Treatment Of Tuberculosis Disease Research Articles

State-of-the-art detection of Mycobacterium tuberculosis in blood during tuberculosis infection using phage technology

Tuberculosis (TB), an aerosol-transmitted infection caused by Mycobacterium tuberculosis (Mtb), remains the commonest cause of death globally, from an infectious bacterial disease. Nine years on from the launch of the World Health Organization (WHO)'s END-TB strategy, disease incidence rates are stubbornly unchanged [1]. While this represents, in part, a reversal of improving trends caused by the COVID-19 pandemic, it also reflects the fragility and inadequacy of healthcare systems to sustain TB control [2]. Although multifactorial, a key reason for this is the ineffectiveness of existing clinical tools to meet the two key objectives of the END-TB strategy-(i) early diagnosis and treatment of TB disease (to limit onward transmission); and (ii) disease prevention through screening for asymptomatic TB infection (TBI). Meeting both objectives will rely on the development of new biomarkers with high accuracy, but the global nature of the TB problem also requires that new tests are rapid, low cost and can be measured in patients by sampling from universally accessible sites. In this review, we will present the accumulating evidence for circulating Mtb in both TB disease and asymptomatic TBI and discuss the potential utility of novel bacteriophage-based technology for blood-based detection of Mtb.

Potential energy surface, effect of solvents in molecular level, experimental spectra (FTIR, Raman, UV–visible & NMR), electronic, and dynamics simulation of isobavachalcone –Anti tuberculosis agent

The spectroscopic characteristics, molecular structure, and biological characteristics of the Isobavachalcone (IBC) structure have been studied using computational techniques utilizing the usual B3LYP/6-311++G (d,p). PED (Potential Energy Distribution) is used throughout process of assigning the fundamental wave-numbers of IBC. In this work, we have reported the correlation between experimental and computed examination of molecular configuration, FT:IR & Raman, UV–Visible absorption, and NMR (Nuclear Magnetic Resonance) spectrum of the title compound. Potential energy scan (PES) analysis of IBC was enhanced in the initial stage with same basis set. FMO (Frontier Molecular Orbital), MEP (Molecular Electrostatic Potential), local reactivity and quantum chemical descriptors has also been analyzed. Furthermore, drug-likeness and ADMET predictions of the present ligand shows good pharmacological activity. ELF (Electron Localised Function), LOL (Localised Orbital Locator) and RDG (Reduced Density Function) enacted for both the gas and solvents phases. A docking simulation performed with the 2FUM receptor using the Auto Dock software showed that the IBC compound has inhibitory activity against Mycobacterium tuberculosis disease. All our results suggest that the IBC molecule could have a great effect in the treatment of tuberculosis disease. MD simulations been executed over 100 ns to predict the RMSD, RMSF, and the radius-of gyration analyses.

The Effect of the Community-Based- Directly Observed Therapy on the Treatment Outcome of Tuberculosis Patients in Mitooma District, Western-Uganda

Tuberculosis (TB) remains the ninth leading cause of death in the world and a leading cause of death among infectious diseases. Sub-Saharan Africa has nearly all high TB burden countries including Uganda which contributes to the highest Tuberculosis related mortality globally. Poor adherence to Tuberculosis treatment can lead to prolonged infection and poor treatment outcomes. Directly Observed Treatment (DOT) seeks to improve adherence to TB treatment by observing patients while they take their anti-TB medications. The aim of the study was to determine the effect of the Community Based- DOT on the Treatment Outcomes of Tuberculosis Patients in Mitooma District, Western Uganda. A cross-sectional survey research design was adopted and data were collected from the TB patients. Results revealed that TB patients who were not educated were 9.01 times more likely to get cured compared to the educated patients (AOR=9.01; 95% CI (1.6-5.9); p=0.013). Duration or time spent on TB medication was associated with TB treatment outcome because the patients who had spent 6 months on TB medication (AOR=2.9; 95% CI (1.14 – 7.9); p=0.004) were threefold more likely to get cured compared to those who had spent less than one month. Similarly, patients who had spent six months and above (AOR=4.1; 95%CI (0.07 – 0.87); p=0.026) were more than four times more likely to get cured compared to those who had spent less than one month. Results further showed that patients who were neutral in attributing their health state to the way they swallowed the TB medication (AOR = 0.33; 95%CI (0.12 – 0.9); p=0.001) were 67% less likely to get cured compared to patients who strongly agreed that their health status were attributed to the way they swallowed TB medication. Majority of the TB patients described the program as vital in treatment of TB disease as health caregivers would work closely with TB patients to adhere to treatment. Further, the study revealed that CB-DOT improved TB treatment outcomes. Monitoring the swallowing of TB drugs by health workers, health education and regular visits were highly recommended. Therefore, studies on policies for implementation of patient-centered and community-centered CB-DOT deserve further attention.

A Review on Prevention, Diagnosis, Treatment and Rehabilitation of Tuberculosis

Tuberculosis (TB), known as the White Plague is of great significance to humanity for the magnitude of morbidity and mortality it has generated over centuries from the very start of human civilization. In this Review, we will describe the history of prevention (vaccination and management of TB infection), diagnosis, treatment, and pulmonary rehabilitation of post-treatment sequelae. The article leads the reader through the main discoveries which paved the way to the modern approach to TB prevention and care. The history of the Bacille Calmette-Guerin (BCG) vaccine and of the diagnosis and treatment of TB infection are presented, together with that of the diagnosis and treatment of TB disease. Pivotal was in 1882 the discovery by Robert Koch of the aetiological agent of TB, and his pioneering work in culturing the bacillus and developing tuberculin. Also of enormous importance was, in 1895, the discovery of the X-rays by Wilhelm Conrad Rontgen, € discovery which paved the way for the development of modern imaging technologies. To complement this, the more recent history of rehabilitation of post-treatment sequelae is summarized, given the importance, this issue has on patients’ well-being and Quality of Life.

The cascade of care in tuberculosis infection screening and management in newly arrived refugees in Aarhus, Denmark

BackgroundScreening for tuberculosis (TB) disease and infection is often a part of health screening programs offered to refugees, but the yield of screening varies and losses along the steps from screening to treatment completion was reported. MethodsA retrospective cohort study was performed investigating a newly arrived refugee population offered a systematic refugee health assessment in Aarhus, Denmark. Data was collected on screening, referral, diagnosis and treatment for TB disease and infection. ResultsAmong both adults and children IGRA positivity was associated with origin in a high TB incidence country and increasing age. The number needed to screen (NNS) to find one case of TB infection was 7 among adult refugees and 19 among children, while NNS for TB disease was 266 and 164 respectively. The proportion of the eligible population with a valid result was 78.1% for adults and 71.3% for children, while 43.1% and 50% of adults and children with presumed TB infection completed preventive treatment. DiscussionScreening for TB disease and infection among refugees in Aarhus had a high yield in terms of diagnosis, however significant losses were seen during screening, follow-up and preventive treatment completion.

Enhanced Integration of TB Services in Reproductive Maternal Newborn and Child Health (RMNCH) Settings in Eswatini.

Tuberculosis (TB) primarily affects women during their reproductive years and contributes to maternal mortality and poor pregnancy outcomes. For pregnant women living with HIV (WLHIV), TB is the leading cause of non-obstetric maternal mortality, and pregnant WLHIV with TB are at increased risk of transmitting both TB and HIV to their infants. TB diagnosis among pregnant women, particularly WLHIV, remains challenging, and TB preventive treatment (TPT) coverage among pregnant WLHIV is limited. This project aimed to strengthen integrated TB and reproductive, maternal, neonatal and child health (RMNCH) services in Eswatini to improve screening and treatment for TB disease, TPT uptake and completion among women receiving RMNCH services. The project was conducted from April-December 2017 at four health facilities in Eswatini and introduced enhanced monitoring tools and on-site technical support in RMNCH services. We present data on TB case finding among women, and TPT coverage and completion among eligible WLHIV. A questionnaire (S1 Appendix) measured healthcare provider perspectives on the project after three months of project implementation, including feasibility of scaling-up integrated TB and RMNCH services. A total of 5,724 women (HIV-negative or WLHIV) were screened for active TB disease while attending RMNCH services; 53 (0.9%) were identified with presumptive TB, of whom 37 (70%) were evaluated for TB disease and 6 (0.1% of those screened) were diagnosed with TB. Among 1,950 WLHIV who screened negative for TB, 848 (43%) initiated TPT and 462 (54%) completed. Forty-three healthcare providers completed the questionnaire, and overall were highly supportive of integrated TB and RMNCH services. Integration of TB/HIV services in RMNCH settings was feasible and ensured high TB screening coverage among women of reproductive age, however, symptom screening identified few TB cases, and further studies should explore various screening algorithms and diagnostics that optimize case finding in this population. Interventions should focus on working with healthcare providers and patients to improve TPT initiation and completion rates.

Chapter 5: Treatment of tuberculosis disease

Chapter 5: Treatment of tuberculosis disease

Diagnostic Challenges in Childhood Pulmonary Tuberculosis-Optimizing the Clinical Approach.

The management of childhood tuberculosis (TB) is hampered by the low sensitivity and limited accessibility of microbiological testing. Optimizing clinical approaches is therefore critical to close the persistent gaps in TB case detection and prevention necessary to realize the child mortality targets of the End TB Strategy. In this review, we provide practical guidance summarizing the evidence and guidelines describing the use of symptoms and signs in decision making for children being evaluated for either TB preventive treatment (TPT) or TB disease treatment in high-TB incidence settings. Among at-risk children being evaluated for TPT, a symptom screen may be used to differentiate children who require further investigation for TB disease before receiving TPT. For symptomatic children being investigated for TB disease, an algorithmic approach can inform which children should receive TB treatment, even in the absence of imaging or microbiological confirmation. Though clinical approaches have limitations in accuracy, they are readily available and can provide valuable guidance for decision making in resource-limited settings to increase treatment access. We discuss the trade-offs in using them to make TB treatment decisions.

History of prevention, diagnosis, treatment and rehabilitation of pulmonary sequelae of tuberculosis

Tuberculosis (TB), known as the White Plague’ is of great significance to humanity for the magnitude of morbidity and mortality it has generated over centuries from the very start of human civilization. In this Review, we will describe the history of prevention (vaccination and management of TB infection), diagnosis, treatment and pulmonary rehabilitation of post-treatment sequelae. The article leads the reader through the main discoveries which paved the way to the modern approach to TB prevention and care. The history of Bacille Calmette-Guérin (BCG) vaccine and of the diagnosis and treatment of TB infection are presented, together with that of diagnosis and treatment of TB disease. Pivotal was in 1882 the discovery by Robert Koch of the aetiological agent of TB, and his pioneering work in culturing the bacillus and developing tuberculin. Also of enormous importance was, in 1895, the discovery of the X-rays by Wilhelm Conrad Röntgen, discovery which paved the way to the development of the modern imaging technologies.To complement this, the more recent history of rehabilitation of post-treatment sequelae is summarized, given the importance this issue has on patients’ wellbeing and Quality of Life.

Scaling up investigation and treatment of household contacts of tuberculosis patients in Brazil: a cost-effectiveness and budget impact analysis

In Brazil, investigation and treatment of tuberculosis infection (TBI) in households contacts (HHC) of TB patients is not a priority. We estimated the cost-effectiveness and budget-impact of scaling-up an enhanced HHC management in Brazil. We conceptualized a cascade-of-care that captures how HHC of tuberculosis patients are investigated in Brazil (status quo) and two enhanced strategies for management of HHC focusing on: (1) only tuberculosis disease (TBD) detection and, (2) TBD and TBI detection and treatment. Effectiveness was the number of HHC diagnosed with TBD and completing TBI treatment. Proportions in the cascades-of-care were derived from a meta-analysis. Health-system costs (2019 US$) were based on literature and official data from Brazil. The impact of enhanced strategies was extrapolated using reported data from 2019. With the status quo, 0 (95% uncertainty interval: 0-1) HHC are diagnosed with TBD and 2 (0-16) complete TBI treatment. With strategy(1), an additional 15 (3-45) HHC would be diagnosed with TBD at a cost of US$346 each. With strategy(2), 81 (19-226) additional HHC would complete TBI treatment at a cost of US$84 each. A combined strategy, implemented nationally to enhance TBD detection and TBI treatment would result in an additional 9,711 (845-28,693) TBD being detected, and 51,277 (12,028-143,495) more HHC completing TBI treatment each year, utilizing 10.9% and 11.6% of the annual national tuberculosis program budget, respectively. Enhanced detection and treatment of TBD and TBI among HHC in Brazil can be achieved at a national level using current tools at reasonable cost. None.

Achieving a \u201cstep change\u201d in the tuberculosis epidemic through comprehensive community-wide intervention: a model-based analysis

BackgroundGlobal progress towards reducing tuberculosis (TB) incidence and mortality has consistently lagged behind the World Health Organization targets leading to a perception that large reductions in TB burden cannot be achieved. However, several recent and historical trials suggest that intervention efforts that are comprehensive and intensive can have a substantial epidemiological impact. We aimed to quantify the potential epidemiological impact of an intensive but realistic, community-wide campaign utilizing existing tools and designed to achieve a “step change” in the TB burden.MethodsWe developed a compartmental model that resembled TB transmission and epidemiology of a mid-sized city in India, the country with the greatest absolute TB burden worldwide. We modeled the impact of a one-time, community-wide screening campaign, with treatment for TB disease and preventive therapy for latent TB infection (LTBI). This one-time intervention was followed by the strengthening of the tuberculosis-related health system, potentially facilitated by leveraging the one-time campaign. We estimated the tuberculosis cases and deaths that could be averted over 10 years using this comprehensive approach and assessed the contributions of individual components of the intervention.ResultsA campaign that successfully screened 70% of the adult population for active and latent tuberculosis and subsequently reduced diagnostic and treatment delays and unsuccessful treatment outcomes by 50% was projected to avert 7800 (95% range 5450–10,200) cases and 1710 (1290–2180) tuberculosis-related deaths per 1 million population over 10 years. Of the total averted deaths, 33.5% (28.2–38.3) were attributable to the inclusion of preventive therapy and 52.9% (48.4–56.9) to health system strengthening.ConclusionsA one-time, community-wide mass campaign, comprehensively designed to detect, treat, and prevent tuberculosis with currently existing tools can have a meaningful and long-lasting epidemiological impact. Successful treatment of LTBI is critical to achieving this result. Health system strengthening is essential to any effort to transform the TB response.

High burden of tuberculosis infection and disease among people receiving medication-assisted treatment for substance use disorder in Tanzania.

ObjectiveTo determine the prevalence of tuberculosis (TB) disease and infection as well as incident TB disease among people who use drugs (PWUD) attending Medication Assisted Treatment (MAT) clinics in Dar-es-Salaam, Tanzania.MethodsIn this prospective cohort study, a total of 901 consenting participants were enrolled from November 2016 to February 2017 and a structured questionnaire administered to them through the open data kit application on android tablets. Twenty-two months later, we revisited the MAT clinics and reviewed 823 of the 901 enrolled participant’s medical records in search for documentation on TB disease diagnosis and treatment. Medical records reviewed included those of participants whom at enrolment were asymptomatic, not on TB disease treatment, not on TB preventive therapy and those who had a documented tuberculin skin test (TST) result.ResultsOf the 823 medical records reviewed 22 months after enrolment, 42 had documentation of being diagnosed with TB disease and initiated on TB treatment. This is equivalent to a TB disease incidence rate of 2,925.2 patients per 100,000 person years with a total follow up time of 1,440 person-years. At enrolment the prevalence of TB disease and TB infection was 2.6% and 54% respectively and the HIV prevalence was 44% and 16% among females and males respectively.ConclusionPWUD attending MAT clinics bear an extremely high burden of TB and HIV and are known to have driven TB epidemics in a number of countries. Our reported TB disease incidence is 12 times that of the general Tanzanian incidence of 237 per 100,000 further emphasizing that this group should be prioritized for TB screening, testing and treatment. Gender specific approaches should also be developed as female PWUDs are markedly more affected with HIV and TB disease than male PWUDs.

Blood transcriptomic biomarkers for tuberculosis screening: time to redefine our target populations?

Blood transcriptomic biomarkers for tuberculosis screening: time to redefine our target populations?

Effect of the Vaccine on the Dynamics of Speread of Tuberculosis SIR Models

Tuberculosis (TB) is an infectious disease that is very dangerous and can cause death and Tuberculosis (TB) is an infectious disease that causes the most deaths or is called the world’s biggest killer among infectious diseases, claiming more than 4000 lives every day. The unprecedented Corona Virus pandemic has a serious impact on people with pre-existing health conditions such as Tuberculosis. Tuberculosis is not caused by heredity and Tuberculosis is curable. Treatment of TB disease is time-consuming and costly. Therefore the term prevention is better than cure very precisely for Tuberculosis. One of the efforts made by the government is to provide vaccines. This study uses the SIR (susceptible, infected, and recovered) model by considering the effect of vaccines. Also, this study adopts the application of the Optimum Control theory which aims to provide control over the parameters that affect the spread of Tuberculosis. The purpose of this study is not only to show the dynamics of the spread of tuberculosis but also to see to what extent the effect of vaccines reduces the spread of tuberculosis. And how does the optimal control theory influence the spread of tuberculosis?This research is proposed to estimate the basic reproduction number (R0) from the dynamics of the Tuberculosis epidemic. The basic reproductive number ((R0) is often used as a threshold parameter to determine the boundary betweenextinction and endemic. If R0<1 indicates the dengue virus will become extinct and if R0> 1 shows the Tuberculosis is endemic. By considering vaccines identified a slowing of the spread of tuberculosis.

Drug-induced liver injury: Asia Pacific Association of Study of Liver consensus guidelines.

Idiosyncratic drug-induced liver injury mimics acute and chronic liver disease. It is under recognized and underrecognised because of the lack of pathognomonic diagnostic serological markers. Its consequences may vary from being asymptomatic to self-limiting illness to severe liver injury leading to acute liver failure. Its incidence is likely to be more common in Asia than other parts of the world, mainly because of hepatotoxicity resulting from the treatment of tuberculosis disease and the ubiquitous use of traditional and complimentary medicines in Asiancountries. This APASL consensus guidelines on DILI is a concise account of the various aspects including current evidence-based information on DILI with special emphasis on DILI due to antituberculosis agents and traditional and complementary medicine use in Asia.

Long-term Prognosis of Tuberculosis Infection and Disease in Swedish Children

Reports of the outcome of treatment of tuberculosis (TB) disease and infection (TBI) in children are scarce. Since 2010, we routinely use interferon-gamma release assays in addition to clinical history for the exclusion of TBI, although the safety of this approach has been questioned. We present the frequency of recurrent TB or progression to TB after treatment for TB disease or TB infection, respectively, and progression to disease in children considered TB uninfected at our pediatric TB clinic. We included 4707 patients from 1990 to 2017. At the initial assessment, 96 (2.0%) had previously received TB treatment, 253 (5.4%) had TB disease, 1625 (35%) had TBI and 2733 (58%) children were considered uninfected. Patients were passively followed at our clinic, at the adult TB clinics in Stockholm and at the Swedish national TB registry. During a median follow-up time of 8.4 years, we found 36 cases of TB disease, with true relapses in 3/243 (1.2%) successfully treated TB patients. Preventive treatment of TBI reduced the risk of progression to TB by 85%, from 4.3% (15/349) to 0.6% (8/1262). In children considered uninfected, the risk of later developing TB was 0.07% (2/2733). The effectiveness of TB management was acceptable. Our routine procedures for the exclusion of TBI appear safe.

A Review: History, Structure, Diagnosis and Treatment of Tuberculosis Disease

In the present scenario, tuberculosis is of the most infectious disease which is caused when Mycobacterium tuberculosis gets encountered into the body. Tuberculosis being a communicable disease or transferrable disease, it is easily passed down to other person who remains in contact to the infected person by the process of inhaling air droplets carrying that particular bacteria. Tuberculosis mainly affects the lungs, but it can also affect the other organs. When this bacteria encounters in the body, the immune cells checks and control pathogen. However this disease remains latent but can become active at any time after some years when the particular immune system is weakened. If this disease is not treated at that time, then this disease can also become life- threating illness.

Immigrant screening for latent tuberculosis in Norway: a cost-effectiveness analysis.

The incidence of tuberculosis (TB) disease has increased in Norway since the mid-1990s. Immigrants are screened, and some are treated, for latent TB infection (LTBI) to prevent TB disease (reactivation). In this study, we estimated the costs of both treating and screening for LTBI and TB disease, which has not been done previously in Norway. We developed a model to indicate the cost-effectiveness of four different screening algorithms for LTBI using avoided TB disease cases as the health outcome. Further, we calculated the expected value of perfect information (EVPI), and indicated areas of LTBI screening that could be changed to improve cost-effectiveness. The costs of treating LTBI and TB disease were estimated to be €1938 and €15,489 per case, respectively. The model evaluates four algorithms, and suggests three cost-effective algorithms depending on the cost-effectiveness threshold. Screening all immigrants with interferon-gamma release assays (IGRA) requires the highest threshold (€28,400), followed by the algorithms "IGRA on immigrants with risk factors" and "no LTBI screening." EVPI is approximately €5 per screened immigrant. The costs for a cohort of 20,000 immigrants followed through 10years range from €12.2 million for the algorithm "screening and treatment for TB disease but no LTBI screening," to €14 million for "screening all immigrants for both TB disease and LTBI with IGRA." The results suggest that the cost of TB disease screening and treatment is the largest contributor to total costs, while LTBI screening and treatment costs are relatively small. Increasing the proportion of IGRA-positive immigrants who are treated decreases the costs per avoided case substantially.

Commentary: A targets framework: Dismantling the invisibility trap for children with drug-resistant tuberculosis

Tuberculosis (TB) is an airborne infectious disease that is both preventable and curable, yet it kills more than a million people every year. Children are highly vulnerable, but often invisible casualties. Drug-resistant forms of TB are on the rise globally, and children are as vulnerable as adults but less likely to be counted as cases of drug-resistant disease if they become sick. Four factors make children with drug-resistant TB 'invisible': first, the nature of the disease in children; second, deficiencies in existing diagnostic tools; third, overreliance on these tools; and fourth, our collective failure to deploy one effective tool for finding and treating children - contact investigation. We describe a nascent science-advocacy network - the Sentinel Project on Pediatric Drug-Resistant Tuberculosis - whose goal is to end child deaths from this disease. Provisional annual targets, focused on children exposed at home to multidrug-resistant TB, to be updated every year, constitute a framework to focus attention and collective actions at the community, national, and global levels. The targets in two age groups, under 5 and 5-14 years old, tell us the number of: (i) children who require complete evaluation for TB disease and infection; (ii) children who require treatment for TB disease; and (iii) children who would benefit from preventive therapy.

Cyclic AMP signalling in mycobacteria: redirecting the conversation with a common currency

cAMP is an ancient second messenger, and is used by many organisms to regulate a wide range of cellular functions. Mycobacterium tuberculosis complex bacteria are exceptional in that they have genes for at least 15 biochemically distinct adenylyl cyclases, the enzymes that generate cAMP. cAMP-associated gene regulation within tubercle bacilli is required for their virulence, and secretion of cAMP produced by M. tuberculosis bacteria into host macrophages disrupts the host's immune response to infection. In this review, we discuss recent advances in our understanding of the means by which cAMP levels are controlled within mycobacteria, the importance of cAMP to M. tuberculosis during host infection, and the role of cAMP in mycobacterial gene regulation. Understanding the myriad aspects of cAMP signalling in tubercle bacilli will establish new paradigms for cAMP signalling, and may contribute to new approaches for prevention and/or treatment of tuberculosis disease.