Approach For Treatment Of Tuberculosis Research Articles

Nanocarriers in Tuberculosis Treatment: Challenges and Delivery Strategies.

The World Health Organization identifies tuberculosis (TB), caused by Mycobacterium tuberculosis, as a leading infectious killer. Although conventional treatments for TB exist, they come with challenges such as a heavy pill regimen, prolonged treatment duration, and a strict schedule, leading to multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. The rise of MDR strains endangers future TB control. Despite these concerns, the hunt for an efficient treatment continues. One breakthrough has been the use of nanotechnology in medicines, presenting a novel approach for TB treatment. Nanocarriers, such as lipid nanoparticles, nanosuspensions, liposomes, and polymeric micelles, facilitate targeted delivery of anti-TB drugs. The benefits of nanocarriers include reduced drug doses, fewer side effects, improved drug solubility, better bioavailability, and improved patient compliance, speeding up recovery. Additionally, nanocarriers can be made even more targeted by linking them with ligands such as mannose or hyaluronic acid. This review explores these innovative TB treatments, including studies on nanocarriers containing anti-TB drugs and related patents.

Time for Isoniazid Pharmacogenomic-Guided Therapy of Tuberculosis Based on NAT2 Acetylation Profiles in India.

Tuberculosis (TB), caused by a bacterial pathogen Mycobacterium tuberculosis, is a highly contagious infectious disease. India ranks top in TB burden among other countries in the world. The current treatment of TB in India includes isoniazid (INH) as the first-line drug, based on the "one dose fits all'' concept. It is widely known that INH is not equally tolerated by all patients, as the metabolization process of INH is highly dependent on the acetylation profile of an individual based on the pharmacogenomic profile of the N-acetyltransferase (NAT2) gene. Also, several experimental studies in several TB endemic countries have established that redosing of INH based on genetic profiles of TB patients of the NAT2 can help in effective TB treatment and minimize adverse drug reactions (ADRs). Moreover, acetylation phenotype-based INH dosing has been shown to be cost-effective as well as successful in terms of treatment outcomes and the increase in the quality of life of the patients. Considering a genetically heterogenous population with high vulnerability to TB, we here argue that India could lead in establishing a pharmacogenomic-guided therapy (PGT) under the INH-NAT2 model. With such an approach, not only could an innovative step towards 'End-TB' by the year 2025 be taken but a personalized medicine approach for TB treatment be initiated in India, particularly in tribal communities.

Clionamines stimulate autophagy, inhibit Mycobacterium tuberculosis survival in macrophages, and target Pik1

The pathogen Mycobacterium tuberculosis (Mtb) evades the innate immune system by interfering with autophagy and phagosomal maturation in macrophages, and, as a result, small molecule stimulation of autophagy represents a host-directed therapeutics (HDTs) approach for treatment of tuberculosis (TB). Here we show the marine natural product clionamines activate autophagy and inhibit Mtb survival in macrophages. A yeast chemical-genetics approach identified Pik1 as target protein of the clionamines. Biotinylated clionamine B pulled down Pik1 from yeast cell lysates and a clionamine analog inhibited phosphatidyl 4-phosphate (PI4P) production in yeast Golgi membranes. Chemical-genetic profiles of clionamines and cationic amphiphilic drugs (CADs) are closely related, linking the clionamine mode of action to co-localization with PI4P in a vesicular compartment. Small interfering RNA (siRNA) knockdown of PI4KB, a human homolog of Pik1, inhibited the survival of Mtb in macrophages, identifying PI4KB as an unexploited molecular target for efforts to develop HDT drugs for treatment of TB.

Debridement and bone grafting with internal fixation via anterior approach for the treatment of tuberculosis of lower cervical vertebrae

To evaluate the clinical effects of debridement and bone grafting with internal fixation via anterior approach in treatment of tuberculosis of lower cervical vertebrae. The clinical data of 15 patients with tuberculosis of lower cervical vertebrae who accepted the treatment of one-stage debridement and bone grafting with internal fixation from June 2010 to December 2018 were retrospectively analyzed. There were 9 males and 6 females, aged from 39 to 72 years with an average of (54.67±10.75) years. The lesion segment was C4 to C6. Pre- and post-operative neurologic functions were evaluated by ASIA grade. All the patients underwent the X-ray films of positive and lateral of cervical spine before and after the operation and accepted the periodic review of CT to evaluate the bone grafting. All the 15 operations were successful, no neurological or vascular injury occurred during the operation, and all patients were followed up for 18 to 52 months. The clinical symptoms improved significantly during the follow-up period and CT showed good bone grafting fusion. One patient suffered a relapse of the illness 3 years later, but was healed during the follow-up visit by strengthening the anti tuberculosis therapy. For the patients with vertebral destruction and loss of cervical stability, one-stage debridement and bone grafting with internal fixation via anterior approach has definite curative effects. On the basis of standard anti tuberculosis treatment before operation, the long-term standard anti-tuberculosis treatment after operation is the key to healing the tuberculosis of lower cervical vertebrae.

Debridement and bone grafting with internal fixation via anterior approach for the treatment of tuberculosis of lower cervical vertebrae

To evaluate the clinical effects of debridement and bone grafting with internal fixation via anterior approach in treatment of tuberculosis of lower cervical vertebrae. The clinical data of 15 patients with tuberculosis of lower cervical vertebrae who accepted the treatment of one-stage debridement and bone grafting with internal fixation from June 2010 to December 2018 were retrospectively analyzed. There were 9 males and 6 females, aged from 39 to 72 years with an average of (54.67±10.75) years. The lesion segment was C4 to C6. Pre- and post-operative neurologic functions were evaluated by ASIA grade. All the patients underwent the X-ray films of positive and lateral of cervical spine before and after the operation and accepted the periodic review of CT to evaluate the bone grafting. All the 15 operations were successful, no neurological or vascular injury occurred during the operation, and all patients were followed up for 18 to 52 months. The clinical symptoms improved significantly during the follow-up period and CT showed good bone grafting fusion. One patient suffered a relapse of the illness 3 years later, but was healed during the follow-up visit by strengthening the anti tuberculosis therapy. For the patients with vertebral destruction and loss of cervical stability, one-stage debridement and bone grafting with internal fixation via anterior approach has definite curative effects. On the basis of standard anti tuberculosis treatment before operation, the long-term standard anti-tuberculosis treatment after operation is the key to healing the tuberculosis of lower cervical vertebrae.

Interfering With DNA Decondensation as a Strategy Against Mycobacteria

Tuberculosis is once again a major global threat, leading to more than 1 million deaths each year. Treatment options for tuberculosis patients are limited, expensive and characterized by severe side effects, especially in the case of multidrug-resistant forms. Uncovering novel vulnerabilities of the pathogen is crucial to generate new therapeutic strategies. Using high resolution microscopy techniques, we discovered one such vulnerability of Mycobacterium tuberculosis. We demonstrate that the DNA of M. tuberculosis can condense under stressful conditions such as starvation and antibiotic treatment. The DNA condensation is reversible and specific for viable bacteria. Based on these observations, we hypothesized that blocking the recovery from the condensed state could weaken the bacteria. We showed that after inducing DNA condensation, and subsequent blocking of acetylation of DNA binding proteins, the DNA localization in the bacteria is altered. Importantly under these conditions, Mycobacterium smegmatis did not replicate and its survival was significantly reduced. Our work demonstrates that agents that block recovery from the condensed state of the nucleoid can be exploited as antibiotic. The combination of fusidic acid and inhibition of acetylation of DNA binding proteins, via the Eis enzyme, potentiate the efficacy of fusidic acid by 10 and the Eis inhibitor to 1,000-fold. Hence, we propose that successive treatment with antibiotics and drugs interfering with recovery from DNA condensation constitutes a novel approach for treatment of tuberculosis and related bacterial infections.

A Novel Approach in Treatment of Tuberculosis by Targeting Drugs to Infected Macrophages Using Biodegradable Nanoparticles.

Mycobacterium tuberculosis, the causative agent of tuberculosis is now causing death of more than 10 million people. Because of the development of drug-resistant TB, drug delivery to the infected site through nanoparticle had been studied for long time. Nanoparticles indicate different sorts of association with the natural particles of the body. Nanoparticles can be used as controlled or specific drug delivery system. It can be through temporal controlled or can be distribution controlled. Glucose polymer-based nanoparticles might play an important role as drug delivery system in case of targeted drug delivery in the infected site of the body or in infected macrophages, as they are biodegradable so there should not be any side effects of these particles in the body and also they show very slow immune response. CD4, Beta 1, TGFb-1, IL-2, IL-13 SEC14L1, GUSB, BPI, and CCR7 are major biomarkers secreted after infection of this bacterium by the macrophages which can be used for targeted drug delivery in infected macrophages. As these markers can be used for delivery of drugs at destined position, they can be very beneficial in reducing toxicities of antituberculer drugs to the other uninfected sites and in operating only the infected macrophages.

Host-Directed Therapeutics as a Novel Approach for Tuberculosis Treatment.

Despite significant efforts to improve the treatment of tuberculosis (TB), it remains a prevalent infectious disease worldwide owing to the limitations of current TB therapeutic regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors may be beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs may be more effective than the currently approved TB drugs, which are limited by the long durations of treatment needed and the emergence of drug-resistant strains. Targets of HDTs include host factors such as cytokines, immune checkpoints, immune cell functions, and essential enzyme activities. This review article discusses examples of potentially promising HDTs and introduces novel approaches for their development.

Patient’s Perception on Adverse Drug Reaction of Tuberculosis Treatment in a Teaching Hospital

Tuberculosis is a life- threatening infectious disease which still account to a mortality rate in India. The situation in the country is worsening every year, although there has been a significant advancement in the treatment approaches for tuberculosis. The occurrence of Adverse Drug Reaction (ADR) of tuberculosis is one of the challenges in our effort to control the disease complications. The aim of the study was to assess the Patient's Perception on emergence of Adverse Drug Reactions of tuberculosis in Pulmonology Department of teaching Hospital.

Human Immunodeficiency Virus Infection (HIV)/Acquired Immunodeficiency Syndrome (AIDS): The Frontiers and Global Challenges

HIV/AIDS continues to be a major health threat. An estimated 2.7 million new infections and an estimated 2 million deaths from HIV/AIDS-related illnesses were demonstrated in 2007. The World Health Organization (WHO) estimates that 8-10 million new cases of tuberculosis (TB) globally occur each year and accounts for 25% of AIDS deaths. Although AIDS is the same disease as HIV disease in all part of the world, this microorganism is mostly in many tropical countries. In tropical countries, TB and bacterial pneumonia represent the major pulmonary infections among the patients with HIV-infection/AIDS. Although the spectrum of HIV disease/AIDS is quite broad, the majority of the pulmonary infections in HIV-1 infected patients are similar to those observed in non-HIV infected persons. The geographical differences are primarily due to varying frequencies rather than the kinds of infections. Of all the pulmonary infections encountered in the tropics obviously Mycobacterium tuberculosis is one of the most significant pathogenic microorganisms. Great effort and resources have been invested in the improvement of diagnostic and treatment approaches for TB, and in identification of the close association between the two diseases. The developments have simultaneously benefited many living with HIV. Not all co-infections, nevertheless, have received sufficient attention. Donated funds would require paying for AIDS treatment, and funds remain insufficient for prevention strategies. Making therapy a priority could have the result of reducing fund, thus, increasing the numbers of cases which need therapy. When treatment and prevention ideals meet reality, prevention must be the highest priority. The United States Centers for Disease Control and Prevention (CDC) has recommended HIV testing of all pregnant women as part of the basic package of prenatal services for nearly two decades. Unfortunately, in the past, the focus of global mother-to-child HIV prevention efforts was on Editorial Volume 1 Issue 2 2014

Co-infection: new battlegrounds in HIV/AIDS

Co-infection: new battlegrounds in HIV/AIDS