Tuberculosis (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.

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.