36 research outputs found
Biomarkers in asthmatic inflammation: a study of pharmacological immunomodulation, in vitro and in vivo.
No full textEffect of α(+)-Thalassaemia on Episodes of Fever due to Malaria and Other Causes: A Community-Based Cohort Study in Tanzania.
No full textIt is controversial to what degree α(+)-thalassaemia protects against episodes of uncomplicated malaria and febrile disease due to infections other than Plasmodium. In Tanzania, in children aged 6-60 months and height-for-age z-score < -1.5 SD (n = 612), rates of fevers due to malaria and other causes were compared between those with heterozygous or homozygotes α(+)-thalassaemia and those with a normal genotype, using Cox regression models that accounted for multiple events per child. The overall incidence of malaria was 3.0/child-year (1, 572/526 child-years); no differences were found in malaria rates between genotypes (hazard ratios, 95% CI: 0.93, 0.82-1.06 and 0.91, 0.73-1.14 for heterozygotes and homozygotes respectively, adjusted for baseline factors that were predictive for outcome). However, this association strongly depended on age: among children aged 6-17 months, those with α(+)-thalassaemia experienced episodes more frequently than those with a normal genotype (1.30, 1.02-1.65 and 1.15, 0.80-1.65 for heterozygotes and homozygotes respectively), whereas among their peers aged 18-60 months, α(+)-thalassaemia protected against malaria (0.80, 0.68-0.95 and 0.78, 0.60-1.03; p-value for interaction 0.001 and 0.10 for hetero- and homozygotes respectively). No effect was observed on non-malarial febrile episodes. In this population, the association between α(+)-thalassaemia and malaria depends on age. Our data suggest that protection by α(+)-thalassaemia is conferred by more efficient acquisition of malaria-specific immunity
Intrapancreatic accessory spleens in African swine fever infection of wild boar (Sus scrofa)
No full textAuthor contributions: NP: Conceptualization, Data curation, Investigation, Methodology, Software, Writing – original draft. BC: Data curation, Formal analysis, Methodology, Visualization, Writing – review & editing. AR-B: Conceptualization, Resources, Supervision, Visualization, Writing – review & editing, Investigation. JB: Data curation, Methodology, Resources, Supervision, Visualization, Writing – review & editing. AK: Data curation, Methodology, Visualization, Writing – review & editing. EV-F: Methodology, Visualization, Writing – review & editing. PS-C: Resources, Supervision, Visualization, Writing – review & editing. JS-V: Funding acquisition, Project administration, Resources, Supervision, Visualization, Writing – review & editing.Intrapancreatic accessory spleen (IPAS) is one of the most frequent congenital splenic anomalies in humans; however, studies in veterinary medicine are scarce. This study aimed to describe the macroscopic, histopathological and immunohistochemical features of 11 suspected cases of IPAS in wild boar piglets of 3–4 months old. Seven of the 11 animals were immunised with a low virulence isolate of African swine fever virus (ASFV) and subsequently challenged with a highly virulent ASFV isolate (LVI-HVI group). The remaining four animals were exclusively infected with a highly virulent isolate of ASFV (HVI group). Grossly, lesions comprised focal or multifocal reddish areas of variable shape, located on the surface of the pancreatic tail or within the parenchyma. Histological and immunohistochemical studies (anti-CD79 and CD3) confirmed the presence of IPAS in eight of the 11 cases. IPAS shared the same histological structure and alterations as those observed in the original spleen. The immunohistochemical study against ASFV revealed the presence of VP72+ cells in both the spleen and IPAS of seven of the eight piglets. The results of this study describe for the first time the presence of IPAS in ASFV infection of wild boar (Sus scrofa) regardless the isolate and suggest that the infection may induce the development of ectopic splenic tissue due to an increased demand for phagocytic cells from the reticuloendothelial system. However, further studies are needed to understand the immunological mechanisms that trigger the formation of these accessory organs.European ComissionDepto. de Producción AnimalDepto. de Medicina y Cirugía AnimalDepto. de Sanidad AnimalFac. de VeterinariaTRUEpu
The bactericidal activity of moxifloxacin in patients with pulmonary tuberculosis
No full textPatients in whom acid-fast bacilli smear-positive pulmonary tuberculosis was newly diagnosed were randomized to receive 400 mg moxifloxacin, 300 mg isonaizid, or 600 mg rifampin daily for 5 days. Sixteen-hour overnight sputa collections were made for the 2 days before and for 5 days of monotherapy. Bactericidal activity was estimated by the time taken to kill 50% of viable bacilli (vt(50)) and the fall in sputum viable count during the first 2 days designated as the early bactericidal activity (EBA). The mean vt(50) of moxifloxacin was 0.88 days (95% confidence interval [Cl], 0.43-1.33 days) and the mean EBA was 0.53 (95% CI 0.28-0.79). For the isoniazid group, the mean vt(50) was 0.46 days (95% Cl, 0.31-0.61 days) and the mean EBA was 0.77 (95% Cl, 0.54-1.00). For rifampin, the mean vt(50) was 0.71 days (95% Cl, 0.48-0.95 days) and the mean EBA was 0.28 (95% Cl, 0.15-0.41). Using the EBA method, isoniazid was significantly more active than rifampin (p < 0.01) but not moxifloxacin. Using the vt(50) method, isoniazid was more active than both rifampin and moxifloxacin (p = 0.03). Moxifloxacin has an activity similar to rifampin in human subjects with pulmonary tuberculosis, suggesting that it should undergo further assessment as part of a short course regimen for the treatment of drug-susceptible tuberculosis
Targeted delivery of advanced functionality by nanomaterials : focus on nucleic acids delivery by novel block copolymers
No full textAbstract: Smart drug delivery systems are versatile examples of successful nanomedicine with
potential in diagnostics and medical therapy. The thesis presents selected
approaches in current drug delivery systems in the (pre-)clinical trials, and deals with
potential side effects, including complement activation and hypersensitivity reactions
as well as the design requirements of the delivery systems. Furthermore, it presents
approaches of cationic block copolymers, which are capable to condense negatively
charged nucleic acid molecules such as plasmid deoxyribonucleic acid (pDNA) and
small interfering ribonucleic acid (siRNA) with the aim of efficient cell gene delivery
and specific gene suppression, respectively.
The first part addresses the transfection efficiency of circular versus linearized
plasmid DNA using a green fluorescent protein expressing vector with Lipofectamine
2000 and linear 25 kDA polyethylenimine (PEI). These results show a considerably
improved transfection efficiency with the circular compared to the linearized DNA for
the two transfection reagents. The electron microscopy images with Lipofectamine or
PEI demonstrate that the circular DNA gives rise to random coil appearance of
compact, spherical shape, while linearized DNA appear as worm-like strands.
Particle size and shape are important in the cell biology of endocytosis and
phagocytosis. The findings indicate that the shape of the transfection particle is vital
for successful gene transfer.
To develop a delivery system for gene therapy, two cationic diblock copolymers
consisting of primary and tertiary amines were synthesized and analyzed with
respect to DNA condensation properties, morphology of the condensed plasmid DNA
and transfection efficiency using two cell lines. This study revealed proof-of-concept
showing an order of magnitude lower transfection efficiency of primary amine diblock
copolymers compared to PEI after 48 h with increasing plasmid DNA concentration.
Furthermore, primary amines compared to tertiary ones show much stronger binding
to DNA and improved transfection efficiency. Transmission electron and atomic force
microscopy data revealed morphologies of primary and tertiary amines regarding the
condensation of the plasmid DNA, in agreement with the transfection efficiency.
In a second part the design and characterization of pentablock-based polyplexes
based on the combination of cationic pentablock copolymers with folic acid
functionalized copolymers for targeted specific siRNA delivery is described. The
achieved 31 % knockdown efficiency shows its potential regarding cancer gene
therapy. The pentablock architecture allows the formation of highly stable
micelleplexes of (21 ± 3) nm in 10 mM PBS buffer solution with a neutral surface
charge, excellent siRNA condensation properties, outstanding colloidal stability in
10 % serum over 24 h and biocompatibility deduced from the absence of
considerable cytotoxicity even after 48 h incubation. Furthermore, selective delivery
of the siRNA could be proven by the introduction of a ligand-linked block copolymer,
resulting in 31 % compared to 8 % gene suppression for targeted a non-targeted
micelleplexes. This pentablock-based delivery system might yield impact to future
delivery systems as well as being a potential platform to be applied in vivo for cancer
gene therapy. ---------- Zusammenfassung
Innerhalb des Bereichs der Nanomedizin weisen intelligente Wirkstoffabgabesysteme
ein großes Potenzial auf, sowohl hinsichtlich der Diagnostik wie auch der
medizinischen Therapie. Die vorliegende Arbeit stellt im Rahmen einer
Literaturrecherche ausgewählte Wirkstoffabgabesysteme vor, welche sich in (vor-)
klinischen Studien befinden, den Nebenwirkungen welche durch diese entstehen
können, im speziellen der Komplementaktivierung und Überempfindlichkeitsreaktionen,
sowie deren Konstruktionsanforderungen. Des weiteren werden in einem
experimentellen Teil kationische Block-Kopolymere präsentiert, welche in der Lage
sind, negativ geladene Nukleinsäuremoleküle zu binden - wie etwa Plasmid
Desoxyribonukleinsäure (pDNA) und kleine interferierende Ribonukleinsäuren
(siRNA) - mit dem Ziel der Transfektion von fremder DNA in die Wirtszellen und
damit der spezifischen Unterdrückung der Genexpression.
Der erste Teil der experimentellen Arbeit untersucht die Transfektionseffizienz von
zirkulärer gegenüber linearisierter Plasmid-DNA mittels eines Vektors, welcher ein
grün fluoreszierendes Protein exprimiert. Transfiziert wurde einerseits mit
Lipofectamine 2000 und andererseits mit linearem 25 kDa Polyethylenimin (PEI),
zwei etablierten Transfektionsreagenzien. Die Ergebnisse zeigen eine wesentlich
verbesserte Transfektionseffizienz der zirkulären, verglichen mit der linearisierten
DNA für beide Transfektionsreagenzien. Die elektronenmikroskopischen Bilder von
Lipofectamine sowie PEI komplexiert mit DNA zeigen, dass die zirkuläre DNA
zufällige, kompakte Kugelformen bildet, während die linearisierte DNA wurmartige
Stränge aufweist. Partikelgröße und -form spielen in der Zellbiologie eine wichtige
Rolle bei der Endozytose und Phagozytose. Die Ergebnisse legen die Vermutung
nahe dass die Form der zu transfizierenden DNA-Transfektions-Komplexen eine
wichtige Rolle einnimmt für einen erfolgreichen Gentransfer.
Für die Entwicklung eines intelligenten Wirkstoffabgabe-Systems für die Gentherapie
wurden zwei kationische Diblock-Kopolymere, die aus primären und tertiären Aminen
bestehen synthetisiert und im Hinblick auf deren DNA-Kondensationseigenschaften,
Morphologie der kondensierten Plasmid-DNA sowie Transfektionseffizienz unter
Verwendung von zwei Zelllinien analysiert. Die Studie bestätigt trotz einer um den
Faktor 10 schwächeren Transfektionseffizienz der primären Amin-DiblockKopolymeren
im Vergleich zu PEI nach 48 h mit zunehmender pDNA Konzentration
eine Bestätigung des Konzepts. Außerdem weisen die primären Amin-Block-
Kopolymere im Vergleich zu den tertiären eine viel stärkere Komplexbildung der DNA
auf - wie transmissions-elektronen- und rasterkraft-mikroskopische Daten ergaben -
als auch eine verbesserte Transfektionseffizienz. Diese physikalischmorphologischem
Erkenntnisse über die Kondensation der primären und tertiären
Amine mit Plasmid-DNA konnten mittels der biologischen Transfektionseffizienzdaten
validiert werden.
Der zweite Teil der experimentellen Arbeit befasst sich mit dem Design sowie der
Charakterisierung von pentablock-basierten Polyplexen für einen gezielten siRNA
Transport. Diese Polyplexe beruhen auf einer Kombination von kationischen
Pentablock-Kopolymeren mit folsäure-funktionalisierten Kopolymeren. Die erreichten
31% Gen-Suppression in einem Krebszellkulturmodell, zeigen das Potenzial des
Wirkstoffabgabesystems in Bezug auf eine Krebstherapie auf. Die Architektur
ermöglicht die Bildung von sehr stabilen Mizellen mit einer Grösse von (21 ± 3) nm in
10 mM PBS Pufferlösung, eine neutrale Oberflächenladung, ausgezeichneten siRNAKondensationseigenschaften,
hervorragender kolloidaler Stabilität in
Zellkulturmedium supplementiert mit 10 % Serum über 24 h, sowie guter
Biokompatibilität aufgrund fehlender erheblicher Zytotoxizität auch nach 48 h
Inkubation in einem Zellkulturmodell. Ferner konnte durch die Einführung eines
liganden-gebundenen Block-Kopolymers der selektive Transport der siRNA
nachgewiesen werden, was zu einer Gen Suppression von 31% gegenüber 8% nicht
funktionalisierter Polyplexen führte. Das in dieser Arbeit eingeführte und
charakterisierte pentablock-basierte Wirkstoffabgabesystem könnte Auswirkungen
auf das Design zukünftiger Wirkstoffabgabesystem haben als auch als eine
potentielle Plattform für in vivo-Krebsgentherapien angewendet werden
DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
No full textSingle Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be
associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose
polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p,0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03– 1.16), p = 2.761023) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03–1.21,
p = 4.861023). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/ 2 mutation carriers and should be more comprehensively studied
Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals with Anorexia Nervosa - A Coordinated Analysis by the ENIGMA Eating Disorders Working Group
No full textThe pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in grey matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy controls. Recent weight regain before scanning may explain some of this heterogeneity across studies. To clarify the extent, magnitude, and dependencies of grey matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. We analyzed T1-weighted structural MRI scans assessed with standardized methods from 685 female AN patients and 963 female healthy controls across 22 sites worldwide. In addition to a case-control comparison, we conducted a three-group analysis comparing healthy controls to acutely underweight AN patients (n = 466), and to those in treatment and partially weight-restored (n = 251). In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area, were sizable (Cohen’s d up to 0.95), widespread and co-localized with hub regions. Highlighting the effects of undernutrition, these deficits associated with lower BMI in the AN sample and were less pronounced in partially weight-restored patients. Notably, the effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was supported by the Carus Promotionskolleg (KB), the Ministerio de Igualdad, Spain (grant number 234/09) and by the Generalitat de Catalunya (2009 SGR 1119) (SA), NIH R21MH86017, NIH R01MH113588 (ABG), Biomedical Research Centre (BRC) UK (ICC), the Alicia Koplowitz Foundation (FAK) (DN040546) and by the Generalitat de Catalunya 2017SGR4881 (JCF), German Ministry for Education and Research (grants 01GV0602 and 01GV0623) (BD), NIMH R01MH105662, NIMH R01MH093535 (JDF), NIMH K23MH080135, R01MH096777 (GKWF), NIH RC1MH088678 (JLG), German Ministry for Education and Research (grants 01GV0602 and 01GV0623) (BHD), the CAMH AFP Innovation Fund (ASK), Swiss Anorexia Nervosa Foundation (project no. 19-12), the Palatin Foundation, and the Gottfried and Julia Bangerter-Rhyner-Foundation (LKK), NIH R01MH042984- 17A1, Price Foundation, NIH R01MH113588 (WHK), NIMH K23MH112949 (SSK), NIH RC1MH088678 (KSL), the Carlos III Research Institute of the Spanish Ministry of Health, FIS PI040829 and by the Generalitat de Catalunya (2009 SGR 1119) (LL), the CAMH AFP Innovation Fund (AEM), Swiss Anorexia Nervosa Foundation (project no. 19-12), the Palatin Foundation, and the Gottfried and Julia Bangerter-Rhyner-Foundation (GFM), Biomedical Research Centre (BRC) UK (OOD), Biomedical Research Centre (BRC) UK (UHS), German Ministry for Education and Research (grants 01GV0602 and 01GV0623) (JS), NIMH K23MH080135, R01MH096777 (MES), DFG: SI 2087/2-1, BR 4852/1-1, Swiss Anorexia Nervosa Foundation: 57-16 (JJS), Research Council of Norway (#288083, #223273); South-Eastern Norway Regional Health Authority (#2019069, #2021070, #500189) (CKT), the CAMH AFP Innovation Fund (ANV), German Ministry for Education and Research (grants 01GV0602 and 01GV0623) (GGvP), NIH R21MH86017, R01MH113588 (CEW), NIH RC1MH088678 (NLZ), NIH RC1MH088678 (JAK), a National Institute of Health Research (NIHR) Senior Investigator Award (US), the NIHR Mental Health Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and Kings College London (ICC, US and OOD), K23MH118418; NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (LAB), and SFB 940, DFG: EH 367/5-1, EH 367/7-1 and the Swiss Anorexia Nervosa Foundation (SE). This work is further supported by the European Unions Horizon 2020 research and innovation programme (EarlyCause, grant number 848158, to EW). The ENIGMA Working Group acknowledges the NIH Big Data to Knowledge (BD2K) award for foundational support and consortium development (U54 EB020403 to Paul M. Thompson).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:All participating sites obtained approval from local institutional review boards and ethics committees, and all study participants provided written informed consent (SM section 1.1). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors
Predictive effectiveness of the Framingham and PROCAM scales for establishing cardiovascular risk in patients with systemic lupus erythematosus, in third level care institutions
No full textLos pacientes con lupus eritematoso sistémico (LES) presentan factores de riesgos intrínsecos de la enfermedad, como la aterogénesis acelerada y el estado proinflamatorio crónico. En Colombia, las escalas Framingham y PROCAM se encuentran validadas para la prediccion de riesgo cardiovascular, no incluyen variables del LES.
Objetivo: establecer la efectividad predictiva de las escalas de Framingham y PROCAM para el establecimiento de riesgo cardiovascular en pacientes con LES.
Metodologia: estudio de cohorte retrospectivo, multicéntrico, basado en registros disponibles entre 2010 y 2023, de pacientes s con LES atendidos en instituciones de tercer nivel de atención de la ciudad de Barranquilla. Se considero como cohorte expuesta, pacientes con puntaje riesgo cardiovascular mayor al 20% en la escalas Framingham y PROCAM.
Resultados: . Durante los años de estudio registraron 42 casos de MACE, el hábito tabáquico, niveles elevados de colesterol (promedio LDL, 99,5 ± 40,9 mg/dL) y complemento disminuido tuvieron significancia estadística con su aparición. Los pacientes con MACE, fueron clasificados en su predominio como bajo riesgo (menor de 10%) según las escalas predictivas. La escala predictiva Framingham, mostro sensibilidad del 14%, especificidad del 87%, valor predictivo positivo (VPP) de 31%, valor predictivo negativo (VPN) del 71%, con AUC de 0.554. La escala predictiva PROCAM mostro una sensibilidad del 12%, especificidad del 90%, VPP 33%, VPN 71%, AUC de 0.593.
Conclusión: se demostró una baja sensibilidad, valor predictivo positivo y AUC bajas, con modesto valor predictivo negativo y aceptable especificidad de las escalas predictivas Framingham y PROCAM en el cribaje de riesgo cardiovascular.Universidad Libre Seccional Barranquilla -- Facultad de Ciencias de la Salud -- Especialización en Medicina InternaPatients with systemic lupus erythematosus (SLE) present intrinsic risk factors for the disease, such as accelerated atherogenesis and a chronic proinflammatory state. In Colombia, the Framingham and PROCAM scales are validated for the prediction of cardiovascular risk; they do not include SLE variables.
Objective: to establish the predictive effectiveness of the Framingham and PROCAM scales for establishing cardiovascular risk in patients with SLE.
Methodology: retrospective, multicenter cohort study, based on records available between 2010 and 2023, of patients with SLE treated in tertiary care institutions in the city of Barranquilla. The exposed cohort was considered to be patients with a cardiovascular risk score greater than 20% on the Framingham and PROCAM scales.
Results: . During the study years, 42 cases of MACE were recorded; smoking, high cholesterol levels (average LDL, 99.5 ± 40.9 mg/dL) and decreased complement had statistical significance with its appearance. Patients with MACE were predominantly classified as low risk (less than 10%) according to predictive scales. The Framingham predictive scale showed sensitivity of 14%, specificity of 87%, positive predictive value (PPV) of 31%, negative predictive value (NPV) of 71%, with AUC of 0.554. The PROCAM predictive scale showed a sensitivity of 12%, specificity of 90%, PPV 33%, NPV 71%, AUC of 0.593.
Conclusion: low sensitivity, positive predictive value and low AUC were demonstrated, with modest negative predictive value and acceptable specificity of the Framingham and PROCAM predictive scales in cardiovascular risk screening
Active trachoma and ocular Chlamydia trachomatis infection in two Gambian regions: on course for elimination by 2020?
No full textBACKGROUND: Trachoma has been endemic in The Gambia for decades. National trachoma control activities have been in place since the mid-1980's, but with no mass antibiotic treatment campaign. We aimed to assess the prevalence of active trachoma and of actual ocular Chlamydia trachomatis infection as measured by polymerase chain reaction (PCR) in the two Gambian regions that had had the highest prevalence of trachoma in the last national survey in 1996 prior to planned national mass antibiotic treatment distribution in 2006. METHODOLOGY/PRINCIPAL FINDINGS: Two stage random sampling survey in 61 randomly selected Enumeration Areas (EAs) in North Bank Region (NBR) and Lower River Region (LRR). Fifty randomly selected children aged under 10 years were examined per EA for clinical signs of trachoma. In LRR, swabs were taken to test for ocular C. trachomatis infection. Unadjusted prevalences of active trachoma were calculated, as would be done in a trachoma control programme. The prevalence of trachomatous inflammation, follicular (TF) in the 2777 children aged 1-9 years was 12.3% (95% CI 8.8%-17.0%) in LRR and 10.0% (95% CI 7.7%-13.0%) in NBR, with significant variation within divisions (p<0.01), and a design effect of 3.474. Infection with C. trachomatis was found in only 0.3% (3/940) of children in LRR. CONCLUSIONS/SIGNIFICANCE: This study shows a large discrepancy between the prevalence of trachoma clinical signs and ocular C. trachomatis infection in two Gambian regions. Assessment of trachoma based on clinical signs alone may lead to unnecessary treatment, since the prevalence of active trachoma remains high but C. trachomatis infection has all but disappeared. Assuming that repeated infection is required for progression to blinding sequelae, blinding trachoma is on course for elimination by 2020 in The Gambia
The innate immune response to Mycobacterium tuberculosis is dependent on strain lineage and on host population
No full textIncludes abstract.Includes bibliographical references.The genome structure of Mycobacterium tuberculosis is strongly clonal, in the absence of horizontal gene transfer. Thus it is feasible that clonal lineages may exhibit particular phenotypic characteristics, which may, in turn, result in differences in virulence or influence their association with particular host populations. Indeed, the global distribution of M. tuberculosis strains is not uniform and certain strain lineages predominate in particular geographical areas. Further, there is evidence that some strain lineages are emerging, suggesting differences in virulence. Firstly, we investigated the association between strain genotype of M. tuberculosis and in vitro correlates of virulence such as growth phenotype and cytokine induction in the monocyte-derived macrophage (MDM) model
