Tuberculosis (TB)

European-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.

We aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.

The Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries of origin.

Data on 9,116 foreign-born TB patients in 30 countries of residence were collected. Main countries of origin were Eritrea, India, Pakistan, Morocco, Romania and Somalia. Tuberculosis IRs were highest in patients of Eritrean and Somali origin in Greece and Malta (both > 1,000/100,000) and lowest among Ukrainian patients in Poland (3.6/100,000). They were mainly lower in countries of residence than countries of origin. However, IRs among Eritreans and Somalis in Greece and Malta were five times higher than in Eritrea and Somalia. Similarly, IRs among Eritreans in Germany, the Netherlands and the UK were four times higher than in Eritrea.

Country of origin TB IR is an insufficient indicator when targeting foreign-born populations for active case finding or TB prevention policies in the countries covered here. Elimination strategies should be informed by regularly collected country-specific data to address rapidly changing epidemiology and associated risks.

Migrants in low tuberculosis (TB) incidence countries in the European Union (EU)/European Economic Area (EEA) are an at-risk group for latent tuberculosis infection (LTBI) and are increasingly included in LTBI screening programmes.

To investigate current approaches and implement LTBI screening in recently arrived migrants in the EU/EEA and Switzerland.

At least one TB expert working at a national level from the EU/EEA and one TB expert from Switzerland completed an electronic questionnaire. We used descriptive analyses to calculate percentages, and framework analysis to synthesise free-text responses.

Experts from 32 countries were invited to participate (30 countries responded): 15 experts reported an LTBI screening programme targeting migrants in their country; five reported plans to implement one in the near future; and 10 reported having no programme. LTBI screening was predominantly for asylum seekers (n = 12) and refugees (n = 11). Twelve countries use ‘country of origin’ as the main eligibility criteria. The countries took similar approaches to diagnosis and treatment but different approaches to follow-up. Six experts reported that drop-out rates in migrants were higher compared with non-migrant groups. Most of the experts (n = 22) called for a renewed focus on expanding efforts to screen for LTBI in migrants arriving in low-incidence countries.

We found a range of approaches to LTBI screening of migrants in the EU/EEA and Switzerland. Findings suggest a renewed focus is needed to expand and strengthen efforts to meaningfully include migrants in these programmes, in order to meet regional and global elimination targets for TB.

Not all treated tuberculosis (TB) patients achieve long-term recovery and reactivation rates reflect effectiveness of TB treatment.

We aimed to estimate rates and risk factors of TB reactivation and reinfection in patients treated in the Netherlands, after completed or interrupted treatment.

Retrospective cohort study of TB patients with available DNA fingerprint data, registered in the Netherlands Tuberculosis register (NTR) between 1993 and 2016. Reactivation was defined as an identical, and reinfection as a non-identical Mycobacterium tuberculosis strain in sequential episodes.

Reactivation rate was 55/100,000 person-years (py) for patients who completed, and 318/100,000 py for patients who interrupted treatment. The risk of reactivation was highest in the first 5 years after treatment in both groups. The incidence rate of reactivation was 228/100,000 py in the first 2 years and 57/100,000 py 2–5 years after completed treatment. The overall rate of reinfection was 16/100,000 py. Among those who completed treatment, patients with male sex, mono or poly rifampicin-resistant TB and a previous TB episode had significantly higher risk of reactivation. Extrapulmonary TB was associated with a lower risk. Among patients who interrupted treatment, directly observed treatment (DOT) and being an undocumented migrant or people experiencing homelessness were associated with a higher risk of reactivation.

Both patients who completed or interrupted TB treatment should be considered as risk groups for reactivation for at least 2–5 years after treatment. They patients should be monitored and guidelines should be in place to enhance early detection of recurrent TB.

In low tuberculosis (TB) incidence countries, contact investigation (CI) requires not missing contacts with TB infection or disease without unnecessarily evaluating non-infected contacts.

We assessed whether updated guidelines for the stone-in-the-pond principle and their promotion improved CI practices.

This retrospective study used surveillance data to compare CI outcomes before (2011–2013) and after (2014–2016) the guideline update and promotion. Using negative binomial regression and logistic regression models, we compared the number of contacts invited for CI per index patient, the number of CI scaled-up according to the stone-in-the-pond principle, the TB and latent TB infection (LTBI) testing coverage, and yield.

Pre and post update, 1,703 and 1,489 index patients were reported, 27,187 and 21,056 contacts were eligible for CI, 86% and 89% were tested for TB, and 0.70% and 0.73% were identified with active TB, respectively. Post update, the number of casual contacts invited per index patient decreased statistically significantly (RR = 0.88; 95% CI: 0.79–0.98), TB testing coverage increased (OR = 1.4; 95% CI: 1.2–1.7), and TB yield increased (OR = 2.0; 95% CI: 1.0–3.9). The total LTBI yield increased from 8.8% to 9.8%, with statistically significant increases for casual (OR = 1.2; 95% CI: 1.0–1.5) and community contacts (OR = 2.0; 95% CI: 1.6–3.2). The proportion of CIs appropriately scaled-up to community contacts increased statistically significantly (RR = 1.8; 95% CI: 1.3–2.6).

This study shows that promoting evidence-based CI guidelines strengthen the efficiency of CIs without jeopardising effectiveness. These findings support CI is an effective TB elimination intervention.

Essential health services, including for tuberculosis (TB), are being affected by public health and social measures (PHSM) introduced to control COVID-19. In many settings, TB resources, facilities and equipment are being redirected towards COVID-19 response.

We sought to assess the COVID-19 pandemic’s impact on TB services in the World Health Organization (WHO) European Region.

The fifty-three European Region Member States were asked to report qualitative and quantitative data in quarter one and two (Q1 and Q2) 2020. TB notifications were triangulated with the severity score on domestic movement restrictions to assess how they may have influenced TB detection.

Twenty-nine countries reported monthly TB notifications for the first half of 2019 and 2020. TB notifications decreased by 35.5% during Q2 2020 compared with Q2 2019, which is six-fold more than the average annual decrease of 5.1% documented during 2015–2019. The number of patients enrolled in rifampicin-resistant/multidrug-resistant TB treatment also decreased dramatically in Q2 2020, by 33.5%. The highest movement restriction severity score was observed between April and May 2020, which coincided with the highest observed decrease in TB notifications.

A decrease in TB detection and enrolment to treatment may cause increases in TB burden and threatens the Region’s ability to reach the TB targets of the 2030 Sustainable Development Goals, still this might be mitigated with rapid restoration of TB services and the implementation of targeted interventions during periods with severe PHSM in place, such as those introduced in response to the COVID-19 pandemic.

In 2006, the Bacillus Calmette–Guérin (BCG) vaccination policy in Finland changed from universal to selective.

We assessed the impact of the policy change on tuberculosis (TB) morbidity in children under 5 years and epidemiological trends of paediatric TB in Finland.

We conducted a nationwide, population-based, retrospective registry study of all newly diagnosed active TB cases younger than 15 years in Finland from 1995 to 2015 by linking data from the National Infectious Diseases Register, Finnish Care Register for Health Care, medical patient records and Finnish Population Information System. We compared the TB incidence rate ratio of under 5 year-olds with universal and selective BCG vaccinations with a Poisson log-linear model and analysed incidence trends among those younger than 15 years with a negative binomial model.

We identified 139 paediatric TB cases: 50 native (including 24 second-generation migrants) and 89 foreign-born children. The TB rate of under 5 year-olds remained stable after changing to selective BCG vaccination (incidence rate ratio (IRR): 1.3; 95% confidence interval (CI): 0.7–2.3). TB rate in the native population under 15 years increased slightly (IRR = 1.06; 95% CI: 1.01–1.11).

Paediatric TB cases in Finland were concentrated in families with migrant background from high-TB incidence countries. The native TB morbidity in under 5-year-olds did not increase after the BCG policy revision, suggesting that selective vaccinations can prevent TB in the most vulnerable age group in low-incidence settings. Second-generation migrants under 15 years in Finland with high TB risk are probably increasing.

Improving the surveillance of tuberculosis (TB) is especially important for multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. The large amount of publicly available whole genome sequencing (WGS) data for TB gives us the chance to re-use data and to perform additional analyses at a large scale.

We assessed the usefulness of raw WGS data of global MDR/XDR Mycobacterium tuberculosis isolates available from public repositories to improve TB surveillance.

We extracted raw WGS data and the related metadata of M. tuberculosis isolates available from the Sequence Read Archive. We compared this public dataset with WGS data and metadata of 131 MDR- and XDR M. tuberculosis isolates from Germany in 2012 and 2013.

We aggregated a dataset that included 1,081 MDR and 250 XDR isolates among which we identified 133 molecular clusters. In 16 clusters, the isolates were from at least two different countries. For example, Cluster 2 included 56 MDR/XDR isolates from Moldova, Georgia and Germany. When comparing the WGS data from Germany with the public dataset, we found that 11 clusters contained at least one isolate from Germany and at least one isolate from another country. We could, therefore, connect TB cases despite missing epidemiological information.

We demonstrated the added value of using WGS raw data from public repositories to contribute to TB surveillance. Comparing the German with the public dataset, we identified potential international transmission events. Thus, using this approach might support the interpretation of national surveillance results in an international context.

Surveillance of tuberculosis (TB) treatment outcome, for which reporting has been mandatory in France since 2007, is a key component of TB control.

We aimed to present surveillance data for non-multidrug-resistant (MDR) cases reported between 2008 and 2014, and identify factors associated with potentially unfavourable treatment outcome.

Patients were classified according to their treatment outcome 12 months after beginning treatment. Poisson regression with a robust error variance was used to investigate factors associated with potentially unfavourable treatment outcome. Missing data were handled using multiple imputation.

A total of 22,526 cases were analysed for treatment outcome. Information available on treatment outcome increased between 2008 (60%) and 2014 (71%) (p < 0.001). During this period, 74.1% of cases completed treatment, increasing from 73.0% in 2008 to 76.9% in 2014 (p < 0.001). This proportion was 74.0% in culture-positive pulmonary cases. Overall, 19.8% of cases had a potentially unfavourable outcome, including lost-to-follow-up, transferred out, still on treatment, death related to TB and interrupted treatment. Potentially unfavourable outcome was significantly associated with TB severity, residing in congregate settings, homelessness, being a smear-positive pulmonary case, being born abroad and residing in France for < 2 years, history of previous anti-TB treatment and age > 85 years.

Monitoring of treatment outcome is improving over time. The increase in treatment completion over time suggests improved case management. However, treatment outcome monitoring needs to be strengthened in cases belonging to population groups where the percentage of unfavourable outcome is the highest and in cases where surveillance data shows poorer documented follow-up.

Whole genome sequencing (WGS) is a reliable tool for studying tuberculosis (TB) transmission. WGS data are usually processed by custom-built analysis pipelines with little standardisation between them.

To compare the impact of variability of several WGS analysis pipelines used internationally to detect epidemiologically linked TB cases.

From the Netherlands, 535 Mycobacterium tuberculosis complex (MTBC) strains from 2016 were included. Epidemiological information obtained from municipal health services was available for all mycobacterial interspersed repeat unit-variable number of tandem repeat (MIRU-VNTR) clustered cases. WGS data was analysed using five different pipelines: one core genome multilocus sequence typing (cgMLST) approach and four single nucleotide polymorphism (SNP)-based pipelines developed in Oxford, United Kingdom; Borstel, Germany; Bilthoven, the Netherlands and Copenhagen, Denmark. WGS clusters were defined using a maximum pairwise distance of 12 SNPs/alleles.

The cgMLST approach and Oxford pipeline clustered all epidemiologically linked cases, however, in the other three SNP-based pipelines one epidemiological link was missed due to insufficient coverage. In general, the genetic distances varied between pipelines, reflecting different clustering rates: the cgMLST approach clustered 92 cases, followed by 84, 83, 83 and 82 cases in the SNP-based pipelines from Copenhagen, Oxford, Borstel and Bilthoven respectively.

Concordance in ruling out epidemiological links was high between pipelines, which is an important step in the international validation of WGS data analysis. To increase accuracy in identifying TB transmission clusters, standardisation of crucial WGS criteria and creation of a reference database of representative MTBC sequences would be advisable.

Migrants account for the majority of tuberculosis (TB) cases in low-incidence countries in western Europe. TB incidence among migrants might be influenced by patterns of migration, but this is not well understood.

To investigate differences in TB risk across migrant groups according to migrant status and region of origin.

This prospective cohort study included migrants ≥ 18 years of age who obtained residency in Denmark between 1 January 1993 and 31 December 2015, matched 1:6 to Danish-born individuals. Migrants were grouped according to legal status of residency and region of origin. Incidence rates (IR) and incidence rate ratios (IRR) were estimated by Poisson regression.

The cohort included 142,314 migrants. Migrants had significantly higher TB incidence (IR: 120/100,000 person-years (PY); 95% confidence interval (CI): 115–126) than Danish-born individuals (IR: 4/100,000 PY; 95% CI: 3–4). The IRR was significantly higher in all migrant groups compared with Danish-born (p < 0.01). A particularly higher risk was seen among family-reunified to refugees (IRR: 61.8; 95% CI: 52.7–72.4), quota refugees (IRR: 46.0; 95% CI: 36.6–57.6) and former asylum seekers (IRR: 45.3; 95% CI: 40.2–51.1), whereas lower risk was seen among family-reunified to Danish/Nordic citizens (IRR 15.8; 95% CI: 13.6–18.4) and family-reunified to immigrants (IRR: 16.9; 95% CI: 13.5–21.3).

All migrants had higher TB risk compared with the Danish-born population. While screening programmes focus mostly on asylum seekers, other migrant groups with high risk of TB are missed. Awareness of TB risk in all high-risk groups should be strengthened and screening programmes should be optimised.

In 2007, a new federal legislation in Belgium prohibited non-biosafety level 3 laboratories to process culture tubes suspected of containing mycobacteria.

To present mycobacterial surveillance/diagnosis data from the Belgian National Reference Centre for mycobacteria (NRC) from 2007 to 2016.

This retrospective observational study investigated the numbers of analyses at the NRC and false positive cultures (interpreted as containing mycobacteria at referring clinical laboratories, but with no mycobacterial DNA detected by PCR in the NRC). We reviewed mycobacterial species identified and assessed trends over time of proportions of nontuberculous mycobacteria (NTM) vs Mycobacterium tuberculosis complex (MTBc), and false positive cultures vs NTM.

From 2007 to 2016, analyses requests to the NRC doubled from 12.6 to 25.3 per 100,000 inhabitants. A small but significant increase occurred in NTM vs MTBc proportions, from 57.9% (587/1,014) to 60.3% (867/1,437) (p < 0.001). Although NTM infection notification is not mandatory in Belgium, we annually received up to 8.6 NTM per 100,000 inhabitants. M. avium predominated (ca 20% of NTM cultures), but M. intracellulare culture numbers rose significantly, from 13.0% (74/587) of NTM cultures in 2007 to 21.0% (178/867) in 2016 (RR: 1.05; 95% CI: 1.03–1.07). The number of false positive cultures also increased, reaching 43.3% (1,097/2,534) of all samples in 2016.

We recommend inclusion of NTM in sentinel programmes. The large increase of false positive cultures is hypothesised to result from processing issues prior to arrival at the NRC, highlighting the importance of sample decontamination/transport and equipment calibration in peripheral laboratories.

Management of health issues presented by newly arrived migrants is often limited to communicable diseases even though other health issues may be more prevalent. We report the results of infectious disease screening proposed to 462 recently-arrived asylum seekers over 14 years of age in Verona province between April 2014 and June 2015. Methods: Screening for latent tuberculosis (TB) was performed via tuberculin skin test (TST) and/or QuantiFERON-TB Gold in-tube assay and/or chest X-ray. An ELISA was used to screen for syphilis. Stool microscopy was used to screen for helminthic infections, and serology was also used for strongyloidiasis and schistosomiasis. Screening for the latter also included urine filtration and microscopy. Results: Most individuals came from sub-Saharan Africa (77.5%), with others coming from Asia (21.0%) and North Africa (1.5%). The prevalence of viral diseases/markers of human immunodeficiency virus (HIV) infection was 1.3%, HCV infection was 0.85% and hepatitis B virus surface antigen was 11.6%. Serological tests for syphilis were positive in 3.7% of individuals. Of 125 individuals screened for TB via the TST, 44.8% were positive and of 118 screened via the assay, 44.0% were positive. Of 458 individuals tested for strongyloidiasis, 91 (19.9%) were positive, and 76 of 358 (21.2%) individuals from sub-Saharan Africa were positive for schistosomiasis. Conclusions: The screening of viral diseases is questionable because of low prevalence and/or long-term, expensive treatments. For opposing reasons, helminthic infections are probably worth to be targeted by screening strategies in asylum seekers of selected countries of origin.

In Germany, the incidence of tuberculosis (TB) in children has been on the rise since 2009. High numbers of foreign-born asylum seekers have contributed considerably to the disease burden. Therefore, effective screening strategies for latent TB infection (LTBI) and active TB in asylum seeking children are needed. Aim: Our aim was to investigate the prevalence of LTBI and active TB in asylum seeking children up to 15 years of age in two geographic regions in Germany. Methods: Screening for TB was performed in children in asylum seeker reception centres by tuberculin skin test (TST) or interferon gamma release assay (IGRA). Children with positive results were evaluated for active TB. Additionally, country of origin, sex, travel time, TB symptoms, TB contact and Bacille Calmette-Guérin (BCG) vaccination status were registered. Results: Of 968 screened children 66 (6.8%) had TB infection (58 LTBI, 8 active TB). LTBI prevalence was similar in children from high (Afghanistan) and low (Syria) incidence countries (8.7% vs 6.4%). There were no differences regarding sex, age or travel time between infected and non-infected children. Children under the age of 6 years were at higher risk of progression to active TB (19% vs 2% respectively, p=0,07). Most children (7/8) with active TB were asymptomatic at the time of diagnosis. None of the children had been knowingly exposed to TB. Conclusions: Asylum seeking children from high and low incidence countries are both at risk of developing LTBI or active TB. Universal TB screening for all asylum seeking children should be considered.