Regimens For Treatment Of Latent Tuberculosis Infection Research Articles

Latent tuberculosis infection in liver transplant patients: a review.

Latent tuberculosis infection in liver transplant patients: a review.

Effectiveness and safety of available preventive tuberculosis treatment regimens for children and adolescents: protocol for a systematic review and network meta-analysis

IntroductionApproximately 5%–10% of individuals with untreated latent tuberculosis infection (LTBI) will progress to active tuberculosis (TB). Children are at a higher risk for progression to TB disease than adults. Isoniazid...

Efeitos colaterais da isoniazida: relato de caso

Treatment of latent tuberculosis infection (LTBI) is an important preventive measure and deserves international interest. Although other LTBI treatment regimens exists, the use of isoniazid is established. The present case report is of a 9-year-old boy with asthma and epilepsy who presented adverse reactions to the use of isoniazid prescribed as a therapy for ILTB. After withdrawing the drug that was replaced by rifampicin, the patient showed clinical improvement.

Prevention of Tuberculosis Reactivation


 It is not known if screening for latent tuberculosis infection (LTBI) is useful for reducing the risk of tuberculosis reactivation among people at risk (no evidence was found).
 In people with LTBI, providing treatment for the latent infection may be helpful for preventing the development of active tuberculosis disease. (In addition, LTBI treatments do not appear to increase the risk for hepatotoxicity.) Treatment effectiveness may depend on the specific LTBI treatment regimen used.
 For people at an increased risk for tuberculosis ― including those from areas with high rates of tuberculosis ― guidelines recommend screening and treatment for LTBI, as this may help prevent TB reactivation. Treatment is recommended for those who are 65 years old or younger and with a positive LTBI result (recommendation from 1 high-quality guideline).

Latent Tuberculosis Infection Testing and Treatment at a Federally Qualified Health Center in Southern California: A Quality Improvement Project.

A key strategy to eliminate tuberculosis (TB) in the United States is to increase latent tuberculosis infection (LTBI) screening, testing, and treatment among non-US-born Asian populations. The purpose was to increase LTBI screening, testing, and treatment at a community clinic. Retrospective baseline LTBI data were retrieved through electronic medical record review. Interventions included adoption of standardized TB risk assessment, training providers to use shorter LTBI treatment regimens, and use of a care coordinator. Chart abstraction to examine outcomes was conducted postintervention at 4 months. In 2017, only 3 patients (7%) with LTBI were started on treatment. At 4 months postintervention, 28 (72%) patients with LTBI were started on treatment, of which 27 (96%) were placed on 3- to 4-month regimens. Training for providers and changes to clinic workflow, including use of a care coordinator, can help increase LTBI screening, testing, and treatment in community clinics.

Interferon gamma release assay tests are associated with persistence and completion of latent tuberculosis infection treatment in the United States: Evidence from commercial insurance data.

Risk-targeted testing and treatment of latent tuberculosis infection (LTBI) is a critical component of the United States' (US) tuberculosis (TB) elimination strategy, but relatively low treatment completion rates remain a challenge. Both treatment persistence and completion may be facilitated by diagnosing LTBI using interferon gamma release assays (IGRA) rather than tuberculin skin tests (TST). We used a national sample of administrative claims data to explore associations diagnostic test choice (TST, IGRA, TST with subsequent IGRA) and treatment persistence and completion in persons initiating a daily dose isoniazid LTBI treatment regimen in the US private healthcare sector between July 2011 and March 2014. Associations were analyzed with a generalized ordered logit model (completion) and a negative binomial regression model (persistence). Of 662 persons initiating treatment, 327 (49.4%) completed at least the 6-month regimen and 173 (26.1%) completed the 9-month regimen; 129 (19.5%) persisted in treatment one month or less. Six-month completion was least likely in persons receiving a TST (42.2%) relative to persons receiving an IGRA (55.0%) or TST then IGRA (67.2%; p = 0.001). Those receiving an IGRA or a TST followed by an IGRA had higher odds of completion compared to those receiving a TST (aOR = 1.59 and 2.50; p = 0.017 and 0.001, respectively). Receiving an IGRA or a TST and subsequent IGRA was associated with increased treatment persistence relative to TST (aIRR = 1.14 and 1.25; p = 0.027 and 0.009, respectively). IGRA use is significantly associated with both higher levels of LTBI treatment completion and treatment persistence. These differences are apparent both when IGRAs alone were administered and when IGRAs were administered subsequent to a TST. Our results suggest that IGRAs contribute to more effective LTBI treatment and consequently individual and population protections against TB.

Essential Components of a Public Health Tuberculosis Prevention, Control, and Elimination Program: Recommendations of the Advisory Council for the Elimination of Tuberculosis and the National Tuberculosis Controllers Association.

SummaryThis report provides an introduction and reference tool for tuberculosis (TB) controllers regarding the essential components of a public health program to prevent, control, and eliminate TB. The Advisory Council for the Elimination of Tuberculosis and the National Tuberculosis Controllers Association recommendations in this report update those previously published (Advisory Council for the Elimination of Tuberculosis. Essential components of a tuberculosis prevention and control program. Recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR Recomm Rep 1995;44[No. RR-11]). The report has been written collaboratively on the basis of experience and expert opinion on approaches to organizing programs engaged in diagnosis, treatment, prevention, and surveillance for TB at state and local levels.This report reemphasizes the importance of well-established priority strategies for TB prevention and control: identification of and completion of treatment for persons with active TB disease; finding and screening persons who have had contact with TB patients; and screening, testing, and treatment of other selected persons and populations at high risk for latent TB infection (LTBI) and subsequent active TB disease.Health departments are responsible for public safety and population health. To meet their responsibilities, TB control programs should institute or ensure completion of numerous responsibilities and activities described in this report: preparing and maintaining an overall plan and policy for TB control; maintaining a surveillance system; collecting and analyzing data; participating in program evaluation and research; prioritizing TB control efforts; ensuring access to recommended laboratory and radiology tests; identifying, managing, and treating contacts and other persons at high risk for Mycobacterium tuberculosis infection; managing persons who have TB disease or who are being evaluated for TB disease; providing TB training and education; and collaborating in the coordination of patient care and other TB control activities. Descriptions of CDC-funded resources, tests for evaluation of persons with TB or LTBI, and treatment regimens for LTBI are provided (Supplementary Appendices; https://stacks.cdc.gov/view/cdc/90289).

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. Am J Respir Crit Care Med 161:S221-S247, 2000). 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 (eg 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 3months of once-weekly isoniazid plus rifapentine, 4months of daily rifampin, or 3months 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 9months; 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 (6-9month) 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.

Ethical issues in expanding latent TB management in high burden countries.

Global efforts are being made to eliminate tuberculosis (TB) as a public health problem by 2030. These efforts are being thwarted by the challenge of effective management to minimise the progression of latent TB infection (LTBI) to TB, thereby interrupting the chain of transmission. Approximately 5%-10% LTBI cases eventually develop TB in their lifetime with the risk being higher in children, people living with HIV/AIDS (PLHIV), undernourished people, and patients with diabetes, chronic kidney disease, silicosis, and other comorbid conditions. Apart from operational barriers, complex ethical issues govern decision-making processes in either retaining current LTBI management practices or advocating implementation of the latest World Health Organization guidelines, which suggest extending treatment to vulnerable groups who have a higher risk of progression to TB. Newer LTBI treatment regimens have a diminished risk of toxicity that allays threats to patient safety. Public health justification for treating LTBI can also override patient autonomy, but the lack of a patient-centred approach is associated with poor adherence and treatment outcomes. Cost-effectiveness studies need to evaluate the gains and losses accruing from funding treatment of LTBI versus similar costs in nutritional interventions for managing undernutrition. Similarly, the impact of diverting resources available for management of the existing active TB control programmes to expanding LTBI treatment also needs to be assessed. In conclusion, a comprehensive LTBI treatment strategy built on the basis of high-quality evidence is the best way forward for resolving the ethical considerations at the heart of LTBI management in the developing world. Keywords: Tuberculosis; India; Latent TB; Medical ethics.

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

SummaryComprehensive 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.

Management of Latent Tuberculosis Infection in Children from Developing Countries.

Tuberculosis (TB), once widely prevalent throughout the world, experienced falling incidence rates in early twentieth century in developed nations, even before the introduction of anti-TB drugs, attributed to improved hygiene and living conditions. Active TB may develop following fresh infection or activation of latent tuberculosis infection (LTBI). LTBI is a state of persistent bacterial viability, however, the host stays asymptomatic and there is no evidence of clinically active tuberculosis. Therefore, treatment of all LTBI is considered as one of the ways to control tuberculosis. Diagnosis of LTBI relies on presence of immune-reactivity to TB antigen and commonly used tests include tuberculin skin test and interferon gamma release assay (IGRA). At present there is no diagnostic test that can identify an individual with LTBI who will progress to develop active disease or remain asymptomatic. Therefore, it is unclear whom to treat. In the current scenario, treatment for LTBI is restricted to high risk groups which include under-5 y contacts of adults with pulmonary TB. Various regimens for treatment of LTBI are evolving and consist of isoniazid (INH) alone for 6-9 mo or combination of INH and rifampicin for 3-4 mo or once a week combination of rifapentin and INH for 3 mo. There is a need for research to identify LTBI, risk factors for progression of LTBI to active disease and a shorter regimen for treatment.

Cost-effectiveness of 3 months of weekly rifapentine and isoniazid compared with other standard treatment regimens for latent tuberculosis infection: a decision analysis study.

Latent tuberculosis infection (LTBI) is a critical driver of the global burden of active TB, and therefore LTBI treatment is key for TB elimination. Treatment regimens for LTBI include self-administered daily isoniazid for 6 (6H) or 9 (9H) months, self-administered daily rifampicin plus isoniazid for 3 months (3RH), self-administered daily rifampicin for 4 months (4R) and weekly rifapentine plus isoniazid for 3 months self-administered (3HP-SAT) or administered by a healthcare worker as directly observed therapy (3HP-DOT). Data on the relative cost-effectiveness of these regimens are needed to assist policymakers and clinicians in selecting an LTBI regimen. To evaluate the cost-effectiveness of all regimens for treating LTBI. We developed a Markov model to investigate the cost-effectiveness of 3HP-DOT, 3HP-SAT, 4R, 3RH, 9H and 6H for LTBI treatment in a cohort of 10000 adults with LTBI. Cost-effectiveness was evaluated from a health system perspective over a 20 year time horizon. Compared with no preventive treatment, 3HP-DOT, 3HP-SAT, 4R, 3RH, 9H and 6H prevented 496, 470, 442, 418, 370 and 276 additional cases of active TB per 10000 patients, respectively. All regimens reduced costs and increased QALYs compared with no preventive treatment. 3HP was more cost-effective under DOT than under SAT at a cost of US$27948 per QALY gained. Three months of weekly rifapentine plus isoniazid is more cost-effective than other regimens. Greater recognition of the benefits of short-course regimens can contribute to the scale-up of prevention and achieving the 'End TB' targets.

Outcomes of Treatment for Latent Tuberculosis Infection in Patients With Inflammatory Bowel Disease Receiving Biologic Therapy.

Treatment for latent tuberculosis infection (LTBI) is of particular concern in patients with inflammatory bowel disease (IBD) initiating biologic therapies to prevent tuberculosis (TB) reactivation. This study aimed to evaluate the effectiveness of LTBI treatment in IBD patients receiving biologic therapy. There was a retrospective review of all IBD patients diagnosed with LTBI following a tuberculin skin test (TST) and/or interferon gamma release assay (IGRA) and who received biologic therapy between 2002 and 2016. The primary outcome was tuberculosis reactivation after completion of LTBI treatment. Three-hundred twenty-nine IBD patients were identified, and 35 (27 Crohn's disease; 8 ulcerative colitis) met the study inclusion criteria. The mean age was 38.3 years, and 68.6% were male. The most common LTBI treatment regimen was isoniazid (INH) for 9 months (74%). Biologic therapies used were infliximab (40%), adalimumab (29%), vedolizumab (20%), and certolizumab pegol (11%). Combination therapy with an immunomodulator was administered in 57% of cases. The median time from initiation of LTBI treatment to biologics was 43 days. The mean duration of follow-up was 2.9 years. The estimated median annual risk of TB reactivation without treatment was 0.52% by a prediction formula. Only 1 patient taking adalimumab monotherapy developed reactivation of TB several years after completing 6 months of isoniazid therapy. The estimated TB reactivation rate was 0.98 cases per 100 patient-years of follow-up in our cohort. Treatment for LTBI in patients with IBD treated with biologics is effective but does not eliminate the risk of reactivation. 10.1093/ibd/izy133_video1izy133.video15776720675001.

The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA: a systematic review.

BackgroundMigrants account for a large and growing proportion of tuberculosis (TB) cases in low-incidence countries in the European Union/European Economic Area (EU/EEA) which are primarily due to reactivation of latent TB infection (LTBI). Addressing LTBI among migrants will be critical to achieve TB elimination. Methods: We conducted a systematic review to determine effectiveness (performance of diagnostic tests, efficacy of treatment, uptake and completion of screening and treatment) and a second systematic review on cost-effectiveness of LTBI screening programmes for migrants living in the EU/EEA. Results: We identified seven systematic reviews and 16 individual studies that addressed our aims. Tuberculin skin tests and interferon gamma release assays had high sensitivity (79%) but when positive, both tests poorly predicted the development of active TB (incidence rate ratio: 2.07 and 2.40, respectively). Different LTBI treatment regimens had low to moderate efficacy but were equivalent in preventing active TB. Rifampicin-based regimens may be preferred because of lower hepatotoxicity (risk ratio = 0.15) and higher completion rates (82% vs 69%) compared with isoniazid. Only 14.3% of migrants eligible for screening completed treatment because of losses along all steps of the LTBI care cascade. Limited economic analyses suggest that the most cost-effective approach may be targeting young migrants from high TB incidence countries. Discussion: The effectiveness of LTBI programmes is limited by the large pool of migrants with LTBI, poorly predictive tests, long treatments and a weak care cascade. Targeted LTBI programmes that ensure high screening uptake and treatment completion will have greatest individual and public health benefit.

Diagnosis and therapeutic approach of latent tuberculosis infection

Detection and treatment of latent tuberculosis infection (LTBI) is an essential measure for tuberculosis (TB) control in low-incidence countries. However, such strategy is limited by the low predictive ability of the diagnostic tests for the development of active TB among infected people and the long-term and toxic treatment regimens. The in vitro interferon-gamma release assays are more specific and sensitive than the tuberculin skin test (TST), and enable a better selection of cases requiring treatment. Nonetheless, their capacity to predict development of TB is still poor. In addition, treatment regimens for LTBI are long, and compliance rates are low. This review discusses the use of the available diagnostic tests and the new approaches to the diagnosis of LTBI, as well as its management in different clinical scenarios.

Better Completion of Pediatric Latent Tuberculosis Treatment Using 4 Months of Rifampin in a US-based Tuberculosis Clinic.

Children less than 5 years of age have the highest age-specific rate of progression from latent tuberculosis infection (LTBI) to active disease. Therefore, regimens for treatment of pediatric LTBI must be not only efficacious but practical enough to overcome the unique childhood barriers to regimen adherence. Since 2012, a 4-month regimen of daily rifampin (4R) has been the standard recommendation for pediatric LTBI at the Denver Metro Tuberculosis Clinic. Using univariate and multivariate analyses, we compared treatment completion rates between 4R and 9-month isoniazid (9H) regimens for all pediatric patients treated for LTBI at the Denver Metro Tuberculosis Clinic between January 1, 2006, and December 31, 2015, and assessed the influence of clinical and demographic characteristics on successful completion of the 2 regimens. There were 395 children in the 4R cohort and 779 in the 9H cohort. Completion rates overall were significantly higher for 4R than 9H (83.5% vs. 68.8%, P < 0.001). Drug toxicity leading to treatment noncompletion was low in both groups (1.5% in 4R and 0.7% in 9H, P = 0.23), and no patient progressed to active tuberculosis in either cohort. The 9H cohort was more likely to fail treatment completion because of barriers potentially related to the longer duration of treatment such as relocation or loss to follow-up. Pediatric patients were significantly more likely to complete LTBI treatment using a 4R than with a 9-month isoniazid regimen. Better completion rates of 4R may increase efficacy of tuberculosis prevention and decrease demand on public health resources.

Tuberculosis Recommendations for Solid Organ Transplant Recipients and Donors.

Tuberculosis Recommendations for Solid Organ Transplant Recipients and Donors.

Diagnóstico y abordaje terapéutico de la infección tuberculosa latente

Detection and treatment of latent tuberculosis infection (LTBI) is an essential measure for tuberculosis (TB) control in low-incidence countries. However, such strategy is limited by the low predictive ability of the diagnostic tests for the development of active TB among infected people and the long-term and toxic treatment regimens. The in vitro interferon-gamma release assays are more specific and sensitive than the tuberculin skin test (TST), and enable a better selection of cases requiring treatment. Nonetheless, their capacity to predict development of TB is still poor. In addition, treatment regimens for LTBI are long, and compliance rates are low. This review discusses the use of the available diagnostic tests and the new approaches to the diagnosis of LTBI, as well as its management in different clinical scenarios.

Management of Latent Tuberculosis Infection Among Healthcare Workers: 10-Year Experience at a Single Center

The risk of infection with Mycobacterium tuberculosis among healthcare workers (HCWs) is estimated to be higher than the general population. However, HCW acceptance and compliance with available latent tuberculosis infection (LTBI) treatment regimens has been problematic. Recently, regimens have become available that might improve HCW acceptance and compliance with LTBI treatment. A retrospective single-center review of Employee Health and Wellness Services records of all HCWs diagnosed with LTBI was conducted. HCWs diagnosed with LTBI were offered 9-month isoniazid (INH), 4-month rifampin (RIF), weekly rifapentine/isoniazid (RPT/INH) for 12 weeks, or no treatment. Acceptance, completion rates, and side effects were reported for each regimen. Comparisons of regimens were assessed using Fisher exact test. Between 2005 and 2014, 363 of 927 (39%) HCWs diagnosed with LTBI accepted treatment. Of 363, 202 chose INH, 106 RIF, and 55 RPT/INH. Completion rates for each regimen were 58%, 80%, and 87%, respectively. HCWs were significantly more likely to have completed treatment with RIF (P < .0001) or RPT/INH (P < .0001) than INH. Rates of discontinuation owing to side effects were 35% for INH, 21% for RIF, and 10% for RPT/INH. Discontinuation of therapy due to side effects was significantly more frequent in the INH than the RPT/INH group (P = .0042). Completion of RIF and RPT/INH for LTBI in an HCW population is more likely than INH. Rates of discontinuation due to side effects were lower among those taking RPT/INH. Shorter LTBI treatment regimens should be more widely considered for HCWs in the United States.

Treatment of Latent Tuberculosis Infection: An Updated Network Meta-analysis.

Treatment of latent tuberculosis infection (LTBI) is an important component of tuberculosis (TB) control, and this study updates a previous network meta-analysis of the best LTBI treatment options to inform public health action and programmatic management of LTBI. To evaluate the comparative efficacy and harms of LTBI treatment regimens aimed at preventing active TB among adults and children. PubMed, Embase, and Web of Science from indexing to 8 May 2017; clinical trial registries; and conference abstracts. No language restrictions were applied. Randomized controlled trials that evaluated human LTBI treatments and recorded at least 1 of 2 prespecified end points (hepatotoxicity and prevention of active TB). 2 investigators independently extracted data from eligible studies and assessed study quality according to a standard protocol. The network meta-analysis of 8 new and 53 previously included studies showed that isoniazid regimens of 6 months (odds ratio [OR], 0.65 [95% credible interval {CrI}, 0.50 to 0.83]) or 12 to 72 months (OR, 0.50 [CrI, 0.41 to 0.62]), rifampicin-only regimens (OR, 0.41 [CrI, 0.19 to 0.85]), rifampicin-isoniazid regimens of 3 to 4 months (OR, 0.53 [CrI, 0.36 to 0.78]), rifampicin-isoniazid-pyrazinamide regimens (OR, 0.35 [CrI, 0.19 to 0.61]), and rifampicin-pyrazinamide regimens (OR, 0.53 [CrI, 0.33 to 0.84]) were efficacious compared with placebo. Evidence existed for efficacy of weekly rifapentine-isoniazid regimens compared with no treatment (OR, 0.36 [CrI, 0.18 to 0.73]). No conclusive evidence showed that HIV status altered treatment efficacy. Evidence was sparse for many comparisons and hepatotoxicity outcomes, and risk of bias was high or unknown for many studies. Evidence exists for the efficacy and safety of 6-month isoniazid monotherapy, rifampicin monotherapy, and combination therapies with 3 to 4 months of isoniazid and rifampicin. U.K. National Institute for Health Research. (PROSPERO: CRD42016037871).