Treatment Of Tuberculosis Infection Research Articles

Time-Lapse Atomic Force Microscopy Reveals New End Take Off (Neto) Dynamics in Mycobacteria

Tuberculosis is a lung infection caused by Mycobacterium tuberculosis. One third of the world population is thought to be infected. Antibiotic treatment with antibiotics lasts 6 month, which is difficult to achieve in low-income countries. The uncommon ability of tuberculosis bacteria to persist during long periods is linked to various factors, one of which potentially being cell growth asymmetry. However, growth symmetry or asymmetry of mycobacteria remains a controversial topic as opposing descriptions have been reported in the literature. Observing bacterial growth at the single cell level is inherently challenging due to the diffraction limit of optical microscopes and the small size of the cells. We built a new dedicated platform for long-term, correlated Atomic Force Microscopy (AFM) and fluorescence microscopy and obtained time-lapses of bacterial growth at an unprecedented resolution. Surprisingly, the AFM high-resolution time-lapses did not match any of the two previously reported models of pure symmetry and pure asymmetry. Mycobacterial pole growth dynamics was rather an intermediate between the two, reminiscent of the well-known “new end take off” mechanism for fission yeast. Using AFM nanomanipulation we show that growth asymmetry is not a physical occlusion phenomenon, but is inherent to mycobacterial growth. Finally, using fluorescent photoconversion microscopy we identify biomolecular mechanisms linked to growth asymmetry, which in the future could be used to develop novel treatments for tuberculosis infection.

Demanding an end to tuberculosis: treatment of tuberculosis infection among persons living with and without HIV.

More than two billion people are infected with Mycobacterium tuberculosis and few of them are ever offered therapy in spite of such treatment being associated with reduced rates of morbidity and mortality. This article reviews the current recommendations on the diagnosis and treatment of TB infection (or what is commonly referred to as 'prophylaxis' or 'preventive therapy' of latent TB) and discusses barriers to implementation that have led to low demand for this life-saving therapeutic intervention. Treatment of infection for both TB and drug-resistant TB is well tolerated and effective, and several new, shorter regimens - including rfiapenitine-based regimens of 1 month and 12 weeks duration - have been shown to be effective. Not all persons infected with TB go on to develop disease and the risk is the highest in the first 2 years after infection. Given this, additional work is needed to better identify those at the highest risk of developing active TB. Practitioners should offer newer, shorter regimens to persons who are infected with TB and at high risk of developing disease, including people living with HIV and household contacts of people living with TB who are age 5 years and under. This includes individuals who have been exposed to drug-resistant forms of disease. Socioeconomic risk factors may play a key role in the development of TB disease and should also be addressed.

Properties of Therapeutic Deep Eutectic Solvents of l-Arginine and Ethambutol for Tuberculosis Treatment.

The treatment for tuberculosis infection usually involves a prolonged regimen of multiple antibacterial drugs, which might lead to various secondary effects. For preventing drug resistance and side-effects of anti-tuberculosis drugs, new methods for improving the bioavailability of APIs were investigated. The strategy proposed consists of the preparation of therapeutic deep eutectic solvents (THEDES), that incorporate l-arginine and ethambutol. The eutectic mixtures were prepared by mixing the components at a certain molar ratio, until a clear liquid solution was formed. The prepared mixtures were characterized by differential scanning calorimetry (DSC), polarized optical microscopy (POM) and nuclear magnetic resonance spectroscopy (1H and 13C-NMR). The solubility and permeability of the drugs when they are in the THEDES form was evaluated at 37 °C, in phosphate buffered saline (PBS). Solubility studies showed an increase of the solubility of ethambutol when incorporated in the eutectic system. The cytotoxicity was evaluated using a model cell line (Caco-2), comparing the cytotoxicity of the API incorporated in the eutectic system. We observed that the cell viability in the THEDES was affected by the presence of citric acid, and higher cytotoxicity values were observed. Nonetheless, these findings do not compromise the possibility to use these systems as new delivery systems for ethambutol and arginine.

Determinants and characteristics of tuberculosis in liver transplant recipients

Solid organ transplant (SOT) recipients have increased risk of tuberculosis (TB). We aimed to investigate the prevalence and features of TB in liver transplant (LT) recipients at our transplantation canter. All patients who underwent LT between January 2004 and December 2013 and whose data were accessible were included in the study. Demographic features, tuberculin skin test (TST) results, and TB prevalence were recorded. Characteristics of LT recipients who developed TB were evaluated. A total of 403 patients underwent LT during this period. Mean age was 47.27 ± 11.04 years; 280 (69.47%) were males. The TST was administered to 108 (25.91%) and the QuantiFERON-TB test to 1 patient. TST positivity was determined in 28 (25.93%). Latent TB infection (LTBI) treatment was not recommended to any of the LT candidates. In the posttransplant period, 5 patients (1.24%) developed TB over a median duration of 14 (min: 7, max: 84) months, 2 of whom were found to have had LTBI in the pretransplant period. The prevalence of TB in LT recipients at our center was similar to that in the current literature. LTBI screening, including risk factor assessment and TST/QuantiFERON-TB testing, is necessary in the early diagnostic workup for TB in LT recipients.

Treatment of Multidrug-Resistant Tuberculosis Infection in Children.

Treatment of Multidrug-Resistant Tuberculosis Infection in Children.

Tuberculosis preventive treatment: the next chapter of tuberculosis elimination in India

The End TB Strategy envisions a world free of tuberculosis—zero deaths, disease and suffering due to tuberculosis by 2035. This requires reducing the global tuberculosis incidence from >1250 cases per...

Treatment of Multidrug-resistant Tuberculosis Infection in Children.

Treatment of Multidrug-resistant Tuberculosis Infection in Children.

Prevention and treatment of tuberculosis infection in candidates for biologic therapy: A multidisciplinary consensus statement adapted to the dermatology patient

Patients with chronic inflammatory diseases being treated with immunosuppressive drugs, and with tumor necrosis factor inhibitors in particular, have an increased risk of infection by Mycobacterium tuberculosis. Screening for latent tuberculosis infection and preventive therapy to reduce the risk of progression to active tuberculosis are mandatory in this group of patients. This updated multidisciplinary consensus document presents the latest expert opinions on the treatment and prevention of tuberculosis in candidates for biologic therapy and establishes recommendations based on current knowledge relating to the use of biologic agents.

A bioactive implant in situ and long-term releases combined drugs for treatment of osteoarticular tuberculosis

Anti-tuberculosis chemotherapy with a long duration and adequate dosing is the mainstay for treatment of osteoarticular tuberculosis (TB). However, it is difficult for systemic administration to reach adequate local drug concentrations and achieve effective treatment. Herein, a hydroxyapatite (HA) scaffold implant combined with a drug-releasing system was designed to achieve in situ and long-term anti-TB drug release and highly efficient therapeutic activity in vitro and in vivo. The clinical anti-TB drugs hydrophilic isoniazid (INH) and hydrophobic rifampicin (RFP) were molecularly dispersed into polyvinyl alcohol (PVA) through immersion-curing techniques and were steadily adhered onto the surfaces of HA scaffolds (HA-drug@PVA). The HA-drug@PVA scaffolds showed a long-term, sustained drug release profile and killed proliferating Mycobacterium in vitro. In vivo experimental results revealed that the HA-drug@PVA scaffolds provided over 10- and 100-fold higher concentrations in muscles and bones, respectively, as well as a much lower concentration (<0.025) in blood. Furthermore, the HA-drug@PVA scaffold implanted in an osteoarticular TB rabbit model showed obvious bone regeneration and fusion due to the inhibition of TB-associated inflammatory changes. The excellent therapeutic effects indicate that in situ implant materials combined with a long-term drug release system are promising for the treatment of osteoarticular TB and other osteoarticular infections.

Prospects for Tuberculosis Elimination in the United States: Results of a Transmission Dynamic Model.

We estimated long-term tuberculosis (TB) trends in the US population and assessed prospects for TB elimination. We used a detailed simulation model allowing for changes in TB transmission, immigration, and other TB risk determinants. Five hypothetical scenarios were evaluated from 2017 to 2100: 1) maintain current TB prevention and treatment activities (base case); 2) provision of latent TB infection testing and treatment for new legal immigrants; 3) increased uptake of latent TB infection screening and treatment among high-risk populations, including a 3-month isoniazid-rifapentine regimen; 4) improved TB case detection; and 5) improved TB treatment quality. Under the base case, we estimate that by 2050, TB incidence will decline to 14 cases per million, a 52% (95% posterior interval (PI): 35, 67) reduction from 2016, and 82% (95% posterior interval: 78, 86) of incident TB will be among persons born outside of the United States. Intensified TB control could reduce incidence by 77% (95% posterior interval: 66, 85) by 2050. We predict TB may be eliminated in US-born but not non-US-born persons by 2100. Results were sensitive to numbers of people entering the United States with latent or active TB, and were robust to alternative interpretations of epidemiologic evidence. TB elimination in the United States remains a distant goal; however, strengthening TB prevention and treatment could produce important health benefits.

Tuberculosis in immunosuppressed patients

Tuberculosis (TB) is one of the most significant infections in immunosuppressed patients due to its high frequency and high morbidity and mortality. TB is the leading cause of death among HIV-infected patients. The diagnosis and early treatment of latent tuberculosis infection is vital to preventing it progression to disease. Similarly, the early diagnosis of TB is key to improving the prognosis of patients and preventing its transmission. The clinical expression of TB in immunosuppressed patients is conditioned by the patient's degree of immunosuppression. It is important to keep this peculiarity in mind so as not to delay the diagnosis of suspected TB. TB treatment is basically the same in immunosuppressed patients as in the general population and any differences mainly derive from pharmacological interactions. We examined the diagnosis and treatment of TB and latent tuberculosis infection in immunosuppressed patients.

Tuberculosis Recommendations for Solid Organ Transplant Recipients and Donors.

Tuberculosis Recommendations for Solid Organ Transplant Recipients and Donors.

Factorials Experiment for Directly Observed Treatment Short Course (Dots): Treatment of Tuberculosis Infection in Abia State, Nigeria

Factorials Experiment for Directly Observed Treatment Short Course (Dots): Treatment of Tuberculosis Infection in Abia State, Nigeria

Tuberculosis en pacientes inmunodeprimidos

Tuberculosis (TB) is one of the most significant infections in immunosuppressed patients due to its high frequency and high morbidity and mortality. TB is the leading cause of death among HIV-infected patients. The diagnosis and early treatment of latent tuberculosis infection is vital to preventing it progression to disease. Similarly, the early diagnosis of TB is key to improving the prognosis of patients and preventing its transmission. The clinical expression of TB in immunosuppressed patients is conditioned by the patient's degree of immunosuppression. It is important to keep this peculiarity in mind so as not to delay the diagnosis of suspected TB. TB treatment is basically the same in immunosuppressed patients as in the general population and any differences mainly derive from pharmacological interactions. We examined the diagnosis and treatment of TB and latent tuberculosis infection in immunosuppressed patients.

Lessons learned from continued TB outbreaks in a high school.

We investigated the aftereffects of confirmatory QuantiFERON testing (QFT) added to a positive tuberculin skin test (TST). We reviewed the pre and post course of sequential tuberculosis (TB) outbreaks in a high school where massive 43 active TB cases had been found within one year before delayed contact investigation. And we investigated the TB development in relation to initial TST and QFT during mean follow-up of 3.9 ± 0.9 years. After delayed contact investigation for two subsequent TB outbreaks, 925 contacts were divided into the following 3 groups: TST- (n = 632), TST+/QFT+ (n = 24), TST+/QFT- (n = 258). QFT- was more prevalent than QFT+ in contacts with 10mm ≤ TST <15mm (158, 61.2%) compared with TST ≥15mm (100, 38.8%) among the TST+ reactors (P < 0.001). Among the 258 TST+/QFT- subjects, 256 received no latent TB infection (LTBI) treatment, but 7 contacts developed TB during follow-up. Among these 7 patients, 4 had initial TST ≥15mm and 3 had 10mm ≤ TST <15mm. In conclusion, the delayed contact investigation for LTBI in a high school resulted in continued TB developments. False-negative QFT performed late among the TST+ reactors should not be considered criteria for LTBI treatment. Additionally, the contacts only with TST ≥15mm should be considered for LTBI treatment in congregate settings of intermediate-burden countries.

Treatment of Tuberculosis Infection in Children

AbstractThe last decade has seen publication of more robust data for shorter course regimens for tuberculosis infection. These regimens are associated with higher completion rates than the traditional 6- to 9-month course of daily isoniazid (INH). These shorter regimens include 4 months of daily rifampin (RIF) and 12 once-weekly doses of INH and a long-acting rifamycin and rifapentine. In addition, a widely used regimen in the United Kingdom is 3 or 4 months of daily INH and RIF. All regimens have demonstrated efficacy in the ideal conditions of clinical studies, and all have very low rates of hepatotoxicity in children. These newer regimens likely are more effective than longer courses of INH once patient and family adherence is considered. Clinicians need to be cognizant of poor completion rates with traditional INH therapy and how the use of rifamycin-containing regimens offers more palatable options for children and their families.

Diagnosis and treatment strategy of tuberculosis infection after total knee arthroplasty

To review the diagnosis and treatment of tuberculosis infection after total knee arthro-plasty (TKA). The recent literature concerning the diagnosis and treatment of tuberculosis infection after TKA were extensively reviewed and summarized. The diagnosis of tuberculosis infection after TKA is difficult. It should be combined with the patient's medical history, symptoms, signs, blood examinations, and imaging examinations, among which the bacterial culture and histopathological examination are the gold standard of diagnosis. Treatment strategy is combined with the drug treatment and a variety of surgical procedures that depends on the clinical situation. At present, there is no guideline for the diagnosis and treatment of tuberculosis infection after TKA, it still needs further study and improvement.

Feasibility of district wide screening of health care workers for tuberculosis in Zambia

BackgroundMany health care workers (HCWs) are at increased risk for tuberculosis (TB). The World Health Organization (WHO) recommends screening HCWs for TB in high burden settings but this is often not implemented in countries with a high TB incidence. We assessed the feasibility of TB screening among HCWs, including participation rate and yield, as part of a project introducing facility specific TB interventions.MethodsThis study had a cross-sectional design. HCWs (including paid staff and community volunteers) from 13 clinics and two hospitals in the Ndola district of Zambia participated. HCWs were screened by a designated person in their own facility. The agreed screening algorithm for HCWs included annual symptom screening, with sputum smear, culture (or Xpert) and chest x-ray offered to HCWs with at least one TB symptom, i.e. those with presumptive TB.ResultsA total of 1011 out of 1619 (62%) staff and 71 out of 138 (51%) community volunteers were screened within one year, total 1082/1757 (62%). Five percent (52/1082) of those screened were presumptive TB patients. Seventy-three percent (38/52) of presumptive TB patients received all diagnostic tests according to the agreed algorithm. Eighteen out of 1757 staff and volunteers combined were diagnosed with TB within a calendar year, showing a notified TB incidence of 1%. At least five of them were diagnosed during the screening appointment (0.5% of those screened). One of the 18 HCWs died of TB. Seventy-six percent (822/1082) of screened HCWs indicated that they already knew their HIV status. Screening was considered feasible if confidentiality can be guaranteed although challenges such as the time required for screening and sample transport were reported.ConclusionsIt is feasible to conduct and implement screening programs for TB among HCWs in hospitals and clinics, and the notified incidence and yield is high. Advocacy is needed to educate managers and HCWs on the importance of screening and the implementation of locally relevant screening algorithms. It is essential to ensure access to TB infection control, diagnostics, treatment and confidential registration for HCW.

Knowing about you: eliciting dimensions of personhood within tuberculosis care.

Knowing someone with tuberculosis (TB) as a person, rather than defining them by their illness, is part of recognising their dignity and unique individuality, and a requirement for effective care. An adaptation of the Patient Dignity Question (PDQ) was formalised for persons receiving treatment for active TB or latent tuberculous infection (LTBI), and its impact was evaluated for both the person and health care providers (HCPs). Individuals with active TB or LTBI receiving treatment in Winnipeg, MB, Canada, were asked the PDQ as part of routine care. Patients and HCPs were subsequently invited to evaluate the application of the PDQ. Of the 58 participants who responded to the PDQ, 97% felt both that it was important to ask about them as an individual, and that the PDQ should be asked of all patients, while 55% thought it made a difference to their care. Thirty-eight per cent of HCPs said they learned something new about their patient, and 31% said it influenced their sense of connectedness with and sense of empathy for patients, as well as their personal satisfaction in providing care. Formalising a dignity question as part of person-centred care provides a mechanism to create a respectful environment that is caring of the most marginalised who carry the burden of TB.

Discovery of cofactor-specific, bactericidal Mycobacterium tuberculosis InhA inhibitors using DNA-encoded library technology

Millions of individuals are infected with and die from tuberculosis (TB) each year, and multidrug-resistant (MDR) strains of TB are increasingly prevalent. As such, there is an urgent need to identify novel drugs to treat TB infections. Current frontline therapies include the drug isoniazid, which inhibits the essential NADH-dependent enoyl-acyl-carrier protein (ACP) reductase, InhA. To inhibit InhA, isoniazid must be activated by the catalase-peroxidase KatG. Isoniazid resistance is linked primarily to mutations in the katG gene. Discovery of InhA inhibitors that do not require KatG activation is crucial to combat MDR TB. Multiple discovery efforts have been made against InhA in recent years. Until recently, despite achieving high potency against the enzyme, these efforts have been thwarted by lack of cellular activity. We describe here the use of DNA-encoded X-Chem (DEX) screening, combined with selection of appropriate physical properties, to identify multiple classes of InhA inhibitors with cell-based activity. The utilization of DEX screening allowed the interrogation of very large compound libraries (1011 unique small molecules) against multiple forms of the InhA enzyme in a multiplexed format. Comparison of the enriched library members across various screening conditions allowed the identification of cofactor-specific inhibitors of InhA that do not require activation by KatG, many of which had bactericidal activity in cell-based assays.