Caring for Adolescents and Young Adults With Tuberculosis or at Risk of Tuberculosis: Consensus Statement From an International Expert Panel.

Each year, an estimated 1.8 million adolescents (aged 10–19 years) and young adults (aged 20–24 years) become sick with tuberculosis (TB), representing approximately 18% of the annual global TB incidence [[1]Snow K.J. Sismanidis C. Denholm J. et al.The incidence of tuberculosis among adolescents and young adults: A global estimate.Eur Respir J. 2018; 51: 1702352Crossref PubMed Scopus (90) Google Scholar,[2]Snow K.J. Cruz A.T. Seddon J.A. et al.Adolescent tuberculosis.Lancet Child Adolesc Health. 2020; 4: 68-79Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar]. Although it is preventable and treatable, TB is a leading cause of death among adolescents and young adults (AYAs) globally [[3]Guthold R. Baltag V. Katwan E. et al.The top global causes of adolescent mortality and morbidity by age and sex, 2019.J Adolesc Health. 2021; 69: 540Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar,[4]UNICEFAdolescent health dashboard: Regional dashboard.https://data.unicef.org/resources/adolescent-health-dashboard-regional-profiles/Date accessed: August 19, 2022Google Scholar]. The World Health Organization (WHO) estimates that in 2019, 71,000 adolescents (11,000 between 10 and 14 years of age and 60,000 between the ages of 15 and 19 years) and 90,000 young adults died of TB (Figure 1) [[5]World Health OrganizationMaternal, newborn, child and adolescent health and ageing: Data portal. WHO.https://platform.who.int/data/maternal-newborn-child-adolescent-ageing/adolescent-data/adolescent-mortality-causes-of-deathDate accessed: August 19, 2022Google Scholar,[6]World Health OrganizationThe global health observatory. Global health estimates: Leading causes of death.https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates/ghe-leading-causes-of-deathDate accessed: October 11, 2022Google Scholar]. TB is a leading cause of hospitalization and mortality among people with HIV, including AYAs [7Ferrand R.A. Bandason T. Musvaire P. et al.Causes of acute hospitalization in adolescence: Burden and spectrum of HIV-related morbidity in a country with an early-onset and severe HIV epidemic: A prospective survey.PLoS Med. 2010; 7: e1000178Crossref PubMed Scopus (95) Google Scholar, 8Ford N. Matteelli A. Shubber Z. et al.TB as a cause of hospitalization and in-hospital mortality among people living with HIV worldwide: A systematic review and meta-analysis.J Int AIDS Soc. 2016; 19: 20714Crossref PubMed Scopus (86) Google Scholar, 9Hamada Y. Getahun H. Tadesse B.T. Ford N. HIV-associated tuberculosis.Int J STD AIDS. 2021; 32: 780-790Crossref PubMed Scopus (10) Google Scholar]. AYAs face unique challenges with respect to TB and TB care. The risks of Mycobacterium tuberculosis infection and progression to TB disease increase during this period [[10]Seddon J.A. Chiang S.S. Esmail H. Coussens A.K. The wonder years: What can primary school children teach us about immunity to Mycobacterium tuberculosis?.Front Immunol. 2018; 9: 2946Crossref PubMed Scopus (50) Google Scholar,[11]Baguma R. Mbandi S.K. Rodo M.J. et al.Inflammatory determinants of differential tuberculosis risk in pre-adolescent children and young adults.Front Immunol. 2021; 12: 639965Crossref PubMed Scopus (7) Google Scholar]. Females are at greater risk for TB than males during early adolescence; risk among males increases during late adolescence [[10]Seddon J.A. Chiang S.S. Esmail H. Coussens A.K. The wonder years: What can primary school children teach us about immunity to Mycobacterium tuberculosis?.Front Immunol. 2018; 9: 2946Crossref PubMed Scopus (50) Google Scholar]. Risk for TB progression is exacerbated by HIV infection, which is a substantial concern in this age group. In 2021, approximately 28% of new HIV infections worldwide occurred in individuals between 15 and 24 years of age; moreover, AYAs experience worse outcomes in the HIV care cascade as compared to other age groups [12IN DANGER: UNAIDS global AIDS update.https://www.unaids.org/sites/default/files/media_asset/2022-global-aids-update_en.pdfDate: 2022Date accessed: September 20, 2022Google Scholar, 13Enane L.A. Davies M.A. Leroy V. et al.Traversing the cascade: Urgent research priorities for implementing the 'treat all' strategy for children and adolescents living with HIV in sub-Saharan Africa.J Virus Erad. 2018; 15: 40-46Crossref Scopus (36) Google Scholar, 14Enane L.A. Vreeman R.C. Foster C. Retention and adherence: Global challenges for the long-term care of adolescents and young adults living with HIV.Curr Opin HIV AIDS. 2018; 13: 212-219Crossref PubMed Scopus (83) Google Scholar]. Among AYAs with TB, those who are living with HIV, living in conditions of extreme poverty and/or violence, and/or were previously treated for TB disease are at risk for poor adherence to TB treatment and loss to follow-up [15Enane L.A. Lowenthal E.D. Arscott-Mills T. et al.Loss to follow-up among adolescents with tuberculosis in Gaborone, Botswana.Int J Tuberc Lung Dis. 2016; 20: 1320-1325Crossref PubMed Scopus (33) Google Scholar, 16Reif L.K. Rivera V. Bertrand R. et al.Outcomes across the tuberculosis care continuum among adolescents in Haiti.Public Health Action. 2018; 8: 103-109Crossref PubMed Google Scholar, 17Mulongeni P. Hermans S. Caldwell J. et al.HIV prevalence and determinants of loss-to-follow-up in adolescents and young adults with tuberculosis in Cape Town.PLoS One. 2019; 14: e0210937Crossref PubMed Scopus (27) Google Scholar, 18Chiang S.S. Beckhorn C.B. Wong M. et al.Patterns of suboptimal adherence among adolescents treated for tuberculosis.Int J Tuberc Lung Dis. 2020; 24: 723-725Crossref PubMed Scopus (3) Google Scholar, 19de Oliveira M.C.B. Sant'Anna C.C. Raggio Luiz R. Kristki A.L. Unfavorable outcomes in tuberculosis: Multidimensional factors among adolescents in Rio de Janeiro, Brazil.Am J Trop Med Hyg. 2020; 103: 2492-2500Crossref PubMed Scopus (10) Google Scholar, 20Kohlenberg A. Kodmon C. van den Boom M. van der Werf M.J. Tuberculosis surveillance in adolescents: What to learn from European Union/European economic area data?.Int J Tuberc Lung Dis. 2020; 24: 347-352Crossref PubMed Scopus (4) Google Scholar]. Between the ages of 10 and 24 years, individuals undergo rapid growth and development; acquire the physical, cognitive, emotional, and social resources required for achieving health and well-being in adulthood; and become more autonomous and independent of caregivers [[21]Sawyer S.M. Azzopardi P.S. Wickremarathne D. Patton G.C. The age of adolescence.Lancet Child Adolesc Health. 2018; 2: 223-228Abstract Full Text Full Text PDF PubMed Scopus (1148) Google Scholar,[22]Patton G.C. Sawyer S.M. Santelli J.S. et al.Our future: A Lancet Commission on Adolescent Health and Wellbeing.Lancet. 2016; 387: 2423-2478Abstract Full Text Full Text PDF PubMed Scopus (1708) Google Scholar]. TB illness and treatment impact these transitions, and these transitions, in turn, shape how AYAs experience TB illness and treatment. The WHO and other institutions have highlighted the need for health care services and research to address the specific needs of AYAs [22Patton G.C. Sawyer S.M. Santelli J.S. et al.Our future: A Lancet Commission on Adolescent Health and Wellbeing.Lancet. 2016; 387: 2423-2478Abstract Full Text Full Text PDF PubMed Scopus (1708) Google Scholar, 23World Health OrganizationMaking health services adolescent friendly: Developing national quality standards for adolescent-friendly health services.https://apps.who.int/iris/bitstream/handle/10665/75217/9789241503594_eng.pdf?sequence=1Date accessed: February 21, 2022Google Scholar, 24World Health OrganizationGlobal standards for quality health care services for adolescents.https://www.who.int/maternal_child_adolescent/documents/global-standards-adolescent-care/en/Date accessed: February 21, 2022Google Scholar, 25World Health OrganizationGlobal accelerated action for the health of adolescents (AA-HA!): Guidance to support country implementation.https://apps.who.int/iris/bitstream/handle/10665/255415/9789241512343-eng.pdf?sequence=1Date accessed: February 21, 2022Google Scholar, 26Zeitvogel K. Fogarty’s adolescent research key to future good health.https://www.fic.nih.gov/News/GlobalHealthMatters/march-april-2018/Pages/adolescent-health-research.aspxDate accessed: February 21, 2022Google Scholar]. However, policies and practices by most national TB programs (NTPs) do not currently account for AYA-specific needs and considerations [27Blok N. van den Boom M. Erkens C. et al.Variation in policy and practice of adolescent tuberculosis management in the WHO European Region.Eur Respir J. 2016; 48: 943-946Crossref PubMed Scopus (6) Google Scholar, 28Laycock K.M. Eby J. Arscott-Mills T. et al.Towards quality adolescent-friendly services in TB care.Int J Tuberc Lung Dis. 2021; 25: 579-583Crossref PubMed Scopus (5) Google Scholar, 29Moscibrodzki P. Enane L.A. Hoddinott G. et al.The impact of tuberculosis on the well-being of adolescents and young adults.Pathogens. 2021; 10: 1591Crossref PubMed Scopus (11) Google Scholar]. In 2021, to inform the update of the WHO guidelines and operational handbook for the management of TB in children and adolescents [[30]World Health OrganizationWHO operational handbook on tuberculosis, module 5: Management of tuberculosis in children and adolescents.https://www.who.int/publications/i/item/9789240046832Date accessed: June 29, 2022Google Scholar,[31]World Health OrganizationWHO consolidated guidelines on tuberculosis, module 5: Management of tuberculosis in children and adolescents.https://www.who.int/publications/i/item/9789240046764Date accessed: June 29, 2022Google Scholar], the WHO commissioned an evidence review to answer the following background question: How can adolescents with TB or eligible for TB preventive treatment be optimally engaged in care? Given the dearth of evidence on best practices in this area [[2]Snow K.J. Cruz A.T. Seddon J.A. et al.Adolescent tuberculosis.Lancet Child Adolesc Health. 2020; 4: 68-79Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar,[27]Blok N. van den Boom M. Erkens C. et al.Variation in policy and practice of adolescent tuberculosis management in the WHO European Region.Eur Respir J. 2016; 48: 943-946Crossref PubMed Scopus (6) Google Scholar,[29]Moscibrodzki P. Enane L.A. Hoddinott G. et al.The impact of tuberculosis on the well-being of adolescents and young adults.Pathogens. 2021; 10: 1591Crossref PubMed Scopus (11) Google Scholar], we convened an international expert panel to generate a consensus statement regarding needed interventions to optimize TB care for this age group. To inform the consensus process, we conducted a background review evaluating published and unpublished data on the impact of TB and its treatment on five domains of adolescent well-being: (1) good health; (2) connectedness and contribution to society; (3) safety and a supportive environment; (4) learning, competence, education, skills, and employability; and (5) agency and resilience [[29]Moscibrodzki P. Enane L.A. Hoddinott G. et al.The impact of tuberculosis on the well-being of adolescents and young adults.Pathogens. 2021; 10: 1591Crossref PubMed Scopus (11) Google Scholar,[32]Ross D.A. Hinton R. Melles-Brewer M. et al.Adolescent well-being: A definition and conceptual framework.J Adolesc Health. 2020; 67: 472-476Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar]. Authors S.S.C., P.M., L.A.E., and staff from the WHO's Global TB Programme invited individuals from the following groups to participate in an international expert panel: clinicians who treat adolescents with TB; researchers with expertise in adolescent TB and/or adolescent health; adolescent/youth advocates; and survivors of TB illness during adolescence. We aimed to include panelists from diverse settings, including all six WHO regions. Invitations were issued via e-mail. All invitees agreed to participate with the exception of two individuals from the Eastern Mediterranean Region, who did not respond to the invitations. The 34 participants identified themselves as one or more of the following: researchers (n = 26), clinicians (n = 19), advocates (n = 10), and/or TB survivors (n = 4). Panelists were from 16 countries and reported working in adolescent TB, working in adolescent health, and/or receiving TB treatment in 36 countries (Figure 2). Those working as researchers, clinicians, and/or advocates reported a median of 10 (interquartile range: 7–14) years' experience. We convened two meetings of the international expert panel; the first occurred on May 17, 2021, and the second, on June 3, 2021. Both meetings were held virtually using the Zoom (Zoom Video Communications, San Jose, USA) platform. Meetings were conducted in English with simultaneous interpretation in Spanish and in Russian. Ahead of the first meeting, we emailed a draft of the background review to all panelists [[29]Moscibrodzki P. Enane L.A. Hoddinott G. et al.The impact of tuberculosis on the well-being of adolescents and young adults.Pathogens. 2021; 10: 1591Crossref PubMed Scopus (11) Google Scholar]. In addition, using a structured, open-ended survey on Google Forms (Google LLC, Mountain View, USA), we asked panelists to propose interventions to improve the screening, diagnosis, and treatment of M. tuberculosis infection and TB disease in adolescents. Interventions were specifically sought for implementation at each of the levels of the health facility, the community, or in national policy. During the first meeting, we summarized findings from the background review. We then divided into two groups to discuss and begin to prioritize proposed interventions for (1) screening and diagnosis, and (2) treatment. Based on these discussions, S.S.C., P.M., and L.A.E. drafted a set of proposed interventions, which were shared with all panelists by e-mail. Through a second Google Forms survey, panelists were asked to provide feedback on each proposed intervention. S.S.C., P.M., and L.A.E. further revised the interventions based on this feedback. During the second meeting of the international expert panel, using the anonymous polling feature on Zoom, each panelist voted to approve, approve with modifications, or reject each proposed intervention. We had established an a priori requirement of ≥80% approval to include each intervention in the consensus statement. We discussed all suggested modifications until we reached 100% consensus. The final consensus statement was e-mailed to all panelists for endorsement. Although the WHO defines adolescents as individuals between the ages of 10–19 years [[23]World Health OrganizationMaking health services adolescent friendly: Developing national quality standards for adolescent-friendly health services.https://apps.who.int/iris/bitstream/handle/10665/75217/9789241503594_eng.pdf?sequence=1Date accessed: February 21, 2022Google Scholar], panelists overwhelmingly voted to expand the age range for this consensus statement to include young adults (20–24 years old). As detailed elsewhere [[21]Sawyer S.M. Azzopardi P.S. Wickremarathne D. Patton G.C. The age of adolescence.Lancet Child Adolesc Health. 2018; 2: 223-228Abstract Full Text Full Text PDF PubMed Scopus (1148) Google Scholar], the physical and social transitions of adolescence–including brain development, completion of education, and independence from caregivers–often extend beyond 19 years of age; therefore, this expanded age range better reflects the group that would benefit from the proposed interventions. Part 1 of the consensus statement (Table 1) proposes nine interventions to reform current practices that are detrimental to the well-being of AYAs. A key obstacle to addressing TB in AYAs is that TB programs have traditionally reported data for children <15 years of age and adults ≥15 years of age. Although a modeling approach has been used to estimate the global incidence of TB in AYAs [[1]Snow K.J. Sismanidis C. Denholm J. et al.The incidence of tuberculosis among adolescents and young adults: A global estimate.Eur Respir J. 2018; 51: 1702352Crossref PubMed Scopus (90) Google Scholar], the lack of epidemiologic data makes it challenging to measure the setting-specific public health impact of TB in this age group. Moreover, grouping younger AYAs with children and older AYAs with adults prevents examination of the unique clinical, developmental, and psychosocial needs of AYAs with TB. Given the age-related differences in TB presentation, diagnosis, and treatment across pediatric and AYA age groups [[10]Seddon J.A. Chiang S.S. Esmail H. Coussens A.K. The wonder years: What can primary school children teach us about immunity to Mycobacterium tuberculosis?.Front Immunol. 2018; 9: 2946Crossref PubMed Scopus (50) Google Scholar], and building on the 2019 WHO request that NTPs with electronic case-based reporting systems stratify case notifications by 5-year age bands for individuals <25 years old [[33]World Health OrganizationGlobal tuberculosis report 2020. World Health Organization.https://www.who.int/publications/i/item/9789240013131Date accessed: February 12, 2021Google Scholar], the expert panel emphasized the critical need for data disaggregated by age and, ideally, further disaggregated by sex.Table 1Proposed interventions to address needs of AYAs with or at risk of TB, part IReforming current practices to improve AYA well-being. 1. AYAs—defined as individuals 10–24 years of age—have unique healthcare needs, dynamic trajectories in growth and development, and TB-related risks. Therefore, NTPs should report age-disaggregated data for AYAs aged 10–14, 15–19, and 20–24 years. Ideally, the data should be further disaggregated by sex. 2. AYAs have high epidemiological risks for TB exposure and biological risks for developing TB disease after infection. They also have a propensity to develop cavitary lung disease, with its potential for high transmissibility of TB to others in the household or community. Thus, AYAs should be included as a priority group for active TB case-finding, contact tracing, treatment of M. tuberculosis infection and TB disease, and TB education. 3. Facility-based treatment support (historically referred to as directly observed treatment, or DOT) disrupts AYAs' social relationships, education, and vocational training; creates additional financial burdens and barriers to adherence; and exacerbates anticipated and enacted stigma associated with accessing TB care. Therefore, developmentally-appropriate, family-oriented, community-based models of care should be ensured for AYAs, with delivery of treatment support by community health workers, peer supporters, and/or digital adherence technologies such as video supported treatment. Alternatively, for select AYAs and contexts, treatment support may be delivered by family members or caregivers who are trained and supported by health providers. 4. AYAs treated for TB across global settings report loss of interpersonal relationships, interruptions to education, and mental health burdens that are exacerbated by prolonged isolation and/or hospitalization for TB treatment. Thus, country-specific approaches should minimize isolation and hospitalization for AYA with TB, with implementation of isolation policies based in evidence for infectiousness (i.e., allowing AYAs to return to school or higher education, vocational training, or work as soon as they are no longer infectious and appropriate support and treatment adherence structures are in place). 5. AYAs younger than 18 years of age are often excluded from TB research; as a result, they are unable to benefit from new advances in TB therapeutics. AYAs–especially those aged under 18 years–should be prioritized for inclusion in clinical trials and observational studies of treatments for infection and disease caused by drug-susceptible and drug-resistant M. tuberculosis, as well as research on diagnostics and social determinants of disease and outcomes. 6. AYAs experience substantial barriers to treatment adherence and are at risk for loss to follow-up from TB care, and TB treatment often interferes with their education and psychosocial development. These challenges distinguish them as a group that would benefit substantially from shorter regimens for TPT and for TB treatment. The shortest possible effective TPT and TB treatment regimens recommended by the WHO should be implemented for adolescents to facilitate adherence and minimize interference with education and other developmental tasks. 7. Adverse effects of first- or second-line treatment, including consideration of the acceptability to AYAs of a medicine's potential adverse effects, should be discussed with AYAs and their caregivers prior to starting treatment. For example, the reversible skin discoloration associated with clofazimine can lead to discrimination and negative impacts on social relationships. Sharing clear information with AYAs and caregivers regarding potential adverse effects, including the reversibility of certain effects, may help avert significant distress for AYAs and their families. 8. Sexual and reproductive health care is important for AYA health and well-being. Rifamycins render hormone-based contraception less effective. TB providers should counsel AYAs on contraception methods and ensure that AYAs have access to effective contraception. 9. Injectable agents should be avoided for AYAs, unless absolutely needed as part of a salvage regimen. Hearing loss associated with injectable agents is particularly devastating for AYAs. Moreover, facility-based daily administration of injectable agents is time-intensive and interrupts schooling, vocational training, and work.Key recommendations are in bold.AYAs = adolescents and young adults; DOT = directly observed treatment; NTPs = national TB programs; TB = tuberculosis; TPT = TB preventive treatment; WHO = World Health Organization. Open table in a new tab Key recommendations are in bold. AYAs = adolescents and young adults; DOT = directly observed treatment; NTPs = national TB programs; TB = tuberculosis; TPT = TB preventive treatment; WHO = World Health Organization. NTPs generally do not recognize AYAs as a priority group for active TB case-finding, contact tracing, provision of TB preventive treatment, or treatment of TB disease [[27]Blok N. van den Boom M. Erkens C. et al.Variation in policy and practice of adolescent tuberculosis management in the WHO European Region.Eur Respir J. 2016; 48: 943-946Crossref PubMed Scopus (6) Google Scholar]. Yet, as consistently demonstrated by data from the last century, the risk of progression from TB infection to disease increases throughout adolescence and young adulthood [[10]Seddon J.A. Chiang S.S. Esmail H. Coussens A.K. The wonder years: What can primary school children teach us about immunity to Mycobacterium tuberculosis?.Front Immunol. 2018; 9: 2946Crossref PubMed Scopus (50) Google Scholar,34Horsburgh Jr., C.R. Priorities for the treatment of latent tuberculosis infection in the United States.N Engl J Med. 2004; 350: 2060-2067Crossref PubMed Scopus (530) Google Scholar, 35Marais B.J. Gie R.P. Schaaf H.S. et al.The natural history of childhood intra-thoracic tuberculosis: A critical review of literature from the pre-chemotherapy era.Int J Tuberc Lung Dis. 2004; 8: 392-402PubMed Google Scholar, 36Martinez L. Cords O. Horsburgh C.R. et al.The risk of tuberculosis in children after close exposure: A systematic review and individual-participant meta-analysis.Lancet. 2020; 395: 973-984Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar]. Moreover, the risk of primary infection and/or reinfection rises, likely due to AYAs' increased social contacts and higher risk of transmitting M. tuberculosis, in comparison to both younger and older age groups [37Middelkoop K. Bekker L.G. Liang H. et al.Force of tuberculosis infection among adolescents in a high HIV and TB prevalence community: A cross-sectional observation study.BMC Infect Dis. 2011; 11: 156Crossref PubMed Scopus (60) Google Scholar, 38Mossong J. Hens N. Jit M. et al.Social contacts and mixing patterns relevant to the spread of infectious diseases.PLoS Med. 2008; 5: e74Crossref PubMed Scopus (1789) Google Scholar, 39Johnstone-Robertson S.P. Mark D. Morrow C. et al.Social mixing patterns within a South African township community: Implications for respiratory disease transmission and control.Am J Epidemiol. 2011; 174: 1246-1255Crossref PubMed Scopus (98) Google Scholar, 40Wood R. Racow K. Bekker L.G. et al.Indoor social networks in a South African township: Potential contribution of location to tuberculosis transmission.PLoS One. 2012; 7: e39246Crossref PubMed Scopus (46) Google Scholar, 41Grijalva C.G. Goeyvaerts N. Verastegui H. et al.A household-based study of contact networks relevant for the spread of infectious diseases in the highlands of Peru.PLoS One. 2015; 10: e0118457Crossref PubMed Scopus (54) Google Scholar, 42Ajelli M. Litvinova M. Estimating contact patterns relevant to the spread of infectious diseases in Russia.J Theor Biol. 2017; 419: 1-7Crossref PubMed Scopus (43) Google Scholar, 43Zurcher K. Riou J. Morrow C. et al.Estimating tuberculosis transmission risks in a primary care clinic in South Africa: Modeling of environmental and clinical data.J Infect Dis. 2022; 225: 1642-1652Crossref PubMed Scopus (2) Google Scholar]. Furthermore, AYAs are often parents or caregivers to young children, who are vulnerable to rapidly developing life-threatening forms of TB when they become infected in their households [[44]Perez-Velez C.M. Marais B.J. Tuberculosis in children.N Engl J Med. 2012; 367: 348-361Crossref PubMed Scopus (396) Google Scholar]. Because of these increased risks to both individual and public health, AYAs should be prioritized in TB diagnosis, treatment, and prevention. In some settings, TB treatment is delivered via facility-based treatment support (historically referred to as directly observed treatment, or DOT) [[45]World Health OrganizationOrganization WH WHO consolidated guidelines on tuberculosis, module 4: Treatment: Tuberculosis care and support. World Health Organization, Geneva2022Google Scholar]. However, schedule conflicts between facility hours and school, vocational training, and work can result in AYAs missing classes, work, and/or treatment doses. Facility-based treatment support creates additional treatment barriers, including transportation costs and wait times, that further contribute to inadequate treatment and/or loss to follow-up. This treatment delivery approach also adds to the burden of caregivers, who may face further barriers to accompany younger AYAs to the health facility, such as missed work and/or loss of income. Furthermore, facilities' separate, labeled entrances or treatment areas for TB services can result in disclosure of TB status. Not only does this facility layout violate patients' right to privacy, it also contributes to both anticipated and enacted stigma, as AYAs fear being seen engaging in TB services and can suffer discrimination from this disclosure [[15]Enane L.A. Lowenthal E.D. Arscott-Mills T. et al.Loss to follow-up among adolescents with tuberculosis in Gaborone, Botswana.Int J Tuberc Lung Dis. 2016; 20: 1320-1325Crossref PubMed Scopus (33) Google Scholar,[28]Laycock K.M. Eby J. Arscott-Mills T. et al.Towards quality adolescent-friendly services in TB care.Int J Tuberc Lung Dis. 2021; 25: 579-583Crossref PubMed Scopus (5) Google Scholar,[46]Enane L.A. Eby J. Arscott-Mills T. et al.TB and TB-HIV care for adolescents and young adults.Int J Tuberc Lung Dis. 2020; 24: 240-249Crossref PubMed Scopus (7) Google Scholar]. For these reasons, the expert panel states that family-oriented, community-based models of care should replace facility-based treatment support for AYAs. Within developmentally appropriate treatment models, treatment support may be delivered in a context-specific manner by community health workers, peer treatment supporters, and/or using digital adherence technologies such as video-supported treatment. Alternatively, medication administration by a family member or another trusted adult who is trained and supported by health providers may be considered for select AYAs. To prevent TB transmission, AYAs with pulmonary TB are required to isolate at the beginning of treatment. The criteria for ending isolation vary between settings. According to the widely accepted “two-week rule,” individuals with TB are released from isolation after 2 weeks if they are clinically improving and adherent to and tolerating treatment [[30]World Health OrganizationWHO operational handbook on tuberculosis, module 5: Management of tuberculosis in children and adolescents.https://www.who.int/publications/i/item/9789240046832Date accessed: June 29, 2022Google Scholar]. The “two-week rule” is not based on scientific evidence; in fact, multiple human-to-guinea pig studies suggest that in most cases, infectiousness ceases within a few days of effective therapy [47Petersen E. Khamis F. Migliori G.B. et al.De-isolation of patients with pulmonary tuberculosis after start of treatment - clear, unequivocal guidelines are missing.Int J Infect Dis. 2017; 56: 34-38Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar, 48Migliori G.B. Nardell E. Yedilbayev A. et al.Reducing tuberculosis transmission: A consensus document from the World Health Organization regional office for Europe.Eur Respir J. 2019; 53: 1900391Crossref PubMed Scopus (76) Google Scholar, 49Dharmadhikari A.S. Mphahlele M. Venter K. et al.Rapid impact of effective treatment on transmission of multidrug-resistant tuberculosis.Int J Tuberc Lung Dis. 2014; 18: 1019-1025Crossref PubMed Scopus (112) Google Scholar]. However, in other settings, individuals with TB may be required to isolate for longer periods. For instance, in Lima,