Tuberculose in Nederland 2012

Op de gedrukte exemplaren van het rapport is het nummer 15000204. Het rapportnummer heeft een 0 te weinig; na versturing van de rapporten is dit pas opgemerktIn 2012 werden 958 patiënten met tuberculose gemeld aan het Nederlands Tuberculose Register (NTR). Dit komt overeen met een incidentie van tuberculose van 5,7 per 100.000 inwoners. Ten opzichte van 2011 en 2010 is de incidentie met respectievelijk vier procent en tien procent afgenomen. Sinds 2002 is het aantal tbc-patiënten in Nederland met 32% gedaald. In 2012 werd bij 53 procent van de gemelde patiënten longtuberculose geconstateerd. Het aantal patiënten met longtuberculose (pulmonale tbc) daalt sneller dan het aantal met extrapulmonale tbc (tuberculose buiten de longen). Het percentage extrapulmonale gevallen was het hoogste onder tbc-patiënten die in het buitenland zijn geboren. De meest voorkomende vorm van extrapulmonale tuberculose was tuberculose van de perifere lymfklieren. Achttien procent (177) van de tbc-patiënten in 2012 had sputumpositieve longtuberculose, de meest besmettelijke vorm van tuberculose. De incidentie van sputumpositieve longtuberculose in 2012 was 1,1 per 100.000 inwoners. Tuberculose komt in Nederland vaker voor bij personen geboren in het buitenland (eerstegeneratieallochtonen) en tweedegeneratieallochtonen. Bijna drie kwart van het aantal tbc-patiënten in 2012 was geboren in het buitenland (73%). Van de groep eerstegeneratieallochtonen met tuberculose in Nederland was de groep Somaliërs net als voorgaande jaren het grootste (170). Het percentage tbc-patiënten afkomstig uit Somalië was daarmee even groot als het percentage autochtone Nederlanders met tuberculose (18 procent), maar de incidentie onder Somaliërs in Nederland is bijna 500 maal hoger dan onder autochtone Nederlanders (respectievelijk 1,3 en 691 per 100.000 inwoners). Multiresistente tuberculose Het aantal patiënten met multiresistente tuberculose (MDR-tbc) in Nederland schommelt de laatste vijf jaar tussen tien en twintig patiënten; dat is 1-2% van het totaal aantal patiënten. In 2012 werden elf patiënten met multiresistente tuberculose gediagnosticeerd. Eén van de elf patiënten met mulitresistente tuberculose was afkomstig uit Nederland, de tien andere patiënten uit het buitenland. Resultaat van de behandeling Van alle in 2011 geregistreerde tbc-patiënten voltooide 87% de tbc-behandeling met succes. Bij nieuwe patiënten met longtuberculose was dit percentage iets lager (85%). Patiënten met multiresistente tuberculose voltooiden minder vaak de behandeling. Van de elf MDR-tbc-patiënten gediagnosticeerd in 2010 voltooiden zeven (64%) de behandeling met succes, één patiënt (9%) brak de behandeling voortijdig af, één patiënt zette de behandeling in het buitenland voort, één patiënt is overleden aan een andere oorzaak dan tuberculose en van één patiënt is het behandelresultaat (nog) niet bekend. Sterfte aan tuberculose Van de tbc-patiënten geregistreerd in het NTR in 2011 en 2012 overleden respectievelijk achttien (1,8%) en zes personen (0,6%) aan tuberculose. Patiënten met ernstige comorbiditeit hebben grotere kans op sterfte aan tuberculose. In 2012 overleed één persoon met diabetes, twee personen met een maligniteit en één persoon met nierinsufficiëntie aan tuberculose. Latente tbc-infectie (LTBI) In 2012 zijn 1.293 nieuwe gevallen van LTBI geregistreerd. Bij 855 personen werd de diagnose bij bron- en contactonderzoek vastgesteld. In 2011 startten in totaal 1.027 van de 1.297 personen (79%) een preventieve behandeling. Van hen voltooide 84% de LTBI-behandeling met succes. Delay Op grond van de gegevens in het NTR is de gemiddelde duur van het diagnostisch delay in de periode 2005-2012 niet toegenomen, hoewel bij illegalen, dak- en thuislozen, en drugs- en alcoholverslaafden wel aanwijzingen zijn voor een langer patient delay. Bij ruim een kwart van de patiënten die passief worden gevonden is wel sprake van een 'te lang' of 'ongunstig delay'. Voor doctor delay geldt hetzelfde: er is bij ruim een kwart van de patiënten die passief worden gevonden sprake van een 'te lang' of 'ongunstig delay'. Case finding In totaal 15% van alle tbc-patiënten werd in 2012 gevonden door actieve opsporing door de afdeling tbc-bestrijding van de GGD. Het percentage tbc-patiënten dat gevonden wordt door screening van risicogroepen zoals nieuwe immigranten, asielzoekers, drugsverslaafden en dak- en thuislozen neemt al langere tijd af. In de jaren 1993-1998 werd 14% van de tbc-patiënten gevonden door screening, maar in 2012 was dit nog maar 8%. Het percentage patiënten gevonden via bron- en contactonderzoek was in 2012 hetzelfde als in voorgaande jaren (7%). Tbc-patiënten met verminderde weerstand Het percentage tbc-patiënten met een co-infectie met hiv was 3% in 2012. Het percentage tbc-patiënten die op co-infectie met hiv werden getest nam toe van 28% in 2008 naar 49% in 2011, maar is in 2012gestagneerd (47%). Van patiënten uit risicogebieden zoals sub-Sahara Afrika was in 59% van de gevallen de hiv-status bekend. Het aantal tbc-patiënten die behandeld worden met TNF-alfaremmers neemt toe. In 2012 betrof het achttien (1,9%) patiënten. Transmissie en clustersurveillance Van de patiënten met kweekpositieve tuberculose clusterde de helft met een voorgaande patiënt. Bij een derde van de clusterende patiënten was sprake van recente clustering, een mogelijk gevolg van recente transmissie in Nederland. In 2012 vertoonden vier van de clusters een groei van meer dan vijf patiënten. De laatste jaren zijn er minder snelgroeiende clusters, een teken dat transmissie van M. tuberculosis in Nederland afneemt of dat de bestrijdingsmaatregelen effectief zijn.In 2012 958 cases of tuberculosis (TB) were reported to the Netherlands Tuberculosis Register (NTR). The incidence rate was 5.7 per 100,000 population. Since 2002 the number of TB patients in the Netherlands declined with 32%. In 2012 53% of the notified cases was diagnosed with pulmonary tuberculosis. Over the years the number of patients with extrapulmonary TB declined less than the number with pulmonary TB. The percentage extrapulmonary cases is highest among foreign-born TB patients. Tuberculosis of the extra thoracic lymph nodes is the most common site of disease in extrapulmonary cases. 18% (177) of all TB cases in 2012 was sputum-smear positive. The incidence rate of smear-positive pulmonary TB was 1.1 per 100,000 population. The majority of TB patients in the Netherlands was foreign-born (73%). As in previous years the largest population group with TB in 2012 was Somalian (170). The percentage of TB patients born in Somalia is in 2012 the same as the percentage native Dutch TB patients (18%). The incidence rate among people coming from Somalia is almost 500 times higher than the incidence rate of the native Dutch population (respectively 691 and 1.3 per 100,000 population). Multidrug-resistant tuberculosis In the last five years the number of patients with multidrug-resistant tuberculosis (MDR-TB) in the Netherlands varies between ten and twenty patients, 1-2% of the total number of TB patients. In 2012 eleven patients with MDR-TB were registered; ten were foreign-born. Treatment Outcome In 2011 87% of all TB patients completed treatment successfully. Of new cases with pulmonary TB 85% completed treatment successfully. Patients with MDR-TB completed treatment less often. Seven (64%) out of eleven MDR-TB-patients diagnosed in 2010 completed treatment successfully, one patient (9%) interrupted treatment, one patient continued treatment abroad, one patient died due to another cause than tuberculosis and of one patient treatment outcome is (still) unknown. TB-patients with co-morbidity or immune disorders The percentage of hiv-infected TB patients was 3% in 2012. The percentage TB patients tested for hiv increased from 28% in 2008 to 49% in 2011, but did not increase in 2012 (47%). Hiv-status was known in 59% of TB patients coming from sub-Saharan Africa, a hiv endemic area. The number of TB patients associated with TNF-alfa inhibitors treatment increases. In 2012 18 patients were registered (1.9%). Tuberculosis deaths Respectively 18 (1.8%) and 6 (0.6%) TB patients in 2011 and 2012 died due to tuberculosis. TB patients with serious co-morbidity have a higher risk of dying. In 2012 one person with diabetes, two persons with cancer and one person with renal insufficiency died due to tuberculosis. Respectively 20 (2.0%) and 20 (2.1%) TB patients in 2011 and 2012 died of other causes. Latent Tuberculosis Infection (LTBI) In 2012 1,293 new cases of LTBI were reported. 855 of these cases were detected through contact investigation. In 2011 1,027 of 1,297 cases (79%) started preventive treatment. Eighty-four percent of all persons with LTBI who received preventive treatment completed treatment successfully. Delay The mean length of the diagnostic delay over the years 2005-2012 did not increase, although undocumented TB patients, homeless TB patients, and drug and alcohol addicts with TB are associated with a longer patient delay. In more than a quarter of the passively detected cases a too long or 'unfavorable' patient delay was registered. This also applies to doctor delay; in more than a quarter of the passively detected cases a too long or 'unfavorable' delay was registered. Case finding Fifteen percent of all TB patients was detected by active case finding by the TB department of the Municipal Health Services. The percentage TB patients detected through screening of risk groups such as new immigrants, asylum seekers, drug addicts and homeless people has been decreasing for some time; in the years 1993-1998 14% of all TB patients was detected through screening, in 2012 only 8%. The number and percentage of cases found through contact investigation stayed more or less the same (7%). Transmission and cluster surveillance In 2012 50% of the cases with a positive culture belonged to a cluster. In one third of these cases recent clustering was registered, possibly as a result of recent transmission in the Netherlands. In 2012 four existing clusters showed growth of more than five patients. In the last few years there were no large outbreaks registered in the Netherlands

A Mycobacterium tuberculosis cluster demonstrating the use of genotyping in urban tuberculosis control

Background: DNA fingerprinting of Mycobacterium tuberculosis isolates offers better opportunities to study links between tuberculosis (TB) cases and can highlight relevant issues in urban TB control in low-endemic countries. Methods: A medium-sized molecular cluster of TB cases with identical DNA fingerprints was used for the development of a visual presentation of epidemiologic links between cases. Results: Of 32 cases, 17 (53%) were linked to the index case, and 11 (34%) to a secondary case. The remaining four (13%) could not be linked and were classified as possibly caused by the index patient. Of the 21 cases related to the index case, TB developed within one year of the index diagnosis in 11 patients (52%), within one to two years in four patients (19%), and within two to five years in six patients (29%). Conclusion: Cluster analysis underscored several issues for TB control in an urban setting, such as the recognition of the outbreak, the importance of reinfections, the impact of delayed diagnosis, the contribution of pub-related transmissions and its value for decision-making to extend contact investigations. Visualising cases in a cluster diagram was particularly useful in finding transmission locations and the similarities and links between patients

Revisiting susceptibility testing in MDR-TB by a standardized quantitative phenotypic assessment in a European multicentre study

Objectives Treatment outcome of MDR-TB is critically dependent on the proper use of second-line drugs as per the result of in vitro drug susceptibility testing (DST). We aimed to establish a standardized DST procedure based on quantitative determination of drug resistance and compared the results with those of genotypes associated with drug resistance. Methods The protocol, based on MGIT 960 and the TB eXiST software, was evaluated in nine European reference laboratories. Resistance detection at a screening drug concentration was followed by determination of resistance levels and estimation of the resistance proportion. Mutations in 14 gene regions were investigated using established techniques. Results A total of 139 Mycobacterium tuberculosis isolates from patients with MDR-TB and resistance beyond MDR-TB were tested for 13 antituberculous drugs: isoniazid, rifampicin, rifabutin, ethambutol, pyrazinamide, streptomycin, para-aminosalicylic acid, ethionamide, amikacin, capreomycin, ofloxacin, moxifloxacin and linezolid. Concordance between phenotypic and genotypic resistance was >80%, except for ethambutol. Time to results was short (median 10 days). High-level resistance, which precludes the therapeutic use of an antituberculous drug, was observed in 49% of the isolates. The finding of a low or intermediate resistance level in 16% and 35% of the isolates, respectively, may help in designing an efficient personalized regimen for the treatment of MDR-TB patients. Conclusions The automated DST procedure permits accurate and rapid quantitative resistance profiling of first- and second-line antituberculous drugs. Prospective validation is warranted to determine the impact on patient car

A Geographically-Restricted but Prevalent Mycobacterium tuberculosis Strain Identified in the West Midlands Region of the UK between 1995 and 2008

Background: We describe the identification of, and risk factors for, the single most prevalent Mycobacterium tuberculosis strain in the West Midlands region of the UK.Methodology/Principal Findings: Prospective 15-locus MIRU-VNTR genotyping of all M. tuberculosis isolates in the West Midlands between 2004 and 2008 was undertaken. Two retrospective epidemiological investigations were also undertaken using univariable and multivariable logistic regression analysis. The first study of all TB patients in the West Midlands between 2004 and 2008 identified a single prevalent strain in each of the study years (total 155/3,056 (5%) isolates). This prevalent MIRU-VNTR profile (32333 2432515314 434443183) remained clustered after typing with an additional 9-loci MIRU-VNTR and spoligotyping. The majority of these patients (122/155, 79%) resided in three major cities located within a 40 km radius. From the apparent geographical restriction, we have named this the "Mercian" strain. A multivariate analysis of all TB patients in the West Midlands identified that infection with a Mercian strain was significantly associated with being UK-born (OR = 9.03, 95% CI = 4.56-17.87, p 65 years old (OR = 0.25, 95% CI = 0.09-0.67, p < 0.01). A second more detailed investigation analyzed a cohort of 82 patients resident in Wolverhampton between 2003 and 2006. A significant association with being born in the UK remained after a multivariate analysis (OR = 9.68, 95% CI = 2.00-46.78, p < 0.01) and excess alcohol intake and cannabis use (OR = 6.26, 95% CI = 1.45-27.02, p = .01) were observed as social risk factors for infection.Conclusions/Significance: The continued consistent presence of the Mercian strain suggests ongoing community transmission. Whilst significant associations have been found, there may be other common risk factors yet to be identified. Future investigations should focus on targeting the relevant risk groups and elucidating the biological factors that mediate continued transmission of this strain

Mycobacterium canettii, the smooth variant of M. tuberculosis, isolated from a Swiss patient exposed in Africa.

An exceptionally smooth and glossy morphotype of Mycobacterium tuberculosis complex was isolated from a 56-year-old Swiss patient with mesenteric tuberculosis. Direct 16S rRNA sequence analysis of the hypervariable signature gene regions revealed a 100% homology to the specific M. tuberculosis complex sequence. Spoligotyping and restriction fragment length polymorphism analyses using the insertion sequences IS6110 and IS1081 and the polymorphic GC-rich sequence as additional genetic markers identified the isolate as the novel taxon M. canettii. Like a Somali child with a similar case, this patient probably contracted the infection in Africa, which raises questions about the geographic distribution of M. canettii

Ziehl-Neelsen microscopy in the diagnosis of tuberculosis in settings of high human immunodeficiency virus prevalence

Objective: To determine the accuracy of Ziehl-Neelsen microscopy in the diagnosis of TB in setings of high HIV prevalence.Design: Cross-sectional descriptive study.Setting: Hospitals serving areas of high human immunodeficiency virus prevalence in western Kenya. The study was conducted between September 2007 and September 2009.Results: In total, 341/872 (39.1%) of the TB suspects were positive in ZN, 53.1% (181/341) of them culture positive. Only 3.8% (20/531) of the ZN smear negatives were culture positive. Of the 695 suspects evaluated for both Mycobacterium and HIV infection, 255 (36.7%) were ZN smear positive, 42.7% of them HIV positive. Out of the 440 ZN smear negatives, 37% were HIV positive. Similarly, 168 suspects were culture positive, 46.4% of them HIV positive. The HIV infection did not significantly reduce ZN smear positivity rate (P = 0.42) and culture sensitivity (P = 0.09). The ZN sensitivity and specificity were 88.1% and 79.7%, respectively. The predictive values were 58.0 (PPV), and 95.5% (NPV), respectively. However, the area under the ROC curve was 0.84, with 95% CI between 0.80-0.87 and P&lt; 0.001). The ZN smear microscopy had a lesser ability to distinguish between TB and non-TB cases compared to culture.Conclusion: ZN microscopy causes a significant over-diagnosis of TB in settings of high HIV/AIDS prevalence. There is need for further studies on this subject taking into consideration the various confounding factors

A novel approach : the propensity to propagate (PTP) method for controlling for host factors in studying the transmission of Mycobacterium tuberculosis

RATIONALE: Understanding the genetic variations among Mycobacterium tuberculosis (MTB) strains with differential ability to transmit would be a major step forward in preventing transmission. OBJECTIVES: To describe a method to extend conventional proxy measures of transmissibility by adjusting for patient-related factors, thus strengthening the causal association found with bacterial factors. METHODS: Clinical, demographic and molecular fingerprinting data were obtained during routine surveillance of verified MTB cases reported in the Netherlands between 1993 and 2011, and the phylogenetic lineages of the isolates were inferred. Odds ratios for host risk factors for clustering were used to obtain a measure of each patient's and cluster's propensity to propagate (CPP). Mean and median cluster sizes across different categories of CPP were compared amongst four different phylogenetic lineages. RESULTS: Both mean and median cluster size grew with increasing CPP category. On average, CPP values from Euro-American lineage strains were higher than Beijing and EAI strains. There were no significant differences between the mean and median cluster sizes among the four phylogenetic lineages within each CPP category. CONCLUSIONS: Our finding that the distribution of CPP scores was unequal across four different phylogenetic lineages supports the notion that host-related factors should be controlled for to attain comparability in measuring the different phylogenetic lineages' ability to propagate. Although Euro-American strains were more likely to be in clusters in an unadjusted analysis, no significant differences among the four lineages persisted after we controlled for host factors.Portuguese Foundation for Science and Technology (FCT) (SFRH/BD/33902/2009 to HN-G). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript