• barriers of adherence
• children
• isoniazid preventive therapy
• prevention and control
• tuberculosis

• Diagnosis
• Guideline
• Latent Tuberculosis Infection
• Treatment

• 2023040B557-00 Korea Disease Control and Prevention Agency

• Tuberculosis

• Humans
• Isoniazid/therapeutic use
• Isoniazid/administration & dosage
• China/epidemiology
• Male
• Prospective Studies
• Female
• Antitubercular Agents/therapeutic use
• Antitubercular Agents/administration & dosage
• Adult
• HIV Infections/drug therapy
• HIV Infections/epidemiology
• Tuberculosis/prevention & control
• Tuberculosis/epidemiology
• Middle Aged
• Incidence
• Minority Groups/statistics & numerical data
• Risk Factors
• Assessment of Medication Adherence

• National Mega Project on Major Infectious Disease Prevention

• Antitubercular therapy
• Donor
• Interferon-gamma release assays
• Isoniazid
• Kidney transplantation
• Latent
• Rifampicin
• Tuberculin
• Tuberculosis

• Adolescent
• Child
• Humans
• Ambulatory Care Facilities
• Latent Tuberculosis
• Qualitative Research
• Tuberculosis/diagnosis
• Tuberculosis/therapy

• Children
• Completion
• Latent Tuberculosis Infection
• Prescription
• Regimen
• Treatment

• Humans
• Child
• Isoniazid/therapeutic use
• Antitubercular Agents/therapeutic use
• Retrospective Studies
• Latent Tuberculosis/drug therapy
• Latent Tuberculosis/diagnosis
• Rifampin/therapeutic use
• Outpatients
• Republic of Korea

• Catholic University of Korea

• Humans
• Rifampin/adverse effects
• Isoniazid/adverse effects
• Antitubercular Agents/adverse effects
• Network Meta-Analysis
• Latent Tuberculosis/epidemiology
• Drug Therapy, Combination
• Tuberculosis/prevention & control
• Tuberculosis/drug therapy

• CC999999 Intramural CDC HHS

• Fogarty International Center
• Stop TB Partnership

• Latent TB infection (LTBI)
• Mycobacterium tuberculosis (MTB)
• Pediatric
• Tuberculosis (TB)

• Adult
• Adolescent
• Child
• Humans
• Latent Tuberculosis/diagnosis
• Latent Tuberculosis/drug therapy
• Latent Tuberculosis/epidemiology
• Evidence Gaps
• Tuberculosis/epidemiology
• Tuberculin Test
• Prevalence

• Child
• Humans
• Pandemics
• COVID-19/diagnosis
• COVID-19/epidemiology
• Tuberculosis/diagnosis
• Tuberculosis/drug therapy
• Tuberculosis/epidemiology

• Antitubercular agents
• Infant
• Network meta-analysis
• Systematic review
• Tuberculosis

Tuberculosis (TB) continues to disproportionately affect Inuit populations in Canada with some communities having over 300 times higher rate of active TB than Canadian-born, non-Indigenous people. Inuit Tuberculosis Elimination Framework has set the goal of reducing active TB incidence by at least 50% by 2025, aiming to eliminate it by 2030. Whether these goals are achievable with available resources and treatment regimens currently in practice has not been evaluated. We developed an agent-based model of TB transmission to evaluate timelines and milestones attainable in Nunavut, Canada by including case findings, contact-tracing and testing, treatment of latent TB infection (LTBI), and the government investment on housing infrastructure to reduce the average household size. The model was calibrated to ten years of TB incidence data, and simulated for 20 years to project program outcomes. We found that, under a range of plausible scenarios with tracing and testing of 25%–100% of frequent contacts of detected active cases, the goal of 50% reduction in annual incidence by 2025 is not achievable. If active TB cases are identified rapidly within one week of becoming symptomatic, then the annual incidence would reduce below 100 per 100,000 population, with 50% reduction being met between 2025 and 2030. Eliminating TB from Inuit populations would require high rates of contact-tracing and would extend beyond 2030. The findings indicate that time-to-identification of active TB is a critical factor determining program effectiveness, suggesting that investment in resources for rapid case detection is fundamental to controlling TB.

•

TB elimination in Inuit populations would likely extend beyond timelines outlined in action plans.

• Mycobacterium tuberculosis infection
• cascade
• children
• human immunodeficiency virus
• isoniazid
• preventive therapy

• Antitubercular Agents/therapeutic use
• Child
• HIV Infections/complications
• HIV Infections/drug therapy
• HIV Infections/epidemiology
• Humans
• Isoniazid/therapeutic use
• Kenya/epidemiology
• Tuberculosis/diagnosis
• Tuberculosis/drug therapy
• Tuberculosis/epidemiology

• D43 TW011817 FIC NIH HHS
• K23 AI120793 NIAID NIH HHS
• D43 TW009345 FIC NIH HHS
• UL1 TR000423 NCATS NIH HHS
• R25 TW009345 FIC NIH HHS
• Fogarty International Center
• Division of Intramural Research, National Institute of Allergy and Infectious Diseases
• National Institutes of Health

• HIV
• contact tracing
• global health
• prevention and control
• tuberculosis

• Adult
• Child
• Contact Tracing
• HIV Infections/diagnosis
• HIV Infections/drug therapy
• HIV Infections/epidemiology
• Humans
• Isoniazid
• Levonorgestrel
• Rifampin
• Tuberculosis/diagnosis
• Tuberculosis/drug therapy
• Tuberculosis/epidemiology

• K01 TW011482 FIC NIH HHS
• TB REACH Initiative of the Stop TB Partnership
• Global Affairs Canada

• Child
• Diagnosis
• Prevention
• TB
• Treatment
• Tuberculosis

• tuberculosis
• tb preventive therapy
• tb infection tests
• clinical standards

• Caregivers
• Child
• Humans
• Latent Tuberculosis
• Mass Screening
• Reference Standards
• Tuberculosis/diagnosis
• Tuberculosis/prevention & control

• K01 TW011482 FIC NIH HHS

In this article, we highlight technological pediatric TB research advances across the TB care cascade; discuss recently completed or ongoing work in adults and corresponding significant research gaps for children; and offer recommendations and opportunities to increase investments and accelerate pediatric TB R&D.

• Childhood tuberculosis
• Contact tracing
• Preventive treatment
• Source case

The 2021 Global Tuberculosis (TB) report shows slow progress towards closing the pediatric TB detection gap and improving the TB preventive treatment (TPT) coverage among child and adolescent contacts. This review presents the current knowledge around contact case management (CCM) in low-resource settings, with a focus on child contacts, which represents a key priority population for CCM and TPT. Compelling evidence demonstrates that CCM interventions are a key gateway for both TB case finding and identification of those in need of TPT, and their yield and effectiveness should provide a strong rationale for prioritization by national TB programs. A growing body of evidence is now showing that innovative models of care focused on community-based and patient-centered approaches to household contact investigation can help narrow down the CCM implementation gaps that we are currently facing. The availability of shorter and child-friendly TPT regimens for child contacts provide an additional important opportunity to improve TPT acceptability and adherence. Prioritization of TB CCM implementation and adequate resource mobilization by ministries of health, donors and implementing agencies is needed to timely close the gap.

• contact case management
• contact investigation
• implementation gaps
• prevention
• tuberculosis
• tuberculosis preventive therapy

The greatest human cost of the rapidly moving pandemic of SARS-CoV-2 may be due to its impact on the response to other diseases. One such other disease is tuberculosis (TB). All indications suggest that COVID-19-related diversions of healthcare resources and disruptions to public health programming will exacerbate the slower moving pandemic of TB. This is expected to set back TB elimination efforts by years. This is a prediction that is especially relevant to Canada, which has repeatedly failed to meet pre-set targets for the elimination of TB even before the COVID-19 pandemic began. A collaborative approach to achieve TB elimination, one that engages all care providers, has recently been emphasized by the STOP-TB Partnership. Among TB elimination strategies, frontline providers (e.g., family physicians, emergency room physicians, and others) are well positioned to identify candidates for the treatment of latent TB infection, and make the diagnosis of infection-spreading cases of TB in a timely manner, thereby interrupting forward-moving chains of transmission. Electronic medical records offer the promise of automating these processes. In this commentary, we promote broader engagement of the workforce across multiple sectors of medicine to reduce TB associated morbidity and mortality, interrupt transmission, and shrink the reservoir of latent TB infection.

• Diagnosis
• Public health
• Pulmonary tuberculosis

• paediatric drug delivery
• patient compliance
• semi-solid extrusion 3D printing
• soft tablets
• tuberculosis

Majority of active tuberculosis (TB) cases in children in low-incidence countries are due to rapid progression of infection (latent TB infection (LTBI)) to disease. We aimed to assess common practice for managing paediatric LTBI in Austria, Germany and Switzerland prior to the publication of the first joint national guideline for paediatric TB in 2017.

Online-based survey amongst pediatricians, practitioners and staff working in the public health sector between July and November 2017. Data analysis was conducted using IBM SPSS.

A total of 191 individuals participated in the survey with 173 questionnaires included for final analysis. Twelve percent of respondents were from Austria, 60% from Germany and 28% from Switzerland. Proportion of children with LTBI and migrant background was estimated by the respondents to be >50% by 58%. Tuberculin skin test (TST) and interferon-γ-release-assay (IGRA), particularly Quantiferon-gold-test, were reported to be used in 86% and 88%, respectively. In children > 5 years with a positive TST or IGRA a chest x-ray was commonly reported to be performed (28%). Fifty-three percent reported to take a different diagnostic approach in children ≤ 5 years, mainly combining TST, IGRA and chest x-ray for initial testing (31%). Sixty-eight percent reported to prescribe isoniazid-monotherapy: for 9 (62%), or 6 months (6%), 31% reported to prescribe combination therapy of isoniazid and rifampicin. Dosing of isoniazid and rifampicin below current recommendations was reported by up to 22% of respondents. Blood-sampling before/during LTBI treatment was reported in >90% of respondents, performing a chest-X-ray at the end of treatment by 51%.

This survey showed reported heterogeneity in the management of paediatric LTBI. Thus, regular and easily accessible educational activities and national up-to-date guidelines are key to ensure awareness and quality of care for children and adolescents with LTBI in low-incidence countries.

• Adolescent
• Austria/epidemiology
• Child
• Child, Preschool
• Follow-Up Studies
• Geography
• Germany/epidemiology
• Humans
• Latent Tuberculosis/diagnosis
• Latent Tuberculosis/epidemiology
• Latent Tuberculosis/therapy
• Surveys and Questionnaires
• Switzerland/epidemiology
• Tuberculosis, Multidrug-Resistant/diagnosis

• Ludwig Maximilian University Munich, Germany

• child health
• health systems
• paediatrics
• treatment
• tuberculosis

• Adolescent
• Adult
• Child
• Delivery of Health Care
• Humans
• Latent Tuberculosis/diagnosis
• Latent Tuberculosis/drug therapy
• Latent Tuberculosis/epidemiology
• Tuberculosis/diagnosis
• Tuberculosis/drug therapy
• Tuberculosis/epidemiology
• Young Adult

• K24 MH114732 NIMH NIH HHS
• T32 HS000063 AHRQ HHS
• AHRQ
• National Institute of Mental Health

This study identified factors associated with adherence to a 6-month isoniazid preventive therapy (IPT) course among adolescents and children living with HIV. Forty adolescents living with HIV and 48 primary caregivers of children living with HIV completed a Likert-based survey to measure respondent opinions regarding access to care, quality of care, preferred regimens, perceived stigma, and confidence in self-efficacy. Sociodemographic data were collected and adherence measured as the average of pill counts obtained while on IPT. The rates of suboptimal adherence (< 95% adherent) were 22.5% among adolescents and 37.5% among the children of primary caregivers. Univariate logistic regression was used to model the change in the odds of suboptimal adherence. Independent factors associated with suboptimal adherence among adolescents included age, education level, the cost of coming to clinic, stigma from community members, and two variables relating to self-efficacy. Among primary caregivers, child age, concerns about stigma, and location preference for meeting a community-health worker were associated with suboptimal adherence. To determine whether these combined factors contributed different information to the prediction of suboptimal adherence, a risk score containing these predictors was constructed for each group. The risk score had an AUC of 0.87 (95% CI: 0.76, 0.99) among adolescents and an AUC of 0.76 (95% CI: 0.62, 0.90), among primary caregivers suggesting that these variables may have complementary predictive utility. The heterogeneous scope and associations of these variables in different populations suggests that interventions aiming to increase optimal adherence will need to be tailored to specific populations and multifaceted in nature. Ideally interventions should address both long-established barriers to adherence such as cost of transportation to attend clinic and more nuanced psychosocial barriers such as perceived community stigma and confidence in self-efficacy.

• Elimination
• Exposure
• Infection
• Prevention
• Preventive
• TB
• Tuberculosis

• India
• Latent
• TB Infection

Tuberculosis (TB) prevalence is high among Tibetan refugees in India, with almost half of cases occurring in congregate facilities, including schools. A comprehensive program of TB case finding and treatment of TB infection (TBI) was undertaken in schools for Tibetan refugee children.

Schoolchildren and staff in Tibetan schools in Himachal Pradesh, India, were screened for TB with an algorithm using symptoms, chest radiography, molecular diagnostics, and tuberculin skin testing. Individuals with active TB were treated and those with TBI were offered isoniazid-rifampicin preventive therapy for 3 months.

From April 2017 to March 2018, we screened 5391 schoolchildren (median age, 13 years) and 786 staff in 11 Tibetan schools. Forty-six TB cases, including 1 with multidrug resistance, were found in schoolchildren, for a prevalence of 853 per 100 000. Extensively drug-resistant TB was diagnosed in 1 staff member. The majority of cases (66%) were subclinical. TBI was detected in 930 of 5234 (18%) schoolchildren and 334 of 634 (53%) staff who completed testing. Children in boarding schools had a higher prevalence of TBI than children in day schools (915/5020 [18%] vs 15/371 [4%]; P < .01). Preventive therapy was provided to 799 of 888 (90%) schoolchildren and 101 of 332 (30%) staff with TBI; 857 (95%) people successfully completed therapy.

TB prevalence is extremely high among Tibetan schoolchildren. Effective active case finding and a high uptake and completion of preventive therapy for children were achieved. With leadership and community mobilization, TB control is implementable on a population level.

• Tibet
• case finding
• pediatrics
• preventive therapy
• tuberculosis

This 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).

• Advisory Committees
• Disease Eradication/organization & administration
• Humans
• Latent Tuberculosis/epidemiology
• Latent Tuberculosis/prevention & control
• Mass Screening
• Program Development
• Public Health
• Tuberculosis/epidemiology
• Tuberculosis/prevention & control
• United States/epidemiology

• Isoniazid
• Latent tuberculosis infection
• Prevention and control
• Review
• Rifampin
• Rifapentine
• Treatment
• Tuberculosis

• Human immunodeficiency virus
• isoniazid preventive therapy
• people living with HIV

• clinical trials
• diagnostic testing
• latent tuberculosis infection
• mathematical modeling
• noninferiority

• Equivalence Trials as Topic
• Humans
• Interferon-gamma Release Tests
• Latent Tuberculosis/diagnosis
• Latent Tuberculosis/drug therapy
• Latent Tuberculosis/epidemiology
• Models, Theoretical
• Prevalence
• Sensitivity and Specificity
• Tuberculin Test

• UM1 AI104681 NIAID NIH HHS

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.

• Centers for Disease Control and Prevention, U.S.
• Humans
• Latent Tuberculosis/drug therapy
• Practice Guidelines as Topic
• Randomized Controlled Trials as Topic
• United States

• Peru
• Pérou
• contact investigation
• investigation des contacts
• isoniazid preventive therapy
• paediatric tuberculosis
• thérapie préventive à l'isoniazide
• tuberculose
• tuberculose pédiatrique
• tuberculosis

• enteric infections
• migrant health
• schistosomiasis
• screening
• strongyloidiasis
• tuberculosis

• Aminoglycoside phosphotransferase
• DosR regulon
• Escherichia coli
• MSMEG_3942
• Mycobacterium smegmatis
• Mycobacterium tuberculosis
• Rv2004c
• SM

• Anti-Bacterial Agents/pharmacology
• Bacterial Proteins/genetics
• DNA-Binding Proteins
• Drug Resistance, Bacterial/genetics
• Escherichia coli/drug effects
• Escherichia coli/genetics
• Humans
• Kanamycin Kinase/metabolism
• Macrophages/microbiology
• Molecular Docking Simulation
• Mycobacterium smegmatis/drug effects
• Mycobacterium smegmatis/genetics
• Mycobacterium tuberculosis/genetics
• Protein Binding
• Protein Kinases/genetics
• Regulon
• Streptomycin/pharmacology
• THP-1 Cells

• Chemoprophylaxis
• Children
• Compliance
• Isoniazid
• Latent tuberculosis infection
• Tuberculosis

• Antitubercular Agents/therapeutic use
• Chemoprevention
• Child
• Child, Preschool
• Female
• Humans
• Infant
• Isoniazid/therapeutic use
• Latent Tuberculosis/drug therapy
• Male
• Patient Compliance
• Retrospective Studies
• Tuberculosis/drug therapy

• INH prophylaxis
• IPT
• Interferon gamma assay
• Rifapentin
• Tuberculin skin test

• Latent tuberculosis infection
• Prevention
• Therapy
• Treatment
• Tuberculosis