Gotowa bibliografia na temat „Anti-TB Therapy”

Abstract Background Anti-tumor necrosis factor (TNF) therapy increased the risk of tuberculosis(TB), and the characteristic clinical feature of western patients with inflammatory bowel disease (IBD) receiving anti-TNF therapy were predominantly extrapulmonary TB. We aimed to analyze the clinical features of patients with IBD who in TB-endemic area (China) that developed active tuberculosis after receiving anti-TNF therapy. Methods Patients from 9 hospital in 7 provinces developed active TB after the initial treatment with infliximab. Demographics, interval between the time at the first dose of anti-TNF therapy and active TB development, tests for latent TB infection (LTBI), concomitant medications, and the details of diagnosis were analyzed in our study. The diagnosis of active TB and LTBI were made based on comprehensive evaluation including TB skin test (TST), interferon gamma releasing assay (IGRA), X-ray test and computed tomography (CT). Results Totally 43 patients developed active TB during infliximab therapy. Among 43 patients, 6 patients had a past TB history and 11 patients were confirmed as LTBI before infliximab treatment. Six patients with LTBI received anti-TB prophylaxis as the same time as anti-TNF treatment. The mean time between initiation of infliximab therapy and active tuberculosis diagnosis in patients with LTBI was significantly shorter than patients without LTBI (216.9±83.2 days versus 410.9±220.3 days, p=0.042). Among 43 active TB patients, 29 patients (29/43, 67.4%) had isolated pulmonary tuberculosis and 11 patients (11/43, 25.6%) had pulmonary TB concomitantly with other organ involvement. Conclusion IBD patients with LTBI develop TB earlier than those without LTBI during anti-TNF treatment, and history of treatment and anti-TB prophylaxis didn’t fully prevent active TB. The most common disease site is lung in China, most of cases were diagnosed by imaging. Chinese physicians should be aware of the potential for TB development during anti-TNF therapy, especially pulmonary tuberculosis.

Patients with an autoimmune disease, such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn's disease, ulcerative colitis, uveitis or psoriasis, and treated with the anti-tumour necrosis factor (TNF) alpha inhibitors are at high risk of developing various infections including tuberculosis (TB). Serious infections are the result of the patients' immunocompromised status that is caused by the primary disease itself, as well as by previous immunosuppressive therapy. In order to decrease the risk of developing TB, prior to the introduction of the anti-TNF alpha therapy, all patients should undergo screening for TB. Experiences from the countries that have already implemented recommendations for TB screening show a significant decrease in TB occurrence in the anti-TNF alpha treated patients. The PPD skin test result is considered positive if induration is of size ?5 mm. The BCG vaccine applied at birth has no effect on interpretation of PPD test results in adults. The diagnosis of active TB is contraindicated for the introduction of the anti-TNF alpha therapy; first, such patients should receive the TB treatment; and 6 months after the completion of the TB treatment, the introduction of the anti-TNF alpha therapy may be considered. The patients with the diagnosis of the latent TB infection (LTBI) should not immediately start with the anti-TNF alpha therapy, but they should first receive the TB chemoprophylaxis; not earlier than a month upon the introduction of the TB chemoprophylaxis, the anti-TNF alpha therapy may be introduced. The first TB follow-up screening during the anti-TNF alpha therapy is recommended 6 months after the anti-TNF alpha therapy has been introduced and the next one should be scheduled after 12 months.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB) remains one of the deadliest, infectious diseases worldwide. The detrimental effects caused by the existing anti-TB drugs to TB patients and the emergence of resistance strains of M. tuberculosis has driven efforts from natural products researchers around the globe in discovering novel anti-TB drugs that are more efficacious and with less side effects. There were eleven main review publications that focused on natural products with anti-TB potentials. However, none of them specifically emphasized antimycobacterial phenolic compounds. Thus, the current review’s main objective is to highlight and summarize phenolic compounds found active against mycobacteria from 2000 to 2017. Based on the past studies in the electronic databases, the present review also focuses on several test organisms used in TB researches and their different distinct properties, a few types of in vitro TB bioassay and comparison between their strengths and drawbacks, different methods of extraction, fractionation and isolation, ways of characterizing and identifying isolated compounds and the mechanism of actions of anti-TB phenolic compounds as reported in the literature.

Tuberculosis spondylitis, or spinal tuberculosis, is a disease that occurs throughout the world. Conservative therapy that is given to patients with spinal tuberculosis actually gives good results, but in certain cases, it requires surgery and rehabilitation therapy. The incidence of tuberculous spondylitis varies worldwide and is usually associated with the quality of available public health service facilities as well as the social factors in the country. Currently, tuberculosis spondylitis is a major source of morbidity and mortality in underdeveloped countries, especially in Asia, where malnutrition and population still remains a major issue. The goals of therapy in tuberculosis spondylitis are eradication of infection or at least to prevent neurological deterioration, and prevention or correction of a deformity or neurological deficit. Administration of anti-tuberculosis drugs is a major therapeutic principle in all cases including spinal tuberculosis. Early administration of anti-tuberculous drugs can significantly reduce morbidity and mortality.

Abstract Background In adults, anti–tumor necrosis factor-α (TNF-α) therapy is associated with progression of latent tuberculosis (TB) infection (LTBI) to TB disease, but pediatric data are limited. Methods Retrospective multicenter study within the Paediatric Tuberculosis Network European Trials Group, capturing patients <18 years who developed TB disease during anti–TNF-α therapy. Results Sixty-six tertiary healthcare institutions providing care for children with TB participated. Nineteen cases were identified: Crohn’s disease (n = 8; 42%) and juvenile idiopathic arthritis (n = 6; 32%) were the commonest underlying conditions. Immune-based TB screening (tuberculin skin test and/or interferon-γ release assay) was performed in 15 patients before commencing anti–TNF-α therapy but only identified 1 LTBI case; 13 patients were already receiving immunosuppressants at the time of screening. The median interval between starting anti–TNF-α therapy and TB diagnosis was 13.1 (IQR, 7.1–20.3) months. All cases presented with severe disease, predominantly miliary TB (n = 14; 78%). One case was diagnosed postmortem. TB was microbiologically confirmed in 15 cases (79%). The median duration of anti-TB treatment was 50 (IQR, 46–66) weeks. Five of 15 (33%) cases who had completed TB treatment had long-term sequelae. Conclusions LTBI screening is frequently false-negative in this patient population, likely due to immunosuppressants impairing test performance. Therefore, patients with immune-mediated diseases should be screened for LTBI at the point of diagnosis, before commencing immunosuppressive medication. Children on anti–TNF-α therapy are prone to severe TB disease and significant long-term morbidity. Those observations underscore the need for robust LTBI screening programs in this high-risk patient population, even in low-TB-prevalence settings.

Abstract Background Anti-tumour necrosis factor (anti-TNF) therapy use in patients with inflammatory bowel disease (IBD) leads to increased risk of tuberculosis (TB) reactivation despite LTB screening, especially in TB endemic regions. We evaluated the effect of stringent screening strategy and latent tuberculosis (LTB) prophylaxis on TB reactivation. Methods We performed an ambispective comparison between patients who were started on anti-TNF therapy after January 2019 (Cohort A) and between Jan 2005-Dec 2018 (Cohort B). Cohort A patients were subjected to stringent screening criteria which included all: history of past TB/recent contact with active TB, CT (computed tomography) chest, IGRA (interferon-gamma release assay), TST (tuberculin skin test), and if any positive were given chemoprophylaxis. A cohort comparison was done to evaluate for risk reduction of TB following the stringent screening strategy. Results One hundred seventy-one patients (63-Ulcerative colitis/108-Crohn’s disease; mean age diagnosis-28.5±13.4 years; 60% males; median follow-up duration after anti-TNF:33months [interquartile range, 23–57 months]) were included. Among 112 in Cohort B 22(19.6%) had LTB and 19(17%) developed TB. In comparison, 26(44%) had LTB and only 1(1.7%) developed TB in Cohort A (p<0.01). On survival analysis, patients in Cohort B had a higher probability of TB reactivation compared to Cohort A at 5 years of follow up, HR-14.39 (95% CI,1.88- 109.81[p=0.010]) after adjusting for gender, age at anti-TNF therapy initiation, concomitant immunosuppression, the total number of anti-TNF doses and therapy escalation. *Log rank p value=0.006 Figure 1: Kaplan Meier curve analysis for probability of remaining free from tuberculosis between patients who were started on anti- TNF therapy till January 2019 (Cohort B) and those who were started on anti-TNF after January 2019 (Cohort A). *Log rank p value=0.02 Figure 2: Kaplan Meier curve analysis for probability of remaining free from tuberculosis between patients who had incomplete latent TB screening and those with complete TB screening. Conclusion The high risk of TB reactivation with anti-TNF therapy in TB endemic regions can be significantly mitigated with stringent LTB screening and chemoprophylaxis.

BACKGROUND: Chronic tuberculous granulomatous mastitis (CTGM) is a rare form of tuberculosis (TB) treated primarily with anti-TB drugs. Oncoplastic surgery (OS) has been proposed as adjuvant therapy for CTGM.METHOD: We followed for 1 year every CTGM patients and assessed the efficacy (defined as non-recurrence and no need for corticosteroids) and safety attributable to the standard anti-TB drugs therapy with and without OS.RESULTS: We analysed 128 CTGM cases, including 78 (61%) treated with OS plus anti-TB drugs and 50 (39%) with anti-TB drugs only. We observed a significantly higher efficacy among those exposed vs. unexposed to OS (100% vs. 92%; prevalence ratio [PR] 1.09, 95% CI 1.00–1.18), with no difference in the number of complications (21% vs. 8%; PR 2.56, 95% CI 0.91–7.26). We also observed that the incidence of post-operative complications decreased by 50% when OS was postponed from after Month 1 to after completing Month 2 of anti-TB drugs treatment (19% to 8%; PR 0.46, 95% CI 0.13–1.62).CONCLUSION: OS appears to represent an efficacious and safe adjuvant therapy when combined with anti-TB drugs in the treatment of CTGM patients, but clinical trials are needed to prove this observation.

Rationale: Latent tuberculosis (TB) infection screening before inducing anti-tumor necrosis factor (anti-TNF) alpha agents is important to prevent TB reactivation. However, latent TB infection reactivation may still occur, and the ideal therapeutic strategy for patients with inflammatory bowel disease (IBD) who develop active TB infection has not been established. Vedolizumab (VDZ) has a good safety profile, with low incidence rates of serious infections. However, its safety in patients with latent TB infection reactivation associated with anti-TNF-alpha agents remains unknown. Patient concerns: A 21-year-old Vietnamese male patient presented to our hospital with hemorrhagic stool. He had no personal or family history of IBD or TB. Diagnoses: Colonoscopy revealed multiple longitudinal ulcers and a cobblestone appearance in the terminal ileum, as well as multiple small erosions and aphtha throughout the colon. Computed tomography revealed a right lung nodular lesion. Serological interferon-gamma release assay and several culture tests were all negative. Thus, he was diagnosed with ileocolonic Crohn’s disease (CD) without TB. Interventions: The intravenous anti-TNF-alpha agent administration with an immunomodulator was initiated. Outcomes: Computed tomography revealed nodular lesion expansion at the right lung, and serological interferon-gamma release assay was positive. He was diagnosed with latent TB infection reactivation. Anti-TNF-alpha agent with an immunomodulator was immediately discontinued, and anti-TB therapy was initiated. His endoscopic findings were still active, and VDZ was selected for maintenance therapy because VDZ has a favorable safety profile with low incidence rates of serious infections. Consequently, mucosal healing was achieved without active TB relapse. Lessons: This case report presented a patient in whom VDZ was continued as maintenance therapy without inducing TB relapse in a patient with CD who developed latent TB infection reactivation associated with anti-TNF-alpha agents and summarized the safety profile of VDZ for patients with IBD with active or latent TB infection. VDZ may be a safe option for induction and maintenance therapy in patients with CD, even in cases with latent TB infection reactivation.

Background: Tuberculosis (TB) remains a global health issues and mostly located in developing countries. As cases of HIV/AIDS increase every year, it is estimated that TB cases also increase. TB is the leading cause of death in people with HIV and HIV infection, and became the biggest risk factor in the conversion of latent TB cases to become active TB. Radiographic manifestation of TB in AIDS patients depends on antiretroviral therapy (ART).Materials and Methods: This is an observational study which compares 2 and 6 months chest radiographs from TB-HIV patients with anti-TB drugs+ART in 24 adults patients with TB-HIV in the Internal Medicine Polyclinic and Ward at Dr. Kariadi Hospital and BKPM Semarang.Result: Most patients were male with 19 subjects (79.2%). The large stage group based on the proportion of AIDS cases is 20-29 years (45.84%). After 6 months of anti-TB drugs+ART there were radiographic improvement in consolidation, cavitation, lymphadenopathy and pleural e?usion. Wilcoxon Signed Ranks Test showed signifcant changes in consolidation and lymphadenopathy between 2 and 6 months of anti-TB drugs+ART, but no signifcant changes in cavity and pleural e?usion.Discussion: At 6 months chest radiographs examination, not all patients with anti-TB drugs+ART show radiographic improvement. Therefore, the decision to stop TB therapy in HIV patients in 6 months time seems inadequate.Conclusion: There are signifcant change between 2 and 6 months of anti-TB drugs+ART with radiographic improvement are consolidation and lymphadenopathy.

AIM. To develop an investigation complex for IBD-patients with the anti-TNF therapy to decrease the risk of active TB. METHODS. In Moscow Research and Clinical Center for TB Control 454 patients with IBD were screened prior to initiation of anti-TNF treatment and 167 (36,8%) of them - during the anti-TNF therapy. Tuberculin skin test (TST) and chest radiography were used for screening and evaluation of pulmonary adverse effects (every 6 months and additionally in cases of any respiratory signs). RESULTS. Of 454 patients investigated during screening X-ray, chest radiography findings were detected in 29 (6,4%), which required additional investigation, among them in 14 patients, findings considered as residual TB lesions. In the other 15 patients, the radiographic findings caused by previous non-specific pulmonary infections. Positive TST implicates preventive antituberculosis therapy, which was provided 37 patients (before and under anti-TNF therapy). During provided to 167 patients the anti-TNF therapy, were developed pulmonary adverse effects: 10 incidences of active TB lung infection 3 case of sarcoidosis, 1 case of fibrosing alveolitis, and two case of non-CONCLUSION. The patients with IBD, treated by anti-TNF therapy, have a risk of development of a wide variety of infectious and non-infectious pulmonary complications, including TB. It is therefore highly important to carefully monitor the patients prior and during the anti-TNF therapy (every 6 months) for a timely detection of pulmonary conditions potentially associated with the treatment.

Thesis (MScMedSc (Pathology. Medical Virology))--University of Stellenbosch, 2009.
ENGLISH ABSTRACT: In 2007, AIDS caused an estimated 2.1 millions deaths worldwide; about 70% in sub-Saharan Africa. HIV preferentially targets activated CD4 T cells, expressing the major HIV receptor CD4, as well as the major chemokine coreceptors CCR5 and CXCR4. These coreceptors play a prominent role during HIV cell entrance phase, HIV transmission and also disease progression. They have been found to be differentially expressed by CD4 T cell subsets. Tuberculosis coinfection may enhance immune activation in vivo thus accelerating HIV disease progression and has become a major challenge in the control of TB in Africa. Introduction of HAART has reduced disease progression to AIDS, as well as risk of further morbidity and mortality. HAART results in a rapid decline of viral load and an initial increase of peripheral CD4 count, however little is known on the effect of HAART in regulation of coreceptor expression, immune activation status and CD4 T cell subset distribution in HIV infection and HIV/TB coinfection. This study is a cross-sectional analysis of coreceptor expression, immune activation status and CD4 T cell subpopulation distribution in South African HIV and HIV/TB coinfected patients before and after ARV. A total of 137 South African individuals were investigated, comprising 15 healthy normal donors (healthy subgroup), 10 patients with active pulmonary tuberculosis (PTB subgroup), 33 HIV-1 positive patients without active PTB (HIV subgroup), 23 positive patients with active PTB (HIV/PTB subgroup), 36 HIV-1 positive patients on ARV (HIV on ARV subgroup) and 20 HIV-1 positive patients with active PTB on ARV (HIV/PTB on ARV subgroup). CD4 absolute count and plasma viral load were determined for all donors. Freshly isolated PBMC were classified by flow cytometry into the following CD4+ T lymphocyte subsets: naïve (CD45+, CD27+), effector memory (CD45-, CD27-), central memory (CD45-, CD27+), and effector (CD45+, CD27-). Coreceptor expression and activation status was assessed by CCR5, CXCR4 and CD38 expression on CD4 T cell subsets. HIV, TB and HIV/TB coinfection was associated with a decrease in percentage CCR5+ T cells as compared to healthy controls, with the HIV/TB group showing the most extensive decrease. In treatment naive patients, CD4 T cells showed elevated surface expression of CCR5 and CD38 as determined by mean fluorescence intensity in HIV/TB co-infection compared to HIV infection alone. The percentage of antigen-experienced cells was higher in the HIV/TB co-infected group compared to the HIV group. The percentage of naïve T cells was decreased in both the HIV infected and the HIV/TB co-infected groups compared to healthy controls. HIV patients with more than 6 months of ARV showed decreased CCR5 and CD38 surface level expression in the HIV and the HIV/ TB co-infected subgroups. An increased percentage of naïve T cells was observed in the HIV infected subgroup, but not in the HIV/TB subgroup, similarly, a decreased percentage of antigen-experienced cells was observed in the HIV subgroup, but not in the HIV/TB co-infected subgroup. A positive correlation was found between CCR5 and CD38 expression, and CXCR4 and CD38 expression (Spearman coefficient of correlation respectively: r=0.59, p<0.001 and r=0.55, p<0.001). Furthermore we found plasma viral load positively associated with CD38 expression (r=0.31, p<0.001) and percentage activated CCR5+ expressing CD4 T cells positively related to viral load (r=0.31, p<0.001). Percentage naïve CD4 T cells was positively associated with CD4 count (r=0.60, p<0.001) and negatively correlated to viral load (r=-0.42, p<0.001). These results indicate that TB coinfection exacerbates certain aspects of dysregulation of CD4 T cell homeostasis and activation caused by HIV infection. In addition, ARV-associated decrease in coreceptor expression, immune activation status and a normalisation of CD4 T cell subset distribution was observed in HIV infected individuals, but not in HIV/TB coinfection. Despite viral suppression after ARV treatment, the decline in the immune activation marker CD38 and coreceptor CCR5 expression, increase in percentage naïve CD4 T cells and decrease of antigen-experienced cells did not reach the levels displayed in the healthy control group. This may indicate that ongoing (albeit reduced) T cell immune activation may occur in the presence of ARV. Further longitudinal studies are needed to closely monitor immune activation during ARV treatment. This study highlighted an association of TB disease with immune activation in HIV infection, the importance of T-cell activation in HIV pathogenesis and its impact on ARV treatment. Further studies are needed to identify causative factors that may lead to a persistent immune activation status during ARV treatment, and how TB coinfection confounds normal responses to ARV.
AFRIKAANSE OPSOMMING: In 2007 was ongeveer 2.1 miljoen sterftes wêreldwyd veroorsaak deur VIGS; ongeveer 70% in Sub-Sahara Afrika. CD4 T selle is die hoof teiken van MIV, aangesien dit die primêre CD4 reseptor, sowel as een of beide van die vernaamste chemokien koreseptore CCR5 en CXCR4 vrystel. Hierdie koreseptore speel ‘n prominente rol wanneer die MIV die sel binnedring, asook tydens MIV oordrag en verloop van die siekte. Dit word ook deur verskillende fraksies van CD4 T selle vrygestel. Gelyktydige TB infeksie mag immuunaktivering in vivo verhoog en dus die siekeproses versnel. MIV het ‘n groot uitdaging geword in die beheer van TB in Afrika. Bekendstelling van HAART het die ontwikkeling van VIGS vertraag, asook die risiko van verdere morbiditeit en mortaliteit. HAART veroorsaak ‘n vinnige afname in virale lading ‘n toename in CD4 telling, hoewel die spesifieke invloed van HAART op die regulering van koreseptor vrystelling, immuunaktivering en verspreiding van CD4 fraksies in MIV en MIV/TB infeksies nog onduidelik is. Hierdie studie het gepoog om koreseptor vrystelling, immuunaktiveringstatus en die verspreiding van CD4 subpopulasies in pasiënte met MIV en MIV/TB voor en na ARV behandeling te ondersoek. ‘n Totaal van 137 Suid-Afrikaanse individue is ondersoek en die studiegroep het bestaan uit 15 normale persone (gesonde subgroep), 10 pasiënte met aktiewe pulmonale TB (PTB subgroup), 33 MIV positiewe pasiënte sonder PTB (MIV subgroep), 23 MIV positiewe pasiënte met aktiewe PTB (MIV/PTB subgroep), 36 MIV positiewe pasiënte op ARV (MIV op ARV subgroep) en 20 MIV positiewe pasiënte met aktiewe PTB op ARV (MIV/PTB op ARV subgroep). Absolute CD4 telling en virale ladings was bepaal vir alle deelnemers. Vars geïsoleerde perifere bloed mononukleêre selle is geklassifiseer deur middel van vloeisitometrie as die volgende CD4 T limfosiet subgroepe: naïewe selle (CD45+, CD27+), effektor geheueselle (CD45-, CD27-), sentrale geheueselle (CD45-, CD27+), en effektor selle (CD45+, CD27-). Koreseptor vrystelling en aktivering was beoordeel volgens CCR5, CXCR4 en CD38 vrystelling op CD4 T sel subgroepe. HIV, TB en MIV/TB ko-infeksie is geassosieer met ‘n afname in die persentasie CCR5+ T selle, vergeleke met gesonde kontroles, waar die MIV/TB subgroep die grootste afname getoon het. In onbehandelde pasiënte het die CD4 T selle verhoogde vrystelling van CCR5 en CD38 op die oppervlakte getoon en dit is bevestig deur die gemiddelde fluoresserende vii intensiteit in die MIV/TB subgroep vergeleke met die subgroep met slegs MIV. Die MIV/TB subgroep het verder ook ‘n verhoogde persentasie totale geheue T selle getoon vergeleke met die MIV subgroep. Die persentasie naïewe T selle was egter verlaag in beide die MIV en MIV/TB subgroepe vergeleke met normale kontroles. MIV pasiënte wat langer as 6 maande op ARV behandeling was in beide die MIV en MIV/TB subgroepe, het ‘n verlaagde vrystelling van CCR5 en CD38 op die oppervlakte van die CD4 selle getoon. ‘n Verhoogde persentasie naïewe T selle het in die MIV subgroep voorgekom, maar nie in die MIV/TB subgroup nie. ‘n Soortgelyke tendens is gevind waar die persentasie totale geheueselle verlaag was in die MIV subgroep, maar nie in die MIV/TB subgroep nie. ‘n Positiewe korrelasie is gevind tussen CCR5 en CD38 vrystelling, asook CXCR4 en CD38 vrystelling (Spearman korrelasie koëffisiënt: r=0.59, p<0.001 en r=0.55, p<0.001 onderskeidelik). Verder het die plasma virale lading ‘n positiewe assosiasie getoon met CD38 vrystelling (r=0.31, p<0.001) en die persentasie geaktiveerde CCR5+ vrystellende CD4 T selle met virale lading (r=0.31, p<0.001). Die persentasie naïewe CD4 T selle het ‘n positiewe assosiasie getoon met CD4 telling (r=0.60, p<0.001) en ‘n negatiewe korrelasie met virale lading (r=-0.42, p<0.001). Volgens hierdie resultate vererger TB ko-infeksie sekere aspekte van die disregulasie van CD4 T selhomeostase en aktivering as gevolg van MIV infeksie. Verder kon ‘n ARVgeassosieerde afname in koreseptor vrystelling, immuunaktivering en normalisering van CD4 T sel fraksies bespeur word in die MIV subgroep, maar nie in die MIV/TB subgroep nie. Ten spyte van virale onderdrukking veroorsaak deur ARV behandeling, het die afname in die immuunmerker CD38 en koreseptor CCR5, toename in die persentasie naïewe CD4 selle en afname in totale geheue CD4 T selle nie die vlakke van die normale kontrolegroep bereik nie. Dit is moontlik dat volgehoue verlaagde T sel immuunaktivering nog steeds mag plaasvind in die teenwoordigheid van ARV. Verdere longitudinale studies is nodig om immuunaktivering tydens ARV behandeling te monitor. Hierdie studie het die belangrikheid van T sel aktivering in MIV patogenese en dit impak daarvan op ARV behandeling beklemtoon. Verdere studies is nodig om moontlike oorsake of bydraende faktore te identifiseer wat tot volgehoue immuunaktivering tydens ARV behandeling kan lei, asook tot mate waartoe TB ko-infeksie kan inmeng met die normale werking van ARV behandeling.

Reactivation of latent infection is the major cause of tuberculosis (TB). Cholesterol is a critical carbon source during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the sterol-ring degradation and is essential for intracellular survival. NAT from M. tuberculosis (TBNAT) can utilise propionyl-CoA and therefore was proposed as a target for TB-drug development. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. NAT inhibitors, including the piperidinol class, were identified by high-throughput screening. The insolubility of recombinant TBNAT has been a major limitation in pursuing it as a drug target. Subcloning tbnat into a pVLT31 vector resulted in a yield of 6-16 mg/litre-bacterial-culture of pure-soluble recombinant TBNAT. The increased yield allowed for extensive screening for crystallisation conditions. However, since a structure was not obtained, the model NAT from M. marinum (MMNAT) was employed to further understand NAT as a target. Screening against a panel of Acyl-CoA cofactors showed that MMNAT can also utilise propionyl-CoA. The MMNAT structure in complex with the high affinity substrate hydralazine was determined (2.1 Å) and the architecture of the arylamine pocket was delineated. A novel mechanism for the acetylation reaction of hydralazine has emerged. It is proposed that the acetyl group is transferred from acetyl-CoA to the heterocyclic aromatic nitrogen of hydralazine, which explains the immediate cyclisation of the acetylated metabolite into an N-methyltriazolophthalazine. By employing mass spectroscopy, enzyme assays, computational docking and structural studies, a covalent mechanism of inhibition by the piperidinol class was established, and the inhibitor-binding pocket was identified. Inhibitors with new scaffolds were identified using the in silico 3D-shape screening and thermal shift assay.

Emergence of MDR-TB is highly associated with morbidity and mortality and it needs high concerns about the possibility of a future TB epidemic as limited therapeutic options are available. The current treatment against TB needs daily administration for at least 6 months. That in turn leads to the development and spread of drug-resistant TB. Plenty of work has been done in nanomedicine that provides hope to encounter TB effectively. In the developing world the development of nanoparticle-based aerosol vaccines for tuberculosis has potential applications using on a large scale at relatively low cost, and particularly attractive for use. This book review examines the current TB diagnostic assays and treatment by nanotechnologies and highlight recent advances in Anti-TB Drug (ATD) delivery systems and anti-TB drug encapsulation. It also discusses the impact of the nanoparticles as an emerging treatment against MDR-TB and discusses the current knowledge and potential nanomedicine to improve MDR-TB therapy.

Emergence of MDR-TB is highly associated with morbidity and mortality and it needs high concerns about the possibility of a future TB epidemic as limited therapeutic options are available. The current treatment against TB needs daily administration for at least 6 months. That in turn leads to the development and spread of drug-resistant TB. Plenty of work has been done in nanomedicine that provides hope to encounter TB effectively. In the developing world the development of nanoparticle-based aerosol vaccines for tuberculosis has potential applications using on a large scale at relatively low cost, and particularly attractive for use. This book review examines the current TB diagnostic assays and treatment by nanotechnologies and highlight recent advances in Anti-TB Drug (ATD) delivery systems and anti-TB drug encapsulation. It also discusses the impact of the nanoparticles as an emerging treatment against MDR-TB and discusses the current knowledge and potential nanomedicine to improve MDR-TB therapy.

Tuberculosis is considered a fatal respiratory disease commonly seen in developing countries. This chapter includes the global scenario of TB patients and brief description of TB history, its pathogenesis, types, diagnosis tests, emergence of MDR (multi drug resistance) and XDR (extensively drug resistance). The traditional chemotherapy of TB includes first and second line drug therapy. These lines of therapies face many difficulties such as low solubility, low bioavailability, and stability issues. Therefore, some new drugs were introduced in the market that showed effective results to the patients. Nanoparticulate drug delivery gained much focus in recent years due to its advantages and ideal characteristics. Numerous nanoparticles, liposomal formulations, and polymeric micelles were reported by the researchers with significant and considerable results. Inhalable formulations were also prepared by scientists that showed effective and remarkable anti-tuberculosis action on TB patients. Many efforts are awaited to completely eradicate TB from the planet.

Background: Hepatotoxicity is very frequent and is a dangerously adverse effect of anti-TB medications. This effect can reduce the effectiveness of the treatment by compromising treatment regimens. Among these first-line quadruple therapy drugs (INH, RMP, PZA, and EMB), INH, RMP, and PZA are metabolized mostly by the liver, and due to this, are likely hepatotoxic. However, the survival times of hepatotoxicity among patients with TB in Thailand are currently not available. The aims of the present study were to assess the prevalence and survival time of drug-induced hepatotoxicity in patients with TB. Methods: A cross-sectional retrospective study was performed to explore the survival time of the development of drug-induced hepatotoxicity among 327 patients with TB who received standard drug treatment at the TB clinic in Phichit Hospital. Data was collected from the HOSxP program and medical records from 2016 to 2018. Kaplan-Meier and Cox’s regressions were used for data analysis. Results: The results showed that prevalence of drug-induced hepatotoxicity was 6.42% and confirmed that patients with TB who were <50 years of age will be a median survival time on drug-induced hepatotoxicity is 17 days and 30 days for those who age group ≥50 years. Conclusion: The median survival time of drug-induced hepatotoxicity among patients with TB who were <50 years of age is 17 days. So, patients with TB whose ages are less than 50 years should receive liver function tests such as AST and ALT and investigate risk behavior before receiving the anti- TB treatment.

Spinal tuberculosis (TB) is a worldwide public health issue which is one of the main causes of disability. In regions with high TB incidence, Pott’s disease, also known as spinal tuberculosis, is also highly prevalent. Osteoarticular tuberculosis, which affects 1–2% of people with tuberculosis, is always a secondary infection that individuals with primary TB elsewhere in the body have. The most serious kind of bone TB is Pott’s paraplegia. The spinal cord is compressed, there is a gradual neurologic loss, and there may be deformity as the infection often starts from the vertebral body with noticeable damage and creation of a cold abscess. The management and treatment of spinal TB is challenging and intricate. Despite the availability of cutting-edge surgical techniques, imaging modalities, and anti-tubercular chemotherapy, managing Pott’s paraplegia can be challenging, particularly for those strains having multidrug resistant capacity. In order to achieve the desired neurological outcome, therapy should be tailored to each patient’s unique needs. Early diagnosis and prompt therapy are the main initial challenges in the management. The pathophysiology, imaging differential diagnosis, neuroimaging characteristics, surgical choice, and neurological prognosis of Pott’s paraplegia patients from previous literatures have been highlighted in this chapter.

The pharmacovigilance has been evolved as a professional and ethical practice in ensuring the safety of medicines. The Adverse Drug Reactions (ADRs) associated with the use of medicines including Anti-Tuberculous Therapy (ATT) through a robust system of pharmacovigilance helps in promoting the safety of patients at large. The occurrence of ADRs associated with the use of ATT is expected, a large number of medicines are combined and used for prolonged duration. The suspected ADRs associated with first line ATT are well documented. However, the drugs used in second line or multidrug resistant to tuberculosis (TB), namely bedaquiline, reported to cause QT prolongation in electrocardiogram reading as one of the most common ADRs. Therefore, early identification and prevention of ADRs during ATT is essential for promoting the rational use and reduce the burden of anti-microbial resistance, besides achieving better treatment outcomes.

Mycobacterium tuberculosis has a large spectrum of extra-pulmonary manifestations, and ocular tuberculosis is one of them. Diagnosis of ocular tuberculosis is often presumptive due to its extreme variability of ocular manifestations and difficulty isolating the organism through biopsy or culture. We report three cases of primary ocular tuberculosis with varied clinical presentations, namely neuroretintis, panuveitis, and occlusive vasculitis. Patients were aged 23 to 45 presented with symptoms of blurring of vision from 3 days to one week prior to presentation. Visual acuity ranged from 6/18 to 2/60. For all three cases, chest X-ray and serological investigation for infective causes were normal. Mantoux test and TB Quantiferon test were negative, and ESR was raised for the first two cases. Mantoux was positive, and ESR was not raised for the third case. Patients were diagnosed to have Presumed Ocular Tuberculosis. An anti-tubercular therapy was administered. There was significant improvement at post-initiation of medication. A high index of clinical suspicion is crucial due to the diverse clinical presentations of ocular tuberculosis. Early initiation of anti-tubercular therapy is vital for successful treatment.