Pathophysiological Implications of Cell Envelope Structure in Mycobacterium tuberculosis and Related Taxa

Mycobacterium tuberculosis has a cell envelope incorporating a peptidoglycan-linked arabinogalactan esterified by long-chain mycolic acids. A range of “free” lipids are associated with the “bound” mycolic acids, producing an effective envelope outer membrane. The distribution of these lipids is discontinuous among mycobacteria and such lipids have proven potential for biomarker use in tracing the evolution of tuberculosis. A plausible evolutionary scenario involves progression from an environmental organism, such as Mycobacterium kansasii, through intermediate “smooth” tubercle bacilli, labelled “Mycobacterium canettii”; cell envelope lipid composition possibly correlates with such a progression. M. kansasii and “M. canettii” have characteristic lipooligosaccharides, associated with motility and biofilms, and glycosyl phenolphthiocerol dimycocerosates (“phenolic glycolipids”). Both these lipid classes are absent in modern M. tuberculosis sensu stricto, though simplified phenolic glycolipids remain in certain current biotypes. Dimycocerosates of the phthiocerol family are restricted to smaller phthiodiolone diesters in M. kansasii. Diacyl and pentaacyl trehaloses are present in “M. canettii” and M. tuberculosis, where they are accompanied by related sulfated acyl trehaloses. In comparison with environmental mycobacteria, subtle modifications in mycolic acid structures in “M. canettii” and M. tuberculosis are notable. The probability of essential tuberculosis evolution taking place in Pleistocene megafauna, rather than Homo sapiens, is reemphasised

Mycobacterium abscessus: An environmental mycobacteria being a human pathogen

Background: Mycobacterium abscessus is an opportunistic organism common in the environment. This species rarely cause infections in immunocompetent individuals. Certain patient groups, however, can get severe infections, e.g., in skin, soft tissues or lungs, as well as disseminated infections. During the last years, this organism has emerged as a major pathogen in patients with cystic fibroses. M. abscessus exhibits two different colony types: one with smooth and shining morphology, the other with rough and dry morphology. The smooth strains are considered wild-types, which become rough due to mutation. These features make the M. abscessus variants particularly interesting for scientific studies, since the results of such analyses can be a basis for creating theories also concerning other mycobacteria. Aim; The aim of this study is to analyze potential differences between smooth and rough strains of M. abscessus concerning human host response. Methods: M. abscessus strains isolated at the Mycobacterial Laboratory in Gothenburg, Sweden were analyzed morphologically. The ability of monocytes to internalize the two colony variants of M. abscessus was studied, as well as the cytokine response. Results: The analyses showed that isolates from the wound mainly exhibit smooth colony formation, while those from airways generally are of the rough phenotype. Human monocytes easily internalized the smooth varieties of M. abscessus, whereas the rough ones rarely were internalized. Differences between the two types, concerning the capacity to induce cytokines, were also revealed. Discussion and conclusions: The wound isolates of M. abscessus were mainly smooth, while the lung isolates were rough. The rough variants that lack certain surface glycolipids are likely to be more hydrophobic and aerosol transmissible than the smooth strains, which might explain why the rough ones are more often associated with infections in the airways than are the smooth ones. Studies on other mycobacteria have also shown a link between hydrophobicity and aerosol transmission. These studies showed that human monocytes easily internalize smooth M. abscessus cells, but rarely the rough ones. This capacity of the rough cells to avoid internalization is in all probability also due to absence or reduction of certain surface glycolipids. The lack of these surface lipids makes the rough bacteria stick to each other forming so-called cords, which are aggregates of many cells and thus difficult to internalize. The absence of glycolipids exposing other surface structures of the bacteria cell may also contribute to prevent internalization. Even if intracellular survival is regarded as the most important virulence factor of mycobacteria, it is nevertheless likely that the capacity to avoid internalization can contribute to pathogenesis at several mycobacterioses. It is possible that this phenomenon is important at tuberculosis, since Mycobacterium tuberculosis cells form rough colonies

New options in Tuberculosis Care: Visions for the future are crucial for controlling the disease

New scientific approaches are necessary: The current strategies for controlling tuberculosis (TB) are not sufficient. Improved prophylactic and diagnostic tools are imperative, being crucial for decreasing TB incidence and mortality and for preventing outbreaks. Furthermore, new and better drugs are badly needed, particularly considering the increase in cases with multidrug-resistant strains. The current TB vaccine—the Bacillus Calmette–Guérin vaccine—has a preventive impact on disseminated TB in children, but little effect on the most common form of TB, that is, lung TB in adults and young adults. For many years extensive scientific efforts have been made in order to develop new vaccines against TB that are better and more effective than Bacillus Calmette–Guérin. No such vaccine exists, however, to date. During the last few years it has become increasingly clear that TB patients can be infected with more than one strain and that a previous TB infection increases rather than decreases the risk for getting a new one. Mycobacterium tuberculosis organisms are thus not capable of inducing protective immunity to such an extent that a new TB infection is prevented. This phenomenon highlights the problems of developing effective vaccines against TB. A new TB vaccine based on general immunological protection models would in all probability only have a limited capacity to hamper TB incidence and mortality. The question whether or not it is feasible to make a vaccine of sufficient efficacy must therefore be discussed. Prophylaxis is practically always far better than therapy and we all wish we had an effective TB vaccine. However, considering the problems with vaccines, scientific efforts could well focus on developing new therapies rather than new vaccines. New scientific approaches are highly necessary and we need ideas and visions. Some examples of recent projects will hereby be presented. One study concerns the mycobacterial cell envelope and its unique macromolecules as targets for new drugs. Another study concerns new ways of administrating the drugs which could enhance the effects of new as well as of already available drugs. In addition, what can be learnt from cancer therapy—is supporting the patient's own defense by immune modularly methods a possible approach? We also need to look back since ample knowledge on TB has been assembled during many years. Unfortunately some of this valuable knowledge is about to be forgotten, particularly, the experience from the time when TB was an incurable disease

Ledarstilar - en studie om ledarstilarnas betydelse i undervisning

Sammanfattning Inom läraryrket ställs det väldigt höga krav på pedagogerna, både socialt och yrkesmässigt. Uppgifterna och kraven som ställs på pedagogerna är både fler och annorlunda idag mot vad de var tidigare. Pedagogernas roll idag är mer mångfacetterad. Pedagogerna ska inte bara ge eleverna fakta kunskaper utan även vara förebilder i det sociala samspelet med andra. Pedagogerna behöver således ha en förståelse för de olika ledarstilarna. Detta för att kunna anpassa sin ledarstil efter olika situationer och elevers behov. Med hjälp av detta examensarbete vill vi visa hur viktig pedagogens ledarstil är för klassrumsklimatet. En pedagog kan, med hjälp av sin ledarstil, förändra klassrumsklimatet i såväl positiv som i negativ riktning. Våra frågeställningar är följande: 1. Vilka ledarstilar möter en klass under en vecka? 2. Förändrar pedagoger sin ledarstil allt eftersom gruppen förändras? För att få svar på dessa två frågeställningar använde vi oss av en observationsmetod. Vi observerade en klass under en vecka och därefter analyserade vi varje genomförd observation. Våra analyser bygger på forskning kring ämnesområdet ”pedagogers ledarstil”. De ledarstilar som alla pedagoger har någon eller några influenser från är från de mest omskrivna ledarstilarna nämligen; den auktoritära, den demokratiska, den assisterande eller den överlåtande ledarstilen. Våra observationer samt analyser visade att den observerade klassen mötte alla de ovan nämnda ledarstilarna under en vecka samt att pedagoger kan förändra sin ledarstil om gruppen förändras. Våra observationer visade också att pedagogens ledarstil är av yttersta vikt för att få ett bra klassrumsklimat då en pedagog kan, med hjälp av situationsanpassad ledarstil, få ett bra klassrumsklimat. Samma pedagog kan också få ett sämre klassrumsklimat genom att inte reflektera över sin ledarstil. Det är med andra ord av yttersta vikt att pedagoger blir mer medvetna om sin ledarstil och vilken betydelse den har för klassrumsklimatet. Nyckelord: Förhållningssätt, klassrumsklimat, ledarskap, ledarstil samt observationer

Implementing joint tuberculosis projects in Somaliland and Sweden for mutual strengthening of programs and research

Aim and objectives: To implement a collaborative tuberculosis (TB) project involving a low- and a high-endemic country for improved prevention and treatment of TB in both countries. Methods: Descriptive analyses in Somaliland and in Sweden based on the experiences of healthcare staff. The pattern of resistance of Mycobacterium tuberculosis (MTB) and the treatment outcome in the two countries will be compared. Background: Somaliland has among the highest incidence of TB in the world. It is also a poor country which is why every measure has to be valued depending on its cost-effectiveness. A strict standardized approach for case detection and application of treatment is therefore necessary. Active case-finding focusing on smear positivity and contagiousness is given priority before preventive therapy, though the health authorities aim at ensuring easy access to TB care in all rural areas and detection at an early stage of the disease. The general circumstances and underlying social determinants are, however, of major importance in low-resource settings, though less possible to influence. Sweden has among the lowest incidence of TB in the world, but TB is nevertheless not addressed properly among the most vulnerable and hard-to-reach groups, e.g., the newly arrived immigrants from high-incidence countries. The majority of new cases in Sweden are from the Horn of Africa. Cluster analyses have revealed a spread of TB in Sweden within the risk groups and delayed measures for preventing transmission have been observed. Patients’ delay in seeking treatment is for many reasons common, and since TB is not a generally recognized disease in Sweden, doctors taking time to give a correct diagnosis may also occur. Identified priorities are to provide information about TB, particularly for those at risk and their providers and healthcare staff. In accordance with the recommendations by WHO and the European Respiratory Society, the Swedish healthcare system screens for active and latent TB in the most vulnerable and hard-to–reach groups and have a focus on the special needs of migrants. Discussion and conclusions: Herein this study presents a planned TB project aiming at cooperation between healthcare staff from a low- and a high-endemic country. For such a project, several baseline data are required, e.g., the pattern of resistance of MTB and the treatment outcome in Somaliland, as well as among immigrants in Sweden. The social circumstances for any patient with TB, whether in Somaliland or Sweden, during disease and when recovered is a main issue for health from a holistic perspective. Further, the nutritional status is not satisfactory for TB patients in either country, and a dietary intervention may be of importance in both countries. Baseline data according to the above are necessary for assessment of the interventions and are part of ongoing pre-studies. For the Swedish party the exchange of clinical knowledge is beneficial since TB is rare in Sweden and access to TB research and clinical implantation of new methods will be facilitated and possible through the joint project. Ultimately, an expanded project could curb TB at the source and decrease TB in both countries

Molecular Epidemiology of Mycobacterium tuberculosis in Western Sweden

The genetic diversity of Mycobacterium tuberculosis isolates among patients from Sweden was determined by a combination of two PCR-based techniques (spoligotyping and variable number of tandem repeats analysis). It resulted in a clustering of 23.6% of the isolates and a rate of recent transmission of 14.1%. The clustered isolates mainly belonged to the Haarlem family (23.2%), followed by the Beijing (9.8%), Latin American and Mediterranean (LAM; 8%), and East African-Indian (EAI; 6.2%) families. A comparison of the spoligotypes with those in the international spoligotyping database showed that 62.5% of the clustered isolates and 36.6% of all isolates typed were grouped into six major shared types. A comparison of the spoligotypes with those in databases for Scandinavian countries showed that 33% of the isolates belonged to an ill-defined T family, followed by the EAI (22%), Haarlem (20%), LAM (11%), Central Asian (5%), X (5%), and Beijing (4%) families. Both the highest number of cases and the proportion of clustered cases were observed in patients ages 15 to 39 years. Nearly 10% of the isolates were resistant to one or more drugs (essentially limited to isoniazid monoresistance). However, none of the strains were multidrug resistant. Data on the geographic origins of the patients showed that more than two-thirds of the clustered patients with tuberculosis were foreign-born individuals or refugees. These results are explained on the basis of both the historical links within specific countries and recently imported cases of tuberculosis into Sweden

Epidemiological analyses of tuberculosis in Archangelsk, Russia and implementation of a rapid assay for detection of resistance in this high burden setting

Background: Tuberculosis (TB) is a major problem in Russia, particularly regarding multidrug-resistant tuberculosis (MDR-TB). Rapid drug susceptibility testing methods are therefore needed. Objectives: To perform epidemiological analyses of TB in the Archangelsk region and to evaluate the molecular method GenoType®MTBDRplus in this type of setting. Materials and methods: Clinical and microbiological data of all TB patients in Archangelsk were collected in 2010. Smear-positive sputa were analysed by MTBDRplus and Bactec MGIT 960. Results: The number of TB cases was 812 (incidence 65/105) and among these patients, 151 cases were registered in the penitentiary system (incidence 1162/105). Most patients were men, 94% had pulmonary TB and 22% were relapses. Out of all cases, 341 (42%) were smear positive and thus contagious and 176 (22%) had MDR-TB, among which one had extensively drug resistant tuberculosis (XDR-TB). Furthermore, two TB patients had strains being resistant to rifampicin, but susceptible to isoniazid. The number of cases being both contagious and MDR-TB was 128 representing 15.8% of all TB cases (incidence 10.2/105). Among these 128 TB patients 37 were relapses representing 25.7% of all the relapse cases. The results of MTBDRplus and Bactec MGIT analyses corresponded in 98.8%. Conclusions: In Archangelsk many TB patients had contagious MDR-TB thus being hazardous in society and relapsing pulmonary TB was common. The TB situation in the prisons was particularly severe. The analyses showed furthermore that MTBDRplus is of major value in this setting