key: cord-0030780-d9singck authors: Berrocal-Almanza, Luis C; Harris, Ross J; Collin, Simon M; Muzyamba, Morris C; Conroy, Olivia D; Mirza, Adil; O'Connell, Anne-Marie; Altass, Lynn; Anderson, Sarah R; Thomas, H Lucy; Campbell, Colin; Zenner, Dominik; Phin, Nick; Kon, Onn Min; Smith, E Grace; Lalvani, Ajit title: Effectiveness of nationwide programmatic testing and treatment for latent tuberculosis infection in migrants in England: a retrospective, population-based cohort study date: 2022-03-23 journal: Lancet Public Health DOI: 10.1016/s2468-2667(22)00031-7 sha: a12bfaeacacf2bba9c0ad33bf6a44dd67ade94ae doc_id: 30780 cord_uid: d9singck BACKGROUND: In low-incidence countries, tuberculosis mainly affects migrants, mostly resulting from reactivation of latent tuberculosis infection (LTBI) acquired in high-incidence countries before migration. A nationwide primary care-based LTBI testing and treatment programme for migrants from high-incidence countries was therefore established in high tuberculosis incidence areas in England. We aimed to assess the effectiveness of this programme. METHODS: We did a retrospective, population-based cohort study of migrants who registered in primary care between Jan 1, 2011, and Dec 31, 2018, in 55 high-burden areas with programmatic LTBI testing and treatment. Eligible individuals were aged 16–35 years, born in a high-incidence country, and had entered England in the past 5 years. Individuals who tested interferon-γ release assay (IGRA)-negative were advised about symptoms of tuberculosis, whereas those who tested IGRA-positive were clinically assessed to rule out active tuberculosis and offered preventive therapy. The primary outcome was incident tuberculosis notified to the national Enhanced Tuberculosis Surveillance system. FINDINGS: Our cohort comprised 368 097 eligible individuals who had registered in primary care, of whom 37 268 (10·1%) were tested by the programme. 1446 incident cases of tuberculosis were identified: 166 cases in individuals who had IGRA testing (incidence 204 cases [95% CI 176–238] per 100 000 person-years) and 1280 in individuals without IGRA testing (82 cases [77–86] per 100 000 person-years). Overall, in our primary analysis including all diagnosed tuberculosis cases, a time-varying association was identified between LTBI testing and treatment and lower risk of incident tuberculosis (hazard ratio [HR] 0·76 [95% CI 0·63–0·91]) when compared with no testing. In stratified analysis by follow-up period, the intervention was associated with higher risk of tuberculosis diagnosis during the first 6 months of follow-up (9·93 [7·63–12·9) and a lower risk after 6 months (0·57 [0·41–0·79]). IGRA-positive individuals had higher risk of tuberculosis diagnosis than IGRA-negative individuals (31·9 [20·4–49·8]). Of 37 268 migrants who were tested, 6640 (17·8%) were IGRA-positive, of whom 1740 (26·2%) started preventive treatment. LTBI treatment lowered the risk of tuberculosis: of 135 incident cases in the IGRA-positive cohort, seven cases were diagnosed in the treated group (1·87 cases [95% CI 0·89–3·93] per 1000 person-years) and 128 cases were diagnosed in the untreated group (10·9 cases [9·16–12·9] per 1000 person-years; HR 0·14 [95% CI 0·06–0·32]). INTERPRETATION: A low proportion of eligible migrants were tested by the programme and a small proportion of those testing positive started treatment. Despite this, programmatic LTBI testing and treatment of individuals migrating to a low-incidence region is effective at diagnosing active tuberculosis earlier and lowers the long-term risk of progression to tuberculosis. Increasing programme participation and treatment rates for those testing positive could substantially impact national tuberculosis incidence. FUNDING: National Institute for Health Research Health Protection Research Unit in Respiratory Infections. Marginal effects of effect modification 9 Table S1 Country and region of origin of evaluation participants 11 Table S2 Percentage of missing information, variables and models used for multiple imputation 12 Table S20 Treatment regime and adverse reactions 29 used for probabilistic record linkage were first and last name, date of birth, sex and NHS number. A matching threshold was calculated and one author (LCBA) performed a manual review of records with a matching score of 67 10 above and below the matching threshold. In a separate multivariate model, we explored area-level variation using a three-level mixed-effects parametric 80 survival-time model with CCG and general practice level random intercepts; for this analysis, we assumed a Log Normal conditional distribution of the response given the random effects based on its lowest Akaike's information 82 criterion when compared with Weibull and Log Logistic distributions. We did sensitivity analyses to account for the imputation method using complete case analysis, and for treatment 85 completion using only participants with confirmed date of treatment completion. We used a multiple imputation by chained equations (MICE) model to impute missing values, while accounting 89 for the uncertainty in missing information. 8 The creation and analysis of 5 imputed datasets is described in this 90 section. The country of origin for some individuals who had programmatic LTBI testing was not captured from the data 93 returned to the UKHSA for programme monitoring and evaluation. 0·13; 95% CI 0·03 to 0·55) and imputed analysis (HR 0·08; 95% CI 0·02 to 0·26) respectively as shown in supplementary tables S14 and S15. The effectiveness of treatment was lower in the sensitivity analysis when TB cases diagnosed within 60 and 90 198 days of primary care registration or LTBI testing were excluded. We first performed the analysis using the 199 complete dataset of cases without missing data, this analysis yielded effectiveness of 83% (HR 0·17; 95%CI 0·04- 0·77) and 79% (HR 0·21; 95%CI 0·04-0·95) for 60 and 90 days respectively (tables supplementary tables S16 201 and S17). The parameter estimates of this analysis were used to derive the adjusted numbers needed to treat, these 202 were 33·7 (95%CI 19-48·4) and 34·8 (95%CI 19·8-49·8) for 60 and 90 days respectively (tables supplementary 203 tables S16 and S17). Next, we carried out the analysis with the dataset in which all missing values were imputed, the effectiveness of treatment of 77% (HR 0·23; 95% CI 0·09 -0·57) and 75% (HR 0·25; 95% CI 0·09 -0·67) for 60 and 90 days respectively supplementary tables S18 and S19. Thus, although there was variation in treatment 206 effectiveness when these cases were excluded, it did not affect much the adjusted number needed to treat. The reason for this is that the latter value was derived using the parameter estimates of the complete case analysis 1·99 (0·75-5·33) 0·165 1·24 (0·40-3·82) 0·699 2·01 (0·66-6·11) 0·214 Latent TB testing and treatment for 412 migrants: a practical guide for commissioners and practitioners Public Health England (PHE). Guidance for epidemiological 416 surveillance to control tuberculosis (TB) and to identify cases for 417 cohort review 420 3. NHS Digital. Primary Care registrations The effectiveness of primary care 423 based risk stratification for targeted latent tuberculosis infection screening in recent immigrants to 424 the UK: a retrospective cohort study Accuracy of Probabilistic Linkage Using the 429 Enhanced Matching System for Public Health and Epidemiological Studies Effectiveness of pre-entry active tuberculosis 431 and post-entry latent tuberculosis screening in new entrants to the UK: a retrospective, population-432 based cohort study StataCorp LLC