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IntroductionIn Malawi, cholera outbreaks occur frequently during the rainy season between November and March,' with districts surrounding Lake Chilwa among the most affected. (1) Particularly at risk are people living [...], Objective To evaluate vaccination coverage, identify reasons for non-vaccination and assess satisfaction with two innovative strategies for distributing second doses in an oral cholera vaccine campaign in 2016 in Lake Chilwa, Malawi, in response to a cholera outbreak.Methods We performed a two-stage cluster survey. The population interviewed was divided in three strata according to the second-dose vaccine distribution strategy: (i) a standard strategy in 1477 individuals (68 clusters of 5 households) on the lake shores; (ii) a simplified cold-chain strategy in 1153 individuals (59 clusters of 5 households) on islands in the lake; and (iii) an out-of-cold-chain strategy in 295 fishermen (46 clusters of 5 to 15 fishermen) in floating homes, called zimboweras.Finding Vaccination coverage with at least one dose was 79.5% (1153/1451) on the lake shores, 99.3% (1098/1106) on the islands and 84.7% (200/236) on zimboweras. Coverage with two doses was 53.0% (769/1451), 91.1% (1010/1106) and 78.8% (186/236), in the three strata, respectively. The most common reason for non-vaccination was absence from home during the campaign. Most interviewees liked the novel distribution strategies.Conclusion Vaccination coverage on the shores of Lake Chilwa was moderately high and the innovative distribution strategies tailored to people living on the lake provided adequate coverage, even among hard-to-reach communities. Community engagement and simplified delivery procedures were critical for success. Off-label, out-of-cold-chain administration of oral cholera vaccine should be considered as an effective strategy for achieving high coverage in hard-to-reach communities. Nevertheless, coverage and effectiveness must be monitored over the short and long term.Objectif Evaluer la couverture vaccinale, Identifier les raisons de non-vaccination et estimer le degre de satisfaction vis-a-vis de deux strategies innovantes de distribution de la seconde dose vaccinale, dans le cadre d'une campagne de vaccination orale anticholerique menee en 2016 sur le lac Chilwa et ses environs, au Malawi, en reponse a une flambee de cholera.Methodes Nous avons realise une enquete en grappes a deux degres. La population interrogee a ete divisee en trois strates, en fonction de la strategie de distribution employee pour la seconde dose du vaccin: (i) une strategie standard pour 1477 personnes (68 grappes de 5 menages) residant en bordure du lac; (ii) une strategie de chaine du frold simpllfiee pour 1153 personnes (59 grappes de 5 menages) residant sur des iles du lac; et (iii) une strategie sans chaine du froid pour 295 pecheurs (46 grappes de 5 a 15 pecheurs) vivant dans des maisons flottantes appelees zimboweras.Resultats La couverture vaccinale avec administration d'au molns une dose de vaccin a ete de 79,5% (1153/1451) dans la population du rivage du lac, de 99,3% (1098/1106) dans la population des iles et de 84,7% (200/236) chez les habitants des zimboweras. Dans ees trois strates, la couverture vaccinale avec deux doses a ete respectivement de 53,0% (769/1451), 91,1 % (1010/1106) et 78,8% (186/236). La raison la plus courante de non-vaccination a ete l'absence du domicile durant la campagne. La plupart des personnes interrogees ont apprecle les nouvelles strategies de distribution.Conclusion La couverture vaccinale sur les rives du lac Chilwa a ete moderement elevee, et les strategies innovantes de distribution spedfiquement adaptees pour les personnes vivant sur le lac ont permis une couverture adequate, y compris parml les populations difficiles a atteindre. L'lmpllcationde la communauteet l'utillsatlon de procedures simplifiees de distribution ont ete des facteurs determinants de succes. L'administration hors AMM, sans chaine du frold, de vaccins oraux anticholeriques devrait etre consideree comme une strategie efficace pour obtenir une couverture vaccinale elevee dans les communautes difficiles a atteindre. Neanmoins, la couverture et son efficacite doivent etre surveillees a court et a long termes.Objetivo Evaluar la cobertura de vacunacion, identificar los motivos de la no vacunacion y evaluar la satisfaccion con dos estrategias innovadoras para la distribucion de segundas dosis en una campana de vacunacion oral contra el colera en 2016 en el Lago Chilwa, Malawi, en respuesta a un brote de colera.Metodos Se llevo a cabo una encuesta de conglomerados en dos etapas. La poblacion entrevistada se dividio en tres estratos de acuerdo con la estrategia de distribucion de la segunda dosis de la vacuna: (i) una estrategia estandar en 1477 individuos (68 grupos de 5 hogares) a orillas del lago; (ii) una estrategia simplificada de la cadena de frio en 1153 individuos (59 grupos de 5 hogares) en las islas del lago; y (iii) una estrategia fuera de la cadena de frio en 295 pescadores (46 grupos de 5 a 15 pescadores) en hogares flotantes, llamados zimboweras. Resultados La cobertura de vacunacion con al menos una dosis fue del 79,5 % (1153/1451) en las orillas del lago, del 99,3 % (1098/1106) en las islas y del 84,7 % (200/236) en las zimboweras. La cobertura con dos dosis fue del 53,0 % (769/1451), del 91,1 % (1010/1106) y del 78,8 % (186/236) en los tres estratos, respectivamente. La razon mas comun para no vacunarse fue estar ausentes del hogar durante la campana. A la mayoria de los entrevistados les gustaron las nuevas estrategias de distribucion.Conclusion La cobertura de vacunacion a las orillas del lago Chilwa fue moderadamente alta y las innovadoras estrategias de distribucion adaptadas a las personas que viven en el lago proporcionaron una cobertura adecuada, incluso entre las comunidades de dificil acceso. La participacion de la comunidad y la simplificacion de los procedimientos de administracion fueron fundamentales para el exito. La administracion de la vacuna oral contra el colera sin receta y fuera de la cadena de frio deberia considerarse una estrategia eficaz para lograr una cobertura alta en comunidades de dificil acceso. No obstante, la cobertura y la eficacia deben ser objeto de seguimiento a corto y largo plazo.

Background The number of reported cholera cases worldwide, as well as the frequency and scale of cholera epidemics, are increasing [1]. Traditional prevention measures, which focus on provision of safe [...]

Background: Patients with liver cirrhosis have a highly elevated risk of developing bacterial infections that significantly decrease survival rates. One of the most relevant infections is spontaneous bacterial peritonitis (SBP). Recently, NOD2 germline variants were found to be potential predictors of the development of infectious complications and mortality in patients with cirrhosis. The aim of the INCA (Impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver Cirrhosis and Ascites) trial is to investigate whether survival of this genetically defined high-risk group of patients with cirrhosis defined by the presence of NOD2 variants is improved by primary antibiotic prophylaxis of SBP. Methods/Design: The INCA trial is a double-blind, placebo-controlled clinical trial with two parallel treatment arms (arm 1: norfloxacin 400 mg once daily; arm 2: placebo once daily; 12-month treatment and observational period). Balanced randomization of 186 eligible patients with stratification for the protein content of the ascites (<15 versus ⩾15 g/L) and the study site is planned. In this multicenter national study, patients are recruited in at least 13 centers throughout Germany. The key inclusion criterion is the presence of a NOD2 risk variant in patients with decompensated liver cirrhosis. The most important exclusion criteria are current SBP or previous history of SBP and any long-term antibiotic prophylaxis. The primary endpoint is overall survival after 12 months of treatment. Secondary objectives are to evaluate whether the frequencies of SBP and other clinically relevant infections necessitating antibiotic treatment, as well as the total duration of unplanned hospitalization due to cirrhosis, differ in both study arms. Recruitment started in February 2014. Discussion: Preventive strategies are required to avoid life-threatening infections in patients with liver cirrhosis, but unselected use of antibiotics can trigger resistant bacteria and worsen outcome. Thus, individualized approaches that direct intervention only to patients with the highest risk are urgently needed. This trial meets this need by suggesting stratified prevention based on genetic risk assessment. To our knowledge, the INCA trial is first in the field of hepatology aimed at rapidly transferring and validating information on individual genetic risk into clinical decision algorithms. [ABSTRACT FROM AUTHOR]

Objective: The pharmacokinetics of phylloquinone (vitamin K1) were evaluated in healthy human adult volunteers (15 male and 15 female) following oral and intravenous administration of a mixed micelles formulation (Konakion® MM 2 mg) in an open label study design. The subjects were allocated to one of three genotype-specific groups ( n = 10 in each group) in terms of VKORC1 promoter polymorphism c.-1639 G > A to explore the relationship between genotype and pharmacokinetic parameters. Methods: Blood samples were collected for up to 24 h after administration. Phylloquinone serum levels were determined by reversed phase HPLC with fluorometric detection after post-column zinc reduction. Pharmacokinetic evaluation was performed using non-compartmental analysis. Results: Pharmacokinetic analysis of serum phylloquinone concentration versus time profiles revealed significant differences in the main pharmacokinetic parameters between groups. Upon oral administration, VKORC1 AG carriers showed 41 % higher mean bioavailability ( p = 0.01) compared with homozygous AA individuals. Furthermore, AG subjects exhibited 30 % ( p = 0.042) and 36 % ( p = 0.021) higher mean AUC compared with GG and AA respectively. Terminal half-life was 32 % and 27 % longer for AG carriers in comparison to GG ( p = 0.004) and AA ( p = 0.015) genotypes respectively. Conclusion: Pharmacokinetic differences indicated significant inter-individual variance of vitamin K fate in the human body. The influence of the VKORC1 promoter polymorphism c.-1639 G > A on the pharmacokinetic properties of phylloquinone could be demonstrated in humans. To gain deeper insight in other potential genetic determinants of systemic vitamin K exposure, further correlation of the phenotype-genotype relationship of different players in vitamin K turnover has to be gained. [ABSTRACT FROM AUTHOR]

Cholera remains a grave public health problem in Africa. It is endemic with seasonal variations around the central African Great Lakes. Along the coasts, it occurs mostly in rapidly expanding epidemics, with intercalated 3–5 year lull-periods. Case-fatality ratios remain high at 2–5% against the global declining trend. Insufficient safe water and sanitation coverage are the main causes of persistent cholera in Africa and this is unlikely to improve soon. However, an efficacious oral cholera vaccine is now available and new groups and initiatives like the African Cholera Surveillance Network (Africhol) allow countries to enhance their capacities for an integrated cross-border approach using all means necessary to tackle cholera in Africa. [ABSTRACT FROM AUTHOR]