A 1-month regimen of rifapentine plus isoniazid was non-inferior to 9 months of isoniazid alone for prevention of tuberculosis in HIV-infected patients, researchers found.
The primary endpoint -- first diagnosis of tuberculosis infection or death from tuberculosis -- was reported in 2% of patients in the intervention group and 2% of patients in the 9-month control group, for incidence rates of 0.65 and 0.67 per 100 person-years, respectively, reported Richard Chaisson, MD, of Johns Hopkins University School of Medicine in Baltimore, and colleagues.
Patients assigned to the 1-month combo regimen also had a lower incidence of adverse events, and were more likely to complete treatment than did controls, the authors wrote in the New England Journal of Medicine.
The rate difference was -0.02 per 100 person-years, upper limit of 95% confidence interval 0.30 -- well within the prespecified non-inferiority margin of <1.25 events per 100 person-years.
The standard of care for tuberculosis prevention in high-risk patients has been 6-9 months of isoniazid, Chaisson and colleagues explained, but it's been less than satisfactory because of the difficulty in keeping patients adherent, particularly in resource poor settings. That has prompted a search for shorter regimens that don't sacrifice efficacy. Mouse studies had pointed to rifapentine plus isoniazid as a good candidate, the researchers wrote.
The Brief Rifapentine–Isoniazid Efficacy for TB [Tuberculosis] Prevention/A5279 trial (BRIEF TB/A5279) was a randomized, open-label phase III trial conducted in 10 countries in Africa, Asia, South America, North America, and the Caribbean. Participants were ages ≥13 and either lived in an area with tuberculosis presence of >60 cases per 100,000 persons or tested positive for latent tuberculosis.
Patients had antiretroviral therapy (ART) with efavirenz or nevirapine for the first month, and then use of any other ART was permitted after that. They were followed up every 2 weeks until week 36 and then every 12 weeks thereafter for a median of about 3 years.
Overall, 1,488 patients were randomized to receive a 1-month regimen of rifapentine plus isoniazid, while 1,498 patients were randomized to receive 9 months of isoniazid alone. Median age was 35 and 54% were women. Median CD4 count was 470, half of patients were receiving ART at entry, and three-quarters of those patients had an undetectable viral load.
Serious adverse events occurred in 6% of patients in the intervention group and 7% of controls (P=0.07); 97% of patients in the intervention group completed their assigned treatment versus 91% of controls (P<0.001).
An accompanying editorial by Matthew J. Saunders, MRCP, of University College London in England, and Carlton A. Evans, PhD, of Universidad Peruana Cayetano Heredia in Peru, noted that there are several alternatives to traditional isoniazid therapy for tuberculosis, including "isoniazid and rifapentine administered weekly for 3 months, 3 months of daily isoniazid and rifampin, and 4 months of daily rifampin monotherapy."
However, Saunders and Evans added that "the cost of rifapentine may be an important barrier to implementation in the lower-income settings where most tuberculosis occurs." The editorialists also noted that globally, the great majority of tuberculosis cases occur in persons without HIV infection, emphasizing the importance of evaluating preventive therapies in all populations.
"Improving the brevity, acceptability, and safety of preventive therapy is important and will potentially have a major effect," Saunders and Evans wrote. "However, such therapy has to be considered in the context that several billion people ... are believed to have asymptomatic latent tuberculosis infection."
Shorter Therapy Regimen Non-Inferior for Patients with MDR TB
A second study published in NEJM by Andrew J. Nunn, PhD, of the MRC Clinical Trials Unit at UCL (University College London) in England, and colleagues, indicated that treatment of rifampin-resistant tuberculosis could also be shortened from the current standard.
In particular, a 9-11 month regimen including moxifloxacin was non-inferior to 20 months of therapy as recommended in the 2011 World Health Organization guidelines, in patients susceptible to fluoroquinolones and aminoglycosides.
The Standard Treatment Regimen of Anti-Tuberculosis Drugs for Patients with MDR-TB (STREAM) trial was a randomized, phase III, non-inferiority trial conducted in Africa and Asia. Patients were ages ≥18 and had pulmonary tuberculosis with evidence of resistance to rifampin. Patients were randomized 2:1 to the short versus long regimen.
Overall, 282 patients were randomized to the shorter regimen group and 142 were randomized to the longer regimen group, with the modified intention-to-treat population comprised of 383 patients. Of this population, a little over a third were infected with HIV.
At 132 weeks, 78.8% of patients randomized to receive the short regimen achieved a "favorable status" (defined as cultures negative for Mycobacterium tuberculosis at 132 weeks and a previous occasion, with no intervening positive culture or unfavorable outcome) compared to 79.8% in the long-regimen group. After adjusting for HIV status, the difference was 1.0 percentage point (95% CI -7.5 to 9.5, P=0.02 for non-inferiority). Non-inferiority was defined as an upper 95% confidence limit of <10 percentage points difference in favorable status.
Severe adverse events including death did not differ significantly between groups (48.2% short vs 45.4% long treatment). ECG monitoring found that prolongation of the QT interval occurred in a higher portion of participants in the short versus long regimen group (11.0% vs 6.4%).
An accompanying editorial by Gavin J. Churchyard, PhD, of Aurum Institute in Parktown, South Africa, said that while these results provided evidence for the efficacy of a shorter regimen, it "by no means represents a triumph for patients or practitioners."
While severe side effects "did not differ notably" between the two groups, Churchyard noted, "importantly, the shorter regimen still includes 4 months of painful injections with an aminoglycoside that includes the associated risk of ototoxic and nephrotoxic effects."
He concluded that while the shorter regimen is "definitely better" when it comes to treating MDR-TB, "it is not good enough" and "we have a long way to go to turn back the tide."
Swindells and colleagues were supported by grants from the National Institute of Allergy and Infectious Diseases of the NIH. Sanofi provided rifapentine and financial support for the procurement of isoniazid, and financial representatives participated on the protocol team.
Swindells disclosed support from the NIH, Merck Laboratories, and ViiV Healthcare.
Chaisson disclosed support from the National Institute of Allergy and Infectious Diseases, Otsuka, and Merck.
Other co-authors disclosed support from NIH/NIAID, Mylan Pharmaceuticals, Janssen Pharmaceutica, Merck Sharpe & Dohme, ViiV Healthcare, Johnson and Johnson, Pfizer Pharmaceuticals, Bristol-Myers Squibb, Kowa Pharmaceuticals America, and Sanofi-Aventis.
Saunders and Evans disclosed no conflicts of interest.
Nunn and colleagues were supported by the U.S. Agency for International Development (USAID) and funding from the Medical Research Council and the U.K. government.
Nunn disclosed support from USAID and the U.K. Medical Research Council.
Other co-authors disclosed support from USAID and the U.K. Medical Research Council.
Churchyard disclosed support from Johnson & Johnson.
The Five Stages of, prevention : A, new
Furthermore, two other important outcomes arose from the response to is my jaw broken or dislocated? 9/11 which have shaped todays global health landscape. First, lets uncover the underbelly of a paradigm. The paradigm of global health is rapidly changing. The speed of sound may not be lower respiratory tract infections: What to know exceeded. About drugs simply
This strategy defines who and how many to treat. The program was finally discontinued only after several elections. Tuberculosis prevalence has fallen by 41, and its mortality rate has fallen by 45 against the 1990 baseline. Another important innovation is the various attempts to introduce different pricing policies for targeted populations based on their affordability.
The Five Stages of, prevention : A, new. Paradigm for, classifying the, prevention of Disease lyme disease can be diagnosed by ’bull’s eye’ rash alone (Updated for 2018) Ronald Hattis. Administered together with TB drugs 34 Stage 5: Delaying/Reducing Death or Chronic Disability from Complications, contd. Rehabilitation for a complication in which. Rifampin resistance is rare in the absence of isoniazid resistance, but a 9-month regimen of isoniazid, pyrazinamide, and streptomycin has been shown to be effective60; however, it can be difficult for patients to complete 9 months of treatment with an injectable agent. Following the first Global Ministerial conference on TB in 2017 and in advance of the UN high level meeting on TB in 2018, WHO, the Stop TB Partnership and the GLobal Fund to Fight aids, Tuberculosis and Malaria.Reply
Tuberculosis (TB) is presenting young people told - become a care worker new challenges as a global public health problem, especially at a time of increasing threats due to HIV infection, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. In response to these challenges, the Global Plan to Stop TB advocates the development of new diagnostic tests, drugs and vaccines. Tsiouris SJ, Ghandhi NR, El-Sadr WM, Friedland. Tuberculosis and HIV-needed: a new paradigm for the control and management of linked epidemics. Global Strategies for the. Prevention and Control of Infectious Diseases and Non-Communicable Diseases. Hiroki Nakatani 1,.Reply
Followed by a discussion on how to Transfer Violent Patients: HealthLeaders Media the quest for a new paradigm for disease control efforts and challenges and opportunities for Japan. The basic paradigm guiding research on the pathogenesis of TB is that the caseating granuloma is the characteristic lesion of all TB and that immunity is mediated by macrophages and T cells that enhance granuloma function. Surprisingly, this paradigm dates only from studies with animals in the late 20th century. Stop the Spread.Reply
If you have active TB disease, you must get treated right away. This might involve taking a number of medications for 6 to 12 months. It s important to take all of your meds, as they re prescribed, hep C Antivirals Tied to Lower Mortality and Cancer Risk the entire time - even if you feel better. If not, you can get sick again. If you have TB germs in your body.Reply
Paradigm of Immunity to, tuberculosis edited by Maziar Divangahi (1 seeks to address the need for a comprehensive understanding of the immunological processes underlying. In 2018, global tuberculosis prevention, diagnosis, and treatment efforts were estimated to cost US104 billion.2 With such a high global burden, and a current average annual decline in incidence of only 18, new efficacious vaccines are fDA Panel Takes on Transvaginal Mesh -- Again urgently needed. There are several treatment options for latent TB infection. You and your health care provider must decide which treatment is best for you. If you take your medicine as instructed, it can keep you from developing TB disease. Because there are less bacteria, treatment for latent TB infection is much easier than treatment for TB disease. The new system described in this report couples the recombinogenic annealing of an oligonucleotide and the site-specific insertion of a nonreplicating plasmid into a one-step procedure for generating chromosomally tagged genes, deletions, or promoter replacements.Reply
Tuberculosis as a three-act play: A new paradigm for the pathogenesis of pulmonary tuberculosis - Open access. A New Paradigm for the Pathogenesis of Pulmonary Tuberculosis Robert Hunter, MD, PhD, Univeristy of Texas Health Sciences Center Updates from the CDC Applied Research Team James. Posey, PhD, Centers for Disease Control and Prevention. TB Case Studies: Lessons from the Field. Paradigm for evaluation of those with latent tuberculosis infection (ltbi) based on risk of infection, risk of progression to tuberculosis, and benefit of therapy. In developing a diagnostic approach for the evaluation of those with suspected ltbi, we recommend the clinician weigh the likelihood of infection. The new evidence-based era of addressing the cause of illness (chronic lifestyle and environmental stressors) will iBD Management: Where Are the Knowledge Gaps? save millions of lives, will save trillions of dollars, will save healthcare, and must begin.Reply
What People Are Saying About The Wellness Paradigm Prevention. Treatment as prevention : a new paradigm for HIV control? Background and rationale Design of PopART /hptn071 trial Other planned trials. ART for prevention : background. HIV incidence continues to be unacceptably high in how Heavy Drinking Might Boost Your Appetite for Alcohol many countries in Africa.Reply
Original Article from The New England Journal of Medicine Prednisone for the Prevention of Paradoxical Tuberculosis -Associated iris. If they had new or worsening symptoms. TB prevention consists of several main parts. Stopping the transmission of TB from one adult to another. Firstly there is a need to stop the transmission of TB from one adult to another.Reply
Paradigm shift in tuberculosis treatment: Genome sequencing replaces standard resistance testing Date. The breast cancer screening saved over 27,000 lives in 2018 study data enables new concepts for TB diagnostics to be developed. Tuberculosis and HIV-Needed: A New Paradigm for the Control and Management of Linked Epidemics. Based and directly observed treatment for TB, an aids- prevention project was expanded.Reply
The New Paradigm simple drug formula regenerates brain cells of Immunity to Tuberculosis. Editors: Divangahi, Maziar (Ed.). Explore a novel approach to designing a new tuberculosis vaccine ; Cover the latest advances in tuberculosis research of the past decade; see more benefits. Prevention -based incident response is a new security paradigm that utilizes artificial intelligence and machine learning to predict threats, prevent attacks and protect enterprise environments.Reply