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

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

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< 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

Mycobacterium tuberculosis Beijing genotype emerging in Vietnam.

To assess whether the Mycobacterium tuberculosis Beijing genotype is emerging in Vietnam, we analyzed 563 isolates from new cases by spoligotyping and examined the association between the genotype and age, resistance, and BCG vaccination status. Three hundred one (54%) patients were infected with Beijing genotype strains. The genotype was associated with younger age (and hence with active transmission) and with isoniazid and streptomycin resistance, but not with BCG vaccination

Discovery and application of colorectal cancer protein markers for disease stratification

Colorectal cancer (CRC) is a major cause of cancer mortality. Whereas some patients respond well to therapy, others do not, and thus more precise methods of CRC stratification are needed. The intracellular protein expression from 28 CRC primary tumours and corresponding normal intestinal mucosa was analysed using saturation-DIGE/MS and Explorer antibody microarrays. Changes in protein abundance were identified at each stage of CRC. Proteins associated with proliferation, glycolysis, reduced adhesion, endoplasmic reticulum stress, angiogenesis, and response to hypoxia represent changes to CRC and its microenvironment during development. Molecular changes in CRC cells and their microenvironment can be incorporated into clinic-pathological data to help sub-classify tumours and personalise treatment. DotScan antibody microarray analysis was used to profile the surface proteome of cells derived from 50 CRC samples and corresponding normal intestinal mucosa. Fluorescence multiplexing enabled the analysis of two different sub-populations of cells from each sample: EpCAM+ cells (CRC cells or normal epithelial cells in normal mucosa) and CD3+ T-cells (tumour-infiltrating lymphocytes). Unsupervised hierarchical clustering of the CRC and T-cell surface profiles defined four clinically relevant clusters, which showed some correlation with histopathological and clinical characteristics such as cancer cell differentiation, peri-tumoural inflammation and stimulation of infiltrating T-cells. The observed relationship between the surface antigen expression profiles of patients’ CRC cells and their corresponding tumour infiltrating T-cells suggests that CRC surface proteins may play a direct role in influencing the activity (and hence surface protein expression) of neighbouring T-cells and/or vice versa. We conclude that the application of surface profiling may provide improved patient stratification, allowing more reliable prediction of disease progression and patient outcome

A high rate of recurrent tuberculosis in western Kenya independent of human immunodeficiency virus infection

Background: Previous studies have shown that recurrent TB develops in about 2-5% of the patients after curative treatment with short-course anti-TB chemotherapy. With the advent of HIV/AIDS, the rate TB recurrence is anticipated to rise. Objectives: To determine whether HIV infection and TB recurrence are associated with anti-TB drug resistance and the rates of ZN microscopy and culture positivity among the recurrent TB cases in western Kenya. Design and methods: A cross-sectional study was carried out between 2007 and 2009. Sputa from 872 tuberculosis suspects underwent mycobacteriologic evaluation using Ziehl Neelsen smear microscopy, LowensteinJensen and BACTEC MGIT 960 culturing, and Hain’s GenoType® Mycobacterium CM and GenoType® Mycobacterium AS molecular identification tests. Consenting participants were screened for HIV infection using Uni-Gold TM test and positives were confirmed with the enzyme linked immunosorbent assay. Results: In total, 361/872 (41%) of the suspects mycobacterial disease (346 TB, 4.2% non-tuberculous mycobacterial disease). HIV testing was accepted by 695 (79.7%) and 39.1% of these (272/695) were found positive. Recurrence of TB constituted 44.8% (155/346) of the TB cases, with 41.9% (65/155) of them co-infected with HIV. There was nosignificant difference in TB recurrence rates with HIV status [OR = 0.57; 95% CI: 0.29-1.13; P = 0.10]. Conclusions and recommendations: This study reports a much higher (44.8%) rate of recurrent TB, compared to that of National TB control Programme of 5% in 2008 and a combined retreatment rate of 14% in 2009. The HIV co-infection and TB recurrence were not associated with anti-TB drug resistance. The majority of TB recurrent cases were ZN smear negative (67.7%) and culture negative (80%). The high TB recurrence observed in this study calls for studies to determine the proportions of the disease attributable to endogenous re-activation (relapse) and exogenous re-infection. Keywords: Recurrent tuberculosis; HIV co-infectio