Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020.

Comprehensive guidelines for treatment of latent tuberculosis infection (LTBI) among persons living in the United States were last published in 2000 (American Thoracic Society. CDC targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221-47). Since then, several new regimens have been evaluated in clinical trials. To update previous guidelines, the National Tuberculosis Controllers Association (NTCA) and CDC convened a committee to conduct a systematic literature review and make new recommendations for the most effective and least toxic regimens for treatment of LTBI among persons who live in the United States.The systematic literature review included clinical trials of regimens to treat LTBI. Quality of evidence (high, moderate, low, or very low) from clinical trial comparisons was appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition, a network meta-analysis evaluated regimens that had not been compared directly in clinical trials. The effectiveness outcome was tuberculosis disease; the toxicity outcome was hepatotoxicity. Strong GRADE recommendations required at least moderate evidence of effectiveness and that the desirable consequences outweighed the undesirable consequences in the majority of patients. Conditional GRADE recommendations were made when determination of whether desirable consequences outweighed undesirable consequences was uncertain (e.g., with low-quality evidence).These updated 2020 LTBI treatment guidelines include the NTCA- and CDC-recommended treatment regimens that comprise three preferred rifamycin-based regimens and two alternative monotherapy regimens with daily isoniazid. All recommended treatment regimens are intended for persons infected with Mycobacterium tuberculosis that is presumed to be susceptible to isoniazid or rifampin. These updated guidelines do not apply when evidence is available that the infecting M. tuberculosis strain is resistant to both isoniazid and rifampin; recommendations for treating contacts exposed to multidrug-resistant tuberculosis were published in 2019 (Nahid P, Mase SR Migliori GB, et al. Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med 2019;200:e93-e142). The three rifamycin-based preferred regimens are 3 months of once-weekly isoniazid plus rifapentine, 4 months of daily rifampin, or 3 months of daily isoniazid plus rifampin. Prescribing providers or pharmacists who are unfamiliar with rifampin and rifapentine might confuse the two drugs. They are not interchangeable, and caution should be taken to ensure that patients receive the correct medication for the intended regimen. Preference for these rifamycin-based regimens was made on the basis of effectiveness, safety, and high treatment completion rates. The two alternative treatment regimens are daily isoniazid for 6 or 9 months; isoniazid monotherapy is efficacious but has higher toxicity risk and lower treatment completion rates than shorter rifamycin-based regimens.In summary, short-course (3- to 4-month) rifamycin-based treatment regimens are preferred over longer-course (6-9 month) isoniazid monotherapy for treatment of LTBI. These updated guidelines can be used by clinicians, public health officials, policymakers, health care organizations, and other state and local stakeholders who might need to adapt them to fit individual clinical circumstances

Potential Economic Viability of Two Proposed Rifapentine-Based Regimens for Treatment of Latent Tuberculosis Infection

Rationale: Rifapentine-based regimens for treating latent tuberculosis infection (LTBI) are being considered for future clinical trials, but even if they prove effective, high drug costs may limit their economic viability. Objectives: To inform clinical trial design by estimating the potential costs and effectiveness of rifapentine-based regimens for treatment of latent tuberculosis infection (LTBI). Methods: We used a Markov model to estimate cost and societal benefits for three regimens for treating LTBI: Isoniazid/ rifapentine daily for one month, isoniazid/rifapentine weekly for three months (self-administered and directly-observed), and isoniazid daily for nine months; a strategy of ‘‘no treatment’ ’ used for comparison. Costs, quality-adjusted life-years gained, and instances of active tuberculosis averted were calculated for all arms. Results: Both daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months were less expensive and more effective than other strategies under a wide variety of clinically plausibly parameter estimates. Daily isoniazid/rifapentine for one month was the least expensive and most effective regimen. Conclusions: Daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months should be studied in a large-scale clinical trial for efficacy. Because both regimens performed well even if their efficacy is somewhat reduced

A Literature Review Of Current Tuberculosis Prophylaxis Strategies For Plhiv In Namibia

INTRODUCTION: The HIV and TB co-epidemic remains a big obstacle in reducing PLHIV mortality and morbidity in Namibia. The solution to that has been the implementation of isoniazid preventative therapy (IPT) alongside ART for PLHIV to prevent the development of active tuberculosis. As newer shorter regimens of IPT (3HP) are released it is important to Namibia’s Ministry of Health to evaluate the efficacy of these newer IPT regimens prior to their implementation. OBJECTIVES: The objective of this review is to compare the benefit of 3HP to that of 6-month or continuous (36-month) daily IPT for PLHIV to make future TB prophylaxis recommendations for MOH of Namibia. The review will take into consideration outcomes such as TB incidence, mortality, completion rate, and adverse events. METHODS: The qualifying studies were randomized controlled trials which consisted of participants being provided with 3HP and daily IPT (6 month or continuous). Only studies that primarily enrolled PLHIV were included in this review. Out of all the results of these studies the interest is in the development of active tuberculosis, mortality, adverse events, and treatment completion rate. RESULTS: The analysis of the two studies that qualified for this review informs us that 3HP has similar efficacy in preventing active tuberculosis to that of IPT. The Sterling study reported that discontinuation due to hepatotoxicity was significantly higher in the 9-month IPT arm (4%) than in the 3HP (1%) arm. Hepatoxicity was reported in 1.4% (3/207) of the participants in the 3HP group compared to 6.5% (12/193) of the 9-month IPT groups. Both studies reported a higher completion and adherence rate for 3HP than for 6-month or 9-month IPT. The highest adherence was reported for the 3HP in the Martinson study at 95.7% whereas 6-month IPT had an adherence rate for only 83.8%. CONCLUSION: Largely, this review suggests that further research be done to evaluate the complexity of 3HP in different settings with different populations. However, based on these preliminary findings it is preferable for Namibia to adopt 3HP once it is cost-effective to raise their IPT completion rates, increase implementation of IPT in all local sites, and prevent adverse outcomes

JAMA Pediatr

IMPORTANCEThree months of a once-weekly combination of rifapentine and isoniazid for treatment of latent tuberculosis infection is safe and effective for persons 12 years or older. Published data for children are limited.OBJECTIVESTo compare treatment safety and assess noninferiority treatment effectiveness of combination therapy with rifapentine and isoniazid vs 9 months of isoniazid treatment for latent tuberculosis infection in children.DESIGN, SETTING, AND PARTICIPANTSA pediatric cohort nested within a randomized, open-label clinical trial conducted from June 11, 2001, through December 17, 2010, with follow-up through September 5, 2013, in 29 study sites in the United States, Canada, Brazil, Hong Kong (China), and Spain. Participants were children (aged 2\u201317 years) who were eligible for treatment of latent tuberculosis infection.INTERVENTIONSTwelve once-weekly doses of the combination drugs, given with supervision by a health care professional, for 3 months vs 270 daily doses of isoniazid, without supervision by a health care professional, for 9 months.MAIN OUTCOMES AND MEASURESWe compared rates of treatment discontinuation because of adverse events (AEs), toxicity grades 1 to 4, and deaths from any cause. The equivalence margin for the comparison of AE-related discontinuation rates was 5%. Tuberculosis disease diagnosed within 33 months of enrollment was the main end point for testing effectiveness. The noninferiority margin was 0.75%.RESULTSOf 1058 children enrolled, 905 were eligible for evaluation of effectiveness. Of 471 in the combination-therapy group, 415 (88.1%) completed treatment vs 351 of 434 (80.9%) in the isoniazid-only group (P = .003). The 95% CI for the difference in rates of discontinuation attributed to an AE was 122.6 to 0.1, which was within the equivalence range. In the safety population, 3 of 539 participants (0.6%) who took the combination drugs had a grade 3 AE vs 1 of 493 (0.2%) who received isoniazid only. Neither arm had any hepatotoxicity, grade 4 AEs, or treatment-attributed death. None of the 471 in the combination-therapy group developed tuberculosis vs 3 of 434 (cumulative rate, 0.74%) in the isoniazid-only group, for a difference of 120.74% and an upper bound of the 95% CI of the difference of +0.32%, which met the noninferiority criterion.CONCLUSIONS AND RELEVANCETreatment with the combination of rifapentine and isoniazid was as effective as isoniazid-only treatment for the prevention of tuberculosis in children aged 2 to 17 years. The combination-therapy group had a higher treatment completion rate than did the isoniazid-only group and was safe.TRIAL REGISTRATIONclinicaltrials.gov Identifier: NCT00023452CC999999/Intramural CDC HHS/United StatesP30 AI050409/AI/NIAID NIH HHS/United StatesP30 AI094189/AI/NIAID NIH HHS/United States2019-07-12T00:00:00Z25580725PMC66248316464vault:3253

MMWR Recomm Rep

Comprehensive guidelines for treatment of latent tuberculosis infection (LTBI) among persons living in the United States were last published in 2000 (American Thoracic Society. CDC targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221-47). Since then, several new regimens have been evaluated in clinical trials. To update previous guidelines, the National Tuberculosis Controllers Association (NTCA) and CDC convened a committee to conduct a systematic literature review and make new recommendations for the most effective and least toxic regimens for treatment of LTBI among persons who live in the United States.The systematic literature review included clinical trials of regimens to treat LTBI. Quality of evidence (high, moderate, low, or very low) from clinical trial comparisons was appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. In addition, a network meta-analysis evaluated regimens that had not been compared directly in clinical trials. The effectiveness outcome was tuberculosis disease; the toxicity outcome was hepatotoxicity. Strong GRADE recommendations required at least moderate evidence of effectiveness and that the desirable consequences outweighed the undesirable consequences in the majority of patients. Conditional GRADE recommendations were made when determination of whether desirable consequences outweighed undesirable consequences was uncertain (e.g., with low-quality evidence).These updated 2020 LTBI treatment guidelines include the NTCA- and CDC-recommended treatment regimens that comprise three preferred rifamycin-based regimens and two alternative monotherapy regimens with daily isoniazid. All recommended treatment regimens are intended for persons infected with Mycobacterium tuberculosis that is presumed to be susceptible to isoniazid or rifampin. These updated guidelines do not apply when evidence is available that the infecting M. tuberculosis strain is resistant to both isoniazid and rifampin; recommendations for treating contacts exposed to multidrug-resistant tuberculosis were published in 2019 (Nahid P, Mase SR Migliori GB, et al. Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med 2019;200:e93-e142). The three rifamycin-based preferred regimens are 3 months of once-weekly isoniazid plus rifapentine, 4 months of daily rifampin, or 3 months of daily isoniazid plus rifampin. Prescribing providers or pharmacists who are unfamiliar with rifampin and rifapentine might confuse the two drugs. They are not interchangeable, and caution should be taken to ensure that patients receive the correct medication for the intended regimen. Preference for these rifamycin-based regimens was made on the basis of effectiveness, safety, and high treatment completion rates. The two alternative treatment regimens are daily isoniazid for 6 or 9 months; isoniazid monotherapy is efficacious but has higher toxicity risk and lower treatment completion rates than shorter rifamycin-based regimens.In summary, short-course (3- to 4-month) rifamycin-based treatment regimens are preferred over longer-course (6-9 month) isoniazid monotherapy for treatment of LTBI. These updated guidelines can be used by clinicians, public health officials, policymakers, health care organizations, and other state and local stakeholders who might need to adapt them to fit individual clinical circumstances.2020CurrentTreatment and Intervention32053584PMC7041302823

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone

Management of latent Mycobacterium tuberculosis infection:WHO guidelines for low tuberculosis burden countries

ABSTRACT Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of &lt;100 per 100000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing an

An introduction to tuberculosis

Tuesday 24 March is the World Health Organization’s World Tuberculosis Day. The goal is to end the global epidemic by 2035. Tuberculosis (TB) is one of the top 10 causes of death worldwide; one third of the world population is believed to be affected. Mycobacterium tuberculosis is the most common causative organism. Mycobacterium africanum and Mycobacterium canetti cause rare cases of TB in Africa. DNA analysis indicates that the M. tuberculosis complex emerged approximately 70,000 years ago and accompanied migration out of Africa, expanding as a result of increasing population density in the Neolithic period. Between the 17th and 19th centuries, TB killed 1 in 5 adults in North America and Europe. In the developing world today, it is a cause of both high morbidity and mortality. In the World Health Organization’s 2018 Global Tuberculosis Report, it was identified as ‘the leading cause [of death] from a single infectious agent.

Publications and presentations of the Tuberculosis Trials Consortium (as of 1 February 2014)

The TBTC is a collaboration of researchers from the CDC, domestic and international public health departments, academic medical centers, and selected Veterans Administration medical centers whose mission is to conduct programmatically relevant research concerning the diagnosis, clinical management, and prevention of tuberculosis (TB) infection and disease. The purposes of the TBTC are to conduct research that expands clinical and epidemiologic knowledge of TB and facilitates the diagnosis, clinical management, and prevention of tuberculosis infection and disease; to integrate research into the care of persons with TB infection and disease; to develop research questions that are relevant to program settings in general; to promote research within local TB control programs through collaboration on clinical research of relevance to public health settings; and to provide a forum for international collaborative research of importance to both domestic and international TB control.I. Publications [1999-2013, in press] -- II. Presentations and abstracts [1997-2013] -- III. Manuscripts and presentations/abstracts submitted or in preparation: A. Manuscripts; B. Presentations and abstracts.OtherInfectious Diseas

Controlling Latent TB Tuberculosis Infection in High-Burden Countries: A Neglected Strategy to End TB

In a Perspective, Gavin Churchyard and Sue Swindells discuss the importance of strategies to target latent tuberculosis infection in high risk populations and thus disrupt a reservoir for new infections in high burden countries