Initiation and completion of treatment for latent tuberculosis infection in migrants globally: A systematic review and meta-analysis

Summary Background Latent Tuberculosis (LTBI) is one of the most prevalent infections globally and is key in development of active tuberculosis disease (TB). In many low-burden countries, LTBI is concentrated within migrant populations reflecting higher disease burden in some countries of origin; national programmes may consequently focus on screening and treating LTBI in migrants to prevent future TB cases. However, little is known about the extent to which migrants initiate treatment for LTBI when testing positive, and their treatment outcomes, which is urgently needed if we are to strengthen these programmes, improve migrant health, and meet TB elimination targets. Methods We did a systematic review and meta-analysis, following PRISMA guidelines and PROSPERO registered (CRD42019140338) to pool global data on LTBI initiation and completion amongst migrants (defined as foreign born), and secondary outcomes to explore the range of both personal and provider level factors associated with initiation and completion. We searched Embase, Medline and Global Health, and hand-searched grey literature (from Jan 1 2000 to Apr 21 2020). Inclusion criteria were primary research articles reporting on LTBI treatment initiation and/or completion amongst migrants; we excluded papers where data were not stratified by migrant status, or where the data related to outcomes prior to the year 2000. There were no geographical or language restrictions. Results 39 publications were included from 13 countries, with treatment initiation and completion data for 31,598 LTBI positive migrants. Overall, 69% (95% CI⍰=⍰51–84%; I 2 ⍰=⍰99.62%) of these initiated treatment; 74% (95% CI⍰=⍰66–81%; I 2 ⍰=⍰99.19%) of migrants who initiated treatment, completed it; among studies with data on the complete pathway from screening positive to completing treatment, 52% (95% CI⍰=⍰40–64%; I 2 ⍰=⍰98.90%) successfully completed treatment. Meta-regression showed that LTBI programmes are improving, with more recent reported data (2010-2020) associated with better rates of treatment initiation and completion. European studies also appeared to have more successful outcomes than those in the Americas and Western Pacific WHO regions. Conclusions LTBI treatment initiation and completion amongst migrants have room for improvement. Though the data show improvements in the past decade, the delivery of these programmes will need further strengthening if we are to meet targets to eradicate TB in low-incidence countries. Greater focus will need to be placed on engaging migrants more effectively in the clinic and understanding the diverse barriers and facilitators to migrants initiating and completing treatment. Such efforts must be mindful of, and sensitive to the unique experiences individuals arriving in a new country. Funding This study was funded by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) through a joint ESCMID Study Group for Infections in Travellers and Migrants (ESGITM) and ESCMID Study Group for Mycobacterial Infections (ESGMYC) Study Group Research grant, the Rosetrees Trust (PhD studentship grant M775), the NIHR (NIHR Advanced Fellowship NIHR300072), and the Academy of Medical Sciences (SBF005\1111). Panel: Research in Context Evidence before this study Latent tuberculosis infection (LTBI) is one of the most prevalent infections globally, affecting an estimated 25% of the population; re-activation of LTBI is a major driver of tuberculosis (TB) cases worldwide. In low-incidence TB countries, TB and LTBI are often disproportionately concentrated amongst foreign born individuals, with national programmes increasingly focusing on the diagnosis and treatment of LTBI in migrants and other high-risk groups to prevent future TB cases and meet global elimination targets. However, little is known about the success of these programmes in engaging migrants and ensuring treatment completion – a population who often face multiple barriers to accessing health care on arrival to the host country. Prior to this review we scoped the literature and found two relevant reviews on this topic (Sandgren et al., 2016 & Alsdurf et al., 2016) but which did not specifically focus on migrants and/or lacked formal meta-analyses, and one/both used earlier data pre 2000 that may be less relevant now to current policy. Other studies have reported on migrant-specific outcomes in LTBI programmes globally, but the focus is often on screening practices rather than outcomes and all evidence in this area has not yet been effectively consolidated. Added value of this study This is the first systematic review and meta-analysis specifically exploring LTBI treatment initiation and completion among migrant populations. We report LTBI treatment outcome data on 31,598 migrants from the year 2000 onwards within 13 low-incidence countries (<10 cases per 100,000). The research provides robust insights into the proportion of individuals initiating and completing treatment, using meta-regression to explore heterogeneity. The data show that between 2000-2020, 69% of migrants testing positive for LTBI initiated treatment, and of those starting treatment, approximately 74% completed it. Amongst studies capturing data on both initiation and completion, 52% of LTBI positive migrants successfully initiated and completed. The data also indicate higher initiation and completion in more recent years (2010-2020) with renewed focus on this approach to TB control, and a trend toward more positive outcomes amongst migrants in programmes in the WHO European region. The data show that multiple complex factors impact on treatment outcomes in migrants, including patient demographics and health systems. The evidence was ambivalent with some studies demonstrating positive and detrimental outcomes associated with foreign-born status. Implications of all the available evidence Delivery of LTBI programmes will need to be strengthened to improve outcomes in migrants and meet targets to eradicate TB in low-incidence countries. Greater focus will need to be placed on engaging migrants more effectively in the clinic, understanding the varied reasons for migrants’ declining treatment when testing positive, and ensuring treatment adherence using innovative approaches that are mindful of and sensitive to the unique experiences of this group on arrival to the host country.

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