G. de Vries

Dose dependent increased mortality risk in COPD patients treated with oral glucocorticoids

Systemic corticosteroids are often administered in COPD patients. The relationship between systemic glucocorticoids and mortality in patients with moderate to severe chronic obstructive pulmonary disease (COPD) was retrospectively analysed. Baseline characteristics of the patients, in stable clinical condition, were collected on admission to a pulmonary rehabilitation centre. Overall mortality was asessed at the end of follow-up. The Cox proportional hazards model was used to quantify the relationship between glucocorticoid use, distinguishing administration route (oral/inhalation) and oral dose, and overall mortality, adjusted for the influence of age, sex, smoking, lung function, resting arterial blood gases and body mass index. On multivariate analysis, oral glucocorticoid use at a (prednisone equivalent) dose of 10 mg x day(-1) without inhaled glucocorticoids, was associated with an increased risk (RR=2.34, 95% confidence interval (CI) 1.24-4.44) while 15 mg x day(-1) carried a relative risk of 4.03, CI = 1.99-8.15). A significant interaction was observed between inhaled and oral glucocorticoid use. Combined with inhaled glucocorticoids, the relative risk of oral glucocorticoid use appeared to be significantly smaller. It is concluded that in severe chronic obstructive pulmonary disease, maintenance treatment with oral glucocorticoids is associated with increased mortality in a dose-dependent manner. Since the present study design cannot exclude the possibility of bias by indication, further prospective studies are indicated using a broader patient characterization.

Tuberculosis screening in migrants in selected European countries shows wide disparities

Well-established tuberculosis screening units in Western Europe were selectively sampled. Three screening units in Norway, two in the UK, one in the Netherlands and one in Switzerland were evaluated. The aim of this study was to describe a range of service models used at a number of individual tuberculosis units for the screening of new entrants into Europe. Semi-structured interviews were conducted with clinicians, nurses and administrators from a selected sample of European tuberculosis screening units. An outline of key themes to be addressed was forwarded to units ahead of scheduled interviews. Themes included the history of the unit, structure, processes and outputs involved in screening new entrants for tuberculosis. Considerable variation in screening services exists in the approaches studied. Units are sited in transit camps or as units within hospital facilities. Staff capacity and administration varies from one clinic per week with few dedicated staff to fully dedicated units. Only one site recorded symptoms; tuberculin testing was universal in children, but varied in adults; chest radiograph screening was universal except at one site where a positive tuberculin skin test or symptoms were required in those <35u2005yrs of age before ordering a radiograph. Few output data are routinely and systematically collected, which hinders comparison and determination of effectiveness and efficiency. Service models for screening new immigrants for tuberculosis appear to vary in Western Europe. The systematic collection of data would make international comparisons between units easier and help draw conclusions that might usefully inform service development.

Comparative Study of IS6110 Restriction Fragment Length Polymorphism and Variable-Number Tandem-Repeat Typing of Mycobacterium tuberculosis Isolates in the Netherlands, Based on a 5-Year Nationwide Survey

ABSTRACT In order to switch from IS6110 and polymorphic GC-rich repetitive sequence (PGRS) restriction fragment length polymorphism (RFLP) to 24-locus variable-number tandem-repeat (VNTR) typing of Mycobacterium tuberculosis complex isolates in the national tuberculosis control program in The Netherlands, a detailed evaluation on discriminatory power and agreement with findings in a cluster investigation was performed on 3,975 tuberculosis cases during the period of 2004 to 2008. The level of discrimination of the two typing methods did not differ substantially: RFLP typing yielded 2,733 distinct patterns compared to 2,607 in VNTR typing. The global concordance, defined as isolates labeled unique or identically distributed in clusters by both methods, amounted to 78.5% (n = 3,123). Of the remaining 855 cases, 12% (n = 479) of the cases were clustered only by VNTR, 7.7% (n = 305) only by RFLP typing, and 1.8% (n = 71) revealed different cluster compositions in the two approaches. A cluster investigation was performed for 87% (n = 1,462) of the cases clustered by RFLP. For the 740 cases with confirmed or presumed epidemiological links, 92% were concordant with VNTR typing. In contrast, only 64% of the 722 cases without an epidemiological link but clustered by RFLP typing were also clustered by VNTR typing. We conclude that VNTR typing has a discriminatory power equal to IS6110 RFLP typing but is in better agreement with findings in a cluster investigation performed on an RFLP-clustering-based cluster investigation. Both aspects make VNTR typing a suitable method for tuberculosis surveillance systems.

Low-level rifampicin-resistant Mycobacterium tuberculosis strains raise a new therapeutic challenge.

In an outbreak of multidrug-resistant tuberculosis, the outbreak strain had an Asp516Tyr rpoB gene mutation. Phenotypically, low-level rifampicin (RMP) resistance (minimum inhibitory concentration [MIC] 1-2 mg/l) was observed. Based on drug susceptibility test results, three patients were treated with 12-15 month rifabutin-based regimens and one with a 12-month RMP-based regimen. We retrospectively performed pharmacokinetic calculations to assess the potential for RMP treatment, from which we conclude that MICs for RMP up to 1 μg/ml may be safely overcome by applying 20 mg/kg RMP doses in treatment regimens.

Tuberculosis control in big cities and urban risk groups in the European Union: a consensus statement

In low-incidence countries in the European Union (EU), tuberculosis (TB) is concentrated in big cities, especially among certain urban high-risk groups including immigrants from TB high-incidence countries, homeless people, and those with a history of drug and alcohol misuse. Elimination of TB in European big cities requires control measures focused on multiple layers of the urban population. The particular complexities of major EU metropolises, for example high population density and social structure, create specific opportunities for transmission, but also enable targeted TB control interventions, not efficient in the general population, to be effective or cost effective. Lessons can be learnt from across the EU and this consensus statement on TB control in big cities and urban risk groups was prepared by a working group representing various EU big cities, brought together on the initiative of the European Centre for Disease Prevention and Control. The consensus statement describes general and specific social, educational, operational, organisational, legal and monitoring TB control interventions in EU big cities, as well as providing recommendations for big city TB control, based upon a conceptual TB transmission and control model.

Completeness of notification of tuberculosis in The Netherlands: how reliable is record-linkage and capture–recapture analysis?

The aim of this study was to describe a systematic process of record-linkage, cross-validation, case-ascertainment and capture-recapture analysis to assess the quality of tuberculosis registers and to estimate the completeness of notification of incident tuberculosis cases in The Netherlands in 1998. After record-linkage and cross-validation 1499 tuberculosis patients were identified, of whom 1298 were notified, resulting in an observed under-notification of 13.4%. After adjustment for possible imperfect record-linkage and remaining false-positive hospital cases observed under-notification was 7.3%. Log-linear capture-recapture analysis initially estimated a total number of 2053 (95% CI 1871-2443) tuberculosis cases, resulting in an estimated under-notification of 36.8%. After adjustment for possible imperfect record-linkage and remaining false-positive hospital cases various capture-recapture models estimated under-notification at 13.6%. One of the reasons for the higher than expected estimated under-notification in a country with a well-organized system of tuberculosis control might be that some tuberculosis cases, e.g. extrapulmonary tuberculosis, are managed by clinicians less familiar with notification of infectious diseases. This study demonstrates the possible impact of violation of assumptions underlying capture-recapture analysis, especially the perfect record-linkage, perfect positive predictive value and absent three-way interaction assumptions.

Highly successful treatment outcome of multidrug-resistant tuberculosis in the Netherlands, 2000-2009

SETTINGnResistance to the two key anti-tuberculosis drugs isoniazid and rifampicin is a characteristic of multidrug-resistant tuberculosis (MDR-TB). MDR-TB is a scourge requiring toxic, prolonged treatment and is associated with poor outcomes. The Netherlands is a country with a long-standing, integrated, well-resourced TB service where all patients are offered culture-confirmed diagnosis by a central reference laboratory.nnnOBJECTIVEnTo assess the treatment outcomes of MDR-TB patients over a period of 10 years in The Netherlands.nnnDESIGNnDemographic, clinical and microbiological features of all patients with MDR-TB who started treatment in 2000-2009 in the Netherlands were analysed from national registry and patient records.nnnRESULTSnCharacteristics of the 113 MDR-TB patients were as follows: male/female ratio 1.57, 96% foreign born, median age 29 years, 96 (85%) pulmonary TB, 56 (50%) smear-positive, 14 (12%) human immunodeficiency virus (HIV) co-infected. Of the 104 (92%) patients who started MDR-TB treatment, 86% had a successful outcome using a median of six active drugs; eight underwent pulmonary surgery. HIV negativity was associated with successful outcome (adjusted OR 2.1, 95%CI 1.1-3.8).nnnCONCLUSIONnHigh success rates for MDR-TB treatment were achieved with close collaboration of all stakeholders, reaching the targets set for drug-susceptible TB. HIV remained an independent risk factor for unsuccessful treatment outcome.

Estimating the coverage of a targeted mobile tuberculosis screening programme among illicit drug users and homeless persons with truncated models

Truncated models are indirect methods to estimate the size of a hidden population which, in contrast to the capture-recapture method, can be used on a single information source. We estimated the coverage of a tuberculosis screening programme among illicit drug users and homeless persons with a mobile digital X-ray unit between 1 January 2003 and 31 December 2005 in Rotterdam, The Netherlands, using truncated models. The screening programme reached about two-third of the estimated target population at least once annually. The intended coverage (at least two chest X-rays per person per year) was about 23%. We conclude that simple truncated models can be used relatively easily on available single-source routine data to estimate the size of a population of illicit drug users and homeless persons. We assumed that the most likely overall bias in this study would be overestimation and therefore the coverage of the targeted mobile tuberculosis screening programme would be higher.

Transmission classification model to determine place and time of infection of tuberculosis cases in an urban area.

ABSTRACT We conducted a population-based study in the Rotterdam region of The Netherlands to determine the place and time of infection of tuberculosis (TB) cases using conventional epidemiological and genotyping information. In particular, we focused on the extent of misclassification if genotyping was not combined with epidemiological information. Cases were divided into those with a unique mycobacterial DNA fingerprint, a clustering fingerprint, and an unknown fingerprint. We developed transmission classification trees for each category to determine whether patients were infected in a foreign country or recently (≤2 years) or remotely (>2 years) infected in The Netherlands. Of all TB cases during the 12-year study period, 38% were infected in a foreign country, 36% resulted from recent transmission in The Netherlands, and 18% resulted from remote infection in The Netherlands, while in the remaining cases (9%) either the time or place of infection could not be determined. The conventional epidemiological data suggested that at least 29% of clustered cases were not part of recent chains of transmission. Cases with unknown fingerprints, almost all culture negative, relatively frequently had confirmed epidemiological links with a recent pulmonary TB case in The Netherlands and were more often identified by contact tracing. Our findings highlight the idea that genotyping should be combined with conventional epidemiological investigation to establish the place and time of infection of TB cases as accurately as possible. A standardized way of classifying TB into recently, remotely, and foreign-acquired disease provides indicators for surveillance and TB control program performance that can be used to decide on interventions and allocation of resources.

Cross-border collaboration for improved tuberculosis prevention and care: policies, tools and experiences

As tuberculosis (TB) spreads beyond borders with people movements, several interventions ensuring the continuity of care are essential, although difficult to put in place in the absence of well-defined agreements allowing data sharing and easy referral of patients to appropriate health facilities. This article first sets out general principles for cross-border collaboration and continuity of care. It then presents a series of case studies. Policies and practices on cross-border collaboration in selected low-incidence countries (Australia, Italy, Norway, The Netherlands, the United Kingdom and the United States) are described and critically appraised. Details of the World Health Organizations (WHOs) European Respiratory Society TB Consilium for transborder migration and those of the Health Networks TBNet activities are described. With increasing population movement, including migrants and travellers, it is time to build on good practices and existing tools and to remove legal, financial and social barriers to ensure early diagnosis, full treatment and continuity of care across our world. Data sharing between the sending and the receiving countries is of utmost importance and must be conducted in line with privacy protection rules. Successful implementation of these interventions is key to being on track with the WHOs End TB strategy targets for 2030.