Interpreting changes in measles genotype: the contribution of chance, migration and vaccine coverage

<p>Abstract</p> <p>Background</p> <p>In some populations, complete shifts in the genotype of the strain of measles circulating in the population have been observed, with given genotypes being replaced by new genotypes. Studies have postulated that such shifts may be attributable to differences between the fitness of the new and the old genotypes.</p> <p>Methods</p> <p>We developed a stochastic model of the transmission dynamics of measles, simulating the effects of different levels of migration, vaccination coverage and importation of new genotypes on patterns in the persistence and replacement of indigenous genotypes.</p> <p>Results</p> <p>The analyses illustrate that complete replacement in the genotype of the strain circulating in populations may occur because of chance. This occurred in >50% of model simulations, for levels of vaccination coverage and numbers of imported cases per year which are compatible with those observed in several Western European populations (>80% and >3 per million per year respectively) and for the given assumptions in the model.</p> <p>Conclusion</p> <p>The interpretation of genotypic data, which are increasingly being collected in surveillance programmes, needs to take account of the underlying vaccination coverage and the level of the importation rate of measles cases into the population.</p

Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer's disease

Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer's disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.Acknowledgements: This work was supported by grants from the International Society for Neurochemistry (ISN) and Alexander von Humboldt Foundation (to M.C.D.); Agencia Nacional de Promoción Científica y Tecnológica (PBIT/09 2013, PICT-2015-0285 and PICT-2016-4647 to L.M.; PICT-2014-1537 to M.C.D.); GENMED Labex and JPND PERADES grant; and JPND EADB grant (German Federal Ministry of Education and Research, BMBF: 01ED1619A)

Chemical Synthesis of Staphyloferrin B Affords Insight into the Molecular Structure, Iron Chelation, and Biological Activity of a Polycarboxylate Siderophore Deployed by the Human Pathogen

Staphyloferrin B (SB) is a citrate-based polycarboxylate siderophore produced and utilized by the human pathogen Staphylococcus aureus for acquiring iron when colonizing the vertebrate host. The first chemical synthesis of SB is reported, which enables further molecular and biological characterization and provides access to structural analogues of the siderophore. Under conditions of iron limitation, addition of synthetic SB to bacterial growth medium recovered the growth of the antibiotic resistant community isolate S. aureus USA300 JE2. Two structural analogues of SB, epiSB and SBimide, were also synthesized and employed to investigate how epimerization of the citric acid moiety or imide formation influence its function as a siderophore. Epimerization of the citric acid stereocenter perturbed the iron-binding properties and siderophore function of SB as evidenced by experimental and computational modeling studies. Although epiSB provided growth recovery to S. aureus USA300 JE2 cultured in iron-deficient medium, the effect was attenuated relative to that of SB. Moreover, SB more effectively sequestered the Fe(III) bound to human holo-transferrin, an iron source of S. aureus, than epiSB. SBimide is an imide analogous to the imide forms of other citric acid siderophores that are often observed when these molecules are isolated from natural sources. Here, SBimide is shown to be unstable, converting to native SB at physiological pH. SB is considered to be a virulence factor of S. aureus, a pathogen that poses a particular threat to public health because of the number of drug-resistant strains emerging in hospital and community settings. Iron acquisition by S. aureus is important for its ability to colonize the human host and cause disease, and new chemical insights into the structure and function of SB will inform the search for new therapeutic strategies for combating S. aureus infections.Alfred Benzon Foundation (Postdoctoral fellowship)Pacific Southwest Regional Center of ExcellenceAlfred P. Sloan Foundatio

Diabetes mellitus und Immunantwort bei pyogenen Infektionen

Diabetes mellitus predisposes to variety of infectious diseases. The risk for pyogenic infections is increased 2aEuro to 4aEurofold, with Staphylococcus aureus being among the most important pathogens. Apart from comorbidities, dysfunction of the immune system leads to an increased susceptibility to infections. Despite conflicting results, several disturbances of the immune system have been described. Impairments of granulocyte function comprise reduced chemotaxis, phagocytosis, and bacterial killing with reduced oxidative burst. Decreased pathogen-induced granulocyte apoptosis leads to prolonged inflammation and production of inflammatory cytokines. Lower IgG (Ig: immunoglobulin) levels and inhibition of complement activation and opsonization are found on the side of the humoral immune response. Disturbed prostaglandin E2 production leads to a reduced maturation of dendritic cells and a lower Th17 response (Th17: T helper 17 cell). Additionally, evidence suggests that pathogens adapt to increased glucose concentrations with altered gene expression and increased virulence. A multifactorial genesis of the increased susceptibility to infections observed in patients with diabetes mellitus is assumed. Besides predisposing comorbidities mainly disturbances of the innate immune system in combination with the virulence of typical pathogens form the basis of the increased incidence of pyogenic infections

Empirische Antibiotikatherapie in der Notaufnahme

Due to the frequency of infectious diseases, antibiotic drugs are important and frequently life-saving medications in the emergency department (ED). On the other hand, rapid treatment decisions have to be made and a significant proportion of inadequate antibiotic prescriptions are observed in clinical practice although decisions in the ED set the course for adequate antibiotic treatment. In order to choose an appropriate treatment strategy, acute life-threatening infections (diagnostics and immediate empirical therapy) have to be differentiated in the ED from less complicated infections (mainly empirical therapy) and complicated infections of a frequently chronic nature (adequate diagnostics, no or delayed therapy). Additionally, this article gives a review of important general aspects of antibiotic therapy in the ED as well as the specific therapy of the most important infectious diseases

Epidemiologie von SARS-CoV-2-Infektion und COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new beta-Coronavirus that was first detected in 2019 in Wuhan, China. In the ensuing months it has been transmitted worldwide. Here the authors present the current knowledge on the epidemiology of this virus. SARS-CoV-2 replicates mainly in the upper and lower respiratory tract and is primarily transmitted by droplets from asymptomatic and symptomatic infected subjects. The estimate for the basic reproduction number (R) is currently between 2 and 3, while the incubation period is 6 (median, range 2-14) days. Although most infections are uncomplicated, 5-10% of cases develop pneumonia, which can lead to hospitalization, respiratory failure and multiorgan failure. Risk factors for a complicated disease course include age, hypertension, chronic cardiovascular and pulmonary disease and immunodeficiency. The overall case fatality rate is 1.4%, with the rate rising in the sixth decade of life. Nosocomial and infections in medical personnel have been reported. Drastic reductions in social contact have been implemented in many countries with outbreaks of SARS-CoV-2, leading to rapid reductions in R. Which of the measures have been effective is still unknown

Aktuelle Therapie der Endokarditis

Despite many novel diagnostic strategies and advances in treatment, infective endocarditis (IE) remains a severe disease. The epidemiology of IE has shifted and staphylococci have replaced streptococci as the most common cause and nosocomially acquired infections, invasive procedures, indwelling cardiac devices and acquired infections due to intravenous drug abuse are more frequent. The incidence of IE has steadily increased in recent years and the patients affected are older and have more comorbidities. The modern treatment of IE is interdisciplinary. The pharmacotherapy of IE depends on the pathogen and its sensitivity. The presence of a bioprosthetic valve and implantable cardiac devices plays a significant role in selection of antibiotics and duration of treatment. This article provides an update and overview of the current clinical practice in diagnostics and pharmacotherapy of IE in adults with a special focus on partial oral therapy and the role of aminoglycosides