diagnosed, grievance during the initiation of treatment, high and then low desire to follow treatment. Reminder messages aimed at improving treatment adherence should correspond to those conditions and motivate, inform, and facilitate TB patients to overcome all the obstacles during treatment. SMS reminders should also be short, informal, and easy to understand. Treatment adherence was significantly higher among the intervention group compared to the control group (odds ratio = 10.73) after controlling for demographics, accessibility, and adverse drug reaction.Conclusions:SMS through mobile phone is a feasible form of media to remind TB patients and to improve adherence to treatment in low-resource facilities.

Prospective study of surgical management of drug resistant and complications associated with pulmonary tuberculosis

Introduction: Tuberculosis (TB) is a ubiquitous, highly fatal contagious chronic granulomatous bacterial infection. It is mainly an infection of the lungs but can affect almost any part of the body. Although TB is a preventable and treatable disease, yet it still poses a significant threat globally. In 2012, an estimated 8.6 million people developed TB and 1.3 million died from the disease. Modern tuberculosis treatment relies on chemotherapy, surgery is accepted as adjuvant treatment for MDR TB.Methodology: This study include total of 40 diagnosed cases of MDR or XDR pulmonary tuberculosis with it’s complications.Known cases of pulmonary tuberculosis with multidrug resistance and Extensive drug resistance with complications in Department of surgery, M.G.M medical college and M.Y Hospital, Indore.Result: The mean age of presentation was 38.82 ± SD years, Thoracotomy with Decortication was the most commonly performed procedure in (72.5% patients), Lobectomy in 20%patients, Pneumonectomy in 5% patients and Segmentectomy3% patients. Postoperative complication occurred in 10 patients (25%), 2 deaths occured in this study within 3rd postoperative day. Overall mortality was 5%, Out of 40 Patients complete cure was obtained in 85% of the treated patients, All patients had adjuvant chemotherapy post operatively for mean duration of 15.58 months with follow up for 12 to 18 months.Conclusion: The resectional surgery has a distinct role in the management of MDR/XDR tuberculosis. The proper selection of the patients and early decision for surgical intervention can achieve a high success rate of drug resistant pulmonary tuberculosis with well localised pulmonary lesion.

TB's Chinese travels.

Statistical modelling from an impressively large genetic dataset traces the historical origins and spread of China’s modern tuberculosis (TB) epidemic. But there is more scope in the future to harness the potential of ancient TB genomes to model its evolution.

Pyrazinoic Acid Inhibits a Bifunctional Enzyme in Mycobacterium tuberculosis.

Pyrazinamide (PZA), an indispensable component of modern tuberculosis treatment, acts as a key sterilizing drug. While the mechanism of activation of this prodrug into pyrazinoic acid (POA) by Mycobacterium tuberculosis has been extensively studied, not all molecular determinants that confer resistance to this mysterious drug have been identified. Here, we report how a new PZA resistance determinant, the Asp67Asn substitution in Rv2783, confers M. tuberculosis resistance to PZA. Expression of the mutant allele but not the wild-type allele in M. tuberculosis recapitulates the PZA resistance observed in clinical isolates. In addition to catalyzing the metabolism of RNA and single-stranded DNA, Rv2783 also metabolized ppGpp, an important signal transducer involved in the stringent response in bacteria. All catalytic activities of the wild-type Rv2783 but not the mutant were significantly inhibited by POA. These results, which indicate that Rv2783 is a target of PZA, provide new insight into the molecular mechanism of the sterilizing activity of this drug and a basis for improving the molecular diagnosis of PZA resistance and developing evolved PZA derivatives to enhance its antituberculosis activity.

Optimally capturing latency dynamics in models of tuberculosis transmission

Although different structures are used in modern tuberculosis (TB) models to simulate TB latency, it remains unclear whether they are all capable of reproducing the particular activation dynamics empirically observed. We aimed to determine which of these structures replicate the dynamics of progression accurately. We reviewed 88 TB-modelling articles and classified them according to the latency structure employed. We then fitted these different models to the activation dynamics observed from 1352 infected contacts diagnosed in Victoria (Australia) and Amsterdam (Netherlands) to obtain parameter estimates. Six different model structures were identified, of which only those incorporating two latency compartments were capable of reproducing the activation dynamics empirically observed. We found important differences in parameter estimates by age. We also observed marked differences between our estimates and the parameter values used in many previous models. In particular, when two successive latency phases are considered, the first period should have a duration that is much shorter than that used in previous studies. In conclusion, structures incorporating two latency compartments and age-stratification should be employed to accurately replicate the dynamics of TB latency. We provide a catalogue of parameter values and an approach to parameter estimation from empiric data for calibration of future TB-models.

Treatment Outcome of Pulmonary Tuberculosis Patients at Tehsil Head Quarter Hospital Dargai

Even in this modern era Tuberculosis (TB) poses a serious challenge for the world. Due to emerging of resistance strain and coinfection with Human Immuno Deficiency Virus (HIV)/Acquired Immuno Deficiency Syndrome (AIDS) it is difficult to control the disease. Among the 22 high TB burden countries Pakistan ranks 5th, in case of multi drug resistant its position is 27th [1]. In the year 2013, approximately 12997 incident cases of drug resistant TB in which only 1570 (13%) were registered for treatment [2]. Aim of this study was to find out treatment success rate of pulmonary tuberculosis (PTB) at Tehsil Head Quarter Dargai, Khyber Pakhtunkhwa, Pakistan from 1st January 2011 to 31st December 2014. A total of 410 PTB patients were enrolled. Of the total cases, 373 (90.98%) were diagnosed as new cases, 17 (4.15%) were relapse cases, 13 (3.17%) were transfer in cases, 7 (1.7%) were others cases while no case of treatment failure and treatment default were recorded. The treatment success rate (cured and treatment completed) was reported 333 (81.22%), 8 (1.95%) cases were died from PTB, only 1 (0.24%) case was failure, 2 (0.49%) cases were default while 4 (0.98%) were transfer out and 62 (15.12%) cases were no record of treatment outcome.