Recurrent tuberculosis in the Netherlands - a 24-year follow-up study, 1993 to 2016.

BackgroundNot all treated tuberculosis (TB) patients achieve long-term recovery and reactivation rates reflect effectiveness of TB treatment.AimWe aimed to estimate rates and risk factors of TB reactivation and reinfection in patients treated in the Netherlands, after completed or interrupted treatment.MethodsRetrospective 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.ResultsReactivation 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.ConclusionsBoth 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.

High Incidence of Active Tuberculosis in Asylum Seekers from Eritrea and Somalia in the First 5 Years after Arrival in the Netherlands.

Three quarters of tuberculosis (TB) patients in the Netherlands are foreign-born; 26% are from Eritrea or Somalia. We analyzed TB incidence rates in asylum seekers from Eritrea and Somalia in the first 5 years after arrival in the Netherlands (2013-2017) and performed survival analysis with Cox proportional hazards regression to analyze the effect of age and sex on the risk for TB. TB incidence remained high 5 years after arrival in asylum seekers from Eritrea (309 cases/100,000 person-years) and Somalia (81 cases/100,000 person-years). Age >18 years was associated with a higher risk for TB in asylum seekers from Eritrea (3.4 times higher) and Somalia (3.7 times higher), and male sex was associated with a 1.6 times higher risk for TB in asylum seekers from Eritrea. Screening and treating asylum seekers from high-incidence areas for latent TB infection upon arrival would further reduce TB incidence in the Netherlands.

Completeness of tuberculosis (TB) notification: inventory studies and capture-recapture analyses, six European Union countries, 2014 to 2016.

BackgroundProgress towards the World Health Organization's End TB Strategy is monitored by assessing tuberculosis (TB) incidence, often derived from TB notification, assuming complete case detection and reporting. This assumption is unlikely to hold in many settings, including European Union (EU) countries.AimWe aimed to assess observed and estimated completeness of TB notification through inventory studies and capture-recapture (CRC) methodology in six EU countries: Croatia, Denmark, Finland, the Netherlands, Portugal Slovenia.MethodsWe performed record linkage, case ascertainment and CRC analyses of data collected retrospectively from at least three national TB-related registers in each country between 2014 and 2016.ResultsObserved completeness of TB notification by inventory studies was 73.9% in Croatia, 98.7% in Denmark, 83.6% in Finland, 81.6% in the Netherlands, 85.8% in Portugal and 100% in Slovenia. Subsequent CRC analysis estimated completeness of TB notification to be 98.4% in Denmark, 76.5% in Finland and 77.0% in Portugal. In Croatia, CRC analyses produced implausible results while in the Netherlands and Slovenia, it was methodologically considered not meaningful.ConclusionInventory studies and CRC methodology suggest a TB notification completeness between 73.9% and 100% in the six EU countries. Mandatory reporting by clinicians and laboratories, and cross-checking of registers, strongly contributes to accurate notification rates, but hospital episode registers likely contain a considerable proportion of false-positive TB records and are thus less useful. Further strengthening routine surveillance to count TB cases, i.e. incidence, accurately by employing record-linkage of high-quality TB registers should make CRC studies obsolete in EU countries.

Monitoring latent tuberculosis infection diagnosis and management in the Netherlands.

Targeted diagnosis and treatment of latent tuberculosis (TB) infection (LTBI) among persons with a high risk of exposure to TB or of developing TB when infected has been performed and monitored routinely in the Netherlands since 1993. We describe trends in target groups, diagnostic methods and treatment regimens, and explore determinants for treatment initiation, treatment completion and adverse events.In total, 37 729 persons were registered with LTBI from 1993 to 2013, of whom 28 931 (77%) started preventive treatment; 82% of those completed preventive treatment and 8% stopped preventive treatment due to adverse events. Two-thirds of the notified cases were detected through contact investigation.Increasing numbers of persons with immunosuppressive disorders, elderly persons and foreign-born persons were notified in recent years, due to policy changes and the introduction of the interferon-γ release assay. Children (96%) and the immunosuppressed (95%) were more likely to start preventive treatment. Children (93%) were also more likely to complete preventive treatment, as were persons treated with rifampicin or rifampicin/isoniazid regimens (91% and 92%, respectively). The latter groups were also 40% less likely to stop preventive treatment due to adverse events.Under these operational conditions, the estimated risk reduction on incident TB in the target population for LTBI management is 40-60%.

Risk of developing tuberculosis disease among persons diagnosed with latent tuberculosis infection in the Netherlands.

Diagnosis and preventive treatment of latent tuberculosis infection (LTBI) among high-risk groups is recommended to achieve tuberculosis (TB) elimination in low-incidence countries.We studied TB incidence rates among those notified with LTBI in the Netherlands from 2005 to 2013 and analysed associated risk factors. We stratified analyses by target group for screening, and by initiation and completion of preventive treatment.The incidence for those completing, stopping and not receiving preventive treatment was 187, 436 and 355 per 100 000 person-years for contacts of TB patients, respectively, and 63, 96 and 110 per 100 000 person-years for other target groups. The rate ratio for TB development among contacts compared to other target groups was 3.1 (95% CI 2.0-4.9). In both groups, incidence was highest in the first year after diagnosis. Independent factors associated with progression to TB among contacts were age <5 years and stopping preventive treatment within 28 days compared to those not receiving preventive treatment. Among other target groups, being foreign born was the only risk factor associated with the risk of developing TB.We conclude that the epidemiological impact of preventive treatment is highest in contacts of TB patients and limited in other target groups for LTBI management in the Netherlands.

Epidemiological links between tuberculosis cases identified twice as efficiently by whole genome sequencing than conventional molecular typing: A population-based study.

BACKGROUND: Patients with Mycobacterium tuberculosis isolates sharing identical DNA fingerprint patterns can be epidemiologically linked. However, municipal health services in the Netherlands are able to confirm an epidemiological link in only around 23% of the patients with isolates clustered by the conventional variable number of tandem repeat (VNTR) genotyping. This research aims to investigate whether whole genome sequencing (WGS) is a more reliable predictor of epidemiological links between tuberculosis patients than VNTR genotyping. METHODS: VNTR genotyping and WGS were performed in parallel on all Mycobacterium tuberculosis complex isolates received at the Netherlands National Institute for Public Health and the Environment in 2016. Isolates were clustered by VNTR when they shared identical 24-loci VNTR patterns; isolates were assigned to a WGS cluster when the pair-wise genetic distance was ≤ 12 single nucleotide polymorphisms (SNPs). Cluster investigation was performed by municipal health services on all isolates clustered by VNTR in 2016. The proportion of epidemiological links identified among patients clustered by either method was calculated. RESULTS: In total, 535 isolates were genotyped, of which 25% (134/535) were clustered by VNTR and 14% (76/535) by WGS; the concordance between both typing methods was 86%. The proportion of epidemiological links among WGS clustered cases (57%) was twice as common than among VNTR clustered cases (31%). CONCLUSION: When WGS was applied, the number of clustered isolates was halved, while all epidemiologically linked cases remained clustered. WGS is therefore a more reliable tool to predict epidemiological links between tuberculosis cases than VNTR genotyping and will allow more efficient transmission tracing, as epidemiological investigations based on false clustering can be avoided.

Correction: Epidemiological links between tuberculosis cases identified twice as efficiently by whole genome sequencing than conventional molecular typing: A population-based study.

[This corrects the article DOI: 10.1371/journal.pone.0195413.].

[Tuberculosis among asylum-seekers in the Netherlands: a descriptive study among the two largest groups of asylum-seekers]. / Tuberculose bij asielzoekers in Nederland: descriptief onderzoek onder de 2 grootste groepen asielzoekers.

OBJECTIVE: To investigate the prevalence and incidence of tuberculosis (TB) among the two largest groups of asylum-seekers in the Netherlands, i.e. Syrians and Eritreans/Ethiopians. DESIGN: Descriptive study. METHOD: We collected data from the screening of Syrian and Eritrean/Ethiopian asylum-seekers for the period January 2013 - September 2015 and linked these to notifications in the Netherlands Tuberculosis Register. RESULTS: Asylum-seekers from Syria and Eritrea/Ethiopia represented 65% and 72% of all asylum applications in 2014 and in the first nine months of 2015 respectively. Fourteen Syrian asylum-seekers applying during the study period were diagnosed with tuberculosis. The prevalence was 22 cases per 100,000 persons screened upon arrival (95% CI: 10-44), while the incidence within the first year after arrival was 19 per 100,000 persons (95% CI: 3-62). Tuberculosis was diagnosed in 133 Eritrean/Ethiopian asylum-seekers applying during the study period. The prevalence was 283 cases per 100,000 persons screened upon arrival (95% CI: 198-393) and the incidence in the first year after arrival was 1394 per 100,000 persons (95% CI: 1095-1751). CONCLUSION: In the last two years, most asylum-seekers have originated from Syria and among them tuberculosis is relatively uncommon. However, among Eritrean/Ethiopian asylum-seekers, prevalence and incidence in the first year in the Netherlands are high. This suggests that many of them have been recently infected, in their country of origin or during the journey. Other interventions are required, such as screening for latent infection, to prevent tuberculosis among high-risk asylum-seekers and further reduce the incidence of this disease in the Netherlands.

TB-HIV co-infection in the Netherlands: estimating prevalence and under-reporting in national registration databases using a capture-recapture analysis.

BACKGROUND: Knowledge of the HIV status in patients with tuberculosis (TB) and vice versa is crucial for proper individual patient management, while knowledge of the prevalence of co-infection guides preventive and therapeutic strategies. The aim of the study was to assess if national disease databases on TB and HIV are adequate sources to provide this information. METHODS: A two way capture-recapture analysis to assess the completeness of the registers, and to obtain the prevalence of TB-HIV co-infection in the Netherlands in the years 2002-2012. RESULTS: HIV testing was performed in less than 50% of the patients with TB. Of the 932 TB-HIV infected patients, just 293 (31.4%) were registered in both registers. Under-reporting of TB-HIV co-infection ranged from 50% to 70% in the national TB register, and from 31% to 37% in the HIV database. Prevalence of TB-HIV co-infection in the Netherlands in 2012 was 7.1% (95% CI 6.0% to 8.3%), which was more than double of the prevalence estimated from the national TB database. CONCLUSIONS: TB-HIV co-infection is markedly under-reported in national disease databases. There is an urgent need for improved registration and preferably a routine data exchange between the two surveillance systems.