I de vesteuropeiske landene har nedgangen i forekomst av tuberkulose stagnert de senere tiårene hovedsakelig på grunn av økt tilstrømning av mennesker fra høyinsidensland for tuberkulose. Det er stilt spørsmål om tuberkulosekunnskapene blant helsepersonell er tilstrekkelige. Studier har vist betydelige variasjoner i utformingen av tuberkulosekontrollen av innvandrere. WHO har medvirket til utvikling av policydokumenter for tuberkulosekontroll i europeiske lavinsidensland. Hensikten med denne studien var tosidig: 1) å se på i hvilket omfang nasjonale og engelskspråklige legetidsskrifter hadde publisert fagartikler om tuberkulose blant innvandrere i Danmark, Norge og Sverige og beskrive artiklene som kunnskapskilder for leger og annet helsepersonell, og 2) å beskrive de tre landenes policydokumenter for tuberkulosekontroll på noen spesifikke områder. Materialet består av 27 tidsskriftsartikler publisert i 1995-2004 og 18 policydokumenter. Studien er utvidet og oppdatert på basis av en tidligere publisert undersøkelse. Tidsskriftsartiklene inneholdt mye relevant fagstoff for helsepersonell. Artiklene viste at tuberkuloseforekomst, smitteforhold og praktisk kliniske utfordringer har mange likhetstrekk i de tre landene. Antallet artikler i nasjonale tidsskrifter ble imidlertid vurdert som for lavt til å kunne utgjøre en viktig kunnskapskilde. Det bør publiseres mer om tuberkulose blant innvandrere i nasjonale tidsskrifter da disse har en viktig klinisk og helsepolitisk betydning. Policydokumentene viste forskjeller i landenes policy for ankomstscreening, forebyggende behandling, BCG-vaksinering og bruk av direkte observert terapi. Ankomstscreening for personer fra høyinsidensland for tuberkulose er frivillig i Danmark og Sverige og obligatorisk i Norge. Studien kunne ikke forklare ulikhetene i de tre nabolandenes policy. Lokal motstand mot internasjonale føringer på tuberkuloseområdet er vist ved studier fra andre land. Obligatorisk ankomstscreening er omdiskutert og reiser etiske problemstillinger når det gjelder individers integritet og slike undersøkelsers betydning for folkehelsen / In recent decades, the decline of tuberculosis has stagnated in Western Europe mainly due to increased immigration from high-prevalence countries. Policies for control of tuberculosis among immigrants in these countries are very varied. Frameworks for tuberculosis control in European countries with a low incidence of disease have been published in collaboration with the WHO. The aim of this study was twofold: 1) To find out what has been published on tuberculosis among immigrants in Denmark, Norway and Sweden in medical journals and to describe the scientific literature as a source for updated knowledge for doctors and other health professions, and 2) to describe national policy documents on specified parts of the policy. The material consists of 27 medical papers published between 1995 and 2004 and 18 policy documents. This paper is based on a previously published study and an updated literature review. The medical papers were highly relevant as scientific information for health personnel. The review of the papers showed that there were many similarities between the three countries. However, the number of papers in the national medical journals was too low to represent an important source of knowledge. More publishing in national medical journals is recommended because these have clinically and health political importance. The policy documents showed differences in the countries policy on screening on arrival, preventive therapy, BCG-vaccination and use of direct observed therapy. Screening on arrival for people from countries with a high incidence of tuberculosis is voluntary in Denmark and Sweden and mandatory in Norway. The study could not explain the differences in policy in the three neighbouring countries. Local resistance to international guidelines for tuberculosis control is described in studies from other countries. Mandatory screening of new entrants is controversial and raises ethical issues concerning individuals’ integrity and the importance of screening for public health. / <p>ISBN 91-7997-150-4</p>

According to the World Health Organization (WHO), M. tuberculosis, the causative agent of TB, accounts for approximately 1.7 million deaths annually. Further contributing causes to the worldwide TB incidence, is the widespread unavailability and ineffectiveness of TB vaccines, time consuming diagnostic methods and unsuccessful treatment approaches. Research for better characterising mycobacteria in general, or other Mycobacterium species, may help us to better understand M. tuberculosis and TB disease mechanisms, which will in turn lower the future TB disease prevalence, as this may lead to the development of better treatments, diagnostics and vaccines. Mycobacteria use various secretion pathways, including the ESX- or type VII secretion (T7S) system, to ensure transport across the complex cell wall. The genome of M. tuberculosis has five copies of a gene cluster known as the ESX gene cluster region, which is associated with virulence and viability of mycobacteria. The ESX-3 gene cluster is thought to be essential for growth of M. tuberculosis and proposed to be involved in iron / zinc homeostasis. Mycobacteria synthesise siderophores, which are proposed to be involved in the uptake of iron over their cell wall. M. tuberculosis are known to produce two types of siderophores, namely: carboxymycobactins and mycobactins. Loots and colleagues, however illustrated, that ESX-3 knockouts, show signs of iron overload, despite the absence of the mycobactins induced by knocking out the ESX-3 gene cluster. It was hypothesised, that this overload occurs due to an increase in exochelin synthesis, another iron uptake protein not associated with ESX-3, overcompensating for the perceived iron depletion in the knockout organism. A Metabolomics research approach was subsequently used in this study, to generate new information in order to better characterise the role of iron on the metabolism of these organisms, and additionally confirm the role of ESX-3 in iron uptake. In this study, we firstly determined the most optimal extraction conditions for this metabolomics investigation. Two extraction methods were subsequently investigated and compared, considering their repeatability and their respective capacities to extract those compounds which best differentiate the M. smegmatis ESX-3 knockouts and wild-type parent strains. Considering the results generated, the total metabolome method was chosen for further analyses, for the following reasons: 1) it is simpler, 2) faster, 3) showed better repeatability, 4) extracts those compounds best differentiating the compared groups and 5) has been previously described for metabolomics analyses characterising ESX-3 gene functionality, hence potentially allowing us to compare results to that previously generated and published data. Subsequently, we used the chosen extraction method, followed by GCxGC-TOFMS analysis of the separately cultured M. smegmatis wild-type sample extracts, cultured in normal, low and high iron conditions, to determine the influence of varying iron concentrations on the metabolome of this organism, by metabolomics comparisons of these groups. Following this, an identical research approach was used to compare the metabolome of a M. smegmatis ESX-3 knock-out strain, to that of a M. smegmatis wild type parent strain, both cultured in normal / standardised iron concentrations. Considering the results generated when comparing the metabolome of a M. smegmatis ESX-3 knock-out strain to that of a M. smegmatis wild type parent strain, the altered metabolome of the M. smegmatis ESX-3 knockouts correlated well to that of the M. smegmatis wild type cultured in elevated iron growth conditions. This suggests ESX-3 is involved in iron uptake, and that knocking out the ESX-3 gene cluster of M. smegmatis does in fact result in a metabolome profile suggesting iron overload, as was proposed by Loots et al (2012), most probably due the exochelins overcompensating for the absence of mycobactins, in M. smegmatis ESX-3 knockouts. / MSc (Biochemistry) North-West University, Potchefstroom Campus 2013.

Tuberculosis (TB) is one of the deadliest infectious diseases of our time, with 1.4 million deaths globally, recorded in 2010 (3800 deaths a day) by the World Health Organization (WHO). Currently, South Africa ranks third on the 2011 list of 22 high-burden TB countries in the world and it was estimated that each active-TB person could potentially infect 10–15 people annually. The WHO additionally reported that in the year 2009, 87% of all TB patients worldwide were successfully treated, with a treatment success rate of 74% reported for South Africa. Despite this however, non-adherence to anti-TB treatment is still a major issue, due to it resulting in a global increased prevalence of drug resistant TB and subsequently TB treatment failure. Treatment failure is thought to be caused by a number of factors, however, it still remains largely misunderstood. One aspect of this, that isn't clearly addressed in the literature, is the underlying variation in each patient, resulting in his/her varying reaction to the drug regimen, and hence it’s varying efficacy from one patient to the next. Furthermore, little is known about the underlying variation of the host to the primary TB infection or response to the TB disease state, and how some patients have more effective mechanisms for eliminating the infection, or recovering from the disease. Considering this, a metabolomics research study using GC×GC-TOFMS was conducted, in order to identify potential metabolite markers which may be used to better characterise the underlining mechanisms associated with poor treatment outcomes (treatment failure). The first aim was to evaluate the accuracy and efficiency of the methodology used, as well as to determine the capability and accuracy of the analyst to perform these methods. In order to evaluate the GCxGC-TOFMS analytical repeatability, one QC sample was extracted and injected repeatedly (6 times) onto the GC×GC-TOFMS. Similarly, the analyst's repeatability for performing the organic acid extraction and analyses was also determined, using 10 identical QC samples, which were extracted and injected separately. CV values were subsequently calculated from the collected and processed data as a measure of this. Of all the compounds detected from the 6 QC sample repeats used for GCxGC-TOFMS repeatability, 95.59% fell below a 50% CV value, and 93,7% of all the compounds analysed for analyst repeatability had a CV < 50. Subsequently, using the above metabolomics approach, in addition to a wide variety of univariate and multivariate statistical methods, two patient outcome groups were compared. A sample group cured from TB after 6 months of treatment was compared vs a sample group where treatment failed after the 6 month period. Using urine collected from these two patient groups at various time points, the following metabolomics comparisons where made: 1) at time of diagnosis, before any anti-TB treatment was administrated, 2) during the course of treatment, in order to determine any variance in these groups due to a varying response to the anti-TB drugs, 3) over the duration of the entire 6 months treatment regimen, in order to determine if differences exist between the two groups over time. A clear natural differentiation between the cured and failed outcome groups were obtained at time of diagnosis, and a total of 39 metabolites markers were subsequently identified. These metabolites were classified according to their various origins, and included (1) those associated with the presence of M. tuberculosis bacteria, (2) those resulting from an altered host metabolism due to the TB infection, and (3) metabolites of various exogenous origins. The detailed interpretation of these metabolites suggests that a possible underlying RCD or some sort of mitochondrial dysfunction may be present in the treatment failure group, which may also be induced through an external stimulus, such as alcohol consumption. We hypothesise that this may possibly result in a far greater severity to M. tuberculosis infection in this group, subsequently causing a reduced capacity for a successful treatment outcome, also considering the critical role of the mitochondria in the metabolism of anti-TB drugs. Furthermore, 20 metabolite markers were identified when comparing the two outcome groups during the treatment phase of this metabolomics investigation. A vast majority of these 20 metabolites were also identified as markers for time 0 (time of diagnosis). Additionally, metabolites associated with anti-TB drug induced side effects, were also found to be comparatively increased in the treatment failure group, indicative of more pronounced liver damage, accompanied by metabolites characteristic of a MADD metabolite profile, due to a deficient electron transport flavoprotein, confirming previous experiments done in rats. These side effects have also previously been implicated as a major contributor of poor treatment compliance, and ultimately treatment failure. Lastly, 35 metabolite markers were identified by time dependent statistical analysis and represented those metabolites best describing the variation between the treatment outcome groups over the entire study duration (from diagnosis, to week 26). This time dependent statistical analysis identified markers, using an alternative statistical approach, and confirmed previous findings and added in a better characterisation of treatment failure. Considering the above, we successfully applied a metabolomics approach for identifying metabolites which could ultimately aid in the prediction and monitoring of treatment outcomes. This additionally led to a better understanding and or characterisation of the phenomenon known as treatment failure, as well as the underlying mechanisms related to this occurrence. / MSc (Biochemistry), North-West University, Potchefstroom Campus, 2013

According to the World Health Organization (WHO), M. tuberculosis, the causative agent of TB, accounts for approximately 1.7 million deaths annually. Further contributing causes to the worldwide TB incidence, is the widespread unavailability and ineffectiveness of TB vaccines, time consuming diagnostic methods and unsuccessful treatment approaches. Research for better characterising mycobacteria in general, or other Mycobacterium species, may help us to better understand M. tuberculosis and TB disease mechanisms, which will in turn lower the future TB disease prevalence, as this may lead to the development of better treatments, diagnostics and vaccines. Mycobacteria use various secretion pathways, including the ESX- or type VII secretion (T7S) system, to ensure transport across the complex cell wall. The genome of M. tuberculosis has five copies of a gene cluster known as the ESX gene cluster region, which is associated with virulence and viability of mycobacteria. The ESX-3 gene cluster is thought to be essential for growth of M. tuberculosis and proposed to be involved in iron / zinc homeostasis. Mycobacteria synthesise siderophores, which are proposed to be involved in the uptake of iron over their cell wall. M. tuberculosis are known to produce two types of siderophores, namely: carboxymycobactins and mycobactins. Loots and colleagues, however illustrated, that ESX-3 knockouts, show signs of iron overload, despite the absence of the mycobactins induced by knocking out the ESX-3 gene cluster. It was hypothesised, that this overload occurs due to an increase in exochelin synthesis, another iron uptake protein not associated with ESX-3, overcompensating for the perceived iron depletion in the knockout organism. A Metabolomics research approach was subsequently used in this study, to generate new information in order to better characterise the role of iron on the metabolism of these organisms, and additionally confirm the role of ESX-3 in iron uptake. In this study, we firstly determined the most optimal extraction conditions for this metabolomics investigation. Two extraction methods were subsequently investigated and compared, considering their repeatability and their respective capacities to extract those compounds which best differentiate the M. smegmatis ESX-3 knockouts and wild-type parent strains. Considering the results generated, the total metabolome method was chosen for further analyses, for the following reasons: 1) it is simpler, 2) faster, 3) showed better repeatability, 4) extracts those compounds best differentiating the compared groups and 5) has been previously described for metabolomics analyses characterising ESX-3 gene functionality, hence potentially allowing us to compare results to that previously generated and published data. Subsequently, we used the chosen extraction method, followed by GCxGC-TOFMS analysis of the separately cultured M. smegmatis wild-type sample extracts, cultured in normal, low and high iron conditions, to determine the influence of varying iron concentrations on the metabolome of this organism, by metabolomics comparisons of these groups. Following this, an identical research approach was used to compare the metabolome of a M. smegmatis ESX-3 knock-out strain, to that of a M. smegmatis wild type parent strain, both cultured in normal / standardised iron concentrations. Considering the results generated when comparing the metabolome of a M. smegmatis ESX-3 knock-out strain to that of a M. smegmatis wild type parent strain, the altered metabolome of the M. smegmatis ESX-3 knockouts correlated well to that of the M. smegmatis wild type cultured in elevated iron growth conditions. This suggests ESX-3 is involved in iron uptake, and that knocking out the ESX-3 gene cluster of M. smegmatis does in fact result in a metabolome profile suggesting iron overload, as was proposed by Loots et al (2012), most probably due the exochelins overcompensating for the absence of mycobactins, in M. smegmatis ESX-3 knockouts. / MSc (Biochemistry) North-West University, Potchefstroom Campus 2013.

Tuberculosis (TB) is one of the deadliest infectious diseases of our time, with 1.4 million deaths globally, recorded in 2010 (3800 deaths a day) by the World Health Organization (WHO). Currently, South Africa ranks third on the 2011 list of 22 high-burden TB countries in the world and it was estimated that each active-TB person could potentially infect 10–15 people annually. The WHO additionally reported that in the year 2009, 87% of all TB patients worldwide were successfully treated, with a treatment success rate of 74% reported for South Africa. Despite this however, non-adherence to anti-TB treatment is still a major issue, due to it resulting in a global increased prevalence of drug resistant TB and subsequently TB treatment failure. Treatment failure is thought to be caused by a number of factors, however, it still remains largely misunderstood. One aspect of this, that isn't clearly addressed in the literature, is the underlying variation in each patient, resulting in his/her varying reaction to the drug regimen, and hence it’s varying efficacy from one patient to the next. Furthermore, little is known about the underlying variation of the host to the primary TB infection or response to the TB disease state, and how some patients have more effective mechanisms for eliminating the infection, or recovering from the disease. Considering this, a metabolomics research study using GC×GC-TOFMS was conducted, in order to identify potential metabolite markers which may be used to better characterise the underlining mechanisms associated with poor treatment outcomes (treatment failure). The first aim was to evaluate the accuracy and efficiency of the methodology used, as well as to determine the capability and accuracy of the analyst to perform these methods. In order to evaluate the GCxGC-TOFMS analytical repeatability, one QC sample was extracted and injected repeatedly (6 times) onto the GC×GC-TOFMS. Similarly, the analyst's repeatability for performing the organic acid extraction and analyses was also determined, using 10 identical QC samples, which were extracted and injected separately. CV values were subsequently calculated from the collected and processed data as a measure of this. Of all the compounds detected from the 6 QC sample repeats used for GCxGC-TOFMS repeatability, 95.59% fell below a 50% CV value, and 93,7% of all the compounds analysed for analyst repeatability had a CV < 50. Subsequently, using the above metabolomics approach, in addition to a wide variety of univariate and multivariate statistical methods, two patient outcome groups were compared. A sample group cured from TB after 6 months of treatment was compared vs a sample group where treatment failed after the 6 month period. Using urine collected from these two patient groups at various time points, the following metabolomics comparisons where made: 1) at time of diagnosis, before any anti-TB treatment was administrated, 2) during the course of treatment, in order to determine any variance in these groups due to a varying response to the anti-TB drugs, 3) over the duration of the entire 6 months treatment regimen, in order to determine if differences exist between the two groups over time. A clear natural differentiation between the cured and failed outcome groups were obtained at time of diagnosis, and a total of 39 metabolites markers were subsequently identified. These metabolites were classified according to their various origins, and included (1) those associated with the presence of M. tuberculosis bacteria, (2) those resulting from an altered host metabolism due to the TB infection, and (3) metabolites of various exogenous origins. The detailed interpretation of these metabolites suggests that a possible underlying RCD or some sort of mitochondrial dysfunction may be present in the treatment failure group, which may also be induced through an external stimulus, such as alcohol consumption. We hypothesise that this may possibly result in a far greater severity to M. tuberculosis infection in this group, subsequently causing a reduced capacity for a successful treatment outcome, also considering the critical role of the mitochondria in the metabolism of anti-TB drugs. Furthermore, 20 metabolite markers were identified when comparing the two outcome groups during the treatment phase of this metabolomics investigation. A vast majority of these 20 metabolites were also identified as markers for time 0 (time of diagnosis). Additionally, metabolites associated with anti-TB drug induced side effects, were also found to be comparatively increased in the treatment failure group, indicative of more pronounced liver damage, accompanied by metabolites characteristic of a MADD metabolite profile, due to a deficient electron transport flavoprotein, confirming previous experiments done in rats. These side effects have also previously been implicated as a major contributor of poor treatment compliance, and ultimately treatment failure. Lastly, 35 metabolite markers were identified by time dependent statistical analysis and represented those metabolites best describing the variation between the treatment outcome groups over the entire study duration (from diagnosis, to week 26). This time dependent statistical analysis identified markers, using an alternative statistical approach, and confirmed previous findings and added in a better characterisation of treatment failure. Considering the above, we successfully applied a metabolomics approach for identifying metabolites which could ultimately aid in the prediction and monitoring of treatment outcomes. This additionally led to a better understanding and or characterisation of the phenomenon known as treatment failure, as well as the underlying mechanisms related to this occurrence. / MSc (Biochemistry), North-West University, Potchefstroom Campus, 2013

Mål: Å vurdere effekten av det norske BCG-vaksinasjonsprogrammet blant ungdommer ved(1) å vurdere om forskjeller i tuberkuloseepidemiologi i fire nordiske land er assosiert med forskjeller i bruk av BCG og (2) å estimere betydningen av BCG vaksinasjon blant ungdommer i Norge. Metode: Studieperioden var 1975-2005, med hovedvekt på 1996-2005. Artikler, overvåkingsrapporter, EuroTB-databasen og nasjonale tuberkuloseregistre var datakilder. Data fra EuroTB ble brukt til å beregne insidensrater for tilfeller rapportert som “born in country/national” i Norge, Sverige, Finland og Danmark. Data fra de norske og svenske tuberkuloseregistrene ble brukt til å beregne insidensrater for tilfeller som var født i de respektive land og som hadde foreldre som begge var født i et land med lav insidens av tuberkulose. Insidensrater for aldersgruppene 0-14 and 15-29 år ble sammenlignetHovedresultater: Fra 1975 til 2005 var det et fall i insidensrate i alle landene, mest uttalt i Finland. I 1996-2005 hadde Finland lavest insidensrate i aldergruppen 0-14 år, og Norge hadde lavest insidensrate i gruppen 15-29 år. Dette er forenlig med beskyttende effekt som følge av BCG-vaksinasjon av nyfødte i Finland og av 12-14-åringer i Norge. Vi estimerer at det norske BCG vaksinasjonsprogrammet blant ungdommer gir 61-64% beskyttelse i aldersgruppen 15-29 år. Om man forutsetter 50-80% beskyttelse, er det nødvendig med 14918 - 51409 vaksinasjoner for å forebygge ett tilfelle av tuberkulose. I 1996-2005 kan tidligere BCG-vaksinasjon blant ungdommer ha forebygget 1,2 – 3,9% av tilfeller av tuberkulose blant norskfødte, og 0,4 – 1,2% av totalt antall tilfeller. Konklusjoner: BCG-vaksinasjon av norske ungdommer med lav risiko for tuberkulose kan ha bidratt til redusert risiko for tuberkulose i en periode på 15 år etter vaksinering. Men et stort antall vaksinasjoner er nødvendig for å forebygge ett tilfelle. / Purpose: to assess the effectiveness of the Norwegian adolescent BCG vaccinationprogramme by (1)examining if differences in tuberculosis epidemiology in four Nordiccountries is associated with different use of BCG and (2) using evidence from this and paststudies on BCG efficacy to estimate the impact of vaccination in the present epidemiologicalsituation. Method: The study period was 1975-2005, with main focus on 1996-2005. Data sourceswere articles, surveillance reports, the EuroTB database, and national tuberculosis registers.EuroTB data were used to calculate incidence rates for cases reported as “born incountry/national” in Norway, Sweden, Finland and Denmark. Data from the Norwegian andSwedish tuberculosis registers were used to calculate incidence rates for cases that were born in the respective countries and that had parents who were both born in countries with low incidence of tuberculosis. Incidence rates in the age groups 0-14 and 15-29 years were compared. Main results: From 1975 to 2005 all countries experienced a reduction in incidence rates,most pronounced in Finland. During 1996-2005 Finland had the lowest incidence rate in the0-14 year age group, and Norway had the lowest incidence rate in the 15-29 year group. Thisis consistent with protection by BCG vaccination of newborns in Finland and of 12-14 yearolds in Norway. We estimated that the Norwegian adolescents BCG vaccination programme confers 61-64% protection in the age group 15-29 years. Assuming 50-80% protection, 14918 - 51 409 vaccinations are needed to prevent one case of tuberculosis. During 1996-2005,prior BCG vaccination of Norwegian teenagers may have prevented 1.2 - 3.9% of cases oftuberculosis among Norwegian-born and 0.4 - 1.2% of total cases. Conclusions: BCG vaccination of low-risk Norwegian adolescents may have contributed to reduced risk of tuberculosis for a period of 15 years after vaccination. However, a large number of vaccinations must be given in order to prevent one case of tuberculosis. / <p>ISBN 978-91-85721-59-7</p>

Tuberculosis is a major public health problem in Ethiopia. The aims of this study were (i) to investigate the recovery rate of M. tuberculosis from smear positive single morning sputum specimens subjected to long-term storage at -20°C, (ii) to assess the level and risk factors for first- and second-line anti-TB drug resistance, (iii) to evaluate the performance of the GenoType®MTBDRplus and GenoType®MTBDRsl assays for drug susceptibility testing compared to the BacT/ALERT 3D system as reference method, (iv) to analyze the frequency of gene mutations associated with resistance to isoniazid (INH), rifampicin (RMP) and ethambutol (EMB) among M. tuberculosis isolates, and (v) to study the population structure and transmission dynamics of M. tuberculosis isolates from patients in Amhara region, Northwest Ethiopia. The median specimen storage time was 132 days. Of 319 specimens, 90.0% were culture positive. The length of time of sputum storage had no significant effect on the recovery rate of M. tuberculosis. Of 260 M. tuberculosis isolates, 15.8% were resistant to at least one first-line drug, 5.0% were multidrug resistant (MDR) and 3.5% were resistant to all first-line drugs. Any resistance to INH, RMP, streptomycin (STM), EMB and pyrazinamide (PZA) was 13.8%, 5.8%, 10.0%, 7.3% and 4.6%, respectively. All isolates were susceptible to second-line drugs. The GenoType®MTBDRplus assay had a sensitivity of 92% and specificity of 99% to detect INH resistance, and 100% sensitivity and specificity to detect RMP resistance and MDR. The GenoType®MTBDRsl assay had a sensitivity of 42% and specificity of 100% to detect EMB resistance. According to the molecular methods, mutations conferring resistance to INH, RMP, or EMB were detected in 13.5%, 5.8%, and 3.1% of the isolates, respectively, while mutation conferring MDR was present in 5.0% of the isolates. Of 244 M. tuberculosis isolates, 59.0% were classified as known lineages; Dehli/CAS (38.9%), Haarlem (8.6%), Ural (3.3%), LAM (3.3%), TUR (2.0%), X-type (1.2%), S-type (0.8%), Beijing (0.4%) and Uganda II (0.4%) lineage. Interestingly, 31.6% of the isolates were grouped in to four previously undefined phylogenetic lineages and were named as Ethiopia_3 (13.1%), Ethiopia_1 (7.8%), Ethiopia_H37Rv like (7.0%) and Ethiopia_2 (3.7%) lineages. The remaining 9.4% of the isolates could not be assigned to the known or new lineages. Overall, 45.1% of the isolates were grouped in clusters, indicating high rate of recent transmission. Similarly, 66.7% of MDR strains were grouped in clusters.

Introduksjon: QuantiFERON®TB Gold (QFT) er en ny blodtest for påvisning av tuberkulosesmitte, men med få data så langt fra undersøkelse av immigranter. Målet med studien var å sammenligne resultat av QFT og tuberkulin hudtest blant nyankomne asylsøkere i Norge og å vurdere hvilken rolle QFT bør ha i screening for latent tuberkulose. Metode: Alle asylsøkere, 18 år eller eldre, som ankom Tanum asylmottak fra september 2005 ble invitert til å delta og ble inkludert etter informert samtykke. Inkludering pågikk inntil et forhåndsbestemt antall på 1000 inkluderte ble nådd. Siste deltager ble inkludert i juni 2006. Deltagelse innebar en QFT test og standardiserte spørsmål, i tillegg til den lovpålagte tuberkulintesten og lungerøntgen. Resultat: Totalt 2813 asylsøkere ankom Tanum asylmottak i inkluderingsperioden (sept 05-juni 06).  Blant de 1000 deltagerne hadde 912 gyldige testresultater og ble inkludert i analysen, 29 % (264) hadde positiv QFT, mens 50 % (460) hadde positiv tuberkulintest (indurasjon &gt; 6mm). Det indikerer en høy andel smittede personer i denne gruppen. Blant deltagere med positiv tuberkulintest hadde 50 % negativ QFT, mens 7 % av dem med negativ tuberkulintest hadde positiv QFT. Det var en signifikant sammenheng mellom økning i tuberkulinutslag og sannsynligheten for å ha positiv QFT. Samsvar mellom testene var 71-79%, avhengig av grenseverdi for tuberkulin. Det var bedre samsvar mellom testene for ikke-vaksinerte personer. Konklusjon: Ved å implementere QFT som rutine kan videre oppfølging avsluttes for 42% av dem som ville ha blitt henvist basert kun på tuberkulinresultat (&gt; 6mm). Andelen som henvises vil være den samme enten QFT implementeres som erstatning for eller som supplement for å bekrefte en positiv tuberkulinreaksjon, men antallet som testes vil variere mye. Ulike tilnærminger vil identifisere samme andel (88-89%) av asylsøkere med positiv QFT og/eller sterkt positiv tuberkulinutslag (&gt;15mm), men ulike grupper vil mistes. / Introduction: QuantiFERON®TB Gold (QFT), a new blood test that detects tuberculosis infection, currently provides few data from immigrant screening. This study aimed to compare results of QFT and tuberculin skin tests (TST) among newly arrived asylum seekers in Norway and also assess the role of QFT in screening for latent tuberculosis. Methods: All asylum seekers, 18 years or older, who arrived at Tanum reception center from September 2005 were invited to participate and included after informed consent. Enrollment was continued until a fixed sample size of 1000 participants was reached. The last participant was included in June 2006. In addition to mandatory TST and chest X-ray, study participants underwent a QFT test and answered standardized questions. Results: A total of 2813 asylum seekers arrived at Tanum reception center during the inclusion period. Among the 1000 study participants, 912 showed valid test results and were included in analysis; 29% (264) had a positive QFT test and 50% (460) tested positive with TST (indurations &gt;6 mm), indicating a high proportion of latent infection within this population. Among the TST-positive participants, 50% were QFT-negative, whereas 7% of the TST-negative participants were QFT-positive. A significant association occurred between increase in size of TST induration and positive QFT result. Test agreement (71%–79%) depended on the chosen TST cut-off and was higher for nonvaccinated individuals. Conclusions: By implementing QFT as a routine screening test further follow up can be avoided for 42% of asylum seekers who would have been referred based only on a positive TST (&gt;6 mm). The proportion of individuals referred remained the same whether QFT replaced TST or confirmed a positive TST; however, the number of individuals tested varied greatly. Different approaches would identify the same proportion (88%-89%) of asylum seekers with either a positive QFT or a strongly positive TST (&gt;15 mm), but different groups will be missed. / <p>ISBN 978-91-85721-53-5</p>

Introduktion: Tuberkulose er fortsat en sygdom, man skal tage alvorligt i Grønland. Forekomsten er høj med 150-200 tilfælde per 100.000 indbyggere årligt, hvoraf 20-30 % er børn og unge. Trods BCG-vaccination af nyfødte samt en ihærdig indsats med hensyn til kontaktopsporing, behandlings-kontrol, forebyggelse og smitteopsporing har incidensen været vedvarende høj i de seneste 10 år. Formål: at undersøge, hvordan forekomsten af TB blandt børn og unge i Grønland havde udviklet sig fra 1988-92 og til 2002-06. Videre at sammenligne TB incidensen blandt grønlændere med inuitbefolk-ningerne i Alaska og Canada med særligt fokus på territoriet Nunavut, hvor den største andel af canadiske inuit bor. Endelig var det formålet at belyse om de TB-ramte børn og unge adskilte sig fra andre på tilsvarende alderstrin, set i relation til social baggrund og levevilkår, samt endelig at opgøre dækningen af BCG. Materiale og metode: Anmeldelser af TB tilfælde fra 1988-92 og fra 2002-06 blev sammenlignet. Registerdata fra Alaska og Canada blev sammenholdt med data fra Grønland til belysning af forekomsten af TB blandt inuit. Data fra et case-control studie foretaget i perioden fra 1.marts 2004 til 28.februar 2007 bestående af anmeldeskemaer, spørgeskemaer til belysning af sociale forhold og levevilkår samt oplysning om BCG-vaccination fra journaler blev analyseret. Resultater og konklusion: TB incidensen var fra 1988-92 til 2002-06 steget fra 67 til 141 tilfælde pr. 100.000/år. Størst stigning sås blandt børn og unge, idet den forholdsmæssige andel af 0-19 årige steg med 6 %. En stigende andel af TB tilfælde i byerne syntes snarere at være forårsaget af flytning fra bygd til by i de hårdest ramte distrikter end et ændret smittemønster. Inuit i de undersøgte arktiske regioner har stærkt forhøjet TB incidens i forhold til den øvrige befolkning, og incidensen var højest i Grønland. Andelen af TB syge i alderen 0-19 årige var i Grønland 27 %, kun overgået af Nunavut (33 %). De vanskelige levevilkår er fælles for inuit i Nunavut og Grønland, men årsagerne til smittespredning er komplekse. Resultaterne af case-control studiet var pga. den lille population ikke statistisk signifikante, men tyder på en sammenhæng mellem levevilkår og TB, såsom højt antal beboere pr. m² og rygning, som også fundet af andre. Studiet indikerer en beskyttende effekt af BCG hos mindre børn (&lt;10 år). Mange smittede og syge børn er et tegn på aktiv smittespredning, og de smittede børn vil være kilde til fremtidens TB. Der derfor god grund til at følge udviklingen blandt børn og unge nøje, samt at igangsætte initiativer for at bremse fortsat smittespredning. / Introduction: Tuberculosis is still a disease to be taken seriously in Greenland. The occurrence is high with 150-200 cases yearly per 100,000 inhabitants, 20-30 % of these are children and young people. The latest 10 years the incidents have been high continuously, in spite of BCG-vaccination of new-borns, and a persistent effort as regards contact tracing, control of treatment, preventive interventions, and tracking sources of infection. Objective: To examine how the occurrence of TB among children and young people in Greenland has developed from 1988-92 and up till 2002-06. Further to compare the TB incidence among Greenlanders to that among Inuit populations in Alaska and Canada, with special focus on the territory of Nunavut, where the largest share of Canadian Inuit live. Furthermore, it was the intention to examine whether the TB-infected children and young people differed from the population in general at the same age level, in relation to social background and living-conditions, and finally to estimate the coverage of BCG. Material and method: Notifications of TB-cases from l988-92 and from 2002-06 were compared. Register data from Alaska and Canada were related to data from Greenland to illustrate the occurrence of TB among Inuit people. Data from a case-control carried out in the period from March 2004 to February 2007 were analysed, consisting of notification forms, questionnaires regarding social conditions and living-conditions, plus information about BCG from case records. Results and conclusion: The TB-incidence from 1988-92 to 2002-06 increased from 67 to 141 incidents per l00,000. The largest increase was seen among children and young people, as the relative share of 0-19 yearers increased by 6 %. An increasing share of TB incidents in the towns seemed more likely to have been caused by migration from settlement to town in the districts most affected, rather than by a changed pattern of infection. In the arctic regions examined, Inuit people have a strongly increased TB-incidence compared to the remaining population, and the incidence was highest in Greenland. In Greenland 27 % of TB patients were at the age of 0-19 years, and only surpassed by Nunavut (33 %). Difficult living-conditions are common for Inuit in Nunavut and in Greenland, but the causes of the spread of infection are complex. Because of the small population involved, the results of the case-control study were not statistically significant, but they indicate a correlation between living-conditions and TB, such as crowding and smoking, as also found by others. The study indicates a protective effect of BCG on small children (&lt; 10 years). Occurrence of many infected and ill children indicates active spreading of the disease, and the infected children will be the source of TB of the future. Therefore, it is advisable to follow the development among children and young people closely, and to launch initiatives to prevent further dissemination of infection. / <p>ISBN 978-91-85721-41-2</p><p></p><p></p>

Tuberculosis is a widely spread zoonotic disease caused by acid-fast bacteria of the Mycobacterium tuberculosis complex in a variety of mammalian species. In pinnipeds, tuberculosis has been reported in different captive and wild sea lions and fur seals. The causative agent, Mycobacterium pinnipedii, is part of the M. tuberculosis complex and has shown pathogenicity in other mammalian species including human beings. Since 2000 the Heidelberg zoo has been dealing with tuberculosis in its collection of South American sea lions (Otaria flavescens). After a Malayan tapir (Tapirus indicus) was transferred to a zoological institution in France it transmitted the disease to the other tapirs that succumbed to tuberculosis. Culturing and spoligotyping confirmed the origin, the sea lions at the Heidelberg zoo. An investigation of the sea lion group housed at Heidelberg in addition to different species of mammals living in adjacent exhibits as well as a sea lion, born in Heidelberg but then living in Hamburg, revealed multiple cases of pinniped tuberculosis.