Treatment Of Tuberculosis Infection Research Articles

Impact of Latent M. tuberculosis Infection Treatment on Time to CD4/CD8 Recovery in Acute, Recent, and Chronic HIV Infection.

In people living with HIV, active and latent tuberculosis (TB) coinfections are associated with immune activation that correlate with HIV progression and mortality. We investigated the effect of initiating antiretroviral therapy (ART) during acute (AHI), recent (RHI), or chronic HIV infection (CHI) on CD4/CD8 ratio normalization and associated factors, the impact of latent TB infection treatment, and prior/concomitant TB diagnosis at the time of ART initiation. We included sex with men and transgender women individuals initiating ART with AHI, RHI and CHI between 2013 and 2019, from a prospective cohort in Brazil. We compared time from ART initiation to the first normal CD4/CD8 ratio (CD4/CD8 ≥1) using Kaplan-Meier curves and multivariable Cox proportional hazards models. Sociodemographic and clinical variables were explored. Variables with P -values <0.20 in univariable analyses were included in multivariable analyses. Five hundred fifty participants were included, 11.8% classified as AHI and 6.4% as RHI, 46.7% with CHI-CD4 cell counts ≥350 cells/mm 3 and 35.1% with CHI-CD4 cell counts <350 cells/mm 3 . Time to normalization was shortest among AHI patients, followed by RHI and CHI individuals with higher baseline CD4. In the multivariable model, AHI was associated with a six-fold increased likelihood of achieving a CD4/CD8 ratio ≥1 (hazard ratio [HR]: 6.03; 95% confidence interval [CI]: 3.70 to 9.82; P < 0.001), RHI with HR: 4.47 (95% CI: 2.57 to 7.76; P < 0.001), and CHI CD4 ≥350 cells/mm 3 with HR: 1.87 (95% CI: 1.24 to 2.84; P = 0.003). Latent TB infection treatment was significantly associated with a higher likelihood of the outcome (HR: 1.79; 95% CI: 1.22 to 2.62; P = 0.003). Previous history or concomitant active TB at ART initiation was associated with a lower likelihood of the outcome (HR: 0.41; 95% CI: 0.16 to 1.02; P = 0.054). Initiating ART early during AHI may offer an opportunity to mitigate immune damage. Efforts to implement HIV diagnosis and ART initiation during AHI are critical to amplify ART benefits.

Overcoming Mycobacterium tuberculosis Drug Resistance: Novel Medications and Repositioning Strategies.

Mycobacterium tuberculosis, the bacterium responsible for tuberculosis, is a global health concern, affecting millions worldwide. This bacterium has earned a reputation as a formidable adversary due to its multidrug-resistant nature, allowing it to withstand many antibiotics. The development of this drug resistance in Mycobacterium tuberculosis is attributed to innate and acquired mechanisms. In the past, rifampin was considered a potent medication for treating tuberculosis infections. However, the rapid development of resistance to this drug by the bacterium underscores the pressing need for new therapeutic agents. Fortunately, several other medications previously overlooked for tuberculosis treatment are already available in the market. Moreover, several innovative drugs are under clinical investigation, offering hope for more effective treatments. To enhance the effectiveness of these drugs, it is recommended that researchers concentrate on identifying unique target sites within the bacterium during the drug development process. This strategy could potentially circumvent the issues presented by Mycobacterium drug resistance. This review primarily focuses on the characteristics of novel drug resistance mechanisms in Mycobacterium tuberculosis. It also discusses potential medications being repositioned or sourced from novel origins. The ultimate objective of this review is to discover efficacious treatments for tuberculosis that can successfully tackle the hurdles posed by Mycobacterium drug resistance.

Tuberculosis preventive therapy – Clinical practice issues

Latent tuberculosis (LTB) is now termed as tuberculosis infection (TBI). Prevention of active TB disease by treatment of tuberculosis infection is a critical component of the National Strategic Plan 2017-25 for TB Elimination in India by 2025. Programmatic Management of Tuberculosis Preventive Therapy (PMTPT) is a public health document while treatment of tuberculosis infection is essentially a clinical approach. Here we have attempted to address the gray areas answering from clinical viewpoint.

Tuberculous Meningitis in Male Child and Cavitary Pulmonary Tuberculosis in Mother: Concurrent Familial Infective Disease as Evidence of Recent Transmission from Mother to Baby!

Tuberculosis (TB) is one of the leading causes of mortality in children worldwide, but there remain significant challenges in diagnosing and treating TB infection and disease. Tuberculous (TB) meningitis is the commonest infectious disease of the central nervous system in paediatric and geriatric cases. Childhood TB is an indication of failing TB control in the community. It allows disease persistence in the population. Tuberculosis can be prevented in children by diagnosing and treating cases of active TB amongst adults, as paediatric cases always acquire it passively from household contact of adults suffering from TB as disease in adults is multibacillary. Although significant data is available for the prevention of childhood extra-pulmonary and disseminated TB, offering Bacillus Calmette-Guerin (BCG) vaccination, it is still not routinely offered during vaccination. In this case report, a two-year child with a history of failure to thrive and constitutional symptoms diagnosed with disseminated extra-pulmonary TB presenting as TB meningitis with a history of contact with the mother suffering from active sputum positive pulmonary TB receiving anti-TB treatment. Child was evaluated with CT brain plain and contrast and documented meningeal enhancement. Cerebrospinal fluid analysis revealed tuberculous etiology in presence of lymphocytic predominance and raised ADA level in fluid. CSF fluid sent for cartridge based nucleic acid amplification test documented MTB genome with rifampicin sensitivity. We retrospectively analysed mothers’ sputum examination and observed higher grades of sputum AFB and her cartridge based nucleic acid amplification test revealed MTB genome with rifampicin sensitivity. Child and mother were treated with standard protocol recommended by NTEP (National Tuberculosis elimination program). In conclusion, we recommend BCG vaccination to all newborns, and tuberculin skin testing and isoniazid prophylaxis to the contact of adults with sputum positive pulmonary TB cases in India to prevent transmission of disease from mother to baby. A high index of suspicion is must while evaluating these cases and all possible measures should be taken to confirm tuberculosis to have successful treatment outcome.

Variation in Treatment of Pediatric Tuberculosis Infection in Different Provider Settings

To evaluate implementation of rifamycin-based regimens (RBR) for pediatric tuberculosis infection (TBI) treatment among 3 provider settings in a high-incidence county. A multicenter, retrospective observational study was performed across 3 sites in Los Angeles County: an academic center (AC), a general pediatrics federally qualified health center (FQHC), and department of public health (DPH) tuberculosis clinics. Patients initiated on TBI treatment age 1months to 17years between 2018 and 2020 were included. RBRs were defined as regimens: 3 months of weekly rifapentine and isoniazid, 4 months of daily rifampin, and 3months of daily isoniazid and rifampin. We included 424 patients: 51 from AC, 327 from DPH, and 46 from FQHC. RBR use nearly doubled during the study period (from 43% in 2018 to 82% in 2020; P<.001). FQHC had the shortest time to chest radiograph and treatment initiation; however, AC and DPH were 4 times as likely to prescribe an RBR compared to FQHC (95% CI, 2.1-7.8). AC and DPH had similar completion rates (74%) and were 2.6 times as likely to complete treatment compared to FQHC (95% CI, 1.4-4.9). The use of RBRs for pediatric TBI varies significantly by clinical setting but is improving over time. Strategies are needed to improve RBR uptake, standardize care, and increase treatment completion, particularly among general pediatricians.

Burden of Chronic Obstructive Pulmonary Disease Attributable to Tuberculosis: A Microsimulation Study.

Tuberculosis (TB) is a risk factor for chronic obstructive pulmonary disease (COPD), but COPD is also a predictor of TB. The excess life-years lost to COPD caused by TB can potentially be saved by screening for and treating TB infection. We examined the number of life-years that could be saved by preventing TB and TB-attributable COPD. We compared the observed (no intervention) and counterfactual microsimulation models constructed from observed rates in the Danish National Patient Registry (covering all Danish hospitals between 1995 and 2014). In the Danish population of TB and COPD-naive individuals (n=5,206,922), 27,783 persons (0.5%) developed TB. Among those who developed TB, 14,438 (52.0%) developed TB with COPD. Preventing TB saved 186,469 life-years overall. The excess number oflife-years lost to TB alone was 7.07 years per person, and the additional number oflife-years lost among persons who developed COPD after TB was 4.86 years per person. The life-years lost to TB-associated COPD are substantial, even in regions where TB can be expected to be identified and treated promptly. Prevention of TB could prevent a substantial amount of COPD-related morbidity; the benefit of screening and treatment for TB infection is underestimated by considering morbidity from TB alone.

First evaluation of the performance of portable IGRA, QIAreach® QuantiFERON®-TB in intermediate TB incidence setting.

Diagnosis and treatment of tuberculosis infection (TBI) are the core elements of tuberculosis elimination. Interferon gamma release assays have advantages over the tuberculin skin test, although their implementation in low-resource settings is challenging. The performance of a novel digital lateral flow assay QIAreach® QuantiFERON®-TB (QIAreach QFT) against the QuantiFERON®-TB Gold Plus (QFT-Plus) assay was evaluated in an intermediate incidence setting (Malaysia) according to the manufacturer's instructions. Individuals aged 4-82 years, who were candidates for TB infection screening for contact investigation were prospectively recruited. On 196 samples, the QIAreach-QFT showed a positive percent agreement (sensitivity) was 96.5% (CI 87.9-99.6%), a negative percent agreement (specificity) 94.2% (CI 88.4% to 97.6%) and an overall percentage of agreement was 94.9% (95% CI 90.6-97.6%) with a Cohen's κ of 0,88. Out of 196, 5.6% (11/196) samples gave an error result on QIAreach-QFT and 4.1% (8/196) samples gave indeterminate result on QFT-plus. The TTR for QIAreach QFT positive samples varied from 210-1200 seconds (20 min) and significantly correlated with IFN-γ level of QFT-Plus. QIAreach QFT could be considered an accurate and reliable point-of-need test to diagnose TB infection helping to achieve the WHO End TB programme goals even in decentralised settings where laboratory expertise and infrastructure may be limited.

Optimising diagnosis and treatment of tuberculosis infection in community and primary care settings in two urban provinces of Viet Nam: a cohort study

ObjectivesTo end tuberculosis (TB), the vast reservoir of 1.7–2.3 billion TB infections (TBIs) must be addressed, but achieving global TB preventive therapy (TPT) targets seems unlikely. This study assessed the...

Factors Affecting Visual Recovery in Patients with Ethambutol-Induced Optic Neuropathy.

To study visual recovery and identify the factors that may affect it in patients with ethambutol-induced optic neuropathy (EON). Medical charts of patients who developed optic neuropathy after ethambutol (EMB) treatment for tuberculosis infection were retrospectively reviewed. Demographic details and clinical data were examined to assess visual recovery after discontinuation of ethambutol treatment. The univariate and multivariate relationships between various factors and visual recovery were evaluated using regression analysis. Of 5394 patients diagnosed with tuberculosis infection and treated with EMB, 23 patients (0.43%) were diagnosed with EON. Logistic regression analysis found that female sex was the categorical factor significantly associated with good visual recovery with an odds ratio of 12.0 (95% confidence interval 1.56, 92.29; p = 0.02), while linear regression analysis identified good initial visual acuity as the numerical factor significantly related with it (p < 0.001). After adjustment with multivariate analysis, initial visual acuity was found to be the only significant factor associated with visual recovery. All patients with initial visual acuity of better than 20/200 at first visit achieved good visual recovery. The incidence of EON in patients treated with EMB was 0.43% in this hospital-based study. Good visual recovery was noted in 39.13% of these patients, and initial visual acuity was the factor that affected visual recovery. It is recommended that patients on EMB have regular screening by an ophthalmologist for early detection of the disease, and if it is discovered, that the use of the drug be immediately discontinued in order to prevent potentially devastating visual loss.

Challenges and the Way forward in Diagnosis and Treatment of Tuberculosis Infection.

Globally, it is estimated that one-quarter of the world's population is latently infected with Mycobacterium tuberculosis (Mtb), also known as latent tuberculosis infection (LTBI). Recently, this condition has been referred to as tuberculosis infection (TBI), considering the dynamic spectrum of the infection, as 5-10% of the latently infected population will develop active TB (ATB). The chances of TBI development increase due to close contact with index TB patients. The emergence of multidrug-resistant TB (MDR-TB) and the risk of development of latent MDR-TB has further complicated the situation. Detection of TBI is challenging as the infected individual does not present symptoms. Currently, there is no gold standard for TBI diagnosis, and the only screening tests are tuberculin skin test (TST) and interferon gamma release assays (IGRAs). However, these tests have several limitations, including the inability to differentiate between ATB and TBI, false-positive results in BCG-vaccinated individuals (only for TST), false-negative results in children, elderly, and immunocompromised patients, and the inability to predict the progression to ATB, among others. Thus, new host markers and Mtb-specific antigens are being tested to develop new diagnostic methods. Besides screening, TBI therapy is a key intervention for TB control. However, the long-course treatment and associated side effects result in non-adherence to the treatment. Additionally, the latent MDR strains are not susceptible to the current TBI treatments, which add an additional challenge. This review discusses the current situation of TBI, as well as the challenges and efforts involved in its control.

A scoping review on the risk of tuberculosis in specific population groups: can we expand the World Health Organization recommendations?

Since 2015, the World Health Organization (WHO) has recommended prioritising testing and treatment of tuberculosis (TB) infection (TBI) in 11 high-risk groups. With new options emerging for TB preventive treatment, we conducted a scoping review, in consultation with the WHO's Global Tuberculosis Programme, to explore the evidence for other population groups at potentially high risk of progression to active TB. We searched six databases for preprints and articles published between 2000 and August 2022. 18 out of 33 668 screened records were included (six meta-analyses and 12 original research studies). Most were observational studies reporting the incidence of active TB in a risk group versus control. Glomerular diseases had the strongest association with active TB (standardised incidence ratio 23.36, 95% CI 16.76-31.68) based on an unpublished study. Other conditions associated with increased risk of active TB included hepatitis C, malignancies, diabetes mellitus, rheumatoid arthritis and vitamin D deficiency. Corticosteroid use was also associated with increased risk in several studies, although heterogeneous definitions of exposure and indications for use challenge interpretation. Despite methodological limitations of the identified studies, expanding the recommendations for TBI screening and treatment to new risk groups such as those reported here should be considered. Further group-specific systematic reviews may provide additional data for decision-making.

Tuberculosis Infection in Children and Adolescents.

The burden of tuberculosis (TB) in children and adolescents remains very significant. Several million children and adolescents are infected with TB each year worldwide following exposure to an infectious TB case and the risk of progression from TB infection to tuberculosis disease is higher in this group compared to adults. This review describes the risk factors for TB infection in children and adolescents. Following TB exposure, the risk of TB infection is determined by a combination of index case characteristics, contact features, and environmental determinants. We also present the recently recommended approaches to diagnose and treat TB infection as well as novel tests for infection. The tests for TB infection have limitations and diagnosis still relies on an indirect immunological assessment of cellular immune response to Mycobacterium tuberculosis antigens using immunodiagnostic testing. It is recommended that TB exposed children and adolescents and those living with HIV receive TB preventive treatment (TPT) to reduce the risk of progression to TB disease. Several TPT regimens of similar effectiveness and safety are now available and recommended by the World Health Organisation.

Tuberculosis Infection in Pregnant People: Current Practices and Research Priorities.

Women are significantly more likely to develop tuberculosis (TB) disease within the first 90 days after pregnancy than any other time in their lives. Whether pregnancy increases risk of progression from TB infection (TBI) to TB disease is unknown and is an active area of investigation. In this review, we discuss the epidemiology of TB and TBI in pregnancy, TBI diagnostics, and prevalence in pregnancy. We also review TBI treatment and highlight research priorities, such as short-course TB prevention regimens, drug-resistant TB prevention, and additional considerations for safety, tolerability, and pharmacokinetics that are unique to pregnant and postpartum people.

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.

Towards Shorter, Child-Friendly Regimens for Treatment of Tuberculosis Disease and Infection in Children.

Towards Shorter, Child-Friendly Regimens for Treatment of Tuberculosis Disease and Infection in Children.

The Role of Amino Acids in Tuberculosis Infection: A Literature Review.

Recently, there was an abundance of studies being conducted on the metabolomic profiling of tuberculosis patients. Amino acids are critical metabolites for the immune system, as they might contribute to providing nutrients for the host intracellular pathway. In tuberculosis, several amino acids play important roles in both the mycobacteria infection mechanism and the host. Individual studies showed how the dynamics of metabolite products that result from interactions between Mycobacterium tuberculosis (Mtb) and the host play important roles in different stages of infection. In this review, we focus on the dynamics of amino-acid metabolism and identify the prominent roles of amino acids in the diagnostics and treatment of tuberculosis infection. Online resources, including PubMed, ScienceDirect, Scopus, and Clinical Key, were used to search for articles with combination keywords of amino acids and TB. The inclusion criteria were full-text articles in English published in the last 10 years. Most amino acids were decreased in patients with active TB compared with those with latent TB and healthy controls. However, some amino acids, including leucine, isoleucine, valine, phenylalanine, aspartate, and glutamate, were found to be at higher levels in TB patients. Additionally, the biomarkers of Mtb infection included the ratios of kynurenine to tryptophan, phenylalanine to histidine, and citrulline to arginine. Most amino acids were present at different levels in different stages of infection and disease progression. The search for additional roles played by those metabolomic biomarkers in each stage of infection might facilitate diagnostic tools for staging TB infection.

The aspartate metabolism pathway

Recent research has been conducted to find potential new avenues of drug discovery for treating tuberculosis infection. This endless “arms race” is due to the ability of the bacteria to develop resistance towards the already established antibiotic regimen. Various pathways within Mycobacterium tuberculosis are being studied extensively to open new possibilities in drug development. One of which is the aspartate metabolism pathway. This amino acid pathway is proven to be pivotal for the survival of M. tuberculosis both in vitro and in vivo. Furthermore, this pathway also is absent in humans, making it a very promising candidate for further research and development in drug discovery. However, inhibitors against this pathway are not yet available as most suggested inhibitors against the various enzymes within this pathway only made it until the in-silico stage while few studies managed to synthesize their suggested inhibitors and had tested its anti-tuberculosis activity. This review will discuss said attempts in suggesting inhibitors against the critical enzymes that work within this pathway. The inhibitors that are reviewed in this paper are both synthetic and derived from natural products. The multitude of inhibitors proposed and the various enzymes that they are able to inhibit proved that this pathway has potential that is yet to be explored further.

Care cascade of tuberculosis infection treatment for people living with HIV in the era of antiretroviral therapy scale-up

Testing and treatment of tuberculosis infection (TBI) are recommended for people living with HIV (PLWH). We aimed to evaluate the care cascade of TBI treatment among PLWH in the era of antiretroviral therapy (ART) scale-up. This retrospective study included adult PLWH undergoing interferon-gamma release assay (IGRA)-based TBI screening during 2019–2021. PLWH testing IGRA-positive were advised to receive directly-observed therapy for TBI after active TB disease was excluded. The care cascade was evaluated to identify barriers to TBI management. Among 7951 PLWH with a median age of 38 years and CD4 count of 616 cells/mm3, 420 (5.3%) tested positive and 38 (0.5%) indeterminate for IGRA. The TBI treatment initiation rate was 73.6% (309/420) and the completion rate was 91.9% (284/309). More than 80% of PLWH concurrently received short-course rifapentine-based regimens and integrase strand transfer inhibitor (InSTI)-containing ART. The main barrier to treatment initiation was physicians’ concerns and patients’ refusal (85.6%). The factors associated with treatment non-completion were older age, female, anti-HCV positivity, and higher plasma HIV RNA. Our observation of a high TBI completion rate among PLWH is mainly related to the introduction of short-course rifapentine-based regimens in the InSTI era, which can be the strategy to improve TBI treatment uptake.

57-Year-Old Man With Headache, Vomiting, and Gait Instability

57-Year-Old Man With Headache, Vomiting, and Gait Instability

Costs of Tuberculosis at 3 Treatment Centers, Canada, 2010–2016

We estimated costs of managing different forms of tuberculosis (TB) across Canada by conducting a retrospective chart review and cost assessment of patients treated for TB infection, drug-susceptible TB (DS TB), isoniazid-resistant TB, or multidrug-resistant TB (MDR TB) at 3 treatment centers. We included 90 patients each with TB infection and DS TB, 71 with isoniazid-resistant TB, and 62 with MDR TB. Median per-patient costs for TB infection (in 2020 Canadian dollars) were $804 (interquartile range [IQR] $587–$1,205), for DS TB $12,148 (IQR $4,388–$24,842), for isoniazid-resistant TB $19,319 (IQR $7,117–$41,318), and for MDR TB $119,014 (IQR $80,642–$164,015). Compared with costs for managing DS TB, costs were 11.1 (95% CI 9.1–14.3) times lower for TB infection, 1.7 (95% CI 1.3–2.1) times higher for isoniazid-resistant TB, and 8.1 (95% CI 6.1–10.6) times higher for MDR TB. Broadened TB infection treatment could avert high costs associated with managing TB disease.