No description available.

BACKGROUND AND AIMS OF THE THESIS: Group A β-haemolytic Streptococcus (GAS) also known as Streptococcus pyogenes, is responsible for a wide range of invasive and non-invasive GAS diseases. Prevalence and incidence data on GAS from developing countries are largely lacking when compared with industrialised nations. This thesis sought to (1) establish the South African arm of the AFROStrep biorepository and clinical database for patients with invasive and non-invasive GAS infection, (2) identify and summarize all published studies of laboratory-confirmed GAS infection in Africa, (3) describe, from national laboratory data, the incidence of invasive and non-invasive GAS in South Africa and, (4) conduct a prospective, surveillance study in order to determine the molecular epidemiology of GAS in Cape Town, South Africa over a 12-month period. METHODS: A systematic review was conducted on population-based studies reporting on the prevalence of laboratory-confirmed GAS infection among patients living in Africa (Study 1). A retrospective study of the incidence of GAS infection was conducted on data obtained from the National Health Laboratory Service between 2003 – 2015 (Study 2). The AFROStrep registry and biorepository (based in Cape Town) was established and through passive surveillance, laboratory confirmed invasive and non-invasive GAS cases were collected over a 12-month period. The molecular analysis of invasive and non-invasive infection was determined using emm type sequencing to provide insight into vaccine development (Study 3). RESULTS AND DISCUSSION: The pooled prevalence of GAS pharyngitis in Africa was determined to be 21% (95% CI, 17% to 26%). The incidence rates of laboratory-confirmed non-invasive GAS infection in the South African public sector appears to have declined over the last 13 years. Given the possibility that the lower incidence of invasive and non-invasive GAS infection found in our study is due to infrequent submission of specimens for microbiological culture by health practitioners, our findings may be an underestimate of the true burden of disease in South Africa. In our prospective surveillance study, 46 different emm types were identified. The most prevalent emm types were M76 (16% of isolates), M81 (10%), M80 (6%), M43 (6%), and M183 (6%) and were almost evenly distributed between invasive and non-invasive GAS isolates. When compared against the putative 30-valent vaccine under development, four of our most prevalent emm types are not included; vaccine coverage (i.e. vaccine type and non-vaccine type-killing) for non-invasive and invasive GAS infection in our setting was 60% and 59% respectively, notably lower than coverage in developed countries. CONCLUSION: This work provides evidence for a significantly high prevalence of GAS pharyngitis in Africa. While GAS surveillance in South Africa indicates a declining incidence of GAS disease in parts of the country over the last thirteen years, the findings may be an underestimate of the true burden of disease, demonstrating the need for accurate and comprehensive surveillance of GAS in South Africa. Finally, this research showed a low potential vaccine coverage in our setting and thus, emphasises the need for a reworking of the potential vaccine formulation to improve coverage in areas where the burden of disease is high.

No abstract available. / Thesis (Ph.D.)-University of Natal, Durban, 1973.

Hereditary Spherocytosis (HS) is a common inherited haemolytic anaemia with variable clinical expression. Fifty subjects with HS from KwaZulu-Natal were studied with the aim of providing further information on the protein abnormalities of the red blood cell (RBC) membrane and their relationship with clinical presentations. Haematological and biochemical tests were performed by routine procedures. Mean Corpuscular Haemoglobin Concentration ( MCHC) in the HS group was 35.1g /dl. This was significantly higher than in normal control subjects (33.6g /dl) (p value < 0.001); indicating its usefulness for the screening of HS. Mean Red Cell Distribution Width (RDW) was also significantly higher in subjects with HS (p<0.001); thus providing an additional screening tool. Erythrocyte membrane proteins from 21 subjects were analysed by SDS - polyacrylamide gel electrophoresis (SDS-PAGE) using the Laemmli and Fairbanks methods. The most common abnormality was a deficiency of band 3 (10 subjects), followed by a combined spectrin and ankyrin deficiency in five subjects. One subject had increased band 6 and in five cases no abnormality was detected. A decreased ratio of protein 4.1a / 4.1b on the Laemmli SDS PAGE correlated with an increased reticulocyte count. The degree of haemolysis and clinical findings did not correlate with the type of red cell membrane protein defect. In this study red cell membrane analysis did not contribute further to the initial laboratory diagnosis. In addition it did not influence clinical management. The presence of red cell membrane abnormalities, either single or multiple, did not correlate with disease severity. Red cell membrane analysis, however, will play an important role for future management such as gene therapy. Red cell membrane analysis is also useful as a research tool to determine the underlying molecular defect and to assess racial or ethnic differences. It is also of value as a differential diagnostic tool in cases where the clinical and laboratory findings are not conclusive for HS. / Thesis (M.Med.Sci)-University of KwaZulu-Natal, Durban, 2006.

Faculty of Science School of Pathology(Molecular Medicine and Haematology). 9707563v tridium@acenet.co.za / The erythrocyte carries gases between the cells and the lungs, and has to distort to negotiate narrow splenic sinuses and capillaries. This distortion necessitates a high surface area to volume ratio that is maintained by the erythrocyte membrane skeleton, a network of proteins including spectrin and protein 4.1. The skeleton anchors the lipid bilayer through attachment to integral membrane proteins, notably the anion exchange protein, band 3. Abnormalities of the erythrocyte membrane proteins cause loss of cell elasticity and ultimately the erythrocytes become prematurely trapped in the spleen where they are phagocytosed, resulting in haemolytic anaemia. Three mutations causing band 3-deficient hereditary spherocytosis (HS), a haemolytic anaemia characterised by spherical erythrocytes, were located using restriction enzyme analysis and DNA sequencing. Proband A (Black) is heterozygous for band 3 Pinhal (R490H) and has mild clinical symptoms. Proband B and his mother (Caucasian) are heterozygous for band 3 Bicetre (R490C) and have severe anaemia requiring transfusions and splenectomy, respectively. These results confirm codon 490 as a hotspot for mutations and indicate the effect of different amino acid substitutions in the same position on clinical severity. Proband C (Black) is homozygous for a novel mutation (E508K) for which her parents are heterozygous. The proband is severely affected and transfusion- dependent whereas her father has moderate anaemia and her mother is asymptomatic. It is speculated that a secondary factor modulates their clinical symptoms. All of these mutations occur in a CpG dinucleotide, a common source of DNA mutations, and are located within the highly conserved exon 13, which encodes the third to fifth α-helices and the second extracellular loop of the transmembrane region of band 3. The mutations are likely to alter the conformation of band 3, impairing its insertion into the erythrocyte membrane. No causative mutations were located in another 12 band 3-deficient HS kindred using restriction enzymes and single strand conformation polymorphism analysis. Ten protein 4.1-deficient patients with hereditary elliptocytosis, a haemolytic anaemia characterised by elliptical erythrocytes, were also studied. Immunoblot analyses ruled out abnormally sized protein 4.1 and three known DNA mutations were excluded using restriction enzyme analysis. Further studies are required to elucidate the cause of the haemolytic anaemia in these kindred. This study advanced our knowledge of the molecular basis of HS in South African kindred and highlighted the susceptibility of CpG dinucleotides to mutations.

The plasma protein complement factor H (fH, 155 kDa) regulates the activity of the alternative pathway of complement activation. Factor H is monomeric, and its 20 CCP modules are arranged in a predominantly elongated conformation, joined by linking sequences that vary in length, with the longest linkers occurring in the central portion of the molecule. CCP modules 1 through 4 of fH host its capacity to act as a cofactor for fI-mediated proteolytic degradation of C3b and its ability to accelerate the decay of the C3 convertase, C3bBb, thereby regulating the so-called tick-over activation of the alternative pathway. Mutations in this part of fH might compromise its function and lead to underregulation of the alternative pathway. It is hypothesized that this can cause predisposition to diseases such as atypical haemolytic uraemic syndrome (aHUS) and age-related macular degeneration (AMD). In the current work, the known disease-associated mutations R53H and R78G were compared to wild-type in terms of fluid-phase cofactor assays, C3b-binding affinity and the ability to accelerate the decay of the convertase. In addition, the protective variant, I62, was also inspected because its protective role might be explained by an increased regulatory activity. The second, linked, aim of this project was to employ Forster resonance energy transfer (FRET) to study the link between conformation and function in fH. FRET is valuable for obtaining long-distance restraints up to a maximum of 100 °A and is therefore particularly useful for inferring domain orientations within multidomain proteins. This approach to measure long-range inter- and intramolecular distances is a convenient way to complement NMR-based structural investigations, which rely on short-range restraints. It is also a valuable complement to X-ray crystallography since it is a solution technique that can be conducted under physiological conditions. By using site-directed mutagenesis in the current work, free cysteines were introduced into CCP modules 1-4 at strategic points, which were then used for attachment of fluorescent tags. C3 possesses an internal thioester which can be labelled with a fluorophore upon activation to C3b. Intermolecular FRET measurements were thus undertaken to gain information about the interaction between the two proteins that is crucial for understanding functional activity. The CCP modules in the centre of fH may be responsible for introducing a bend into fH that brings the N-teminus close to the C-terminus (the latter is important for host versus non-host discrimination) joined by the longest linkers occurring in the whole molecule. This coincidence of two relatively small CCP modules, 12 and 13, with the highest number of eight amino acids between them, is hypothesised to reflect some unique architectural features. To explore the structural details of this portion of fH by FRET, single-labelled cysteine mutants were further modifed to provide a recognition site for transglutaminase (TGase), which can be enzymatically labeled with a second fluorophore. This stoichiometrically-labelled protein was used for intramolecular FRET studies.

Le syndrome hémolytique et urémique atypique (SHUa) est une microangiopathie thrombotiquecomplément-dépendante dont l'atteinte majoritairement rénale reste, à ce jour, incomprise.L'objectif de ce travail était d'améliorer la compréhension de ce tropisme d’organe au moyen dedeux axes d'étude : i) la susceptibilité de l'endothélium glomérulaire à l'hémolyse, celle-ci étant à la fois la conséquence des microthromboses dans le SHUa et un amplificateur de la voie alterne du complément via l'hème libre, molécule issue des globules rouges lysés ; ii) le rôle potentiel du récepteur aux produits de glycation avancés ou RAGE. Ce récepteur membranaire aux fortes propriétés pro inflammatoires et pro thrombotiques a en effet été impliqué dans de nombreuses pathologies rénales, et sa liaison au C3a - anaphylatoxine libérée dans l'activation du complément - a été rapportée par une équipe.La première partie de ce travail a visé à expliquer la vulnérabilité de l'endothélium glomérulaire sous l'effet d'une hémolyse. Nous avons étudié plusieurs types de cellules endothéliales exposées +/- à l'hème, et mis au point un modèle murin traité par de l'hème. En conditions hémolytiques, plusieursfacteurs pouvant participer à cette susceptibilité endothéliale glomérulaire ont ainsi été mis en avant: i) une moindre liaison du facteur H, principal régulateur du complément, à sa surface ; ii) une faible expression de la thrombomoduline, protéine de la coagulation et régulatrice du complément ; iii) une faible expression de l'enzyme principale de dégradation de l'hème, l'hème-oxygénase 1. Ces deux derniers points étaient rattachés à une faible induction endothéliale glomérulaire de leurs facteurs de transcription, KFL2 et KLF4.La seconde partie de ce travail s'est concentrée sur le RAGE. N'ayant pas réussi à reproduire l'interaction RAGE/C3a, nous avons exploré l'hypothèse d'une liaison du RAGE à l'hème. En effet, le seul récepteur endothélial connu jusqu'à présent est le Toll Like Receptor 4 (TLR4), qui partage plusieurs ligands communs avec le RAGE (LPS - lipopolysaccharide, HMGB1 - high–mobility group box1). Nous avons découvert que le RAGE était un récepteur de l'hème, et identifié que le site de liaisonse trouvait sur le domaine V. A l'aide d'un modèle murin invalidé pour le RAGE et traité +/- par l'hème, nous avons mis en évidence que : i) l'invalidation de RAGE avait un effet protecteur en cas d’exposition à l'hème, marqué par une diminution de l'expression de gènes de l'inflammation (IL1β,TNFα) et du facteur tissulaire au niveau pulmonaire, organe exprimant le plus fortement RAGE ; ii)l'hème activait la phosphorylation des voies ERK1/2 et Akt via le RAGE.Par ces travaux, nous avons précisé les liens entre activation du complément, hémolyse et susceptibilité endothéliale glomérulaire dans le SHUa. Parallèlement, nous avons identifié le RAGE comme un nouveau récepteur à l'hème, dont la liaison à ce récepteur activerait différentes voies designalisation de l'inflammation. Le contrôle de l'hème et du RAGE pourrait ainsi constituer de nouvelles voies thérapeutiques dans le SHUa et les maladies hémolytiques. / The atypical haemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy of which the predominantly renal damage remains, to date, misunderstood. The aim of this work was to improve the understanding of this organ tropism by two axes of study: i) the susceptibility of the glomerular endothelium to hemolysis, which is the consequence of microthrombosis in aHUS, and also an complement pathway enhancer via free heme, hemoglobin-mediated hemolysis molecule, ii) the potential role of the receptor for advanced glycation end products, RAGE. Indeed, RAGE is described as an endothelial receptor with high proinflammatory and prothrombotic potential, involved in many kidney diseases; a team also reported that it was a receptor for the C3a molecule, anaphylatoxin released in complement activation.The first part of this work aimed to explain the vulnerability of the glomerular endothelium under the effect of hemolysis. We studied several types of endothelial cells exposed +/- to heme, and developed a murine model treated with heme. In hemolytic conditions, several factors that could participate in the endothelial glomerular susceptibility have been put forward: i) less binding of factor H, the main complement regulator, on its surface; ii) low expression of thrombomodulin, coagulation protein and complement regulator; iii) low expression of heme-oxygenase 1, the main heme degradation enzyme. These last two points were related to low induction, on glomerular endothelial cells, of transcription factors, KFL2 and KLF4.The second part of this work focused on RAGE. Having failed to reproduce the RAGE / C3a interaction, we explored the hypothesis of a linkage of RAGE to heme. Indeed, the only known endothelial receptor is Toll Like Receptor 4 (TLR4), which shares several common ligands (LPS - lipopolysaccharide, HMGB1 - high-mobility group box 1). We found that RAGE was a heme receptor, and identified that the binding site was on domain V. Using a mouse model knock out for RAGE and treated +/- with heme, we demonstrated that i) the invalidation of RAGE had a protective effect in case of exposure to heme, marked by a decrease in the expression of genes of inflammation (IL1β; TNFα; and tissue factor) at the pulmonary level, organ expressing most strongly RAGE, ii) the heme is an activator or the phosphorylation of ERK1 / 2 and Akt pathways via RAGE.Through this work, we have clarified the links between complement activation, hemolysis and glomerular endothelial susceptibility in aHUS. At the same time, we have identified RAGE as a new heme receptor, whose RAGE/heme bindind would activate different signaling pathways for inflammation. The control of heme and RAGE could constitute new therapeutic pathways in the aHUS, and hemolytic diseases.

Fresh produces, fruit juices and herbal teas used in our regular diet may have importance in the protective treatment of some infectious diseases. In this study, dietary produces were investigated for their antioxidant activities and antimicrobial activities against group A &szlig / -haemolytic streptoccoci. Streptococcus pyogenes, a member of the group A &szlig / -haemolytic streptococci, is a very dangerous pathogen, which may cause diseases such as tonsillopharyngitis, meningitis, rheumatic arthritis. Fruits and vegetables / onion, radish, carrot, plum, fruit juices / orange, peach, pomegranate, grape and teas / sage, anise, rosehip, chamomile were chosen as samples of regular daily diets. Dry extracts were obtained either by lyophilizing or fractionating in ethyl acetate. Antioxidant activities of extracts were examined by total phenolic content determination, and 2,2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH) methods. Antimicrobial activities of extracts were studied by disk diffusion test, minimum inhibitory and bactericidal concentration methods. Sage, plum, onion and radish displayed high radical scavenging activity with EC50 values of 0.043, 0.049, 0.148 and 0.414 mg/mL, respectively. Plum, sage, onion and radish were found high in total phenolic contents with &amp / #956 / g gallic acid equivalent of 50.506, 48.299, 44.427 and 13.135 in mg extract, respectively. High antimicrobial activities were obtained by onion, radish, anise, carrot and peach extracts as tested by disk diffusion method with respective 20, 16, 16, 14 and 14 millimeters clear growth inhibition zones. Carrot, onion and radish extracts were found as effective bacteriostatic and bactericidal agents with minimum inhibitory and bactericidal respective concentrations of 0.008, 0.125, 0.250 mg/mL and 0.06, 0.5, 1 mg/mL.

<p>Silicon-based electric chip arrays were developed for characterization of Bacillus</p><p>cereus with respect to the capacity to produce toxins involved in food poisoning and foodborne infections. Bacteria of the B. cereus group contain different sets of four toxins encoded by eight genes. The purpose of this work was to develop a fast method for determination of the presence of these genes in colonies from primary enrichment cultures. The specific DNA detection was based on immobilization of DNA capture probes, which hybridize to specific sites on the target genes. Biotin-labeled detection probes were designed to hybridize with the target DNA adjacent to the capture probes. An extravidin - alkaline phosphatase complex was subsequently bound to the hybridized detection probes. Finally, p-aminophenyl phosphate was added as substrate for the enzyme, and the product p-aminophenol was brought in contact with the interdigitated gold electrode on the silicon chips surface. The p-aminophenol was oxidized at the anode to quinoneimine, which was then reduced back to paminophenol at the cathode. This redox recycling generates a current that was used as the DNA-chip response to the target DNA. Two versions of the assay were used. In the first version the capture probes were immobilized on magnetic beads and all</p><p>chemical reactions until and including the enzymatic reaction took place in an</p><p>eppendorf tube while the redox recycling was used to measure the amount of paminophenol produced after transfer from the tube to the silicon chip surface. In the second version a silicon chip array was used with 16 parallel electrode positions, each activated by immobilization of one type of capture probes on the gold electrodes. With this system all chemical reactions took place at the chip surface. The kinetics of cell disruption and DNA fragmentation from B. cereus by ultrasonication was determined. Maximum cell disruption was achieved within 5 min and the chip response increased in proportion to the ultrasonic time. Further ultrasonication up to 10 min resulted in further increasing current although no further cell disruption was observed. If the sonication time was extended above 10 min the signal declined. Based on analysis of the DNA size distribution by early end-point PCR and gel electrophoresis, it is suggested that the first 5 min ultrasonication increased the signal by increasing the release of target DNA molecules. Thereafter the signal was increased by fragmentation of target DNA which increases the diffusion rate and also the accessibility of the hybridization site. Finally, the DNA fragment sizes approached that of the hybridization site (51-bp) which may reduce the signal because of cleavage of the target DNA in the hybridization region. These studies were performed with the bead-based hybridization assay. The assay was highly specific to the target gene (hblC) of both B. cereus and B. thuringiensis with no response from negative control</p><p>cells of B. subtilis. The 16 positions of the silicon chip array were activated by</p><p>immobilization of all known toxin-coding genes of B. cereus and also included both a positive control and a negative control electrode positions. When these chips were exposed to ultrasonicated B. cereus, the gold electrodes were fouled by some component in DNA cell lysates. To circumvent this, the released large DNA was first extracted and then ultrasonicated again, since the extract mainly contains large molecular weight DNA. This DNA extract was applied to characterize one “diarrheal” and one “emetic” strain of B. cereus with the DNA chip arrays. The results agreed with PCR control analysis which means that these electric DNA chip arrays can be used to characterize bacterial colonies with respect to the genes coding of all known toxins of B. cereus: haemolysin (hblA, hblC, hblD), non-haemolytic enterotoxin (nheA, nheB, nheC), cytotoxin K-2 (cytK-2), and cereulide (ces). The chip assay required about 30 min after application of DNA samples. Due to the generic properties of the chips, this technique should also be applicable for characterization of the pathogenicity potential of many other organisms. Keywords: Bacillus cereus, haemolysin, non-haemolytic enterotoxin, cytotoxin K-2, cereulide, toxin-coding genes, bacterial colony, electric DNA chip, ultrasonication, DNA fragmentation.</p>

Abstract The aims of this work were to study the carriage of respiratory bacteria and to identify risk factors affecting pharyngeal colonisation by these pathogens among young Finnish men during military service, and also to investigate the role of mannose-binding lectin (MBL) concentrations and MBL2 gene polymorphisms in the carriage of respiratory bacteria. A total of 892 military recruits entering the Kainuu Brigade, including 224 men with asthma, were followed up prospectively to the end of their military service. Carriage of Streptococcus pneumoniae, Neisseria meningitidis and beta-haemolytic streptococci appeared to be higher during and at the end of military service than at the beginning. Smoking was found to be a significant risk factor for colonisation by these bacteria. S.pneumoniae was more common in the asthmatic than military conscripts in the non-asthmatic ones at the beginning of military service. A low MBL level increased the risk of carrying N. meningitidis and beta-haemolytic streptococci during military service among non-smokers but not among smokers. Low MBL levels producing MBL2 haplotypes seemed to be associated with the carriage of N. meningitidis and S. pneumoniae. Characterisation of all the oropharyngeal N.meningitidis isolates obtained (n=215) by phenotypic and genotypic methods showed that most of them belonged to the carriage-associated ST-60 clonal complex. Clonal complexes ST-41/44, ST-32, and ST-23, which have previously been associated with disease, also accounted for a third of the carriage strains. Furthermore, a significant association was indicated between an acute upper respiratory infection and oropharyngeal carriage of the virulent meningococcal ST-23 clone. In conclusion, the results reported here show a significant increase in bacterial carriage during military service and provide new information on the association between MBL and carriage of respiratory bacteria. These findings also highlight the importance of smoking cessation, especially among military conscripts, who have been found to be a risk group for invasive bacterial diseases, and they also point to the importance of meningococcal vaccination for military recruits and the need for an efficacious vaccine against serogroup B meningococci. / Tiivistelmä Hengitystieinfektiot ovat yleisiä varusmiespalvelun aikana. Myös oireeton bakteerien nielukantajuus on lisääntynyt. Useimmiten infektiot ovat lieviä virusinfektioita, mutta bakteerien nielukantajuus voi johtaa myös vaikeisiin bakteeritulehduksiin. Tämän väitöskirjatyön tarkoituksena oli tutkia bakteerien nielukantajuutta varusmiespalveluksen alkaessa ja päättyessä sekä mahdollisten hengitystieinfektioiden aikana ja näin saada uutta tietoa bakteerien nielukantajuuteen vaikuttavista tekijöistä. Lisäksi tavoitteena oli selvittää mannoosia sitovan lektiinin (MBL) sekä MBL2-geenin polymorfismien yhteyttä bakteerien nielukantajuuteen. Työn tarkoituksena oli myös feno- ja genotyypittää varusmiehiltä palveluksen aikana eristetyt meningokokkikannat ja verrata niitä vastaavana ajankohtana invasiivista tautia sairastaneista henkilöistä eristettyihin meningokokkikantoihin. Tutkimuksessa seurattiin prospektiivisesti 892 varusmiestä, jotka suorittivat asepalveluksen Kainuun Prikaatissa vuosina 2004–2006. Tutkimukseen osallistuneista varusmiehistä 224:llä oli astma. Tutkimuksessa havaittiin, että oireeton bakteerien nielukantajuus lisääntyy merkitsevästi varusmiespalveluksen aikana. Lisäksi havaittiin, että tupakointi oli merkittävä itsenäinen riskitekijä pneumokokin, meningokokin sekä beta-hemolyyttisten streptokokkien nielukantajuudelle varusmiespalveluksen aikana. Astmaatikkojen pneumokokin nielukantajuus varusmiespalveluksen alussa oli yleisempi kuin terveiden varusmiesten. Tutkimuksessa osoitettiin myös pienen seerumin MBL-pitoisuuden sekä MBL2-geenin polymorfismin eksoni 1:n alueella ja geenin säätelyalueella olevan riskitekijöitä meningokokin, pneumokokin sekä beta-hemolyyttisten streptokokkien nielukantajuudelle tupakoimattomilla varusmiehillä. Meningokokin nielukannoista jopa kolmasosa kuului genotyyppiryhmään, jonka on aiemmissa tutkimuksissa havaittu liittyvän invasiiviseen tautiin. Tutkimuksessa osoitettiin myös tietyn hyperinvasiivisen meningokokin genotyypin (ST-23) liittyvän hengitystieinfektioepisodeihin. Tässä väitöskirjatyössä osoitettiin, että bakteerien nielukantajuus lisääntyy merkitsevästi varusmiespalveluksen aikana ja että oireettomilla varusmiehillä tavataan myös hyperinvasiivisia meningokokkikantoja. Tutkimus antoi myös uutta tietoa hyperinvasiivisten meningokokin genotyyppien liittymisestä hengitystieinfektioihin sekä MBL:n vaikutuksesta bakteerien nielukantajuuteen. Tutkimushavainnot tukevat tupakoimattomuuden edistämisen tärkeyttä myös varusmiespalveluksen aikana.