Table 3

Facilitators and barriers affecting retention in the paediatric TB infection care cascade, interventions used and knowledge gaps

Cascade step		Facilitators/factors associated with higher retention	Barriers/factors associated with lower retention	Interventions used	Knowledge gaps
1)Intended for testing → initial testing	LMIC	No analytic studies.	Caregiver non-acceptance.66 Child non-acceptance/refusal.66 Medical contraindications (concurrent infectious disease and chronic disease).66 75 Low perceived risk.49 Older age50. Patient mobility/inability to contact at-risk patients.29 49 74 75 Test stock-outs.61 74	Multimodal solutions targeting knowledge, stigma and cost associated with diagnosis and treatment.*43 Contact tracing programmes.49 50 56 61 74 School-based screening.56	Improving availability of TST and IGRA. Populations at risk for low testing uptake. Strategies to improve testing uptake. Yield of primary care and community-based screening.
1)Intended for testing → initial testing	HIC	Hospital-based and community health centre-based care.76 Sociodemographic factors (language at home).76	Caregiver non-acceptance.37 Child non-acceptance/refusal.69 Patient mobility/inability to contact at-risk patients.46 51 58 73 Older age.70 Younger age.72	Contact tracing programs.36 38 41 44–46 51 53–55 57–59 73 77 School-based screening.36 53–55 57–60
2) Initially tested → received test result	LMIC	No analytic studies.	No analytic studies.	No analytic studies.	Comparison of TST and IGRA in loss to follow-up. Reasons for loss to follow-up.
2) Initially tested → received test result	HIC	Hospital-based and community health centre-based care.76	Forgetfulness.71 Older age.18 70 Other sociodemographic factors (race/ethnicity; language; parent citizenship status).70 76 Transportation/financial barriers.71	Home nursing follow-up.71 Phone reminders.71 Positive and negative reinforcements.*71
3) Received test result → referral for evaluation	LMIC	No analytic studies.	No analytic studies.	No analytic studies.	Reasons for loss to follow-up. ·Strategies to strengthen referral process.
3) Received test result → referral for evaluation	HIC	No analytic studies.	No analytic studies.	No analytic studies.
4) Referral for evaluation → completion of evaluation	LMIC	No analytic studies.	No analytic studies.	Symptom-based screening.28	Reasons for loss to follow-up. Strategies to strengthen referral process.
4) Referral for evaluation → completion of evaluation	HIC	No analytic studies.	Location of family origin.40 Moving prior to completion of medical evaluation.78 Refusal of TB clinic visit.40 Transitioning care to other facilities.84	No analytic studies.
5) Completion of evaluation → recommendation for treatment	LMIC	No analytic studies.	Medical contraindications (concurrent infectious disease).102	No analytic studies.	Prevalence of medical contraindications. Strategies to shorten time between evaluation and recommendation.
5) Completion of evaluation → recommendation for treatment	HIC	No analytic studies.	Clinicians’ concerns about patients’ adherence.103 Medical contraindications (medical instability/elevated transaminases).38	No analytic studies.
6) Recommendation for treatment → initiation of treatment	LMIC	Knowledge about TB transmission, treatment and policy.104 Relationships with patients with TB.104	Concern about medication adverse effects.104 Patient/caregiver refusal.33 81 93 102	No analytic studies.	Reasons for patient/caregiver refusal. Strategies to improve treatment uptake. Treatment uptake among patients with MDR-TB infection.
6) Recommendation for treatment → initiation of treatment	HIC	Refugees.64	Concern about medication adverse effects.51 Country of origin.40 99 166 Living in ‘blended families’.40 Moving away/transferred care before starting therapy.83 95 Patient/caregiver refusal.17 36 40 46 59 60 68 90 95 97 99	No analytic studies.
7) Initiation of treatment → completion of treatment	LMIC	Caregiver education.56 Caregiver knowledge about TB infection and BCG.81 Close relationship and close contact with TB index patients.112 Personal health knowledge/beliefs.56 81 136 Shorter therapy regimens.22 106 Sociodemographic factors (Human Development Index).30	Experience of or concerns about adverse medication effects.56 102 107 Contact with adult TB contacts not receiving TB treatment.30 Low income.81 Medical contraindications (pregnancy, concurrent infectious disease).93 107 Stigma.56 Transportation-related factors (distance and cost).81	Cash incentives.107 DOPT.34 35	Benefits and downsides of joint therapy management between specialists and primary care providers. Location of treatment/prescription (primary care clinics and health department clinics). Scalability or durability of effective pilot programmes, and translation to resource-limited settings. Use of novel adherence measurement strategies (eg, mHealth).
7) Initiation of treatment → completion of treatment	HIC	Female sex.31 Family members undergoing TB testing.68 Family support.139 History of receiving care at the clinic.82 Location of origin.40 99 115 124 Psychological well-being and perceived mastery.113 115 116 Refugees.31 School achievement.137 139 Shorter therapy regimens.14 34 35 105 106 120 126 140 145 146 Treatment at health department and non-hospital clinics.99 108 Younger age.13 18 40 68 82 99 116 125 137 138 Other sociodemographic factors (eg, language at home, family composition and race/ethnicity).40 51 83 113 115 116 138 143	Adverse home/family environment.125 Delays in diagnostic steps.40 82 Experience of or concerns about adverse medication effects.17 19 31 35 36 82 83 108 109 118 120 121 125 126 132–135 Caregiver work conflicts.135 Early discontinuation by physicians.35 126 Forgetfulness.51 Lack of cooperation from children.51 Lack of patient/caregiver knowledge about TB infection.135 Lack of caregiver understanding about treatment instructions.126 Medical contraindications (pregnancy and concurrent infectious disease).51 83 133 Movement away during treatment.68 83 90 100 101 118 124 Patient/caregiver lack of knowledge about TB and treatment.51 Prescriber type.32 Time since immigration.68 Younger age.88	Adherence counselling/coaching31 139 142. Contingency contracting for adolescents.116 DOPT13 14 17 85 88 90 94 118 125–127 129 130 132 Home nursing assessments/outreach.131 Life skills peer counselling.139 Multimodal treatment-tailoring to address convenience and social/structural barriers.88 125 Provision of free medication.119 Reward-based incentive programme.143 Self-esteem coaching.*142 Telemedicine DOPT.127

*Evaluated in comparative effectiveness studies.
DOPT, directly observed preventive treatment; HIC, high-income country; IGRA, interferon gamma release assay; LMIC, low-income and middle-income country; MDR, multidrug resistant; TB, tuberculosis; TST, tuberculin skin test.